Plasma adiponectin and leptin levels,body composition,and glucose utilization in adult women with wide ranges of age and obesity

OBJECTIVE: The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span. RESEARCH DESIGN AND METHODS: We studied 148 women aged 18-81 years with a BMI range of 17.2-44.3 kg/m(2). Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose utilization (M) was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol x m(-2) x min(-1)). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (<40, 40-59, and >or=60 years, respectively), as well as by glucose tolerance status. RESULTS: Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, VO(2max), and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P < 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and BMI, percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P < 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P < 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and VO(2max). CONCLUSIONS: The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat, insulin, and leptin levels in women. Adiponectin is positively associated with M across the age span in women.     

2型糖尿病患者血清脂联素水平与胰岛素抵抗的关系

【目的】探讨2型糖尿病（T2DM）患者血清脂联素（APN）水平与肥胖、胰岛素及胰岛素抵抗的关系。【方法】采用病例对照研究,T2DM伴有肥胖组（DO）42例,T2DM不伴肥胖组（NDO）42例,正常对照组（NC）28名。检测三组对象血脂、血糖、空腹胰岛素（Fins）、APN水平。用HOMA模型公式计算胰岛素抵抗指数（HOMAIR）。【结果JDO组和NDO组的血清APN水平均明显低于NC组[DO组（8．02±3．57）mg／L,NDO组（8．35±2．68）mg／L比NC组（14．04±4．75）mg／L,均P〈O．01],DO组与NDO组APN水平差异无显著性。APN与体质指数（BMI）、腰围（w）、腰臀比（WHR）、空腹血糖（FBG）、甘油三脂（TG）、Fins、HO—MAIR呈显著负相关（P〈0．01）,APN与高密度脂蛋白（HDL-C）呈显著正相关（P〈0．01）。多元逐步回归分析显示HOMAIR和WHR是血清APN浓度的主要影响因素。【结论】脂联素参与了胰岛素抵抗的发生,与2型糖尿病的发生相关。     

Features of the metabolic syndrome predict higher risk of diabetes and impaired glucose tolerance: a prospective study in Mauritius

OBJECTIVE: To assess the independent and joint effects of the components of the metabolic syndrome, including leptin, which is a recently proposed addition to this syndrome, in predicting the cumulative incidence of impaired glucose tolerance (IGT) and diabetes among individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: This prospective study involved 2,605 residents of Mauritius with normal glucose tolerance who were followed for 5 years for IGT or diabetes onset in relation to total and regional adiposity (BMI, waist-to-hip ratio [WHR]), fasting and 2-h 75-g oral glucose load glucose and insulin, total and HDL cholesterol, blood pressure, serum uric acid, triglyceride, and leptin levels. RESULTS: A multivariate logistic regression model adjusted for age, sex, ethnicity, and diabetes family history showed a significantly higher linear increase in risk of IGT and diabetes in association with the following variables only: fasting glucose (odds ratio 1.89 [95% CI 1.51-2.34]), 2-h glucose (1.68 [1.50-1.88]), WHR (1.30 [1.10-1.52]), BMI (1.04 [1.00-1.08]), and serum uric acid (1.37 [1.20-1.57]). However, a nonlinear increase was seen with serum triglyceride and plasma leptin concentrations. No risk factors resulted in joint effects that were greater than expected from combining individual effects. CONCLUSIONS: Metabolic syndrome features independently predict a higher risk of diabetes or IGT in normoglycemic subjects but in combination confer no higher-than-expected risk of these outcomes. At higher concentrations of triglycerides and leptin, risk plateaus and even declines slightly.     

Effects of a 3-day low-fat diet on metabolic control, insulin sensitivity, lipids and adipocyte hormones in Norwegian subjects with hypertriacylglycerolaemia and type 2 diabetes

