A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population

Aim

Recent genome-wide association scans (GWAS) and replication studies have expanded the list of validated type 2 diabetes (T2DM) susceptibility loci. We replicated T2DM association of 19 SNPs from 15 candidate loci in Lebanese Arabs.

Methods

Case–control association study, comprising 995 T2DM patients and 1076 control participants. We genotyped by the allelic discrimination method 19 SNPs in/near ADAM30, NOTCH2, THADA, TMEFF2, COL8A1, ADAMTS9-AS2, WFS1, JAZF1, SLC30A8, KCNQ1, LOC387761, ALX4, TSPAN8, FTO, and HNF1.

Results

Allele frequencies of the tested SNPs were comparable with those of Caucasians. COL8A1 rs792837 (P = 2.9 × 10⁻⁹), KCNQ1 rs2237892 (P = 1.8 × 10⁻¹⁸) and rs2237895 (P = 0.002), ALX4 rs729287 (Pc = 7.5 × 10⁻⁵), and HNF1 rs4430796 (P = 0.003) were significantly associated with T2DM, with similar effect sizes to those of Europeans. While FTO rs8050136 and rs17817449, ADAMTS9 rs4607103, and WFS1 rs10010131 were initially associated with T2DM, this was lost upon multiple testing correction. The remaining variants were not associated with T2DM, possibly resulting from insufficient power to detect smaller allele effects.

Conclusion

In addition to previous findings on the association of IGF2BP2, CDKAL1, TCF7L2 variants with T2DM among Lebanese, here we extend these by validating the association of five additional loci with T2DM in Lebanese Arabs.     

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

Aims/hypothesis  New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods  The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A−CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results  Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34–1.79, p = 4.17 × 10⁻⁹) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29–1.72, p = 1.05 × 10⁻⁷) in the CDKN2A−CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09–1.49, p = 0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01–1.38, p = 0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07–1.43, p = 0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03–2.43, p = 0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A–CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation  Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. Y. M. Cho and T. H. Kim contributed equally to this study.     

Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes

Aims

Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case–control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association.

Methods

Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender.

Results

In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT + GG, 95% CI = 1.10–2.96, p = 0.019) and 1.89 for rs1063537 CC (vs. CT + TT, 95% CI = 1.15–3.11, p = 0.013). In the Kaplan–Meier survival curve, males carrying rs2241766 TT (vs. GT + GG, p = 0.050) and rs1063537 CC (vs. CT + TT, p = 0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r² ≥ 0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN.

Conclusions

ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations.     

Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Aims

Recent epidemiological studies indicated that use of metformin might decrease the risk of various cancers among patients with type 2 diabetes mellitus (T2DM). However, its influence on pancreatic cancer was controversial. Therefore, we did a meta-analysis of currently available observational studies on the issue.

Methods

We did a PubMed and ISI Web of Science search for observational articles. The pooled relative risk (RR) was estimated using a random-effect model. Heterogeneity was evaluated using I² statistic. Subgroup analysis was performed to explore the source of heterogeneity and confirm the overall estimates. Publication bias was also examined.

Results

The analysis included 11 articles (13 studies) comprising 10 cohort studies and 3 case–control studies. Use of metformin was associated with a significant lower risk of pancreatic cancer [RR 0.63, 95% confidence internal (CI) 0.46–0.86, p = 0.003]. In a total 11 subgroup analyses, 5 provided the consistent result with pooled effect estimates of overall analysis. No publication bias was detected by Begg's (Z = −0.79, p = 0.428) and Egger's test (t = −0.92, p = 0.378).

Conclusions

From present observational studies, use of metformin appears to be associated with a reduced risk of pancreatic cancer in patients with T2DM. Further investigation is needed.     

Do physicians with diabetes have differences in dialysis use and survival than other patients with diabetes

Aims

To assess whether the increased knowledge and resources available to physicians led to differences in dialysis and survival rates between physicians and non-physician patients with diabetes.

Methods

All newly diagnosed (1997–2009) type 2 diabetes patients aged ≥35 years from the National Health Insurance Program of Taiwan database were included. After propensity score matching (1:10), we estimated the relative risk of dialysis and death using Cox proportional hazards model adjusted for demographic characteristics and comorbidities.

Results

Physicians with diabetes were more likely to start dialysis than general patients, with a 48% increased hazard risk (HR) (P = 0.006). Physicians with diabetes had significantly lower risk of death (HR: 0.88; P = 0.025). However, those requiring dialysis had a non-significant increased risk of death (HR: 1.19). There was an increased HR for death in older physicians (HR: 1.81; P < 0.001) and those with cancer or catastrophic illness. The HR of dialysis (7.89; P < 0.0001) increased dramatically with increasing Charlson Comorbidity Index scores.

Conclusions

Physicians with DM survived longer than other patients with diabetes, likely benefiting from their professional resources in disease control and prevention. Nonetheless, they displayed no advantage from their medical backgrounds compared with the general patients if they developed end stage renal disease.     

Carotid intima-media thickness progression predicts cardiovascular events in Japanese patients with type 2 diabetes

Aims

The aim of this retrospective study was to investigate the relationship between progression of carotid intima-media thickness (cIMT) and cardiovascular events in Japanese patients with type 2 diabetes mellitus (T2DM) and free of history of cardiovascular events.

Methods

Patients with T2DM (n = 342) without history of cardiovascular events whose cIMT was assessed more than twice by ultrasonography were recruited and followed up for cardiovascular events.

Results

During a mean follow-up of 7.6 years, 56 (16.4%) cardiovascular events (27 coronary events and 29 cerebrovascular events) were recorded. Multivariate analysis with the Cox proportional hazard model identified cIMT progression as a significant determinant of cardiovascular events, with a hazard ratio (HR) of 2.24 (95% confidence interval; CI, 1.25–4.03, P < 0.01), in addition to baseline cIMT. The Kaplan–Meier curves also showed significantly higher event rate in patients with high cIMT progression compared with those with low cIMT progression (log-rank χ² = 6.65; P < 0.01). Furthermore, the combination of high baseline cIMT and high cIMT progression was a significant predictor of cardiovascular events.

Conclusion

Our findings suggest that cIMT progression, in addition to baseline cIMT, is a predictor of cardiovascular events in patients with T2DM without history of cardiovascular events, and that the combination of cIMT progression and baseline cIMT has a strong predictive power for such events.     

Replication of recently described type 2 diabetes gene variants in a South Indian population

Recent genomewide association studies have identified several new gene variants associated with type 2 diabetes mellitus (T2D) mostly in European populations. These need to be replicated in other populations. We studied 926 unrelated T2D and 812 normal glucose-tolerant subjects randomly selected from the Chennai Urban Rural Epidemiology Study in Southern India. A total of 45 single nucleotide polymorphisms (SNPs) from 15 genes and 13 unannotated loci identified from recent genomewide association T2D studies were genotyped. Only 6 of 45 SNPs studied were replicated in this South Indian population. Three SNPs—rs7756992 (P = .007), rs7754840 (P = .015), and rs6931514 (P = .029)—of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population. Large-scale studies are needed in our population to validate our findings.     

The increasing detection of asymptomatic left ventricular dysfunction in patients with type 2 diabetes mellitus without overt cardiac disease: Data from the SHORTWAVE study

Aims

Type 2 diabetes mellitus (DM) is associated with higher risk of heart failure. Over the last three decades several studies demonstrated the presence of asymptomatic systolic and/or diastolic left ventricular (LV) dysfunction (asymLVD) in patients with normal LV ejection fraction (LVEF). Purpose of our study was to assess the prevalence and factors associated with asymLVD in DM patients by echocardiographic indexes more sensitive than LVEF and transmitral flow detected by pulsed Doppler.

