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Abstract The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

The pathogenesis involved in glucose metabolism disorders (GMDs) in patients with liver cirrhosis remains unclear. We investigated the effects of acute-on-chronic liver failure (ACLF) development and bacterial infections (BIs) on pancreatic β-cell function and glucose homeostasis in individuals with liver cirrhosis. A retrospective analysis was conducted on 327 patients experiencing acute deterioration of liver cirrhosis. Oral glucose tolerance tests (OGTTs) and OGTT-based β-cell function indices were employed to assess β-cell function and glucose homeostasis. Univariate and multivariate logistic regression analyses were employed to identify GMD-associated risk factors. Both the development of ACLF and BIs significantly increased the prevalence of GMDs. Both ACLF and BIs markedly elevated the homeostasis model of assessment 2-insulin resistance (HOMA2-IR). ACLF significantly impaired glucose-stimulated insulin secretion, as evidenced by reduced insulinogenic index (IGI). Patients with GMDs exhibited significantly lower IGI levels than those without GMDs. Independent risk factors associated with GMDs were prothrombin activity (odds ratio [OR]=0.981, 95% confidence interval [CI]: 0.960–0.995), HOMA2-IR (OR=1.749, 95% CI: 1.130–2.707), and IGI (OR=0.963, 95% CI: 0.947–0.978). In liver cirrhosis, the onset of ACLF impairs glucose-stimulated insulin secretion from β-cells. Both liver impairment and BIs contribute to increased insulin resistance, ultimately disturbing glucose homeostasis. [ABSTRACT FROM AUTHOR]

• The standard oral glucose tolerance test (OGTT) for cystic fibrosis-related diabetes (CFRD) is limited by sensitivity, specificity, and reproducibility. We are looking for ways to improve the information we get from the OGTT to make it a more valuable test. • The insulinogenic index (IGI) can easily be estimated from glucose and insulin measurements collected at baseline and after 30 min during an OGTT. This measure can tell us how well a person's insulin-producing beta cells are responding to a sugar load. • In our prospective CF cohort (n = 189), participants with a low IGI had a higher risk of glycemic deterioration and development of CFRD over the study follow up of up to 15 years. • IGI is easily measured in a clinical setting and could be a way to get more information from the OGTT about patients most at risk of progressing to CFRD. Measures of stimulated insulin secretion are emerging as important predictors of diabetes mellitus in at-risk populations. We analyzed the utility of clinical estimates of insulin secretion in a prospective cohort at risk for cystic fibrosis-related diabetes (CFRD). We divided the profiles of 189 people with CF (pwCF) followed longitudinally in the Montreal CF cohort (mean follow up 6.6 ± 1.2 years) according to quartiles of the insulinogenic index (IGI; (I 30 -I 0)/(G 30 -G 0)); area under the curve for insulin normalized for glucose (AUC ins/glu), and HOMA-B at baseline to compare clinical characteristics and risk of CFRD according to quartiles for each measure. We also compared characteristics of 40 pwCF found to have de novo CFRD at baseline. At baseline, IGI and AUC ins/glu were lower in subjects with de novo CFRD and those who later developed CFRD than those who never developed CFRD (p < 0.0001 for each). Subjects with the lowest quartiles of IGI, AUC ins/glu, and AUC ins/glu 0–30 had increased risk of developing CFRD by Kaplan-Meier analysis (p = 0.0244, p = 0.0024, and p = 0.0338, respectively). There was no significant difference in risk between quartiles of HOMA-B. Subjects in the lowest quartile of IGI showed a significant increase in 2-hour OGTT glucose and AUC glu between the initial and final study visits (p = 0.0027 and p = 0.0044, respectively). IGI is easily measured in a clinical setting and needs to be validated in prospective studies as a potential tool to improve risk stratification in CFRD with direct relevance to pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Research on the associations of physical activity and cardiorespiratory fitness with β-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with β-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults. Method: In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess β-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-b index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL) (mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations. Results: Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 (± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05). Conclusion: Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with β-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve β-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA. [ABSTRACT FROM AUTHOR]

AimsGlucagon-like peptide-1 (GLP-1) contributes to insulin secretion after meals. Though Hispanics have increased risk for type 2 diabetes mellitus, it is unknown if impaired GLP-1 secretion contributes to this risk. We therefore studied plasma GLP-1 secretion and action in Hispanic adults.MethodsHispanic (H; n = 31) and non-Hispanic (nH; n = 15) participants underwent an oral glucose tolerance test (OGTT). All participants were categorized by glucose tolerance into four groups: normal glucose tolerant non-Hispanic (NGT-nH; n = 15), normal glucose tolerant Hispanic (NGT-H; n = 12), impaired glucose tolerant Hispanic (IGT-H; n = 11), or newly diagnosed type 2 diabetes mellitus, Hispanic (T2D-H; n = 8).ResultsGlucose-induced increments in plasma GLP-1 (Δ-GLP-1) were not different in NGT-H and NGT-nH (p = .38), nor amongst Hispanic subgroups with varying degrees of glucose homeostasis (p = .6). In contrast, the insulinogenic index in T2D-H group was lower than the other groups (p = .016). Subjects with abnormal glucose homeostasis (AGH), i.e., T2D-H plus IGT-H, had a diminished glucagon suppression index compared to patients with normal glucose homeostasis (NGT-H plus NGT-nH) (p = .035).ConclusionsGLP-1 responses to glucose were similar in Hispanic and Non-Hispanic NGT. Despite similar glucose-induced Δ-GLP-1, insulin and glucagon responses were abnormal in T2D-H and AGH, respectively. Thus, impaired GLP-1 secretion is unlikely to play a role in islet dysfunction in T2D. Although GLP-1 therapeutics enhance insulin secretion and glucagon suppression, it is likely due to pharmacological amplification of the GLP-1 pathways rather than treatment of hormonal deficiency.

