Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation

Background Both beta‐cell dysfunction and decreased insulin sensitivity are involved in the pathogenesis of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), while their relative contribution in the progression to type 2 diabetes still remains controversial. The aim of the present study is to clarify this process in Chinese subjects by using cross‐sectional method. Methods 2975 Chinese subjects were classified into: normal glucose tolerance (NGT), impaired glucose regulations (IGR), and diabetes mellitus (DM) based on oral glucose tolerance test (OGTT). The IGR group was sub‐classified as isolated IFG, isolated IGT and combined glucose intolerance (CGI). The DM group was sub‐classified as normal fasting plasma glucose and 2‐hour hyperglycemia (N0D2), fasting hyperglycemia and normal 2‐hour plasma glucose (D0N2), and both fasting and 2‐hour hyperglycemia (D0D2). Results As far as insulinogenic index (IGI) was concerned, there was no difference between IFG and IGT in either gender, however, HOMA2‐B% (homeostasis model assessment for beta‐cell function) of IGT was higher than that of IFG and CGI in both male and female (P < 0.05). In the diabetic sub‐groups, IGI of N0D2 was higher than that of D0N2, and both deteriorated compared with those of IGT and IFG, respectively. HOMA2‐B% of N0D2 was still higher than that of D0N2 and D0D2. No significant difference was detected in OGIS and HOMA2‐S% (homeostasis model assessment for insulin sensitivity) between IFG and IGT, and this was the case between N0D2 and D0N2. OGIS and HOMA‐IR of IGR sub‐groups were not different from those of their diabetic counterparts. Conclusion Failure of beta‐cell function might be the main reason for both IGT and IFG developing into diabetes instead of aggravated insulin resistance. Copyright © 2008 John Wiley & Sons, Ltd.     

Comparing the effects of 12 months aerobic exercise and resistance training on glucose metabolism among prediabetes phenotype: A explorative randomized controlled trial

AimsThe pathophysiology of each phenotype of prediabetes is unique that promotes different levels of diabetes and cardiovascular disease risks. Exercise guidelines for individuals with prediabetes including both aerobic and resistance training could improve metabolic control, but its effects on different prediabetes subtypes are unclear. The aim of this explorative randomized controlled trial was to evaluate the effects of aerobic training (AT) or resistance training (RT) on glucose metabolism and lipid profile by different prediabetes subtypes with.MethodsA randomized controlled trial in which 128 individuals with isolated impaired fasting glucose (i-IFG; n = 39), isolated impaired glucose tolerance (i-IGT; n = 29), combined glucose tolerance (CGI; n = 27) and isolated elevated HbA_1c (n = 33) were randomly assigned to the control group, AT group and RT group, respectively. Supervised exercise training, including AT and RT were completed at moderate intensity for 60 min per day, three non-consecutive days per week for 12 months. The primary outcome was improvement in glucose metabolism. Secondary outcomes included measure of lipid profile and if these effects were moderated by the prediabetes phenotype.ResultsOf the initial 128 participants, 118 finished the study, but all participants were included in the intention-to-treat analyses. The improvement in 2 h postprandial plasma glucose (2 hPG) between group difference (AT vs. RT) at 12 months was 0.87 (95% CI, -1.59 to-0.16; p < 0.05). Compared with RT group, AT significantly decreased the 2hPG in participants with i-IGT at 12 months (-1.66, 95% CI -3.04 to -0.28; p < 0.05).ConclusionsAT program conferred benefits in improving 2 h PG and HbA_1c compared with RT for prediabetes. These findings may moderate by prediabetes phenotype, and AT appeared more effective in i-IGT. A future trial with large sample size and long time follow up of prediabetes phenotype groups are needed.     

Association of serum ferritin concentrations with prevalence of prediabetes,type 2 diabetes mellitus,and metabolic syndrome in a Chinese population from Sichuan

Body iron stores reflected by serum ferritin levels have been implicated in many chronic diseases. We investigated associations between serum ferritin concentrations and the risk of prediabetes, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) in a Chinese population. For a cross-sectional study, 3040 subjects were recruited from three communities in Sichuan. Subjects were grouped by prediabetes or T2DM status, or components of MetS. Subjects with prediabetes were classified as having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both (IFG + IGT). The odds ratios, assessed by gender, for the associations between serum ferritin concentration and prediabetes, T2DM, and MetS were calculated using multivariate logistic regression. The prevalence of IGT, IFG + IGT, T2DM, and MetS in the highest quartile of ferritin concentrations was higher than those in the lowest quartile, in both genders. In women, the adjusted odds ratios of IGT, IFG + IGT, T2DM, and MetS were higher in the highest ferritin quartile than the lowest; in men, only that of IFG + IGT was higher. In both genders, high ferritin levels were associated with higher odds ratios of hypertriglyceridemia and hyperglycemia, components of MetS. IGT, IFG + IGT, T2DM, and MetS were more common in the highest ferritin quartile for both genders. Elevated ferritin concentrations were associated with an increased risk for IGT and IFG + IGT in prediabetes, T2DM, and MetS, especially in women.

     

Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism

Prediabetes is a heterogeneous term that encompasses different origins of insulin resistance and insulin secretion that contribute to distinct patterns of hyperglycemia. In fact, prediabetes is an umbrella term that characterizes individuals at high risk for developing type 2 diabetes (T2D) and/or cardiovascular disease (CVD). Based on current definitions there are at least 3 distinct phenotypes of prediabetes: impaired fasting glucose (IFG), impaired glucose tolerant (IGT), or the combination of both (IFG + IGT). Each phenotype is clinically relevant as they are uniquely recognized as having different levels of risk for progressing to T2D and CVD. Herein, we discuss the underlying pathophysiology that characterizes IFG, IGT and the combination, as well as examine how some of these phenotypes appear resistant to traditional exercise interventions. We propose that substrate metabolism differences between the prediabetes phenotypes may be a unifying mechanism that explains the inter-subject variation in response to exercise seen across obese, metabolic syndrome, pre-diabetic and T2D patients in the current literature. Ultimately, a better understanding of the pathophysiologic mechanisms that govern disturbances responsible for fasting vs. postprandial hyperglycemia and the combination of both is important for designing optimal and personalized exercise treatment strategies that treat and prevent hyperglycemia and CVD risk.     

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AimsThe clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.MethodsWe recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3–6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7–6.4%, 39–46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.ResultsEighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥165 mg/dL and a 30-min C-peptide <5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98–26.16) of developing diabetes than other prediabetic subjects.ConclusionsIn Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.     

Sex differences in lipid profiles in relation to the progression of glucose abnormalities

Background: In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM). Methods: An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n = 589); (ii) those with pre‐diabetes (pre‐T2DM), who were further divided into those with impaired fasting glucose (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol, triglycerides, high‐density lipoprotein–cholesterol (HDL‐C), low‐density lipoprotein–cholesterol (LDL‐C), apolipoprotein (apo) A‐I, apoB, and the apoB:apoA‐I ratio were determined in each patient. Differences in lipids between the different groups were assessed using Student’s t‐test. Results: Significantly higher triglyceride levels and an apoB:apoA‐I ratio were found in NGT men (P < 0.0001), along with lower HDL‐C and apoA‐I (P < 0.0001). Men in the pre‐T2DM group maintained a higher apoB:apoA‐I ratio (P < 0.05) and lower HDL‐C (P < 0.0001) compared with women. In the T2DM group, only HDL‐C was lower in men compared with women (P < 0.05). Conclusions: The progression of glucose intolerance from NGT to pre‐T2DM and T2DM exhibits striking sex differences regarding the lipid profile. The data demonstrate a worsening of plasma lipid composition in women who become diabetic. This could explain, at least in part, the loss of the more favorable cardiovascular risk normally associated with NGT women.     

Differences in insulin resistance and pancreatic B‐cell function in obese subjects with isolated impaired glucose tolerance and isolated impaired fasting glucose

Aims To investigate changes in insulin action and insulin secretion in obese subjects with different categories of impaired glucose regulation (IGR): impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG/IGT (CGI). Methods A total of 222 subjects underwent an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test (FSIGTT); 100 had normal glucose tolerance (subdivided into 32 lean NGT, 68 obese NGT), and 122 were obese with IGR (82 IGT, 14 IFG and 26 CGI). The insulin sensitivity index (S_I) was assessed by Bergman's minimal model method with FSIGTT; insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S_I, was used to determine whether AIRg was adequate to compensate for insulin resistance. Results S_I was similar in NGT and IGR obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT, significantly reduced in IGT, and further reduced in IFG and CGI subjects as compared with obese NGT subgroups. DI was reduced in NGT obese individuals. Within the obese IGR subgroups, IFG and CGI subjects had even lower DI value than IGT subjects. Conclusions Obese Chinese subjects with IGR have a similar degree of insulin resistance but differ in insulin secretion. Subjects with IFG and CGI have a more prominent deficiency in insulin secretion than subjects with IGT.     

The change of plasma ghrelin and leptin levels by the development of type 2 diabetes mellitus in patients with alcohol dependence

Background: There have been lots of studies about the relationship between chronic use of alcohol and the development of type 2 diabetes mellitus (T2DM). Chronic use of alcohol can be affected by the altered level of ghrelin and leptin which regulate food‐seeking behavior having similar mechanism of controlling alcohol‐craving behavior. Those peptides are known to be correlated with T2DM. Ghrelin and leptin also have been regarded as possible regulators of glucose metabolism and insulin function. Hence, there is the possibility that ghrelin and leptin can be related with deteriorated pathophysiology of T2DM in alcoholic patients. Methods: Patients with alcohol dependence diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) underwent an 75 g oral glucose‐tolerance test (OGTT), to classify them to normal glucose tolerance (NGT, n = 52), pre‐diabetes including impaired glucose tolerance (IGT), impaired fasting glucose level (IFG) and combination of IGT and IFG (Pre‐DM, n = 26) and T2DM (n = 24) groups. Fasting plasma ghrelin and leptin levels were compared among groups. Results: There was no difference of ghrelin concentration among the groups but the leptin concentration was significantly different between NGT and T2DM group (p < 0.05). Increased leptin levels were significantly correlated with body mass index (BMI), insulin level, and insulin resistance. Conclusions: Chronic alcohol drinking might produce leptin resistance which makes leptin significantly correlated with fasting insulin concentration and insulin resistance. Therefore, we suppose that increased level of leptin by chronic alcohol use could be one of the main mechanisms that develop insulin resistance in alcoholic patients.     

The utility of fasting glucose for detection of prediabetes

Treatment of prediabetes attenuates progression to type 2 diabetes mellitus. The American Diabetes Association (ADA) previously defined prediabetes as either impaired fasting glucose (IFG) = 6.1 to 6.9 mmol/L (110-125 mg/dL) and/or impaired glucose tolerance (IGT) (2-hour postload glucose of 7.8-11.0 mmol/L [140-199 mg/dL]). For practical reasons, fasting plasma glucose (FPG) is commonly used for diabetes screening. Recently, the ADA lowered the fasting glucose threshold value for IFG from 110 to 100 mg/dL. Our objective was to determine the utility of FPG alone for detecting prediabetes in African Americans. Oral glucose tolerance test (OGTT) data from a cohort of 304 young adult African American men and women were examined. We calculated prediabetes prevalence using the previous ADA criteria and examined the effect of lowering the IFG threshold value for IFG to 100 mg/dL. The prediabetes prevalence in this cohort using the previous ADA criteria was 20.4% (n = 62). Of the 62 cases, 8 had IFG, 45 had IGT, and 9 had IFG together with IGT. Fasting plasma glucose testing alone detected 17 (27.4%) prediabetic cases, whereas a complete OGTT detected 54 (87.1%). Lowering the IFG threshold value to FPG = 100 mg/dL identified 13 of the 45 IGT-only cases. However, this lower IFG threshold increased prediabetes prevalence in the overall cohort from 20.4% to 31.9%. In conclusion, in young adult African Americans, an ethnic group at high risk for developing diabetes, FPG testing alone may be inadequate for diagnosing prediabetes. Until alternative strategies are identified, an OGTT is presently the best method for detecting the prediabetic condition in these high-risk patients.     

The fat-to-lean mass ratio,a novel anthropometric index,is associated to glucose metabolic disorders

ObjectiveThe aim was to evaluate whether the Fat-to-Lean Mass (FyM) ratio is associated to glucose metabolic disorders (GMD).DesignCross-sectional population based study.MethodsEligible subjects were healthy men and non-pregnant women with new diagnosis of GMD that were allocated into following groups: 1) Normal Glucose Tolerance (NGT), 2) Diabetes, 3) impaired fasting glucose (IFG) + impaired glucose tolerance (IGT), 4) IGT, and 5) IFG. The FyM index [Total body fat (Kg)/total lean mass (Kg)], and the odds ratio (OR) between FyM index and GMD were estimated.ResultsA total of 875 individuals with average age 41.62 ± 12.3 were enrolled; of them, 645 (73.1%) women and 230 (22.8%) men; 521 (59.5%), 71 (8.1%), 85 (9.7%), 53 (6.0%), and 145 (16.6%) individuals were allocated into groups with NGT, diabetes, IFG + IGT, IGT, and IFG, respectively. The FyM was significantly associated with prediabetes and diabetes in women (OR 4.2; _95%CI 3.0–11.1 and OR = 7.2; _95%CI 2.0–15.2) and men (OR = 2.6; _95%CI 1.1–6.7 and OR = 4.6; _95%CI 1.4–15.1). In the overall population, the OR between FyM index with IGT, IFG, and IFG + IGT was 8.4 (_95%CI 2.6–17.4), 5.2 (_95%CI 2.6–10.6), and 6.1 (_95%CI 1.8–9.5).ConclusionThe FyM index was strongly associated with all categories of GMD.     

Progression rates from HbA1c 6.0–6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis

Aims/hypothesis

Precise estimates of progression rates from ‘prediabetes’ to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA_1c-defined prediabetes ranges, with some favouring 6.0–6.4% (42–46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories.

Methods

Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6–6.9 mmol/l], WHO-defined IFG [6.1–6.9 mmol/l], IGT (7.8–11.0 mmol/l) or raised HbA_1c [6.0–6.4%/42–46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models.

Results

Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA_1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes.

Conclusions/interpretation

This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA_1c 6.0–6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.     

The effect of defective early phase insulin secretion on postload glucose intolerance in impaired fasting glucose

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk groups for type 2 diabetes. Type 2 diabetes is characterized by both impaired insulin secretion and insulin resistance but their relative contribution to the development of hyperglycemia may differ due to heterogeneity of the disease. Combined glucose intolerance (CGI), on the other hand, seems to represent a more advanced stage of prediabetes that bears a distinctly higher risk of progression to diabetes and its comorbidities. This study has the aim to compare isolated IFG and CGI categories with respect to the degree of early phase insulin secretion abnormalities and insulin resistance. Subjects who had IFG (fasting glucose: 110-126 mg/dl) were included in the study. A 75-g oral glucose tolerance test (OGTT) with insulin response was done and subjects were classified according to the WHO criteria. Six subjects were excluded because they had diabetic glucose tolerance. A total of 66 patients (53.4 +/- 11.1 years, female/male: 48/18) were divided into two groups according to their glucose tolerance in OGGT (Group 1: isolated IFG and group 2: CGI). Early phase insulin secretion was measured by intravenous glucose tolerance test (IVGTT) and OGTT. Insulin resistance was assessed by the R value of the homeostasis model assessment (HOMA). We did not find any statistically significant difference between groups according to age, gender, body mass index (BMI), fasting glucose, fasting insulin, insulin-AUC (0-180 min) and HOMA-R values. In OGGT there was no statistically significant difference between 0', 30', 60' and 90' insulin levels of the groups; only 120' and 180' insulin levels were higher in CGI than in IFG group (p<0.05). In IVGTT, there was no statistically significant difference between glucose levels of the groups. Furthermore, insulin response to intravenous glucose was higher in IFG than in CGI (p<0.05). Our data demonstrate that isolated IFG and CGI are similar with respect to the degree of insulin resistance, and that subjects with CGI had a more prominent deficit in early phases of insulin secretion.     

Family history of diabetes is associated with higher risk for prediabetes: a multicentre analysis from the German Center for Diabetes Research

Aims/hypothesis

Prediabetes is a collective term for different subphenotypes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) with different pathophysiologies. A positive family history for type 2 diabetes (FHD) is associated with increased risk for type 2 diabetes. We assumed that it would also associate with prediabetes, but wondered whether all subphenotypes are related to a positive family history.

Methods

In a study population of 8,106 non-diabetic individuals of European origin collected from four study centres (normal glucose tolerance, NGT n?=?5,482, IFG and/or IGT n?=?2,624), we analysed whether having at least one first degree relative with diabetes is associated with prediabetes. The analyses were performed using the same models in each population separately. Afterwards, a meta-analysis was performed.

Results

FHD was significantly associated with the risk for prediabetes (IFG and/or IGT, OR 1.40; 95% CI 1.27, 1.54). This association remained significant in multivariable logistic regression models including sex, age and BMI (OR 1.26; 95% CI 1.14, 1.40). When different prediabetic outcomes were considered separately, the association was found for isolated IFG (OR 1.37; 95% CI 1.20, 1.57), isolated IGT (OR 1.25; 95% CI 1.07, 1.46) as well as for the combination IFG+IGT (OR 1.64; 95% CI 1.40, 1.93). After stratification on BMI, association between FHD and prediabetes was seen only in non-obese individuals (BMI?<?30 kg/m²).

Conclusions/interpretation

We found that FHD is an important risk factor for prediabetes, especially for combined IGT and IFG. Its relevance seems to be more evident in the non-obese.     

Exercise training improves cardiovascular autonomic modulation in response to glucose ingestion in obese adults with and without type 2 diabetes mellitus

This study examined the effect of aerobic exercise training on vagal and sympathetic influences on the modulations of heart rate and systolic blood pressure in response to an oral glucose load in obese individuals with and without type 2 diabetes mellitus (T2D). Beat-to-beat arterial pressure and continuous electrocardiogram were measured after a 12-hour overnight fast and in response to glucose ingestion (75 g dextrose) in obese subjects with (T2D group, n = 23) and without (OB group, n = 36) T2D before and after 16 weeks of aerobic exercise training at moderate intensity. Autonomic modulation was assessed using spectral analysis of systolic blood pressure variability (BPV), heart rate variability (HRV), and analysis of baroreflex sensitivity (BRS). Glucose ingestion significantly increased low-frequency (LF_SBP), low-frequency HRV (LF_RRI), and the ratio of low- to high-frequency components of HRV (LF_RRI/HF_RRI), and decreased the high-frequency power (HF_RRI) (P < .05). Exercise training increased LF_RRI and LF_RRI/HF_RRI responses, and reduced HF_RRI and LF_SBP to glucose ingestion in both groups (P < .05), but increased fasted BRS in the OB group only (P < .05); glucose intake had no effect on BRS (P > .05). In conclusion, a 16-week exercise training program improved cardiac autonomic modulation in response to an oral glucose load in obese adults, independently of diabetes status, and in the absence of remarkable changes in body weight, body composition, fitness level, and glycemic control.     

Uric acid,impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity

Background and aimThe relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB).Methods and resultsA cross-sectional study was performed in 2248 youths with OW/OB (age 5–17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025–0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005–0.0001).ConclusionsIn youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post–challenge condition rather than in fasting state.     

Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose

Subjects with impaired fasting glucose (IFG) are at increased risk for type 2 diabetes. We recently demonstrated that IFG subjects have increased hepatic insulin resistance with normal insulin sensitivity in skeletal muscle. In this study, we quantitated the insulin secretion rate from deconvolution analysis of the plasma C-peptide concentration during an oral glucose tolerance test (OGTT) and compared the results in IFG subjects with those in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). One hundred and one NGT subjects, 64 subjects with isolated IGT, 24 subjects with isolated IFG, and 48 subjects with combined (IFG + IGT) glucose intolerance (CGI) received an OGTT. Plasma glucose, insulin, and C-peptide concentrations were measured before and every 15 min after glucose ingestion. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide concentration. Inverse of the Matsuda index of whole body insulin sensitivity was used as a measure of insulin resistance; 56 subjects also received a euglycemic hyperinsulinemic clamp. The insulin secretion/insulin resistance (disposition) index was calculated as the ratio between incremental area under the ISR curve (∆ISR[AUC]) to incremental area under the glucose curve (∆G[AUC]) factored by the severity of insulin resistance (measured by Matsuda index during OGTT or glucose disposal during insulin clamp). Compared to NGT, the insulin secretion/insulin resistance index during first 30 min of OGTT was reduced by 47, 49, and 74% in IFG, IGT, and CGI, respectively (all < 0.0001). The insulin secretion/insulin resistance index during the second hour (60–120 min) of the OGTT in subjects with IFG was similar to that in NGT (0.79 ± 0.6 vs. 0.72 ± 0.5, respectively, P = NS), but was profoundly reduced in subjects with IGT and CGI (0.31 ± 0.2 and 0.19 ± 0.11, respectively; P < 0.0001 vs. both NGT and IFG). Early-phase insulin secretion is impaired in both IFG and IGT, while the late-phase insulin secretion is impaired only in subjects with IGT.     

Exercise capacity in relation to body fat distribution and muscle fibre distribution in elderly male subjects with impaired glucose tolerance, type 2 diabetes and matched controls

Background

The aim of this study was to examine the impact of insulin sensitivity and muscle fibre composition to exercise capacity in individuals with type 2 diabetes (T2D), impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).

Methods

Thirty-nine male patients with T2D, 44 male subjects with IGT and 58 subjects with NGT matched for age, weight and body mass index (BMI) participated in the study. Insulin sensitivity was obtained with hyperinsulinemic-euglycemic clamps, muscle fibre distribution with a biopsy and exercise capacity from an incremental exercise test. Anthropometric measurements as height, weight, waist and hip circumference were performed.

Results

There were small differences between groups in waist hip ratio (WHR) with significance attained between NGT and T2D. There was a progressive reduction in exercise capacity, both expressed as VO_2peak and work rate from subjects with NGT to IGT to T2D. Multiple regression analysis with VO_2peak as dependent variable showed insulin sensitivity to be the most important factor followed by Type I fibres. WHR and capillary density also influenced the variance of VO_2peak.

Conclusion

Exercise capacity is independently related to insulin sensitivity, muscle fibre composition and WHR in subjects with NGT, IGT and T2D who are matched for age and BMI.     

External validation of the Finnish diabetes risk score in Venezuela using a national sample: The EVESCAM

AimsTo evaluate the performance of the Latin American Finnish Diabetes Risk Score (LA-FINDRISC) compared with the original O-FINDRISC in general population. To establish the best cut-off to detect unknown type 2 diabetes (uT2D) and prediabetes.MethodsThe EVESCAM was a national population-based, cross-sectional, randomized cluster sampling study, which assessed 3454 adults from July 2014 to January 2017. Those with self-report of diabetes were excluded; a total of 3061 subjects were analyzed. Waist circumference adapted for Latin America was the difference between the LA-FINDRISC and the O-FINDRISC. The area under the curve (AUC), sensitivity, and specificity were calculated.ResultsThe prevalence of uT2D and prediabetes were 3.3% and 38.5%. The AUC with the LA-FINDRISC vs. the O-FINDRISC were: for uT2D, 0.722 vs. 0.729 in men (p = 0.854) and 0.724 vs. 0.732 in women (p = 0.896); for prediabetes (impaired fasting glucose [IFG] + impaired glucose tolerance [IGT], 0.590 vs. 0.587 in men (p = 0.887) and 0.621 vs. 0.627 in women (p = 0.777); for IFG, 0.582 vs. 0.580 in men (p = 0.924) and 0.607 vs. 0.617 in women (p = 0.690); for IGT, 0.691 vs. 0.692 in men (p = 0.971) and 0.672 vs. 0.671 in women (p = 0.974). Using the LA-FINDRISC, the best cut-offs to detect uT2D were 9 in men and 10 in women and to detect IGT was 9 in both genders.ConclusionLA-FINDRISC has similar performance than O-FINDRISC in Venezuelan adults and showed a good performance to detect uT2D and IGT, but not IFG. The best cut-offs to detect glucose alterations were established.     

The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: The MASALA study

AimsWe assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States.MethodsA 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISI_M) estimated insulin sensitivity, and the Disposition Index (DI_o) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia.ResultsMean age was 57 ± 8 years and BMI 26.1 ± 4.6 kg/m². Log ISI_M and log DI_o were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DI_o remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-years) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β (OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression.ConclusionsThe association of DI_o with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia.     

Role of skeletal muscle-fibre type in regulation of glucose metabolism in middle-aged subjects with impaired glucose tolerance during a long-term exercise and dietary intervention

AIM: The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance (IGT) during a 2-year exercise and dietary intervention. METHODS: Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGT(slow) (n=10) with a high proportion of MHC I isoforms and IGT(fast) (n=12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1+/-2.7 h/week in the IGT(slow) and 5.1+/-2.8 h/week in the IGT(fast) group. RESULTS: Fasting glucose (p<0.05), 2-h glucose (p<0.05), fasting insulin (p<0.05), haemoglobin A1c (HbA(1c)) (p<0.01) and insulin resistance (p<0.05) [homeostasis model assessment for insulin resistance (HOMA-IR)] decreased in the IGT(fast) group, whereas only the 2-h glucose and HbA(1c) concentrations decreased in the IGT(slow) group. The amount of the glycogen synthase kinase-3-alphabeta (GSK-3-alphabeta) decreased in the IGT(fast) group (p<0.05). Exercise training increased the lactate dehydrogenase (LDH) (p<0.01), LDH-1 (p<0.05) and citrate synthase (CS) (p<0.05) activities in the vastus lateralis muscle in the IGT(slow) group, but only the CS activity (p<0.05) in the IGT(fast) group. CONCLUSIONS: The glucose metabolism improved both in the IGT(slow) and IGT(fast) group during the 2-year exercise and dietary intervention. The change was more prominent in the IGT(fast) group than in the IGT(slow) group, associated with the decrease of the GSK-alphabeta protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGT(slow) group and the oxidative capacity in both groups.