Comparative Informativity of Computing Methods of Insulin Resistance Assessment.

We conducted a comparative study of the calculated indices of insulin resistance HOMA-R, Caro, FGIR, and QUICKI in 29 healthy volunteers (mean age 26.21±0.93 years) with normal body mass index (23.34±0.55 kg/m2). Among the used methods for insulin resistance assessment, QUICKI is the only method that has characteristics required for the diagnostic criterium: low variability coefficient, 100% reproducibility, and minimum coefficient of variation.

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension.

PURPOSE: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL). METHOD: Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS + HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ group: n = 22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated. RESULTS: Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS + HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not. CONCLUSIONS: LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.

Type-2 diabetes related intermediate phenotypic traits in north Indian diabetics.

Asian Indians are known to be at a higher risk of developing T2DM, but the underlying genetic factor in this population is still not well understood. T2DM is a complex genetic trait and assessment of disease related intermediate phenotypic traits is an important initial step towards any systematic genomic study. Therefore, in the present study we have assessed diabetes related intermediate phenotypic traits of insulin secretion and insulin resistance in the patients belonging to this population. The study included 157 T2DM patients of either sex ranging in age from 45-80 years and 84 non-diabetic subjects with no family history of diabetes, ranging in age from 45 to 75 years served as controls. Intermediate phenotypic traits studied were BMI, W: H ratio, fasting free fatty acid level and Insulin resistance and secretion. Diabetics were found to have significantly higher W: H ratio (p<0.001), FFA (p<0.001) and HOMA-R (p<0.001) as compared to non-diabetics. However, there was no significant difference in their BMI and HOMA-ß. There was a positive correlation between FFA level and HOMA-R among diabetics, but not among controls. These findings suggest that in abdominal obesity FFA mediated insulin resistance is an important causative factor underlying T2DM in this population. Moreover, comparable HOMA-ß in diabetics reflects compensatory insulin hyper secretion in these subjects. There is a need to examine relative contribution and precise nature of genetic factor in their tendency for central obesity, free fatty acidemia and insulin resistance.

Relationship between hypothalamic-pituitary-adrenal axis dysregulation and insulin resistance in elderly patients with depression.

Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients.

Normal menstrual cycle steroid hormones variation does not affect the blood levels of total adiponectin and its multimer forms.

OBJECTIVE: Plasma total adiponectin reveals a sexual dimorphism indicating that gonadal steroids may be involved in its secretion and/or metabolism. However, results from previous reports are conflicting and data regarding the influence of ovarian steroids on adiponectin's multimer forms are scarce. The objective of the study was to assess if total adiponectin and its isoforms are affected by the changes of estradiol and progesterone during the normal menstrual cycle and the association of total adiponectin and its isoforms with the gonadal steroid levels. MATERIALS/METHODS: Quantitative determination of plasma adiponectin and its multimers was conducted in the three phases of an ovulatory cycle in 13 premenopausal women, in the follicular phase of 10 more premenopausal women, in 20 postmenopausal women and in 21 men. Moreover, serum levels of FSH, LH, prolactin, estradiol, progesterone, and testosterone, sex hormone binding globulin, glucose, and insulin were measured. RESULTS: The circulating levels of total adiponectin and its multimers were not affected by the normal variation of estradiol and progesterone across the ovulatory menstrual cycle. In the whole number of participants, the total adiponectin and high molecular weight adiponectin levels were significantly different between genders and associated positively with age and sex hormone binding globulin levels, and negatively with testosterone and progesterone levels and the waist/hip ratio. In the multiple logistic regression analysis, after adjustment for age, gender, and sex hormone binding globulin and progesterone levels, significant predictors of total adiponectin levels were the waist/hip ratio and testosterone levels, and of high molecular weight adiponectin the testosterone levels. CONCLUSIONS: Normal menstrual cycle ovarian steroids are not involved directly in the regulation of secretion and/or metabolism of total adiponectin and its multimers. Testosterone seems to be responsible for the adiponectin's sexual dimorphism.

Apolipoprotein A5 T-1131C variant and risk for metabolic syndrome in obese adolescents.

BACKGROUND: Apolipoprotein A5 (APOA5) gene variants are associated with increased plasma triglycerides, a risk factor for metabolic syndrome (MS). The goal of the current study was the investigation of the distribution of T-1131C variant among obese adolescents with MS compared with healthy controls. SUBJECTS AND METHODS: The study included 150 obese adolescents (75 males and 75 females) with MS and 204 age and sex matched normal healthy controls (100 males and 104 females). The mean age of the patients was 15.47 ± 2.54 years, ranged from 17 to 20 years. They were genotyped by polymerase chain reaction-restriction fragment length polymorphism for the mutation (T-1131C). RESULTS: The blood pressure, triglyceride and HOMA-R levels were significantly higher and HDL-C levels were significantly lower in carrier (TC+CC) compared to non-carrier (TT) MS patients. There was accumulation of -1131C allele frequency in the MS group (31.33% vs. control group 11.76%), p<0.001. The genotypes were in Hardy-Weinberg equilibrium both in the patients with metabolic syndrome and in the control subjects. Results of analysis of multiple regression models showed that the ApoA5 -1131C carriers showed an increased incidence of MS (OR=1.73, 95% CI: 1.41-2.11). CONCLUSIONS: The present study suggests that the 1131T>C polymorphism is a risk factor for the development of metabolic syndrome in obese adolescents.

Association of genetic variants of the incretin-related genes with quantitative traits and occurrence of type 2 diabetes in Japanese.

BACKGROUND: None of the high frequency variants of the incretin-related genes has been found by genome-wide association study (GWAS) for association with occurrence of type 2 diabetes in Japanese. However, low frequency and rare and/or high frequency variants affecting glucose metabolic traits remain to be investigated. METHOD: We screened all exons of the incretin-related genes (GCG, GLP1R, DPP4, PCSK1, GIP, and GIPR) in 96 patients with type 2 diabetes and investigated for association of genetic variants of these genes with quantitative metabolic traits upon test meal with 38 young healthy volunteers and with the occurrence of type 2 diabetes in Japanese subjects comprising 1303 patients with type 2 diabetes and 1014 controls. RESULT: Two mutations of GIPR, p.Thr3Alafsx21 and Arg183Gln, were found only in patients with type 2 diabetes, and both of them were treated with insulin. Of ten tagSNPs, we found that risk allele C of SNP393 (rs6235) of PCSK1 was nominally associated with higher fasting insulin and HOMA-R (P = 0.034 and P = 0.030), but not with proinsulin level, incretin level or BMI. The variant showed significant association with occurrence of type 2 diabetes after adjustment for age, sex, and BMI (P = 0.0043). CONCLUSION: Rare variants of GIPR may contribute to the development of type 2 diabetes, possibly through insulin secretory defects. Furthermore, the genetic variant of PCSK1 might influence glucose homeostasis by altered insulin resistance independently of BMI, incretin level or proinsulin conversion, and may be associated with the occurrence of type 2 diabetes in Japanese.

An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat.