Plasma adiponectin is related to other cardiovascular risk factors in nondiabetic Korean men with CAD, independent of adiposity and cigarette smoking: cross-sectional analysis

BACKGROUND: Circulating adiponectins have multiple protective roles as anti-diabetic, anti-atherosclerotic, and anti-inflammatory factors. We examined the relationship between plasma adiponectin concentration and other cardiovascular risk in nondiabetic coronary artery disease (CAD) men and the relationship can be maintained even after adjusted for major environmental factors that contribute to adiponectin concentrations. METHODS: Nondiabetic CAD men (n=613) were 31-70 y and had body mass index (BMI) of 18.5-29.9 kg/m2. RESULTS: Circulating adiponectins positively correlated with age and negatively with BMI, waist circumference and % body fat (p-values of all <0.001). Plasma adiponectin concentrations were higher in never-smokers (5.07+/-0.30 microg/ml) than current (4.15+/-0.12 microg/ml) and ex-smokers (3.75+/-0.20 microg/ml) both before and after adjusted for age and adiposity (p=0.002 and p=0.008, respectively), however they were not significantly different according to alcohol drinking status. After adjusted for age, adiposity and cigarette smoking, plasma adiponectin still have positive correlations with HDL cholesterol, apolipoprotein AI and LDL particle size, and inversely with fasting triglyceride, atherogenic index, insulin resistance and C-reactive protein (CRP). However there was no significant relationships between adiponectin and apolipoprotein B, total cholesterol or LDL cholesterol. In subset analysis by tertile adiponectin concentrations (lowest: <2.92, moderate: 2.92or=4.75 microg/ml), 'moderate' and 'highest' adiponectin groups had lower triglyceride (p<0.001), lower atherogenic index (p=0.001), lower fasting insulin (p=0.004), lower insulin resistance (p=0.001), lower CRP (p=0.001), higher HDL cholesterol (p<0.001), higher apolipoprotein AI (p=0.005) and higher LDL particle size (p<0.001) as compared with 'lowest' adiponectin group when adjusted for age, adiposity and cigarette smoking. Platelets were lower in 'highest' adiponectin groups as compared with 'lowest' and 'moderate' adiponectin group after the adjustment. However, there was no significant difference in total cholesterol (p=0.145), LDL cholesterol (p=0.145), apolipoprotein B (p=0.222) and fasting glucose (p=0.157). CONCLUSION: An increase of adiponectin concentrations or the maintenance of higher concentration may be negatively associated with cardiovascular risk factors in nondiabetic CAD male patients, independent of adiposity and smoking status.     

Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol,independent of body mass index,in the Japanese population

Adiponectin, which is secreted specifically by adipose tissue, has been shown to act as an anti-atherosclerotic protein by direct effects on endothelial cells. Clinical studies have shown that adiponectin levels are lower in individuals with obesity, diabetes and coronary artery disease. The present study investigated relationships between serum adiponectin levels and body mass index (BMI), blood pressure, insulin resistance index, lipid profile, uric acid and high-sensitivity C-reactive protein levels in a large number of Japanese subjects not taking any medication for metabolic disease and without severe illness (705 men and 262 women; age 30-65 years; BMI 22.5+/-2.9 kg/m(2)). The serum adiponectin concentration was measured by ELISA, without a protein-denaturing step. The insulin resistance index was assessed by homoeostasis model assessment (HOMA-IR). The serum concentration of adiponectin in women (13.5+/-7.9 microg/ml) was significantly higher than that in men (7.2+/-4.6 microg/ml). The serum adiponectin level was negatively correlated with BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, total cholesterol, triacylglycerols, low-density lipoprotein (LDL)-cholesterol and uric acid, and positively correlated with high-density lipoprotein (HDL)-cholesterol. The correlations between serum adiponectin level and insulin, HOMA-IR, triacylglycerols, HDL-cholesterol, LDL-cholesterol and uric acid were significant even after adjustment for age, sex and BMI. Stepwise multiple regression analysis revealed that HDL-cholesterol, sex, BMI and HOMA-IR were independently correlated with the serum adiponectin level (R(2)=0.377). These findings suggest that the serum adiponectin level is negatively correlated with HOMA-IR and positively correlated with HDL-cholesterol, independent of age, sex and BMI, in the Japanese population.     

