Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents

Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.     

Retinol-binding protein 4 levels are elevated in polycystic ovary syndrome women with obesity and impaired glucose metabolism

OBJECTIVE: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4), a new fat-derived adipokine, has been described to be elevated in obesity and type 2 diabetes. The aim of the present study was to investigate whether serum RBP4 levels are correlated with metabolic parameters, indices of insulin resistance, and endocrine variables in German PCOS women. DESIGN: We assessed the correlation between metabolic and endocrine parameters with RBP4 levels in 200 PCOS patients and 64 healthy controls. METHODS: Serum RBP4 was measured by enzyme-linked immunosorbent assay (Immundiagnostik AG, Bensheim, Germany). In addition, anthropometric variables, clinical signs of hyperandrogenism, and body fat were evaluated, and a glucose tolerance test was performed to assess parameters of insulin resistance and glucose metabolism. RESULTS: Taking the entire PCOS cohort, RBP4 levels were positively correlated with body mass index (BMI), body fat, waist circumference, fasting glucose, and area under the curve for glucose (all P<0.05), but not with indices of insulin resistance. On the other hand, PCOS women with impaired glucose metabolism had higher RBP4 levels than PCOS women with normal glucose metabolism (median 30.6, range 23.3-73.9 versus median 26.3, range 6.4-61.4, P<0.05). Furthermore, no differences were found in RBP4 levels between lean PCOS women and BMI-matched healthy controls. CONCLUSION: In German PCOS women, serum RBP4 levels are associated with obesity and parameters of glucose metabolism but not with PCOS per se.     

Study of insulin resistance in relation to serum IGF-I levels in subjects with different degrees of glucose tolerance

AIM:

We studied the correlations between fasting and post-lunch serum IGF-I concentrations, and insulin resistance and insulin sensitivity in subjects with various degrees of glucose tolerance.

MATERIALS AND METHODS:

A total of 12 nondiabetic subjects, 09 subjects with impaired glucose tolerance (IGT) and 18 patients with newly diagnosed type-2 diabetes of either sex (mean age, 46 years) were recruited. None of the participants received any drug treatment at the commencement of the study. Fasting as well as post-lunch blood samples were collected from all the subjects and anthropometric and biochemical parameters were analyzed.

RESULTS:

Fasting serum IGF-I concentrations were negatively correlated with fasting serum glucose, insulin, C-peptide, triglycerides, total LDL and VLDL cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR), and age. Fasting serum IGF-I concentrations were positively correlated with fasting blood HDL cholesterol and homeostatic model assessment of insulin sensitivity (HOMA-S) in only diabetic subjects. Post-lunch serum IGF-I concentrations were positively correlated with HDL and LDL cholesterol. Correlations with HOMA-S with these metabolic anthropometric variables were of similar magnitude and direction as that of IGF-I concentrations. IGF-I concentrations were significantly lower in the subjects with World Health Organization-defined metabolic syndrome compared with the subjects without metabolic syndrome (P < 0.0001).

CONCLUSIONS:

Our data indicate that IGF-I could be a useful marker in the insulin resistance syndrome. The post-lunch low-IGF-I levels help in better identification of subjects at risk for type-2 diabetes mellitus and cardiovascular disease.     

Elevated serum RBP4 is associated with insulin resistance in women with polycystic ovary syndrome

Retinol binding protein 4 (RBP4) is a novel adipocyte-secreted protein that contributes to systemic insulin resistance. Experiments in mice suggest that elevated RBP4 causes insulin resistance. In the present study, we determined serum RBP4 concentration and evaluated its association with insulin resistance in women with polycystic ovarian syndrome (PCOS); 39 PCOS women and 45 healthy control subjects were enrolled in this study. Serum RBP4, fasting plasma glucose (FPG) and fasting serum insulin (FINS) were measured in all subjects. Furthermore, oral glucose tolerance test (OGTT), Botnia clamp (an intravenous glucose tolerance test followed by an euglycemic hyperinsulinemic clamp), and measurements of sex hormones were performed in 13 control subjects and all the PCOS women. The levels of serum RBP4 were elevated in PCOS women compared with the control (11.69 +/- 6.72 versus 7.75 +/- 5.96 microg/mL, p = 0.006). RBP4 levels were positively correlated with WHR (r = 0.216, p = 0.048), and intravenous glucose tolerance test beta cell index (IVGTT-beta index) which reflected beta cell function (r = 0.309, p = 0.028), but were inversely correlated with M value during Botnia clamp, which represented insulin sensitivity (r = -0.362, p = 0.008). No correlation was found between RBP4 and age, BMI, blood pressure, FPG, FINS, 2-h postprandial glucose, 2-h postprandial insulin, free testosterone, total testosterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH). In a linear stepwise regression analysis with a model including age, BMI, WHR, free testosterone, IVGTT-beta index, and M value as independent variables, only M value showed significant correlation with serum RBP4 levels (r2 = 0.105, f = 6.640, p = 0.012). In conclusion, serum RBP4 levels are significantly increased in PCOS women and associated with insulin resistance, which indicates that RBP4 may be a contributing factor linking adipose tissue with insulin resistance in PCOS.     

