IGT Subjects Research Articles

To Evaluate the Association of Serum Adiponectin with Fasting and Postprandial Plasma Glucose and Fasting Lipids in Control, IGT and T2DM Subjects

Background: Association of adiponectin with insulin resistance occurs early in obesity development; however it remains unclear if this association is of further importance in prediabetes and early stages of type 2 diabetes and remains the same through all glucose intolerance development stages. The present study was undertaken to evaluate the association of dysglycemia and dyslipidemia with adiponectin in prediabetic subjects as well as in T2DM subjects. Objective: The objective of our study was to evaluate adiponectin level in subjects with pre-diabetes and to compare it with the levels in newly diagnosed type 2 diabetes and healthy (normal glucose tolerance) subjects. Method: It was an observational analytic study with a group compare design. The study was conducted in the Biomedical Research Group and Department of Biochemistry & Cell Biology of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka. This study was done during the period of July 2012 to June 2013. Results: Bivariate Spearman’s correlation analyses were performed for adiponectin with clinical, anthropometrical and other biochemical variables in the Control, IGT and T2DM groups. Postprandial glucose (p=0.023) and age (p=0.011) had a positive correlation with adiponectin in control subjects. A negative correlation was observed between adiponectin and BMI in IGT subjects (p=0.004). A positive correlation with adiponectin and serum HDL (p=0.03) and a negative correlation with serum LDL (p=0.03) were found in T2DM subjects. Conclusion: From our study we can conclude that, BMI has a negative association with adiponectin in IGT subjects. Serum LDL has a negative association and HDL has a positive association with adiponectin in IGT and T2DM subjects.

Association of Serum Adiponectin with Dysglycemia and Dyslipidemia in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus

Background: The association of low adiponectin concentration and type 2 diabetes is well studied but the association of adiponectin with prediabetes is still unresolved. Data from Bangladeshi population shows that both insulin secretory defect and insulin resistance are present in T2DM subjects, but the secretory defects seem to have a predominant role. In a search for the downward factors regulating the basic defects attention has also been focused to inflammatory markers and adipocytokines. Adiponectin is one of the major targets for such studies and few studies have already been conducted on the association of adiponectin with prediabetes in our population. Objective: The objective of our study was to evaluate adiponectin level in subjects with pre-diabetes and to compare it with the levels in newly diagnosed type 2 diabetes and healthy (normal glucose tolerance) subjects. Method: It was an observational analytic study with a group compare design. The study was conducted in the Biomedical Research Group and Department of Biochemistry & Cell Biology of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka. This study was done during the period of July 2012 to June 2013. Results: IGT and Controls subjects were age and BMI matched. Mean (±SD) age of Control, IGT and T2DM subjects were 38.75±8.40, 42.71±7.65 and 44.61±7.00 years respectively. Age of T2DM subjects were higher compared to controls (p=0.022). Mean (SD) BMI of the Control, IGT and T2DM subjects were 20.53±2.43, 20.89±2.22 and 21.14±2.23 respectively. Conclusion: From our study we can conclude that, type 2 DM subjects have lower adiponectin level compared to controls. Prediabetic subjects do not have lower adiponectin level, but they have a lower adiponectin- glucose ratio compared to controls.

Adaptation of Insulin Clearance to Metabolic Demand Is a Key Determinant of Glucose Tolerance.

With the development of insulin resistance (IR), there is a compensatory increase in the plasma insulin response to offset the defect in insulin action to maintain normal glucose tolerance. The insulin response is the result of two factors: insulin secretion and metabolic clearance rate of insulin (MCRI). Subjects (104 with normal glucose tolerance [NGT], 57 with impaired glucose tolerance [IGT], and 207 with type 2 diabetes mellitus [T2DM]), divided in nonobese and obese groups, received a euglycemic insulin-clamp (40 mU/m2 ⋅ min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCRI was calculated during the insulin-clamp performed with [3-3H]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production × fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid × FPI). MCRI during the insulin clamp was reduced in obese versus nonobese NGT (0.60 ± 0.03 vs. 0.73 ± 0.02 L/min ⋅ m2, P < 0.001), in nonobese IGT (0.62 ± 0.02, P < 0.004), and in nonobese T2DM (0.68 ± 0.02, P < 0.03). The MCRI during the insulin clamp was strongly and inversely correlated with IR (r = -0.52, P < 0.0001). During the OGTT, the MCRI was suppressed within 15-30 min in NGT and IGT subjects and remained suppressed. In contrast, suppression was minimal in T2DM. In conclusion, the development of IR in obese subjects is associated with a decline in MCRI that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM.

Circulating MicroRNA-15a Associates With Retinal Damage in Patients With Early Stage Type 2 Diabetes.

Circulating microRNAs are potential biomarkers of type 2 diabetes mellitus (T2DM) and related complications. Here, we investigated the association of microRNA-15a with early retinal damage in T2DM. A cohort of untreated subjects screened for intermediate/high risk of T2DM, according to a score assessment questionnaire, and then recognized to have a normal (NGT) or impaired (IGT) glucose tolerance or T2DM was studied. The thickness of the ganglion cell complex (GCC), an early marker of retinal degeneration anteceding overt retinopathy was assessed by Optical Coherence Tomography. Total and extracellular vesicles (EV)-associated microRNA-15a quantity was measured in plasma by real time PCR. MicroRNA-15a level was significantly higher in subjects with IGT and T2DM compared with NGT. MicroRNA-15a abundance was correlated to body mass index and classical diabetes biomarkers, including fasting glucose, HbA1c, insulinemia, and HOMA-IR. Moreover, GCC thickness was significantly reduced in IGT and T2DM subjects compared with NGT controls. Importantly, total microRNA-15a correlated with GCC in IGT subjects, while in T2DM subjects, EV-microRNA-15a negatively correlated with GCC, suggesting that microRNA-15a may monitor initial retinal damage. The assessment of plasma microRNA-15a may help refining risk assessment and secondary prevention in patients with preclinical T2DM.

Circulating alarin concentrations are high in patients with type 2 diabetes and increased by glucagon-like peptide-1 receptor agonist treatment: An Consort-compliant study.

Context:Alarin has been reported to be relative to food intake and an increase in body weight. However, to date, no report has demonstrated the relationship between circulating alarin and diabetes in humans.Objective:The objective of this study is to gain insight into the possible role of alarin in humans.Design and methods:164 patients with newly diagnosed type 2 diabetes mellitus (nT2DM), 112 IGT and 134 healthy subjects were recruited for this study. In an interventional study, 29 nT2DM patients were treated by a weekly GLP-1RA for 6 months. Plasma alarin concentrations were measured by ELISA.Results:Circulating alarin concentrations were significantly higher in both IGT and nT2DM subjects than in healthy individuals (0.40 ± 0.14 and 0.54 ± 0.24 vs 0.37 ± 0.10 μg/L, P < .05 or P < .01), whereas in T2DM patients, circulating alarin levels were higher than in IGT subjects. Circulating alarin positively correlated with FBG, HbA1c, HOMA-IR, AUCglucose and TNFα (P < .05 or P < .01). Multivariate logistic regression revealed that circulating alarin levels were correlated with IGT and T2DM. GLP-1RA treatment for 6 months increased circulating alarin levels in T2DM patients (from 0.34 ± 0.10 for baseline, to 0.39 ± 0.14 for 12 weeks, and finally to 0.38 ± 0.15 μg/L for 24 weeks; vs. pre-treatment P < .05).Conclusions:These data suggest that alarin might be involved in the pathogenesis of T2DM in humans.Clinical Trial Registration Number:ChiCTR-OCS-13003185 (18/03/2013 ).

1840-P: Pioglitazone Increases Metabolic Insulin Clearance (MCRI) in IGT Subjects: The ACT NOW Study

Recent studies have documented that the MCRI plays a major role in determining the plasma insulin response to ingested glucose. We evaluated the long-term effect of pioglitazone (PIO) on MCRI in 441 IGT subjects (ACT NOW study) who were randomized to PIO (45 mg/day) or placebo and followed for an average of 2.4 years. OGTT was performed at baseline and study end. 50 placebo-treated subjects developed type 2 diabetes versus 15 PIO-treated subjects (p&amp;lt;0.005). Insulin secretion rate (ISR) was measured from deconvolution of plasma C-peptide curve. MCRI was measured as ISR/mean insulin conc during OGTT. Data were correlated with changes in liver enzymes and peripheral insulin sensitivity measured with the Matsuda index (MI). Results: PIO improved MI from to 3.9 ±1 to 7.5 ±3 (p&amp;lt;0.0001), glucose tolerance (mean glucose OGTT from 172±2to 148±1mg/dl, p&amp;lt;0.0001) and reduced ALT(from 30±1 to 24±1, p&amp;lt;0.0001). Fasting insulin secretion increased in the placebo group (420 ±14 to 558 ±21 pmol/min, p &amp;lt; 0.0001 vs. baseline) and did not change in the PIO group (411 ±14 to 446 ± 19; p &amp;lt;0.0001, PIO vs. placebo). During the OGTT (0- 120 min) ISR increased in both groups (PIO, 165 ±3 to 189 ± 5 nmol; placebo, 167 ±3 to 202 ±6; p &amp;lt; 0.0001 vs. baseline in both groups; p = NS, PIO vs. placebo).The MCRI increased in both groups but the increase was much greater in PIO (3.5 ± 0.2 to 6.0±0.2 ml/min; placebo, 3.5 ± 0.1 to 4.7±0.2; p &amp;lt; 0.0001 vs. baseline in both groups; p &amp;lt;0.0001, PIO vs. placebo). In the whole dataset the improvement in insulin clearance was associated with improvement in peripheral insulin sensitivity (r=0.62, p&amp;lt;0.0001), the reduction in mean plasma glucose concentration during OGTT (r=-0.31, p&amp;lt;0.0001) and decrease in ALT (r=-0.14, p&amp;lt;0.009). Conclusion: PIO treatment results in an increase in MCRI that is associated with improved hepatic function, glucose metabolism and peripheral insulin sensitivity. Disclosure A. Gastaldelli: Consultant; Self; A. Menarini Diagnostics, Eli Lilly and Company, Genentech, Inc., Gilead Sciences, Inc., Inventiva Pharma. D. Tripathy: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.

Optimal Cut-off Points of BMI WC and WHR for Screening of Pre-Diabetes and Diabetes Over 35 Years Old People

Using BMI, WC and WHR to investigate and compare these screening tool for IFG, IGT and diabetes subjects in Shanghai China; and to identify the optimal cut-off points of BMI, WC and WHR for screening pre-diabetes (Pre-DM) and diabetes (DM) over 35 years old people. Totally 3,195 aged 35 years old and above people who attended community epidemiological survey of diabetes mellitus. Using ADA criteria (2010), the participants were classified as normal, Pre-DM or DM according to test results of blood glucose. The area under ROC curve (AUROC) for BMI, WC and WHR were calculated; as well as the sensitivity, specificity and Youden index under different BMI or WHR cut-off points. Among these people, age is (61.07±10.08), and BMI and WHR are respectively (25.12±3.29) and (0.87±0.06). The positive rate of screening of DM is 11.36% and that of Pre-DM is 38.57%. There are correlation between blood glucose and BMI or WHR (p<0.05). With the increase of BMI or WHR cut-off point, the screening sensitivity (YI, Sp and Se) for DM or pre-DM are decreasing; but the area under ROC (AUROC) increases firstly and then decreases (inflection point: WHR≥0.8~0.9 and BMI≥23 for pre-DM, WHR≥0.9 and BMI≥24 for DM). The combined screening efficacy of BMI merged WHR is the best combination choice (cut-off point of BMI and WHR are respectively 23 and 0.8), and YI is the highest. Using HbA1C as standard of judgment seems to be better than blood glucose in screening for DM. BMI≥23, WC≥90 cm or WHR≥0.8 is the optimal cut-off point for screening DM and pre-DM, and the screening efficacy of BMI is better than WC and WHR. BMI merged WHR is the best combination choice (cut-off point of BMI and WHR are respectively 23 and 0.8). HbA1C is better than FBG and OGTT as standard of judgment in screening.

A unique plasma microRNA profile defines type 2 diabetes progression.

A major unmet medical need to better manage Type 2 Diabetes (T2D) is the accurate disease prediction in subjects who show glucose dysmetabolism, but are not yet diagnosed as diabetic. We investigated the possibility to predict/monitor the progression to T2D in these subjects by retrospectively quantifying blood circulating microRNAs in plasma of subjects with i) normal glucose tolerance (NGT, n = 9); ii) impaired glucose tolerance (IGT, n = 9), divided into non-progressors (NP, n = 5) and progressors (P, n = 4) based on subsequent diabetes occurrence, and iii) newly diagnosed T2D (n = 9). We found that impaired glucose tolerance associated with a global increase of plasma circulating microRNAs. While miR-148 and miR-222 were specifically modulated in diabetic subjects and correlated with parameters of glucose tolerance, the most accentuated microRNA dysregulation was found in NP IGT subjects, with increased level of miR-122, miR-99 and decreased level of let-7d, miR-18a, miR-18b, miR-23a, miR-27a, miR-28 and miR-30d in comparison with either NGT or T2D. Interestingly, several of these microRNAs significantly correlated with parameters of cholesterol metabolism. In conclusion, we observed the major perturbation of plasma circulating microRNA in NP pre-diabetic subjects and identified a unique microRNA profile that may become helpful in predicting diabetic development.

The progressive increase in fasting adipose insulin resistance during the natural history of type 2 diabetes

The role of β-cell dysfunction and peripheral insulin resistance (IR) is well established in the transition from normal glucose tolerance (NGT) to type 2 diabetes mellitus (T2DM). However, the impact of dysfunctional adipose tissue has not been fully elucidated. In the 66th issue of Diabetes in 2017, a paper entitled as Role of Adipose Tissue Insulin Resistance in the Natural History of T2DM: Results from the San Antonio Metabolism Study was published [Diabetes, 2017, 66(4): 815-822]. The aim of the study is to evaluate the role of resistance to the antilipolytic effect of insulin (Adipo-IR) in a large group of NGT, IGT and T2DM subjects. With the permission of Diabetes, we translated the paper into Chinese.(Chin J Endocrinol Metab, 2017, 33: 438-442)

Study of Modified Oral Minimal Model using n-Order Decay Rate of Plasma Insulin for the Oral Glucose Tolerance Test in Subjects with Normal, Impaired and Diabetic Glucose Tolerance

: In this present study, the modified Oral Minimal Model (OMM), with secretion of insulin from pancreas was assumed that the insulin decay rate was not always a ?rst-orderly process in the Oral Glucose Tolerance Test (OGTT), had been developed to study Normal Glucose Tolerance (NGT), Impaired Glucose Tolerance (IGT or pre-diabetes) and type 2 Diabetes Mellitus (T2DM) subjects. The modified OMM model was used to assess physiological functions which were insulin sensitivity (SI) and glucose effectiveness (SG) from the OGTT data. The results of the modified OMM model fit to the measured glucose and insulin concentration-time profiles in the OGTT process of the subjects. The single-step ?tting process to optimize the real pAarameters of the SI and SG index from the experimental data using the modi?ed OMM. Our results showed that all NGT subjects had higher the SI and SG index than all IGT and T2DM subjects following the OGTT process. Basal and large peak glucose were lower in all NGT subjects than in all IGT and T2DM subjects. Insulin extraction was lower in all subjects with T2DM but was almost similar for the NGT and IGT subjects. The averaged correlation between measured and this present model, commonly called R2 value, showed that these four cases were 0.96 which indicated good agreement.

Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation.

AimsTo investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR).Methods544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function.ResultsAmong subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters.ConclusionsDyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals.

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT. ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826±25 vs. 634±22μmol/L, P<0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT. ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.

A human model of dietary saturated fatty acid induced insulin resistance

BackgroundIncreased consumption of high-fat diets is associated with the development of insulin resistance and type 2 diabetes. Current models to study the mechanisms of high-fat diet-induced IR in humans are limited by their long duration or low efficacy. In the present study we developed and characterized an acute dietary model of saturated fatty acid-enriched diet induced insulin resistance. MethodsHigh caloric diets enriched with saturated fatty acids (SFA) or carbohydrates (CARB) were evaluated in subjects with normal and impaired glucose tolerance (NGT or IGT). Both diets were compared to a standard eucaloric American Heart Association (AHA) control diet in a series of crossover studies. Whole body insulin resistance was estimated as steady state plasma glucose (SSPG) concentrations during the last 30min of a 3-h insulin suppression test. ResultsSSPG was increased after a 24-h SFA diet (by 83±74% vs. control, n=38) in the entire cohort, which was comprised of participants with NGT (92±82%, n=22) or IGT (65±55%, n=16) (all p<0.001). SSPG was also increased after a single SFA breakfast (55±32%, p=0.008, n=7). The increase in SSPG was less pronounced after an overnight fast following a daylong SFA diet (24±31%, p=0.04, n=10), and further attenuated 24h after returning to the control diet (19±35%, p=0.09, n=11). SSPG was not increased after a 24-h CARB diet (26±50%, p=0.11, n=12). ConclusionsA short-term SFA-enriched diet induced whole body insulin resistance in both NGT and IGT subjects. Insulin resistance persisted overnight after the last SFA meal and was attenuated by one day of a healthy diet. This model offers opportunities for identifying early mechanisms and potential treatments of dietary saturated fat induced insulin resistance.

Cocoa Increases Postprandial GLP‐1 Response in Adults with Impaired Glucose Tolerance

Prediabetes (elevated fasting glucose or impaired glucose tolerance) is an intermediate state in the development of type‐2 diabetes. Strategies are needed to prevent progression from this “at‐risk” state to fully developed disease. Cocoa flavanols offer a unique potential solution to improve glucose homeostasis by inhibiting digestive enzymes and stimulating an incretin hormone response. The purpose of this study was to determine the effects of acute cocoa consumption on postprandial blood glucose, insulin, and incretin hormone levels following a mixed meal in adults. Sixteen adults at risk for developing type‐2 diabetes were enrolled: n=11 had normal glucose tolerance (NGT, blood glucose &lt; 140 mg/dl 2 h after 75 g OGTT) and n=5 had impaired glucose tolerance (IGT, 140–199 mg/dl 2 h after OGTT). Subjects completed two meal challenges consisting of a meal replacement shake blended with a cocoa beverage powder (10 g cocoa) or placebo beverage powder (0 g cocoa) in a randomized crossover design. Intravenous blood samples were taken at baseline and over 4 h post‐meal. For all subjects pooled together, cocoa significantly increased postprandial C‐peptide excursion from baseline compared to placebo (p = 0.0463). When data were split by phenotype (NGT vs. IGT subjects), the IGT cohort had slightly (but not significantly) lower fasting GLP‐1 levels and postprandial GLP‐1 response compared to the NGT cohort. Furthermore, the IGT cohort had significantly increased maximum postprandial GLP‐1 levels (p = 0.0452) with cocoa vs. placebo. In IGT subjects, GLP‐1 area under the curve and excursion from baseline approached significance with cocoa vs. placebo (p = 0.0759 and p = 0.0642, respectively). There were no differences in GLP‐1 response between treatments for the NGT group. There were no effects of cocoa on glucose, insulin, GIP, or adiponectin for either cohort or pooled subjects. Our data suggest that natural cocoa may rescue an impaired GLP‐1 response seen in adults with impaired glucose tolerance; NGT individuals may not experience these improvements, as their incretin and glycemic responses are not impaired. In conclusion, natural cocoa may be helpful in maintaining glucose homeostasis by enhancing the incretin response in a subset of adults at risk of developing type‐2 diabetes.Support or Funding InformationFunding was provided by The Hershey Co., Hershey, PA.

Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy

BackgroundImpaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. Methods and ResultsWe undertook 123I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. ConclusionGlobal and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes.

OBJECTIVEImpaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management.RESEARCH DESIGN AND METHODSThirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years.RESULTSTen subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years.CONCLUSIONSCCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.

Serum Proinsulin in Bangladeshi Subjects with Impaired Glucose Tolerance

Hyperproinsulinemia is commonly present in subjects with impaired glucose tolerance. The present study was undertaken to investigate the proinsulin level in Bangladeshi IGT subjects and to explore its association with insulin resistance. This observational study was conducted under a case-control design with IGT subjects (n=50) and controls (n=44). IGT was diagnosed following the WHO Study Group Criteria. Serum glucose was measured by glucose-oxidase method, serum lipid profile by enzymatic method and serum insulin and serum proinsulin were measured by ELISA method. Insulin secretory capacity (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from fasting serum glucose and fasting serum insulin by homeostasis model assessment. The study subjects were age- and BMI- matched. Mean (±SD) age (yrs) of the control and IGT subjects were 40±6 and 40±5 respectively (p=0.853). Mean (±SD) BMI of the control and IGT subjects were 23±3 and 22±2 respectively (p=0.123). Fasting glucose was not significantly higher in IGT subjects, but serum glucose 2 hours after 75 gm glucose load was significantly higher in IGT subjects. Median (Range) value of fasting serum glucose (mmol/l) of control and IGT subjects were 5.3 (3.8-6) and 5.2 (4-12) respectively; (p=0.297). Median (Range) value of serum glucose (mmol/l) 2 hours after 75 gm glucose load of control and IGT subjects were 6.1 (3-7.8) and 7.9 (5- 21) respectively; (p=0.001). Fasting TG was significantly higher in IGT subjects and LDL-c was significantly lower in IGT subjects. Serum Total cholesterol and HDL-c were not significantly different between the IGT and control subjects. Median (Range) value of fasting serum TG (mg/dl) of control and IGT subjects were 119 (51-474) and 178 (82-540) respectively; (p=0.001). Median (Range) value of fasting serum T chol (mg/dl) of control and IGT subjects were 180 (65-272) and 186 (140-400) respectively; (p=0.191). Median (Range) value of fasting serum HDL-C (mg/dl) of control and IGT subjects were 29 (19-45) and 31 (15-78) respectively; (p=0.914). Median (Range) value of fasting serum LDL-C (mg/dl) of control and IGT subjects were 117(29-201) and 111(41- 320) respectively; (p=0.001). Fasting serum proinsulin was significantly higher in IGT subjects. Median (Range) value of fasting serum proinsulin (pmol/l) of control and IGT subjects were 9.2(1.8-156) and 17(3-51) respectively; (p=0.001). Insulin secretory capacity (HOMA%B) was higher but insulin sensitivity (HOMA%S) was significantly lower in case of IGT subjects. Median (Range) value of HOMA%B of control and IGT subjects were 97(46-498) and 164(17-300) respectively; (p=0.001). Median (Range) value of HOMA%S of control and IGT subjects were 68(19-270) and 39(15-110) respectively (p=0.001). In multiple regression analysis a significant negative association was found between fasting proinsulin and insulin sensitivity (p=0.037). The data led to the following conclusions: a) Insulin resistance is the predominant defect in Bangladeshi IGT subjects. b) Basal proinsulin level is significantly increased in IGT subjects. c) Insulin resistance is negatively associated with serum proinsulin in IGT subjects. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22411 Bangladesh J Med Biochem 2014; 7(2): 41-46

Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes.

Glypican-4 (GPC-4) has been identified as a novel adipokine capable of enhancing insulin signaling. A significant association between circulating GPC-4 levels and nonalcoholic fatty liver disease and cardiometabolic risk factors has been found in women. The aim of the present study was to investigate the relationship between GPC-4 and insulin resistance in cross-sectional and interventional studies. We measured circulating GPC-4 (determined with ELISA) in subjects with NGT, IGT, and nT2DM. Euglycemic-hyperinsulinemic clamps were performed in healthy and T2DM subjects. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of GPC-4. Circulating GPC-4 levels were significantly higher in IGT subjects and lower in nT2DM subjects compared to controls. Circulating GPC-4 was positively correlated with BMI, WHR, HOMA-IS, and FAT%, while it was inversely correlated with FBG and HbA1c. Excluding diabetic subjects, increasing GPC-4 levels were associated with HOMA-IR and M values. Significantly lower GPC-4 mRNA and protein levels were found in muscle and fat of nT2DM patients, compared to controls. GPC-4 levels were significantly increased upon an oral glucose intake. The secretion of GPC-4 exhibited a characteristic diurnal rhythm in humans, with a major rise occurring between afternoon and midnight. Circulating GPC-4 is elevated in prediabetic subjects and is reduced in nT2DM patients. The elevated GPC-4 appears to be associated with insulin resistance and obesity in IGT subjects.

Metabolic Syndrome, Abnormal Glucose Tolerance and High Sensitivity-C-Reactive Protein among Women with a History of Gestational Diabetes Mellitus

Background: Gestational Diabetes Mellitus (GDM) is a risk factor for diabetes and cardiovascular diseases. Early detection of cardio-metabolic risks is recommended for management. This study evaluated the associations between Metabolic Syndrome (MetS), abnormal glucose tolerance and cardiovascular risk factors in Malaysian women with prior GDM. Method: Seventy-seven, non-diabetic women post-GDM, aged 20-40 years (mean BMI: 26.4 ± 4.6kg/m2) with high type 2 diabetes risks, were evaluated at a median of four months postpartum. Their anthropometric and biochemical measurements were obtained. Results: The overall prevalence of MetS and dysglycaemia were 22% and 29% respectively. Dysglycaemic was predominantly impaired glucose tolerance (IGT: 77%).MetS was higher among dysglycaemic subjects although also detected in 13% of normo glycaemic subjects. Eighty percent of IGT subjects did not have MetS. Sixty-eight percent of subjects had intermediate or high CVD risks (hsCRP>1mg/L). hscRP increased with obesity and was not associated with glycaemic status. Infant birth weight, maternal age and triglycerides were independent predictors of dysglycaemia (p<0.05). Conclusion: Despite the low prevalence of MetS, elevated levels of hsCRP among these women with prior- GDM was highly prevalent. Normoglycaemic subjects with MetS demonstrated intermediate to high risk hsCRP levels. The findings also emphasize the importance of performing OGTT mainly in older post-GDM women, with higher triglycerides and infants who are large for gestational age.

Serum Levels of Acylcarnitines Are Altered in Prediabetic Conditions

ObjectiveThe role of mitochondrial function in the complex pathogenesis of type 2 diabetes is not yet completely understood. Therefore, the aim of this study was to investigate serum concentrations of short-, medium- and long-chain acylcarnitines as markers of mitochondrial function in volunteers with normal, impaired or diabetic glucose control.MethodsBased on a 75 g oral glucose tolerance test, 1019 studied subjects were divided into a group with normal glucose tolerance (NGT; n = 636), isolated impaired fasting glycaemia (IFG; n = 184), impaired glucose tolerance (IGT; n = 87) or type 2 diabetes (T2D; n = 112). Serum concentrations of free carnitine and 24 acylcarnitines were measured by mass spectrometry.ResultsSerum levels of acetylcarnitine (C2), propionylcarnitine (C3), octanoylcarnitine (C8), malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH), hexanoylcarnitine (C6), octenoylcarnitine (C8:1), decanoylcarnitine (C10), decenoylcarnitine (C10:1), dodecanoylcarnitine (C12), tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), hydroxytetradecanoylcarnitine (C14OH), hydroxyhexadecanoylcarnitine (C16OH) and octadecenoylcarnitine (C18:1) were significantly different among the groups (all p<0.05 adjusted for age, gender and BMI). Between the prediabetic states C14:1, C14:2 and C18:1 showed significantly higher serum concentrations in persons with IGT (p<0.05). Compared to T2D the IFG and the IGT subjects showed lower serum concentrations of malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) (p<0.05).ConclusionAlterations in serum concentrations of several acylcarnitines, in particular tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2), octadecenoylcarnitine (C18:1) and malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) are associated not only with T2D but also with prediabetic states.