Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL,PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs

BackgroundWhile several type 2 diabetes mellitus (T2DM) susceptibility loci identified through genome-wide association studies (GWAS) have been replicated in many populations, their association in Arabs has not been reported. For this reason, the present study looked at the contribution of ENNP1 (rs1044498), IGF2BP2 (rs1470579), KCNJ11 (rs5219), MLXIPL (rs7800944), PPARγ (rs1801282), SLC30A8 (rs13266634) and TCF7L2 (rs7903146) SNPs to the risk of T2DM in Lebanese and Tunisian Arabs.MethodsStudy subjects (case/controls) were Lebanese (751/918) and Tunisians (1470/838). Genotyping was carried out by the allelic discrimination method.ResultsIn Lebanese and Tunisians, neither ENNP1 nor MLXIPL was associated with T2DM, whereas TCF7L2 was significantly associated with an increased risk of T2DM in both the Lebanese [P < 0.001; OR (95% CI): 1.38 (1.20–1.59)] and Tunisians [P < 0.001; OR (95% CI): 1.36 (1.18–1.56)]. Differential associations of IGF2BP2, KCNJ11, PPARγ and SLC30A8 with T2DM were noted in the two populations. IGF2BP2 [P = 1.3 × 10^?5; OR (95% CI): 1.66 (1.42–1.94)] and PPARγ [P = 0.005; OR (95% CI): 1.41 (1.10–1.80)] were associated with T2DM in the Lebanese, but not Tunisians, while KCNJ11 [P = 8.0 × 10^?4; OR (95% CI): 1.27 (1.09–1.47)] and SLC30A8 [P = 1.6 × 10^?5; OR (95% CI): 1.37 (1.15–1.62)] were associated with T2DM in the Tunisians, but not Lebanese, after adjusting for gender and body mass index.ConclusionT2DM susceptibility loci SNPs identified through GWAS showed differential associations with T2DM in two Arab populations, thus further confirming the ethnic contributions of these variants to T2DM susceptibility.     

Association between PPARγ rs1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis

BackgroundDiabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide.ObjectiveTo determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population.MethodsWe have conducted a case–control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN = 128; T2DM = 148 and controls = 148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models.ResultsThe genotyping of rs1801282 polymorphism showed significant (p-value < 0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value > 0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR = 0.56, (95%CI [0.43–0.74]), p ≤ 0.0001 of Asian and Caucasian populations.ConclusionOverall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case–control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis.     

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.     

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.     

Association of the six transmembrane protein of prostate 2 gene polymorphisms with metabolic syndrome in Han Chinese population

AimThe six-transmembrane protein of prostate 2 (STAMP2) has been demonstrated to play a potential role in the pathogenesis of metabolic syndrome (MetS). The present study was designed to investigate the association of STAMP2 gene polymorphisms with MetS in Han Chinese population.MethodsA case-control study enrolled 350 Han Chinese subjects in two groups: 182 MetS patients and 168 control subjects. The clinical and biochemical characteristics were determined. Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756 and rs10263111 in STAMP2 gene were genotyped. The association of STAMP2 gene polymorphisms with MetS was analyzed.ResultsSNPs rs1981529 and rs10263111 were found to be significantly associated with MetS phenotype in male population (P = 0.014 and 0.025). Moreover, SNP rs1981529 was found to be associated with high density lipoprotein-cholesterol in male cases and with body mass index in female cases (P = 0.014 and 0.049). SNP rs10263111 was found to be associated with both waist circumference and diastolic blood pressure in total cases (P = 0.044 and 0.033). Haplotype analysis yielded significant association of STAMP2 gene with MetS in total (global P = 0.0109) and male population (global P = 0.0004).ConclusionOur findings revealed that STAMP2 gene polymorphisms are likely to significantly contribute to the risk of MetS in male Han Chinese population.     