Aims: The present study aimed to clarify the relationships between diabetic family history (FH), and dysglycemic response to the oral glucose tolerance test (OGTT), insulin secretion, and insulin sensitivity in young Japanese persons with normal glucose tolerance (NGT). Methods: We measured plasma glucose (PG) and immunoreactive insulin levels in 1,309 young Japanese persons (age

IntroductionResearch on the associations of physical activity and cardiorespiratory fitness with β-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with β-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults.MethodIn a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess β-cell dysfunction (defined as insulinogenic index 1.9 (mU/L)/(mmol/L) and Matsuda index 0.05).ConclusionAmong Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with β-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve β-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA.

Abstract Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (

Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (<155 mg/dL) and the High 1h‐PG group (≥155 mg/dL). We compared the metabolic characteristics of the groups, including tissue‐specific insulin sensitivity measured using a two‐step hyperinsulinemic‐euglycemic clamp. Insulinogenic index and adiponectin levels were significantly lower in the High 1h‐PG group than in the Low 1h‐PG group. Other characteristics, including insulin sensitivity, adiposity and ectopic fat accumulation, were similar between the groups. In conclusion, non‐obese Japanese men with high 1h‐PG have impaired early‐phase insulin secretion and lower adiponectin levels. Insulin resistance and abnormal fat distribution were not evident in this population. [ABSTRACT FROM AUTHOR]

[Display omitted] • Blood gene expression analyses for the same 96 participants in 2008 and 2016. • Blood gene expression correlates with insulinogenic index (IGI) variations. • Declining IGI over 8 years correlates with metabolic dysregulation and inflammation. • Individuals with minor change in IGI featured homeostatic and regenerative response. • Gene expression useful for identifying prognostic biomarkers for declining IGI. Diabetes onset is difficult to predict. Since decreased insulinogenic index (IGI) is observed in prediabetes, and blood gene expression correlates with insulin secretion, candidate biomarkers can be identified. We collected blood from 96 participants (54 males, 42 females) in 2008 (age: 52.5 years) and 2016 for clinical and gene expression analyses. IGI was derived from values of insulin and glucose at fasting and at 30 min post-OGTT. Two subgroups were identified based on IGI variation: "Minor change in IGI" group with absolute value variation between –0.05 and +0.05, and "Decrease in IGI" group with a variation between –20 and –0.05. Following the comparison of "Minor change in IGI" and "Decrease in IGI" groups at time 0 (2008), we identified 77 genes correlating with declining IGI, related to response to lipid, carbohydrate, and hormone metabolism, response to stress and DNA metabolic processes. Over the eight years, genes correlating to declining IGI were related to inflammation, metabolic and hormonal dysregulation. Individuals with minor change in IGI, instead, featured homeostatic and regenerative responses. By blood gene expression analysis of non-obese individuals, we identified potential gene biomarkers correlating to declining IGI, associated to a pathophysiology of inflammation and metabolic dysregulation. [ABSTRACT FROM AUTHOR]

Background: The rate of metabolic syndrome (MetS) is exceptionally high in Korea, and the health risks and dietary implications of MetS have been reported extensively. Although most meals include combination foods, little is known about metabolic responses to meals containing various foods (such as a hamburger, which typically includes meat, bread, and vegetables). The purpose of this study was to compare glycemic responses and postprandial-triglyceride (PTG) concentrations after consuming each of four test meals: bibimbap, kimbap, pork cutlet, and hamburger. Methods: A clinical trial was carried out with 32 men using an open 4 × 4 × 4 treatment, sequence, and period crossover design. The blood-glucose concentrations, incremental area under the curve (iAUC), glycemic index (GI), insulinogenic index, and PTG after each test meal were determined. Results: The iAUC2h and Cmax responses were proportional to the amount of carbohydrates in the experimental diets [i.e., higher (p

The anti-diabetic activity of extracts, fractions and compounds of Moringa oleifera have been reported; however, several constituents from this well known medicinal plant are not yet screened for bio-perspecting role for diabetes. Current studies demonstrated the anti-diabetic properties of five chemical constituents of the plant viz, 4-hydroxyphenylacetonitrite (1), fluoropyrazine (3), methyl-4-hydroxybenzoate (4), vanillin (5), and 4-α-L-rhamnopyranosyloxybenzyl isothiocyanate (6) along with one related compound 3,4-dihydroxy benzonitrile (2) for the first time in vitro and in vivo. Furthermore, the mechanism of action of compounds was predicted by utilizing molecular docking with protein kinase A (PKA) and exchange protein activated by cAMP (Epac2A). The structure of compounds was elucidated by UV, IR, MS, and 1H NMR. The compounds 1, 3-5 induced significant insulin secretion at stimulatory (16.7 mM) glucose, but not at basal (3 mM) glucose concentration, and compound 3 seems to be the most active. Compounds 1, 3-5 showed dose-dependent insulin secretory activity with optimum response at 200 μM. In silico studies revealed that compound 3 has a noticeable electrostatic and hydrophobic interaction with protein kinase A (PKA). In vitro studies also showed that there was significant reduction of compounds 1-3 mediated insulin secretion in the presence of PKA inhibitor suggesting that there is a possible role of PKA signaling pathway on insulin secretion. Upon oral administration of 1, 3-5 to diabetic rats, compounds 1 and 3 significantly reduced blood glucose level in diabetic rats in a dose- and time-dependent manner. The oral glucose tolerance test in diabetic rats showed that compound 3 significantly enhanced plasma insulin and improved beta-cell function. In cytotoxicity assay, compounds 1, 3-5 did not show any toxic effect upto 200 μM. The insulin releasing characteristic of different constituents from M. oleifera conceivably correlate the lowering of blood glucose in in vivo diabetic rats by triggering glucose-induced insulin secretion from pancreatic islets possibly by PKA-mediated insulin secretory pathway. [ABSTRACT FROM AUTHOR]