Sex-related differences between adiponectin and insulin resistance in schoolchildren

OBJECTIVE: To study the effect of body composition and adiponectin on insulin resistance and beta-cell function in schoolchildren during puberty. RESEARCH DESIGN AND METHODS: Plasma adiponectin level and its relationships with insulin sensitivity and beta-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6-18 years in a national survey program for diabetes in 1999. Insulin resistance and beta-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay. RESULTS: Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in beta-cell function during this period. A transient drop of adiponectin level with a trough at 10-12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = -0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15-18 years and in girls aged 11-14 years. No association was observed between adiponectin levels and beta-cell function by HOMA. CONCLUSIONS: There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.     

非酒精性脂肪肝合并高血压患者血清脂联素水平的研究

目的 研究非酒精性脂肪肝(NAFLD)合并高血压患者血清脂联素水平与胰岛素抵抗(HO-MA)程度的相关性.方法 性别匹配的NAFLD合并高血压患者65例,单纯NAFLD患者51例,健康体检者54例作为对照组.测定体质指数(BMI),检测空腹血糖(FBS)、丙氨酸氨基转移酶(ALT)、胆固醇、甘油三酯(TG)等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HO-MA-IR).同时酶联免疫法测定血清脂联素水平.并用相关及多元回归分析血清脂联素水平与各参数的相关性.结果 NAFLD患者BMI[(27.12±2.63)kg/m2]、ALT[(35.86±20.16)U/L]、TG[(2.73±1.43)mmol/L]、FBS[(5.71±0.65)mmol/L]、FINS[(12.33±4.16)mIU/L]、HOMA-m(3.11±1.04)]水平较对照组高[(23.14±2.86)kg/m2、(19.72±8.90)U/L、(1.35±0.59)mmol/L、(5.19±0.78)mmol/L、(2.31±1.61)mIU/L、0.53±0.39]P＜0.05),脂联素水平较对照组低([(4.52±2.05)、(8.88±3.37)μg/ml]P＜0.05);NAFLD 合并高血压患者HOMA-IR较单纯NAFLD患者更高(4.47±2.87、3.11±1.04,P＜0.05),脂联素水平更低((3.19±1.52)、(4.52±2.05)μg/ml,P＜0.05).结论 NAFLD合并高血压患者HOMA-IR、FINS较NAFLD更为严重,脂联素水平更低.脂联素与BMI、ALT、FBS、FINS、TG、HOMA呈负相关,与性别相关,与年龄、胆固醇相关不明显.脂联素与TG以及HOMA相关.     

多囊卵巢综合征患者血清脂联素、瘦素水平与胰岛素抵抗相关性的研究

目的研究多囊卵巢综合征(PCOS)患者血清脂联素、瘦素水平与胰岛素抵抗的相关性。方法选58例PCOS患者和46例非PCOS患者,根据体质指数(BMI)分为肥胖组与非肥胖组,根据胰岛素抵抗诊断标准分为胰岛素抵抗组和非胰岛素抵抗组。对所有患者的血清脂联素表达水平、瘦素水平及内分泌代谢等各项指标进行检测并分析相关性。结果①多囊卵巢综合征组患者的血清脂联素表达水平明显低于对照组(P<0.05);非肥胖多囊卵巢综合征组患者的血清脂联素表达水平显著低于非肥胖对照组(P<0.05);胰岛素抵抗组患者的血清脂联素表达水平明显低于非胰岛素抵抗组(P<0.05)。多囊卵巢综合征组患者的瘦素表达水平明显高于对照组(P<0.05);胰岛素抵抗组患者的瘦素表达水平明显高于非胰岛素抵抗组(P<0.05)。②患者血清脂联素表达水平与BMI、胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、腰臀比(WHR)和三酰甘油(TG)等指标呈负相关性关系(P<0.05)。患者血清瘦素表达水平与BMI、FINS、HOMA-IR、WHR和TG)指标呈正相关性关系(P<0.05)。结论多囊卵巢综合征患者大多具有低脂联素表达水平、高瘦素血症等特征,且血清脂联素表达水平与瘦素表达水平、胰岛素抵抗严重程度之间存在着负相关性关系,脂联素和瘦素可作此疾病患者远期出现糖尿病并发症的预测指标之一。     