High plasma retinol binding protein-4 and low plasma adiponectin concentrations are associated with severity of glucose intolerance in women with previous gestational diabetes mellitus

CONTEXT: Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. OBJECTIVE: We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). RESULTS: Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. CONCLUSIONS: The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.     

Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: a population-based study

Serum ceruloplasmin was reported to be an independent risk factor for cardiovascular disease. We investigated whether serum ceruloplasmin level is elevated in subjects with metabolic syndrome (MS, insulin resistance syndrome) in a community-based population. A total 883 subjects over 40 years of age were studied among a population of the Chongup district, a rural area of South Korea. Serum ceruloplasmin levels were measured, and oral glucose tolerance tests were performed. Known cardiovascular risk factors, such as serum lipids, fasting insulin level, and urinary albumin excretion rate (UAER), were also measured. Serum ceruloplasmin levels in the subjects with MS (n = 167, 325 +/- 141 mg/L) were significantly higher than in those without MS (278 +/- 93 mg/L, P <.001). The mean ceruloplasmin level also increased as the glucose tolerance worsened (278 +/- 95 mg/L in normal glucose tolerance [NGT], 303 +/- 108 mg/L in impaired glucose regulation, and 328 +/- 148 mg/L in diabetes; P <.001). Serum ceruloplasmin level was positively correlated with age, fasting glucose, postload 2-hour glucose, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, and UAER and negatively with high-density lipoprotein (HDL)-cholesterol. In multiple regression analysis, serum ceruloplasmin level was independently associated with age, fasting glucose, triglyceride, HDL-cholesterol, and UAER. In conclusion, serum ceruloplasmin level is elevated in the subjects with MS, as well as in subjects with impaired glucose regulation or diabetes mellitus. In addition, serum ceruloplasmin level is associated with various cardiovascular risk factors. These results suggest that elevated serum ceruloplasmin level can be a marker for metabolic stresses associated with MS.     

Association of serum retinol-binding protein 4 and visceral adiposity in Chinese subjects with and without type 2 diabetes

OBJECTIVE: Previous studies have shown that adipose-derived serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant mouse models and in subjects with insulin resistance or type 2 diabetes. However, the association of visceral fat and serum RBP4 has not been studied. The purpose of this study was to investigate the relationship between serum RBP4 and regional fat distribution in Chinese subjects with and without type 2 diabetes. DESIGN: We measured serum RBP4 concentrations from 1033 Chinese subjects with various degrees of obesity and tested the association between visceral adiposity and serum RBP4. In a subgroup of this study, euglycemic-hyperinsulinemic clamp was performed to measure insulin sensitivity. The association between visceral adiposity and serum RBP4 was also determined in response to rosiglitazone treatment in a subgroup of patients with diabetes. RESULTS: Serum RBP4 level was positively correlated with visceral adipose area in male (r = 0.171; P < 0.001) and female (r = 0.215; P < 0.001) subjects. However, there was no correlation between serum RBP4 and body mass index. Subjects with visceral obesity had higher serum RBP4 concentrations than those without visceral obesity in both men and women. Rosiglitazone treatment in patients with diabetes resulted in a lower serum RBP4 level (35.2 +/- 10.2 vs. 24.9 +/- 5.6 microg/ml, before vs. after treatment). These changes were accompanied by improved insulin sensitivity and reductions in visceral fat area. The latter was found to be highly correlated with the decline of serum RBP4 levels (r = 0.471; P = 0.027). CONCLUSIONS: Serum RBP4 level is positively associated with visceral adiposity in both men and women. Our data suggest that RBP4 may contribute to the development of insulin resistance along with other adipokines.     

Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes

AIMS/HYPOTHESIS: Pregnancy is characterised by temporarily increased insulin resistance. Gestational diabetes occurs when pancreatic beta cell function is unable to compensate for this insulin resistance. Retinol-binding protein 4 (RBP4) could be related to insulin resistance. We hypothesised that RBP4 is elevated in gestational diabetes. METHODS: Serum RBP4, transthyretin and retinol were cross-sectionally measured in 42 women with gestational diabetes and 45 pregnant controls. Of these, 20 women with and 22 without gestational diabetes were included in an additional longitudinal study. RBP4 was determined by enzyme immunometric assay (EIA) and western blot. RESULTS: Women with gestational diabetes had lower RBP4 EIA and western blot levels than controls (median 6.8 [interquartile range, 3.9-14.3] vs 11.3 [7.8-19.9] microg/ml, p < 0.001 and 25.1 [21.7-29.6] vs 26.6 [23.5-32.2] microg/ml, p = 0.026). Transthyretin and the RBP4:transthyretin molar ratio were comparable between the groups. Serum retinol was lower (p < 0.001) and the RBP4 Western blot level: retinol molar ratio was higher in women with gestational diabetes (p = 0.044). RBP4 was not associated with the glucose or homeostasis model assessment of insulin resistance (HOMA-IR), but in gestational diabetes the RBP4:retinol molar ratio correlated with blood glucose and negatively with 2 h post-load insulin. The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls. In women with gestational diabetes RBP4 EIA and western blot levels increased after delivery. Retinol increased in both groups, while transthyretin and the RBP4:transthyretin ratio were not altered after parturition. CONCLUSIONS/INTERPRETATION: RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes. Thus, the RBP4:retinol ratio and the RBP4:transthyretin ratio are more informative than RBP4 levels alone when assessing insulin-glucose homeostasis during pregnancy.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

探讨中国汉族人群血清视黄醇结合蛋白4(RBP4)水平与妊娠糖尿病的关系.收集2005年7月至2007年12月在瑞金医院妇产科行常规产前检查的孕妇195例(妊娠糖尿病组99例,正常糖耐量组96例),同时收集65例非妊娠期健康育龄期妇女作为对照组,所有受试者均排除急慢性疾病,并统一用酶联免疫法检测血清RBP4水平.与非妊娠正常对照组相比,妊娠期妇女血清RBP4水平均明显升高,妊娠糖尿病患者血清RBP4水平较正常妊娠妇女显著升高[(43.04±1.85对33.84±2.17)ms/L,P<0.01].在妊娠期妇女中,多元逐步回归分析显示,胰岛素抵抗指数(HOMA-IR)和甘油三酯是血清RBP4水平升高的独市危险因素(r2=0.165).本研究结果提示,妊娠期妇女血清RBP4水平较非妊娠妇女显著升高,而与正常孕妇相比,妊娠糖尿病患者血清RBP4水平更高;在妊娠期妇女中胰岛素抵抗和甘油三酯水平与RBP4水平显著正相关.     

Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children

CONTEXT: Although retinol-binding protein (RBP)-4 concentrations are elevated in animal models of obesity and insulin resistance (IR), the link between RBP4 and IR in humans is less clear. There are few published data on RBP4 levels in overweight children, and most previous studies did not control for vitamin A (VA) status and/or subclinical inflammation. OBJECTIVE: The objective of the study was to measure serum RBP4, serum retinol (SR), the RBP4-to-SR molar ratio, and dietary VA intakes in normal-weight and overweight children and investigate the relationship of these variables to IR, subclinical inflammation, and the metabolic syndrome in this age group. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in Northern Switzerland. PATIENTS: Patients included 6- to 14-yr-old normal-weight, overweight, and obese children (n = 79). MAIN OUTCOME MEASURES: Body mass index, body fat percentage, waist-to-hip ratio, dietary VA intakes, serum RBP4, and SR were determined. IR was assessed using fasting insulin and the quantitative insulin sensitivity check index, and components of the metabolic syndrome and indices of subclinical inflammation were measured. RESULTS: Only 3% of children had low VA status. Independent of age, VA intakes, and C-reactive protein, body mass index, body fat percentage, and waist-to-hip ratio were significant predictors of RBP4, SR, and RBP4/SR. Independent of adiposity, RBP4 and RBP4/SR were significantly correlated with serum triglycerides, and RBP4/SR was correlated with fasting insulin. The RBP4-to-SR ratio more strongly correlated with components of the metabolic syndrome than serum RBP4. CONCLUSION: Independent of subclinical inflammation and vitamin A intakes, serum RBP4 and the RBP4-to-SR ratio are correlated with obesity, central obesity, and components of the metabolic syndrome in prepubertal and early pubertal children.     

