Effects of exercise training on indicators of adipose tissue angiogenesis and hypoxia in obese rats

ObjectiveTo investigate the effects of obesity and exercise training on regional adipose tissue angiogenesis and hypoxia markers in rats.MethodsLean (Fa/Fa) and obese (fa/fa) male Zucker rats at 2 months of age were randomly assigned to a sedentary or an exercise training group (lean sedentary: n = 7, lean exercise: n = 8, obese sedentary: n = 7, obese exercise: n = 8). The exercise group walked on a rat treadmill 5 times per week for 8 weeks. Inguinal and epididymal adipose tissue vascular endothelial growth factor A (VEGF-A) and lactate levels were determined.ResultsThere were significant effects of obesity in increasing inguinal (P < 0.001) and epididymal (P < 0.05) adipose tissue VEGF-A, and a significant effect of exercise training in increasing epididymal adipose tissue VEGF-A (P < 0.05). There was a significant effect of obesity in increasing inguinal adipose tissue lactate levels (P < 0.001). Compared to lean sedentary animals, obese sedentary animals had significantly higher epididymal adipose tissue lactate levels (P < 0.001); compared to obese sedentary animals, obese exercise rats had significantly lower epididymal adipose tissue lactate levels (P < 0.05).ConclusionsExercise training increased adipose tissue VEGF-A, an important factor of tissue angiogenesis, and lowered adipose tissue lactate, an indicator of adipose tissue hypoxia in obese rats. However, these effects are depot-specific and only observed in intra-abdominal adipose tissue.     

Irisin and leptin concentrations in relation to obesity,and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study

ObjectiveTo investigate the associations between irisin and leptin levels in obesity and insulin resistance in a cross sectional study. To assess the potential role of irisin and leptin as a predictive marker of T2DM using a nested case-control study.MethodsBoth studies were designed within the longitudinal VA NAS cohort. The cross sectional study involved 111 non obese and 105 obese subjects who were subdivided into two groups based on their fasting glucose tolerance. In the nested 1:3 case-control study, 47 subjects with T2DM and 140 non-diabetic controls were selected. Serum samples collected 3-5 years before the diagnosis of T2DM were analyzed. Irisin and leptin concentrations were measured using a validated ELISA and radioimmunoassay respectively.ResultsIn the cross-sectional study, irisin did not differ between groups based on their fasting glucose tolerance. When subjects were grouped based on obesity status, both irisin and leptin concentrations were significantly higher in obese compared to the non-obese group (p = 0.03 and < 0.001, respectively). Irisin concentrations positively correlated with leptin concentrations (r = 0.392, P < 0.001). In the nested case control study, leptin concentrations were a significant predictor of developing diabetes (p = 0.005) in unadjusted models, but not after correcting for BMI, whereas irisin concentrations did not play a role of comparable significance.ConclusionsLeptin concentrations are higher in the obese group irrespective of their glucose tolerance. Obese individuals with impaired fasting glucose have higher concentrations of circulating irisin compared to non-obese subjects with normal glucose tolerance. Irisin concentrations do not predict risk of developing diabetes prospectively.     

Interleukin-20 circulating levels in obese women: Effect of weight loss

Background and aimsObesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight.Methods and resultsFifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P = 0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r = 0.35; P = 0.02) and visceral fat (waist–hip ratio; r = 0.32; P = 0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153) pg/ml (median and 25%/75%; P = 0.03), and it was positively associated with changes in body mass index and waist–hip ratio.ConclusionIn premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist–hip ratio, and are reduced by weight loss.     

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.     

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.     

The Impact of a Family History of Type 2 Diabetes on Insulin Secretion and Insulin Sensitivity in Individuals With Varying Glucose Tolerance

