Metabolic Medicine for Patients: How Does a Low ...



left13716000Metabolic Medicine for Patients: How Does a Low Carbohydrate Diet Work?Obesity and weight gain are mediated by hormones, not just calories.Insulin helps get glucose from the blood stream into our tissues and is our main energy storage hormone. Insulin resistance occurs when our body has to produce more insulin for the same effect in getting glucose into our tissues. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"uvP0fc08","properties":{"formattedCitation":"\\super 1\\uc0\\u8211{}3\\nosupersub{}","plainCitation":"1–3","noteIndex":0},"citationItems":[{"id":558,"uris":[""],"uri":[""],"itemData":{"id":558,"type":"article-journal","title":"Insulin and Insulin Resistance","container-title":"Clinical Biochemist Reviews","page":"19-39","volume":"26","issue":"2","source":"PubMed Central","abstract":"As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits.","ISSN":"0159-8090","note":"PMID: 16278749\nPMCID: PMC1204764","journalAbbreviation":"Clin Biochem Rev","author":[{"family":"Wilcox","given":"Gisela"}],"issued":{"date-parts":[["2005",5]]}}},{"id":2381,"uris":[""],"uri":[""],"itemData":{"id":2381,"type":"article-journal","title":"Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease","container-title":"International Journal of Molecular Sciences","page":"6184-6223","volume":"15","issue":"4","source":"PubMed Central","abstract":"Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines.","DOI":"10.3390/ijms15046184","ISSN":"1422-0067","note":"PMID: 24733068\nPMCID: PMC4013623","title-short":"Obesity and Its Metabolic Complications","journalAbbreviation":"Int J Mol Sci","author":[{"family":"Jung","given":"Un Ju"},{"family":"Choi","given":"Myung-Sook"}],"issued":{"date-parts":[["2014",4,11]]}}},{"id":2419,"uris":[""],"uri":[""],"itemData":{"id":2419,"type":"article-journal","title":"The Metabolic Syndrome in Australia: Prevalence using four definitions","container-title":"Diabetes Research and Clinical Practice","page":"471-478","volume":"77","issue":"3","source":"Crossref","abstract":"Objective: To compare the prevalence of the Metabolic Syndrome (MetS) de?ned by four de?nitions and to determine which de?nition best identi?es those at high cardiovascular disease (CVD) risk and with insulin resistance.\nMethods: AusDiab is a population-based survey of 11,247 Australians. Participants had anthropometry, blood pressure, and fasting biochemistry. Ten-year CVD risk was calculated.\nResults: The prevalence of the MetS using the ATPIII, WHO, IDF, and EGIR de?nitions was 22.1% (95%Cl: 18.8, 25.4), 21.7% (19.0, 24.3), 30.7% (27.1, 34.3), and 13.4% (11.8, 14.9), respectively. Comparing those with to those without the MetS, the odds ratios (95%CI) for having a 10 year CVD risk !15% were 6.6 (5.4, 8.2), 5.5 (4.7, 6.5), 5.6 (4.8, 6.6), and 3.5 (3.0, 4.1), for the WHO, ATPIII, IDF, and EGIR de?nitions, respectively. The population attributable risk (PAR) of high CVD risk due to the MetS was highest for the IDF (23.4%). Insulin resistance was detected in 56.1, 69.7, 50.9, and 91.1% of those meeting the ATPIII, WHO, IDF, and EGIR de?nitions, respectively.\nConclusion: The WHO de?nition was associated with the greatest CVD risk, but is not practical for clinical use. The higher PAR due to the IDF de?nition, with only slightly lower CVD risk than WHO, and clinical utility of the IDF de?nition, indicates that it may be a useful tool for CVD prevention.","DOI":"10.1016/j.diabres.2007.02.002","ISSN":"01688227","title-short":"The Metabolic Syndrome in Australia","language":"en","author":[{"family":"Cameron","given":"Adrian J."},{"family":"Magliano","given":"Dianna J."},{"family":"Zimmet","given":"Paul Z."},{"family":"Welborn","given":"Tim"},{"family":"Shaw","given":"Jonathan E."}],"issued":{"date-parts":[["2007",9]]}}}],"schema":""} 1–3 This occurs at the liver and muscle tissue, but the fat still remains sensitive to insulin and keeps storing fat. Once we are insulin resistant, all carbohydrates including “healthy” carbohydrates stimulate a large and prolonged insulin surge ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Pt0A7YZU","properties":{"formattedCitation":"\\super 4\\nosupersub{}","plainCitation":"4","noteIndex":0},"citationItems":[{"id":2191,"uris":[""],"uri":[""],"itemData":{"id":2191,"type":"article-journal","title":"Patterns of Insulin Concentration During the OGTT Predict the Risk of Type 2 Diabetes in Japanese Americans","container-title":"Diabetes Care","page":"1229-1235","volume":"36","issue":"5","source":"PubMed Central","abstract":"OBJECTIVE\nTo examine whether the patterns of insulin concentration during the oral glucose tolerance test (OGTT) predict type 2 diabetes.\n\nRESEARCH DESIGN AND METHODS\nWe followed 400 nondiabetic Japanese Americans for 10–11 years. Insulin concentrations at 30, 60, and 120 min during a 2-h 75-g OGTT at baseline were used to derive the following possible patterns of insulin: pattern 1 (30-min peak, higher insulin level at 60 than at 120 min), pattern 2 (30-min peak, lower or equal level at 60 vs. 120 min), pattern 3 (60-min peak); pattern 4 (120-min peak, lower level at 30 than at 60 min), and pattern 5 (120-min peak, equal or higher level at 30 vs. 60 min). Insulin sensitivity was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Insulin secretion was estimated by the insulinogenic index (IGI) [Δinsulin/Δglucose (30–0 min)] and disposition index (IGI/HOMA-IR).\n\nRESULTS\nThere were 86 incident cases of type 2 diabetes. The cumulative incidence was 3.2, 9.8, 15.4, 47.8, and 37.5% for patterns 1, 2, 3, 4, and 5, respectively. Compared with pattern 1, patterns 4 and 5, characterized by a lasting late insulin response, were associated with significantly less insulin sensitivity as measured by the Matsuda index and lower early insulin response by the disposition index. The multiple-adjusted odds ratios of type 2 diabetes were 12.55 (95% CI 4.79–32.89) for pattern 4 and 8.34 (2.38–29.27) for pattern 5 compared with patterns 1 and 2. This association was independent of insulin secretion and sensitivity.\n\nCONCLUSIONS\nThe patterns of insulin concentration during an OGTT strongly predict the development of type 2 diabetes.","DOI":"10.2337/dc12-0246","ISSN":"0149-5992","note":"PMID: 23275353\nPMCID: PMC3631850","journalAbbreviation":"Diabetes Care","author":[{"family":"Hayashi","given":"Tomoshige"},{"family":"Boyko","given":"Edward J."},{"family":"Sato","given":"Kyoko Kogawa"},{"family":"McNeely","given":"Marguerite J."},{"family":"Leonetti","given":"Donna L."},{"family":"Kahn","given":"Steven E."},{"family":"Fujimoto","given":"Wilfred Y."}],"issued":{"date-parts":[["2013",5]]}}}],"schema":""} 4, and we develop the “Metabolic Syndrome”. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"eum2JCru","properties":{"formattedCitation":"\\super 5,6\\nosupersub{}","plainCitation":"5,6","noteIndex":0},"citationItems":[{"id":2194,"uris":[""],"uri":[""],"itemData":{"id":2194,"type":"article-journal","title":"Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials","container-title":"The British Journal of Nutrition","page":"466-479","volume":"115","issue":"3","source":"PubMed","abstract":"The effects of low-carbohydrate (LC) diets on body weight and cardiovascular risk are unclear, and previous studies have found varying results. Our aim was to conduct a meta-analysis of randomised controlled trials (RCT), assessing the effects of LC diets v. low-fat (LF) diets on weight loss and risk factors of CVD. Studies were identified by searching MEDLINE, Embase and Cochrane Trials. Studies had to fulfil the following criteria: a RCT; the LC diet was defined in accordance with the Atkins diet, or carbohydrate intake of <20% of total energy intake; twenty subjects or more per group; the subjects were previously healthy; and the dietary intervention had a duration of 6 months or longer. Results from individual studies were pooled as weighted mean difference (WMD) using a random effect model. In all, eleven RCT with 1369 participants met all the set eligibility criteria. Compared with participants on LF diets, participants on LC diets experienced a greater reduction in body weight (WMD -2·17 kg; 95% CI -3·36, -0·99) and TAG (WMD -0·26 mmol/l; 95% CI -0·37, -0·15), but a greater increase in HDL-cholesterol (WMD 0·14 mmol/l; 95% CI 0·09, 0·19) and LDL-cholesterol (WMD 0·16 mmol/l; 95% CI 0·003, 0·33). This meta-analysis demonstrates opposite change in two important cardiovascular risk factors on LC diets--greater weight loss and increased LDL-cholesterol. Our findings suggest that the beneficial changes of LC diets must be weighed against the possible detrimental effects of increased LDL-cholesterol.","DOI":"10.1017/S0007114515004699","ISSN":"1475-2662","note":"PMID: 26768850","title-short":"Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors","journalAbbreviation":"Br. J. Nutr.","language":"eng","author":[{"family":"Mansoor","given":"Nadia"},{"family":"Vinknes","given":"Kathrine J."},{"family":"Veier?d","given":"Marit B."},{"family":"Retterst?l","given":"Kjetil"}],"issued":{"date-parts":[["2016",2,14]]}}},{"id":2166,"uris":[""],"uri":[""],"itemData":{"id":2166,"type":"article-journal","title":"Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors: A Multi-Center, Cross-Sectional, Clinical Study","container-title":"High Blood Pressure & Cardiovascular Prevention","page":"389-394","volume":"22","issue":"4","source":"PubMed Central","abstract":"Introduction\nObesity is a constantly growing illness in developed countries and it is strictly related to cardiovascular (CV) diseases, i.e. the main cause of mortality throughout industralised areas.