Correlation of plasma leptin and adiponectin with insulin sensitivity and beta-cell function in children - the Taipei Children Heart Study

To investigate the association between plasma leptin and adiponectin and insulin sensitivity in children, 580 school children (294 boys and 286 girls) with mean age of 13.3 years (12-16 years) were randomly selected from the Taipei Children Heart Study. Baseline measurements included body weight, body mass index (BMI), plasma glucose, insulin, proinsulin, leptin and adiponectin levels. Insulin resistance and beta-cell function were assessed using the method of homeostatic model, HOMA-IR and HOMA-beta, respectively. We found that girls had higher levels of plasma leptin, adiponectin and HOMA-beta than boys. There was no significant difference in HOMA-IR between boys and girls. Plasma leptin concentrations were positively correlated with body weight, BMI, insulin and proinsulin concentrations, HOMA-IR and HOMA-beta, whereas plasma adiponectin levels were inversely associated with body weight, BMI and proinsulin levels in both sexes. In girls, adiponectin concentrations were negatively correlated with insulin concentration and HOMA-IR. In multiple regression analyses, plasma leptin was more positively associated with insulin and proinsulin levels, HOMA-IR and HOMA-beta than was adiponectin in boys. This association persisted even after adjusting for body weight, BMI and pubertal status. In conclusion, plasma leptin was more strongly associated with insulin sensitivity and beta-cell function than was adiponectin among children, particularly in boys.     

2型糖尿病患者血浆脂联素浓度改变及其与胰岛素抵抗的关系

目的　了解 2型糖尿病患者血浆脂联素浓度的改变 ,并探讨与胰岛素抵抗的关系。方法　测定 64例 2型糖尿病和 3 0例正常对照组的血浆脂联素、空腹血糖 (FPG)、糖化血红蛋白 (HbA1c)、空腹血浆胰岛素 (FINS)、血脂、体重指数(BMI) ,计算胰岛素抵抗指数 (HOMA IR)及 β 细胞功能指数 (HOMA β)。比较脂联素浓度的改变 ,以及与其它因素的相关性。结果　正常对照组、非肥胖糖尿病组及肥胖糖尿病组 ,脂联素浓度依次降低 ,且均有统计学意义。大中血管并发症糖尿病组血浆脂联素水平较无大中血管并发症糖尿病组明显降低。在糖尿病患者中血浆脂联素与BMI、HOMA IR呈负相关 (P <0 0 5 ) ,与高密度脂蛋白胆固醇 (HDL c)呈正相关 (P <0 0 5 )。与FBG、HbA1c、甘油三酯 (TG)、总胆固醇 (TC)及 β 细胞功能指数 (HOMA β)相关性不明显。结论　 2型糖尿病患者血浆脂联素水平明显下降 ,并且与胰岛素抵抗有一定的相关性     

