The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study

Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.     

Pro12Ala of the peroxisome proliferator-activated receptor-gamma2 gene is associated with lower serum insulin levels in nonobese African Americans: the Atherosclerosis Risk in Communities Study

Recent research suggests that the Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with diabetes- and obesity-related traits, and that its effects may be modified by obesity status. We characterized this variant in a population-based sample of 1,441 middle-aged African-American individuals with respect to diabetes-, obesity-, and other cardiovascular-related traits, both cross-sectionally and prospectively. The overall frequency of Ala12 was 1.9% (95% CI 1.5-2.5%), significantly lower than in Caucasian populations. Consistent with previous findings in Caucasians, African Americans with type 2 diabetes tended to be less likely to have the Pro/Ala genotype than those without (odds ratio [OR] 0.64, 95% CI 0.34-1.20); however, this OR was not statistically significant. Among nonobese individuals, the Pro/Ala genotype was associated with significantly lower ln(insulin) (P = 0.001), lower ln(HOMA-IR) (homeostasis model assessment of insulin resistance) (P = 0.002), higher fasting glucose-to-insulin ratio (P = 0.005), and lower diastolic blood pressure (P = 0.02). Among overweight individuals (BMI 25-29.9 kg/m(2)), the Pro/Ala genotype was associated with greater BMI (P = 0.02), waist-to-hip ratio (P = 0.01), and waist circumference (P = 0.04). Among obese individuals, there was no association between any of the diabetes- or obesity-related traits and the Pro12Ala PPAR-gamma2 variant. We conclude that among nonobese African Americans, the Pro/Ala genotype is associated with markers of greater insulin sensitivity.     

The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant: association with type 2 diabetes and trait differences

Recent studies have identified a common proline-to-alanine substitution (Pro12Ala) in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), a nuclear receptor that regulates adipocyte differentiation and possibly insulin sensitivity. The Pro12Ala variant has been associated in some studies with diabetes-related traits and/or protection against type 2 diabetes. We examined this variant in 935 Finnish subjects, including 522 subjects with type 2 diabetes, 193 nondiabetic spouses, and 220 elderly nondiabetic control subjects. The frequency of the Pro12Ala variant was significantly lower in diabetic subjects than in nondiabetic subjects (0.15 vs. 0.21; P = 0.001). We also compared diabetes-related traits between subjects with and without the Pro12Ala variant within subgroups. Among diabetic subjects, the variant was associated with greater weight gain after age 20 years (P = 0.023) and lower triglyceride levels (P = 0.033). Diastolic blood pressure was higher in grossly obese (BMI >40 kg/m2) diabetic subjects with the variant. In nondiabetic spouses, the variant was associated with higher fasting insulin (P = 0.033), systolic blood pressure (P = 0.021), and diastolic blood pressure (P = 0.045). These findings support a role for the PPAR-gamma2 Pro12Ala variant in the etiology of type 2 diabetes and the insulin resistance syndrome.     

Evidence for gene-nutrient interaction at the PPARgamma locus

The importance of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) in regulating insulin resistance and blood pressure has been demonstrated in families with loss of function mutations. Gain of function mutations has been associated with severe obesity. However, previous population studies of the common variant Pro12Ala have produced conflicting results. As it is likely that the natural ligands for this receptor may include fatty acids, we hypothesized that the effect of this common variant may be altered by the character of the diet, particularly the ratio of dietary polyunsaturated fat to saturated fat (P:S ratio). We studied 592 nondiabetic participants in an ongoing population-based cohort study who were genotyped for the Pro12Ala polymorphism in the PPAR gamma2 isoform. As the Ala homozygotes were uncommon (2.0%), all analyses were conducted comparing Pro homozygotes (79.1%) to Ala allele carriers. There was no difference in fasting insulin concentration or BMI between Ala allele carriers and Pro homozygotes. The fasting insulin concentration was negatively associated with the P:S ratio (P = 0.0119) after adjustment for age and sex, and a strong interaction was evident between the P:S ratio and the Pro12Ala polymorphism for both BMI (P = 0.0038) and fasting insulin (P = 0.0097). The data suggest that when the dietary P:S ratio is low, the BMI in Ala carriers is greater than that in Pro homozygotes, but when the dietary ratio is high, the opposite is seen. This gene-nutrient interaction emphasizes the difficulty of examining the effect of common polymorphisms in the absence of data on nongenetic exposures, and may explain the heterogeneity of findings in previous studies.     