The metabolic and hormonal impact of rapid dietary changes in type 2 diabetes has not been clarified. The objective of this study was to test whether a short-term, low-fat diet affected metabolic control, insulin sensitivity, lipids and adipocyte hormones in patients with type 2 diabetes with hypertriacylglycerolaemia. Nineteen outpatient subjects (10 M, 9 F) with type 2 diabetes and triacylglycerols >2.2 mmol/L at screening were included in the study. Dietary intake was assessed by weighing during two periods of 3-day baseline diet followed by a 3-day low-fat dietary intervention. The two periods of baseline diet did not differ with respect to relevant variables during intervention. Subjects were advised to increase fibre-rich and low-fat foods and to decrease intake of visible fat in an isoenergetic manner. The percentage of energy from fat was reduced from 39 to 22 (p < 0.0001), median values. Daytime blood glucose did not change and fasting insulin and fasting glucose to insulin ratios were unaffected. Total cholesterol decreased from 6.3 to 6.2 mmol/L (p < 0.005), high-density lipoprotein cholesterol from 1.13 to 1.10 mmol/L (p < 0.048) and the ratio of n-6 to n-3 fatty acids in phospholipids from 2.5 to 1.9 (p < 0.003). Concentrations of leptin decreased from 12.1 to 9.9 ng/mL (p < 0.005) and adiponectin increased from 8.6 to 10.5 microg/mL (p < 0.024). The effect on leptin was confined to women. A low-fat diet intervention for 3 days in insulin-resistant type 2 diabetes affects lipid, adiponectin and leptin levels but fails to improve insulin sensitivity and metabolic control.     

血清丝氨酸蛋白酶抑制剂与肥胖及2型糖尿病的相关性

目的 探讨2型糖尿病患者血清中脂肪特异性丝氨酸蛋白酶抑制剂(vaspin)、瘦素、脂联素的变化及其与2型糖尿病和肥胖的关系.方法 对80例2型糖尿病患者,69例空腹糖耐量受损患者,73例健康对照者采集病史.进行体格检查并留取血清测定其血糖、vaspin、瘦素、脂联素水平.结果 2型糖尿病组vaspin、瘦素水平显著高于对照组和空腹糖耐量受损组(P<0.05),脂联素水平显著低于对照组和空腹糖耐量受损组(P<0.05).空腹糖耐量受损组vaspin、瘦素水平显著高于对照组(P<0.05),脂联素水平显著低于对照组(P<0.05).两组中肥胖亚组的vaspin、瘦素水平均显著高于非肥胖亚组(P<0.05),脂联素水平均显著低于非肥胖亚组(P<0.05).2型糖尿病组vaspin与瘦素水平呈显著正相关(r分别0.362,P<0.05),与脂联素呈负相关(r=-0.397,P<0.05).结论 Vaspin水平与肥胖、2型糖尿病密切相关,在2型糖尿病的发生、发展中具有重要的作用.     

不同人群血清脂联素、瘦素水平与胰岛素抵抗的关系

【目的】研究不同人群（健康人群、肥胖和2型糖尿病患者）血清脂联素（APN）、瘦素（LEP）水平及其与肥胖、胰岛素抵抗的关系。【方法】采用病例对照研究,2型糖尿病（T2DM）伴有肥胖组（DO）42例,T2DM不伴肥胖组（NDO）42例,单纯性肥胖组（OB）37例,正常对照组（NC）28名。检测了4组研究对象血脂、血糖、空腹胰岛素（Fins）、APN、LEP水平,用HOMA模型公式计算胰岛素抵抗指数（HOMAIR）。[结果]NC组的APN水平明显高于其他3组（均P〈0．05）。DO组、OB组的LEP水平明显高于NDO组及NC组（P〈0．05）。相关分析显示：APN与HOMAIR、体质指数（BMI）、腰围（WC）、腰臀比（WHR）、空腹血糖（FBG）、甘油三脂（TG）和Fins呈显著负相关（P〈0．01）;LEP与BMI和体脂百分含量（BFC）呈显著正相关（P〈0．01）,与WC和Fins呈正相关（P〈0．05）;APN与LEP无相关性。多元逐步回归分析显示：APN与Fins呈显著负相关（P〈0．01）,与WHR、FBG呈负相关（P〈0．05）;LEP与BFC呈显著正相关（P〈0．01）。【结论】血清APN水平与2型糖尿病及肥胖相关。血清瘦素水平与2型糖尿病无关,但与肥胖有关。APN与瘦素之间无相关性,APN对于胰岛素抵抗的影响程度明显大于瘦素。     

Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus

OBJECTIVE: Women with prior gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes and associated vasculopathy. Because increased fat mass and inflammatory processes are angiopathic risk factors, the relationship between insulin sensitivity, parameters of subclinical inflammation, and plasma concentrations of adipocytokines was investigated in pGDM both at 3 months and 12 months after delivery. RESEARCH DESIGN AND METHODS: Insulin sensitivity (through a frequently sampled intravenous glucose tolerance test) and plasma concentrations of ultrasensitive C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor (PAI)-1, tumor necrosis factor-alpha, leptin, and interleukin-6 were measured in 89 pGDM (BMI 26.9 +/- 0.5 kg/m(2), age 32 +/- 0.5 years) and in 19 women with normal glucose tolerance during pregnancy (NGT) (23.7 +/- 0.9 kg/m(2), 31 +/- 1.3 years). RESULTS: pGDM showed lower (P < 0.0001) plasma adiponectin (6.7 +/- 0.2 microg/ml) than NGT (9.8 +/- 0.6 microg/ml) and a decreased (P < 0.003) insulin sensitivity index (S(i)) and disposition index (P < 0.03), but increased plasma leptin (P < 0.003), PAI-1 (P < 0.002), and CRP (P < 0.03). After adjustment for body fat mass, plasma adiponectin remained lower in pGDM (P < 0.004) and correlated positively with S(i) (P < 0.003) and HDL cholesterol (P < 0.0001) but negatively with plasma glucose (2-h oral glucose tolerance test [OGTT]) (P < 0.0001), leptin (P < 0.01), CRP (P < 0.007), and PAI-1 (P < 0.0001). On regression analysis, only HDL cholesterol, postload (2-h OGTT) plasma glucose, and S(i) remained significant predictors of plasma adiponectin, explaining 42% of its variability. Of note, adiponectin further decreased (P < 0.05) only in insulin-resistant pGDM despite unchanged body fat content and distribution after a 1-year follow-up. CONCLUSIONS: Lower plasma adiponectin concentrations characterize women with previous GDM independently of the prevailing insulin sensitivity or the degree of obesity and are associated with subclinical inflammation and atherogenic parameters.     

Hyperinsulinemia in cord blood in mothers with type 2 diabetes and gestational diabetes mellitus in New Zealand

OBJECTIVE: In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. We therefore examined whether cord insulin and leptin concentrations are increased in offspring of Maori and Pacific Island mothers with type 2 and gestational diabetes mellitus (GDM) and varying degrees of glycemic control (HbA(1c)). RESEARCH DESIGNS AND METHODS: Maori and Pacific Island mothers were prospectively recruited at Middlemore Hospital, South Auckland. Cord blood was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation to 138 mothers with GDM, 39 mothers with type 2 diabetes, and 95 control mothers. RESULTS: Babies born to mothers with both type 2 diabetes and GDM had higher birth weight and skinfold thickness and markedly higher concentrations of insulin (median [interquartile range] type 2 diabetes 77 pmol/l [42-143], GDM 67 pmol/l [42-235], and control subjects 33 pmol/l [18-62]; P < 0.001) and leptin (type 2 diabetes 39 ng/ml [18-75], GDM 31 ng/ml [17-58], and control subjects 13 ng/ml [8-22]; P < 0.001) in cord blood. Cord insulin concentrations >120 pmol/l were found in 29% of offspring of mothers with GDM and 31% of mothers with type 2 diabetes. Many mothers with GDM had abnormalities of glucose tolerance postpartum (20% type 2 diabetes, 34% impaired glucose tolerance or impaired fasting glucose). Higher cord insulin (57 pmol/l [40-94]) and leptin (26 ng/ml [17-39]) concentrations were found even in offspring of GDM mothers with normal glucose tolerance postpartum. CONCLUSIONS: Raised cord insulin and leptin concentrations are a common finding in offspring of mothers with type 2 diabetes and GDM in this population.     

Retinol-binding protein 4 and lipocalin-2 in childhood and adolescent obesity: when children are not just "small adults"

BACKGROUND: although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children. METHODS: we investigated the circulating concentrations of RBP4 and lipocalin-2 in 80 obese girls (ages 9- 15 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and lean controls [-0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations. RESULTS: unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P < 0.03, respectively). These results were different from those of adults and were not correlated with the HOMA index. In contrast, hs-CRP and leptin concentrations were positively correlated with BMI SDS values (P < 0.0001, and P < 0.00001, respectively), as expected, whereas the adiponectin concentration was negatively correlated (P = 0.008). CONCLUSIONS: although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long-standing severe insulin resistance and type 2 diabetes.     

