Early-phase Disposition Index Research Articles

Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin.

The pathophysiology is distinct in various state of glucose metabolism abnormalities. As the defect of individuals with normal oral glucose tolerance (NGT) but isolated high glycosylated hemoglobin (HbA1c), i.e. iHH, was ambiguous, we aimed to investigate the insulin sensitivity and β-cell function of iHH. According to the ADA criteria of HbA1c cut-off point (5.7%), 3,517 subjects with NGT screened from a total of 7,855 middle-aged and elderly Chinese without known diabetes were divided into two groups, 1,877 subjects with HbA1c < 5.7% and 1,640 with HbA1c ≥ 5.7% (i.e. iHH). A variety of indexes from blood glucose and insulin levels of oral glucose tolerance were calculated to evaluate insulin sensitivity and β-cell function. Compared with subjects with HbA1c < 5.7%, individuals with iHH had increased homeostasis model assessment of insulin resistance (HOMA-IR), early-phase and total insulin release indexes (insulin release index 30 min and 120 min, i.e. INRS30 and INSR120), and decreased Matsuda insulin sensitivity index (Matsuda ISI) and early-phase disposition index (DI30). After adjustment for confounding factors, the significant difference of HOMA-IR and INSR30 between the two groups vanished, however, Matsuda ISI and DI30 remained significantly lower and INSR120 was still higher in iHH group compared with HbA1c < 5.7%. In conculsion, subjects with NGT may not be perfectly healthy in glycometabolism, those with iHH have impaired early-phase β-cell function and decreased insulin sensitivity.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance but not of β cell function in a Chinese population with different glucose tolerance status.

BackgroundTriglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance.MethodsFour hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI30], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained.ResultsIn all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66–0.75) and 0.71 (95 % CI: 0.65–0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and TG were significantly correlated with total-phase insulin secretion, but they also were not acceptable predictors of total-phase insulin secretion (0.60 < AUROC < 0.70).ConclusionsIn a Chinese population with different levels of glucose tolerance, TG/HDL-C and TG could be the predictors of IR. The lipid ratios could not be reliable makers of β cell function in the population.

Influence of diet on leukocyte telomere length, markers of inflammation and oxidative stress in individuals with varied glucose tolerance: a Chinese population study.

ObjectivesTo explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status.MethodsFive hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes (n = 159), pre-diabetes (n = 197), and normal glucose tolerance (n = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2′-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-ɑ), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion.ResultsIn patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c < 7 % group (log (LTL):1.93 ± 0.25) than in HbA1c ≥ 7 % group (log (LTL):1.82 ± 0.29). LTL was not associated with daily energy intake, diet fat, carbohydrates and protein proportions. Multiple linear regression analysis indicated that legumes, nuts, fish and seaweeds were protective factors for LTL shortening, and sweetened carbonated beverage was a risk factor for LTL shortening ( legumes: β = 0.105, p = 0.018; nuts: β = 0.110, p = 0.011; fish: β = 0.118, p = 0.007; seaweeds: β = 0.116, p = 0.009; sweetened carbonated beverage: β = −0.120, p = 0.004 ). Daily energy intake was positively associated with TNF-ɑ, IL-6 (TNF-ɑ: r = 0.125, p = 0.006;IL-6: r = 0.092, p = 0.04). Fat, carbohydrate proportions were positively associated with TNF-ɑ (fat: r = 0.119, p = 0.008 ; carbohydrate: r = 0.094, p = 0.043). Seaweeds and dairy intake were negatively associated with 8-oxo-dG (seaweed: r = −0.496, p = 0.001;dairy: r = −0.246, p = 0.046 ), vegetables and fruits were positively associated with GR ( vegetables: r = 0.101, p = 0.034;fruits: r = 0.125, p = 0.045). Cereal, meat were positively associated with TNF-ɑ ( cereal: r = 0.091, p = 0.048 ; meat: r = 0.405, p = 0.009).ConclusionDiabetes patients with better plasma glucose (HbA1c < 7 %) had longer LTL, LTL could reflect plasma glucose status in diabetes patients. LTL were probably not influenced by diet carbohydrates/fat proportions but was associated with diet ingredients. Diet ingredients significantly impacted on markers of inflammation and oxidative stress, which probably had an effect on LTL.Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-016-0157-x) contains supplementary material, which is available to authorized users.