脓毒症患者血清脂联素水平的初步研究

目的探讨脓毒症患者中血清脂联素水平的变化及其与胰岛素抵抗（IR）、C反应蛋白（CRP）之间的关系。方法选取本院ICU脓毒症患者45例和健康对照20例,患者被诊断为脓毒症后的第1、5和10d抽取空腹静脉血检测空腹血糖（FBG）、空腹胰岛素（FINS）、CRP、脂联素浓度,使用稳态模式法（HOMA）计算胰岛素抵抗指数（HOMA—IR）。结果脓毒症组第1、5和10d的血清脂联素浓度分别为（4．82±3．29）、（5．15±3．41）、（4．97±3．21）μg／ml,均明显低于对照组（8．81±2．70）μg／ml（P均〈0．01）。脓毒症组各时间点血清脂联素浓度比较,差异无统计学意义（P〉0．05）。脓毒症组血清脂联素与BMI、FBG、FINS、HOMA—IR、急性生理学与慢性健康状况评分系统（APACHE）II评分均存在显著负相关,与CRP无显著相关。结论脓毒症患者血清脂联素水平下降,且与HOMA—IR及APACHEⅡ评分均存在显著负相关。     

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。     

血清铁蛋白与2型糖尿病及其危险因素相关关系的研究

目的探讨血清铁蛋白（SF）与2型糖尿病及其各主要危险因素[体质指数（BMI）、腹内脂肪面积（VA）、血脂及血压水平]的关系。方法测定并比较60例2型糖尿病患者及60例健康对照的身高、体质量、腰围、臀围、SF、腹部脂肪扫描、总胆固醇（TC）、三酯甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FBG）、口服75g葡萄糖粉测量2h血糖、空腹血清胰岛素（FINS）、收缩压（SBP）、舒张压（DBP）、血尿酸（UA）及C反应蛋白（CRP）,计算BMI、腰臀围比（WHR）、胰岛素抵抗指数（HOMR-IR）及VA。结果2型糖尿病组SF水平较对照组升高,差异具显著性（P〈0．01）,SF与BMI、FBG、DBP、TG、LDL-C、UA、VA、CRP呈正相关,与HDL-C负相关,与SBP无相关性。与对照组相比,初诊的2型糖尿病患者具有较高的BMI、WHR、FINS、TG、UA、CRP、VA以及SBP水平（P〈0．05）;HOMA-IR明显升高（P〈0．05）;较低的HDL-C水平（P〈0．05）;而TC、LDL-C水平及DBP无明显差异（P〉0．05）;糖尿病组不论男性与女性SF浓度明显高于对照组（P〈0．05）。通过直线相关分析可知,经对数转换后的2型糖尿病患者SF与TC、TG、LDL-C、UA、CRP呈正相关（P〈0．05）;与FBG、PBG、VA、HOMR-IR及DBP显著正相关（P〈0．01）;与HDL-C呈负相关（P〈0．05）;与SBP、BMI、WHR、FINS非线性关系。经多因素逐步回归分析发现SF是参与HOMR-IR的独立变量。结论SF水平升高即体内储存铁过多是2型糖尿病形成和进展的危险因素之一,并且SF可以预测2型糖尿病代谢控制程度,可能为2型糖尿病的诊治提供新途径。     

Metformin plus low-dose glimeperide significantly improves Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)) without hyperinsulinemia in patients with type 2 diabetes mellitus

