Study On The Serum Cortisol And Polymorphisms Of 11B-HSD1 Gene In Type 2 Diabetic Pedigrees

PARTⅠSTUDY ON THE CHANGE OF SERUM CORTISOL LEVELS & RELATED METABOLISM FACTORS IN TYPE 2 DIABETIC PEDIGREESObjective To study the change of serum cortisol level and its related factors in oral glucose tolerance test (OGTT) in members of type 2 diabetic pedigrees, and to discuss the effect of hypothalamo-pituitary-adrenal (HPA) axis on the development of type 2 diabetes mellitus (T2DM).Methods (1)Survey was conducted in T2DM pedigrees from Chongqing Han population, and glucose tolerance status was judged according to the OGTT results. Except the T2DM who have received therapy, the second degree relatives and spouses who had diabetic relatives or who was diabetic patient. All subjects were divided into three groups: T2DM group, first degree relatives (FDR) group and normal control group. 357 subjects (171 male and 186 female) from 114 pedigrees were enrolled. 97 of them were T2DM, 201 of them were FDR, and 59 of them were normal controls.(2)Anthropometric parameters, blood pressure,serum lipid profile, high-sensitivity C-reactive protein (hsCRP), nonesterified fatty acid (NEFA) were examined. Plasma glucose, insulin and serum cortisol levels in OGTT were measured.(3)Compare the anthropometric parameters, blood pressure, serum lipids, hsCRP and NEFA of three groups, and compare the plasma glucose, insulin, serum cortisol levels in OGTT. Analyse the changes of cortisol and the relationship between metabolism parameters.Results After adjusted for age, body mass index (BMI), waist circumferences and waist-to-hip ratio (WHR) in the FDR group were higher than those in controls, but there were no satistic difference between two groups (P>0.05). After adjusted for age and BMI, the level of systolic blood pressure (SBP) was higher than that in control group(P <0.05), Homeostasis model assessment for beta cell function (Homa-β) was lower than that in control group(P <0.05). FDR group had higher diastolic blood pressure (DBP), triglyceride(TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), Homeostasis model assessment index for insulin resistance (Homa-IR), hsCRP, NEFA and lower high-density lipoprotein cholesterol (HDL-C) than control group, but there were no satistical significance (P>0.05).T2DM group had higher BMI, waist circumference, WHR, SBP, DBP, TG, Homa-IR, NEFA and lower Homa-βthan FDR group and control group (P <0.01). Comparing with the FDR group, T2DM group had higher hsCRP level (P <0.05).After adjusted for age, sex and BMI, plasma glucose and serum cortisol of the four time points in OGTT, fasting insulin (FINS), insulin of 30 minutes after meal, insulin of 1 hour after meal, glucose area under the curve (AUCG), cortisol area under the curve in the T2DM group were higher than those in the FDR group and control group (P <0.05 or P <0.01 ). FDR group had higher cortisol levels of the four time points in OGTT than those of control group, but the difference was not statistically significant(P>0.05). Subset analysis of FDR group showed that cortisol level of normal glucose tolerance (NGT) subgroup and impaired glucose regulation (IGR) subgroup was not statistically significant higher than that of control group(P>0.05).Subset analysis showed those who had higher fasting plasma glucose (FPG), AUCG or Homa-IR in T2DM group had higher fasting serum cortisol level. Correlation analysis showed that: fasting serum cortisol did not related with any other factors in the control group; in the FDR group, fasting serum cortisol correlated with the FPG, r = 0.167(P<0.05),and in T2DM group fasting serum cortisol correlated with the age, FPG, and Homa-β(r respectively -0.213, 0.407, -0.28, P<0.05). Multiple stepwise regression analysis showed FINS was independent risk factor affecting fasting serum cortisol level of control group; FPG and plasma glucose of 2 hours after meal were independent risk factors affecting fasting serum cortisol level in FDR group; and in T2DM group, FPG level was the independent risk factor affecting fasting serum cortisol level.Conclusion There is significant familial aggregation of T2DM and related metabolic diseases such as obesity, hypertension, dyslipidemia.There are more or less metabolic abnormalities in the non-diabetic FDR. T2DM patients had a certain accentuation HPA axis, genetic susceptibility had little effect on cortisol level. Plasma glucose is a independent relevant factor affecting the fasting serum cortisol level of T2DM family members. The mechanism that cortisol involved in the insulin resistance of type 2 diabetes still needs to be further studied. PARTⅡTHE ASSOCIATION BETWEEN THE POLYMORPHISMS OF 11Β-HSD1 GENE AND TYPE 2 DIABETES MELLITUSObjective To study the association of 11β-Hydroxysteroid dehydro -genase Type 1 (11β-HSD1) gene polymorphism with T2DM and related metabolic factors in Han population in Chongqing.Methods In study, 247 T2DM (case group) and 128 normal controls (control group) unrelated were enrolled. A single nucleotide polymorphism (SNP) of rs1474655 in the intron 4 region and rs12086634 in the intron 3 region of 11β-HSD1 gene (HSD11B1) were genotyped by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in all the subjects enrolled.Results (1)The distribution rates of rs1474655 genotype and rs 12086634 genotype in case group were the same as those in the control group (x 2 =0.963,x 2 =2.125 respectively, both P>0.05), and the allele frequency of rs1474655 and rs 12086634 had no significant difference between two groups (x2 =0.845,x2 =1.017 respectively, both P>0.05 ). (2)All metabolic factors in GC+CC genotype group were not significantly different from those in GG genotype of rs1474655 in control group (P> 0.05). HDL-C level in GG genotype of rs1474655 was lower than that in GC+CC genotype in case group. (3)TT genotype and GT genotype of rs12086634 had significantly higher Homa-IR level than that of GG genotype in control group (P<0.05). TT genotype of rs12086634 had significantly higher FPG and Homa-IR levels than those of GT genotype and GG genotype in case group (P<0.05).Conclusion The polymorphism of rs1474655 in HSD11B1 was not associated with T2DM in Han population in Chongqing. TT geneotype of rs12086634 in HSD11B1 related with higher plasma glucose and insulin resistance in T2DM group.