Predictability of childhood adiposity and insulin for developing insulin resistance syndrome (syndrome X) in young adulthood: the Bogalusa Heart Study.

The occurrence of insulin resistance syndrome (syndrome X) is common in the general population. However, information is scant on the childhood predictors of syndrome X. This study examined the relative contribution of childhood adiposity and insulin to the adulthood risk of developing syndrome X in a biracial (black-white) community-based longitudinal cohort (n = 745; baseline age, 8-17 years; mean +/- SD follow-up period, 11.6 +/- 3.4 years). The four criterion risk variables considered were the highest quartile (specific for age, race, sex, and study year) of 1) BMI, 2) fasting insulin, 3) systolic or mean arterial blood pressure, and 4) total cholesterol to HDL cholesterol ratio or triglycerides to HDL cholesterol ratio. Clustering was defined as the combination of all four risk variables. In addition to the criterion risk variables, clustered adults had adverse levels of total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, diastolic blood pressure, and glucose compared with those who did not cluster (P < 0.001). Childhood variables, except glucose, showed adverse trends with increasing number of criterion risk variables present in adulthood (P for trend, 0.01-0.0001). The proportion of individuals who developed clustering as adults increased across childhood BMI (P for trend <0.0001) and insulin (P for trend <0.01) quartiles. The relationship to childhood BMI remained significant even after adjusting for childhood insulin. In contrast, corresponding association with childhood insulin disappeared after adjusting for childhood BMI. In a logistic regression model, childhood BMI and insulin were significant predictors of adulthood clustering, with BMI being the strongest and showing a curvilinear relationship. Using an insulin resistance index instead of insulin did not change the above findings. These results indicate that childhood obesity is a powerful predictor of development of syndrome X and underscore the importance of weight control early in life.     

Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain

This study determined the effects of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala variant on body composition and metabolism and the magnitude of weight regain in 70 postmenopausal women (BMI 25-40 kg/m(2)) who completed 6 months of a hypocaloric diet. At baseline, BMI, percent body fat, intra-abdominal and subcutaneous abdominal fat areas, resting metabolic rate, substrate oxidation, and postprandial glucose and insulin responses were not different between genotypes (Pro/Pro = 56, Pro/Ala and Ala/Ala = 14). The intervention similarly decreased body weight by 8 +/- 1% in women homozygous for the Pro allele and by 7 +/- 1% in women with the Ala allele (P < 0.0001). Fat oxidation did not change in Pro/Pro women but decreased 19 +/- 9% in women with the Ala allele (P < 0.05). Changes in glucose area were not different between groups; however, women with the Ala allele decreased their insulin area more than women homozygous for the Pro allele (P < 0.05). Weight regain during follow-up was greater in women with the Ala allele than women homozygous for the Pro allele (5.4 +/- 0.9 vs. 2.8 +/- 0.4 kg, P < 0.01). PPAR-gamma2 genotype was the best predictor of weight regain (r = 0.50, P < 0.01), followed by the change in fat oxidation (partial r = 0.35, P < 0.05; cumulative r = 0.58). Thus, the Pro12Ala variant of the PPAR-gamma2 gene may influence susceptibility for obesity.     

Combined effects of genetic and environmental factors on insulin resistance associated with reduced fetal growth

It has been suggested that the insulin resistance (IR) associated with reduced fetal growth results from interactions between genetic factors and an unfavorable fetal environment. In addition, the adipose tissue seems to play a key role in this association. We investigated whether polymorphisms in tumor necrosis factor (TNF)-alpha(G-308A), beta3 adrenoreceptor (ADRB3)(G+250C), and peroxisome proliferator-activated receptor (PPAR)-gamma2(Pro12Ala), key molecules of the adipose tissue, might affect the IR associated with reduced fetal growth. They were genotyped in 171 subjects who were born small for gestational age (SGA) and in 233 subjects who were born appropriate for gestational age (AGA) and underwent an oral glucose tolerance test (OGTT). The SGA group showed higher serum insulin concentrations than the AGA group at fasting (P = 0.03) and after stimulation (P = 0.0007), whereas no difference in serum glucose concentrations was observed. The frequencies of the alleles of these three polymorphisms were similar in both groups. In neither group did the polymorphisms affect glucose tolerance. In the SGA group, fasting insulin-to-glucose ratios were significantly higher in the TNF/-308A (P = 0.03), the PPAR/Ala12 (P = 0.01), and the ADRB3/+250G (P = 0.02) carriers than in the noncarriers. Results were comparable for fasting insulin concentration and insulin excursion under OGTT. No such amplification was observed in the AGA group. The effects of the PPAR/ProAla12 (P = 0.005) and the ADRB3/G+250G (P = 0.009) gene polymorphisms on IR indexes were significantly potentiated by BMI in the SGA group. In conclusion, our data exemplify the interaction between intrauterine environmental and genetic factors in the development of the IR associated with reduced fetal growth. They also point to the key role of adipose tissue in this association.     

Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study

The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor (PPAR)-gamma2 has recently been shown to be associated with type 2 diabetes. In the present analysis, we investigated whether PPAR-gamma2 Pro12Ala was associated with microvascular complications of type 2 diabetes, such as albuminuria, end-stage renal failure (ESRF), or retinopathy. A total of 445 patients with type 2 diabetes who were enrolled in the Berlin Diabetes Mellitus Study and in whom we determined albuminuria and the presence of ESRF and retinopathy were genotyped for the PPAR-gamma2 Pro12Ala polymorphism. We also measured potentially important covariables, such as blood pressure, BMI, duration of diabetes, glycosylated hemoglobin, serum creatinine, and serum lipids. Among 445 patients with type 2 diabetes (mean age 59.3 years), the Pro12Ala genotype distribution was in Hardy-Weinberg equilibrium (P = 0.42). The Ala12 allele frequency was 0.14. With adjustment for covariables, the 118 Ala12 allele carriers had significantly lower urinary albumin excretion (UAE) than the 327 noncarriers (17.1 vs. 25.8 mg/d; P = 0.01). The percentage decrease in UAE observed in PPAR-gamma Ala12 allele carriers relative to noncarriers (P = 0.003) rose from 0.2% (P = 0.99) to 54% (P = 0.008) and to 70% (P = 0.01) when the duration of diabetes increased from <10 years to 10-19 years and to >or=20 years, respectively. Similarly, the odds ratios of having albuminuria decreased from 1.22 (P = 0.54) to 0.61 (P = 0.23) and to 0.11 (P = 0.007), respectively. Among patients with type 2 diabetes, PPAR-gamma2 Ala12 allele carriers had significantly lower UAE and tended to develop overt proteinuria less frequently. These observations suggest a protective effect of the Ala12 allele in relation to diabetic nephropathy.     

The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes

The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism has been associated with a decreased risk of type 2 diabetes and a lower albumin excretion rate (AER) in patients with established diabetes. We performed a case-control study aiming to evaluate the association between the Pro12Ala polymorphism and diabetic nephropathy. Genomic DNA was obtained from 104 type 2 diabetic patients (case subjects) with chronic renal insufficiency (78 on dialysis and 26 with proteinuria [AER >or=200 microg/min] and serum creatinine >or=2.0 mg/dl) and 212 normoalbuminuric patients (AER <20 microg/min) with known diabetes duration >or=10 years (control subjects). The genotypic distribution of the PPARgamma2 Pro12Ala polymorphism in these diabetic patients was in Hardy-Weinberg equilibrium, and the Ala allele frequency was 9%. The frequency of Ala carriers (Ala/Ala or Ala/Pro) was 20.3% in control subjects and 10.6% in case subjects (P = 0.031). The odds ratio of having diabetic nephropathy for Ala carriers was 0.465 (95% CI 0.229-0.945; P = 0.034). Carriers of the Ala allele were not different from noncarriers (Pro/Pro) regarding sex (38.9 vs. 44.1% males) or ethnicity (77.4 vs. 71.7% white) distribution, age (61 +/- 10 vs. 61 +/- 10 years), known diabetes duration (17 +/- 7 vs. 16 +/- 7 years), BMI (27 +/- 4 vs. 28 +/- 5 kg/m(2)), fasting plasma glucose (184 +/- 81 vs. 176 +/- 72 mg/dl), HbA(1c) (6.7 +/- 2.3 vs. 6.9 +/- 2.4%; high-performance liquid chromatography reference range: 2.7-4.3%), and systolic (145 +/- 27 vs. 0.144 +/- 24 mmHg) or diastolic (87 +/- 14 vs. 85 +/- 14 mmHg) blood pressure, respectively. In conclusion, the presence of the Ala allele may confer protection from diabetic nephropathy in patients with type 2 diabetes.     

