Early-stage atherosclerosis in newly diagnosed,untreated type 2 diabetes mellitus and impaired glucose tolerance

AimThe aim of this study was to investigate early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT).MethodsThe study subjects underwent an oral glucose tolerance test (OGTT) and were then divided into three groups, according to plasma glucose level: those in the normal glucose tolerance (NGT) group had fasting plasma glucose (FPG) < 6.1 mmol/L and 2 h postload glucose (2hPPG) < 7.8 mmol/L; those in the IGT group had FPG < 6.1 mmol/L and 2hPPG ≥ 7.8 mmol/L; and those in the T2DM group had FPG ≥ 7.0 mmol/L or 2hPPG ≥ 11.1 mmol/L. Haemodynamic variables and brachial–ankle pulse-wave velocities (baPWV) in the three groups were compared.ResultsThe baPWV value increased with increases in plasma glucose, and was significantly and positively correlated to age, FPG, 2hPPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference and waist-to-hip ratio. Significant differences were found between the baPWV values in the NGT and IGT groups (1602 ± 347 vs 1707 ± 351 cm/s, respectively; P = 0.005), and between the NGT and DM groups (1602 ± 347 vs 1762 ± 381, respectively; P < 0.001). The results of multiple regression analyses showed that 2hPPG was closely related to baPWV as well as to SBP and DBP.ConclusionEarly-stage atherosclerosis is present in newly diagnosed, untreated T2DM and IGT patients, and it may be that its early assessment, along with good control of hypertension and hyperglycaemia, will help to delay its progression.     

Association between circadian rhythm of blood pressure and glucose tolerance status in normotensive,non-diabetic subjects

AimsTo examine whether circadian rhythm of blood pressure (BP) is associated with glucose tolerance status in normotensive, non-diabetic subjects.MethodsA cross-sectional study recruited normotensive and non-diabetic subjects, aged 35–79 years. A 75 g oral glucose tolerance test (OGTT) and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed.ResultsAmong 31 impaired glucose tolerance (IGT) and 36 normal glucose tolerance (NGT) study subjects, the mean (±S.D.) diurnal–nocturnal differences of average systolic BP (SBP) were 7.1 ± 6.9 and 9.9 ± 6.2 mm Hg, respectively (p = 0.086). In a linear mixed-effects regression model, however, taking each measurement of BP as the outcome, nighttime reduction of SBP in the IGT group was 7.19 mm Hg, which was significantly smaller compared to a reduction of 9.80 mm Hg in the NGT group (p-value for IGT: nighttime interaction = 0.0014). The prevalence of non-dipping BP pattern was 77.4% in the IGT group which was significantly higher than 52.8% of the NGT group (p = 0.036). Logistic regression revealed a significant effect of IGT for predicting non-dipping pattern with an adjusted odds ratio of 3.71 (95% CI: 1.09, 12.66, p = 0.029).ConclusionsAmong normotensive, non-diabetic subjects, the decreased nocturnal BP reduction was associated with impaired glucose tolerance status.     

Association between impaired glucose tolerance and carotid atherosclerosis: A study in 64-year-old women and a meta-analysis

Background and aimsImpaired glucose tolerance (IGT) is regarded as a transient metabolic state leading to type-2 diabetes, and is known to predict future risk of cardiovascular disease. This study was designed to investigate if IGT is associated with subclinical atherosclerosis.Methods and resultsIn a population-based cohort of 64-year-old women, a group with IGT determined by repeated oral glucose tolerance tests (n = 205) was compared with healthy women with normal glucose tolerance (NGT, n = 188). Intima-media thickness (IMT) and plaques in the common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95% confidence interval (CI) of the difference between the IGT and NGT groups was −0.03 to 0.03 mm. There was no difference in carotid bulb IMT or in the occurrence, size, and characteristics of plaques between the IGT and NGT groups. A meta-analysis was used to calculate summary measures of 12 reviewed studies showing a difference of 0.030 (95% CI 0.012–0.048) mm in carotid IMT between IGT and NGT groups. Heterogeneity in IMT differences between studies was shown.ConclusionsIn our population-based cohort of 64-year-old women, IGT was not associated with increased occurrence of subclinical atherosclerosis. However, a meta-analysis of 12 studies, including our current study, showed that IGT was associated with a small increase in the CCA IMT.     

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, 75 g 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 ± 22 μmol/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.     