\n\nAim\nto test the ability of trained general physician to safely and effectively prescribe a very-low carbohydrate ketogenic (VLCK) diet in clinical practice, with a specific attention to the effect of this approach on overweight related CV risk factors (anthropometric measures) blood pressure, lipid levels, glucose metabolism).\n\nMethods\nThe study has been carried out on a group of 377 patients scattered across Italy and monitored during 1?year. The proposed VLCK diet is a nutritional regimen characterized by low-fat and low- carbohydrates formulations and a \nprotein content of 1.2/1.5?g/kg of ideal body weight, followed by a period of slow re-insertion and alimentary re-education.\n\nResults\nAll the predetermined goals—namely safety, reduction of body weight and CV risk factors levels—have been reached with a significant reduction of body weight (from baseline to 4?weeks (?7?±?5?kg, p?<?0.001), from 4 to 12?weeks (?5?±?3?kg, p?<?0.001), no changes from 12?weeks to 12?months; waistline (from baseline to 4?weeks (?7?±?4?cm, p?<?0.001), from 4 to 12?weeks (?5?±?7?cm, p?<?0.001), no changes from 12?weeks to 12?months; fatty mass (from baseline to 4?weeks (?3.8?±?3.8?%, p?<?0.001), from 4 to 12?weeks (?3.4?±?3.5?%, p?<?0.001), no changes from 12?weeks to 12?months; SBP from baseline to 3?months (?10.5?±?6.4?mmHg, p?<?0.001), no further changes after 1?year of observation).\n\nConclusion\nthe tested VLCD diet suggested by trained general physicians in the setting of clinical practice seems to be able to significantly improve on the middle-term a number of anthropometric, haemodynamic and laboratory with an overall good tolerability.","DOI":"10.1007/s40292-015-0096-1","ISSN":"1120-9879","note":"PMID: 25986079\nPMCID: PMC4666896","title-short":"Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors","journalAbbreviation":"High Blood Press Cardiovasc Prev","author":[{"family":"Cicero","given":"Arrigo F. G."},{"family":"Benelli","given":"Maddalena"},{"family":"Brancaleoni","given":"Marco"},{"family":"Dainelli","given":"Giuseppe"},{"family":"Merlini","given":"Desiré"},{"family":"Negri","given":"Raffaele"}],"issued":{"date-parts":[["2015"]]}}}],"schema":""} 5,6All the features of the metabolic syndrome are effectively treatedThis includes obesity ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"kvF6HyTI","properties":{"formattedCitation":"\\super 7,8\\nosupersub{}","plainCitation":"7,8","noteIndex":0},"citationItems":[{"id":710,"uris":[""],"uri":[""],"itemData":{"id":710,"type":"article-journal","title":"Effects of Low-Carbohydrate and Low-Fat DietsA Randomized TrialEffects of Low-Carbohydrate and Low-Fat Diets","container-title":"Annals of Internal Medicine","page":"309-318","volume":"161","issue":"5","source":"Silverchair","abstract":"Background: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.Objective: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.Design: A randomized, parallel-group trial. (: NCT00609271)Setting: A large academic medical center.Participants: 148 men and women without clinical cardiovascular disease and diabetes.Intervention: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.Measurements: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.Results: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, ?3.5 kg [95% CI, ?5.6 to ?1.4 kg]; P?= 0.002), fat mass (mean difference in change, ?1.5% [CI, ?2.6% to ?0.4%]; P?= 0.011), ratio of total–high-density lipoprotein (HDL) cholesterol (mean difference in change, ?0.44 [CI, ?0.71 to ?0.16]; P?= 0.002), and triglyceride level (mean difference in change, ?0.16 mmol/L [?14.1 mg/dL] [CI, ?0.31 to ?0.01 mmol/L {?27.4 to ?0.8 mg/dL}]; P?= 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P?< 0.001) than those on the low-fat diet.Limitation: Lack of clinical cardiovascular disease end points.Conclusion: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.Primary Funding Source: National Institutes of Health.","DOI":"10.7326/M14-0180","ISSN":"0003-4819","journalAbbreviation":"Ann Intern Med","author":[{"family":"Bazzano","given":"Lydia A."},{"family":"Hu","given":"Tian"},{"family":"Reynolds","given":"Kristi"},{"family":"Yao","given":"Lu"},{"family":"Bunol","given":"Calynn"},{"family":"Liu","given":"Yanxi"},{"family":"Chen","given":"Chung-Shiuan"},{"family":"Klag","given":"Michael J."},{"family":"Whelton","given":"Paul K."},{"family":"He","given":"Jiang"}],"issued":{"date-parts":[["2014",9,2]]}}},{"id":560,"uris":[""],"uri":[""],"itemData":{"id":560,"type":"article-journal","title":"Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet","container-title":"The New England Journal of Medicine","page":"229-241","volume":"359","issue":"3","source":"PubMed","abstract":"BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates.\nMETHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie.\nRESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels).\nCONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. ( number, NCT00160108.)","DOI":"10.1056/NEJMoa0708681","ISSN":"1533-4406","note":"PMID: 18635428","journalAbbreviation":"N. Engl. J. Med.","language":"eng","author":[{"family":"Shai","given":"Iris"},{"family":"Schwarzfuchs","given":"Dan"},{"family":"Henkin","given":"Yaakov"},{"family":"Shahar","given":"Danit R."},{"family":"Witkow","given":"Shula"},{"family":"Greenberg","given":"Ilana"},{"family":"Golan","given":"Rachel"},{"family":"Fraser","given":"Drora"},{"family":"Bolotin","given":"Arkady"},{"family":"Vardi","given":"Hilel"},{"family":"Tangi-Rozental","given":"Osnat"},{"family":"Zuk-Ramot","given":"Rachel"},{"family":"Sarusi","given":"Benjamin"},{"family":"Brickner","given":"Dov"},{"family":"Schwartz","given":"Ziva"},{"family":"Sheiner","given":"Einat"},{"family":"Marko","given":"Rachel"},{"family":"Katorza","given":"Esther"},{"family":"Thiery","given":"Joachim"},{"family":"Fiedler","given":"Georg Martin"},{"family":"Blüher","given":"Matthias"},{"family":"Stumvoll","given":"Michael"},{"family":"Stampfer","given":"Meir J."},{"literal":"Dietary Intervention Randomized Controlled Trial (DIRECT) Group"}],"issued":{"date-parts":[["2008",7,17]]}}}],"schema":""} 7,8 and complications such as high blood pressure, infertility ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jbvQDEVJ","properties":{"formattedCitation":"\\super 9\\nosupersub{}","plainCitation":"9","noteIndex":0},"citationItems":[{"id":285,"uris":[""],"uri":[""],"itemData":{"id":285,"type":"article-journal","title":"Does weight loss in overweight or obese women improve fertility treatment outcomes? A systematic review","container-title":"Obesity Reviews: An Official Journal of the International Association for the Study of Obesity","page":"839-850","volume":"15","issue":"10","source":"PubMed","abstract":"This systematic review assessed the effect of weight loss in overweight and/or obese women undergoing assisted reproductive technology (ART) on their subsequent pregnancy outcome. Weight losses achieved by diet and lifestyle changes, very-low-energy diets, non-surgical medical interventions and bariatric surgery translated into significantly increased pregnancy rates and/or live birth in overweight and/or obese women undergoing ART in 8 of the 11 studies reviewed. In addition, regularization of the menstrual pattern, a decrease in cancellation rates, an increase in the number of embryos available for transfer, a reduction in the number of ART cycles required to achieve pregnancy and a decrease in miscarriage rates were reported. There were also a number of natural conceptions in five of the six studies that reported this outcome. Non-surgical medical weight loss procedures and bariatric surgery induced the greatest weight losses, but their use, as well as that of very-low-energy diets, for weight loss prior to ART requires careful consideration. While the overall quality of the studies included in this review was poor, these results support the clinical recommendation of advising overweight and/or obese women to lose weight prior to ART. Prospective randomized controlled trials are required to establish efficacious evidence-based guidelines for weight loss interventions in overweight and/or obese women prior to ART treatment.","DOI":"10.1111/obr.12217","ISSN":"1467-789X","note":"PMID: 25132280","title-short":"Does weight loss in overweight or obese women improve fertility treatment outcomes?","journalAbbreviation":"Obes Rev","language":"eng","author":[{"family":"Sim","given":"K. A."},{"family":"Partridge","given":"S. R."},{"family":"Sainsbury","given":"A."}],"issued":{"date-parts":[["2014",10]]}}}],"schema":""} 9, sleep apnea ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"xMX6bQ8Q","properties":{"formattedCitation":"\\super 10\\nosupersub{}","plainCitation":"10","noteIndex":0},"citationItems":[{"id":2454,"uris":[""],"uri":[""],"itemData":{"id":2454,"type":"article-journal","title":"Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis","container-title":"Sleep Medicine","page":"92-99","volume":"55","source":"ScienceDirect","abstract":"Objective\nSleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach on sleep quality using a subjective patient-reported sleep questionnaire.\nMethods\nA non-randomized, controlled longitudinal study; 262 T2D and 116 prediabetes patients enrolled in the CCI and 87 separately recruited T2D patients continued usual care (UC) treatment. Patients completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A PSQI score of >5 (scale 0 to 21) was used to identify poor sleepers.\nResults\nGlobal sleep quality improved in the CCI T2D (p?<?0.001) and prediabetes (p?<?0.001) patients after one year of intervention. Subjective sleep quality (component 1), sleep disturbance (component 5) and daytime dysfunction (component 7), also showed improvements in the CCI T2D (p?<?0.01 for sleep quality and sleep disturbance; and p?<?0.001 for daytime dysfunction) and prediabetes patients (p?<?0.001 for all three components); compared to the UC T2D group after one year. The proportion of patients with poor sleep quality was significantly reduced after one year of CCI (T2D; from 68.3% at baseline to 56.5% at one year, p?=?0.001 and prediabetes; from 77.9% at baseline to 48.7% at one year, p?<?0.001).\nConclusion\nThis study demonstrates improved sleep quality as assessed by PSQI in patients with T2D and prediabetes undergoing CCI including nutritional ketosis but not in T2D patients receiving UC. The dietary intervention benefited both sleep quality and the severity of T2D symptoms suggesting that nutritional ketosis improves overall health via multiple mechanisms.","DOI":"10.1016/j.sleep.2018.12.014","ISSN":"1389-9457","journalAbbreviation":"Sleep Medicine","author":[{"family":"Siegmann","given":"Morgan J."},{"family":"Athinarayanan","given":"Shaminie J."},{"family":"Hallberg","given":"Sarah J."},{"family":"McKenzie","given":"Amy L."},{"family":"Bhanpuri","given":"Nasir H."},{"family":"Campbell","given":"Wayne W."},{"family":"McCarter","given":"James P."},{"family":"Phinney","given":"Stephen D."},{"family":"Volek","given":"Jeff S."},{"family":"Van Dort","given":"Christa J."}],"issued":{"date-parts":[["2019",3,1]]}}}],"schema":""} 10, high triglycerides (dissolved fats in the blood), low HDL (the “good” cholesterol particles) and high blood sugars (i.e. pre-diabetes) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"37jb2pcy","properties":{"formattedCitation":"\\super 11,12\\nosupersub{}","plainCitation":"11,12","noteIndex":0},"citationItems":[{"id":2453,"uris":[""],"uri":[""],"itemData":{"id":2453,"type":"article-journal","title":"Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1?year: an open label, non-randomized, controlled study","container-title":"Cardiovascular Diabetology","page":"56","volume":"17","issue":"1","source":"BioMed Central","abstract":"Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.","DOI":"10.1186/s12933-018-0698-8","ISSN":"1475-2840","title-short":"Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1?year","journalAbbreviation":"Cardiovascular Diabetology","author":[{"family":"Bhanpuri","given":"Nasir H."},{"family":"Hallberg","given":"Sarah J."},{"family":"Williams","given":"Paul T."},{"family":"McKenzie","given":"Amy L."},{"family":"Ballard","given":"Kevin D."},{"family":"Campbell","given":"Wayne W."},{"family":"McCarter","given":"James P."},{"family":"Phinney","given":"Stephen D."},{"family":"Volek","given":"Jeff S."}],"issued":{"date-parts":[["2018",5,1]]}}},{"id":2138,"uris":[""],"uri":[""],"itemData":{"id":2138,"type":"article-journal","title":"Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study","container-title":"Diabetes Therapy","source":"Crossref","abstract":"Introduction: Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management.","URL":"","DOI":"10.1007/s13300-018-0373-9","ISSN":"1869-6953, 1869-6961","title-short":"Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year","language":"en","author":[{"family":"Hallberg","given":"Sarah J."},{"family":"McKenzie","given":"Amy L."},{"family":"Williams","given":"Paul T."},{"family":"Bhanpuri","given":"Nasir H."},{"family":"Peters","given":"Anne L."},{"family":"Campbell","given":"Wayne W."},{"family":"Hazbun","given":"Tamara L."},{"family":"Volk","given":"Brittanie M."},{"family":"McCarter","given":"James P."},{"family":"Phinney","given":"Stephen D."},{"family":"Volek","given":"Jeff S."}],"issued":{"date-parts":[["2018",2,7]]},"accessed":{"date-parts":[["2019",1,11]]}}}],"schema":""} 11,12. This means a smaller belt size and less medications ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"oaItTEUQ","properties":{"formattedCitation":"\\super 13\\nosupersub{}","plainCitation":"13","noteIndex":0},"citationItems":[{"id":2452,"uris":[""],"uri":[""],"itemData":{"id":2452,"type":"article-journal","title":"A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes","container-title":"JMIR Diabetes","page":"e5","volume":"2","issue":"1","source":"diabetes.","abstract":"Background: Type 2 diabetes (T2D) is typically managed with a reduced fat diet plus glucose-lowering medications, the latter often promoting weight gain. Objective: We evaluated whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of a comprehensive intervention, thereby improving glycemic control, decreasing medication use, and allowing clinically relevant weight loss. Methods: This study was a nonrandomized, parallel arm, outpatient intervention. Adults with T2D (N=262; mean age 54, SD 8, years; mean body mass index 41, SD 8, kg·m?2; 66.8% (175/262) women) were enrolled in an outpatient protocol providing intensive nutrition and behavioral counseling, digital coaching and education platform, and physician-guided medication management. A total of 238 participants completed the first 10 weeks. Body weight, capillary blood glucose, and beta-hydroxybutyrate (BOHB) levels were recorded daily using a mobile interface. Hemoglobin A1c (HbA1c) and related biomarkers of T2D were evaluated at baseline and 10-week follow-up. Results: Baseline HbA1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had an HbA1c level of <6.5%. After 10 weeks, HbA1c level was reduced by 1.0% (SD 1.1%; 95% CI 0.9% to 1.1%, P<.001), and the percentage of individuals with an HbA1c level of <6.5% increased to 56.1% (147/262). The majority of participants (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10 weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced or eliminated. At follow-up, 47.7% of participants (125/262) achieved an HbA1c level of <6.5% while taking metformin only (n=86) or no diabetes medications (n=39). Mean body mass reduction was 7.2% (SD 3.7%; 95% CI 5.8% to 7.7%, P<.001) from baseline (117, SD 26, kg). Mean BOHB over 10 weeks was 0.6 (SD 0.6) mmol·L?1 indicating consistent carbohydrate restriction. Post hoc comparison of the remote versus on-site means of education revealed no effect of delivery method on change in HbA1c (F1,260=1.503, P=.22). Conclusions: These initial results indicate that an individualized program delivered and supported remotely that incorporates nutritional ketosis can be highly effective in improving glycemic control and weight loss in adults with T2D while significantly decreasing medication use. [JMIR Diabetes 2017;2(1):e5]","DOI":"10.2196/diabetes.6981","language":"en","author":[{"family":"McKenzie","given":"Amy L."},{"family":"Hallberg","given":"Sarah J."},{"family":"Creighton","given":"Brent C."},{"family":"Volk","given":"Brittanie M."},{"family":"Link","given":"Theresa M."},{"family":"Abner","given":"Marcy K."},{"family":"Glon","given":"Roberta M."},{"family":"McCarter","given":"James P."},{"family":"Volek","given":"Jeff S."},{"family":"Phinney","given":"Stephen D."}],"issued":{"date-parts":[["2017"]]}}}],"schema":""} 13.Improvement in pain and inflammatory markersJoint pain and soft tissue injury are among the earliest signs of poor metabolic health and can be seen as an opportunity to restore health. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1XSvt27t","properties":{"formattedCitation":"\\super 14,15\\nosupersub{}","plainCitation":"14,15","noteIndex":0},"citationItems":[{"id":48,"uris":[""],"uri":[""],"itemData":{"id":48,"type":"article-journal","title":"The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis","container-title":"Pain Medicine","source":"Crossref","abstract":"Objective. Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-in?ammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the ef?cacy of a dietary intervention to reduce KOA. Design. A randomized controlled pilot study to test the ef?cacy of two dietary interventions. Subjects. Adults 65–75 years of age with KOA. Methods. Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. Results. Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also signi?cantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. Conclusions. We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.","URL":"","DOI":"10.1093/pm/pnz022","ISSN":"1526-2375, 1526-4637","language":"en","author":[{"family":"Strath","given":"Larissa J"},{"family":"Jones","given":"Catherine D"},{"family":"Philip George","given":"Alan"},{"family":"Lukens","given":"Shannon L"},{"family":"Morrison","given":"Shannon A"},{"family":"Soleymani","given":"Taraneh"},{"family":"Locher","given":"Julie L"},{"family":"Gower","given":"Barbara A"},{"family":"Sorge","given":"Robert E"}],"issued":{"date-parts":[["2019",3,13]]},"accessed":{"date-parts":[["2019",5,4]]}}},{"id":695,"uris":[""],"uri":[""],"itemData":{"id":695,"type":"article-journal","title":"Effect of an advanced glycation end product-restricted diet and exercise on metabolic parameters in adult overweight men","container-title":"Nutrition (Burbank, Los Angeles County, Calif.)","page":"446-451","volume":"31","issue":"3","source":"PubMed","abstract":"OBJECTIVES: The aim of this study was to review the effect of a low advanced glycation end product (AGEs) diet, exercise, and a combination of both on circulating AGE levels as well as on plasma lipids and anthropometric parameters.