Methods

386 DM patients without overt cardiac disease were enrolled from January to October 2011. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S′) were considered as indexes of systolic function of circumferential and longitudinal myocardial fibers, respectively. Early diastolic velocity of transmitral flow was divided by early diastolic Tissue Doppler velocity of mitral annulus for identifying diastolic LVD.

Results

asymLVD was detected in 262 patients (68%). 106 (27%) had isolated systolic asymLVD, 61 (16%) isolated diastolic asymLVD; in 95 (25%) systolic and diastolic asymLVD coexisted. Patients with asymLVD were older, had lower glomerular filtration rate, higher levels of glycated hemoglobin, C reactive protein, LV mass, relative wall thickness and prevalence of valve calcifications. Older age (HR 1.1 [1.02–1.18], p = 0.01), aortic valve calcifications (HR 6.3 [1.31–30.31], p = 0.02), LV concentric geometry defined as relative wall thickness ≥0.43 (HR 15.44 [2.96–80.44], p = 0.001) were independent predictors of asymLVD at multivariate analysis.

Conclusions

Using suitable echocardiographic indexes, asymLVD is detectable in two/third of DM patients without overt cardiac disease and is predicted by older age, cardiac valve calcifications and LV concentric remodeling.     

Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City

Background

Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City.

Methods

We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARγ, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model.

Results

The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non‐synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism.

Conclusions

Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non‐synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS. Copyright © 2010 John Wiley & Sons, Ltd.     

The impact of insulin type on severe hypoglycaemia events requiring inpatient and emergency department care in patients with type 2 diabetes

Aims

To evaluate the risk from different insulin types on severe hypoglycaemia (SHG) events requiring inpatient (IP) or emergency department (ED) care in patients with type 2 diabetes.

Methods

Type 2 diabetes patients newly started on insulin in a large commercial claims database were evaluated for SHG events. Patients were classified into an insulin group based on their most frequently used insulin type. Multivariable Cox models assessed the association between insulin type and the risk of SHG events.

Results

We identified 8626 patients (mean age 53.5 years; 55% female) with type 2 diabetes followed for an average of 4.0 years after insulin initiation. Of these, 161 (1.9%) had a SHG event at an average of 3.1y after insulin initiation. Patients with SHG events were slightly older (56.4 vs. 53.4 years), used a similar number of OADs (1.1 vs. 1.2) but had more co-morbidities compared with those without SHG events. In multivariate Cox models, premixed insulin (HR 2.12; p < 0.01), isophane insulin (NPH) (HR 2.02; p < 0.01), and rapid acting insulin (HR 2.75; p < 0.01) had significantly higher risks of SHG events compared with glargine. No statistically significant difference in SHG events was seen with detemir (HR 1.20; p = 0.73).

Conclusions

Among patients with type 2 diabetes, the use of newer basal insulin analogues was associated with lower rates of SHG events requiring IP or ED care compared with users of other insulin formulations. Future research should examine the impact of hypoglycaemia events of different severity levels.     

The relationship between central hemodynamics,morning blood pressure surge,glycemic control and sodium intake in patients with type 2 diabetes and essential hypertension

Aims

The current study aimed to investigate the relationship between morning blood pressure surge (MBPS), hemodynamic parameters, glycemic control and 24-h urinary sodium excretion (USE) in patients with type 2 diabetes mellitus (T2DM).

Materials and methods

MBPS and central hemodynamic parameters were assessed from ambulatory blood pressure measurements. In addition to routine biochemistry, 24 h urine collection was performed to measure protein, albumin and sodium excretion.

Results

There were 146 (38%) patients with T2DM and 238 (72%) patients without T2DM (control group). Patients with T2DM had statistically higher MBPS compared with patients without T2DM (P < 0.0001). In patients with T2DM, MBPS was correlated with HbA1c (rho = 0.311, P < 0.0001), 24 h urinary sodium excretion (USE) (rho = 0.292, P = 0.004) and various hemodynamic parameters. Additionally, regression analysis showed that being male (P = 0.006), the presence of coronary artery disease (P = 0.023), HbA1c (P = 0.012), and 24 h USE (P = 0.001) were independently related with log MBPS in T2DM patients.

