Sex- and age-related differences of metabolic parameters in impaired glucose metabolism and type 2 diabetes compared to normal glucose tolerance.

AIMS: This study analysed potential sex differences in glucose metabolism of European subjects with different degrees of glucose tolerance impairment. METHODS: Subjects with impaired glucose metabolism, IGM (n = 735), or type 2 diabetes, T2DM (n = 415), were compared to subjects with normal glucose tolerance, NGT (n = 422), with similar BMI. For both males (M) and females (F), 50 years threshold was used for estimation of menopausal/andropausal state. Subjects underwent 75-g OGTT for measurements of insulin sensitivity (OGIS), beta-cell function (insulinogenic index, IGIC), and overall metabolic condition, disposition index (DI). RESULTS: In IGM, OGIS did not change with age in both sexes, whereas marked reduction of IGIC was seen in F (p = 0.0003). In T2DM, again OGIS did not change with age, but M ≥ 50 yrs had reduced IGIC and DI (p < 0.002) compared to M < 50 yrs. CONCLUSIONS: IGM did not reveal relevant changes of insulin resistance with age, but early phase insulin release deteriorated, with higher change in women. T2DM men featured age-related deterioration of glucose metabolism. In women, sex advantage seen in NGT vanished in T2DM, since glucose metabolism was overall not different than in men, both young and elderly.

Insulin resistance and beta-cell dysfunction in people with prediabetes according to criteria based on glycemia and glycosylated hemoglobin.

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are well-known conditions of risk for diabetes. Recently, 1h-hyperglycemia (1h-HG), i.e., glycemia > 8.6 mmol/L, has been suggested as further condition of diabetes risk. Moreover, in 2010 the American Diabetes Association included the measurement of glycosylated hemoglobin (HbA1c) among the criteria of diabetes risk (5.7-6.4%). Aim of this study was investigating all these different conditions of diabetes risk, with specific focus on possible insulin sensitivity and beta-cell function changes, when 1h-HG, and further HbA1c-prediabetes, are added to the already deeply studied condition of IFG/IGT. In this study, we retrospectively analysed 744 participants that underwent 2h-OGTT and HbA1c measurement. Participants were stratified into groups: (i) normal glucose tolerance, NGT (n=178); (ii) IFG and/or IGT (n=88); (iii) IFG/IGT plus 1h-HG (n=342); (iv) IFG/IGT plus 1h-HG plus HbA1c-prediabetes (n=136). We calculated several indices of insulin sensitivity and beta-cell function, as well as an index considering both aspects (disposition index). We found that progressing from group (i) to group (iv) both insulin sensitivity and beta-cell function tended to further deteriorate; the parameter providing more evidence was the disposition index (p<0.008 in any group comparison). In conclusion, for appropriate assessment of the level of diabetes risk (especially in people already known to be at high risk), it may be convenient to measure all the indicated parameters, that is, glycemia at fasting, at one hour and two hours during OGTT, and glycosylated hemoglobin.

Glucose metabolism after renal transplantation.

OBJECTIVE: We determined prevalence, risk factors, phenotype, and pathophysiological mechanism of new-onset diabetes after transplantation (NODAT) to generate strategies for optimal pharmacological management of hyperglycemia in NODAT patients. RESEARCH DESIGN AND METHODS: Retrospective cohort study comparing demographics, laboratory data, and oral glucose tolerance test (OGTT)-derived metabolic parameters from kidney transplant recipients versus subjects not receiving transplants. RESULTS: Among 1,064 stable kidney transplant recipients (≥ 6 months posttransplantation), 113 (11%) had a history of NODAT and 132 (12%) had pretransplant diabetes. In the remaining patients, randomly assigned OGTTs showed a high prevalence of abnormal glucose metabolism (11% diabetes; 32% impaired fasting glucose, impaired glucose tolerance, or both), predominantly in older patients who received tacrolimus as the primary immunosuppressant. Compared with 1,357 nontransplant subjects, stable kidney transplant recipients had lower basal glucose, higher glycated hemoglobin, lower insulin secretion, and greater insulin sensitivity in each of the three subgroups, defined by OGTT 2-h glucose (<140, 140-199, ≥ 200 mg/dL). These findings were reinforced in linear spline interpolation models of insulin secretion and sensitivity (all P < 0.001) and in another regression model in which the estimated oral glucose insulin sensitivity index was substantially higher (by 79-112 mL/min m(2)) for transplant versus nontransplant subjects despite adjustments for age, sex, and BMI (all P < 0.001). CONCLUSIONS: Glucose metabolism differs substantially between kidney transplant recipients and nontransplant controls. Because impaired insulin secretion appears to be the predominant pathophysiological feature after renal transplantation, early therapeutic interventions that preserve, maintain, or improve ß-cell function are potentially beneficial in this population.

Influence of increasing BMI on insulin sensitivity and secretion in normotolerant men and women of a wide age span.

The impact of sex and age on glucose metabolism in the development of overweight/obesity is a matter of debate. We hypothesized that insulin sensitivity (IS) and ß-cell function (BF) in a normal white population will differ between males and females and aimed to evaluate the possible effects of BMI and age on metabolic parameters of both sexes. This study is a cross-sectional analysis of the general community. IS was measured with quantitative insulin sensitivity check index (QUICKI) and oral glucose insulin sensitivity (OGIS) and BF with the insulinogenic index during 75-g 2-h oral glucose-tolerance tests (OGTTs). We studied 611 females and 361 males with normal glycemia according to both fasting and 2-h glucose (85 ± 0.3 mg/dl (means ± SE) in females and 89 ± 0.4 in males (P < 0.0001), and 93 ± 1 in females and 89 ± 1 in males (P = 0.005), respectively). Females were younger (37 ± 1 years) than males (40 ± 1, P < 0.0001), but no difference was found in mean BMI (BMI = 25.8 ± 0.2 kg/m(2) in both). Student's two-sample t-test was used for simple comparison between and within genders, multiple linear regressions to account for covariates. During the OGTT, females had lower glucose (area under the curve (AUC) 133 ± 1 mg/ml·2 h vs. 148 ± 2; P < 0.00001), while insulinemia was comparable (AUC 5.3 ± 0.1 mU/ml·2 h vs. 5.7 ± 0.2, P = 0.15). IS remained higher in females (473 ± 3 ml/min/m(2) vs. 454 ± 3, P < 0.0001) also after having accounted for age and BMI (P = 0.015). No difference was observed in fasting insulin or BF. However, BF increased by 46% with BMI and when accounting for age and BMI, BF of females was significantly higher (P < 0.0001). Because IS and BF are higher in females than in males, sex should be considered in metabolic studies and overweight/obese populations.