Influence of apolipoprotein E gene polymorphism on development of type 2 diabetes mellitus in Chinese Han population: A meta-analysis of 29 studies

ObjectivesPublished data regarding the association between apolipoprotein E (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han population were inconclusive. To derive a more precise estimation of the relationship between this variant and T2DM risk in Chinese Han population, we performed this meta-analysis.Design and methodsA computerized literature search was conducted to identify the relevant studies from PubMed, EMbase, Web of Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All the statistical tests were performed using Stata 11.0.ResultsA total of 29 articles with 4615 T2DM cases and 2867 controls were included in the present meta-analysis. The results showed evidence for significant association between ApoE gene polymorphism and T2DM risk (for ε2/ε3 vs. ε3/ε3: OR = 1.37, 95% CI = 1.12–1.68, P < 0.01; for ε3/ε4 vs. ε3/ε3: OR = 1.53, 95% CI = 1.23–1.91, P < 0.01; for ε4/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.22–2.84, P < 0.01; for ε2 allele vs. ε3 allele: OR = 1.28, 95% CI = 1.08–1.52, P = 0.01; for ε4 allele vs. ε3 allele: OR = 1.43, 95% CI = 1.22–1.68, P < 0.01). In addition, significant association was also found between ApoE gene polymorphism and diabetic nephropathy (DN) risk.ConclusionsThe results of this meta-analysis suggest that the ApoE ε2 and ε4 alleles may be associated with increased risks of T2DM and DN in Chinese Han population. Additional well-designed genome-wide association studies are required to confirm these results.     

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

AimsTo investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients.MethodsWe examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis.ResultsThe genotype distribution among controls and patients was in Hardy–Weinberg equilibrium (p = 0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p = 0.044). The odds ratio 0.66 (95% CI 0.54–0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p = 0.013, p < 0.001, respectively). The odds ratio for the T allele in the CVD + subgroup vs. CVD − was 1.76 (1.35–2.30), p < 0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05–5.42, p < 0.0001).ConclusionOur findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.     

Serum fibroblast growth factor 21 concentrations in type 2 diabetic retinopathy patients

Aims/purposeFibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition.MethodsIn a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis.ResultsSerum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001).ConclusionsSerum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL).     

Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes

AimThis study assessed the impact of regular exercise on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2 diabetes mellitus (T2DM).PatientsFifty overweight patients with T2DM were randomly assigned to two groups: (A) an exercise group (EXG, n = 25), with self-controlled exercise for at least 150 min/week and one additional supervised exercise session/week; and (B) a control group (COG, n = 25), with no exercise instructions. All participants were taking oral antidiabetic drugs, and none had diabetic complications. Clinical parameters, exercise capacity (VO_2peak), ventilatory threshold (VT), insulinresistance indices (fasting insulin, HOMA-IR, HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at baseline and after 16 weeks.ResultsNo significant changes were found in body mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1 throughout the study in either group (P > 0.05). Compared with controls, the EXG showed a significant decrease in systolic and mean blood pressure, total and LDL cholesterol, and HbA_1c (P < 0.05). Also, exercise significantly suppressed levels of fibrinogen (P = 0.047), hsCRP (P = 0.041) and MMP-9 (P = 0.028), and the MMP-9-to-TIMP-1 ratio (P = 0.038), whereas VO_2peak (P = 0.011), VT (P = 0.008) and plasma TIMP-2 levels (P = 0.022) were considerably upregulated in the EXG vs. COG. Standard multiple-regression analyses revealed that MMP-9 changes were independently associated with fibrinogen and HbA_1c changes, while fibrinogen changes independently predicted TIMP-2 alterations with exercise.ConclusionMostly self-controlled exercise of moderate intensity ameliorated serum levels of pro- and anti-atherogenic markers in patients with T2DM, with no effects on body weight. These data offer further insight into the cardioprotective mechanisms of exercise in patients with T2DM.     

Relación entre la expresión de IL-2 e IL-4 y sus polimorfismos y los riesgos de padecer infección por Mycoplasma pneumoniae y asma en niños

IntroductionAsthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children.Methods392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA.ResultsWe found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376).ConclusionsIL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children.     

Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by chronic anovulation, hyperandrogenism, obesity and a predisposition to type 2 diabetes mellitus (T2DM). Since obesity plays an important role in the etiology of PCOS, we sought to determine if variants in the perilipin gene (PLIN), a gene previously implicated in the development of obesity, were also associated with PCOS. We typed six single nucleotide polymorphisms (haplotype tagging and/or previously associated with obesity or related metabolic traits) in PLIN in 305 unrelated non-Hispanic white women (185 with PCOS and 120 without PCOS). None of the variants was associated with PCOS (P < 0.05). However, the variant rs1052700*A was associated with increased risk for glucose intolerance (impaired glucose tolerance or T2DM) in both non-PCOS (OR = 1.75 [1.02–3.01], P = 0.044) and PCOS subjects (OR = 1.67 [1.08–2.59], P = 0.022). It was also associated with increased LDL (P = 0.007) and total cholesterol levels (P = 0.042). These results suggest that genetic variation in PLIN may affect glucose and lipid metabolism in women both with and without PCOS.     

The relationship of family history and risk of type 2 diabetes differs by ancestry

AimType 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.MethodsNondiabetic healthy siblings (n = 1405) of patients with early-onset coronary artery disease (18–59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14 ± 6 years).ResultsBaseline age was 46.2 ± 7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥ 1 affected first-degree relatives versus 53.1% in AA, P < 0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR = 2.53, 95% CI: 1.58–4.06) but not in AA (HR = 1.01, 0.67–1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR = 1.82 (1.08–3.06), 4.83 (2.15–10.85) and 8.46 (3.09–23.91) for 1, 2, and ≥ 3 affected, respectively. In AA only ≥ 3 affected increased risk (HR = 2.45, 1.44–4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.ConclusionsThe presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.     

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

Association of fructosamine to indices of dyslipidemia in older adults with type 2 diabetes

AimsTo evaluate the association of serum fructosamine values to lipid profiles and to other indices of glycemia both at baseline and over time in adults with type 2 diabetes (T2DM).MethodsForty adults aged 45 or older with T2DM, not taking insulin, and an HbA1c of 6–10% were enrolled in a randomized controlled trial regarding the effects of an 8-week yoga program on glycemia and related cardiovascular disease risk indices in adults with T2DM. Fasting blood was drawn to assess glycemia (HbA1c, glucose, and fructosamine) and dyslipidemia (LDL, HDL, total cholesterol, cholesterol:HDL ratio, LDL:HDL ratio, and triglycerides) pre and post-intervention. Because the relation of fructosamine to other indices of glycemia and to lipid profiles did not differ between treatment groups either at baseline or over time, groups were pooled for analysis.ResultsBaseline fructosamine values were significantly correlated with HbA1c (r = 0.77, P < 0.0001), glucose (r = 0.72, P < 0.0001), LDL:HDL ratio (r = 0.46, P = 0.01), cholesterol:HDL ratio (r = 0.55, P = 0.002), and triglycerides (r = 0.39, P = 0.032), but not to other lipid indices at baseline. Change in fructosamine over 8 weeks was significantly correlated with change in HbA1c (r = 0.63, P = 0.0001), glucose (r = 0.39, P = 0.029), cholesterol (r = 0.65, P < 0.0001), LDL (r = 0.55, P = 0.001), LDL:HDL ratio (r = 0.53, P = 0.003), and cholesterol:HDL ratio (r = 0.52, P = 0.002), and was more strongly related to change in lipid values than were other indices of glycemia.ConclusionsFructosamine was significantly correlated with measures of dyslipidemia and glycemia both at baseline and over time, and may represent a relatively sensitive and low cost index of short to medium term change in both glycemia and certain lipid profiles. However, findings from this small pilot study should be interpreted with caution, and warrant replication in larger prospective studies.     

Sex hormone levels are not associated with progression of renal disease in male patients with T2DM

BackgroundGreater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM.ObjectiveThis study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients.Population and methodsTotal testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n = 513) and without (n = 222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD).ResultWith the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8 pmol/L [P = 0.0246] and 2.59 vs 2.36 pmol/L [P = 0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD.ConclusionAlthough positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.