Conclusion

This study demonstrated that T2DM was an independent risk factor for increased MBPS and MBPS was associated with central hemodynamic parameters. Additionally poor glycemic control and sodium intake were associated with worse MBPS in T2DM.     

Polymorphisms in the <Emphasis Type="Italic">TCF7L2</Emphasis>, <Emphasis Type="Italic">CDKAL1</Emphasis> and <Emphasis Type="Italic">SLC30A8</Emphasis> genes are associated with impaired proinsulin conversion

Aims/hypothesis Variation within six novel genetic loci has been reported to confer risk of type 2 diabetes and may be associated with beta cell dysfunction. We investigated whether these polymorphisms are also associated with impaired proinsulin to insulin conversion. Methods We genotyped 1,065 German participants for single nucleotide polymorphisms rs7903146 in TCF7L2, rs7754840 in CDKAL1, rs7923837 and rs1111875 in HHEX, rs13266634 in SLC30A8, rs10811661 in CDKN2A/B and rs4402960 in IGF2BP2. All participants underwent an OGTT. Insulin, proinsulin and C-peptide concentrations were measured at 0, 30, 60, 90 and 120 min during the OGTT. Insulin secretion was estimated from C-peptide or insulin levels during the OGTT using validated indices. We used the ratio proinsulin/insulin during the OGTT as indicator of proinsulin conversion. Results In our cohort, we confirmed the significant association of variants in TCF7L2, CDKAL1 and HHEX with reduced insulin secretion during the OGTT (p < 0.05 for all). Variation in SLC30A8, CDKN2A/B and IGF2BP2 was not associated with insulin secretion. The risk alleles of the variants in TCF7L2, CDKAL1 and SLC30A8 reduced proinsulin to insulin conversion (p < 0.05 for all), whereas the risk alleles in HHEX, CDKN2A/B and IGF2BP2 were not associated with reduced proinsulin to insulin conversion (p > 0.6). Conclusions/interpretation Diabetes-associated variants in TCF7L2 and CDKAL1 impair insulin secretion and conversion of proinsulin to insulin. However, both aspects of beta cell function are not necessarily linked, as impaired insulin secretion is specifically present in variants of HHEX and impaired proinsulin conversion is specifically present in a variant of SLC30A8. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: A meta-analysis

Aims

Visceral adipose tissue-derived serpin (vaspin) was identified as a new adipocytokine. Many studies reported vaspin concentrations in obese subjects and type 2 diabetes mellitus (T2DM) patients. However, large variation in levels of vaspin seen in different studies may be attributable to differences of sample size. The aim of this study is to establish an accurate confidence interval of vaspin levels in obese subjects and T2DM patients using a large-scale meta-analysis.

Methods

Publications of the association between vaspin and obesity and T2DM in the databases of Medline, PubMed and EMBase were collected. The keywords included “vaspin” and “visceral adipose tissue-derived serpin”. Review manager 5.0 was used to process the data.

Results

For the analysis of obesity, 6 studies with 1826 participants were included in our meta-analysis; the level of vaspin was 0.52 ng/ml [95% confidence interval (CI)](0.10–0.93, P = 0.02) higher in obese subjects than that in non-obese healthy controls. Eleven studies with 1570 patients were included for the analysis of T2DM; the level of vaspin was 0.36 ng/ml [95%CI] (0.23–0.49, P < 0.00001) higher compared with that in healthy controls.

Conclusions

Significantly higher levels of serum vaspin were observed in obese subjects and T2DM patients.     

Effect of gender on treatment outcomes in type 2 diabetes mellitus

Aim

To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy.

Methods

This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment.

Results

Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c ≤ 7.0% (53 mmol/mol) (54.3% vs 60.8%, respectively, p = 0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p = 0.4625). Females had significantly greater reductions in FPG (3.1 mg/dL, p = 0.0458), required significantly higher insulin doses (0.03 IU/kg, p = 0.0071), and had significantly higher annual rates of symptomatic (p < 0.0001), glucose-confirmed (<50 and <70 mg/dL) symptomatic (p = 0.0005 and p < 0.0001), and severe hypoglycemia (p = 0.0020) than males.

Conclusions

Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.     

A farnesoid X receptor polymorphism predisposes to spontaneous bacterial peritonitis

Background

In mice, the farnesoid X receptor is involved in bacterial translocation, which can result in spontaneous bacterial peritonitis in patients with cirrhosis. We investigated if polymorphisms in the farnesoid X receptor gene influence the risk for spontaneous bacterial peritonitis.

Methods

Laboratory and clinical data of 293 cirrhotic patients with ascites and 226 healthy controls were prospectively collected. The rs56163822, rs11110390 and rs12313471 polymorphisms of the farnesoid X receptor were determined.

Results

115 (39%) patients had spontaneous bacterial peritonitis. Distribution of all farnesoid X receptor genotypes matched the Hardy–Weinberg equilibrium. Patients with spontaneous bacterial peritonitis had a higher frequency of the rs56163822 GT genotype (7.0%) than patients without (1.7%, OR = 4.4, p = 0.02). This genotype was confirmed as predictor of spontaneous bacterial peritonitis by binary logistic regression analysis (OR = 6.8, p = 0.018).

Conclusion

The farnesoid X receptor rs56163822 GT genotype increases the risk for spontaneous bacterial peritonitis in cirrhotic patients with ascites.     

Correlations between serum levels of 25-hydroxyvitamin D and carotid atherosclerosis in patients with type 2 diabetes in Shanghai

Objective

To explore the potential association between the serum levels of 25-hydroxyvitamin D [25(OH)D] and carotid atherosclerosis in patients with type 2 diabetes.

Material and methods

Three hundred and fifty patients with type 2 diabetes were enrolled in this study in Shanghai, China. B-mode ultrasound was used to detect carotid plaques as indicators of atherosclerosis and measure carotid artery intima-media wall thickness (C-IMT) at two sites of carotid artery. Subjects were divided into group A (patients with carotid plaques) and group B (patients without carotid plaques) and be assessed clinically. Serum levels of 25(OH)D and other clinical parameters were measured. Multivariate logistic regression was performed to find predictors of carotid atherosclerosis in the entire group.

Results

The levels of serum 25(OH)D were lower in group A than in group B[19.60 (13.30–25.73) vs 23.19 (18.10–30.06) ng/ml, P < 0.001]. The C-IMT levels [(1.00 ± 0.17 vs 0.88 ± 0.20) mm, P_trend < 0.001] and proportion of people with carotid plaques(44/88 vs 20/87, P_trend < 0.001) in the lowest quartile of 25(OH)D were higher than in the highest quartile. Vitamin D concentrations were inversely associated with HbA1c in women(r = −0.194, P = 0.006), and C-IMT in men(r = −0.409, P < 0.001). Logistic regression analysis showed age, male sex, current smoke, history of hypertension, SBP, LDL-C and lg[25(OH)D] (OR: 0.924, 95%CI: 0.893–0.955, P < 0.001) were independently associated with the presence of carotid plaques in T2DM.

Conclusions

Serum vitamin D level is significantly and independently associated with carotid atherosclerosis in patients with T2DM in Shanghai, China.     

Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes

Aims

We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.

Methods

Population-based, cross-sectional study conducted 2010–2012 including residents 30–75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.

Results

In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes.In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97–0.99) vs. OR 0.95, 0.92–0.99), as indicated by an interaction between country of birth and ISI (P_interaction = .044).

Conclusion

This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.     

Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus

Aim

Our study aimed to examine the prevalence of non-diabetic renal disease in selected patients with type 2 diabetes mellitus and to determine important risk factors for non-diabetic renal disease.

Methods

We conducted retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetes mellitus patients in whom renal biopsies were performed from January 2004 to February 2013 at Dubrava University Hospital Zagreb Croatia (n = 80).

