C825T Polymorphism of the G Protein β3 Subunit Is Associated with Obesity but Not with Insulin Sensitivity

Objective: The common C825T polymorphism of the gene that encodes the G protein β₃ subunit has been shown to influence lipolysis in human adipocytes and to be associated with hypertension, body fat distribution, and obesity. In addition, it has been shown to be associated with insulin resistance in a small group of hypertensive subjects. We investigated whether this polymorphism contributed to the variability in obesity in our population from southern Germany and whether it was associated with insulin sensitivity of lipolysis and/or glucose disposal. Research Methods and Procedures: We determined percentage body fat, body fat distribution, glucose tolerance [oral glucose‐tolerance test (OGTT)], insulin sensitivity, and serum free fatty acids using data from OGTTs (N = 774) and clamp (euglycemic hyperinsulinemic clamp, N = 216) in normal and impaired glucose tolerant subjects who were genotyped for this polymorphism. Results: Compared with noncarriers of the C825T mutation, subjects with the C825T variant (prevalence ～32%) had higher percentage body fat (p = 0.02) and higher BMI (p = 0.03). No conclusive effect was seen on serum free fatty acids measured either during fasting or at the end of a 2‐hour OGTT. Insulin sensitivity determined during the OGTT and during the clamp, both adjusted for age, gender, and percentage body fat, was not different between the genotypes (p = 0.33 and p = 0.48, respectively). Discussion: We have concluded that the C825T polymorphism in the G protein β₃ subunit played an important role in the determination of obesity in this German population. However, it probably had no direct effects on insulin sensitivity of lipolysis and glucose disposal.     

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。     

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.     

Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin −0.7 ± 0.7%, p ≤ 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 ± 14.5 μmol glucose/min/kg free fat mass, p < 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p ≤ 0.05) with RSG (2.1 ± 2.0 kg and 1.4 ± 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 ± 28.7 cm², p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (−6.7 ± 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.     

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.     

Mediating Effects of Inflammatory Biomarkers on Insulin Resistance Associated with Obesity

Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C‐reactive protein (CRP), E‐selectin, and intercellular adhesion molecule‐1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes. Research Methods and Procedures: We stratified 510 initially non‐diabetic women in the Nurses’ Health Study cohort into four phenotypes above/below median BMI (27 kg/m²) and waist circumference (81 cm): low BMI‐low waist (LBLW; N = 190), low BMI‐high waist (LBHW; N = 74), high BMI‐low waist (HBLW; N = 27), and high BMI‐high waist (HBHW; N = 219). Results: In models assessing associations of weight phenotype with IR [fasting insulin (FI)], adjusted for age and diabetes risk factors, mean FI was higher comparing HBHW women (13.6 μU/mL, p < 0.0001) and LBHW (11.5 μU/mL, p = 0.02) with LBLW women (8.6 μU/mL); HBLW and LBLW women were not significantly different. Differences in FI levels were most strongly attenuated after adjustment for E‐selectin comparing LBHW with LBLW women (11.7 vs. 9.7 μU/mL, p = 0.2). Discussion: In logistic regression models, LBHW predicted diabetes (risk factor‐adjusted relative risk 2.06, 1.05 to 6.40), compared with LBLW, but was no longer significant after adjustment for E‐selectin or CRP. After adjusting for CRP and E‐selectin, only HBHW and E‐selectin were significantly associated with risk of diabetes. In women with central adiposity and low BMI, endothelial dysfunction and inflammation may mediate the relationship among central fat, IR, and incident diabetes.     

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.     

Dietary Fat Intake and Insulin Resistance in Black and White Children

Objective: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. Research Methods and Procedures: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24‐hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above‐AMDR/within‐AMDR guidelines), and differences were analyzed by 2 × 2 analysis of covariance, adjusting for covariates. Results: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above‐AMDR compared with within‐AMDR blacks) and was not seen in whites. Discussion: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

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.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.     

Effect of the Interleukin‐6 (−174) G/C Promoter Polymorphism on Adiponectin and Insulin Sensitivity

We investigated the relation among the interleukin (IL)‐6 (?174) G/C promoter polymorphism, adipose tissue gene expression of IL6, circulating adiponectin, and systemic insulin sensitivity. Eighty‐five Swedish male subjects who had participated in our previous prediabetic phenotype characterization study were genotyped for the IL6 (?174) G/C polymorphism. Subcutaneous adipose tissue gene expression of IL6 and adiponectin was measured in 44 subjects. The IL6 (?174) G allele carriers had higher fasting plasma insulin levels (C/C, 7.8 ± 1.1; G/C, 9.0 ± 0.6; G/G, 10.5 ± 1.0 mU/L) and higher homeostasis model assessment for insulin resistance (C/C, 1.6 ± 0.2; G/C, 1.9 ± 0.1; G/G, 2.2 ± 0.2) compared with subjects with the C/C genotype. The circulating adiponectin levels were lower in the G allele carriers (C/C, 7.93 ± 0.45; G/C, 7.05 ± 0.44; G/G, 7.02 ± 0.46 μg/mL), whereas the IL‐6 levels did not differ among the three genotypes. Adipose tissue IL6 gene expression was significantly higher in the G allele carriers compared with the subjects homozygous for the C allele (C/C, 0.29 ± 0.15; G/C, 0.84 ± 0.29; G/G, 0.62 ± 0.35). Our results suggest that IL6 (?174) G/C polymorphism is associated with insulin resistance and increased adipose tissue IL6 gene expression, which can impair adiponectin production.     

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.     

Association of Total and Central Adiposity Measures with Fasting Insulin in a Biracial Population of Young Adults with Normal Glucose Tolerance: the CARDIA Study

SIDNEY, STEPHEN, CORA E. LEWIS, JAMES O. HILL, CHARLES P. QUESENBERRY, JR, ELIZABETH R. STAMM, ANN SCHERZINGER, KIMBERLY TOLAN, AND BRUCE ETTINGER. Association of total and central adiposity measures with fasting insulin in a biracial population of young adults with normal glucose tolerance: the CARDIA study. Obes Res. Objective: To determine the association of computed tomography (CT)-measured visceral adipose tissue (AT) and other measures of adiposity with fasting insulin in a biracial (African American and Caucasian) study population of young adults. Research Methods and Procedures: The study population consisted of 251 young adults with normal glucose tolerance (NGT), ages 28–40 years, who were volunteers from the Birmingham, Alabama, and Oakland, California centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Results: In regression models with total adiposity measures (body mass index or dual-energy X-ray absorptiometry-measured percent fat), visceral AT (measured as a cross-sectional area in cm²) was generally a stronger predictor of insulin than overall adiposity in all race/gender groups (partial correlation coefficients ranging from 0. 31 to 0. 47) except for black men, in whom the associations were nonsignificant. Partial correlation coefficients between waist circumference and insulin, controlling for percent fat, were nearly identical to those between visceral AT and insulin in women and in white men. Analyses performed on 2060 NGT CARDIA subjects who were not in this study of visceral AT showed significant correlations of waist circumference with insulin in all racelgender groups, including black men, and that black men in the visceral AT study group were significantly leaner than other black male CARDIA subjects. Discussion: We conclude that visceral AT was associated with fasting insulin in NGT participants in three of the four race/gender groups (black men excepted) and that waist circumference was a good surrogate for visceral AT in examining associations of central adiposity with fasting insulin.     

Dysregulation of the Autonomic Nervous System Can Be a Link between Visceral Adiposity and Insulin Resistance

Objective: To evaluate the interplay among abdominal adipose tissue distribution, the cortisol axis, the autonomic nervous system, and insulin resistance. Research Methods and Procedures: Two age‐, sex‐, and BMI‐matched groups were studied. Fifteen subjects were first‐degree relatives of patients with type 2 diabetes (R), and 15 had no family history of diabetes (controls, C). A hyperinsulinemic euglycemic clamp, cortisol measurements, and analysis of heart rate variability (HRV) were performed. Computed tomography was performed in a subgroup (n = 9 + 9) to determine abdominal adipose tissue distribution. Results: R tended to be less insulin‐sensitive than C (M value 9.2 ± 1.0 vs 10.3 ± 0.7 mg/kg per minute, not significant). Stimulation with tetracosactin or corticotropin releasing hormone yielded lower peak serum cortisol levels in R (p = 0.03 and p = 0.06, respectively). The amount of visceral abdominal fat (VAT) tended to be greater in R. In all subjects, VAT was negatively correlated to insulin sensitivity (r = ?0.93, p < 0.001). There was a positive association between VAT and resting heart rate (r = 0.70, p = 0.003) and sympathetic/parasympathetic ratio in HRV assessment after tilt (r = 0.53, p = 0.03). Subcutaneous abdominal tissue was not associated with insulin sensitivity or any of the hormonal or HRV assessments. Discussion: Subjects genetically predisposed for type 2 diabetes had a tendency toward a larger amount of VAT and to lower insulin sensitivity compared with control subjects. The amount of visceral fat was strongly associated with insulin resistance and signs of a high ratio of sympathetic vs. parasympathetic reactivity. A large amount of visceral fat may act in concert with sympathetic/parasympathetic imbalance to promote the development of insulin resistance, and this may be partly independent of genetic background.     

Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study

Objective: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein‐1 (cMCP‐1) and insulin resistance and to compare monocyte chemoattractant protein‐1 (MCP‐1) adipose tissue gene expression and cMCP‐1 in relation with inflammatory markers. Research Methods and Procedures: cMCP‐1 was measured in n = 116 consecutive control male subjects to whom an insulin sensitivity (S_i) test was performed. Circulating levels of soluble CD14, soluble tumor necrosis factor receptor type 2 (sTNFR2), soluble interleukin‐6 (sIL‐6), and adiponectin also were measured. Subcutaneous adipose tissue samples were obtained from n = 107 non‐diabetic and type 2 diabetic subjects with different degrees of obesity. Real‐time polymerase chain reaction was used to measure gene expression of MCP‐1, CD68, tumor necrosis factor‐α (TNF‐α), and its receptor TNFR2. Results: In the S_i study, no independent effect of cMCP‐1 levels on insulin sensitivity was observed. In the expression study, in non‐diabetic subjects, MCP‐1 mRNA had a positive correlation with BMI (r = 0.407, p = 0.003), TNF‐α mRNA (r = 0.419, p = 0.002), and TNFR2 mRNA (r = 0.410, p = 0.003). In these subjects, cMCP‐1 was found to correlate with waist‐to‐hip ratio (r = 0.322, p = 0.048). In patients with type 2 diabetes, MCP‐1 mRNA was up‐regulated compared with non‐diabetic subjects. TNF‐α mRNA was found to independently contribute to MCP‐1 mRNA expression. In this group, CD68 mRNA was found to correlate with BMI (r = 0.455, p = 0.001). Discussion: cMCP‐1 is not associated with insulin sensitivity in apparently healthy men. TNF‐α is the inflammatory cytokine associated with MCP‐1 expression in subcutaneous adipose tissue.     

Plasma Adiponectin Levels in High Risk African‐Americans with Normal Glucose Tolerance,Impaired Glucose Tolerance,and Type 2 Diabetes**

Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR (r = ?0.502, p = 0.046) and with HOMA‐β cell function (r = ?0.498, p = 0.042) but not with the percentage body fat (r = ?0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.     

Effects of Dietary Korean Proso-Millet Protein on Plasma Adiponectin,HDL Cholesterol,Insulin Levels,and Gene Expression in Obese Type 2 Diabetic Mice

We investigated the effect of dietary Korean proso-millet protein concentrate (PMP) on glycemic responses, plasma lipid levels, and the plasma level and gene expression of adiponectin in obese type 2 diabetic mice under normal and high-fat feeding conditions. The findings were that the feeding of PMP clearly elevated plasma high-density lipoprotein cholesterol (HDL cholesterol) and adiponectin levels and brought about effective reduction in the levels of glucose and insulin in mice under high-fat diet conditions as compared with a control diet. Gene expression study revealed that the diet up-regulated expression of adiponectin and down-regulated tumor necrosis factor-α (TNF-α). Considering the central role of adiponectin and HDL cholesterol in improving and ameliorating type 2 diabetes, obesity, and cardiovascular disease, our findings imply that PMP may have potential for therapeutic intervention in type 2 diabetes.     

Positive Reinforcing Mechanisms between GPR120 and PPARγ Modulate Insulin Sensitivity

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Circulating Interleukin‐6 in Relation to Adiposity,Insulin Action,and Insulin Secretion

Objective: Plasma concentrations of interleukin‐6 (IL‐6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL‐6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. Research Methods and Procedures: Fasting plasma IL‐6 concentrations (enzyme‐linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). Results: Fasting plasma IL‐6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = ?0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL‐6 was not related to M (partial r = ?0.23, p = 0.089). Discussion: Fasting plasma IL‐6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL‐6 and insulin action seems to be mediated through adiposity.     

肥胖诱发胰岛素抵抗的炎性机制

肥胖可诱发一系列慢性代谢性疾病,如2型糖尿病、血脂障碍、高血压和非酒精性脂肪肝等.这些疾病构成了当今世界人类健康的极大威胁.胰岛素抵抗是这些疾病的共有特征.胰岛素抵抗的发生与慢性低度系统炎性密切相关,涉及多条炎性信号通路的激活和胰岛素信号转导的缺陷.本文综述了肥胖、炎性与胰岛素抵抗之间的本质联系,以及肥胖诱发胰岛素抵抗的炎性机制,以期为肥胖相关疾病的防治提供重要参考.