Insulin resistance in non -diabetic peritoneal dialysis patients and its influencing factors

Objective To observe insulin resistance (IR) in non-diabetic peritoneal dialysis (PD) patients, and analyze its related factors. Methods The non-diabetic PD patients who had been on stable PD at least three months were eligible to enroll． The patients were measured for their height, weight, waist to hip ratio, fasting glucose, fasting insulin, lipids and other biochemical indicators, dialysis adequacy indicators in August 2012, and divided into two groups depended on median HOMA-IR in August 2012. Results A total of 56 patients were enrolled and divided into two groups according to median HOMA-IR, including high IR group (HOMA-IR≥1.79, n=29) and low IR group (HOMA-IR＜1.79, n=27). Compared to low IR group, high IR group were older [(57.9±14.2) years vs (48.7±14.5) years], had higher daily dialysate glucose load [(138.7±28.5) mmol/L vs (114.0±21.5) mmol/L], higher waist-to-hip ratio [(0.91±0.08) vs (0.86±0.07)], higher BMI [(23.0±3.0) kg/m2 vs (21.2±3.1) kg/m2], higher triglycerides [(2.51±1.36) mmol/L vs (1.42±0.48) mmol/L], lower high-density lipoprotein cholesterol [(1.00±0.27) mmol/L vs (1.23±0.32) mmol/L], and lower Kt/V [(1.74±0.37) vs (2.08±0.56)]. Multivariate logistic regression showed that age (β =0.122, P=0.033), triglycerides (β = 1.798, P=0.030) and daily dialysate glucose load (β =0.094, P=0.031) associated with the degree of insulin resistance. Conclusion More dialysate glucose exposure is a risk factor of the occurrence of insulin resistance in non-diabetic patients with peritoneal dialysis.     

PCOS患者抗苗勒管激素水平与胰岛素抵抗及生殖激素水平的相关性研究

目的探讨多囊卵巢综合征(PCOS)患者血清抗苗勒管激素(AMH)水平与胰岛素抵抗(IR)及生殖激素水平的相关性。方法选取2017年1月至2020年2月在东莞东华医院生殖医学科就诊的PCOS患者62例,根据患者是否存在胰岛素抵抗,分为胰岛素抵抗组(HOMA-IR>2.1,PCOS-IR组,34例)和非胰岛素抵抗组(HOMA-IR<2.1,PCOS-NIR组,28例);选择同时期在同院行健康体检的30例正常女性为对照组。测定所有研究对象的血清生殖激素(AMH、FSH、LH、E2、T、PRL、P)水平,以及硫酸脱氢表雄酮(DHEA)、性激素结合球蛋白(SHBG)及空腹血糖(GLU)空腹胰岛素(FIN)水平等指标,统计分析组间各指标的差异;采用Spearman相关分析分析AMH水平与稳态模型胰岛素抵抗指数(HOMA-IR)的关系。结果3组间平均年龄、体重指数(BMI)及血清FSH、P、PRL、SHBG及DHEA水平均无统计学差异(P>0.05)。与对照组比较,PCOS组(包括PCOS-IR组和PCOS-NIR组)血清AMH、LH及T水平显著升高(P<0.05);与PCOS-NIR组比较,PCOS-IR组FIN[(20.31±12.71)mU/L vs.(5.69±1.98)mU/L]、GLU[(5.58±1.98)mmol/L vs.(4.89±1.98)mmol/L]和HOMA-IR[3.7(2.42,7.09)vs.1.28(0.84,1.63)]显著升高(P<0.05)。相关性分析结果显示,PCOS患者AMH水平与LH水平(r=0.403,P=0.001)及T水平(r=0.403,P=0.000)呈正相关,与FSH水平呈负相关(r=-0.253.P=0.044),而与年龄、BMI、E 2、P、PRL、FIN、GLU、SHBG、DHEA及HOMA-IR不存在显著相关(P>0.05)。结论PCOS患者血清AMH水平高于正常女性,其原因与高雄激素密切相关;PCOS患者血清AMH水平与胰岛素抵抗无相关性。     