单纯性肥胖患者血清瘦素与胰岛素、性激素的相关分析

[目的]观察单纯性肥胖患者血清瘦素水平与胰岛素、性激素浓度的父系。[方法]川放射免疫法测定64例肥胖者和65例非肥胖者的血清瘦素水平,并分析血清瘦素水平与年龄,体重指数（BMI）、腰臀比值（WHR）、胰岛素（INS）、睾酮（T、）雌二醇（E2）的相关性。[结果]1．无论肥胖组还是非肥胖组,女性血清瘦素水平显著高于男性（P〈0．01）;同性别比较,肥胖组显著高于非肥胖组（P〈0．01）。2．相关性分析,无论是男性还是女性,血清瘦素与BMI、WHR旱显著正相关,而与年龄无关。3．血清瘦素水平与胰岛素浓度呈正相关,与血糖浓度无关。4．血清瘦素水平与T,男性呈负相关（r=一0．310,P〈0．01）,而女性呈正相关（r=0．360,P〈0．01）;与E2在男性无相关性,女性呈正相关（r=0．323,P〈0．01）。[结论]肥胖者窄腹血清瘦素水平升高,血清高瘦素与高胰岛索血症的相关性提示瘦素可能在2型糖尿病的发病中起一定作用。BMI足影响血清瘦素水平的主要原因之一,而性别间的差异则与性激素有关。     

Effects of a 3‐day low‐fat diet on metabolic control,insulin sensitivity,lipids and adipocyte hormones in Norwegian subjects with hypertriacylglycerolaemia and type 2 diabetes

The metabolic and hormonal impact of rapid dietary changes in type 2 diabetes has not been clarified. The objective of this study was to test whether a short‐term, low‐fat diet affected metabolic control, insulin sensitivity, lipids and adipocyte hormones in patients with type 2 diabetes with hypertriacylglycerolaemia. Nineteen outpatient subjects (10 M, 9 F) with type 2 diabetes and triacylglycerols >2.2?mmol/L at screening were included in the study. Dietary intake was assessed by weighing during two periods of 3‐day baseline diet followed by a 3‐day low‐fat dietary intervention. The two periods of baseline diet did not differ with respect to relevant variables during intervention. Subjects were advised to increase fibre‐rich and low‐fat foods and to decrease intake of visible fat in an isoenergetic manner. The percentage of energy from fat was reduced from 39 to 22 (p<0.0001), median values. Daytime blood glucose did not change and fasting insulin and fasting glucose to insulin ratios were unaffected. Total cholesterol decreased from 6.3 to 6.2?mmol/L (p<0.005), high‐density lipoprotein cholesterol from 1.13 to 1.10?mmol/L (p<0.048) and the ratio of n‐6 to n‐3 fatty acids in phospholipids from 2.5 to 1.9 (p<0.003). Concentrations of leptin decreased from 12.1 to 9.9?ng/mL (p<0.005) and adiponectin increased from 8.6 to 10.5?μg/mL (p<0.024). The effect on leptin was confined to women. A low‐fat diet intervention for 3 days in insulin‐resistant type 2 diabetes affects lipid, adiponectin and leptin levels but fails to improve insulin sensitivity and metabolic control.     

妊娠期体质量、血清瘦素、脂联素水平与胰岛素抵抗的关系

目的了解妊娠妇女的体质量、血清瘦素、脂联素与胰岛素抵抗之间的关联度。方法通过检测孕妇妊娠早期、中期、晚期血清脂联素(APN),瘦素(LP)、空腹血糖(FINS),同时测量身高,体质量,计算体质指数(BMI)、孕期体质量增加值和胰岛素抵抗指数(HOMA-IR),来探讨孕前体质量、孕期体质量增长与孕妇糖代谢间的关系。结果胰岛素抵抗与孕周无显著性相关,与孕期BMI、血清瘦素以及脂联素水平呈正相关。结论糖尿病对母婴的危害较大,对孕妇的管理和围产期监护,饮食控制治疗尤为重要,要注意补充脂联素充沛的食物,减少可能导致肥胖的食物摄入,才能有效的降低糖尿病的发生率。     

