title: Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans. Relation of weight gain and weight loss on subsequent diabetes risk in overweight adults A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1-year prospective randomized intervention study. Effects of a Mediterranean-inspired diet on blood lipids, vascular function and oxidative stress in healthy subjects. Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Combination of direct and indirect evidence in mixed treatment comparisons. Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity. The Hawthorne Effect: a randomised, controlled trial Biologic and quality-of-life outcomes from the Mediterranean Lifestyle Program: a randomized clinical trial. Dietary strategies for patients with type 2 diabetes in the era of multi-approaches; review and results from the Dietary Intervention Randomized Controlled Trial (DIRECT). Close adherence to a Mediterranean diet improves endothelial function in subjects with abdominal obesity. Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients With Newly Diagnosed Type 2 Diabetes A Mediterranean dietary intervention in healthy American women changes plasma carotenoids and fatty acids in distinct clusters. A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial). Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a randomized cross-over study.
abstract: BACKGROUND Despite their beneficial effects on weight loss and blood lipids , high-protein ( HP ) diets have been shown to increase insulin resistance and diabetes risk , whereas high-cereal-fiber ( HCF ) diets have shown the opposite effects on these outcomes . OBJECTIVE We compared the effects of isoenergetic HP and HCF diets and a diet with moderate increases in both cereal fibers and dietary protein ( Mix diet ) on insulin sensitivity , as measured by using euglycemic-hyperinsulinemic clamps with infusion of [6,6-(2)H(2)]glucose . DESIGN We r and omly assigned 111 overweight adults with features of the metabolic syndrome to 1 of 4 two-phased , 18-wk isoenergetic diets by group-matching . Per 3-d food protocol s , the percentages of energy derived from protein and carbohydrates and the intake of cereal fiber per day , respectively , were as follows-after 6 wk : 17 % , 52 % , and 14 g ( control ) ; 17 % , 52 % , and 43 g ( HCF ) ; 28 % , 43 % , and 13 g ( HP ) ; 23 % , 44 % , and 26 g ( Mix ) ; after 18 wk : 17 % , 51 % , and 15 g ( control ) ; 17 % , 51 % , and 41 g ( HCF ) ; 26 % , 45 % , and 14 g ( HP ) ; and 22 % , 46 % , and 26 g ( Mix ) . Eighty-four participants completed the study successfully and were included in the final analyses . Adherence was supported by the provision of tailored dietary supplements twice daily in all groups . RESULTS Insulin sensitivity expressed as an M value was 25 % higher after 6 wk of the HCF diet than after 6 wk of the HP diet ( subgroup analysis : 4.61 ± 0.38 compared with 3.71 ± 0.36 mg · kg(-1 ) · min(-1 ) , P = 0.008 ; treatment × time interaction : P = 0.005 ) . Effects were attenuated after 18 wk ( treatment × time interaction : P = 0.054 ) , which was likely explained by lower adherence to the HP diet . HP intake was associated with a tendency to increased protein expression in adipose tissue of the translation initiation factor serine-kinase-6 - 1 , which is known to mediate amino acid-induced insulin resistance . Biomarkers of protein intake indicated interference of cereal fibers with dietary protein absorption . CONCLUSION Greater changes in insulin sensitivity after intake of an isoenergetic HCF than after intake of an HP diet might help to explain the diverse effects of these diets on diabetes risk . This trial is registered at clinical trials.gov as NCT00579657 STUDY OBJECTIVE To determine whether long term weight gain and weight loss  are associated with subsequent risk of type 2 diabetes in overweight , non-diabetic adults . DESIGN Prospect i ve cohort . Baseline overweight was defined as BMI ⩾27.3 for women and BMI ⩾27.8 for men . Annual weight change ( kg/year ) over 10 years was calculated using measured weight at subjects ' baseline and first follow up examinations . In the 10 years after measurement of weight change , incident cases of diabetes were ascertained by self report , hospital discharge records , and death certificates . SETTING Community . PARTICIPANTS 1929 overweight , non-diabetic adults . MAIN RESULTS Incident diabetes was ascertained in 251 subjects .  Age adjusted cumulative incidence increased from 9.6 % for BMI < 29 to 26.2 % for BMI ⩾37 . Annual weight change over 10 years was higher in subjects who become diabetic compared with those who did not for all BMI < 35 . Relative to overweight people with stable weight , each kg of weight gained annually over 10 years was associated with a 49 % increase in risk of developing diabetes in the subsequent 10 years . Each kg of weight lost annually over 10 years was associated with a 33 % lower risk of diabetes in the subsequent 10 years .  CONCLUSIONS Weight gain  was associated with substantially increased risk of diabetes among overweight adults , and even modest weight loss was associated with significantly reduced diabetes risk . Minor weight reductions may have major beneficial effects on subsequent diabetes risk in overweight adults at high risk of developing diabetes BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control Mediterranean-inspired diets have been shown to decrease cholesterol levels in patients with hypercholesterolaemia , who frequently exhibit endothelial dysfunction . The aims of the present study are to improve endothelial function by dietary intervention in healthy subjects with lipid levels representative of a Western population . Twenty-two healthy subjects ( mean total cholesterol , 5.6 mmol/l ) were given a Mediterranean-inspired diet rich in omega-3 fatty acids and sterol esters , but low in saturated fat , or an ordinary Swedish diet , for 4 weeks in a r and omized cross-over study . The composition of the diets were : in the Swedish diet , 2090 kcal ( where 1 kcal=4.184 kJ ; 48 % of energy from carbohydrate , 15 % from protein and 36 % from fat ) and 19 g of fibre ; in the Mediterranean-inspired diet , 1869 kcal ( 48 % of energy from carbohydrate , 16 % from protein , 34 % from fat ) and 40 g of fibre . After each dietary period , fasting blood lipids , insulin and glucose levels , as well as apo B ( apolipoprotein B ) and LDL ( low-density lipoprotein ) particle size , were analysed . Endothelial-dependent and -independent vasodilation was measured invasively by venous occlusion plethysmography , and arterial distensibility was assessed by echocardiography tracking . Fibrinolytic capacity across the forearm , as well as oxidative stress measured through urinary F(2)-isoprostane , were evaluated . Total , LDL- and apo B-cholesterol and triacylglycerol ( triglyceride ) concentrations were decreased by 17 % , 22 % , 16 % and 17 % respectively , after the Mediterranean-inspired diet compared with the Swedish diet ( P < 0.05 for all ) . However , no differences in plasma concentrations of insulin and glucose and LDL particle size , endothelial function , arterial distensibility , fibrinolytic capacity or oxidative stress were detected . Treatment for 4 weeks with a Mediterranean-inspired diet decreased blood lipids in healthy individuals with a low-risk profile for cardiovascular disease . This beneficial effect was not mirrored in vascular function or oxidative stress evaluation OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk BACKGROUND The Lyon Diet Heart Study is a r and omized secondary prevention trial aim ed at testing whether a Mediterranean-type diet may reduce the rate of recurrence  after a first myocardial infa rct ion . An intermediate analysis showed a striking protective effect after 27 months of follow-up . This report presents results of an extended follow-up ( with a mean of 46 months per patient ) and deals with the relationships of dietary patterns and traditional risk factors with recurrence . METHODS AND RESULTS Three composite outcomes ( COs ) combining either cardiac death and nonfatal myocardial infa rct ion ( CO 1 ) , or the preceding plus major secondary end points ( unstable angina , stroke , heart failure , pulmonary or peripheral embolism ) ( CO 2 ) , or the preceding plus minor events requiring hospital admission ( CO 3 ) were studied . In the  Mediterranean diet group , CO 1 was reduced ( 14 events versus 44 in the prudent Western-type diet group , P=0.0001 ) , as were CO 2 ( 27 events versus 90 , P=0.0001 ) and CO 3 ( 95 events versus 180 , P=0 . 0002 ) . Adjusted risk ratios ranged from 0.28 to 0.53 . Among the traditional risk factors , total cholesterol ( 1 mmol/L being associated with an increased risk of 18 % to 28 % ) , systolic blood pressure ( 1 mm Hg being associated with an increased risk of 1 % to 2 % ) , leukocyte count ( adjusted risk ratios ranging from 1.64 to 2.86 with count > 9x10(9)/L ) , female sex ( adjusted risk ratios , 0.27 to 0 . 