OBJECTIVE: Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic beta-cells, which have been studied by using euglycemic/hyperinsulinemic clamps. However, it is difficult to study insulin resistance and beta-cell failure by these techniques in humans. Therefore, the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and beta-cell activity by using a mathematical model, Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)). RESEARCH DESIGN AND METHODS: Seventy type 2 diabetic patients were randomly assigned to one of three therapeutic regimens: (A) metformin + American Diabetic Association (ADA)-recommended diet + physical activity; (B) metformin + low-dose glimepiride + ADA diet + physical activity; or (C) ADA diet + physical activity (no drugs). Blood samples were obtained before and after the treatment to determine serum levels of fasting and post-prandial blood glucose, fasting insulin, and glycosylated hemoglobin (HbA1c), and HOMA(IR) and HOMA(beta-cell) were calculated. RESULTS: Fasting and post-prandial levels of glucose, HbA1c, and fasting insulin and calculated HOMA(IR) and HOMA(beta-cell) values before treatment were significantly higher than the respective values after treatment for all groups of patients (P < 0.01). Significant differences were also found when comparing the treatment-induced reduction in fasting blood glucose (51.8%; P < 0.01), post-prandial blood glucose (55.0%; P < 0.05), and HOMA(IR) (65.3%; P < 0.01) in patients of Group B with that in patients receiving other therapeutic options (Groups A and C). CONCLUSIONS: Metformin plus low-dose glimepiride (plus ADA diet and physical activity) is a more effective treatment for type 2 diabetes than either metformin plus ADA diet and physical activity or ADA diet and physical activity alone. Determination of HOMA(IR) and HOMA(beta-cell) values is an inexpensive, reliable, less invasive, and less labor-intensive method than other tests to estimate insulin resistance and beta-cell function in patients with type 2 diabetes mellitus.     

妊娠期糖尿病患者脂联素及C-反应蛋白水平的临床研究

目的探讨妊娠期糖尿病患者早、中孕期的脂联素及C-反应蛋白水平的相关性。为早期预测妊娠期糖尿病提供科学依据。方法选于10-14周已在我院确诊妊娠并产检孕妇,所有孕妇于孕10-14周进行常规体检测身高、体重、血压、血浆脂联素、C-反应蛋白、空腹血糖、孕24-28周复查血浆脂联素、C-反应蛋白、OGTT葡萄糖耐量试验及胰岛素,计算胰岛素抵抗指数,跟踪孕妇至妊娠分娩,根据糖耐量结果分为妊娠期糖尿病组与正常妊娠妇女组对照。对照妊娠期糖尿病孕早、中期血浆脂联素、C-反应蛋白水平及其他检验指标。结果 GDM组10-14周及24-28周血清脂联素均明显低于NGT组,差异显著(P<0.05);GDM组C-反应蛋白明显高于NGT组,差异显著(P<0.05),孕10-14周血清脂联素与C-反应蛋白、孕前体重指数、胰岛素抵抗指数,存在显著负相关性。结论妊娠期糖尿病患者早、中孕期的血浆脂联素及C-反应蛋白水平的存在相关性,脂联素及C-反应蛋白水平是预测妊娠期糖尿病的敏感指标,具有早期预测妊娠期糖尿病的意义。     

LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study.

OBJECTIVE: LDL particles are heterogeneous in terms of size and density; small dense LDL particles are considered more atherogenic than larger LDL particles. The aim of this study was to investigate the interrelationships among LDL size, insulin, proinsulin (intact and split), and insulin sensitivity in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS: Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detectable cross-reactivity with insulin, and LDL size was determined by gradient-gel electrophoresis. RESULTS: In univariate analyses, LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin-to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0.0001). In a multivariate regression model (adjusted for age, BMI, ethnicity, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.0001), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantly inversely related to proinsulin in men (P = 0.005 and P = 0.04 after further adjustment for the glucose tolerance status), but not in women (P > 0.15). CONCLUSIONS: We found an inverse relation of proinsulin to LDL particle size in a large tri-ethnic population with varying degrees of glucose tolerance. This relation was independent of age, BMI, and triglyceride and HDL cholesterol concentrations, and was more pronounced in men than in women.     