不同血糖水平人群血清脂联素水平与胰岛素抵抗的关系

目的研究天津地区不同糖耐量人群血清脂联素水平与胰岛素抵抗的关系。方法290例受试者中2型糖尿病患者(DM组)124例、糖耐量减低者(IGT组)66例、正常对照组(NGT组)100例,各组按体重指数(BMI)分成肥胖亚组和非肥胖亚组。测定受试者的身高、体重、腰围、臀围及血浆胆固醇和甘油三酯,并采用放射免疫法测定胰岛素(FINS)、酶联免疫吸附测定(ELISA)法测定血清脂联素水平。结果(1)IGT组和DM组脂联素水平较NGT组明显降低,分别为5.31±1.20mg/L,4.12±0.73mg/L和8.09±0.39mg/L,DM组降低最显著(P<0.05)。(2)与NGT组相比,IGT组的BMI、腰臀比(WHR)、空腹血糖(FBG)、总胆固醇(TC)明显升高,高密度脂蛋白胆固醇(HDL-C)明显下降(P<0.05或P<0.01);DM组的收缩压(SBP)、BMI、WHR、FBG、胰岛素抵抗指数(IRI)、TG的水平均高于前两组,HDL-C明显低于NGT组(P<0.05或P<0.01)。(3)血清脂联素与BMI、WHR、腰围(YW)及体脂含量(FAT%)呈显著负相关,与血胆固醇(TC)水平无相关性,与甘油三酯呈负相关。在本年龄段中,与年龄关系不大。结论(1)脂联素水平在IGT和DM人群中明显降低,提示脂联素在2型DM发病中可能起着一定作用,可以作为2型DM发病的一个预测指标。(2)各组肥胖亚组中IRI明显升高,说明肥胖人群存在IR,而各组肥胖亚组脂联素水平也明显降低,提示肥胖是影响该脂肪因子的重要因素。脂联素可能是联系肥胖、IR和2型DM的一个纽带。     

2型糖尿病脂联素对胰岛素抵抗及心血管并发症影响的探讨

目的:探讨2型糖尿病血清脂联素水平与胰岛素抵抗及心血管并发症之间的关系。方法:对58例2型糖尿病合并冠心病患者,48例单纯2型糖尿病患者,30例正常人进行血压、空腹血糖(FBG)、胰岛素(FINS)、甘油三酯(TG)、瘦素、肿瘤坏死因子(TNF-α)及脂联素等的测定,同时计算胰岛素敏感性指数(ISI),并以ISI为因变量,年龄、性别、体重指数(BMI)、血压、TG、FBG、FINS、瘦素、TNF-α及脂联素为自变量,进行多元线性逐步回归分析。结果:2型糖尿病合并冠心病组和单纯2型糖尿病组血清脂联素水平低于正常对照组(P<0.01),2型糖尿病合并冠心病组血清脂联素水平低于单纯2型糖尿病组(P<0.01)。多元线性相关分析显示,血清脂联素与血压、TBG、FINS、TG、瘦素、TNF-α呈负相关,与ISI呈独立正相关,进入回归方程的因素为TG、瘦素、TNF-α、脂联素。结论:血清脂联素在2型糖尿病胰岛素抵抗及心血管并发症的发生发展中有重要作用。     

Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality

OBJECTIVE: Leptin and tumor necrosis factor (TNF)-alpha are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis. RESEARCH DESIGN AND METHODS: In this study, fasting plasma leptin, soluble TNF-alpha receptor 2 (TNF-alpha-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2)), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality. RESULTS: At baseline, leptin and TNF-alpha-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P < 0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P < 0.02). CONCLUSIONS: In middle-aged women, MCP-1/CCL2, leptin, and TNF-alpha-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-alpha-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.     

Adipokines and incident type 2 diabetes in an Aboriginal Canadian [corrected] population: the Sandy Lake Health and Diabetes Project

OBJECTIVE—The aim of this study was to investigate associations of adiponectin, leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA), individually or in combinations, with risk of incident type 2 diabetes in a Canadian Aborigine population.RESEARCH DESIGN AND METHODS—Of the 606 Sandy Lake Health and Diabetes Project cohort subjects who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test were obtained at baseline and follow-up to determine incident type 2 diabetes, defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose ≥7.0 mmol/l or 2-h postload plasma glucose ≥11.1 mmol/l at follow-up.RESULTS—Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at baseline were associated with increased risk of incident type 2 diabetes after adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48–0.83], 1.50 [1.02–2.21], and 0.54 [0.37–0.77], respectively). When the models were additionally adjusted for waist circumference or BMI, however, only low adiponectin remained significantly associated with increased incident diabetes (0.68 [0.51–0.90]). Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using either the ratio or joint effects, did not improve diabetes prediction.CONCLUSIONS—Low baseline adiponectin is associated with increased risk of incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic syndrome variables including obesity.Obesity is a major risk factor for insulin resistance and type 2 diabetes (1). The recent focus on adipose tissue as an endocrine organ secreting signaling proteins, collectively termed adipokines, has prompted current interests in associations of adipokines with insulin resistance and diabetes (1–2). Although underlying mechanisms have not been completely explained, adipokines have been linked with obesity-induced inflammation and signaling pathways that contribute to type 2 diabetes (1). Prospectively, adiponectin, an anti-inflammatory, anti-atherogenic, and insulin-sensitizing adipokine (2,3), has been inversely associated with the development of type 2 diabetes (4–7). Several studies associated increased baseline levels of inflammatory markers, including interleukin (IL)-6 (8,9) and C-reactive protein (CRP) (9), with incident type 2 diabetes, while others reported no association of IL-6 (4) and CRP (4,8) with the development of type 2 diabetes after adjustment for adiposity measures. In another prospective study, the association between leptin and diabetes risk was attenuated after adjustment for intra-abdominal fat (10).Recent studies have suggested that adipokines may interact in regulating metabolic homeostasis (11–12). In a cross-sectional study, evidence was presented for CRP inhibiting the binding of leptin to its receptors and leptin stimulating expression of CRP (11). Others identified the adiponectin-to-leptin (A/L) ratio as a reliable marker of insulin resistance (12).Nonetheless, limited population-based data are available on how adipokines in combinations may contribute to the etiology of diabetes. In addition, previous prospective investigations on associations of adipokines with diabetes provide inconsistent findings (4–10). Among those, only a few have reported data from studies of North American Aboriginal people (4,5), while no studies have been conducted among Aboriginal Canadians in whom diabetes is increasingly prevalent (13). The objective of this study was to investigate associations of baseline adiponectin, leptin, CRP, IL-6, and serum amyloid A (SAA), individually and/or in combinations, with the development of type 2 diabetes in a Canadian Aborigine population undergoing rapid cultural transition.     

Alcohol consumption in relation to metabolic regulation, inflammation, and adiponectin in 64-year-old Caucasian women: a population-based study with a focus on impaired glucose regulation

OBJECTIVE: The aims of this study were to examine alcohol drinking patterns in women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) and to investigate whether alcohol intake was associated with improved insulin sensitivity, decreased biomarkers of inflammation, and increased adiponectin levels and if these effects were limited to dysmetabolic women. RESEARCH DESIGN AND METHODS: From a cohort of 64-year-old Caucasian women, 209 with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol consumption and medication use were assessed by questionnaires. Anthropometric data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides, C-reactive protein, white blood cell count, and serum adiponectin were measured. RESULTS: Compared with the NGT group, alcohol consumption was lower in the IGT group and lowest in the diabetes group. Mean alcohol intakes of >9.2 and > or =3-9 g/day were positively associated with adiponectin and insulin sensitivity (homeostasis model assessment [HOMA]), respectively, independently of obesity, metabolic control, and other confounders. Alcohol intake correlated negatively with inflammatory markers, although this did not remain after adjustment for HOMA and waist circumference. The inverse associations between alcohol consumption and factors related to the metabolic syndrome such as HOMA, waist circumference, and inflammatory markers were more obvious among women with diabetes and IGT than in healthy women. CONCLUSIONS: In these women, moderate alcohol consumption showed beneficial associations with the prevalence of type 2 diabetes, IGT, insulin sensitivity, and serum adiponectin. There is a need to clarify whether adiponectin may be a mechanistic link and also to clarify the clinical implications of these observations.     