46 ) , and aspirin use ( adjusted risk ratios , 0.59 to 0.82 ) were each significantly and independently associated with recurrence . CONCLUSIONS The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infa rct ion , confirming previous intermediate analyses . Major traditional risk factors , such as high blood cholesterol and blood pressure , were shown to be independent and joint predictors of recurrence , indicating that the Mediterranean dietary pattern did not alter , at least qualitatively , the usual relationships between major risk factors and recurrence . Thus , a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet . It should be associated with other ( pharmacological ? ) means aim ed at reducing modifiable risk factors . Further trials combining the 2 approaches are warranted Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND AND AIMS Diets high in monounsaturated fatty acids ( MUFA ) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids . Besides being high in MUFA , a Mediterranean diet also contains abundant plant foods , moderate wine and low amounts of meat and dairy products , which may also play a role . We compared the effects of a high MUFA-diet with a diet high in saturated fatty acids ( SFA ) and the additional effect of a Mediterranean diet on insulin sensitivity and serum lipids . METHODS AND RESULTS A r and omized parallel controlled-feeding trial was performed , in 60 non-diabetics ( 40 - 65 y ) with mild abdominal obesity . After a two week run-in diet high in SFA ( 19 energy-% ) , subjects were allocated to a high MUFA-diet ( 20 energy-% ) , a Mediterranean diet ( MUFA 21 energy-% ) , or the high SFA-diet , for eight weeks . The high MUFA and the Mediterranean diet did not affect fasting insulin concentrations . The high MUFA-diet reduced total cholesterol ( -0.41 mmol/L , 95 % CI -0.74 , -0.09 ) and LDL-cholesterol ( -0.38 mmol/L , 95 % CI -0.65 , -0.11 ) compared with the high SFA-diet , but not triglyceride concentrations . The Mediterranean diet increased HDL-cholesterol concentrations ( + 0.09 mmol/L , 95 % CI 0.0 , 0.18 ) and reduced the ratio of total cholesterol/HDL-cholesterol ( -0.39 , 95 % CI -0.62 , -0.16 ) compared with the high MUFA-diet . CONCLUSION Replacing a high SFA-diet with a high MUFA or a Mediterranean diet did not affect insulin sensitivity , but improved serum lipids . The Mediterranean diet was most effective , it reduced total and LDL-cholesterol , and also increased HDL-cholesterol and reduced total cholesterol/HDL-cholesterol ratio Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life Dietary intervention is recognized as a key component in prevention and management of type 2 diabetes ( T2DM ) and the debate persists : which dietary strategy is most effective . In the Dietary Intervention R and omized Controlled Trial ( DIRECT ) 322 moderately obese participants were r and omized for 2 years to one of three diet groups : low-fat , Mediterranean and low-carbohydrate . Differential effects were observed in the sub-group of patients with T2DM at 24 months : participants r and omized to the Mediterranean diet , which had the highest intake of dietary fibers and unsaturated to saturated fat ratio , achieved greater significant improvements in fasting plasma glucose and insulin levels . Patients who were r and omized to the low-carbohydrate diet , which had the minimal intake of carbohydrates , achieved a significant reduction of hemoglobin A1C . Although improvements were observed in all groups , the low-fat diet was likely to be less beneficial in terms of glycemic control and lipid metabolism . Interpretation of results from different studies on dietary strategies may be complex since there is often no consistency in diet compositions , calorie restriction , intensity of intervention , dietary assessment or extent of adherence in the trial . Nevertheless , it seems that low fat restricted calorie diets are effective for weight loss and are associated with some metabolic benefits ; however , some recent trials have shown that low carbohydrate diets are as efficient in inducing weight loss and in some metabolic measures such as serum triglycerides and HDL-cholesterol may be even superior to low fat diets . When addressing the issue of diet quality rather than quantity applying the glycemic index may have some added benefits . Furthermore special features of the Mediterranean diet have apparent additional favorable effects for patients with T2DM BACKGROUND Abdominal obesity ( AO ) is associated with increased risk of cardiovascular disease and type 2 diabetes , whereas the Mediterranean diet exerts a cardioprotective effect . OBJECTIVE We examined whether a close adherence to a Mediterranean-style diet improves endothelial function in individuals with AO . DESIGN We recruited 90 subjects with AO without cardiovascular disease or type 2 diabetes . Participants were r and omly assigned to the intervention or control group . Both groups were instructed to follow a Mediterranean-style diet for 2 mo . Subjects in the intervention group additionally had to follow a specific relevant daily and weekly food plan with close supervision by a dietitian and provision of basic foods .  