Effect of weight loss on insulin sensitivity and cardiovascular risk factors in glucose tolerant and intolerant obese subjects

We observed 170 obese patients during 55 weeks in order to study the influence of insulin resistance and insulin sensitivity on cardiovascular risk factors in such patients as well as the changes occurring on these subjects as a result of weight loss. At the beginning of the study, the patients were divided into two groups, according to the results of an oral glucose tolerance test (OGTT) performed with 75 g of glucose: Group A, glucose tolerant subjects (n = 81), Group B, glucose intolerant subjects (n = 89). Initially Group B patients showed higher values for fasting blood glucose, 2 h after OGTT, systolic and diastolic blood pressure, cholesterol, triglycerides and cholesterol/HDL-cholesterol ratio when compared to Group A patients (p less than 0.05). Fasting and 1 h-post glucose load serum insulin levels in both Group A and Group B patients were higher than those found out in non over-weight tolerant subjects, but there were no differences between both groups. The serum glucose descent slope after an insulin tolerance test (ITT) was lower for group B than for group A (p less than 0.05), whereas both groups demonstrated lower descent slopes than non overweight tolerant subjects (p less than 0.05). After a 55 weeks follow-up period, the patients in Group A had lost 4.6 +/- 0.7 kg and those in Group B 6.2 +/- 1.1 kg. In both groups, the values for SBP, DBP, FBG, triglycerides and cholesterol/HDL-cholesterol ratio had dropped significantly, with a rise in the HDL-cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)     

空腹血糖升高对心血管病危险因素聚集的影响——1503例调查分析

采用分层随机抽样方法对1503名北京市成人进行心血管病危险因素的横断面调查，结果显示，随FPG水平增加，腹型肥胖、高血压、高脂血症等患病率呈线性增加，以代谢综合征（MS）为因变量的logistic回归分析显示自变量FPG的标准化p值为0．698。提示FPG水平升高与心血管病危险因素聚集相关。     

Potential effect of insulin resistance and cardiovascular risk factors on metabolic syndrome in subjects with normal fasting plasma glucose levels

The prevalence of metabolic syndrome has progressively increased with increasing fasting plasma glucose (FPG) levels. This study aimed to investigate the influence of insulin resistance and cardiovascular risk factors on metabolic syndrome in individuals with normal FPG. Study subjects with FPG levels below 100 mg/dL were divided into 5 groups depending on the exact FPG levels. We then evaluated the association of metabolic syndrome with insulin resistance and total cholesterol/ high density lipoprotein-cholesterol ratio (TC/HDL ratio). The odds ratio of insulin resistance in the level of HOMA-IR above 2.34 group [3.483(95 % CI, 1.110?～?10.932)] was significantly increased in the group of FPG level from 93 mg/dL to 99 mg/dL compared to the group below 80 mg/dL. The odds ratio of metabolic syndrome in the group of FPG level from 89 mg/dL to 92 mg/dL [2.459, (95%CI, 1.275?～?4.741)] and 93 mg/dL to 99 mg/dL [2.079, (95%CI, 1.052?～?4.110)] was significantly increased compared to the group below 80 mg/dL after adjusting age, sex, smoking status, physical activity, heavy drinking, TC/HDL ratio. Higher FPG levels within the normoglycemic range may constitute a risk of insulin resistance and is associated more strongly with the risks of metabolic syndrome.     

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients,obese non-diabetic subjects,and healthy subjects

Summary Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of ¹³C fructose (0.3 g · kg fat free mass^–1 · h^–1) for 3 h. Fructose failed to increase EGP (measured with 6,6 ²H glucose) in NIDDM (17.7±1.9 mol · kg fat free mass^–1 · min^–1 basal vs 15.9±0.9 after fructose), in obese non-diabetic subjects (12.1±0.5 basal vs 13.1±0.5 after fructose) and in lean healthy subjects (13.3±0.5 basal vs 13.8±0.6 after fructose) although ¹³C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during ¹³C fructose ingestion + hyperglucagonaemia (232±9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p<0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma ¹³C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors).Abbreviations EGP Endogenous glucose production - CHO carbohydrate - APE atom percent excess - GRd glucose rate of disappearance - FFM fat-free mass     

随访肥胖人群中代谢综合征发生的相关因素分析

目的 探讨影响随访肥胖人群代谢综合征(MS)发生的相关因素.方法 研究对象来自2000年筛查出的413例单纯肥胖者(体重指数≥25 kg/m2)及196名正常体重的健康人,7年后对此人群的体脂、血压、血脂、血糖情况进行随访调查.并测定随访前后胰岛素抵抗指数和血管内皮功能.结果 共随访到553例,其中单纯肥胖者381例(单纯肥胖组),正常体重者172名(正常体重组).单纯肥胖组MS累积发生率35.17％,正常体重组MS累积发生率8.14％.单纯肥胖组有MS者与无MS者比较,基线时的腰围、腰臀比、甘油三酯、空腹血糖、空腹胰岛素、稳态模型评估的胰岛素抵抗指数( HOMA-IR)显著升高(均P＜0.05),内皮依赖性舒张功能(EDD)明显降低(P＜0.01).正常体重组发生MS者的腰围、腰臀比、空腹胰岛素也高于未发生MS者(均P＜0.05),而EDD低于未发生者(P＜0.05).Logistic回归分析显示,男性性别、腰围、腰臀比、空腹血糖、HOMA-IR和EDD是发生MS的危险因素.结论 腹型肥胖、胰岛素抵抗和内皮功能障碍是MS发生的基本病因.     

Periodontitis and cardiovascular risk factors in subjects with and without type 1 diabetes: A cross sectional analysis

AimsThis cross-sectional analysis explored the relationships between periodontal disease (PD) and subclinical CVD in a cohort of patients with type 1 diabetes and non-diabetic controls.MethodsData were collected from adults enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study or enrolled through the Barbara Davis Center for Diabetes Adult Clinic. A clinical periodontal exam measured attachment loss and probing depth. Brachial artery distensibility (brachD), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) were assessed as measures of subclinical cardiovascular structure and function.Results144 participants with T1D and 148 non-diabetics were enrolled. Compared to non-diabetic controls, T1D participants had a higher probing depth (2.6 mm vs. 2.5 mm; p = 0.04), higher attachment loss (2.7 mm vs. 2.4 mm; p < 0.01), lower brachD (mean 5.8 vs. 6.4 mmHg; p < 0.01), a higher cIMT (mean 0.68 vs. 0.64 mm; p < 0.01), and a higher PWV (mean 8.3 vs. 7.8 m/s; p < 0.01). There were no significant associations between PD and CVD metrics.ConclusionsPeriodontal and cardiovascular health was worse in participants with T1D compared to non-diabetics. No significant associations between PD measures and CVD were identified.     

The effects of metformin on metabolic and cardiovascular risk factors in nonobese women with polycystic ovary syndrome

Objective There are conflicting data regarding the effects of metformin in lean women with polycystic ovary syndrome (PCOS). Thus, our aim was to evaluate the effects of 6 months of metformin therapy on various metabolic and cardiovascular risk factors in lean women with PCOS. Design This was a prospective clinical study performed in a University hospital. Patients Twenty nonobese PCOS women and 20 age‐ and BMI‐matched healthy women were included in the study. Metformin (2550 mg/day) was administered for 6 months in women with PCOS. The hormonal and metabolic parameters were evaluated before and after metformin treatment. Measurements The main outcome measures were serum androgens, FSH, LH, oestradiol, 17‐hydroxyprogesterone, glucose, insulin, lipid profile, lipoprotein(a) [Lp(a)] and homocysteine levels. In addition 24‐h ambulatory blood pressure monitoring (ABPM) and carotid intima‐media thickness (IMT) were taken. Results After 6 months of metformin therapy, women with PCOS had decreased LH, total testosterone, free androgen index and slightly increased SHBG levels. Metformin treatment resulted in resumption of regular menses in 12 (60%) patients, and in 8 (40%) of them serum progesterone level was compatible with ovulation. Glucose and insulin responses to oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA‐IR) did not improve after the metformin therapy. There were no significant changes in terms of cardiovascular risk factors such as lipids and homocysteine, IMT and ABPM. Conclusion Metformin may have beneficial effects in lean PCOS women in terms of resumption of menses without any remarkable effect on metabolic and cardiovascular risk factors.     

Effects of cardiovascular risk factors on coronary artery remodeling in patients with mild atherosclerosis

BACKGROUND: Vascular remodeling counteracts luminal encroachment during the progression of coronary artery disease (CAD) and modulates the manifestation of hemodynamically significant lesions. However, the role of cardiovascular risk factors for coronary remodeling has not been fully clarified. METHODS: Therefore, we investigated the role of local plaque burden and systemic risk factors on coronary vascular remodeling in 25 patients (49 segments) with angiographically normal or minimally diseased coronary arteries by intravascular ultrasound. In an additional 12 patients without coronary atherosclerosis, physiological vessel tapering was determined and used to calculate the extent of remodeling in diseased segments. RESULTS: An increase in local plaque burden was directly correlated with positive vascular remodeling (r = 0.54, P<0.001). However, cardiovascular risk factors like hypertension (P<0.001) and hypercholesterolemia (P = 0.03) were associated with reduced positive or even negative remodeling. Moreover, the total number of classical cardiovascular risk factors was a strong predictor for reduced positive remodeling (P for trend <0.001). In contrast, coronary flow reserve, a measure of shear stress imposed on the vessel wall, positively correlated with compensatory enlargement (r = 0.44, P = 0.002). By multivariate analysis, plaque burden (P = 0.001), hypertension (P = 0.001) and coronary flow reserve (P = 0.018) proved to be independent determinants of vascular remodeling of epicardial coronary arteries. CONCLUSIONS: Cardiovascular risk factors impair compensatory arterial enlargement and even predispose to shrinkage of epicardial arteries during the initial stage of atherosclerosis. Reduced positive vascular remodeling might contribute to the clinical manifestation of CAD by facilitating the development of flow-limiting stenoses in patients at risk.     

Effects of exercise on coronary risk factors in obese, middle-aged subjects

The effects of exercise (10000 walk steps/day) and diet (1500 kcal/day) for 4 months on coronary risk factors (obesity, hypertension, serum lipid and lipoprotein abnormalities) were studied in 332 obese, middle-aged subjects. Body weight, skinfold thickness, systolic and diastolic blood pressures, serum lipid and lipoproteins (total cholesterol, triglyceride, and beta-lipoprotein) improved significantly (p less than 0.05) during the program. The degree of improvement in blood pressures, serum lipids and lipoproteins was greater in abnormal blood pressure (greater than 140/90 mmHg) or abnormal serum lipid group than in normal group. A significant correlation was observed between daily number of walk steps and the improvement of body weight, diastolic blood pressure and HDL-cholesterol. Increase of daily steps during the program showed a significant (p less than 0.05) correlation to the change in HDL-cholesterol. It was suggested that mild exercise characterized by brisk walking was effective in the treatment of obesity, hypertension and low HDL-cholesterolemia in obese, middle-aged subjects.     

Association of hemoglobin glycation index with cardiovascular risk factors in non-diabetic adults: A cross-sectional study

Background and aimsThe study aimed to explore the association of hemoglobin glycation index (HGI) with cardiovascular risk factors in non-diabetic adults.MethodsThis cross-sectional study included 200 adults of 20–60 years of age. Predicted glycated hemoglobin (HbA1c) was calculated from linear regression equation. HGI was calculated using the formula HGI = measured HbA1c– predicted HbA1c. The study subjects were classified into three groups based on their HGI tertiles. Cardiovascular risk factors were compared between the groups and Pearson correlation test was done to correlate HGI with cardiovascular risk factors.ResultsSerum total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) showed significant increase with increase in HGI in non diabetic individuals. High HGI group had significantly high serum total cholesterol, triglyceride, LDL-C and VLDL-C compared to low HGI group. Serum total cholesterol, triglyceride, LDL-C and VLDL-C showed a statistically significant positive correlation with HGI.ConclusionWe have found a statistically significant correlation of HGI with serum lipid profile, a significant cardiovascular risk factor in non-diabetic individuals. HGI, a simple derivative of HbA1c and fasting plasma glucose may be used to identify cardiovascular risk in non-diabetic individuals. Further prospective studies are required in larger sample size to confirm the clinical implications of HGI.     

Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes

OBJECTIVES: To measure the effect of metformin on the body composition, insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus (type 2 DM). Design: Placebo-controlled clinical trial. MATERIAL AND METHODS: Twenty-three subjects with risk factors for type 2 DM were randomly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months. Before and after the treatment, the body mass index and waist/hip ratio were calculated, the body composition was measured through bioelectric impedance and the fasting levels of blood glucose, insulin, triglycerides and cholesterol were measured. The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method. The Wilcoxon rank test was used. RESULTS: Twenty-one subjects completed the study, 12 of the metformin group and nine of the placebo group. In the metformin group, there was a decrease in fat weight from 25.9 +/- 9.4 to 20.8 +/- 9.2 kg, p < 0.01, an increase in lean weight from 57.05 +/- 13.6 to 61.9 +/- 16.5 kg, p < 0.01, an increase in basal metabolism from 1735 +/- 413 to 1878 +/- 505 calories/day, p < 0.05 and an increase in body water, p < 0.05. There was no significant decrease in insulin resistance. In the placebo group, the blood glucose increased from 84.7 +/- 13 to 96.7 +/- 16 mg/dl, p < 0.05. There were no significant modifications in lipids. CONCLUSIONS: The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM.     

Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus

In light of the conflicting results of the recent United Kingdom Prospective Study (UKPDS), where diabetic patients on metformin monotherapy had lower all-cause mortality and the addition of metformin in sulfonylurea-treated patients was associated with an increased risk of diabetes-related death, we sought to compare the effects on cardiovascular disease (CVD) risk factors of metformin monotherapy with metformin treatment when added to a sulfonylurea compound in patients with type 2 diabetes. Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks. Measurements were made of (1) fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), lipid, remnant lipoprotein cholesterol (RLP-C) levels, and low-density lipoprotein (LDL) particle size; (2) daylong plasma glucose, insulin, free fatty acid (FFA), triglyceride (TG), and RLP-C concentrations; and (3) fasting levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin). Fasting plasma glucose concentrations decreased to a similar degree after treatment with metformin in both the metformin monotherapy group (12.45 +/- 0.48 v 9.46 +/- 0.47 mmol/L, P <.001) and the combined SU and metformin therapy group (14.09 +/- 0.51 v 10.57 +/- 0.85 mmol/L, P =.001). Fasting plasma lipid concentrations and LDL particle size did not significantly change in either treatment group, whereas fasting RLP-C concentrations were significantly lower in the metformin monotherapy group (0.43 +/- 0.09 v 0.34 +/- 0.07 mmol/L, P =.02). Daylong concentrations of plasma glucose, FFA, TG, and RLP-C were lower to a similar degree in both treatment groups, whereas daylong plasma insulin concentrations were unchanged. Fasting plasma sVCAM-1 levels were significantly lower in both the metformin monotherapy group (484 +/- 19 v 446 +/- 18 ng/mL, P =.02) and the combined SU and metformin therapy group (496 +/- 29 v 456 +/- 31 ng/mL, P =.05), whereas fasting plasma sICAM-1 and sE-selectin levels were essentially unchanged. Administration of metformin, either as monotherapy or in combination with a sulfonylurea drug, improved glycemic control and led to a decrease in several CVD risk factors in patients with type 2 diabetes.     

Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET)

Abstract. Adamsson V, Reumark A, Fredriksson I‐B, Hammarström E, Vessby B, Johansson G, Risérus U (Uppsala University, Uppsala; Lantmännen R&D, Stockholm; Bollnäs Heart Clinic, Mitt Hjärta, Bollnäs; Halmstad University, Halmstad, Sweden). Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET). J Intern Med 2011; 269 : 150–159. Objective. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. Design and subjects. In a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects’ usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low‐density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment‐insulin resistance). The ND was rich in high‐fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low‐fat milk products, but low in salt, added sugars and saturated fats. Results. The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (?16%, P < 0.001), LDL cholesterol (?21%, P < 0.001), high‐density lipoprotein (HDL) cholesterol (?5%, P < 0.01), LDL/HDL (?14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (?1%, P < 0.05) in the ND group. The ND reduced insulin (?9%, P = 0.01) and systolic BP by ?6.6 ± 13.2 mmHg (?5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (?4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. Conclusions. A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects.     

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial

Aim

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy.

Materials and Methods

In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5–7.8 mmol/L (63–140 mg/dL).

Results

Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1–6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4–72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes.

Conclusion

In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.     

A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

Aims/hypothesis

Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance.

Methods

We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment.

Results

Seventy-one individuals were randomised to placebo (n?=?36) or salsalate (n?=?35). Glucose disposal did not change in either group (salsalate 1% [95% CI ?39%, 56%]; placebo 6% [95% CI ?20%, 61%], p?=?0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p?=?0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p?=?0.01) and adiponectin increased by 53% (p?=?0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (?16% vs 42%, p?=?0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n?=?4 vs n?=?2).

Conclusions/interpretation

In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-κB activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement.

Trial registration

ClinicalTrials.gov NCT00330733

Funding

Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214