Adipocytokine profiles as influenced by insulin resistance in obese subjects

ObjectiveThis study aims to explore the baseline adipocytokine profiles of adult Saudis and evaluate their relationship in the development of insulin resistance.MethodsIn this cross-sectional study, 300 adult Saudis with varying glucose tolerance were recruited. They were grouped into NGT, IGT and DM. Anthropometrics, glucose and lipid profiles were analyzed by routine methods; leptin, adiponectin, resistin and CRP were measured by ELISA.ResultsInsulin resistance was significantly correlated with levels of CRP (R = 0.32, p = 0.02) in the NGT; with leptin levels (R = 0.46, p = 0.001) in the IGT; and with adiponectin levels (R = 0.25, p = 0.001) in all groups. In males, resistin and CRP exhibited significant correlations to insulin resistance (R = 0.33, p = 0.005); in females significant correlation was demonstrated between insulin resistance and adiponectin (R = 0.32, p = 0.003). Significant associations exist in the adipocytokine profiles of adults with different glucose tolerance.ConclusionCertain adipocytokines can be used not only as promising markers but also as potential adjunct therapy with regards to insulin sensitivity and obesity.     

A comparative study of insulin resistance for Saudi and Caucasian subjects across a range of glycaemic categories

AimSaudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose.MethodsSubjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit.ResultsSaudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively.ConclusionsOur data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration.     

Studying progression from glucose intolerance to type 2 diabetes in obese children

AimIdentification of metabolic and genetic factors capable to mediate progression from normal glucose tolerance (NGT) through impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity.Patients and methodsThree groups of obese children with NGT (n = 54), IGT (n = 35), and T2D (n = 62) were evaluated. A control group of non-obese normal children (n = 210) was also studied. In obese patients, an oral glucose tolerance test (OGTT) was performed. Insulin resistance (IR) was assessed using HOMA-IR index. Insulin sensitivity (IS) was assessed according to the Matsuda formula. Genomic DNA from obese and control children was genotyped for genetic variants of PPARG, ADIPOQ, ADIPOR1, FTO, TCF7L2, and KCNJ11 using a real-time PCR strategy. The unpaired Student's t-test and Kruskal–Wallis one-way test were used to compare quantitative data in two and more groups. To assess the extent to which the various genetic variants were associated with pathology, ORs (odds ratios) and 95% CI (confidence interval) were estimated.ResultsIn T2D children, HOMA-IR value (7.5 ± 3.1) was significantly (P < 0.001) higher than that in IGT (4.21 ± 2.25) and NGT (4.1 ± 2.4) subjects. The Matsuda IS index was significantly increased in normoglycemic patients compared to IGT individuals (2.8 ± 1.75 vs. 2.33 ± 1.2, P < 0.05). The Pro12Ala polymorphism of PPARG was significantly associated with obesity (OR = 1.74, 95% CI = 1.19–2.55, P = 0.004) and T2D in obesity (OR = 2.01, 95% CI = 1.24–3.26, P = 0.004).ConclusionIR is a major risk factor that mediates progression from NGT to clinical T2D in Russian obese children. This progression may be genetically influenced by the Pro12Ala variant of PPARG.     

Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance

IntroductionObesity is strongly related to type-2 diabetes (T2DM), but there is a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy. This study determined to what extent differences in metabolic health in obese women are associated with differences in adipose tissue and/or systemic inflammation.MethodsThe subject group consisted of age comparable lean (n = 12) and obese women either with T2DM (n = 28) or normal glucose tolerance (NGT; n = 26). Number of crown like structures (CLS) and adipocyte size were measured in subcutaneous and visceral adipose tissue of the obese women. Circulating cytokine and free fatty acid (FFA) levels, as well as number and activation status of peripheral leukocytes were determined.ResultsObese T2DM subjects showed higher circulating levels of IL-6, FFA and glycerol as compared to obese NGT subjects. Obese T2DM subjects had higher absolute numbers of peripheral leukocytes which were mainly due to an increase of T helper cells. Activation status of circulating cytotoxic T (CD8+CD25 +) and B (CD19+CD38 +) cells was significantly increased in obese NGT subjects as compared to lean but was not different between the two obese groups. Subcutaneous adipose tissue of obese T2DM subjects contained more CLS than adipose tissue of obese NGT subjects.ConclusionObese T2DM subjects show higher FFA levels and adipose tissue macrophage infiltration in addition to higher levels of circulating IL-6 and numbers of CD4 + T cells than obese NGT subjects. Hence, obese T2DM subjects show a higher extent of inflammation at both the systemic and adipose tissue level.     

Insulin sensitivity and first-phase insulin secretion in obese Chinese with hyperglycemia in 30 and/or 60 min during glucose tolerance tests

The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucose > or = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (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. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.     