Flow-mediated dilatation ( FMD ) , lipids , C-reactive protein ( CRP ) , and insulin resistance with the homeostasis model assessment ( HOMA-IR ) were measured . RESULTS After 2 mo , subjects in the intervention group increased their intake of total fat due to higher consumption of monounsaturated fatty acids as well as intakes of dietary fiber , vitamin C , and alcohol compared with the control group ( all P < 0.05 ) . The intervention group also increased FMD ( 2.05 % ; 95 % CI : 0.97 , 3.13 % ) , whereas no effect was found in the control group ( -0.32 % ; 95 % CI : -1.31 , 0.67 % ) . Changes in lipids and CRP concentrations did not differ between the 2 groups , whereas diastolic blood pressure decreased in the intervention group ( -6.44 mm Hg ; 95 % CI : -8.57 , -4.31 mm Hg ) compared with the control group ( -0.76 mm Hg ; 95 % CI : -2.83 , 1.31 mm Hg ) . Finally , there was a trend for a reduction in HOMA-IR in the intervention group compared with the control group ( P = 0.072 ) . CONCLUSION Close adherence to a Mediterranean-style diet achieved by close dietetic supervision improves endothelial function in subjects with AO BACKGROUND The rapid emergence of coronary artery disease ( CAD ) in south Asian people is not explained by conventional risk factors . In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid , we assessed the benefits of this diet for patients at high risk of CAD . METHODS We did a r and omised , single-blind trial in 1000 patients with angina pectoris , myocardial infa rct ion , or surrogate risk factors for CAD . 499 patients were allocated to a diet rich in whole grains , fruits , vegetables , walnuts , and almonds . 501 controls consumed a local diet similar to the step I National Cholesterol Education Program ( NCEP ) prudent diet . FINDINGS The intervention group consumed more  fruits , vegetables , legumes , walnuts , and almonds  than did controls ( 573 g [ SD 127 ] vs 231 g [ 19 ] per day p<0.001 ) . The intervention group had an increased intake of whole grains and mustard or soy bean oil . The mean intake of alpha-linolenic acid was two-fold greater in the intervention group ( 1.8 g [ SD 0.4 ] vs 0.8 g [ 0.2 ] per day , p<0.001 ) . Total cardiac end points were significantly fewer in the intervention group than the controls ( 39 vs 76 events , p<0.001 ) . Sudden cardiac deaths were also reduced ( 6 vs 16 , p=0.015 ) , as were non-fatal myocardial infa rct ions ( 21 vs 43 , p<0.001 ) . We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups , but especially in the intervention diet group . In the treatment group , patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group . INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet Context Mediterranean-style diets improve control of coronary risk factors and hyperglycemia , but few direct comparisons of the diet with other st and ard diets have been done . Contribution In this r and omized clinical trial , patients with newly diagnosed type 2 diabetes who were assigned to a low-carbohydrate , Mediterranean-style diet had better glycemic control and were less likely to need oral antihyperglycemic therapy than patients assigned to a low-fat diet . Caution The trial was unblinded , and dietary intake was self-reported . Implication A low-carbohydrate , Mediterranean-style diet seems to be preferable to a low-fat diet for glycemic control in patients with newly diagnosed type 2 diabetes . The Editors The p and emic of type 2 diabetes is an enormous public health problem , with 380 million cases worldwide projected by 2025 ( 1 , 2 ) . Lifestyle intervention studies ( 3 ) have demonstrated large reductions in risk for type 2 diabetes that remain after lifestyle counseling is stopped ( 4 , 5 ) . Despite this beneficial effect , the American Diabetes Association ( ADA ) recommends that patients with newly diagnosed type 2 diabetes be treated with pharmacotherapy as well as lifestyle changes ( 6 ) . The rationale for combination therapy is presumably that each form of treatment alone is imperfect . Lifestyle changes are often inadequate because patients do not lose weight or regain weight or their diabetes