IntroductionThis study was performed to investigate the impact of a family history of type 2 diabetes (T2DM) on insulin resistance and beta-cell dysfunction in populations with varying glucose tolerance.MethodsAmong the total of 142 participants, 73 subjects with no family history of T2DM (FH?) included 42 with normal glucose tolerance (NGT/FH?) and 31 with impaired glucose tolerance (IGT/FH?); and 69 first-degree relatives of patients with T2DM (FH+) included 36 with NGT (NGT/FH+) and 33 with IGT (IGT/FH+). Insulin resistance was evaluated by Insulin Sensitivity Index (ISI) based on the euglycemic hyperinsulinemic clamp. Islet beta-cell function was assessed by disposition index (DI) for the acute insulin response to glucose (AIRg) using intravenous glucose tolerance test. Metabolic data were compared between groups after adjustment for age, sex, body mass index and waist-to-hip ratio.ResultsThe NGT/FH+ group showed lower level of ISI (P = 0.023) than the NGT/FH? group, whereas no difference was found in AIRg or DI between these 2 subgroups. In the FH? individuals, both ISI and DI of the IGT/FH? group decreased compared with the NGT/FH? group (both P < 0.05). In the FH+ individuals, no difference was found in ISI between the IGT/FH+ and NGT/FH+ groups, whereas the IGT/FH+ group had a lower level of AIRg and DI than the NGT/FH+ group (both P < 0.0001).ConclusionsThis study showed that the pathophysiological changes were different between individuals with and without a family history of T2DM during the glucose tolerance aggravation.     

Lower circulating irisin is associated with type 2 diabetes mellitus

AimsIrisin is a novel myokine secreted in response to PPAR-γ co-activator-1α (PGC-1α) activation. Earlier studies suggested that PGC-1α expression and activity were lower in myocytes in type 2 diabetes mellitus (T2DM). Therefore, we hypothesize that circulating irisin levels are lower in T2DM patients.MethodsIn this observational study, we recruited 96 T2DM subjects and 60 non-diabetic control subjects. Among T2DM subjects, 38% were on insulin treatment, 78% were taking statins and 72% were taking renin-angiotensin system antagonists. Circulating irisin was quantified by ELISA and its association with markers of metabolic phenotype was analyzed by Pearson bivariate correlation and multiple linear regression.ResultsCirculating irisin was significantly lower in individuals with T2DM compared with non-diabetic controls (T2DM 204 ± 72 ng/ml vs. non-diabetic control 257 ± 24 ng/ml, p < 0.0001). In non-diabetic subjects, circulating irisin was correlated with age (r = 0.398, p < 0.01), BMI (r = 0.387, p < 0.01), total cholesterol (r = 0.341, p < 0.01), total triglycerides (r = 0.299, p < 0.05), fasting blood glucose (r = 0.430, p < 0.01) and diastolic blood pressure (r = 0.306, p < 0.05). Multiple linear regression model revealed that BMI (β = 0.407, p = 0.012) and FBG (β = 0.315, p = 0.034) were associated with irisin in non-diabetic subjects after adjusting for multiple co-variates. However, similar analysis in T2DM subjects didn’t reveal significant association between circulating irisin and major markers of metabolic phenotype.ConclusionsCirculating irisin is lower in T2DM compared with non-diabetic controls. Plasma irisin levels appear to be associated with important metabolic factors in non-diabetic subjects but not in individuals with type 2 diabetes.     

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes

AimsIn the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes.MethodsVisceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage.ResultsNo significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (P < 0.05). Lower MDA concentration and longer telomere length were seen in subjects with diabetes compared to those without (P < 0.05). DNA damage, analysed via Comet assay, was significantly lower in subjects with diabetes compared to those without (P < 0.05).ConclusionA paradoxical decrease in oxidative stress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue.     

The number and phenotype of myocardial and adipose tissue CD68+ cells is associated with cardiovascular and metabolic disease in heart surgery patients

Background and aimsCD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM.Methods and resultsSamples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm²; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm²; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm²; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024).ConclusionsRegional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.     

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.     

Retrospective comparison of voglibose or acarbose as an add-on therapy to sulfonylureas in Western Indian patients with uncontrolled overweight/obese type 2 diabetes