Lipoprotein(a), apolipoprotein A-I and B serum levels in young families from Tallinn,Estonia. Relationships with other cardiovascular risk factors and nationality

Serum lipid, lipoprotein(a) (Lp(a)), apolipoprotein (apo) A-I and B concentrations were studied in young families of Tallinn: 157 husbands, 81 wives and 149 newborns participated in the study; 48% of subjects were Estonians, 39% Russians and 13% other nationalities. As previous studies among middle-aged men and school children of Estonia revealed clear national differences in serum lipoprotein profiles, our special interest was to study lipoprotein parameters in relation to ethnic origin. Body mass index (BMI), blood pressure (BP) and smoking habits were determined. In newborns, maturity by physical and neurological criteria and Apgar score after birth were assessed. At the age of 18-30 years, Estonian men had significantly higher serum total cholesterol, LDL cholesterol, triglyceride and Lp(a) levels than did Russian men. Estonian newborns had higher serum triglyceride concentration than Russian ones. Among women no national differences were recorded in the measured parameters. Lp(a) levels were not statistically correlated with age, BMI, BP or current smoking. Negative associations were revealed between Lp(a) and serum level of apo A-I (in men) or triglycerides (in newborns). Lp(a) concentrations correlated positively with LDL cholesterol (in women) and apo B (in newborns). Lp(a) levels of newborns were not associated with birthweight or health status, but correlated strongly with the sum of parental and fathers' Lp(a) concentrations, demonstrating that a genetic factor(s) is involved in the values of plasma Lp(a) levels.     

Evaluation of features of syndrome X in offspring of Caribbean patients with Type 2 diabetes

OBJECTIVE: To determine whether the features of metabolic syndrome X are more common in offspring of patients with Type 2 diabetes than in control subjects without immediate family history of diabetes. MATERIALS and METHODS: Thirty-four young offspring of patients with Type 2 diabetes and 27 healthy control subjects underwent a standard oral glucose tolerance tests (OGTT; 75 g glucose in 300 ml water). Anthropometric indices, blood pressure, plasma glucose, serum lipids and insulin levels were measured. Homeostasis model assessment (HOMA) was used to assess basal insulin resistance (IR) and sensitivity (%S). RESULTS: The offspring had significantly higher mean+/-SD BMI (p<0.01) and basal serum triglyceride (p<0.05), insulin (p<0.05), insulin/glucose ratio (p<0.01), and lower %S (p<0.001) than the control subjects, in spite of similar fasting plasma glucose concentrations. Multiple linear regression analysis showed that these differences were independent of BMI. Although, the two groups of subjects had similar serum HDL-Cholesterol, LDL-cholesterol and blood pressure levels, %S was significantly related to diastolic BP (p<0.01) and serum triglyceride levels (p<0.01). CONCLUSIONS: In comparison with the healthy control subjects, the insulin resistant offspring have higher levels of the identified syndrome X features independent of obesity. These features were quantitatively lower than the values reported in offspring of white Caucasian and African-American patients.     

Lipoprotein(a), apolipoprotein A-I and B serum levels in young families from Tallinn, Estonia. Relationships with other cardiovascular risk factors and nationality.

Serum lipid, lipoprotein(a) (Lp(a)), apolipoprotein (apo) A-I and B concentrations were studied in young families of Tallinn: 157 husbands, 81 wives and 149 newborns participated in the study; 48% of subjects were Estonians, 39% Russians and 13% other nationalities. As previous studies among middle-aged men and school children of Estonia revealed clear national differences in serum lipoprotein profiles, our special interest was to study lipoprotein parameters in relation to ethnic origin. Body mass index (BMI), blood pressure (BP) and smoking habits were determined. In newborns, maturity by physical and neurological criteria and Apgar score after birth were assessed. At the age of 18-30 years, Estonian men had significantly higher serum total cholesterol, LDL cholesterol, triglyceride and Lp(a) levels than did Russian men. Estonian newborns had higher serum triglyceride concentration than Russian ones. Among women no national differences were recorded in the measured parameters. Lp(a) levels were not statistically correlated with age, BMI, BP or current smoking. Negative associations were revealed between Lp(a) and serum level of apo A-I (in men) or triglycerides (in newborns). Lp(a) concentrations correlated positively with LDL cholesterol (in women) and apo B (in newborns). Lp(a) levels of newborns were not associated with birthweight or health status, but correlated strongly with the sum of parental and fathers' Lp(a) concentrations, demonstrating that a genetic factor(s) is involved in the values of plasma Lp(a) levels.     