worsens independent of weight ( 6 ) . Pharmacotherapy also often fails with time ( 7 ) , and some drugs have associated cardiovascular and other risks ( 8 , 9 ) . For those reasons , lifestyle changes proven to be more effective than what is typically recommended would be welcome . For example , Mediterranean-style ( MED ) diets with a high proportion of monounsaturated fat provide cardiovascular benefits and increase insulin sensitivity ( 1012 ) , and the ADA recommends low-carbohydrate or low-fat , calorie-restricted diets for weight loss in overweight and obese patients with type 2 diabetes ( 13 ) . However , few direct , long-term comparisons of the 2 diets in patients with diabetes have been done ( 11 ) . We conducted a r and omized trial to compare the effectiveness , durability , and safety of a low-carbohydrate MED diet and a low-fat diet on glycemic control in patients with newly diagnosed type 2 diabetes . Methods We conducted the trial between January 2004 ( first patient enrolled ) and September 2008 ( end of follow-up of the last patient ) at the research center of the Diabetes Clinic of the Azienda Ospedaliera Universitaria , Second University of Naples , Naples , Italy , in accordance with the Declaration of Helsinki and with the institutional review board 's approval . Screening Phase We recruited men and women with newly diagnosed type 2 diabetes by ADA criteria who had never been treated with antihyperglycemic drugs from the clinical practice s of trial investigators and screened them for eligibility . Inclusion criteria were age 30 to 75 years , body mass index ( BMI ) greater than 25 kg/m2 , and hemoglobin A1c ( HbA1c ) level less than 11 % . Participants also had to be sedentary ( < 1 hour of physical activity per week ) with no evidence of participation in weight-reduction programs and with a stable weight ( 2 kg ) in the past 6 months . Exclusion criteria included pregnancy or breastfeeding , use of any investigational drug in the previous 3 months , use of agents affecting glycemic control ( such as systemic glucocorticoids and weight loss drugs ) , and any condition that might compromise adherence to diet regimens . To minimize the likelihood of including participants with late-onset type 1 diabetes , we screened c and i date s by testing for antibodies to glutamate decarboxylase and measuring fasting plasma C-peptides . We excluded patients with positive antibodies or C-peptide levels less than 0.25 pmol/L ( < 0.76 ng/L ) . We also excluded patients with abnormal laboratory test results , including liver enzyme levels ( alanine aminotransferase , aspartate aminotransferase , and alkaline phosphatase ) greater than 3 times the upper limit of normal and serum creatinine levels greater than 123.8 mol/L ( > 1.4 mg/dL ) . We required that participants successfully self-monitor their diet and physical activity over a 2-week run-in period . We provided dietary education during that time that emphasized the importance of eating a healthy diet and being physically active for both weight loss and improvement of glycemic control . Participants were also taught to prepare their own meals at home . We encouraged all individuals who smoked to quit and provided self-help material s , referral to local programs , or both , as appropriate . R and omization and Blinding After obtaining informed consent , we r and omly assigned patients to 1 of the 2 study diets by using a computer-generated r and om-number sequence ( simple r and omization ) . Allocation was concealed in sealed study folders that were held in a central , secured location until after informed consent was obtained . The nurses who scheduled the study visits did not have access to the r and omization list , and laboratory staff did not know the participants ' group assignments . Staff members involved in the intervention were aware of group assignments , but those who assessed achievement of the primary outcome were blinded to the intervention . Participants received no financial compensation or gifts . Dietary Interventions We r and omly assigned patients to a low-carbohydrate MED diet or to a low-fat diet . The MED diet was rich in vegetables and whole grains and low in red meat , which was replaced with poultry and fish . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 50 % of calories from complex carbohydrates , based on evidence that , in the context of a MED diet , a carbohydrate content less than 50 % of daily energy is more beneficial than higher content for weight loss and cardiovascular risk reduction ( 14 ) . The diet had no less than 30 % calories from fat . The main source of added fat was 30 to 50 g of olive oil . The low-fat diet was based on American Heart Association guidelines ( 15 ) ; it was rich in whole grains and restricted additional fats , sweets , and high-fat snacks . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 30 % of calories from fat and no more than 10 % of calories from saturated fat . Nutritionists and dietitians gave dietary advice to participants in both groups in monthly sessions in the first year and bimonthly sessions thereafter . Participants kept diet diaries after being instructed how to record their intake using food models as examples of portion size and using actual weights or amounts in terms of common measures ( such as cups , teaspoons , and dessert spoons ) . We assessed adherence to the diets by session attendance and review of the diaries . Nondietary Interventions Patients in both groups also received guidance on increasing their level of physical activity , mainly walking for a minimum of 30 minutes per day , but also swimming or aerobic ball games . The physical activity program relied heavily on home-based exercise with gradual progression toward a goal of 175 minutes of moderate-intensity physical activity per week . Although walking was encouraged , participants were allowed to choose other types of moderate-intensity physical activity , and programs were tailored on the basis of the results of a baseline physical fitness test and safety concerns . We asked all patients to record occupational , household , and leisure time physical activity . Outcomes We followed patients for 4 years to assess trial outcomes . The primary outcome measure was time to introduction of antihyperglycemic drug therapy . Trial investigators were responsible for initiating drug therapy by the following protocol . As suggested by the ADA for clinical evaluation and management of diabetic patients ( 16 ) , we measured HbA1c at baseline and every 3 months thereafter . Participants who had a HbA1c level greater than 7 % were given an additional 3 months to reinforce dietary guidance and physical activity ; if the HbA1c level remained greater than 7 % , a drug regimen was introduced . Participants with an HbA1c level greater than 7 % at baseline were counted as having experienced the primary outcome if they still had that level at first follow-up . Trial investigators were also responsible for initiating or titrating antihypertensive or lipid-lowering therapy . Secondary outcome measures were changes in weight ( including BMI and waist circumference ) , glycemic control ( HbA1c , glucose , serum insulin , and adiponectin levels and homeostasis model assessment of insulin sensitivity ) , coronary risk factors ( lipid levels and blood pressure ) , and medications and meeting ADA coronary risk factor goals ( HbA1c level < 7 % , blood pressure < 130/80 mm Hg , and low-density lipoprotein cholesterol level < 2.59 mmol/L [ < 100 mg/dL ] ) ( 16 ) . Participants were weighed without shoes and in lightweight clothing to the nearest 0.1 kg at baseline and every month . Height at baseline ( for calculation of BMI ) was measured to the nearest millimeter with the use of a wall-mounted stadiometer ( Seca , Hamburg , Germany ) . Waist circumference was measured halfway between the last rib and the iliac crest . We measured HbA1c levels with high-pressure liquid chromatography by using the fully automated Glycosylated Hemoglobin Analyzer System ( Bio-Rad , Hercules , California ) traceable to the Diabetes Control and Complications Trial reference method , with a reference range of 4.0 % to 6.0 % . Insulin sensitivity in the fasting state was assessed with homeostasis model assessment and calculated with the following formula , as described by Matthews and colleagues ( 17 ) : fasting plasma glucose (mmol/L)fasting serum insulin (U/mL)/25 . High scores indicate low insulin sensitivity ( insulin resistance ) . We assayed plasma insulin and adiponectin levels by radioimmunoassay , as described elsewhere ( 18 ) . We performed assays for serum This study examined patterns of changes in plasma fatty acids and carotenoids when women were asked to follow a  novel , Greek-Mediterranean exchange list diet .  