2型糖尿病肾脏疾病患者血清内脂素、脂联素水平的变化

目的了解2型糖尿病肾脏疾病患者血清内脂素和脂联素水平的变化,并探讨其与2型糖尿病肾脏疾病及各项代谢指标之间的关联。方法选取2型糖尿病肾脏疾病患者52例（DKD组）,46例单纯2型糖尿病患者（T2DM组）及40例正常对照人群（对照组）,采用酶联免疫吸附测定（ELISA）法检测内脂素水平,用放射免疫分析法（RIA）测定脂联素和胰岛素,另外测量体质量、身高、腰围、体质量指数、腰臀比及各项生化指标,并分析内脂素、脂联素与体质量指数、腰臀比、血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗指数（HOMA-IR）等的关系。结果DKD组及T2DM组内脂素水平明显低于对照组,分别为（11．58±7．32）μg／L,（12．04±6．17）μg／L vs（16．89±5．76）μg／L（P〈0．05）,而DKD组与T2DM组之间无明显关联（P〉0．05）;而脂联素水平明显降低,分别为（3．64±0．70）mg／Lvs（6．91±3．26）mg／L,（4．82±1．86）mg／L vs（6．91±3．26）mg／L（P〈0．01）,DKD组与T2DM组相比差异有统计学意义（P〈0．01）;DKD组患者血清内脂素水平与腰臀比呈正相关（r=0．406,P〈0．01）;脂联素与HOMA—IR、体质量指数、腰臀比、甘油三酯、低密度脂蛋白胆固醇、空腹胰岛素、空腹血糖水平呈显著负相关,相关系数分别为-0．612、-0．431、-0．761、-0．623、-0．380、-0．332和-0．393（均P〈0．01）。结论2型糖尿病肾脏疾病患者血清内脂素及脂联素水平下降,且内脂素与脂联素是糖尿病肾脏疾病发生发展的独立危险因素。     

Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults

OBJECTIVE: To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes. RESEARCH DESIGN AND METHODS: A nested case-control study from the Health, Aging, and Body Composition (Health ABC) study. We measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis factor-alpha, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area was determined by computed tomography scan. The 519 case subjects had diabetes defined by fasting plasma glucose level > or =126 mg/dl or by use of diabetes medications. The 519 control subjects had normal glucose tolerance and were matched by sex, race, and study site. Sex-specific logistic models were adjusted for age, race, site, total adiposity, smoking, and physical activity. RESULTS: Higher adiponectin levels were associated with lower risk of diabetes (P < 0.001). Visceral fat was the only adiposity measure associated with diabetes after adjusting for BMI (odds ratio 3.0 [2.1-4.3] in women and 1.3 [1.0-1.6] in men, P < 0.001 between-sex comparison). Adipocytokines attenuated the association between visceral fat and diabetes for both sexes but more strongly in men (women 2.3 [1.5-3.3], men 1.1 [0.9-1.4]). In men, adiponectin, IL-6, and PAI-1 remained independently associated with diabetes after adjusting for fat depots; in women, adiponectin was the only independently associated adipocytokine. Controlling for insulin, HDL, triglycerides, and blood pressure did not change these results. CONCLUSIONS: Adiponectin is associated with lower odds of diabetes in older men and women. Whereas several adipocytokines explained the relationship between visceral adiposity and diabetes in men, only adiponectin partially mediated this association among women.     

Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans.

OBJECTIVE: Plasma leptin levels correlate strongly with increased total adipose tissue, a known risk factor for type 2 diabetes, yet the role of leptin in the etiology of diabetes remains unclear. We sought to determine whether leptin is a risk factor for development of diabetes in Japanese Americans. RESEARCH DESIGN AND METHODS: We compared baseline leptin levels in 370 nondiabetic Japanese Americans who remained nondiabetic for 5-6 years of follow-up with those of 40 nondiabetic Japanese Americans who developed diabetes during follow-up. All participants had computed tomography measurements of baseline subcutaneous chest, abdomen, thigh, and intra-abdominal fat, with total fat defined as the sum of all these measurements. RESULTS: The mean age was 51.7 +/- 11.7 years for men and 51.9 +/- 12.0 years for women. The 23 men who developed diabetes had significantly higher leptin levels than the 212 men who remained nondiabetic (P < 0.01). Among men, baseline leptin levels predicted diabetes risk independent of baseline total fat, insulin, insulin resistance, glucose, or age in separate multiple logistic regression models (relative risk adjusted for baseline total fat = 1.80 per SD increase [2.7 ng/ml], 95% CI 1.02-3.17). This association was particularly strong among men in the top decile for intra-abdominal fat. In contrast, the 17 women who developed diabetes had leptin levels similar to those of the 158 women who remained nondiabetic (P = 0.31). CONCLUSIONS: Among Japanese Americans, increased baseline leptin levels are associated with increased risk of developing diabetes in men but not in women.