The relative contributions of insulin resistance and beta cell failure to the transition from normal to impaired glucose tolerance varies in different ethnic groups

AimTo evaluate ethnic differences in the contribution of decline in insulin secretion and insulin sensitivity in impaired glucose tolerance (IGT).MethodsSeven hundred and eighteen subjects of Arab, Japanese and Mexican American decent received oral glucose tolerance test (OGTT) with plasma glucose and insulin measurement every 30 min. The Matsuda index of insulin sensitivity and the relation between incremental increase under plasma insulin to glucose curves during the OGTT (ΔI_0–120/ΔG_0–120) were calculated.ResultsNGT Japanese subjects had highest insulin sensitivity index (7.1 ± 4.6) and lowest insulin secretion index ((ΔI_0–120/ΔG_0–120 = 1.1 ± 0.9). Mexican Americans and Arabs had lower insulin sensitivity (4.1 ± 2.8 and 3.5 ± 2.3, respectively) and higher insulin secretion indices (2.2 ± 2.0 and 2.5 ± 2.5). IGT subjects in all ethnic groups had reduced insulin sensitivity and insulin secretion compared to NTG subjects. However, the reduction in insulin sensitivity was the largest in Mexican American (30%), the smallest in Arabs (11.5%) and intermediate in Japanese (23%). Conversely, the decrease in insulin secretion was the greatest in Arabs (80%), the smallest in Mexican Americans (41%) and intermediate in Japanese (55%).In a multivariate regression analysis model, the decline in insulin secretion was a stronger determinant of 2-h plasma glucose in Arabs than the reduction in insulin sensitivity while the opposite was observed in Mexican Americans and Japanese.ConclusionDifferences in insulin sensitivity and insulin secretion are present amongst different ethnic groups. The relative contributions of reduced insulin action and impaired insulin secretion are likely to contribute differentially to progression from NGT to IGT (and diabetes) in different ethnic groups.     

Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI₁/ΔG₁ was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.     

Hyperinsulinemia and insulin resistance is associated with low T3/T4 ratio in pre diabetic euthyroid pakistani subjects

ObjectiveTo investigate the relationship of thyroid hormones in glucose homeostasis in impaired glucose-tolerant subjects with normal thyroid functions.MethodsCross-sectional analysis was carried out in (n = 260) impaired glucose-tolerant (IGT) and normal glucose-tolerant (NGT) subjects. Thyrotropin (TSH), total triiodothyronine (TT₃), total thyroxin (TT₄) free T₃ (fT₃), free T₄ (fT₄), and insulin were assessed by enzyme-linked immunoassays (ELISA). Fasting plasma glucose (FPG) and HbA1c were measured by glucose oxidase and low-pressure cation exchange chromatography. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance; fT₃/fT₄ ratio was calculated. Anthropometric measurement and habits were recorded.ResultsMarked hyperinsulinemia and insulin resistance were observed in IGT subjects. Serum TT₃ and fT₃ levels were significantly low in the IGT as compared to normal glucose-tolerant (NGT) controls. TT₄ and TSH were higher in IGT subjects as compared to control subjects. There was a significant positive correlation of TSH with BMI only in the control group (r = 0.351; P < 0.05). Correlation of insulin with TT₃, fT₃,and TSH was significant (P < 0.05) in IGT subjects. A significant low fT₃/fT₄ ratio was observed in IGT subjects as compared to NGT subjects (P < 0.01).In multiple regression analysis, TSH, TT₄ and fT₃ contributed significantly to the variance of fasting insulin and insulin resistance in IGT subjects.ConclusionHyperinsulinemia and insulin resistance are associated with low T₃/T₄ ratio in pre-diabetic euthyroid Pakistani subjects.     

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 association between apolipoprotein M and insulin resistance varies with country of birth

Background and aimsRisk of type 2 diabetes mellitus (T2DM) differs according to ethnicity. Levels of apolipoprotein M (ApoM) have been shown to be decreased in T2DM. However, its role in different ethnicities is not known. We examined the differences in plasma ApoM levels in Swedish residents born in Iraq (Iraqis) and Sweden (Swedes) in relation to T2DM and insulin resistance (IR).Methods and resultsIraqis and Swedes, aged 45–65 years residing in Rosengård area of Malmö were randomly selected from census records and underwent an oral glucose tolerance test. Plasma levels of ApoM were quantified in 162 participants (Iraqis, n = 91; Swedes, n = 71) by a sandwich ELISA method.Age-, sex-, and body mass index (BMI) adjusted plasma ApoM levels differed by country of birth, with Swedes having 18% higher levels compared to Iraqis (p = 0.001). ApoM levels (mean ± SD) were significantly decreased in Swedes with T2DM (0.73 ± 0.18) compared to those with normal glucose tolerance (NGT) (0.89 ± 0.24; p = 0.03). By contrast, no significant difference in ApoM levels was found between Iraqis with T2DM (0.70 ± 0.17) and those with NGT (0.73 ± 0.13; p = 0.41). In multivariate linear regression analysis with an interaction term between IR and country of birth, low ApoM levels remained significantly associated with IR in Swedes (p = 0.008), independently of age, sex, BMI, family history of diabetes, HDL, LDL, and triglycerides, but not in Iraqis (p = 0.35).ConclusionOur results show that ApoM levels differ according to country of birth and are associated with IR and T2DM only in Swedes.     

Carotid intima-media thickness is reduced 12 months after gastric bypass surgery in obese patients with type 2 diabetes or impaired glucose tolerance

AimTo investigate whether Roux-en-Y gastric bypass surgery (RYGB) – an in vivo model for normalisation of hyperglycaemia – improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).MethodsObservational prospective study, 34 obese patients (T2D (n = 14)/IGT (n = 4), and NGT (n = 16)) were investigated before and six and 12 months after RYGB.ResultsMean carotid IMT was significantly reduced 12 months after RYGB in patients with T2D/IGT (− 0.041 mm (95% CI − 0.069; − 0.012, p = 0.005)) but not in patients with NGT (− 0.010 mm (− 0.039; 0.020, p = 0.52)). The between-group difference was not significant (p = 0.13). Twelve months after RYGB, patients with respectively T2D/IGT and NGT demonstrated changes in weight: − 29.9 kg, p < 0.001/− 30.6 kg, p < 0.001, HbA1c: − 0.7%, p < 0.001/− 0.1%, p = 0.33, systolic blood pressure: − 2 mmHg, p = 0.68/− 10 mmHg, p = 0.01 and diastolic blood pressure: − 8 mmHg, p = 0.003/− 11 mmHg, p < 0.001. 80% of T2D patients terminated antihyperglycaemic medication.ConclusionMean carotid IMT was significantly reduced 12 months after RYGB in patients with T2D/IGT which provides evidence to support that the earliest atherosclerotic changes in the arterial wall are reversible. Although numerically different from the changes observed in patients with NGT, the between-group difference was not statistically significant.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Metabolic syndrome of prediabetic and diabetic subjects in a Bangladeshi population

BackgroundThe metabolic syndrome is a cluster of medical disorder that increases the risk of developing cardiovascular disease and diabetes.Aims and objectiveObjective of the study was to determine the metabolic syndrome in prediabetic subjects to know whether this syndrome, which is common in diabetic subjects, appears in earlier stage of the disease.Materials and methodsA group of 17 IFG, 60 IGT, 29 combined IFG–IGT and 68 type 2 DM subjects were studied along with a group of 56 healthy controls. Anthropometric and clinical characteristics were measured using appropriate methods. Serum glucose was measured using glucose-oxidase method; lipid profile by enzymatic–colorimetric method.ResultsWaist hip ratio (WHR) was significantly higher in IFG–IGT and type 2 DM subjects. Systolic blood pressure was significantly higher in IFG–IGT and diastolic blood pressure is significantly higher in IGT, IFG–IGT and type 2 DM compared to controls. Fasting serum TG (p = 0.008) and cholesterol (p = 0.001) level was significantly higher in type 2 DM subjects but the values were not significantly different in prediabetic subjects compared to controls. HOMA B% and HOMA S% were significantly lower in DM and IFG–IGT subjects, IFG subjects have also shown significantly lower HOMA B% compared to controls.ConclusionThese results indicate that hypertension, central obesity (WHR) and insulin resistance, three major factors for metabolic syndrome are present in prediabetic condition in a Bangladeshi population.     

Assessment of small fiber neuropathy to predict future risk of type 2 diabetes

ObjectiveSudomotor dysfunction due to small fiber neuropathy can be observed very early in pre-diabetes. The aim of this study was to assess the predictive power of EZSCAN, a non invasive, quick and simple measurement of sudomotor function to identify glucose impairment.Research design and methodsThe study was performed in 76 German subjects at risk of diabetes. Glucose metabolism was assessed by using, oral glucose tolerance test (OGTT) at baseline and after 2 year follow-up. Sudomotor function was evaluated by measuring hand and foot electrochemical sweat conductances to calculate a risk score.ResultsAt baseline, 38 patients had normal glucose tolerance (NGT), 34 had pre-diabetes (impaired fasting glucose, IFG and/or impaired glucose tolerance, IGT) and 4 had newly diagnosed type 2 diabetes. The AUC values for FPG, 2 h-OGTT glucose, 1 h-OGTT glucose, HbA_1C and EZSCAN score to predict pre-diabetes were 0.50, 0.65, 0.64, 0.72 and 0.76, respectively. Subjects having a moderate or high EZSCAN score (>50) at baseline had a substantially increased risk for having IFG and/or IGT at follow-up visit presented by an odds ratio of 12.0 [1.4–100.5], the OR for having 1 h-OGTT ≥ 8.6 mmol/L at follow-up was 9.8 [1.0–92.8] and for having HbA_1C ≥ 5.7% was 15.7 [1.9–131.5] compared to subjects with low EZSCAN risk.ConclusionsThis preliminary study, which must be confirmed in a larger population, shows that EZSCAN risk score is associated with diabetes progression which have implications for prevention and disease management.     

Elevated level of C-reactive protein is associated with risk of prediabetes in Indians

BackgroundRelationship of high sensitivity C-reactive protein (hsCRP) with prediabetes has not been explored extensively in Indians. Here we sought to investigate the association of hsCRP levels with prediabetes, as represented by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and the influence of risk factors like obesity, decreased HDL cholesterol, hypertension, family history of diabetes and current smoking habit on the relationship.MethodsA cross-sectional study on 1726 Indians, comprising of 1276 individuals with normal glucose tolerance (NGT), 250 IFG and 200 IGT individuals. Subjects were defined according to WHO criteria based on fasting plasma and 2 h glucose levels.ResultsMedian levels of hsCRP were significantly higher in IFG (2.20 mg/l) and IGT (2.32 mg/l) compared to NGT (1.64 mg/l) subjects. Individuals with high risk hsCRP levels (>3 mg/l) had an odds ratio (OR) (95% confidence interval (CI)) of 2.60 (1.56–5.34) [P = 1.3 × 10^?4] for IGT after adjusting the effect of age, sex, medication, body mass index (BMI), waist circumference (WC) and risk factors like decreased high-density lipoprotein cholesterol (HDL-cholesterol), hypertension, family history of diabetes and current smoking. Significant increase in risk of IGT was found with a unit increase in natural log transformed hsCRP levels after adjustment for covariates [OR (95%CI) = 1.57 (1.27–1.94), P = 3.0 × 10^?5]. When subjects were stratified on the basis of risk factors, we found stronger association of elevated hsCRP levels with risk of IFG and IGT in subjects having HDL-cholesterol ≤50 mg/dl and with hypertension.ConclusionsOur study demonstrates that elevated hsCRP levels are independently associated with risk of IFG and IGT in Indians.     

Serum levels of osteocalcin in relation to glucose metabolism and carotid atherosclerosis in Chinese middle-aged and elderly male adults: The Shanghai Changfeng Study

BackgroundThe role of osteocalcin (OCN) in atherogenesis is unclear. We investigated the association between OCN and carotid atherosclerosis in Chinese middle-aged and elderly male adults and further determined whether OCN is independently associated with the carotid atherosclerosis in euglycemic subgroup.MethodsA total of 1077 male participants (mean age, 61.3 years) were enrolled from the Changfeng Study. A total of 638 subjects with normal glucose tolerance (NGT) were included in the subgroup analysis. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima–media thicknesses (CIMTs) were measured using ultrasonography, and the presence of carotid plaques was assessed. The circulating OCN was measured using electrochemiluminescence immunoassay.ResultsOCN was 18.5 ± 7.5 ng/ml in this male population. Both impaired glucose regulation (IGR) and new diagnosed diabetes (NDD) groups had significantly lower OCN levels compared with the NGT group (17.7 ± 0.4 ng/ml, and 17.4 ± 0.6 ng/ml vs 19.2 ± 0.3 ng/ml, respectively). Multivariate linear stepwise regression analysis demonstrated that triglyceride (TG) (standardized β = − 0.065, p = 0.042) and fasting blood glucose (FBG) (standardized β = − 0.063, p = 0.034) were independently and inversely associated with serum OCN. In the NGT subgroup analysis, compared with subjects with OCN in the first quartile, subjects with OCN in the fourth quartile had decreased prevalence of carotid plaque. After adjusting for conventional CVD risk factors, male participants with OCN in the fourth quartile had a 0.57-fold decreased risk of carotid plaques relative to those in the lowest quartile.ConclusionThese results suggest that OCN is independently associated with carotid atherosclerosis in male individuals with NGT and that OCN may be implicated in not only glucose metabolism but also atherosclerosis.