A total of 69 healthy , nonobese women ages 25 to 59 years were r and omized either to continue their own usual diet or to follow a modified Mediterranean diet for 6 months . There were no significant changes in blood lipids , triacylglycerol , insulin , glucose , or C-reactive protein . Mean plasma carotenoids increased by 55 % , which is consistent with a large increase in fruit and vegetable consumption . Likewise , changes in fat intakes were reflected in blood fatty acids , with a 25 % increase in mean plasma monounsaturated fatty acids . Principal component analysis was conducted to examine the sources of interindividual variation for changes in carotenoid and fatty acid levels . Changes in the Mediterranean diet were clustered together in 4 components that accounted for 78 % of the variance in plasma levels . Increases in plasma lutein , alpha-carotene , and beta-carotene clustered together in a " vegetable " pattern , and increases in carotenoids found in fruit , beta-cryptoxanthin and zeaxanthin also clustered together but accounted for less of the variance . Increases in plasma monounsaturated fatty acids were clustered with a decrease in plasma polyunsaturated fatty acids , consistent with substitution in the type of oils consumed . The only association of fatty acid levels with carotenoids was that of lycopene , which clustered together with an increase in saturated fatty acids . The changes in blood levels indicate the exchange list diet was effective for targeting Mediterranean nutrient intakes using foods available in the United States Aims /hypothesisMost studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat , carbohydrate , fibre , fruits and vegetables . Instead , we aim ed to compare diets that were available during human evolution with more recently introduced ones . Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were r and omised to receive ( 1 ) a Palaeolithic ( ‘ Old Stone Age ’ ) diet ( n = 14 ) , based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; or ( 2 ) a Consensus ( Mediterranean-like ) diet ( n = 15 ) , based on whole grains , low-fat dairy products , vegetables , fruits , fish , oils and margarines . Primary outcome variables were changes in weight , waist circumference and plasma glucose AUC ( AUC Glucose0–120 ) and plasma insulin AUC ( AUC Insulin0–120 ) in OGTTs . Results Over 12 weeks , there was a 26 % decrease of AUC Glucose0–120 ( p = 0.0001 ) in the Palaeolithic group and a 7 % decrease ( p = 0.08 ) in the Consensus group . The larger ( p = 0.001 ) improvement in the Palaeolithic group was independent ( p = 0.0008 ) of change in waist circumference ( −5.6 cm in the Palaeolithic group , −2.9 cm in the Consensus group ; p = 0.03 ) . In the study population as a whole , there was no relationship between change in AUC Glucose0–120 and changes in weight ( r = −0.06 , p = 0.9 ) or waist circumference ( r = 0.01 , p = 1.0 ) . There was a tendency for a larger decrease of AUC Insulin0–120 in the Palaeolithic group , but because of the strong association between change in AUC Insulin0–120 and change in waist circumference ( r = 0.64 , p = 0.0003 ) , this did not remain after multivariate analysis . Conclusions /interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P<.001 ) , monounsaturated fat ( 2 % ; P = .009 ) , and fiber ( 7 g/d ; P<.001 ) ; had a lower ratio of omega-6 to omega-3 fatty acids ( -5 ; P<.001 ) ; and had lower energy ( -310 kcal/d ; P<.001 ) , saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P<.001 ) than controls . Body mass index decreased more in the intervention group than in controls ( -4.2 ; P<.001 ) , as did serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance CONTEXT Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) and the interaction 's effect on serum lipid and lipoprotein levels , insulin sensitivity , and circulating antioxidant vitamin and provitamin levels . OBJECTIVE To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids , lipoproteins , antioxidants , and insulin . DESIGN , SETTING , AND PARTICIPANTS R and omized , controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku , southwestern Finl and . INTERVENTIONS After a 4- to 6-week placebo run-in period , participants were r and omly allocated to a habitual diet ( n = 60 ) or dietary treatment group ( n = 60 ) , and each of these groups was further r and omized in a double-blind crossover fashion to receive simvastatin ( 20 mg/d ) or placebo , each for 12 weeks ( n = 30 in each group ) . The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10 % by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits , vegetables , and dietary fiber . MAIN OUTCOME MEASURES Changes in levels of total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; apolipoprotein B ; insulin ; glucose ; and antioxidants at week 12 of each treatment period , compared among the 4 groups . RESULTS Dietary treatment decreased levels of total cholesterol by 