吡格列酮对2型糖尿病患者血清视黄醇结合蛋白4和网膜素1的影响

目的 观察吡格列酮对2型糖尿病患者血清视黄醇结合蛋白4(RBP4)和网膜素1的影响.方法 选择80例新诊断2型糖尿病患者,随机分为对照组和吡格列酮组,每组40例,治疗3个月.比较两组患者治疗前后空腹血糖(FPG)、胰岛素抵抗指数(HOMA-IR)及血清BBP4和网膜素1的水平变化.结果 与对照组比较,吡格列酮组治疗后FPG和HOMA-IR明显降低(P＜0.05),血清RBP4水平也明显降低(P＜0.01),而网膜素1水平明显升高(P＜0.01).Pearson相关分析显示,RBP4与FPG、体质指数及HOMA-IR呈正相关,与低密度脂蛋白呈负相关(P＜0.05);网膜素1与低密度脂蛋白呈正相关,与FPG、体质指数及HOMA-IR呈负相关(P＜0.05).结论 吡格列酮可能通过调节血清RBP4和网膜素1水平而改善胰岛素抵抗.     

Association between insulin-like growth factor binding protein-2 levels and cardiovascular risk factors in Korean children

Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be involved in the development of obesity and insulin resistance like IGFBP-1. The aim of this study was to measure serum IGFBP-2 levels in overweight and obese children and to compare these levels with those of controls. We also analyzed the associations between IGFBP-2 and insulin sensitivity indices and cardiovascular risk factors. 134 Korean children including 55 overweight and 59 obese subjects were enrolled. We measured anthropometric values and determined fasting serum levels of IGFBP-2, glucose, insulin, lipid profiles, and insulin sensitivity indices including the homeostatic model assessment of insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). The subjects were subgrouped based on body mass index (BMI) and pubertal stage, and association analyses between IGFBP-2 levels and measured factors were performed in each group. Serum IGFBP-2 levels in overweight or obese children were significantly lower than those of controls regardless of pubertal development. Serum IGFBP-2 levels were negatively correlated with weight, BMI, waist circumference, fasting insulin levels, and HOMA-IR but were positively correlated with QUICKI. The associations were stronger in pubertal children than those in prepubertal children. However, no association was observed between serum IGFBP-2 levels and auxological or metabolic parameters in children with normal BMIs. These results suggested that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in overweight or obese children, regardless of pubertal stage.     

Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance

CONTEXT: Elevated levels of retinol binding protein-4 (RBP4) are positively correlated with insulin resistance, obesity, diabetes mellitus, and cardiovascular disease (CVD). Subclinical hypothyroidism (SCH) has also been associated with CVD; however, the factors linking SCH to CVD are not clear. OBJECTIVE: The objective of the study was to evaluate risk factors for CVD in elderly patients grouped according to thyroid function. DESIGN: 217 subjects (> or =65 yr old) were randomly selected from a population and allocated to a euthyroid group (n = 177) and an SCH group (n = 40) on the basis of plasma concentrations of TSH and free T(4). We included subjects with normal glucose tolerance by a 75-g oral glucose tolerance test and subjects with impaired fasting glucose. We measured anthropometric parameters, levels of fasting glucose and insulin, hemoglobin A(1c), adiponectin, RBP4, lipid profiles, total body fat content, and the area of sc and visceral fat. RESULTS: The SCH group had higher RBP4 levels than the euthyroid group, irrespective of body mass index and fat content. Subcutaneous and visceral fat areas and total body fat percentage did not differ between groups and were not correlated with RBP4 level. Other CVD risk factors did not differ between groups. RBP4 level was positively correlated with TSH level (r = 0.241, P = 0.001) after adjustment for age, sex, and body mass index. CONCLUSIONS: Plasma RBP4 levels were associated with SCH independent of obesity in elderly subjects with normal glucose tolerance, indicating that RBP4 level could be used as an index of CVD risk in SCH.     