Results

According to renal biopsy findings, isolated diabetic nephropathy was found in 46.25%, non-diabetic renal disease superimposed on diabetic nephropathy in 17.5% and isolated non-diabetic renal disease in 36.25% of the patients. The most common non-diabetic renal diseases found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In univariate analysis shorter duration of diabetes, independence of insulin therapy, lower levels of HbA1c and absence of diabetic retinopathy were found to be significant clinical predictors of non-diabetic renal disease. In multivariate analysis only independence of insulin therapy (OR 4.418, 95%CI = 1.477–13.216) and absence of diabetic retinopathy (OR 5.579, 95%CI = 1.788–17.404) were independent predictors of non-diabetic renal disease.

Conclusions

This study confirmed usefulness of renal biopsy in patients with type 2 diabetes mellitus, due to the high prevalence of non-diabetic renal disease found. Since non-diabetic renal disease are potentially curable, we should consider renal biopsy in selected type 2 diabetes mellitus patients with renal involvement, especially in those with absence of diabetic retinopathy and independence of insulin therapy.     

The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes

Background

The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk.

Methods

In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR < 20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death.

Results

During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR < 20% (n = 79), 20–39% (n = 182) and ≥ 40% (n = 257), respectively, p = 0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model < 0.001). HRR < 20% was associated with 9-fold increased risk (p = 0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p = 0.004). Participants with both abnormal MPI and HRR (n = 8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n = 234), were at extremely low risk (≤ 1%, log-rank p < 0.001).

Conclusions

In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management.     

Association between rs13266634 C/T polymorphisms of solute carrier family 30 member 8 (SLC30A8) and type 2 diabetes, impaired glucose tolerance, type 1 diabetes--a meta-analysis

Aims

To investigate the association of solute carrier family 30 member 8 (SLC30A8) rs13266634 C/T polymorphism with type 2 diabetes (T2DM), impaired glucose tolerance (IGT), and type 1 diabetes (T1DM).

Methods

We searched all the publications about the association between SLC30A8 and diabetes from PubMed, and evaluated the association between SLC30A8 rs13266634 C/T polymorphism and T2DM, IGT and T1DM, respectively, by meta-analysis of all the validated studies. Allelic and genotypic comparisons between cases and controls were evaluated.

Results

Thirty six studies were included in the meta-analysis: 31 studies were analysed for rs13266634 C/T polymorphism with T2DM, 3 studies with IGT and 4 studies with T1DM. The pooled odds ratios (ORs) for allelic and genotypic comparisons (including additive model, co-dominant model, dominant model and recessive model) showed that rs13266634 C/T polymorphism was significantly associated with increased T2DM risk: OR = 1.15, 95% confidence interval (CI) = 1.13-1.17, P < 0.001, P_{heterogeneity} = 0.041, OR = 1.34, 95% CI = 1.26-1.41, P < 0.001, P_{heterogeneity} = 0.908, OR = 1.20, 95% CI = 1.16-1.24, P < 0.001, P_{heterogeneity} = 0.699, and OR = 1.23, 95% CI = 1.17-1.30, P < 0.001, P_{heterogeneity} = 0.801, respectively. In subgroup analyses, we found that rs13266634 C/T polymorphism was associated with T2DM risk both in Asian and European subgroup (P < 0.001), but not in African (P > 0.05). And the pooled odds ratio (OR) for allelic frequency comparison showed that rs13266634 C/T polymorphism was also significantly associated with IGT: OR = 1.15, 95% CI = 1.06-1.26, P < 0.001, P_{heterogeneity} = 0.364. Meanwhile, our meta-analysis did not suggest that rs13266634 C/T polymorphism was associated with T1DM risk (P > 0.05): OR = 1.02, 95% CI = 0.98-1.06, P = 0.328, P_{heterogeneity} = 0.488 for allelic frequency comparison.

Conclusions

Our meta-analysis results revealed the significant association between rs13266634 C/T polymorphism and T2DM and IGT, but did not support the association between this polymorphism and T1DM.