7.6 % ( P<.001 ) , LDL cholesterol by 10.8 % ( P<.001 ) , HDL cholesterol by 4.9 % ( P = .01 ) , apolipoprotein B by 5.7 % ( P = .003 ) , serum insulin by 14.0 % ( P = .02 ) , and alpha-tocopherol by 3.5 % ( P = .04 ) . Simvastatin decreased levels of total cholesterol by 20.8 % , LDL cholesterol by 29.7 % , triglycerides by 13.6 % , apolipoprotein B by 22.4 % , alpha-tocopherol by 16.2 % , beta-carotene by 19.5 % , and ubiquinol-10 by 22.0 % ( P<.001 for all ) and increased levels of HDL cholesterol by 7.0 % ( P<.001 ) and serum insulin by 13.2 % ( P = .005 ) . Glucose levels remained unchanged in all groups . The effects of dietary treatment and simvastatin were independent and additive . CONCLUSIONS A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin , counteracted the fasting insulin-elevating effect of simvastatin , and , unlike simvastatin , did not decrease serum levels of beta-carotene and ubiquinol-10 Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain . The objectives of this study were to actively compare low-fat and Mediterranean-style diets  after first myocardial infa rct ion ( MI ) in a r and omized , controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis . First MI survivors were r and omized to a  low-fat ( n = 50 ) or Mediterranean-style ( n = 51 ) diet . The 2 diets were low in saturated fat ( < or = 7 % kcal ) and cholesterol ( < or = 200 mg/day ) ; the Mediterranean-style diet was distinguished by greater omega-3 fat intake ( > 0.75 % kcal ) . Participants received individual dietary counseling sessions , 2 within the first month and again at 3 , 6 , 12 , 18 , and 24 months , along with 6 group sessions . Combined dietary intervention  groups ( cases , n = 101 ) were compared with a usual-care group ( controls , n = 101 ) matched for age , gender , MI type and treatment , and status of diabetes mellitus and hypertension . Primary - outcome -free survival ( a composite of all-cause and cardiac deaths , MI , hospital admissions for heart failure , unstable angina pectoris , or stroke ) did not differ between low-fat ( 42 of 50 ) and Mediterranean-style ( 43 of 51 ) diet groups over a median follow-up period of 46 months ( range 18 to 72 ; log-rank p = 0.81 ) . Patients receiving dietary intervention had better primary - outcome -free survival ( 85 of 101 ) than usual-care controls ( 61 of 101 ) ( log-rank p < 0.001 ) , with unadjusted and adjusted odds ratios of 0.33 ( 95 % confidence interval 0.18 to 0.60 , p < 0.001 ) and 0.28 ( 95 % confidence interval 0.13 to 0.63 , p = 0.002 ) , respectively . In conclusion , active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI BACKGROUND AND AIMS To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes . METHODS AND RESULTS Twenty-seven subjects ( 47 - 77 yrs ) with type 2 diabetes were r and omly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet . Most of the meals and staple foods for the intervention diet were provided . Lipids , glycemic variables , blood pressure , homocysteine , C-reactive protein , plasma carotenoids and body composition ( anthropometry and dual energy X-ray absorptiometry ) were assessed at baseline , and at the end of both diet periods . Dietary adherence was monitored using plasma carotenoid and fatty acid ( FA ) analysis , complemented by diet diaries . Compared with usual diet , on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1 % ( 95 % CI : 6.5 - 7.7 ) to 6.8 % ( 95 % CI : 6.3 - 7.3 ) ( p=0.012 ) and diet quality improved significantly [ plant : animal ( g/day ) food ratio increased from 1.3 ( 95 % CI : 1.1 - 1.5 ) to 5.4 ( 95 % CI : 4.3 - 6.6 ) ( p<0.001 ) ] , plasma lycopene and lutein/zeaxanthin increased ( 36 % and 25 % , respectively ) , plasma saturated and trans FAs decreased , and monounsaturated FAs increased . CONCLUSION A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes , without adverse effects on weight
target: None of the interventions were significantly better than the others in lowering glucose parameters .
  The Mediterranean diet reduced HbA1c significantly compared to usual care but not compared to the Palaeolithic diet .
  The effect of alterations in dietary practice irrespective of weight loss on glycaemic control can not be concluded from the present review .
background: BACKGROUND Overweight or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management , yet many find this difficult .
  Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated .
  METHODS We conducted a systematic review and meta- analysis aim ing to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss .