Plasma Adiponectin Levels in Overweight and Obese Asians

Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m²], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m²). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Relationship between Plasma Adiponectin Levels and Metabolic Risk Profiles in Taiwanese Children

Objective: Adiponectin, a novel adipokine with antiinflammatory and insulin‐sensitizing properties, has an important role in glucose metabolism and is negatively correlated with body fat amount in adults. The purpose of this study was to evaluate the association of plasma adiponectin level with metabolic risk profiles and insulin resistance status among Taiwanese children. Research Methods and Procedures: We enrolled 1248 children (608 boys and 640 girls) to ascertain their demographic, anthropometric, and cardiovascular risk factors distribution in Taipei. We measured plasma insulin, adiponectin, and leptin levels by radioimmunoassay (Linco Research Inc, St. Charles, MO). We calculated an insulin resistance index (IRI) using the Homeostasis Model Assessment model and also calculated an insulin resistance syndrome (IRS) summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure, serum triglyceride, high‐density lipoprotein‐cholesterol (HDL‐C) (inverse), and insulin levels. Results: In general, the boys had larger BMI, higher systolic blood pressure, serum total cholesterol, and triglyceride, and lower plasma leptin and adiponectin levels than girls. Plasma adiponectin levels were correlated negatively with BMI, leptin, insulin, IRI, and IRS summary score but positively correlated with HDL‐C in both boys and girls. In multivariate regression analyses, adiponectin was negatively associated with insulin (girls only), IRI (girls only), and IRS score, and positively associated with HDL‐C in both genders even after adjusting for age, BMI, plasma leptin level, and other potential confounders. Discussion: These data suggest that plasma adiponectin levels were negatively associated with metabolic risk profiles that may have played a protective role in the development of insulin resistance among Taiwanese school children.     

The Association between Plasma Adiponectin and Insulin Sensitivity in Humans Depends on Obesity

Objective: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. Research Methods and Procedures: We investigated the cross‐sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose‐tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. Results: In cross‐sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin × PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R² = 0.10, p = 0.13, OGTT; and R² = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R² = 0.36, p < 0.0001, OGTT; and R² = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. Discussion: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin‐resistant individuals.     

Adiponectin receptor 1 variants associated with lower insulin resistance in African Americans

Adiponectin has been shown to have a role in insulin resistance. However, little is known about the contribution of genetic variation in the adiponectin receptor 1 gene (ADIPOR1) in this regard. We hypothesized that variation in ADIPOR1 would be associated with significant changes in insulin resistance and tested this hypothesis in a cohort of 483 African-American adolescents. Seven single nucleotide polymorphisms (SNPs) of ADIPOR1 spanning from the promoter to the 3'-untranslated region were genotyped. We analyzed single SNPs and haplotypes for associations with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] in the full cohort as well as lean (BMI < 85%) and non-lean (BMI >or= 85%) subsets. There was no evidence of ADIPOR1 variant effects on HOMA-IR in the full cohort or in the lean subset. However, in the non-lean subset, SNP +5843 (A allele), and haplotypes including SNPs -8505/-5692/+3002/+5843 (ATTA and AGTG) showed significant associations with decreased HOMA-IR after adjustment for sex, puberty, adiponectin, and waist z-score. Our findings suggest not only that ADIPOR1 variants influence insulin resistance in the presence of adiposity, but also that these variants and haplotypes are protective in African Americans.     

Plasma Leptin Response to an Epinephrine Infusion in Lean and Obese Women

Objective: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. Research Methods and Procedures: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 μg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index ± SD: 22.6 ± 1.1 kg/m²) and 15 obese (30.0 ± 1.3 kg/m²) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (−15 and 0 minutes) and at every 30 minutes over the 90-minute period. Results: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = −0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from −12 to −570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = −0.14, p = 0.55). Discussion: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.     

Adiponectin and its association with insulin resistance and type 2 diabetes

Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid (FFA), which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes (T2D). This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponeetinemia at a molecular level.     

脂联素基因单核苷酸多态性与Ⅱ型糖尿病合并肥胖及胰岛素抵抗相关联

脂联素是近年新发现的脂肪组织特异性的细胞因子,其mRNA是脂肪组织中含量最丰富的基因转录产物,该因子可通过多种途径影响个体对胰岛素的敏感性。脂联素基因多态性与肥胖、胰岛素抵抗和2型糖尿病密切相关,而与冠心病相关性研究的报道较少。本研究以中国汉族人群1,098例为对象,其中304例冠心病(CHD)患者,389例糖尿病患者(T2DM),及405例性别年龄相匹配的正常对照,采用PCR-RFLP技术对脂联素基因-4522C/T进行基因分型,并分别对血脂水平、胰岛素抵抗、体重指数等临床数据进行分析比较。研究结果显示,脂联素基因-4522C/T各基因型及等位基因在CHD组与对照组、T2DM组与对照组中的分布差异无显著性;经分组分析发现,T2DM合并肥胖患者BMI≥25kg/m2TT基因型及T等位基因明显多于对照组,差异有显著性,P=0.014和P=0.034;TT基因型T2DM患者胰岛素抵抗指数(HOMA-IR)显著高于携带有C等位基因的T2DM患者,P=0.0069。本研究提示脂联素基因-4522C/T与中国汉族人群T2DM合并肥胖的发生及T2DM患者胰岛素抵抗相关,是引发糖尿病患者肥胖和胰岛素抵抗的重要候选基因,而与冠心病的发生无关联。     

Effect of Glucose Tolerance Status on PAI‐1 Plasma Levels in Overweight and Obese Subjects

Objective: The aim of our study was to examine whether plasminogen activator inhibitor‐1 (PAI‐1) plasma levels varied as a function of differences in glucose tolerance status independently of body fatness, body‐fat distribution, and insulin sensitivity. Research Methods and Procedures: Plasma PAI‐1 antigen levels, along with insulin resistance [measured by homeostatic model assessment (HOMA_IR)], central fat accumulation, body composition, blood pressure, and fasting concentrations of glucose, insulin, and lipids, were measured in 229 overweight and obese [body mass index (BMI) ≥25 kg/m²) subjects with normal glucose tolerance (NGT) and in 44 age‐ and BMI‐matched subjects with impaired glucose tolerance (IGT). Results: Plasma PAI‐1 antigen levels were significantly higher in IGT than in NGT subjects. Log PAI‐1 was positively correlated with BMI, HOMA_IR, and log insulin, and inversely associated with high‐density lipoprotein‐cholesterol both in IGT and in NGT individuals. On the other hand, log PAI‐1 was positively correlated with waist circumference, fat mass (FM), fat‐free mass, systolic and diastolic blood pressure, and log triglycerides only in the NGT group. After multivariate analyses, the strongest determinants of PAI‐1 levels were BMI, FM, waist circumference, and high‐density lipoprotein cholesterol in the NGT group and only HOMA_IR in the IGT cohort. Discussion: This study demonstrates that PAI‐1 concentrations are higher in IGT than in NGT subjects. Furthermore, we suggest that the influences of total adiposity, central fat, and insulin resistance, main determinants of PAI‐1 concentrations, are different according to the degree of glucose tolerance.     

Porcine Adiponectin Receptor 1 Transgene Resists High-fat/Sucrose Diet-Induced Weight Gain,Hepatosteatosis and Insulin Resistance in Mice

Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its beneficial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets.     

Normal Insulin Sensitivity in Lean Offspring of Obese Parents

Objective: Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents. Research Methods and Procedures: Twenty‐one lean offspring of nonobese subjects [(OL) 22 ± 3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram_FFM; where FFM represents fat‐free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (χ² = 30.2, p = 0.001) concordance of BMI between parents and offspring. Results: In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value = 45 ± 12 (OOb) vs. 47 ± 17 μmol/min per kilogram_FFM (OL)], insulin‐induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose‐induced thermogenesis. Discussion: The metabolic similarity between lean offspring of obese parents and those of nonobese parents suggests that insulin resistance and its correlates are not co‐inherited with the predisposition to develop obesity.     

Lower Serum Adiponectin Levels in African‐American Boys

Objective: To examine adiponectin, an adipocyte‐secreted hormone with anti‐inflammatory and insulin‐sensitizing effects, in relation to race or gender in younger subjects. Research Methods and Procedures: The relationship of adiponectin, quantitated by radioimmunoassay, to anthropometric and metabolic factors (fasting insulin, glucose, and leptin) and reproductive hormones was examined in 46 healthy African Americans (25 girls/21 boys) and 40 whites (20 girls/20 boys) ranging in age from 12 to 21 years. Results: There was no statistical difference in BMI or in BMI percentile among the four groups. Sums of skinfolds, but not skinfold percentile, were significantly lower in boys than girls (p = 0.001 and p = 0.896, respectively), whereas there was no difference between racial groups. Leptin was significantly greater in girls (p = 0.0002). There was no difference in fasting serum glucose, insulin, or homeostasis model assessment score among any of the groups. There was a significant negative univariate relationship between serum adiponectin and both BMI and BMI percentile for the entire group (p = 0.006 and p = 0.005). In a multivariate model, BMI percentile (p = 0.005) and the interaction between race and gender (p = 0.026) were significant predictors of serum adiponectin. In this model, African‐American boys had the lowest serum adiponectin level, 37% less than white boys, who had the highest adiponectin levels. Discussion: Serum adiponectin levels are reduced in young obese subjects (African Americans and whites) and are lower in African‐American boys than white boys. A lower adiponectin level in African‐American boys may predispose this group to a greater risk of diabetes and cardiovascular disease.     

Long-term Effects of Water-soluble Corn Bran Hemicellulose on Glucose Tolerance in Obese and Non-obese Patients: Improved Insulin Sensitivity and Glucose Metabolism in Obese Subjects

We examined the effect of soluble corn bran hemicellulose (CBH, 10g/day) on glucose control and serum insulin in three groups: patients with impaired glucose tolerance (IGT) with (20 subjects) or without (8 subjects) obesity and with healthy non-obese controls (10 subjects). Long-term supplementation (6 months) with CBH decreased the post oGTT curve for patients with impaired mild Type II diabetes, but not that for the controls. Hemoglobin A_1c decreased significantly during CBH supplementation in the obese patients, while the fasting glucose level decreased in all three groups, although not significantly. A decreased serum insulin response by oGTT was found in those patients with IGT.

The improved oGTT result was associated with improved insulin release and perhaps with peripheral insulin sensitivity. These findings suggest that CBH at a low dose might contribute to glycemic control and would play a useful role in treating Type II diabetes patients.     

Adiponectin decreases plasma glucose and improves insulin sensitivity in diabetic Swine

To investigate the effects of recombinant human adiponectin on the metabolism of diabeticswine induced by feeding a high-fat/high-sucrose diet (HFSD),diabetic animal models were constructedby feeding swine with HFSD for 6 months.The effects of recombinant adiponectin were assessed bydetecting the change of plasma glucose levels by commercially available enzymatic method test kits andevaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinantadiponectin was produced using a 15-liter fermenter.A single injection of purified recombinant humanadiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin,which triggered atransient decrease in basal glucose level (P<0.05).This effect on glucose was not associated with anincrease in insulin level.Moreover,after adiponectin injection,swine also showed improved insulin sensitivitycompared with the control (P<0.05).Adiponectin might have the potential to be a glucose-lowering agentfor metabolic disease.Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolismcould be useful to treat insulin resistance.     

Decrease in Serum Adiponectin Level Due to Obesity and Visceral Fat Accumulation in Children

Objective: To determine whether serum adiponectin is decreased in obesity and is restored toward normal level after treatment in children. Research Methods and Procedures: Subjects were 53 Japanese obese children, 33 boys and 20 girls (6 to 14 years old), and 30 age‐matched nonobese controls for measuring adiponectin (16 boys and 14 girls). Blood was drawn after an overnight fast, and the obese children were subjected to anthropometric measurements including waist and hip circumferences and skinfold thicknesses. Paired samples were obtained from 21 obese children who underwent psychoeducational therapy. Visceral adipose tissue area was measured by computed tomography. Adiponectin was assayed by an enzyme‐linked immunosorbent assay. Results: The serum levels of alanine aminotransferase, uric acid, triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol, total cholesterol/high‐density lipoprotein‐cholesterol, apo B, apo B/apo A₁, and insulin in obese children were higher than the reference values. Serum adiponectin level was lower in the obese children than in the controls (6.4 ± 0.6 vs. 10.2 ± 0.8 mg/L, means ± SEM, p < 0.001). In 21 obese children whose percent overweight declined during therapy, the adiponectin level increased (p = 0.002). The adiponectin level was correlated inversely with visceral adipose tissue area in obese children (r = ?0.531, p < 0.001). The inverse correlations of adiponectin with alanine aminotransferase, uric acid, and insulin were significant after being adjusted for percentage overweight, percentage body fat, or sex. Discussion: Serum adiponectin level is decreased in obese children depending on the accumulation of visceral fat and is restored toward normal level by slimming.     

Plasma Levels of Adiponectin,a Novel Adipocyte‐Derived Hormone,in Sleep Apnea**

Objective: Obstructive sleep apnea (OSA) is associated with obesity, sympathetic activation, systemic inflammation, and cardiovascular morbidity. Obesity, β‐adrenergic agonists, and inflammation are linked to decreased expression and/or secretion of an adipose tissue‐derived antiatherogenic hormone, adiponectin. The purpose of the study was to investigate whether OSA affected plasma levels of adiponectin, which might help explain OSA‐associated cardiovascular morbidity. Research Methods and Procedures: We randomly selected 68 otherwise healthy male subjects, either with moderate/severe OSA [apnea‐hypopnea index (AHI) ≥ 20; n = 35] or without OSA (AHI ≤ 5; n = 33). The diagnosis of OSA was made based on prospective full polysomnography. Adiponectin was measured before polysomnography between 8 and 10 PM . Results: AHI was higher in the OSA group (49.5 ± 4.4 vs. 2.9 ± 0.4 events/h; p < 0.001). OSA subjects were also more obese, with greater BMI (33 ± 1 vs. 30 ± 1; p = 0.016) and percentage body fat (29 ± 1% vs. 26 ± 1%; p = 0.030). Adiponectin levels were 7.67 ± 0.73 and 6.33 ± 0.51 μg/mL in the OSA and non‐OSA groups, respectively, and this difference was significant in covariate analysis (taking into account age, hemodynamic characteristics, measures of body fat, and OSA severity) (p = 0.009). After excluding from both groups the subjects with extreme BMI, such that the OSA and non‐OSA study cohorts had similar BMI and percentage body fat, subjects with OSA had significantly higher plasma adiponectin (8.49 ± 0.92 vs. 6.32 ± 0.55 μg/mL; p = 0.042), differences also evident in covariate analysis (p = 0.017). Discussion: Plasma adiponectin levels are elevated in otherwise healthy subjects with OSA. Therefore, low adiponectin is unlikely to explain the association between OSA and cardiovascular disease.     

Insulin and Endothelin in the Acute Regulation of Adiponectin in Vivo in Humans

Objective: In vitro, insulin and endothelin (ET) both modulate adiponectin secretion from adipocyte cell lines. The current studies were performed to assess whether endogenous ET contributes to the acute action of insulin infusions on adiponectin levels in vivo in humans. Research Methods and Procedures: We studied 17 lean and 20 obese subjects (BMI 21.8 ± 2.2 and 34.0 ± 5.0 kg/m², respectively). Hyperinsulinemic euglycemic clamp studies were performed using insulin infusion rates of 10, 30, or 300 mU/m² per minute alone or with concurrent infusion of BQ123, an antagonist of type A ET receptors. Circulating adiponectin levels were assessed at baseline and after achievement of steady‐state glucose with the insulin infusion. Results: Adiponectin levels were lower in obese than lean subjects (6.76 ± 3.66 vs. 8.37 ± 2.79 μg/mL, p = 0.0148 adjusted for differences across gender). Insulin infusions suppressed adiponectin by a mean of 7.8% (p < 0.0001). In a subset of 13 lean and 14 obese subjects for whom data with and without BQ123 were available, there was no evident effect of BQ123 to modulate clamp‐associated suppression of adiponectin (p = 0.16). Surprisingly, there was no evident relationship between steady‐state insulin concentrations and adiponectin suppression (r = 0.14, p = 0.30), and again no effect of BQ123 to modify this relationship was seen. Discussion: Despite baseline differences in adiponectin levels, we observed equal suppression of adiponectin with insulin infusions in lean and obese subjects. ET receptor antagonism with BQ123 did not modulate this effect, suggesting that endogenous ET does not have a role in modifying the acute effects of insulin on adiponectin production and/or disposition.     

A Dietary Supplement Containing Cinnamon,Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized,Placebo-Controlled Trial

Background

Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue.

Objectives

Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed.

Methods

In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m², unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization.

Results

Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement.

Conclusions

Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes.

Trial Registration

ClinicalTrials.gov NCT01530685