IgA肾病患者糖代谢异常和胰岛素抵抗的研究

目的:研究原发性IgA肾病(IgA nephropathy,IgAN)患者中糖代谢异常及胰岛素抵抗(insulin resistance,IR)的发生率及相关危险因素。方法:回顾性分析107例IgAN患者(IgAN组)和106例健康对照者(对照组)的口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)结果,并收集一般临床及实验室资料,计算胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI),评估糖代谢异常及胰岛素抵抗发生率。结果:IgAN组糖代谢异常的发生率高于对照组;IgAN组血压、血清肌酐、尿酸、三酰甘油、胆固醇、低密度脂蛋白、血糖(空腹及OGTT2h)、血清胰岛素(空腹及OGTT2h)、HOMA-IR均高于对照组,血清白蛋白、高密度脂蛋白、ISI低于对照组,差异均有统计学意义(P<0.05)。年龄(OR=1.061)、24h尿蛋白定量(OR=1.387)、三酰甘油(OR=2.553)是IgAN患者发生糖代谢异常的独立危险因素。与糖代谢正常的IgAN患者相比,合并糖代谢异常的IgAN患者年龄、BMI、24h尿蛋白定量、三酰甘油、空腹血糖、OGTT2h血糖及血清胰岛素、HOMA-IR均较高(P<0.05),而高密度脂蛋白、ISI较低(P<0.05)。IgAN合并IR的患者BMI、24h尿蛋白定量、三酰甘油、空腹血糖、空腹血胰岛素、OGTT2h血糖及血清胰岛素水平均显著高于不伴IR的IgAN患者(P<0.05),血肌酐、高密度脂蛋白、ISI则较低(P<0.05);BMI(OR=0.059,P<0.05)、血清白蛋白(OR=0.033,P<0.01)、24h尿蛋白定量(OR=0.077,P<0.05)为IgAN患者发生胰岛素抵抗的独立危险因素。结论:IgAN患者糖代谢异常的发生率高于正常人,存在明显的高胰岛素血症及胰岛素抵抗;年龄、24h尿蛋白定量、三酰甘油是IgAN患者发生糖代谢异常的独立危险因素;BMI、血清白蛋白、24h尿蛋白定量为IgAN患者发生胰岛素抵抗的独立危险因素。     

健康男性的胰岛素抵抗指数、肥胖、血清PSA水平间的关系

本研究旨在确定血清PSA水平低于4ngmL^-1的健康男性的胰岛素抵抗指数、肥胖和血清前列腺特异性抗原（PSA）水平之间的关系。调查对象为韩国水力原子力株式会社的11827名健康男性职员,在2003年1月到2008年12月间接受了体检,体检项目包括空腹血糖水平、空腹胰岛素水平和血清PSA水平。用稳态模式评估法（HOMA;[空腹血糖水平×空腹胰岛素水平]／22．5）和定量胰岛素敏感性检验指数（QUICKI;1／[10g（空腹胰岛素水平）＋log（空腹血糖水平）]）测定胰岛素抵抗指数。协方差分析（ANOVA）和Duncan’s多重比较试验显示,随着用HOMA和OuICKI测定的胰岛素抵抗指数四分位的上升,年龄标化体重指数（BMI）也显著增加（P〈0．001）。多变量线性回归分析表明,相对于血清PSA水平,年龄、BMI、以及用HOMA或QUICKI测得的胰岛素抵抗指数都是显著的独立变量（P〈0．001）。本研究说明胰岛素抵抗指数和BMI都是血清PSA水平的独立变量,在健康男性体内,两者都与血清PSA水平呈负相关,两者之间呈正相关。     

Associations of insulin levels with left ventricular structure and function in American Indians: the strong heart study

We evaluated the association of insulin and echocardiographic left ventricular (LV) measurements in 1,388 (45% men) nondiabetic American Indian participants in the Strong Heart Study (SHS). Significant (all P < 0.05) relations were found in men and women between log(10) fasting insulin and LV mass (r = 0.24 and 0.26), left atrial diameter (r = 0.25 and 0.28), posterior wall thickness (r = 0.20 and 0.26), septal thickness (r = 0.19 and 0.24), LV diameter (r = 0.17 and 0.16), and cardiac output (r = 0.20 and 0.24) and in women relative wall thickness (r = 0.11) and peripheral resistance (r = -0.17). In regression analyses, adjusting for BMI, age, height, and systolic pressure, fasting insulin was independently correlated with cardiac output in men and relative wall thickness and septal thickness in women (all P < 0.05). The 97th percentiles of fasting insulin (25 microU/ml for men, and 23 microU/ml for women) in 163 apparently normal (BMI <26; blood pressure <140/90; and absence of diabetes, valvular disease, LV wall motion abnormality, or antihypertensive treatment) SHS participants were used to separate normal from elevated fasting insulin levels. Adjusting for age, BMI, and height, men with elevated insulin levels had larger LV diameters (5.41 vs. 5.16 cm; P = 0.05), higher cardiac output (5.5 vs. 4.9 l/min; P < 0.001), and lower peripheral resistance (1,487 vs. 1,666; P = 0.01), paralleling results of regression analyses. Positive relations between insulin and heart size in nondiabetic adults are largely due to associations with body size; after adjustments for covariates, fasting insulin levels are related to greater LV size and cardiac output in men and more concentric LV geometry in women.     