Gymnema sylvestre is a medicinal plant whose consumption has demonstrated benefits on lipid and glucose levels, blood pressure, and body weight (BWt). The aim of this study was to evaluate the effect of G. sylvestre administration on metabolic syndrome (MetS), insulin secretion, and insulin sensitivity. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (without pharmacological treatment), 30-60 years old, with diagnosis of MetS in accordance with the modified International Diabetes Federation criteria. Patients were randomly assigned to receive G. sylvestre or placebo twice daily before breakfast and dinner in 300 mg capsules for a total of 600 mg per day for 12 weeks. Before and after the intervention, the components of MetS were evaluated as well as BWt, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein (VLDL). Area under the curve of glucose and insulin, phases of insulin secretion, and insulin sensitivity were calculated. Statistical analysis was performed using Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests; P ≤ .05 was considered statistically significant. After G. sylvestre administration, significant decreases in BWt (81.3 ± 10.6 kg vs. 77.9 ± 8.4 kg, P = .02), BMI (31.2 ± 2.5 kg/m2 vs. 30.4 ± 2.2 kg/m2, P = .02), and VLDL levels (0.45 ± 0.15 mmol/dL vs. 0.35 ± 0.15 mmol/dL, P = .05) were observed, without modifying the components of MetS, insulin secretion, and insulin sensitivity. In conclusion, G. sylvestre administration decreased BWt, BMI, and VLDL levels in subjects with MetS, without changes in insulin secretion and insulin sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: We wanted to determine vitamin D status after gestational diabetes mellitus (GDM) and to evaluate whether levels of 25-hydroxyvitamin D3 (25OHD3 ) are associated with beta cell function, insulin resistance or a diagnosis of diabetes after GDM.Material and Methods: Glucose homeostasis was assessed during a 75-g oral glucose tolerance test one to two years after delivery in 376 women with previous GDM (287 European and 78 non-European, including 33 Arab and 35 Asian women). Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to calculate insulin secretion. Concentrations of serum 25OHD3 were determined.Results: Mean (±SD) 25OHD3 concentration was 50.0 ± 22.3 nmol/L and differed significantly among subgroups of body mass index, ethnicity, and glucose tolerance status; 53% had 25OHD3 levels <50 nmol/L and 87% had 25OHD3 levels <75 nmol/L. There was a negative correlation between 25OHD3 concentration and HOMA-IR (p < 0.001) and a positive correlation between 25OHD3 and disposition index (p = 0.002) in univariable regression analysis. Correlations attenuated after adjustment for body mass index. In univariable regression analysis, 25OHD3 concentrations were significantly associated with diabetes after GDM (p = 0.004). However, in a multivariable model, non-European origin, HOMA-IR and insulinogenic index were significantly associated with postpartum diabetes, whereas 25OHD3 concentrations were not.Conclusion: Vitamin D deficiency/insufficiency in previous GDM cases appears to be associated with beta cell dysfunction and insulin resistance, but not with postpartum diabetes when factors well known to influence type-2 diabetes were adjusted for. [ABSTRACT FROM AUTHOR]

Aims: Recent biological and epidemiological studies have found that insulin resistance is linked to iron overload. However, little is known about the association between hemoglobin and/or serum iron levels and pancreatic β-cell function. In this gender-separated cross-sectional study, we aimed to investigate the association of hemoglobin and serum iron levels with early-phase insulin secretion in non-diabetic subjects. Methods: A total of 804 non-diabetic Japanese subjects (482 males and 322 females) aged over 30 years old were enrolled in the study. Early-phase insulin secretion was estimated using the insulinogenic index (IGI [ΔInsulin/ΔGlucose]) during a 75-g oral glucose tolerance test. Results: Simple linear regression analysis showed that IGI negatively correlated with hemoglobin levels in male but not in female subjects. However, IGI did not correlate with serum iron levels in either gender. Multivariate linear regression analysis in male subjects revealed that hemoglobin levels were predictors of IGI, responsible for 3.0 % of IGI variation ( P = 0.008). The association was independent of age, BMI, fasting glucose and insulin levels, and lipid profiles. In non-diabetic Japanese males, hemoglobin levels significantly and negatively correlated with early-phase insulin secretion. Conclusions: Our finding suggests that elevated hemoglobin levels may have a gender-specific impact on β-cell function and could be an independent predictor of β-cell dysfunction. [ABSTRACT FROM AUTHOR]

Objectives:To determine the risk factors for glucose intolerance (GI) during the postpartum period in women with gestational diabetes mellitus (GDM). Methods:This prospective cohort study included 72 Japanese women with GDM who underwent 75 g oral glucose tolerance tests (OGTT) at 12 weeks after delivery. These women were divided into the GI group and the normal group based on postpartum OGTT. Risk factors for GI, including levels of blood glucose (BG), area under the curve (AUC) of glucose, AUC insulin, HbA1c, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-β, insulinogenic index (II) and the oral disposition index (DI) in antepartum OGTT, were analyzed by logistic regression analyses. Results:Of the 72 women, 60 (83.3%) were normal and 12 (16.7%) had GI. By univariate logistic regression analyses, fasting BG, AUC glucose, HOMA-β, II and oral DI were selected as risk factors for GI. Multivariate logistic regression analysis revealed that the level of II in antepartum OGTT was a significant factor that predicted GI after delivery (odds ratio, 0.008; 95% CI, 0.0001–0.9;p < 0.05). Conclusions:II measured by OGTT during pregnancy might be a useful predictor of GI within the early postpartum period in women with GDM. [ABSTRACT FROM PUBLISHER]

Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C ( P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C ( P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C ( P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. [ABSTRACT FROM AUTHOR]