\nMETHODS: Forty-three overweight or obese men (body mass index [BMI] >25 kg/m(2)), 30 to 55 y, participated in a 12-wk study and were randomly assigned to one of three groups: low AGE diet, exercise with habitual food intake, or exercise plus low AGE diet. Exercise was for 45 min at 65% to 75% of their maximum heart rate three times a week. We measured somatometric variables (BMI and waist circumference), blood glucose, lipids, and serum AGEs (N(ε)-[Carboxymethyl]Lysine [CML] and methylglyoxal [MG]) at baseline and at 12 wk.\nRESULTS: Exercise alone was associated with decreased somatometric variables; the low AGE diet had the same effects and decreased serum CML and MG and when combined with exercise reproduced all these effects, but also decreased triacylglycerols and increased high-density lipoprotein. Correlation analysis showed that both changes of CML and MG correlated with changes in dietary AGEs (P < 0.020 and P < 0.038, respectively); change in maximum oxygen consumption correlated inversely with change in weight and triacylglycerols. Regression analyses, including change in dietary AGEs and in dietary calories, showed that change in dietary AGEs was the independent determinant of change in CML (P < 0.020) and MG (P < 0.038).\nCONCLUSIONS: An AGE-restricted diet reduces serum AGE and indices of body fat. The addition of exercise to the restricted diet has the same effects but also improves lipid profile.","DOI":"10.1016/j.nut.2014.10.004","ISSN":"1873-1244","note":"PMID: 25701333","journalAbbreviation":"Nutrition","language":"eng","author":[{"family":"Macías-Cervantes","given":"Maciste Habacuc"},{"family":"Rodríguez-Soto","given":"Juana María Dolores"},{"family":"Uribarri","given":"Jaime"},{"family":"Díaz-Cisneros","given":"Francisco José"},{"family":"Cai","given":"Weijingi"},{"family":"Garay-Sevilla","given":"Ma Eugenia"}],"issued":{"date-parts":[["2015",3]]}}}],"schema":""} 14,15 This is why many Sports Physicians are major advocates for this diet and lifestyle; given the unique advantage of intervening prior to major events like stroke or heart attack.Reversal of metabolic disease, Insulin Resistance and even DiabetesWhen we are young and healthy, we can tolerate a lot of carbohydrates. However, with ageing, time, stress, sugar intake and the development of “insulin resistance”, carbohydrates perpetuate high insulin levels and poor metabolic health. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"69ZTsVGT","properties":{"formattedCitation":"\\super 16,17\\nosupersub{}","plainCitation":"16,17","noteIndex":0},"citationItems":[{"id":697,"uris":[""],"uri":[""],"itemData":{"id":697,"type":"article-journal","title":"Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?","container-title":"Archives of Medical Science : AMS","page":"8-20","volume":"7","issue":"1","source":"PubMed Central","abstract":"The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.","DOI":"10.5114/aoms.2011.20598","ISSN":"1734-1922","note":"PMID: 22291727\nPMCID: PMC3258689","journalAbbreviation":"Arch Med Sci","author":[{"family":"Seneff","given":"Stephanie"},{"family":"Wainwright","given":"Glyn"},{"family":"Mascitelli","given":"Luca"}],"issued":{"date-parts":[["2011",2]]}}},{"id":701,"uris":[""],"uri":[""],"itemData":{"id":701,"type":"article-journal","title":"A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes","container-title":"PloS One","page":"e91027","volume":"9","issue":"4","source":"PubMed","abstract":"We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n?=?18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n?=?16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p?=?0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p?=?0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p?=?0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p?=?0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with , number NCT01713764.","DOI":"10.1371/journal.pone.0091027","ISSN":"1932-6203","note":"PMID: 24717684\nPMCID: PMC3981696","journalAbbreviation":"PLoS ONE","language":"eng","author":[{"family":"Saslow","given":"Laura R."},{"family":"Kim","given":"Sarah"},{"family":"Daubenmier","given":"Jennifer J."},{"family":"Moskowitz","given":"Judith T."},{"family":"Phinney","given":"Stephen D."},{"family":"Goldman","given":"Veronica"},{"family":"Murphy","given":"Elizabeth J."},{"family":"Cox","given":"Rachel M."},{"family":"Moran","given":"Patricia"},{"family":"Hecht","given":"Fredrick M."}],"issued":{"date-parts":[["2014"]]}}}],"schema":""} 16,17 Many patients with Type 2 Diabetes can improve and even reverse their disease with the use of a low carbohydrate diet. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"DiRTQauR","properties":{"formattedCitation":"\\super 12\\nosupersub{}","plainCitation":"12","noteIndex":0},"citationItems":[{"id":2138,"uris":[""],"uri":[""],"itemData":{"id":2138,"type":"article-journal","title":"Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study","container-title":"Diabetes Therapy","source":"Crossref","abstract":"Introduction: Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management.","URL":"","DOI":"10.1007/s13300-018-0373-9","ISSN":"1869-6953, 1869-6961","title-short":"Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year","language":"en","author":[{"family":"Hallberg","given":"Sarah J."},{"family":"McKenzie","given":"Amy L."},{"family":"Williams","given":"Paul T."},{"family":"Bhanpuri","given":"Nasir H."},{"family":"Peters","given":"Anne L."},{"family":"Campbell","given":"Wayne W."},{"family":"Hazbun","given":"Tamara L."},{"family":"Volk","given":"Brittanie M."},{"family":"McCarter","given":"James P."},{"family":"Phinney","given":"Stephen D."},{"family":"Volek","given":"Jeff S."}],"issued":{"date-parts":[["2018",2,7]]},"accessed":{"date-parts":[["2019",1,11]]}}}],"schema":""} 12 While we need fat and protein to survive, there is simply no such thing as carbohydrate deficiency.All critical measures of Cholesterol improve on a low carbohydrate dietThere is concern from patients that cholesterol will rise when more dietary fat is eaten. High quality research continues to show that a higher fat diet is safe and is not linked to heart disease- de-bunking the old “diet-heart” hypothesis of heart disease. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MlqQ3Yyj","properties":{"formattedCitation":"\\super 18\\nosupersub{}","plainCitation":"18","noteIndex":0},"citationItems":[{"id":2186,"uris":[""],"uri":[""],"itemData":{"id":2186,"type":"article-journal","title":"Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)","container-title":"The BMJ","volume":"353","source":"PubMed Central","abstract":"Objective?To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis., Design?The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted., Setting?One nursing home and six state mental hospitals in Minnesota, United States., Participants?Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files., Interventions?Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings., Main outcome measures?Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy., Results?The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline ?13.8% v ?1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10?808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27)., Conclusions?Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.","URL":"","DOI":"10.1136/bmj.i1246","ISSN":"0959-8138","note":"PMID: 27071971\nPMCID: PMC4836695","title-short":"Re-evaluation of the traditional diet-heart hypothesis","journalAbbreviation":"BMJ","author":[{"family":"Ramsden","given":"Christopher E"},{"family":"Zamora","given":"Daisy"},{"family":"Majchrzak-Hong","given":"Sharon"},{"family":"Faurot","given":"Keturah R"},{"family":"Broste","given":"Steven K"},{"family":"Frantz","given":"Robert P"},{"family":"Davis","given":"John M"},{"family":"Ringel","given":"Amit"},{"family":"Suchindran","given":"Chirayath M"},{"family":"Hibbeln","given":"Joseph R"}],"issued":{"date-parts":[["2016",4,12]]},"accessed":{"date-parts":[["2019",1,3]]}}}],"schema":""} 18 The overall effects of a low carbohydrate diet on the body’s processing of cholesterol and fat is favourable and this is consistently seen. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"28CXKGQX","properties":{"formattedCitation":"\\super 11,19\\uc0\\u8211{}22\\nosupersub{}","plainCitation":"11,19–22","noteIndex":0},"citationItems":[{"id":2453,"uris":[""],"uri":[""],"itemData":{"id":2453,"type":"article-journal","title":"Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1?year: an open label, non-randomized, controlled study","container-title":"Cardiovascular Diabetology","page":"56","volume":"17","issue":"1","source":"BioMed Central","abstract":"Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.","DOI":"10.1186/s12933-018-0698-8","ISSN":"1475-2840","title-short":"Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1?year","journalAbbreviation":"Cardiovascular Diabetology","author":[{"family":"Bhanpuri","given":"Nasir H."},{"family":"Hallberg","given":"Sarah J."},{"family":"Williams","given":"Paul T."},{"family":"McKenzie","given":"Amy L."},{"family":"Ballard","given":"Kevin D."},{"family":"Campbell","given":"Wayne W."},{"family":"McCarter","given":"James P."},{"family":"Phinney","given":"Stephen D."},{"family":"Volek","given":"Jeff S."