Retinol-binding protein 4 is associated with impaired glucose regulation and microalbuminuria in a Chinese population

Aims/hypothesis  Increased retinol-binding protein 4 (RBP4) has been reported in association with insulin resistance and type 2 diabetes. We aimed to investigate the association of serum RBP4 with impaired glucose regulation and microalbuminuria in Chinese adults aged 40 years or older. Methods  Serum RBP4 was measured in 763 individuals with normal glucose regulation, 508 with impaired glucose regulation and 524 newly diagnosed diabetic patients. Serum RBP4 was measured using ELISA and urine albumin/creatinine ratio was used to determine the urinary albumin excretion. Results  Serum RBP4 concentrations were significantly higher in participants with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and diabetes than in those with normal glucose regulation, whereas serum RBP4 levels were not different in the four groups with dysregulation of glucose metabolism. RBP4 was associated with a higher risk for impaired glucose regulation (OR 1.011 for each 1 μg/ml increase in RBP4, 95% CI 1.000–1.022, p = 0.04) after adjustment for sex, age, BMI, current smoking and alcohol intake, family history of diabetes, insulin resistance, triacylglycerol, total cholesterol, and HDL- and LDL-cholesterol; the corresponding OR of combined impaired glucose regulation and type 2 diabetes was 1.022 (95% CI 1.009–1.035, p = 0.0009). RBP4 was associated with the risk of microalbuminuria (OR 1.023, 95% CI 1.004–1.042, p = 0.01) after adjustment for sex, age, smoking habit and alcohol intake, BMI, waist/hip ratio, homeostasis model assessment of insulin resistance, GFR, triacylglycerol, total cholesterol, and HDL- and LDL-cholesterol. Conclusions/interpretation  Serum RBP4 level is closely associated with impaired glucose regulation and is an independent risk factor for microalbuminuria. M. Xu and X. Y. Li contributed equally to this study.     

Association of insulin resistance with anti-Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

Objective  To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS).
Design/patients/measurements  We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles.
Results  Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH.
Conclusion  An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.     

不同性别2型糖尿病患者血清γ-谷氨酰转肽酶水平与代谢综合征的相关性研究

目的探讨江苏省成人2型糖尿病（T2DM）患者血清γ-谷氨酰转肽酶（GGT）与代谢综合征（MS）组分的相关性。方法测定T2DM患者（男438例,女300例）的GGT、血脂、空腹血糖（FBG）、空腹胰岛素（FINS）、血压、腰围等。结果①随着GGT四分位数的升高,男、女2组的体质量指数（BMI）、三酰甘油（TG）、FINS及稳态胰岛素评估模型胰岛素抵抗（HOMA—IR）指数升高;②男性组的GGT与腰围、BMI、舒张压（DBP）、TG、总胆固醇（TC）、FINS及MS组分数呈正相关,女性组的GGT与TG呈正相关（P均〈0．01）;③男、女性组GGT与HOMA—IR呈正相关（P均〈0．05）;④线性回归模型的结果显示,男性组中GGT水平主要受腰围及TG水平的影响,女性组中GGT水平主要受TG水平的影响。结论T2DM患者血清GGT与胰岛素抵抗及MS组分相关,同时在MS各组分中,GGT与TG水平最具相关性,提示GGT可能与肝脏胰岛素抵抗密切相关。     

Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people

CONTEXT: High retinol-binding protein 4 (RBP4) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between RBP4 and metabolic diseases is scarce. OBJECTIVE: We evaluated plasma RBP4 distribution and its association with metabolic syndrome (MetS) among middle-aged and older Chinese. RESEARCH DESIGN AND METHODS: We evaluated plasma RBP4 in a cross-sectional sample of 3289 Chinese aged from 50 to 70 yr in Beijing and Shanghai by using an in-house developed and validated sandwich ELISA. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: RBP4 levels were higher in male and Beijing residents, compared with female and Shanghai participants (both P < 0.001). RBP4 levels were associated positively with body mass index, waist circumference, triglycerides, total and low-density lipoprotein cholesterol, blood pressure, fasting insulin, and homeostatic model assessment of insulin resistance and negatively with high-density lipoprotein cholesterol and adiponectin (all P < 0.001). In the highest RBP4 quartile, the MetS risk was significantly higher (odds ratio 2.58; 95% confidence interval 2.08-3.20) than in the lowest quartile after adjustment for potential confounders. This association remained strong (odds ratio 2.25; 95% confidence interval 1.72-2.94) after further controlling for C-reactive protein, adiponectin, homeostatic model assessment of insulin resistance, and body mass index. CONCLUSIONS: This first large-scale population study shows that elevated RBP4 levels are strongly and independently associated with MetS. Prospective studies are needed to establish the role of RBP4 in the development of MetS and related diseases.     