Setting Obesity surgery has been proposed as a treatment option for diabetic patients with body mass index (BMI)<35 kg/m 2 , but the efficacy of metabolic surgery has not been conclusively determined. Objectives To evaluate the long-term metabolic outcome of non–morbidly obese (NMO) patients with type 2 diabetes (T2D) after biliopancreatic diversion (BPD). Material and methods Two groups of T2D patients with different degree of obesity (NMO, 17 cases, BMI 25–35 kg/m 2 ; and morbidly obese [MO], 13 cases, BMI>35 kg/m 2 ) were studied before and at 1 and 5 years after BPD in a university hospital setting. Insulin secretion was assessed by acute insulin response (AIR) to intravenous glucose and by insulinogenic index (IGI). Results In all MO patients, T2D was remitted or controlled (1 case) at 1 year and results were maintained at 5 years; AIR (μU/mL) and IGI (μU/mg) improved ( P <.001) at 1 year (from .1±3.1 to 18.52±21.9, and from 6.0±8.5 to 9.1±22.8, respectively) with a further increase (to 24.8±25.5 and to 14.3±13.8, respectively) at 5 years. Within the NMO group, T2D was remitted in 1/17 and controlled in 14/17 patients at 1 year, and in 2/17 and in 4/17 patients at 5 years, respectively; AIR (μU/mL) and IGI (μU/mg) remained unchanged throughout the postoperative period (from .31±9.26 to 1.5±2.8 at 1 yr and to .4±3.29 at 5 yr for AIR, and from 2.2±4.9 to 1.3±9.0 at 1 yr and to 2.3±3.3 at 5 yr for IGI). Conclusions After BPD, restoration of β-cell secretion/production plays a pivotal role in determining postoperative T2D remission. [ABSTRACT FROM AUTHOR]

Objective To identify the risk factors associated with abnormal glucose tolerance (AGT) on the first postpartum oral glucose tolerance test (OGTT) among Japanese women with gestational diabetes (GDM). Methods In a retrospective study, data were analyzed from women with GDM who underwent their first postpartum OGTT 6–8 weeks post partum at a center in Omura, Japan, between January 1, 2007, and December 31, 2011. Women with diabetes or impaired glucose tolerance were deemed to have postpartum AGT. The association between postpartum AGT and various risk factors was analyzed. Results Among 169 women who underwent a postpartum OGTT, 58 (34.3%) had AGT. The significant risk factors associated with postpartum AGT in univariate analysis were pre-pregnancy body mass index ( P = 0.096), 1-hour plasma glucose ( P = 0.006), hemoglobin A 1c ( P < 0.001), insulinogenic index ( P = 0.05), an insulinogenic index of less than 0.4 ( P = 0.006), and insulin therapy during pregnancy ( P < 0.001). Independent risk factors identified by multivariate logistic regression models were insulinogenic index (odds ratio [OR] 0.10, 95% confidence interval [CI] 0.01–0.74; P = 0.002), an insulinogenic index of less than 0.4 (OR 5.70, 95% CI 1.69–21.66; P = 0.005), and insulin therapy during pregnancy (OR 3.43, 95% CI 1.03–12.55; P = 0.044). Conclusion Among Japanese women with GDM, a lower insulinogenic index and use of insulin therapy during pregnancy are associated with early postpartum AGT. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) is linked to altered calcium metabolism. However, little is known about the relationship between serum calcium levels and early-phase insulin secretion in subjects with normoglycemic tolerance (NGT) or prediabetes (preDM). Methods: In this gender-separated cross-sectional study, 352 subjects with NGT (215 men and 137 women; age: 48.8 ± 9.1 years and 51.6 ± 6.7 years, respectively) and 316 subjects with preDM (231 men and 85 women; age: 52.5 ± 8.6 years and 54.2 ± 8.0 years, respectively) were examined. Following a 75-g oral glucose tolerance test, early-phase insulin secretion was estimated using the insulinogenic index (IGI) [ΔInsulin(30-0 min)/ΔGlucose(30-0 min)]. Results: Simple linear regression analysis showed that IGI was positively correlated with serum calcium and albumin-adjusted calcium levels in men with NGT and preDM. However, IGI was not correlated with calcium levels in women with NGT and preDM. Multivariate linear regression analysis of men with NGT revealed that the albumin-adjusted calcium level was the major predictor of IGI, responsible for 5.1 % of its variation (P = 0.003). In addition, in men with preDM, the albumin-adjusted calcium level was one of the predictors of IGI, responsible for 3.8 % of its variation (P = 0.004). These associations were independent of age, BMI, and HbA1c. Conclusions: In non-diabetic Japanese men, serum calcium levels significantly correlate with early-phase insulin secretion. Serum calcium levels may be an independent predictor of β-cell function in men. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Elevated serum ferritin levels are associated with an increased risk of type 2 diabetes, but the nature of this association remains elusive. The aim of this study was to test the hypothesis that an elevated fasting serum ferritin level is associated with an increased risk of type 2 diabetes due to its association with impaired beta cell function and decreased insulin sensitivity. Methods: We investigated 6,392 individuals from the Danish general population. Surrogate measures of beta cell function and insulin sensitivity were calculated for approximately 6,100 individuals based on OGTT examinations. Results: The ORs for type 2 diabetes were 4.2 (95% CI 2.4, 7.2) for the highest vs the lowest quintile of serum ferritin, and 17 (95% CI 8.9, 33) for serum ferritin levels ≥97.5th percentile vs <20th percentile. Elevated serum ferritin levels were associated with elevated plasma glucose levels at 0, 30 and 120 min ( p < 0.001), elevated serum insulin levels at 0 and 120 min ( p = 0.02 and p < 0.001), decreased beta cell function estimated as the insulinogenic index and corrected insulin response ( p < 0.001), and decreased insulin sensitivity estimated by the Matsuda index of insulin sensitivity and HOMA-IR ( p < 0.001). Whereas the association with impaired beta cell function was present in both men and women, the association with decreased insulin sensitivity was observed among men and older women but not among younger women. Conclusions/interpretation: Elevated fasting serum ferritin levels are associated with surrogate measures of both impaired beta cell function and decreased insulin sensitivity. Menopause seems to modify the association with insulin sensitivity. [ABSTRACT FROM AUTHOR]