}],"issued":{"date-parts":[["2018",5,1]]}}},{"id":2163,"uris":[""],"uri":[""],"itemData":{"id":2163,"type":"article-journal","title":"Dietary Carbohydrates Impair Healthspan and Promote Mortality","container-title":"Cell Metabolism","page":"585-587","volume":"26","issue":"4","source":"","DOI":"10.1016/j.cmet.2017.09.011","ISSN":"1550-4131","note":"PMID: 28978421","journalAbbreviation":"Cell Metabolism","language":"English","author":[{"family":"Ravichandran","given":"Meenakshi"},{"family":"Grandl","given":"Gerald"},{"family":"Ristow","given":"Michael"}],"issued":{"date-parts":[["2017",10,3]]}}},{"id":2092,"uris":[""],"uri":[""],"itemData":{"id":2092,"type":"article-journal","title":"Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke","container-title":"European Journal of Neurology","page":"283-291","volume":"24","issue":"2","source":"Crossref","abstract":"Background and purpose: The e?ect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months.\nMethods: Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and lowdensity lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were de?ned according to the modi?ed Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0–1; good outcome, mRS 0–2; and death, mRS 6).\nResults: In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; speci?city 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; speci?city 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; speci?city 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% con?dence interval 1.89–4.55) compared with patients with a TG/HDLC ≥ 0.87.\nConclusions: A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS.","DOI":"10.1111/ene.13198","ISSN":"13515101","language":"en","author":[{"family":"Deng","given":"Q.-W."},{"family":"Wang","given":"H."},{"family":"Sun","given":"C.-Z."},{"family":"Xing","given":"F.-L."},{"family":"Zhang","given":"H.-Q."},{"family":"Zuo","given":"L."},{"family":"Gu","given":"Z.-T."},{"family":"Yan","given":"F.-L."}],"issued":{"date-parts":[["2017",2]]}}},{"id":2094,"uris":[""],"uri":[""],"itemData":{"id":2094,"type":"article-journal","title":"Association of serum lipids with clinical outcome in acute ischaemic stroke: A systematic review and meta-analysis","container-title":"Journal of Clinical Neuroscience","page":"236-244","volume":"59","source":"Crossref","abstract":"Serum lipid levels have been investigated as prognostic markers in patients with acute ischaemic stroke. However, these results remain inconsistent. This study aimed at assessing the association between serum lipid and clinical outcomes in acute ischaemic stroke. Relevant data were obtained from Cochrane Library, PubMed and Web of Science databases. The heterogeneity of pooled results was determined by the Cochran’s Q test and Higgins I-squared statistic. The random-effect model was performed to calculate the pooled results if PH < 0.05 for Q-test, otherwise the ?xed-effect model was applied. The primary results were death, and the secondary were recurrence, dependency, mRS score 3, and early neurological deterioration. A total of 21 full-text studies was included in the present study. For primary results, the pooled results from 5 studies with 4119 patients showed that triglyceride (TG) was a signi?cant predictor for death (OR = 0.65, 95%CI = 0.43–0.98, PH = 0.028). The pooled data from 11 studies with 12,486 patients for total cholesterol (TC), 4 studies with 7593 patients for low-density lipoprotein cholesterol (LDL-C), and 5 studies with 6933 patients for high-density lipoprotein cholesterol (HDL-C) suggested that TC (OR = 0.79, 95%CI = 0.56–1.13, PH < 0.001), LDL-C (OR = 1.02, 95%CI = 0.66–1.57, PH = 0.042), and HDL-C (OR = 1.18, 95%CI = 0.75–1.86, PH = 0.003) were not associated with death in acute ischaemic stroke. For secondary results, the pooled results of 2 studies with 867 patients indicated that TG was positively associated with early neurological deterioration. This study suggested that serum TG was associated with death and early neurological deterioration in acute ischaemic stroke.","DOI":"10.1016/j.jocn.2018.09.003","ISSN":"09675868","title-short":"Association of serum lipids with clinical outcome in acute ischaemic stroke","language":"en","author":[{"family":"Deng","given":"Qiwen"},{"family":"Li","given":"Shuo"},{"family":"Zhang","given":"Hanqing"},{"family":"Wang","given":"Huan"},{"family":"Gu","given":"Zhengtian"},{"family":"Zuo","given":"Lei"},{"family":"Wang","given":"Lvyue"},{"family":"Yan","given":"Fuling"}],"issued":{"date-parts":[["2019",1]]}}},{"id":2164,"uris":[""],"uri":[""],"itemData":{"id":2164,"type":"article-journal","title":"Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study","container-title":"The Lancet","page":"2050-2062","volume":"390","issue":"10107","source":"Crossref","abstract":"Background The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.","DOI":"10.1016/S0140-6736(17)32252-3","ISSN":"01406736","title-short":"Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE)","language":"en","author":[{"family":"Dehghan","given":"Mahshid"},{"family":"Mente","given":"Andrew"},{"family":"Zhang","given":"Xiaohe"},{"family":"Swaminathan","given":"Sumathi"},{"family":"Li","given":"Wei"},{"family":"Mohan","given":"Viswanathan"},{"family":"Iqbal","given":"Romaina"},{"family":"Kumar","given":"Rajesh"},{"family":"Wentzel-Viljoen","given":"Edelweiss"},{"family":"Rosengren","given":"Annika"},{"family":"Amma","given":"Leela Itty"},{"family":"Avezum","given":"Alvaro"},{"family":"Chifamba","given":"Jephat"},{"family":"Diaz","given":"Rafael"},{"family":"Khatib","given":"Rasha"},{"family":"Lear","given":"Scott"},{"family":"Lopez-Jaramillo","given":"Patricio"},{"family":"Liu","given":"Xiaoyun"},{"family":"Gupta","given":"Rajeev"},{"family":"Mohammadifard","given":"Noushin"},{"family":"Gao","given":"Nan"},{"family":"Oguz","given":"Aytekin"},{"family":"Ramli","given":"Anis Safura"},{"family":"Seron","given":"Pamela"},{"family":"Sun","given":"Yi"},{"family":"Szuba","given":"Andrzej"},{"family":"Tsolekile","given":"Lungiswa"},{"family":"Wielgosz","given":"Andreas"},{"family":"Yusuf","given":"Rita"},{"family":"Hussein Yusufali","given":"Afzal"},{"family":"Teo","given":"Koon K"},{"family":"Rangarajan","given":"Sumathy"},{"family":"Dagenais","given":"Gilles"},{"family":"Bangdiwala","given":"Shrikant I"},{"family":"Islam","given":"Shofiqul"},{"family":"Anand","given":"Sonia S"},{"family":"Yusuf","given":"Salim"},{"family":"Diaz","given":"R"},{"family":"Orlandini","given":"A"},{"family":"Linetsky","given":"B"},{"family":"Toscanelli","given":"S"},{"family":"Casaccia","given":"G"},{"family":"Cuneo","given":"JM 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This means we can measure whether your body has “Fat-adapted” and is burning fat as its main fuel. If you have no ketones, you are not burning fat. A ketone or continuous glucose meter can allow you to find your pitfalls and personalise your carbohydrate intake. Metabolic Medicine and Exercise Medicine- A Powerful Synergy For OsteoarthritisMost patients come to see Sports Physicians for the kinds of treatments we offer Elite Athletes. While some of these treatments include cutting edge technologies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"thDrNi5D","properties":{"formattedCitation":"\\super 23\\uc0\\u8211{}26\\nosupersub{}","plainCitation":"23–26","noteIndex":0},"citationItems":[{"id":7078,"uris":[""],"uri":[""],"itemData":{"id":7078,"type":"article-journal","title":"Osteoarthritis","container-title":"The Lancet","page":"1745-1759","volume":"393","issue":"10182","source":" (Crossref)","DOI":"10.1016/S0140-6736(19)30417-9","ISSN":"01406736","journalAbbreviation":"The Lancet","language":"en","author":[{"family":"Hunter","given":"David J"},{"family":"Bierma-Zeinstra","given":"Sita"}],"issued":{"date-parts":[["2019",4]]}}},{"id":2683,"uris":[""],"uri":[""],"itemData":{"id":2683,"type":"article-journal","title":"The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment","container-title":"Seminars in Arthritis and Rheumatism","page":"211-267","volume":"28","issue":"4","source":"PubMed","abstract":"OBJECTIVES: Structure-modifying osteoarthritis (OA) drugs (SMOADs) may be defined as agents that reverse, retard, or stabilize the underlying pathology of OA, thereby providing symptomatic relief in the long-term. The objective of this review was to evaluate the literature on sodium pentosan polysulfate (NaPPS) and calcium pentosan polysulfate (CaPPS), with respect to the pathobiology of OA to ascertain whether these agents should be classified as SMOADs.\nMETHODS: Published studies on NaPPS and CaPPS were selected on the basis of their relevance to the known pathobiology of OA, which also was reviewed.\nRESULTS: Both NaPPS and CaPPS exhibit a wide range of pharmacological activities. Of significance was the ability of these agents to support chondrocyte anabolic activities and attenuate catabolic events responsible for loss of components of the cartilage extracellular matrix in OA joints. Although some of the anti-catabolic activities may be mediated through direct enzyme inhibition, NaPPS and CaPPS also have been shown to enter chondrocytes and bind to promoter proteins and alter gene expression of matrix metalloproteinases and possibly other mediators. In rat models of arthritis, NaPPS and CaPPS reduced joint swelling and inflammatory mediator levels in pouch fluids. Moreover, synoviocyte biosynthesis of high-molecular-weight hyaluronan, which is diminished in OA, was normalized when these cells were incubated with NaPPS and CaPPS or after intraarticular injection of NaPPS into arthritic joints. In rabbit, canine, and ovine models of OA, NaPPS and CaPPS preserved cartilage integrity, proteoglycan synthesis, and reduced matrix metalloproteinase activity. NaPPS and CaPPS stimulated the release of tissue plasminogen activator (t-PA), superoxide dismutase, and lipases from vascular endothelium while concomitantly decreasing plasma levels of the endogenous plasminogen activator inhibitor PAI-1. The net thrombolytic and lipolytic effects exhibited by NaPPS and CaPPS may serve to improve blood flow through subchondral capillaries of OA joints and improve bone cell nutrition. In geriatric OA dogs, NaPPS and CaPPS reduced symptoms, as well as normalized their thrombolytic status, threshold for platelet activation, and plasma triglyceride levels. These hematologic parameters were shown to be abnormal in OA animals before drug treatment. Similar outcomes were observed in OA patients when CaPPS or NaPPS were given orally or parenterally in both open and double-blind trials.\nCONCLUSIONS: The data presented in this review support the contention that NaPPS and CaPPS should be classified as SMOADs. However, additional long-term clinical studies employing methods of assessing joint structural changes will be needed to confirm this view.","ISSN":"0049-0172","note":"PMID: 10073500","journalAbbreviation":"Semin. Arthritis Rheum.","language":"eng","author":[{"family":"Ghosh","given":"P."}],"issued":{"date-parts":[["1999",2]]}}},{"id":231,"uris":[""],"uri":[""],"itemData":{"id":231,"type":"article-journal","title":"Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis","container-title":"Annals of Internal Medicine","page":"46-54","volume":"162","issue":"1","source":"PubMed","abstract":"BACKGROUND: The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated.\nPURPOSE: To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other.\nDATA SOURCES: MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data.\nSTUDY SELECTION: Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo.\nDATA EXTRACTION: Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up.\nDATA SYNTHESIS: Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33,243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another.\nLIMITATION: Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons.\nCONCLUSION: This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions.\nPRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.","DOI":"10.7326/M14-1231","ISSN":"1539-3704","note":"PMID: 25560713","title-short":"Comparative effectiveness of pharmacologic interventions for knee osteoarthritis","journalAbbreviation":"Ann. Intern. Med.","language":"eng","author":[{"family":"Bannuru","given":"Raveendhara R."},{"family":"Schmid","given":"Christopher H."},{"family":"Kent","given":"David M."},{"family":"Vaysbrot","given":"Elizaveta E."},{"family":"Wong","given":"John B."},{"family":"McAlindon","given":"Timothy E."}],"issued":{"date-parts":[["2015",1,6]]}}},{"id":352,"uris":[""],"uri":[""],"itemData":{"id":352,"type":"article-journal","title":"Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial","container-title":"The American Journal of Sports Medicine","page":"356-364","volume":"41","issue":"2","source":"PubMed","abstract":"BACKGROUND: Specific growth factors have been proposed as therapeutic proteins for cartilage repair.\nHYPOTHESIS: Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee.\nSTUDY DESIGN: Randomized controlled trial; Level of evidence, 1.\nMETHODS: A total of 78 patients (156 knees) with bilateral OA were divided randomly into 3 groups. Group A (52 knees) received a single injection of PRP, group B (50 knees) received 2 injections of PRP 3 weeks apart, and group C (46 knees) received a single injection of normal saline. White blood cell (WBC)-filtered PRP with a platelet count 3 times that of baseline (PRP type 4B) was administered in all. All the groups were homogeneous and comparable in baseline characteristics. Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, and 6 months after treatment. They were also evaluated for pain by a visual analog scale, and overall satisfaction with the procedure and complications were noted.\nRESULTS: Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months, with slight worsening at the 6-month follow-up. The mean WOMAC scores (pain, stiffness, physical function, and total score) for group A at baseline were 10.18, 3.12, 36.56, and 49.86, respectively, and at final follow-up were 5.00, 2.10, 20.08, and 27.18, respectively, showing significant improvement. Similar improvement was noted in group B (mean WOMAC scores at baseline: 10.62, 3.50, 39.10, and 53.20, respectively; mean WOMAC scores at final follow-up: 6.18, 1.88, 22.40, and 30.48, respectively). In group C, the mean WOMAC scores deteriorated from baseline (9.04, 2.70, 33.80, and 45.54, respectively) to final follow-up (10.87, 2.76, 39.46, and 53.09, respectively). The 3 groups were compared with each other, and no improvement was noted in group C as compared with groups A and B (P < .001). There was no difference between groups A and B, and there was no influence of age, sex, weight, or body mass index on the outcome. Knees with Ahlback grade 1 fared better than those with grade 2. Mild complications such as nausea and dizziness, which were of short duration, were observed in 6 patients (22.2%) in group A and 11 patients (44%) in group B.\nCONCLUSION: A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA. The results, however, deteriorate after 6 months. Both groups treated with PRP had better results than did the group injected with saline only.","DOI":"10.1177/0363546512471299","ISSN":"1552-3365","note":"PMID: 23299850","title-short":"Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis","journalAbbreviation":"Am J Sports Med","language":"eng","author":[{"family":"Patel","given":"Sandeep"},{"family":"Dhillon","given":"Mandeep S."},{"family":"Aggarwal","given":"Sameer"},{"family":"Marwaha","given":"Neelam"},{"family":"Jain","given":"Ashish"}],"issued":{"date-parts":[["2013",2]]}}}],"schema":""} 23–26, most athletes already maintain a strict regime of intense exercise, carefully planned rest periods and a very healthful diet.We believe patients should strive for optimal health, and the team at Sports Lab will treat you with the same best evidence-based approach. While we are happy to offer the best science has to offer, the truth is that the largest improvements in health occur with good foundations of diet and exercise. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"XVAOzc4h","properties":{"formattedCitation":"\\super 27,28\\nosupersub{}","plainCitation":"27,28","noteIndex":0},"citationItems":[{"id":424,"uris":[""],"uri":[""],"itemData":{"id":424,"type":"article-journal","title":"OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009","container-title":"Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society","page":"476-499","volume":"18","issue":"4","source":"PubMed","abstract":"OBJECTIVE: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009.\nMETHODS: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence.\nRESULTS: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo.\nCONCLUSION: Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.","DOI":"10.1016/j.joca.2010.01.013","ISSN":"1522-9653","note":"PMID: 20170770","title-short":"OARSI recommendations for the management of hip and knee osteoarthritis","journalAbbreviation":"Osteoarthr. Cartil.","language":"eng","author":[{"family":"Zhang","given":"W."},{"family":"Nuki","given":"G."},{"family":"Moskowitz","given":"R. W."},{"family":"Abramson","given":"S."},{"family":"Altman","given":"R. D."},{"family":"Arden","given":"N. K."},{"family":"Bierma-Zeinstra","given":"S."},{"family":"Brandt","given":"K. D."},{"family":"Croft","given":"P."},{"family":"Doherty","given":"M."},{"family":"Dougados","given":"M."},{"family":"Hochberg","given":"M."},{"family":"Hunter","given":"D. J."},{"family":"Kwoh","given":"K."},{"family":"Lohmander","given":"L. S."},{"family":"Tugwell","given":"P."}],"issued":{"date-parts":[["2010",4]]}}},{"id":470,"uris":[""],"uri":[""],"itemData":{"id":470,"type":"article-journal","title":"OARSI guidelines for the non-surgical management of knee osteoarthritis","container-title":"Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society","page":"363-388","volume":"22","issue":"3","source":"PubMed","abstract":"OBJECTIVE: To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, and allied healthcare professionals worldwide.\nMETHOD: Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1-10 risk and benefit scores.\nRESULTS: Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation).\nCONCLUSION: These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.","DOI":"10.1016/j.joca.2014.01.003","ISSN":"1522-9653","note":"PMID: 24462672","journalAbbreviation":"Osteoarthr. Cartil.","language":"eng","author":[{"family":"McAlindon","given":"T. E."},{"family":"Bannuru","given":"R. R."},{"family":"Sullivan","given":"M. C."},{"family":"Arden","given":"N. K."},{"family":"Berenbaum","given":"F."},{"family":"Bierma-Zeinstra","given":"S. M."},{"family":"Hawker","given":"G. A."},{"family":"Henrotin","given":"Y."},{"family":"Hunter","given":"D. J."},{"family":"Kawaguchi","given":"H."},{"family":"Kwoh","given":"K."},{"family":"Lohmander","given":"S."},{"family":"Rannou","given":"F."},{"family":"Roos","given":"E. M."},{"family":"Underwood","given":"M."}],"issued":{"date-parts":[["2014",3]]}}}],"schema":""} 27,28 Most importantly, through our program, you will obtain the knowledge to seize control over your health long-term. Evidence Based Treatment PlanOur program is designed around high-quality research indicating that patients with osteoarthritis obtain significant benefit from:Individualised Group Exercise that does not exacerbate joint pain ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"kwTWwtk1","properties":{"formattedCitation":"\\super 29\\nosupersub{}","plainCitation":"29","noteIndex":0},"citationItems":[{"id":7098,"uris":[""],"uri":[""],"itemData":{"id":7098,"type":"article-journal","title":"Good Life with osteoArthritis in Denmark (GLA:D?): evidence-based education and supervised neuromuscular exercise delivered by certified physiotherapists nationwide","container-title":"BMC Musculoskeletal Disorders","volume":"18","source":"PubMed Central","abstract":"Background\nThe uptake of evidence-based guidelines in clinical practice is suboptimal in osteoarthritis (OA) and other chronic diseases. Good Life with osteoArthritis in Denmark (GLA:D) was launched in 2013 with the aim of implementing guidelines for the treatment of knee and hip OA in clinical care nationwide. The purpose of this report was to evaluate the effects of the GLA:D intervention from 2013 to 2015, using data from the national GLA:D registry.\n\nMethods\nPatients undergo education and supervised exercise delivered by trained physiotherapists. Outcomes evaluated at baseline, 3 and 12?months are pain intensity (0 to 100, best to worst), objective physical function (30-s chair-stand test and 40-m fast-paced walk test), physical activity (number of days per week being physically active for at least 30?min), quality of life (Knee injury and Osteoarthritis Outcome Score (KOOS) and the Hip disability and Osteoarthritis Outcome Score (HOOS) quality of life subscale, 0–100, worst to best), number of patients on painkillers and sick leave, and access to care according to guidelines.\n\nResults\nData from 9,825 participants from the GLA:D registry were utilised in the analyses. It was demonstrated that GLA:D improved pain intensity and quality of life by 12.4 points and 5.4 points at 3?months, and 13.7 points and 9.4 points at 12?months, respectively. Furthermore, physical function and physical activity improved (only at 3?months), fewer patients took painkillers following the treatment, and fewer patients were on sick leave at 12?months following GLA:D compared with the year prior to GLA:D. GLA:D is offered in all five health care regions in Denmark via 286 active GLA:D units, but the uptake in the Danish municipalities is still low with only 20% of the municipalities offering GLA:D.\n\nConclusion\nThree years after its inception, GLA:D has been rolled out nationwide and has a significant impact not only on patient symptoms and physical function, but also on intake of painkillers and sick leave. The lifestyle changes introduced by education and supervised exercise were largely maintained at 1?year and may have the potential to also improve general health and reduce societal costs.","URL":"","DOI":"10.1186/s12891-017-1439-y","ISSN":"1471-2474","note":"PMID: 28173795\nPMCID: PMC5297181","title-short":"Good Life with osteoArthritis in Denmark (GLA","journalAbbreviation":"BMC Musculoskelet Disord","author":[{"family":"Skou","given":"S?ren T."},{"family":"Roos","given":"Ewa M."}],"issued":{"date-parts":[["2017",2,7]]},"accessed":{"date-parts":[["2019",9,15]]}}}],"schema":""} 29Weight loss, particularly utilising a medically supervised Low Carbohydrate diet ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FiC2ueEX","properties":{"formattedCitation":"\\super 30\\uc0\\u8211{}35\\nosupersub{}","plainCitation":"30–35","noteIndex":0},"citationItems":[{"id":2559,"uris":[""],"uri":[""],"itemData":{"id":2559,"type":"article-journal","title":"Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis","container-title":"Seminars in Arthritis and Rheumatism","source":"Crossref","abstract":"Objectives: The purposes were to (i) determine the effect of diet-only treatments and combined diet and exercise treatments on pain and physical function and (ii) explore the effect of these treatments on inflammatory biomarkers in overweight and obese adults with knee osteoarthritis.\nMethods: Five electronic databases were searched until March, 2017. Randomised controlled trials investigating the effect of non-surgical non-pharmacological weight loss treatment, with or without exercise, on self-reported pain and/or physical function and/or inflammatory biomarkers were selected. Two review authors independently extracted data and assessed risk of bias for each study. Standardised mean differences (SMD) of outcomes were pooled as appropriate, using a random effects approach.\nResults: 2,676 articles were identified, 19 met review criteria and 9 met criteria for metaanalyses. Diet-only treatments did not reduce pain (SMD -0.13; 95% confidence interval, CI: -0.37, 0.10; I2 = 49%) while a combination of diet and exercise treatments did reduce pain moderately (SMD -0.37; 95%CI: -0.69, -0.04; I2 = 54%). Physical function improved moderately with diet treatments (SMD -0.30; 95%CI: -0.52, -0.08; I2 = 47%) and combined diet and exercise treatments (SMD -0.32; 95%CI: -0.56, -0.08; I2 = 24%). Of the inflammatory markers assessed, only IL-6 reduced with diet-only treatments (SMD -0.23 (95%CI: -0.45, -0.02; I2 = 0%).\nConclusion: Overall, moderate pain-relief is achievable with a combination of diet and exercise, but potentially not with diet-only treatments. Findings support that either diet-only treatments or combined diet and exercise treatments moderately improve physical function. Overall, treatment effects on inflammatory biomarkers are questionable.","URL":"","DOI":"10.1016/j.semarthrit.2018.06.005","ISSN":"00490172","title-short":"Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis","language":"en","author":[{"family":"Hall","given":"Michelle"},{"family":"Castelein","given":"Birgit"},{"family":"Wittoek","given":"Ruth"},{"family":"Calders","given":"Patrick"},{"family":"Van Ginckel","given":"Ans"}],"issued":{"date-parts":[["2018",6]]},"accessed":{"date-parts":[["2019",3,18]]}}},{"id":2562,"uris":[""],"uri":[""],"itemData":{"id":2562,"type":"article-journal","title":"Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial","container-title":"Arthritis Care & Research","page":"640-650","volume":"67","issue":"5","source":"PubMed","abstract":"OBJECTIVE: To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or \"no attention\" (C; control group).\nMETHODS: We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria.\nRESULTS: Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41).\nCONCLUSION: A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.","DOI":"10.1002/acr.22504","ISSN":"2151-4658","note":"PMID: 25370359\nPMCID: PMC4657487","title-short":"Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients","journalAbbreviation":"Arthritis Care Res (Hoboken)","language":"eng","author":[{"family":"Christensen","given":"Robin"},{"family":"Henriksen","given":"Marius"},{"family":"Leeds","given":"Anthony R."},{"family":"Gudbergsen","given":"Henrik"},{"family":"Christensen","given":"Pia"},{"family":"S?rensen","given":"Tina J."},{"family":"Bartels","given":"Else M."},{"family":"Riecke","given":"Birgit F."},{"family":"Aaboe","given":"Jens"},{"family":"Frederiksen","given":"Rikke"},{"family":"Boesen","given":"Mikael"},{"family":"Lohmander","given":"L. Stefan"},{"family":"Astrup","given":"Arne"},{"family":"Bliddal","given":"Henning"}],"issued":{"date-parts":[["2015",5]]}}},{"id":1639,"uris":[""],"uri":[""],"itemData":{"id":1639,"type":"article-journal","title":"Body weight changes and corresponding changes in pain and function in persons with symptomatic knee osteoarthritis. A cohort study","container-title":"Arthritis care & research","page":"15-22","volume":"65","issue":"1","source":"PubMed Central","abstract":"Objective\nTo determine if a dose-response relationship exists between percentage body weight changes in persons with symptomatic knee osteoarthritis (OA) and self reported pain and function.\n\nMethods\nData from persons in the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis (MOST) datasets (n=1,410) with symptomatic function limiting knee OA were studied. For the OAI, we used baseline and 3-year follow-up data while for the MOST, baseline and 30-month data were used. Key outcome variables were WOMAC Physical Function and Pain change scores. In addition to covariates, the predictor variable of interest was the extent of weight change over the study period and divided into 5 categories representing different percentages of body weight change.\n\nResults\nA significant dose-response relationship (p< 0.003) was found between the extent of percentage change in body weight and the extent of change in WOMAC Physical Function and WOMAC Pain. For example, persons who gained ≥10% of body weight had WOMAC Physical Function score changes of ?5.4 (95%CI, ?8.7, ?2.00) points indicating worsening relative to the reference group of persons with weight changes of between <5% weight gain and <5% weight reduction.\n\nConclusion\nOur data suggest a dose-response relationship exists between changes in body weight and corresponding changes in pain and function. The threshold for this response gradient appears to be ≥10% body weight shifts. Weight changes of ≥10% have potential to lead to important changes in pain and function for patient groups as well as individual patients.","DOI":"10.1002/acr.21692","ISSN":"2151-464X","note":"PMID: 22505346\nPMCID: PMC3401342","journalAbbreviation":"Arthritis Care Res (Hoboken)","author":[{"family":"Riddle","given":"Daniel L."},{"family":"Stratford","given":"Paul W."}],"issued":{"date-parts":[["2013",1]]}}},{"id":1640,"uris":[""],"uri":[""],"itemData":{"id":1640,"type":"article-journal","title":"Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis","container-title":"JAMA","page":"1263-1273","volume":"310","issue":"12","source":"PubMed Central","abstract":"IMPORTANCE\nKnee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity.\n\nOBJECTIVE\nTo determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone.\n\nDESIGN, SETTING, AND PARTICIPANTS\nSingle-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27–41) with pain and radiographic knee OA.\n\nINTERVENTIONS\nIntensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise.\n\nMAIN OUTCOMES AND MEASURES\nMechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0–20), function (range, 0–68), mobility, and health-related quality of life (range, 0–100).\n\nRESULTS\nAt 18 months, 399 participants (88%) completed the study. Compared with exercise participants, knee compressive forces were lower in diet participants and IL-6 levels were lower in diet and diet + exercise participants., \n \n \n \n \n \n 18-mo Outcomes, Mean (95% CI)\n \n \n Exercise(E)\n Diet (D)\n D + E\n Difference,E vs D\n Difference, Evs D+E\n \n \n \n \n Weight loss, kg\n ?1.8(?5.7to1.8)\n ?8.9(?12.4 to ?5.3)\n ?10.6(?14.1 to ?7.1)\n \n \n \n \n Knee compressiveforces, N\n 2687(2590 to 2784)\n 2487(2393 to 2581)\n 2543(2448 to 2637)\n 200(55 to 345)\n 144(1 to 287)\n \n \n IL-6, pg/mL\n 3.1(2.9 to 3.4)\n 2.7(2.4 to 3.0)\n 2.7(2.5 to 3.0)\n 0.43(0.01 to 0.85)\n 0.39(?0.03 to 0.81)\n \n \n Pain\n 4.7(4.2 to 5.1)\n 4.8(4.3 to 5.2)\n 3.6(3.2 to 4.1)\n ?0.11(?0.81 to 0.59)\n 1.02(0.33 to 1.71)\n \n \n Function\n 18.4(16.9 to 19.9)\n 17.4(15.9 to 18.9)\n 14.1(12.6 to 15.6)\n 0.98(?1.24 to 3.20)\n 4.29(2.07 to 6.50)\n \n \n SF-36 physical\n 41.9(40.5 to 43.2)\n 42.4(41.1 to 43.7)\n 44.7(43.4 to 46.0)\n ?0.55(?2.53 to 1.43)\n ?2.81(?4.76 to ?0.86)\n \n \n \n \n \n a\n Differences were significant.\n \n \n \n \n\nCONCLUSIONS AND RELEVANCE\nAmong overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group.\n\nTRIAL REGISTRATION\ Identifier: NCT00381290","DOI":"10.1001/jama.2013.277669","ISSN":"0098-7484","note":"PMID: 24065013\nPMCID: PMC4450354","journalAbbreviation":"JAMA","author":[{"family":"Messier","given":"Stephen P."},{"family":"Mihalko","given":"Shannon L."},{"family":"Legault","given":"Claudine"},{"family":"Miller","given":"Gary D."},{"family":"Nicklas","given":"Barbara J."},{"family":"DeVita","given":"Paul"},{"family":"Beavers","given":"Daniel P."},{"family":"Hunter","given":"David J."},{"family":"Lyles","given":"Mary F."},{"family":"Eckstein","given":"Felix"},{"family":"Williamson","given":"Jeff D."},{"family":"Carr","given":"J. Jeffery"},{"family":"Guermazi","given":"Ali"},{"family":"Loeser","given":"Richard F."}],"issued":{"date-parts":[["2013",9,25]]}}},{"id":1522,"uris":[""],"uri":[""],"itemData":{"id":1522,"type":"article-journal","title":"Association between weight or body mass index and hand osteoarthritis: a systematic review","container-title":"Annals of the Rheumatic Diseases","page":"761-765","volume":"69","issue":"4","source":"PubMed","abstract":"OBJECTIVE: To investigate the association between weight or body mass index (BMI) and the development of hand osteoarthritis.\nMETHODS: Systematic review of observational studies. Medical databases were searched up to April 2008. Articles that presented data on the association between weight and hand osteoarthritis were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring system. Using the mean scores of all studies as a cut-off value, the studies were deemed as high or low quality. Study quality and study designs were combined to determine the level of evidence using best-evidence synthesis, which consisted of five levels of evidence.\nRESULTS: From the 25 studies included, two had cohort, three case-control and 20 cross-sectional study designs. Fifteen studies were considered high-quality studies. Of these high-quality studies, one cohort, two case-control and seven cross-sectional studies showed a positive association between weight or BMI and hand osteoarthritis. Based on three high-quality studies with preferred study designs (one cohort and two case-control) with a positive association, the level of evidence of the association between overweight and developing hand osteoarthritis is moderate. The approximate risk ratio of this association is 1.9.\nCONCLUSION: Weight or BMI is associated with the development of hand osteoarthritis. The level of evidence of published studies is moderate according to best-evidence synthesis. Further high-quality cohort or case-control studies are needed to elucidate the role of weight in hand osteoarthritis.","DOI":"10.1136/ard.2008.106930","ISSN":"1468-2060","note":"PMID: 19487215","title-short":"Association between weight or body mass index and hand osteoarthritis","journalAbbreviation":"Ann. Rheum. Dis.","language":"eng","author":[{"family":"Yusuf","given":"Erlangga"},{"family":"Nelissen","given":"Rob G."},{"family":"Ioan-Facsinay","given":"Andreea"},{"family":"Stojanovic-Susulic","given":"Vedrana"},{"family":"DeGroot","given":"Jeroen"},{"family":"Osch","given":"Gerjo","non-dropping-particle":"van"},{"family":"Middeldorp","given":"Saskia"},{"family":"Huizinga","given":"Tom W. J."},{"family":"Kloppenburg","given":"Margreet"}],"issued":{"date-parts":[["2010",4]]}}},{"id":7063,"uris":[""],"uri":[""],"itemData":{"id":7063,"type":"article-journal","title":"The Intensive Diet and Exercise for Arthritis (IDEA) trial: 18-month radiographic and MRI outcomes","container-title":"Osteoarthritis and Cartilage","page":"1090-1098","volume":"23","issue":"7","source":"PubMed","abstract":"PURPOSE: Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA).\nMETHODS: Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI?=?27-41?kg?m(-2)) older (age?≥?55?yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D?+?E); or exercise-only control (E). X-rays (N?=?325) and MRIs (N?=?105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender.\nRESULTS: Mean baseline descriptive characteristics of the cohort included: age, 65.6?yrs; BMI 33.6?kg?m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D?-0.07 (SE 0.22)?mm, D?+?E?-0.27 (SE 0.22)?mm and E?-0.16 (SE 0.24)?mm (P?=?0.79). There was also no significant difference in MRI cartilage loss between groups; D?-0.10(0.05)?mm, D?+?E?-0.13(0.04)?mm and E?-0.05(0.04)?mm (P?=?0.42).\nCONCLUSION: Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.","DOI":"10.1016/j.joca.2015.03.034","ISSN":"1522-9653","note":"PMID: 25887362","title-short":"The Intensive Diet and Exercise for Arthritis (IDEA) trial","journalAbbreviation":"Osteoarthr. Cartil.","language":"eng","author":[{"family":"Hunter","given":"D. J."},{"family":"Beavers","given":"D. P."},{"family":"Eckstein","given":"F."},{"family":"Guermazi","given":"A."},{"family":"Loeser","given":"R. F."},{"family":"Nicklas","given":"B. J."},{"family":"Mihalko","given":"S. L."},{"family":"Miller","given":"G. D."},{"family":"Lyles","given":"M."},{"family":"DeVita","given":"P."},{"family":"Legault","given":"C."},{"family":"Carr","given":"J. J."},{"family":"Williamson","given":"J. D."},{"family":"Messier","given":"S. P."}],"issued":{"date-parts":[["2015",7]]}}}],"schema":""} 30–35Individualised Physical and Medical treatments ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hMWZxAJD","properties":{"formattedCitation":"\\super 23\\nosupersub{}","plainCitation":"23","noteIndex":0},"citationItems":[{"id":7078,"uris":[""],"uri":[""],"itemData":{"id":7078,"type":"article-journal","title":"Osteoarthritis","container-title":"The Lancet","page":"1745-1759","volume":"393","issue":"10182","source":" (Crossref)","DOI":"10.1016/S0140-6736(19)30417-9","ISSN":"01406736","journalAbbreviation":"The Lancet","language":"en","author":[{"family":"Hunter","given":"David J"},{"family":"Bierma-Zeinstra","given":"Sita"}],"issued":{"date-parts":[["2019",4]]}}}],"schema":""} 2328270205080000Strong Effects on Pain and FunctionResearch from the International Osteoarthritis Research Society has consistently shown that Weight loss and Exercise are the most effective treatments for pain and function in OA. ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"RQIwUxM0","properties":{"formattedCitation":"\\super 36\\nosupersub{}","plainCitation":"36","noteIndex":0},"citationItems":[{"id":1646,"uris":[""],"uri":[""],"itemData":{"id":1646,"type":"article-journal","title":"OARSI recommendations for the management of hip and knee osteoarthritis: part III: Changes in evidence following systematic cumulative update of research published through January 2009","container-title":"Osteoarthritis and Cartilage","page":"476-499","volume":"18","issue":"4","source":"PubMed","abstract":"OBJECTIVE: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009.\nMETHODS: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence.\nRESULTS: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo.\nCONCLUSION: Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.","DOI":"10.1016/j.joca.2010.01.013","ISSN":"1522-9653","note":"PMID: 20170770","title-short":"OARSI recommendations for the management of hip and knee osteoarthritis","journalAbbreviation":"Osteoarthr. Cartil.","language":"eng","author":[{"family":"Zhang","given":"W."},{"family":"Nuki","given":"G."},{"family":"Moskowitz","given":"R. W."},{"family":"Abramson","given":"S."},{"family":"Altman","given":"R. D."},{"family":"Arden","given":"N. K."},{"family":"Bierma-Zeinstra","given":"S."},{"family":"Brandt","given":"K. D."},{"family":"Croft","given":"P."},{"family":"Doherty","given":"M."},{"family":"Dougados","given":"M."},{"family":"Hochberg","given":"M."},{"family":"Hunter","given":"D. J."},{"family":"Kwoh","given":"K."},{"family":"Lohmander","given":"L. 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