Quantitative measurement of full-length and C-terminal proteolyzed RBP4 in serum of normal and insulin-resistant humans using a novel mass spectrometry immunoassay

Serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant humans and correlate with severity of insulin resistance in metabolic syndrome. Quantitative Western blotting (qWestern) has been the most accurate method for serum RBP4 measurements, but qWestern is technically complex and labor intensive. The lack of a reliable, high-throughput method for RBP4 measurements has resulted in variability in findings in insulin-resistant humans. Many commonly used ELISAs have limited dynamic range. Neither the current ELISAs nor qWestern distinguish among full-length and carboxyl terminus proteolyzed forms of circulating RBP4 that are altered in different medical conditions. Here, we report the development of a novel quantitative mass spectrometry immunoaffinity assay (qMSIA) to measure full-length and proteolyzed forms of RBP4. qMSIA and qWestern of RBP4 were performed in identical serum aliquots from insulin-sensitive/normoglycemic or insulin-resistant humans with impaired glucose tolerance or type 2 diabetes. Total RBP4 qMSIA measurements were highly similar to qWestern and correlated equally well with clinical severity of insulin resistance (assessed by clamp glucose disposal rate, r = -0.74), hemoglobin A1c (r = 0.63), triglyceride/high-density lipoprotein (r = 0.55), waist/hip (r = 0.61), and systolic blood pressure (r = 0.53, all P < 0.001). Proteolyzed forms of RBP4 accounted for up to 50% of total RBP4 in insulin-resistant subjects, and des(Leu)-RBP4 (cleavage of last leucine) correlated highly with insulin resistance (assessed by glucose disposal rate, r = -0.69). In multiple regression analysis, insulin resistance but not glomerular filtration rate was the strongest, independent predictor of serum RBP4 levels. Thus, qMSIA provides a novel tool for accurately measuring serum RBP4 levels as a biomarker for severity of insulin resistance and risk for type 2 diabetes and metabolic syndrome.     

The association of serum gamma glutamyltransferase with components of the metabolic syndrome in the Korean adults

The metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease related to insulin resistance. Recently, serum gamma glutamyltransferase (GGT) has been proposed as a marker of oxidative stress and is associated with a marked increase in the risk of cardiovascular disease. So, we investigated the association between serum GGT and components of the metabolic syndrome in the Korean adults. A total 3246 adults (aged 20-70 years, 1622 men and 1624 women) who visited Center for Health Promotion in Pusan National University Hospital for a medical checkup were included. We measured serum GGT and lipid profiles, fasting glucose, fasting insulin and blood pressure. As the quartile of serum GGT increased, the number of components of MS and prevalence of MS were increased. Serum GGT was also increased according as the number of components of MS was increased. A significant correlation (r=0.200, p<0.001 in men and r=0.133, p<0.001 in women) was noted between the numbers of the components of the MS and serum GGT. In addition, serum GGT was correlated significantly (r=0.266, p<0.001 in men and r=0.264, p<0.001 in women) with homeostasis model assessment of insulin resistance (HOMA-IR). In linear regression model, serum GGT was mainly influenced by the concentration of triglycerides and fasting glucose. In conclusion, serum GGT is closely related with insulin resistance and the increased number of components of MS. Among components of MS, serum GGT may be more associated with dyslipidemia and abnormal glucose tolerance, suggesting that serum GGT has more relationship with hepatic insulin resistance regardless of non-alcoholic fatty liver disease.     

Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus

Patients with primary hyperparathyroidism have impaired glucose tolerance more often than do controls, and parathyroid resection sometimes improves this derangement. However, it is unclear whether serum calcium (Ca) or parathyroid hormone (PTH) is more strongly related to impaired glucose metabolism in subjects without primary hyperparathyroidism. In this cross-sectional study, we examined patients with type 2 diabetes mellitus (DM) (271 men and 209 women) and analyzed the relationships between serum concentrations of Ca or intact PTH and DM-related variables. Simple regression analyses showed that the level of serum Ca was significantly and positively correlated with the levels of fasting plasma glucose, immunoreactive insulin, and homeostasis model assessment insulin resistance in men (P < .05), but not in women. In contrast, intact PTH was not significantly correlated with DM-related parameters in either sex. Multiple regression analyses showed that the significant and positive correlations between serum Ca vs fasting plasma glucose and homeostasis model assessment insulin resistance in men still remained after adjustment for intact PTH as well as age, body weight, height, creatinine, albumin, phosphate, bone metabolic markers, and estradiol (P < .05). Serum Ca level is positively associated with impaired glucose metabolism, independent of PTH or bone metabolism, in men with type 2 DM.