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on insulin sensitivity and insulin metabolism interact with size at birth

Type 2 diabetes is known to be associated with a small body size at birth. Body size at birth is an indicator of the intrauterine environment. There is also a well-established association between the peroxisome proliferator-activated receptor (PPAR)-gamma2 gene and type 2 diabetes. We therefore assessed whether the effects of the Pro12Ala polymorphism of the PPAR-gamma2 gene on insulin sensitivity and insulin concentrations in adult life are modified by size at birth. We found that the effects of the Pro12Pro and Pro12Ala polymorphisms of the PPAR-gamma2 gene in elderly people depended on their body size at birth. The well-known association between small body size at birth and insulin resistance was seen only in individuals with the high-risk Pro12Pro allele. In those who had low birth weight, the Pro12Pro polymorphism of the PPAR-gamma2 gene was associated with increased insulin resistance (P < 0.002) and elevated insulin concentrations (P < 0.003). These interactions between the effects of the Pro12Ala polymorphisms of the PPAR-gamma2 gene on adult traits and the effects of birth weight link two previously unknown associations together within the context of type 2 diabetes. We suggest that these findings reflect gene-environment interaction.     

性激素结合球蛋白检测在评价多囊卵巢综合征治疗中的意义

目的探讨性激素结合球蛋白(SHBG)检测在评价治疗多囊卵巢综合征(PCOS)不育患者中的意义。方法将533例PCOS不育患者按体重指数(BMI)分为非肥胖组(424例)和肥胖组(109例)并再按是否存在胰岛素抵抗(IR)分为四组。A组:非肥胖无IR组(162例)、B组:非肥胖IR组(262例)、C组:肥胖无IR组(42例)、D组:肥胖IR组(67例)。测定黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E_2)、总睾酮(T)、泌乳素(PRL)、SHBG、血糖(FBG)和胰岛素(FINS)水平,计算游离雄激素指数(FAI)及稳态模型指数(HOMA-IR)。A组、C组予达英-35;B组、D组予达英-35+盐酸二甲双胍,均治疗3月后复查各指标。停药后给予枸橼酸氯米芬(克罗米芬,CC)+人绝经期促性腺激素(HMG)促排卵治疗。比较各组排卵及妊娠情况。结果四组治疗后FAI均较治疗前降低,SHBG较治疗前升高差异有显著性;四组治疗后LH、LH/FSH比值、T较治疗前降低差异有显著性;但A组HOMA-IR、FINS较治疗前升高差异有显著性,B、D组HOMA-IR、FINS较治疗前降低差异有显著性。促排卵结果显示治疗后排卵率非肥胖组高于肥胖组(85.60%vs 68.69%,P0.01),两组治疗后有排卵患者SHBG较无排卵患者升高,FAI较无排卵患者降低;非肥胖组LH、LH/FSH比值、FINS降低(P0.05),而肥胖组FINS、HOMA-IR则降低(P0.05)。妊娠结局比较:非肥胖组和肥胖组妊娠分娩患者治疗后T、FAI、FINS、HOMA-IR较自然流产患者降低,SHBG升高(P0.05);此外肥胖组妊娠分娩患者治疗后BMI较自然流产患者降低。结论无论肥胖还是非肥胖的PCOS患者,无论是否存在胰岛素抵抗,SHBG及FAI均可作为评价治疗是否有效的指标之一,可提示促排卵治疗及妊娠结局。因此在PCOS患者治疗中检测SHBG及FAI能指导临床用药,降低流产率,对优生优育有重要指导意义。     

Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P < 0.001), relative to global brain. Insulin's effect was less in ventral striatum and prefrontal cortex in the insulin-resistant subjects (mean +/- SD for right ventral striatum 3.2 +/- 3.9 vs. 7.7 +/- 1.7, P = 0.017). We conclude that brain insulin resistance exists in peripheral insulin resistance, especially in regions subserving appetite and reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.