AimThe study was aimed to investigate the effect of voglibose or acarbose as an add-on treatment in overweight/obese type 2 diabetes (T2DM) patients who are uncontrolled with metformin and sulfonylureas (SUs) in Western part of India.Participants and methodsA retrospective study included 77 participants (BMI ≥ 25 kg/m²; HbA1c level > 8% and < 9.5%) with overweight/obese T2DM. These participants were treated with either voglibose or acarbose. Glycemic parameters (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI and lipid parameters were evaluated at baseline, 3-month, 6-month and 9-month of treatment. Adverse events were also captured at respective time points.ResultsVoglibose showed significant reduction in HbA1c and bodyweight with short duration of treatment (6 months; P < 0.05 and 9 months; P < 0.01) whereas acarbose showed significant reduction with longer duration of treatment (9 months; P < 0.05) when compared with baseline. Moreover, both treatment groups were reported with reduction in BMI. Further, significant improvement in lipid parameters except LDL and HDL were observed in both treatment groups when compared with baseline. None of participant was discontinued due to side effects of the treatment. In addition, the frequency of hypoglycemia was decreased in both treatment groups.ConclusionVoglibose or acarbose as an add-on treatment with metformin and sulfonylureas in uncontrolled obese/overweight T2DM provides desired glycemic control, reduces bodyweight and improves lipid parameters with good tolerability profile.     

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.     

Exercise training improves hemodynamic recovery to isometric exercise in obese men with type 2 diabetes but not in obese women

ObjectivesWomen with type 2 diabetes (T2D) show greater rates of mortality due to ischemic heart disease than men with T2D. We aimed to examine cardiovascular and autonomic function responses to isometric handgrip (IHG) exercise between men and women with T2D, before and after an exercise training program.Materials/MethodsHemodynamic responses were measured in 22 men and women with T2D during and following a 3-min IHG test, and before and after 16 wks of aerobic exercise training.ResultsWomen had a smaller decrease in mean arterial pressure (MAP) and systolic blood pressure (BP) during recovery from IHG (ΔMAP_REC) than men pre- and post-training (P < 0.05). Men showed a greater reduction in diastolic BP during recovery from IHG (P < 0.05), and exercise training improved this response in men but not in women (men, pre-training: ? 13.9 ± 1.8, post-training: ? 20.5 ± 5.3 mmHg vs. women, pre-training: ? 10.7 ± 1.7, post-training: ? 4.1 ± 4.9 mmHg; P < 0.05). Men had a greater reduction in sympathetic modulation of vasomotor tone (P < 0.05), as estimated by blood pressure variability, following IHG. This response was accentuated after training, while this training effect was not seen in women. Post-training ΔMAP_REC was correlated with recovery of low frequency component of the BP spectrum (ΔLF_SBPrec, r = 0.52, P < 0.05).ConclusionsDifferences in BP recovery immediately following IHG may be attributed to gender differences in cardiovascular autonomic modulation. An improvement in these responses occurs following aerobic exercise training in obese men, but not in obese women with T2D which reflects a better adaptive autonomic response to exercise training.     

An association of serum vistafin level and number of circulating endothelial progenitor cells in type 2 diabetes mellitus patients

BackgroundThe decreased number and impaired functions of endothelial progenitor cells (EPCs) may associate with cardiovascular disease (CV) including atherosclerosis. However, the role of vistafin in regulation of angiogenic EPC subset maturation in T2DM patients without known atherosclerosis is still not fully understood.The aim of the studyTo investigate an association of serum vistafin level and number of circulating EPCs in T2DM patients beyond known CV disease.MethodsThis case–control observational investigation was evolved 54 subjects with T2DM and 35 healthy volunteers. The flow cytometry was used for predictably distinguishing cell subsets, which depend on expression of CD45, CD34, CD14, Tie-2, and VEGFR2. Biomarkers were measured at baseline of the study.ResultsAll T2DM patients were divided depending median of vistafin level (5.88 ng/mL) in to two cohorts with low vistafin level (<5.88 ng/mL; n = 29) and high vistafin level (≥5.88 ng/mL; n = 25) respectively. Logistic regression analysis has shown that visfatin, hs-CRP, age and BMI were the best variables in the prediction of EPC number labeled as CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺ cells. After adjustment of the model to age and BMI elevated visfatin level remained the best predictor for both CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺ EPCs (OR 0.92, 95% CI: 0.88–0.95; P = 0.001 and OR 0.90, 95% CI: 0.87–0.96; P = 0.001 respectively).ConclusionWe found that elevated level of vistafin was an independent predictor for declined numerous of non-classical EPCs labeled as CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺, whereas CD34⁺ subsets of EPCs did not associate with vistafin level in T2DM individuals.     

Lack of replication of common EXT2 gene variants with susceptibility to type 2 diabetes in Lebanese Arabs

ObjectiveRecent genome-wide association studies and replication analyses have reported the association of variants of the exostosin-2 (EXT2) gene and risk of type 2 diabetes mellitus (T2DM) in some populations, but not in others. This study investigated the associations of EXT2 variants rs1113132, rs3740878 and rs11037909 with T2DM in a Lebanese Arab population.MethodsThis case-control study involved 995 T2DM patients and 1076 control subjects. Genotyping was done by the allelic exclusion method.ResultsWhile minor allele frequencies (MAFs) of rs11037909 (P = 0.028) and rs3740878 (P = 0.048), but not rs1113132 (P = 0.841), were higher in patients, this was lost after correcting for multiple testing. Apart from EXT2 rs1113132, which was marginally associated with T2DM in the additive model (P = 0.054), but not after adjustment for covariates, none of the tested EXT2 SNPs were associated with T2DM in any of the genetic models tested. However, variable associations of EXT2 variants with T2DM were noted according to BMI status. While the three tested EXT2 variants were not associated with T2DM in obese subjects, rs1113132 and rs11037909, but not rs3740878, were associated with T2DM in non-obese subjects. Meta-analysis revealed a significant association of rs11037909 and a marginal association of rs3740878 with T2DM in the fixed model. Using a common (GTA) haplotype as reference, three-locus (rs1113132/rs11037909/rs3740878) haplotype analysis demonstrated no association between any of the EXT2 haplotypes with T2DM, not even before correcting for multiple testing.ConclusionThis study demonstrated no association of rs1113132, rs3740878 and rs11037909 EXT2 variants with T2DM.     

Frequent delay of coeliac disease diagnosis in symptomatic patients with type 1 diabetes mellitus: Clinical and genetic characteristics

BackgroundPatients with type 1 diabetes mellitus (T1DM) are more prone to develop other auto-immune diseases, including coeliac disease (CD). Paediatric patients with T1DM are screened for CD, whereas in adult T1DM patients screening programs for CD are not standardised. The aim of this study was to investigate clinical and genetic characteristics of patients with both diagnoses so as to lead to better detection of CD in adult patients with T1DM.MethodsWe studied 118 patients with both T1DM and CD identified in The Netherlands. We retrospectively collected data on sex distribution, age of onset of T1DM, age of CD diagnosis, CD complaints, duration of CD complaints before CD diagnosis, family history of CD or T1DM, comorbidity and HLA-DQ type.ResultsThirty-three percent of T1DM + CD patients reported CD related complaints for at least 5 years before CD diagnosis. Two peaks in the age of CD diagnosis in T1DM patients were observed: around 10 and 45 years of age. Women were diagnosed with CD at a younger age than men (median 25 years (IQR 9–38) versus 39 (12–55) years, respectively, P < 0.05).ConclusionA delay of CD diagnosis is frequently found in adult T1DM patients and two peaks in the age of CD diagnosis are present in T1DM patients. This observational study emphasises that more frequent screening for CD in particularly adult T1DM patients is required, preferably by a 5 years interval.     

The change in one-hour postload plasma glucose levels,and an analysis of its related factors in abdominally obese Han Chinese men with normal glucose tolerance

ObjectiveThis study was to observe the difference in one-hour postload plasma glucose levels and analyze its related factors in abdominally obese men with normal glucose tolerance (NGT).DesignThis case–control study included 36 abdominally obese men (waist circumference ≥ 90 cm) and 31 non-abdominally obese men (waist circumference < 90 cm) aged 20–50 years with NGT. Cases and controls were matched in age. All subjects underwent oral glucose tolerance test with 75 g of oral anhydrous glucose.Results0.5 and 1-h postload plasma glucose levels were higher in abdominally obese group than in non-abdominally obese group (P < .05). Fasting plasma glucose (FPG), 2 and 3-h postload plasma glucose were similar in the two groups (P > .05). 1-h postload plasma glucose was positively correlated with body mass index (r = 0.454), waist circumference(WC) (r = 0.519), systolic blood pressure (r = 0.456), diastolic blood pressure (r = 0.338), triglycerides (r = 0.439), and negatively correlated with high density lipoprotein cholesterol (r = ? 0.391), 1/fasting insulin (r = ? 0.459), insulinogenic index (r = ? 0.357) and disposition index (r = ? 0.602) (P < .01). In multiple regression analysis, 1-h postload plasma glucose maintained an independent association with disposition index (β = ? 1.367, P = .000), WC (β = 0.103, P = .000) and triglycerides (β = 0.185, P = .017).ConclusionsThe present study demonstrated that the level of one-hour postload plasma glucose was elevated in abdominally obese men with NGT. Besides FPG and 2-h postload plasma glucose, we must also pay attention to the measurement of one-hour postload plasma glucose. Disposition index, WC and triglycerides were independently related factors for elevated one-hour postload plasma glucose.     

Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs

BackgroundCommon variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits.MethodsThe association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsSignificant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [P = 0.003; OR (95% CI) = 2.07 (1.28–3.33)] and obese [P = 0.021; OR (95% CI) = 1.83 (1.10–3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [Pc = 0.034; OR (95% CI) = 1.22 (1.06–1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls.ConclusionWhile CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated.     

Risk characterization for urinary tract infections in subjects with newly diagnosed type 2 diabetes

AimTo evaluate the risk of urinary tract infections (UTI) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsSubjects aged ≥ 18 years and diagnosed with T2DM between 1/1/10 and 12/31/10 were identified using the MarketScan® databases, which are representative of the commercially insured US population and those with both Medicare and supplemental coverage. The index date was the first T2DM diagnosis date in 2010 (date randomly selected for those without T2DM). Subjects without T2DM were matched (1:1) by index date, age, gender, urban/rural location, and region. All subjects had continuous enrollment for 12 months before (baseline) and after (follow-up) the index date. UTI diagnosis was defined using ICD-9-CM codes. Measurements of glycemic control and body weight were not available. An adjusted logistic regression model assessed the likelihood of UTI.ResultsA total of 89,790 matched pairs were selected. During follow-up, a UTI diagnosis was more common in subjects with T2DM than without T2DM (9.4% vs. 5.7%; p < 0.0001). Recurrence of UTI was also more likely with T2DM (1.6% vs. 0.6%; p < 0.0001). In a logistic regression, subjects with T2DM had a greater likelihood of UTI during follow up (adjusted odds ratio [OR] = 1.54 [95% CI: 1.47–1.60]). This relationship remained after stratifying by gender.ConclusionSubjects with T2DM were more likely to experience a UTI and recurrent UTIs than subjects without T2DM during follow-up.     

Plasma adiponectin level is inversely correlated with albuminuria in overweight and obese nondiabetic individuals

ObjectiveTo explore the relationship between adiponectin and albuminuria in a large group of overweight and obese nondiabetic individuals after controlling for potential confounders.Material and MethodsDetailed anthropometry, computed tomography-measured visceral abdominal adipose tissue, 24-h albuminuria, adiponectin and a series of biochemical parameters were assessed. Four hundred forty patients, predominantly of Caucasian origin, were included (80.2% female). A multiple linear regression model was developed, with albuminuria as the dependent variable and potential predictors as independent variables.ResultsThe mean age was 40 ± 13 years, the mean body mass index was 35.7 ± 6.6 kg/m², and the median visceral abdominal adipose tissue was 142.4 (92.3–194.0) cm². 10.9% of subjects exhibited microalbuminuria. The median adiponectin level was 9.08 (6.23–12.94) μg/ml, and the median fasting serum glucose level was 83 (77–89) mg/dl. The strongest significant univariate correlations with albuminuria were visceral abdominal adipose tissue (r = 0.258, p < 0.001), adiponectin (r = ? 0.265, p < 0.001), waist circumference (r = 0.250, p < 0.001), waist-to-hip ratio (r = 0.236, p < 0.001) and high-density lipoprotein cholesterol (r = ? 0.211, p < 0.001). The multiple linear regression model revealed a significant positive independent correlation between visceral abdominal adipose tissue and albuminuria (r = 0.134, p = 0.033), between fasting glucose levels and albuminuria (r = 0.390, p = 0.029) and between gender and albuminuria (r = 0.107, p = 0.038). A significant independent negative correlation was identified between adiponectin and albuminuria (r = ? 0.255, p = 0.022).ConclusionsWe observed an independent inverse relationship between adiponectin and albuminuria in overweight and obese nondiabetic individuals. Further investigations are needed to confirm this finding and to clarify whether adiponectin is a risk marker or plays a causative role in developing obesity-induced nephropathy.