Insulin resistance and androgens in healthy women with different body fat distributions

OBJECTIVE: To compare androgens and sex hormone-binding globulin (SHBG) levels, and indices of insulin sensitivity (the response of plasma insulin and C-peptide in OGTT, insulin resistance and beta-cell activity estimated with the homeostasis assessment model (HOMA model) in healthy obese premenopausal women with different body fat distributions. PATIENTS AND METHODS: Free testosterone, androstenedione, SHBG levels and responses of plasma glucose, insulin and C-peptide in OGTT were examined in 74 healthy premenopausal women (19 with lower-body obesity (WHR < 0.80), 20 with pure abdominal obesity (WHR > 0.85), 19 with predominant abdominal obesity (WHR 0.81-0.85) and 18 normal-weight women). Insulin resistance and beta-cell function were estimated with the HOMA model. RESULTS: Both fasting and glucose-induced insulin levels were higher in women with pure abdominal obesity than in the controls (p < 0.001) and in those with lower-body obesity (P < 0.01). Insulin resistance was also higher in women with pure abdominal obesity than in the controls (p < 0.01) and those with lower-body obesity (p < 0.05). Free testosterone (p < 0.01) was higher and SHBG (p < 0.001) was lower in women with abdominal obesity than in the control group and those with lower-body obesity. Insulin significantly correlated with SHBG, and this correlation was independent of androgens, obesity and obesity type. Beta-cell function positively correlated with free testosterone, whereas insulin resistance negatively correlated with SHBG, and was independent of obesity and obesity type. CONCLUSIONS: In healthy premenopausal women, increased BMI and more pronounced abdominal fat accumulation was associated with increased androgenic activity (higher free testosterone and lower SHBG levels) and with insulin resistance estimated using the HOMA model, as well as with increasing basal and glucose-induced insulin levels. SHBG levels correlated with insulin and insulin resistance independently of the degree of obesity, obesity type and androgens, whereas beta-cell function correlated only with free testosterone.     

Fasting intact proinsulin is a highly specific predictor of insulin resistance in type 2 diabetes

OBJECTIVE: In later stages of type 2 diabetes, proinsulin and proinsulin-like molecules are secreted in increasing amounts with insulin. A recently introduced chemiluminescence assay is able to detect the uncleaved "intact" proinsulin and differentiate it from proinsulin-like molecules. This investigation explored the predictive value of intact proinsulin as an insulin resistance marker. RESEARCH DESIGN AND METHODS: In total, 48 patients with type 2 diabetes (20 women and 28 men, aged 60 +/- 9 years [means +/- SD], diabetes duration 5.1 +/- 3.8 years, BMI 31.2 +/- 4.8 kg/m2, and HbA1c 6.9 +/- 1.2%) were studied by means of an intravenous glucose tolerance test and determination of fasting values of intact proinsulin, insulin, resistin, adiponectin, and glucose. Insulin resistance was determined by means of minimal model analysis (MMA) (as the gold standard) and homeostatis model assessment (HOMA). RESULTS: There was a significant correlation between intact proinsulin values and insulin resistance (MMA P<0.05 and HOMA P<0.01). Elevation of intact proinsulin values above the reference range (>10 pmol/l) showed a very high specificity (MMA 100% and HOMA 92.9%) and a moderate sensitivity (MMA 48.6% and HOMA 47.1%) as marker for insulin resistance. Adiponectin values were slightly lower in the insulin resistant group, but no correlation to insulin resistance could be detected for resistin in the cross-sectional design. CONCLUSIONS: Elevated intact proinsulin seems to indicate an advanced stage of beta-cell exhaustion and is a highly specific marker for insulin resistance. It might be used as arbitrary marker for the therapeutic decision between secretagogue, sensitizer, or insulin therapy in type 2 diabetes.     

Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance

Background: Statin treatment may be associated with adverse effects on glucose metabolism. Whether this is a class effect is not known. In contrast, ezetimibe monotherapy may beneficially affect insulin sensitivity. Objective: The aim of this study was to compare the effects of three different regimens of equivalent low‐density lipoprotein cholesterol (LDL‐C) lowering capacity on glucose metabolism. Methods: A total of 153 patients (56 men), who had not achieved the LDL‐C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATP III) despite a 3‐month dietary and lifestyle intervention, were randomly allocated to receive open‐label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks. The primary end point was changes in homeostasis model assessment of insulin resistance (HOMA‐IR). Secondary endpoints consisted of changes in fasting insulin levels, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA_1c), the HOMA of β‐cell function (HOMA‐B) (a marker of basal insulin secretion by pancreatic β‐cells), LDL‐C and high sensitivity C reactive protein (hsCRP). Results: At week 12, all three treatment regimens were associated with significant increases in HOMA‐IR and fasting insulin levels (p < 0.05 compared with baseline). No significant difference was observed between groups. No change in FPG, HbA_1c and HOMA‐B levels compared with baseline were noted in any of the three treatment groups. Changes in serum lipids and hsCRP were similar across groups. Conclusion: To the extent that simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance, they appear to be of the same magnitude.     

Fasting serum levels of adiponectin, ghrelin, and leptin in men with spinal cord injury

OBJECTIVES: To measure serum levels of adiponectin, ghrelin, and leptin in men with spinal cord injury (SCI) and to investigate possible correlations between these serum levels and various factors, such as body mass index (BMI), age, injury level, and duration of injury. DESIGN: Cross-sectional. SETTING: A university hospital that is a tertiary referral center. PARTICIPANTS: Eighty-nine men with traumatic neurologically complete SCI (30 with tetraplegia, 59 with paraplegia) and 37 age- and BMI-matched male controls. Subjects with SCI were injured at the mean age +/- standard error of 28.5+/-1.0 years (range, 14.7-59.1 y) and the mean injury duration was 10.8+/-0.7 years (range, 1.1-27.7 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of adiponectin, ghrelin, and leptin and BMI. RESULTS: Serum leptin levels in subjects with SCI (mean, 7.0+/-0.5 mg/mL) [corrected] were significantly higher than those in able-bodied controls (mean, 4.7+/-0.6 mg/mL) [corrected] (P<.01). The group with tetraplegia had higher serum leptin levels than the group with paraplegia, but this did not reach a statistically significant level (8.2+/-1.1 ng/mL vs 6.4+/-0.5 mg/mL [corrected] P=.097). There were significant differences in serum leptin levels among the 3 groups by 1-way analysis of variance (P=.008). Serum adiponectin levels in subjects with SCI (7.1+/-0.5 mg/mL) [corrected] were higher than those in able-bodied controls (5.6+/-0.5 mg/mL) [corrected] but this was not statistically significant (P=.08). In contrast, serum levels of ghrelin in subjects with SCI (302.0+/-17.5 pg/mL) were similar to those in the controls (264.0+/-27.0 pg/mL) (P=.24). Serum leptin levels correlated positively with BMI (SCI, r=.698, P<.001; controls, r=.782, P<.001), whereas serum adiponectin (SCI, r=-.527, P<.001; controls, r=-.315, P=.057) and ghrelin (SCI, r=-.368, P<.001; controls, r=-.447, P=.006) levels correlated negatively with the BMI in both subjects with SCI and controls. CONCLUSIONS: Men with SCI have significantly higher serum leptin levels than able-bodied controls, and serum leptin levels correlated with the degree of neurologic deficit. Men with SCI had a tendency toward higher serum adiponectin level than able-bodied controls. Serum levels of ghrelin in men with SCI were similar to those of controls.