Medical examination of a 60-year-old non-obese female revealed a fasting plasma glucose concentration of 220 mg/dl and a glycated haemoglobin (HbA1c) level of 7.6 %. Because a 75-g oral glucose tolerance test (75-g OGTT) demonstrated fasting and post-prandial hyperglycaemia (>200 mg/dl), she was diagnosed with type-2 diabetes mellitus. Four days after hospitalisation, treatment with the glucagon-like peptide-1 analogue liraglutide was started. The M value, which reflects daily variations in plasma glucose levels, was markedly improved on days 3 and 14 of treatment (12.8 and 0.43, respectively). Her HbA1c level was consistently ≤5.8 % after discharge. OGTT revealed normal glucose levels (<140 mg/dl at 120 min) at 3, 14, and 24 months of liraglutide treatment. The insulinogenic index (μU/ml/mg/dl) increased from 0.067 before treatment to 0.20, 0.44, and 0.48 at 3, 14, and 24 months of treatment, respectively. The proinsulin/C-peptide immunoreactivity ratio, which reflects pancreatic β-cell failure, decreased from 0.03 before treatment to 0.025, 0.016, and <0.01 at 3, 14, and 24 months of treatment, respectively. The woman reported no side effects during liraglutide treatment. In conclusion, early administration of liraglutide was beneficial in our patient in terms of improving glycaemic control and protecting pancreatic β cells from glucotoxicity. [ABSTRACT FROM AUTHOR]

Background Newly detected impaired glucose tolerance ( IGT) or type 2 diabetes mellitus (T2 DM) are common in patients with acute coronary syndrome ( ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta-cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function. Methods Acute coronary syndrome ACS patients with IGT or T2 DM ( n = 71), screened by oral glucose tolerance test ( OGTT) 4-23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg ( n = 34) or placebo ( n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose-lowering agents other than the study drug. The study end-point was beta-cell function assessed using the insulinogenic index ( IGI = ΔInsulin30/ΔGlucose30), derived from an OGTT, and acute insulin response to glucose ( AIRg) assessed by a frequently sampled intravenous glucose tolerance test. Results The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol−1 and 1394 vs. 1106 pmol L−1 min−1 respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group ( P = 0.013) and AIRg was 1909 and 1043 pmol L−1 min−1 ( P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L−1 in sitagliptin-treated patients and 6.0 mmol L−1 in those who received placebo compared with 5.8 and 5.9 mmol L−1 respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group ( P = 0.003). Sitagliptin was well tolerated. Conclusion Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of a negative insulinogenic index (change in plasma insulin/change in plasma glucose from 0 to 30 min) from an oral glucose tolerance test according to glucose tolerance category. Materials and Methods: Data from the San Antonio Heart Study (n=2494), Japanese American Community Diabetes Study (JACDS; n=594) and Genetics of NIDDM Study (n=1519) were examined. Glucose tolerance was defined by ADA criteria. Results: In the combined cohort, the prevalence of a negative insulinogenic index was significantly higher in diabetes 20/616 (3.2%) compared to normal glucose tolerance 43/2667 (1.6%) (p<0.05). Longitudinally, in the JACDS cohort, the prevalence did not change from baseline (3/594; 0.5%) to 5 (4/505; 0.7%) and 10 years (8/426; 1.9%) (p=0.9) and no subject had a repeat negative insulinogenic index. Conclusions: A negative insulinogenic index occurs at a low prevalence across glucose tolerance categories although more often in diabetes, but without recurrence over time. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the association of A1C with beta-cell dysfunction, insulin resistance, and cardiovascular risk factors in Koreans with the relatively high risk for the future development of diabetes. This cross-sectional study recruited subjects from the pre-diabetic cohort of the Korea National Diabetes Program. Among study subjects ( n = 616) aged 21-77 years with a history of hyperglycemia (fasting plasma glucose (FPG) ≥5.5 mmol/mL), analyses were conducted on 504 participants (296 women, 208 men) except for subjects with FPG ≥ 7.0 mmol/L or 120-min post-challenge plasma glucose ≥11.1 mmol/L or A1C ≥ 6.5 %. For insulin sensitivity and β-cell function classified by the categories of A1C levels, ∆Ins/∆Glu was lower in the highest quartile group than other groups. Although there was no significant difference in HOMA-IR according to the A1C categories, even lowest A1C group (≤5.3 %) already included many subjects with abnormal glucose tolerance. A1C showed a significant association with hsCRP, number of metabolic syndrome (MetS) components and ∆Ins/∆Glu after adjusting for age, gender, BMI, and medications whereas HOMA-IR was insignificantly associated with A1C. Stepwise regression analysis for A1C showed that A1C is independently and negatively associated with ∆Ins/∆Glu, and positively associated with hsCRP. Our study showed that higher A1C was associated with impaired early-phase insulin secretion, MetS, and low grade inflammation in Koreans with the relatively high risk for the future development of diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although insulin resistance is involved in nonalcoholic fatty liver disease, role of abnormalities in early phase of insulin secretion has not been examined. Aims: We examined which anthropometric and metabolic parameters, including insulinogenic index during oral glucose tolerant test, were independently associated with the disease activity of nonalcoholic fatty liver disease. Methods: A total of 114 consecutive biopsy-proven nonalcoholic fatty liver disease patients without type 2 diabetes were enrolled. Results: Age, aspartate aminotransferase, free fatty acid, ferritin type IV collagen, hyaluronic acid, procollagen N-terminal peptide, fasting plasma glucose and 2-h insulin after glucose loading were significantly higher in patients with impaired glucose tolerance than those with normal glucose tolerance. Multiple stepwise regression analysis revealed that glycated haemoglobin, decreased density ratio of liver to spleen in computed tomography and increased insulinogenic index were independently associated with nonalcoholic fatty liver disease activity score in normal glucose tolerance patients, whereas aspartate aminotransferase and 2-h insulin in impaired glucose tolerance subjects. However, there were no significant independent correlations between insulinogenic index and steatosis grade/fibrosis stage in normal glucose tolerance patients. Conclusion: The present study suggests that increased early phase of insulin secretion may contribute to nonalcoholic fatty liver disease activity score in patients with normal glucose tolerance. [Copyright &y& Elsevier]

Objective: 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). Materials and methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract: Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. Design: 19 healthy lean (BMI=20.0–24.9) and 12 obese (BMI=30.0–39.9) individuals 18–50 years old completed three separate food test days during which they received preloads containing stevia (290kcal), aspartame (290kcal), or sucrose (493kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20min after the lunch preload. Despite the caloric difference in preloads (290kcal vs. 493kcal), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia=301kcal, p <.01; aspartame=330kcal, p <.01). Self-reported hunger and satiety levels did not differ by condition. Stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads (p <.01), and postprandial insulin levels compared to both aspartame and sucrose preloads (p <.05). When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload. [Copyright &y& Elsevier]

We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes. We monitored 174 women with gestational diabetes by performing oral glucose tolerance tests during pregnancy as well as 1, 2 and 5 years postpartum. Women who developed impaired fasting glucose, impaired glucose tolerance or diabetes were compared with women who remained normoglycaemic at 5 years. Insulinogenic index, disposition index and HOMA-beta cell index were used to assess beta cell function; insulin resistance was estimated by HOMA index of insulin resistance. At 5 years postpartum, 30% of the women had developed diabetes and 51% some form of abnormal glucose tolerance. Women who developed diabetes had higher fasting glucose and HbA1c during pregnancy than those who remained normoglycaemic. They also had lower HOMA-beta cell index, insulinogenic index and disposition index than the normoglycaemic women. HbA1c and fasting glucose during pregnancy as well as the number of previous pregnancies and family history of diabetes were independent predictors of postpartum diabetes. HbA1c ≥4.7% (Swedish Mono S) or ≥5.7% (National Glycohemoglobin Standardization Program) and fasting blood glucose ≥5.2 mmol/l were associated with a four- to sixfold increased risk. Among women with gestational diabetes mellitus, those at risk of future diabetes can be identified by HbA1c and fasting glucose values in the upper normal range during pregnancy. A family history of diabetes and previous pregnancies further increase this risk. [ABSTRACT FROM AUTHOR]

Abstract: To examine the serum 1,5-anhydroglucitol (AG) levels as a surrogate measure of postprandial hyperglycemia (PPH) and insulin secretion in a wide range of hyperglycemia, we compared the relationship between the glycemic index during a 75g oral glucose tolerance test (OGTT) and the insulinogenic index and 1,5-AG according the overall glycemic state. Fasting serum 1,5-AG levels were lower in the type 2 diabetic group (18.0±7.0μg/mL) than in the normal glucose tolerance (NGT, 25.4±4.0μg/mL), impaired fasting glucose (IFG, 24.6±6.2μg/mL), and impaired glucose tolerance (IGT, 22.1±6.2μg/mL) groups and were clearly correlated with glycemic values from the OGTT. 120-min post-challenge plasma glucose (PPG120) emerged as an independent predictor for 1,5-AG levels after multiple linear regression analysis (β =−0.554, P <0.001). Additionally, 1,5-AG levels were significantly correlated with PPG120 in each quartile of A1C, and the coefficients increased with higher A1C quartiles. Subjects with low 1,5-AG levels had both increased insulin resistance and decreased insulin secretion. Decreased 1,5-AG levels are closely correlated with PPH and decreased insulin secretion capacity across a wide range of glycemia, even in relatively well-controlled diabetes. [Copyright &y& Elsevier]

Abstract: The 1-h postchallenge plasma glucose (1-h PG) level is considered to be a good index of the development of glucose intolerance and type 2 diabetes as well as of diabetic complications. In some cases, in Japanese, 1-h PG is elevated despite normal fasting glucose during oral glucose tolerance test (OGTT), but the factors responsible remain unclear. In the present study, subjects with normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), and isolated impaired glucose tolerance (IGT) were divided into subgroups at 1-h PG of 10.0mM, and the four indices of insulin secretion and insulin sensitivity were compared. In all three categories, the insulinogenic index in subjects with elevated 1-h PG was remarkably lower than in those without elevated 1-h PG. In addition, the insulinogenic index was the strongest factor in elevated 1-h PG according to the multiple regression analysis. Interestingly, one third of the NGT subjects enrolled in this study had elevated 1-h PG. These subjects showed significantly elevated area under the curve of glucose (G-AUC) compared to NGT subjects without 1-h PG elevation. Thus, elevated 1-h PG in Japanese subjects indicates mildly impaired glucose tolerance due to decreased early-phase insulin secretion. [Copyright &y& Elsevier]

As the effect of renin-angiotensin system (RAS) blockade on β-cells in clinical situations remains unclear, new evidence has been presented that angiotensin-converting enzyme (ACE) inhibitors and angiotensin ││ receptor blockers (ARBs) may delay or prevent the development of insulin resistance and diabetes through novel mechanisms. This study aimed to determine the effects of ARBs on insulin excretion by β-cells. Hypertensive patients with impaired glucose tolerance were randomly divided into two groups: group A (n = 6), which received 8 mg/day of oral candesartan for three months, and controls (n = 6). Before and after administration, a 75 g oral glucose tolerance test was conducted to compare various parameters. No significant differences in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, or fasting immunoreactive insulin (IRI) were identified between the groups before administration. After three months, there were no significant changes in BMI, SBP, and DBP for the controls and in BMI and DBP for group A. However, SBP was significantly decreased from 144 ± 2.6 mmHg to 125 ± 4.6 mmHg in group A. Insulinogenic index tended to be slightly decreased for controls, but was significantly increased from 0.32 ± 0.0 to 0.47 ± 0.1 for group A. No significant changes in HOMA-R were identified in either group. To the best of our knowledge, no previous studies have documented a RAS inhibitor improving early-phase insulin response; thus, the present study may be the first of its kind. [ABSTRACT FROM AUTHOR]

Abstract: Although it is widely believed that type 2 diabetics with metabolic syndrome (MS) have insulin resistance, the β-cell function of these patients is largely unknown. We evaluated the characteristics of insulin secretion in Japanese type 2 diabetics with MS after minimizing the influence of glucotoxity. A 75-g OGTT was performed in 192 diabetic subjects and 275 subjects with normal glucose tolerance (NGT). Although there was no significant difference of the AUC (insulin0-120) between the MS group and the NGT group, the insulinogenic index (I.I.) was significantly lower in MS patients compared with NGT subjects. The BMI, maximum BMI, waist circumference, and VFA were all positively correlated with I.I. in the MS group (r =0.298–0.376). By stepwise multiple regression analysis, the BMI was shown to be an independent determinant of I.I. in the MS group (standardized regression coefficient: 0.376, p =0.0004), and it accounted for 13% of the variance in I.I. The impaired I.I. was also found in the MS group with untreated type 2 diabetes. These results indicate that early insulin secretion is impaired in type 2 diabetics with MS. The positive association between BMI and I.I. in diabetics with MS may be explained by β-cell compensation for reduced insulin sensitivity. [Copyright &y& Elsevier]

Knowledge of the within-subject variability of a parameter is required to properly design and calculate sample sizes for longitudinal studies. We sought to determine the day-to-day variability of measures of beta cell function derived from an OGTT. Thirty-seven adults (13 with normal glucose tolerance, ten with impaired glucose tolerance, 14 with type 2 diabetes) underwent a standard 2 h 75 g OGTT on two separate days (median time between tests, 7 days; range, 5–14). From these data, the reproducibility of several indices of beta cell function were determined: insulinogenic index (ΔI0–30/ΔG0–30), early C-peptide response (ΔCP0–30/ΔG0–30), incremental AUC insulin to glucose response (incAUCins/incAUCglu), integrated insulin secretion response from 0 to 120 min (IS/Glu0–120) and indices of beta cell function derived from a mathematical model. Within-subject variability for ΔI0–30/ΔG0–30 (CV 57.1%) was higher than ΔCP0–30/ΔG0–30 (CV 34.7%). Measures integrated over the full 120 min of the OGTT, incAUCins/incAUCglu (CV 24.9%) and IS/Glu0–120 (CV 17.4%), demonstrated less variability. The mathematical model-derived measures of beta cell glucose sensitivity (CV 20.3%) and potentiation (CV 33.0%) showed moderate variability. The impact of the different measures’ variability on sample size (30% change from baseline) is demonstrated by calculated sample sizes of 89 for ΔI0–30/ΔG0–30, 37 for ΔCP0–30/ΔG0–30, 21 for incAUCins/incAUCglu and 11 for IS/Glu0–120. Some OGTT-derived indices of beta cell function, in particular the insulinogenic index, demonstrate high within-subject variability. Integrated measures that utilise multiple time points and measures that use C-peptide show less variability and may lead to a reduced sample size requirement. [ABSTRACT FROM AUTHOR]

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the in [insulinogenic index (IGI)] was described by a linear function of In (x) (x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include -1, the relationships between IGI and × were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Patients with acute myocardial infarction (AMI) but without previously known type 2 diabetes have a high prevalence of undiagnosed IGT and type 2 diabetes. Such perturbations have dismal prognostic implications. The aim of this study was to characterise AMI patients in terms of insulin resistance and beta cell function. Methods: A total of 168 consecutive AMI patients were classified by means of an OGTT before hospital discharge as having NGT, IGT or type 2 diabetes. The homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Beta cell responsiveness was quantified as insulinogenic index (IGI) at 30 min (ΔI30/ΔG30). Results: According to the HOMA-IR, patients with type 2 diabetes were more insulin resistant than those with IGT or NGT (p=0.003). Beta cell responsiveness deteriorated with decreasing glucose tolerance as measured by the IGI (median [quartile 1, quartile 3] in pmol/mmol: NGT, 70.1 [42.7, 101.4]; IGT, 48.7 [34.7, 86.8], type 2 diabetes, 38.1 [25.7, 61.6]; p«0.001). The IGI was significantly related to admission capillary blood glucose (r=-0.218, p=0.010) and to the area under the curve for glucose (r=-0.475, p«0.001). Conclusions/interpretation: Glucose abnormalities are very common in patients with AMI but without previously known type 2 diabetes. To a significant extent, this seems to be related to impaired beta cell function and implies that dysglycaemia immediately after an infarction is not a stress epiphenomenon but reflects stable disturbances of glucose regulation preceding the AMI. Early beta cell dysfunction may have important pathophysiological implications and may serve as a future target for treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract: Impaired fasting glucose (IFG) is a subgroup of impaired glucose regulation exhibiting an elevated fasting glucose levels without elevated 2-h glucose levels on oral glucose tolerance test (OGTT). Diabetes mellitus with isolated fasting hyperglycemia (DM/IFH) is a similar subgroup of diabetes having higher fasting glucose levels with 2-h glucose levels within the non-diabetic range. The aim of this study is to profile the characteristics of these subgroups to estimate the factors involved in the development from normal glucose tolerance (NGT) via IFG to DM/IFH. Five hundred and sixty seven Japanese males were classified on the basis of 75g OGTT into four groups, NGT, IFG, DM/IFH, and isolated impaired glucose tolerance (isolated IGT). Insulin secretion was evaluated by insulinogenic index, insulin sensitivity was evaluated by ISI composite, and insulin secretory patterns were compared additionally. IFG and DM/IFH subjects exhibited both lower insulin secretion and lower insulin sensitivity than NGT subjects. There was an insulin peak in NGT, IFG, and DM/IFH at 60min, which did not occur in isolated IGT. Impaired early-phase and basal insulin secretion and decreased insulin sensitivity both are estimated as factors in progression from NGT via IFG to DM/IFH in these subjects. IFG and DM/IFH subjects have definite fasting hyperglycemia in contrast to isolated IGT subjects, 2-h glucose levels being maintained within the non-diabetic range partly by the insulin peak at 60min. [Copyright &y& Elsevier]

Abstract: Objective:: To investigate the clinical characteristics and predisposing metabolic abnormalities in the development of glucose intolerance and diabetes mellitus in obese and non-obese Korean subjects. Methods:: Four hundred Korean subjects were classified into five groups according to degree of glucose tolerance by OGTT: NGT, IGT alone, IFG alone, IFG+IGT, and DM. The groups were also subdivided into obese and non-obese group according to body mass index. Insulin resistance was assessed by using homeostasis model assessment of insulin resistance (HOMA-R), and insulinogenic index was used as an index of early-phase insulin secretion. Results:: Impaired early-phase insulin secretion was seen in non-obese IGT alone, IFG alone, and IFG+IGT, though more profound secretory defects were noted in IFG+IGT and DM. No significant difference were found in HOMA-R among non-obese IGT alone, IFG alone, or IFG+IGT, or in terms of early-phase insulin secretion in obese IGT alone, IFG alone, or IFG+IGT. However, the magnitude of insulin resistance differed in the obese group, IFG+IGT and DM being more insulin resistant than IGT alone or IFG alone. Conclusions:: These results suggest that the predisposing metabolic abnormality in non-obese subjects with IGT alone or IFG alone and in progression to IFG+IGT might be deterioration of early phase insulin secretion, whereas insulin resistance might be the major contributory factor in obese subjects. The predisposing metabolic abnormality leading to diabetes in both obese and non-obese groups was deterioration of early-phase insulin secretion. [Copyright &y& Elsevier]

Saad R, Gungor N, Arslanian S. Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates. The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and relative insulin deficiency in at-risk youth. We-report longitudinal changes in insulin sensitivity and secretion in a high-risk African-American youth with obesity and polycystic ovary syndrome who progressed from normal glucose tolerance to impaired glucose tolerance to T2DM within 5 yr. This report demonstrates that in our patient: (i) insulin resistance was the pre-existing abnormality, but it was the marked decline in insulin secretion which led to T2DM and (ii) surrogate estimates of insulin sensitivity using fasting glucose and insulin concentrations were not reliable indices in reflecting the changes in in vivo insulin sensitivity in this case. [ABSTRACT FROM AUTHOR]

We evaluated both insulin release (IR) and insulin sensitivity (IS) through a single oral glucose tolerance test (OGTT) (blood samples at 0, 60, 120 min, as routinely performed in Europe) in subjects with normal and abnormal glucose tolerance. The value 1/HOMA was used as an index of IS and ΔI/ΔG at 60 min was used as an index of IR. In preliminary experiments, 1/HOMA correlated with glucose infusion rate (GIR) at euglycaemic insulin clamp (r=0.495) and with insulin sensitivity index (ISI) at LDIGIT (r=0.714). At OGTT with blood samples at 0, 30, 60 and 120 min, insulin levels at 30 min correlated with insulin levels at 60 min (I30 vs. I60, r=0.584) and ΔI/ΔG at 30 and at 60 min correlated (r=0.365). Values of 1/HOMA from 345 subjects with normal glucose tolerance (NGT), 32 with impaired fasting glucose (IFG), 186 with impaired glucose tolerance (IGT) and 72 with type 2 diabetic mellitus were divided into quartiles. For each quartile, mean (± SE) and 95% confidence intervals (CI) of ΔI/ΔG at 60 min were calculated, and subjects were represented by plotting IS vs. IR. Plots of NGT, IGT, and type-2 diabetes mellitus described different curves. Values of subjects with IFG, IGT and type 2 diabetes mellitus fell outside the 95% CI of NGT subjects in all quartiles of IS. To validate this finding, 113 morbidly obese subjects (basal OGTT: 55 NGT, 40 IGT, 18 T2DM) who underwent a major reduction of body weight through bariatric surgery received a second OGTT one year after surgery. Glucose tolerance improved in 40 patients, deteriorated in 8, did not change in 65; the new plots were concordant with the new class of glucose tolerance. OGTT can be used to evaluate both IR and IS in subjects with NGT, IFG, IGT, and type 2 diabetes mellitus in population studies and in follow-up studies. IFG, IGT and type 2 diabetes mellitus are characterized by reduced IR compared to IS. [ABSTRACT FROM AUTHOR]

Objective: We verified whether a misdiagnosis of gestational diabetes mellitus can result in pregnant women when glucose tolerance has deteriorated after a low-carbohydrate meal, and tried to elucidate the mechanism behind the different outcome of the test.Study Design: Twenty-seven pregnant women were given directions for their evening meal the day before each of two 75-g oral glucose tolerance tests (OGTT). The evening meal was either a low-carbohydrate meal (carbohydrate, 6.7%; Low), or a high-carbohydrate meal (carbohydrate, 85.7%; High).Results: The OGTT showed that the glucose tolerance was significantly impaired after Low than after High, with a significant increase of fasting plasma non-esterified fatty acids (NEFA) level. Moreover, the insulinogenic index (I-I) after High significantly decreased than that after Low.Conclusions: The present data suggests that there is a risk of misdiagnosis of impaired glucose tolerance with only one intake of this extremely low-carbohydrate meal on the evening before testing. The decrease of insulin secretion and the activation of glucose-fatty acid cycle may be considered as the mechanism. [ABSTRACT FROM AUTHOR]

Insulin secretion dynamics and response to nateglinide were studied in patients with type 2 diabetes and reduced early-phase insulin secretion. On day 1, 24 patients underwent a 75-g oral glucose tolerance test without taking nateglinide. On day 2, they were given oral nateglinide 90 mg immediately before the oral glucose tolerance test. After glucose loading, insulin levels increased significantly at 30, 60, 90, and 120 minutes after the patients took nateglinide, along with insulinogenic indices, the total area under the insulin curve, the area under the 0- to 90-minute insulin curve, and the area under the 90- to 180-minute insulin curve. Both the plasma glucose level at 60, 90, 120, and 180 minutes and the total area under the glucose curve were significantly reduced following nateglinide administration. Compared with the low responders (n=13), the high responders (n=11) had a significantly shorter duration of disease, significantly higher insulinogenic indices in the absence of nateglinide administration, and a higher homeostasis model assessment-β cell performance. Nateglinide demonstrated a rapid-onset and rapidoffset insulin secretion-stimulating effect in this study population. A single dose of nateglinide may be indicated for patients with a relatively high homeostasis model assessment-β cell performance, a short duration of disease, and relatively high insulinogenic indices prior to nateglinide administration. [ABSTRACT FROM AUTHOR]