Diet, insulin secretion and insulin sensitivity--the Dose-Responses to Exercise Training (DR's EXTRA) Study (ISRCTN45977199).

Intakes of saturated fat (SF) and dietary fibre, body mass and physical activity are all associated with the incidence of type 2 diabetes mellitus. Their relative importance for the maintenance of normal glucose metabolism is not fully known. In a population-based sample of 1114 individuals, aged 58-78 years, dietary intakes were assessed by 4d food records and cardiorespiratory fitness as maximal oxygen uptake. Insulin secretion, insulin sensitivity, the early-phase disposition index (DI30) and the total disposition index (DI120) were assessed based on an oral glucose tolerance test. Linear associations were modelled using linear regression. Combined effects were studied by introducing SF and fibre intakes, as well as cardiorespiratory fitness and waist circumference (WC) as dichotomised variables in general linear models. Intakes of dietary fibre and whole-grain bread were positively associated with insulin sensitivity, independent of physical fitness and WC. In women, dietary fibre intake was also positively associated with DI30. The negative association of high WC with DI30 was attenuated by a combination of low SF intake and high cardiorespiratory fitness. In conclusion, dietary fibre and a combination of low SF intake and high cardiorespiratory fitness may contribute to the maintenance of normal glucose metabolism, independent of WC.

Elevated serum thioredoxin‐interacting protein in women with polycystic ovary syndrome is associated with insulin resistance

Women with polycystic ovary syndrome (PCOS) mostly have profound insulin resistance (IR) and β-cell dysfunction. Although thioredoxin-interacting protein (TXNIP) is a major regulator in IR and insulin secretion, no data on the plasma TXNIP level in patients with PCOS are available. This study aimed to determine the plasma TXNIP level and discuss the relationship between TXNIP and β-cell dysfunction/IR in patients with PCOS. Eighty-three women with PCOS and 52 controls. Insulin sensitivity was expressed by M value obtained from euglycaemic-hyperinsulinaemic clamp. Homoeostatic model assessment for β-cell function (HOMA-β), △Ins30/△Glu30 and AUCins/glu were considered as the indices of fasting state, early-phase and total insulin secretion during oral glucose tolerance test, respectively. To evaluate β-cell function adjusted for insulin sensitivity, disposition index (DI) was used: basal DI (DI0), early-phase DI (DI30) and total DI (DI120). Plasma TXNIP levels were measured by enzyme-linked immunosorbent assay. Case-control study. Patients with PCOS had higher serum TXNIP, whereas lower M value, DI0, DI30 and DI120 than controls (P < 0·05); their TXNIP correlated positively with weight, waist-to-hip ratio (WHR), body mass index (BMI), Ins0, Ins120 and HOMA-β and correlated negatively with M value and DI120 (P < 0·05). Multiple stepwise regression analysis indicated that TXNIP remained associated with M value in PCOS subjects, after adjusting weight, BMI, WHR, HOMA-β, Ins0, Ins120 and DI120. However, no relationship between TXNIP and impaired β-cell function was found. Serum TXNIP is elevated in women with PCOS and may be a contributing factor for IR.

Insulin sensitivity and secretion indices in Japanese subjects with normal and impaired glucose tolerance

The aim of this study was to identify clinical factors that were associated with insulin sensitivity and secretion by multiple linear regression analysis in Japanese subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). A total of 2,983 subjects were classified into two groups, NGT and IGT, according to the oral glucose tolerance test criteria. To assess insulin sensitivity, homeostasis model assessment (HOMA)-S and the Matsuda index were used. To determine insulin secretion, HOMA-β, the insulinogenic index (IGI), basal disposition index (DI), and early phase DI were calculated. Stepwise multiple regression analyses were performed to examine the relationships between these indices and certain clinical factors, such as body mass index (BMI), HbA1c, age, sex, and family history. BMI was the only significant factor associated with HOMA-S. For the Matsuda index, the most important factor was BMI, followed by age and sex. BMI, HbA1c, age, sex, and family history were significantly associated with HOMA-β, IGI, basal DI, and early phase DI. The standardized partial regression coefficients of HOMA-β and IGI were highest for BMI. For basal DI and early phase DI, the highest standardized partial regression coefficient was found to be HbA1c, followed by age and BMI. Basal DI and early phase DI were more useful than HOMA-β and IGI to assess insulin secretion. The most important factors associated with insulin sensitivity and secretion are BMI and HbA1c, respectively. Age is more associated with insulin secretion than with insulin sensitivity.

Decreased Beta Cell Function and Insulin Sensitivity Contributed to Coronary Artery Disease in Patients with Normal Glucose Tolerance

To investigate the association among insulin sensitivity, insulin secretion, beta cell function and coronary artery disease (CAD) in patients with normal glucose tolerance. One hundred eighty-nine patients with normal glucose tolerance (NGT) participated in this study and underwent coronary angiography. We estimated the severity of CAD by counting the number of diseased vessels and Gensini score using coronary angiography. The HOMA-IR index and Matsuda index were used to estimate insulin sensitivity. Insulin secretion was assessed using the HOMA-β index, insulinogenic index and AUC-insulin/glucose. Beta cell function was assessed using the basal disposition index, early-phase disposition index and total disposition index. We finally determined the relationship between CAD and these indices. There were statistically significant differences in the HOMA-IR, Matsuda index, basal disposition index, early-phase disposition index and total disposition index both in the single- and multiple-diseased vessel groups when compared to the 0-diseased vessel group; however, there was no significant difference between the single- and multiple- diseased vessel groups. Moreover, HOMA-β, the insulinogenic index and AUC-ins/glu showed no significant difference among the three groups. Multivariate logistic regression analysis suggested that the HOMA-IR, Matsuda index, early-phase disposition index and total disposition index were independent risk factors for the presence of CAD. Insulin resistance and beta cell function were closely related to the incidence of CAD in patients with normal glucose tolerance.

Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population

Our aim was to provide a quantitative analysis of the changes in the principal determinants of insulin sensitivity and secretion in relation to fasting plasma glucose (FPG) or 2-h plasma glucose (2h PG) in a Chinese population with a wide range of glucose tolerance. A total of 5728 adults spanning the entire range of glucose tolerance were included. Insulin sensitivity was measured by Matsuda insulin sensitivity index (ISI(M)) and homeostasis model assessment of 1/homeostasis model assessment of insulin resistance (HOMA-IR). β-Cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at early-phase DI(30) and total DI(120). The exponential curve was established as the best fit for the relationship between insulin sensitivity or β-cell function and FPG or 2h PG. Relative to the trend classified as increasing 2h PG, hepatic insulin sensitivity and insulin secretion showed a decreasing trend to a substantial degree as FPG increased. A 1 mmol/l increase in FPG and 2h PG concentration was associated with a -22 and -21% decline in ISI(M), -16 and -4% in 1/HOMA-IR, -38 and -35% in DI(30) and -36 and -26% in DI(120). The decay constant of ISI(M) and DI(30) in IFG or ISI(M), 1/HOMA-IR, DI(30) and DI(120) in IGT was lower than that in normal glucose tolerance. Significant interactions between sex and glucose levels determining DI were found. We conclude that impairment of insulin sensitivity and insulin secretion contributes to both FPG or 2h PG hyperglycaemia in a Chinese population, but that the decline in insulin secretion is more pronounced with increasing fasting than 2h PG.