Risk Of Diabetic Microvascular Complications Research Articles

Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Long-term exposure to ambient air pollution and risk of microvascular complications among patients with type 2 diabetes: a prospective study.

Patients with type 2 diabetes (T2D) may disproportionately suffer the adverse cardiovascular effects of air pollution, but relevant evidence on microvascular outcome is lacking. We aimed to examine the association between air pollution exposure and the risk of microvascular complications among patients with T2D. This prospective study included 17 995 participants with T2D who were free of macro- and micro-vascular complications at baseline from the UK Biobank. Annual average concentrations of particulate matter (PM) with diameters <2.5 μm (PM2.5), <10 μm (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were assessed using land use regression models. Cox proportional hazards regression was used to estimate the associations of air pollution exposure with incident diabetic microvascular complications. The joint effects of the air pollutant mixture were examined using quantile-based g-computation in a survival setting. In single-pollutant models, the adjusted hazard ratios (95% confidence intervals) for composite diabetic microvascular complications per interquartile range increase in PM2.5, PM10, NO2 and NOx were 1.09 (1.04-1.14), 1.06 (1.01-1.11), 1.07 (1.02-1.12) and 1.04 (1.00-1.08), respectively. Similar significant results were found for diabetic nephropathy and diabetic neuropathy, but not for diabetic retinopathy. The associations of certain air pollutants with composite microvascular complications and diabetic nephropathy were present even at concentrations below the World Health Organization limit values. Multi-pollutant analyses demonstrated that PM2.5 contributed most to the elevated risk associated with the air pollutant mixture. In addition, we found no interactions between air pollution and metabolic risk factor control on the risk of diabetic microvascular complications. Long-term individual and joint exposure to PM2.5, PM10, NO2 and NOx, even at low levels, was associated with an increased risk of diabetic microvascular complications, with PM2.5 potentially being the main contributor.

The Difference Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Risk of Diabetic Microvascular Complications Among Adults With Diabetes: A Population-Based Cohort Study.

The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients.

Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

High triglyceride levels increase the risk of diabetic microvascular complications: a cross-sectional study

BackgroundThe prevalence of microvascular complications in type 2 diabetes mellitus (T2DM) is increasing. The effect of lipid profiles on diabetic microvascular complications remains debated. This research aimed to study the correlation between lipid profiles and microvascular complications.MethodsThis retrospective cross-sectional study included 1096 T2DM patients. The patients were divided into the control, diabetic retinopathy (DR), nephropathy (DKD), and peripheral neuropathy (DPN) groups based on the existence of corresponding complications. The lipid profiles were analyzed, and the effect on complications was assessed by logistic regression.ResultsCompared with the control group, the diabetic microvascular complications group had a higher dyslipidemia rate. The rate of high TGs increased significantly with an increasing number of complications. High TG levels contributed to the risk of DKD, DR, and DPN [odds ratios (ORs): 2.447, 2.267, 2.252; 95% confidence interval: 1.648–3.633, 1.406–3.655, 1.472–3.445]. In the age (years) > 55, T2DM duration (years) > 10, and HbA1c (%) ≥ 7 groups, the risk of high TGs was higher for DKD (ORs: 2.193, 2.419, 2.082), DR (ORs: 2.069, 2.317, 1.993), and DPN (ORs: 1.811, 1.405, 1.427).ConclusionHigh TG levels increase the risk of diabetic microvascular complications, and patients with older age, longer T2DM duration, and higher HbA1c levels are recommended to keep lipid levels more strictly.

Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study.

The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications. A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and β-crosslaps (β-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications. After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, β-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and β-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD. Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.

Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.

Statins and renal disease progression, ophthalmic manifestations, and neurological manifestations in veterans with diabetes: A retrospective cohort study

Statins increase insulin resistance, which may increase risk of diabetic microvascular complications. Little is known about the impact of statins on renal, ophthalmologic, and neurologic complications of diabetes in practice. The objective of this study was to examine the association of statins with renal disease progression, ophthalmic manifestations, and neurological manifestations in diabetes. This is a retrospective cohort study, new-user active comparator design, that included a national Veterans Health Administration (VA) patients with diabetes from 2003 to 2015. Patients were age 30 years or older and were regular users of the VA with data encompassing clinical encounters, demographics, vital signs, laboratory tests, and medications. Patients were divided into statin users or nonusers (active comparators). Statin users initiated statins and nonusers initiated H2-blockers or proton pump-inhibitors (H2-PPI) as an active comparator. Study outcomes were: 1) Composite renal disease progression outcome; 2) Incident diabetes with ophthalmic manifestations; and 3) Incident diabetes with neurological manifestations. Out of 705,774 eligible patients, we propensity score matched 81,146 pairs of statin users and active comparators. Over a mean (standard deviation) of follow up duration of 4.8 (3) years, renal disease progression occurred in 9.5% of statin users vs 8.3% of nonusers (odds ratio [OR]: 1.16; 95% confidence interval [95%CI]: 1.12-1.20), incident ophthalmic manifestations in 2.7% of statin users vs 2.0% of nonusers (OR: 1.35, 95%CI:1.27-1.44), and incident neurological manifestations in 6.7% of statin users vs 5.7% of nonusers (OR: 1.19, 95%CI:1.15-1.25). Secondary, sensitivity, and post-hoc analyses were consistent and demonstrated highest risks among the healthier subgroup and those with intensive lowering of LDL-cholesterol. Statin use in patients with diabetes was associated with modestly higher risk of renal disease progression, incident ophthalmic, and neurological manifestations. More research is needed to assess the overall harm/benefit balance for statins in the lower risk populations with diabetes and those who receive intensive statin therapy.

Tea consumption and long-term risk of type 2 diabetes and diabetic complications: a cohort study of 0.5 million Chinese adults

ABSTRACTBackgroundEvidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes.ObjectivesWe aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes.MethodsThis study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30–79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs.ResultsThe mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers.ConclusionsIn Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications.

Genetic variants of ABCC8 and phenotypic features in Chinese early onset diabetes.

ABCC8 variants cause neonatal diabetes, maturity onset diabetes of the young (MODY), and hyperinsulinemic hypoglycemia because of activating or inactivating variants. In this study we used targeted exon sequencing to investigate genetic variants of ABCC8 and phenotypic features in Chinese patients with early onset diabetes (EOD). A cross-sectional study of 543 Chinese patients with EOD was recruited and the exons of them were conducted targeted sequencing. The pathogenicity of ABCC8 variants was defined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline. The phenotypes of patients owing to ABCC8 variants (ABCC8-MODY) were characterized. Among the 543 participants, eight (1.5%) patients with ABCC8-MODY were identified. They harbored eight missense ABCC8 variants (p.R306C, p.E1326K, and p.R1379H, previously reported; p.R298C, p.F1176C, p.R1221W, p.K1358R, and p.I1404V) classified as likely pathogenic. Two family members with ABCC8-MODY were also confirmed. The average diagnosed age of the 10 patients was 26.8 ± 12.9 years. The majority of them had unsatisfactory glucose control, 80% of them had diabetic kidney disease, and neurological features were not observed. Using targeted exon sequencing followed by pathogenicity analysis, we could be able to make genetic diagnoses for eight (1.5%) patients with ABCC8-MODY. The phenotype was variable with higher risk of diabetic microvascular complications. Genetic diagnosis is conducive for facilitating the personalized treatment of ABCC8-MODY.

The Correlation between Time in Range and Diabetic Microvascular Complications Utilizing Information Management Platform.

Background In recent years, the time of blood glucose within the target range is a new research hotspot in blood glucose management. TIR is expected to be a novel indicator for evaluating the efficacy of glycemic control and predicting diabetic complications. However, its relationship with diabetic complications has not been fully elucidated. Objective To explore the relationship between time in range (TIR) and glycosylated hemoglobin (HbA1C) through the information big data management platform. Possible association between TIR and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was investigated, attempting to provide theoretical basis for the clinical application of TIR and to explore the TIR control scope suitable for diabetic patients. Methods A total of 5,644 type 2 diabetic patients hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Nanchang University, were selected from April 2017 to June 2020. Fingertip capillary blood glucose monitoring (FCGM) was monitored for a total of 455,664 times, and patients who are nondiabetic, pregnant, or with diabetic ketosis were excluded. Patients with 7 blood glucose points monitored for at least three consecutive days were selected as subjects in the study. 1,895 males and 1,513 females with diabetes were included, with an average age of (59.74 ± 13.40) years old and an average course of disease of 8.28 ± 7.11 years. The proportion of time in range (TIR) (70∼180 mg/dl) within the target range and the correlation between TIR and HbA1C were analyzed, as well as the relationship between TIR and the risk of diabetic complications. Results (1) The average of TIR and HbA1C was 49.65 ± 23.36% and 8.92 ± 2.49%, respectively, and was linearly correlated. With the decrease of TIR, HbA1C increased significantly, and the difference was statistically significant (P < 0.01, R2 = 0.458). The correlation coefficient of mean TIR with mean HbA1C was −0.626. (2) There were 836 patients diagnosed with diabetic nephropathy (DN). The difference of TIR value between DN and non-DN was significant (T = 2.250, P < 0.05). Risk assessment showed the lower the TIR was, the higher the risk of DN was. TIR less than 40% was a risk factor for DN (OR = 1.249, 95% CI: 0.915–1.375). (3) There were 1,296 patients diagnosed with diabetic peripheral neuropathy (DPN). The difference of TIR value between DPN and non-DPN was significant (T = 3.844, P < 0.01). TIR value less than 70% was a risk factor for DPN (OR = 1.030, 95% CI: 0.769–1.379). (4) There were 2,077 patients diagnosed with diabetic retinopathy (DR). The difference of TIR value between DPN and non-DPN was significant (T = 3.608, P < 0.01). TIR value less than 50% was a risk factor for DR (OR = 1.092, 95% CI: 0.898–1.264). Summary. TIR may serve as a reference index for short-term blood glucose control, strongly reflecting the clinical blood glucose regulation and predicting the risk of diabetic microvascular complications.

SGLT2 inhibitors and the changing landscape for treatment of diabetes.

Type 2 diabetes mellitus has become an epidemic with rapidly increasing prevalence worldwide. While strict glycemic control has been shown to reduce the risk of diabetic microvascular complications, its role in preventing cardiovascular disease has been less clear. Indeed, anti-hyperglycemic therapies have historically been neutral for cardiovascular benefit. However, recent cardiovascular outcome trials utilizing sodium glucose transporter 2 inhibitors across a broad spectrum of cardiovascular disease patients have demonstrated significant mortality benefit resulting in a paradigm shift in the approach towards patients with heart disease and diabetes mellitus.

531-P: Weight Change and the Incidences of End-Stage Renal Disease and Proliferative Diabetic Retinopathy in Patients with Newly Diagnosed Diabetes Mellitus: A Nationwide Cohort Study

Aims/Hypothesis: This study aimed to investigate the impact of weight changes on the clinical outcomes of diabetic nephropathy and retinopathy among patients with newly diagnosed diabetes. Methods: Using nationally representative data from the Korean National Health Insurance System, 181,872 patients newly diagnosed with diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007-2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. Results: There were 180 cases of ESRD (0.10%) and 780 cases of PDR (0.43%) followed-up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with moderate weight gain (+5% to +10%) showed a significantly higher hazard ratio (HR) for ESRD, compared with those with modest weight changes (−5% to +5%) after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.732; 95% CI 1.125-2.667). Those with severe weight loss (−5% to −10%) showed the lowest HR for PDR (HR, 0.591; 95% CI 0.372-0.938), whereas those with severe weight gain (> +10%) showed the highest HR for PDR (HR, 1.732; 95% CI 1.125-2.667). Conclusion: This study provides direct evidence that a change in body weight affects the risk of diabetic microvascular complications. Strategies to control body weight may reduce the risk of ESRD and PDR in patients with newly diagnosed diabetes. Disclosure H. Kwon: None. K. Song: None.

Associations between erythropoietin polymorphisms and risk of diabetic microvascular complications

We conducted a meta-analysis to evaluate the relationship between erythropoietin (EPO) polymorphisms and diabetic microvascular complications. We searched the PubMed, Embase, Cochrane library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases for appropriate studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations. Ultimately, eight studies consisting of 2,861 cases and 2,136 controls were identified and included in our meta-analysis. Results with our genotype model indicated an association between rs1617640 polymorphisms and diabetic microvascular complications (TT vs. GG: OR = 1.544, 95% CI = 1.089–2.189, P = 0.015). No clear associations between the rs1617640 and rs507392 polymorphisms and diabetic retinopathy were observed. By contrast, rs551238 polymorphisms were associated with increased diabetic retinopathy risk (allele model: OR = 0.774, 95% CI = 0.658–0.911, P = 0.002; genotype model: AC vs. CC: OR = 0.598, 95% CI = 0.402–0.890, P = 0.011; dominant model: OR = 0.561, 95% CI = 0.385–0.817, P = 0.003; recessive model: OR = 0.791, 95% CI = 0.643–0.973, P = 0.026). These results indicate that EPO polymorphisms are a risk factor for diabetic microvascular complications.

Endothelial nitric oxide synthase 27VNTR (4b/4a) gene polymorphism and the risk of diabetic microvascular complications in Chinese populations.

To access the association of endothelial nitric oxide synthase (eNOS) gene 27VNTR (4b/4a) polymorphism with diabetic microvascular complications (DMI) susceptibility in Chinese populations. Data were retrieved in a systematic manner on PubMed database, ISI Web of Knowledge, the Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang, as well as manual searching of the references of the identified articles. Odds ratio (OR) and 95% confidence interval were used to evaluate the strength of associations. Potential sources of heterogeneity and publication bias were explored. Twelve published articles with thirteen outcomes including 1484 DMI patients and 1225 diabetic controls were included in the meta-analysis. The results showed no evidence for significant association of 27VNTR (4b/4a) polymorphism with DMI risk in dominant model (OR=1.36, 95% CI=0.90-2.06, P=0.15), and similar results were obtained in the allelic, additive and the recessive models (P﹥0.05).Our meta-analysis suggests that eNOS gene 27VNTR (4b/4a) polymorphism might not be a risk factor for DMI in Chinese populations.

Serum Magnesium Concentration Is Inversely Associated with Albuminuria and Retinopathy among Patients with Diabetes.

Aim. To investigate the association between serum magnesium levels and microvascular complications among patients with diabetes. Methods. Patients with diabetes were recruited between April 2012 and January 2015. All patients received an assay of serum magnesium concentration, were screened for 24 h albumin excretion rate, and underwent nonmydriatic fundus photography. Albuminuria and retinopathy were defined accordingly. A total of 3,100 patients with normal serum magnesium levels were included in this study. Results. Patients with albuminuria and/or retinopathy had lower levels of serum magnesium than patients without these complications (P < 0.001). The prevalence of isolated albuminuria, isolated retinopathy, and combined albuminuria and retinopathy decreased as the concentration of serum magnesium increased. Multiple logistic regression analysis indicated that the odds ratio for isolated albuminuria, isolated retinopathy, and concomitant albuminuria and retinopathy decreased by approximately 20% for every 0.1 mmol/L increase in serum magnesium concentration. Conclusion. Serum magnesium levels were negatively associated with the risk of diabetic microvascular complications among patients with serum magnesium levels within the normal range.

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes.

The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p < 0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age + 2 years) had a 2.30 (95% CI 1.27, 4.17; p < 0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age ± 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (< mean age - 2 years) did not have any effect on this risk. Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.

Involvement of advanced glycation end-products in 'hyperglycemic memory'.

The series of reports by the DCCT Skin Collagen Ancillary Study Group are very interesting and informative. The hypothesis from these reports clearly indicates that AGEs are a strong candidate for the mechanism of the 'hyperglycemic memory.'

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta-analysis.

Chemokine ligand 5 (CCL5) is a member of the CC-chemokine family expressed in various organs. It contributes to the migration of monocytes/macrophages into injured vascular walls by binding with its receptor chemokine receptor 5 (CCR5). Many studies have accessed the association between CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications (DMI). However, the results are conflicting and inconclusive. The aim of the present study was to evaluate the association more precisely. Trials were retrieved through PubMed, Embase, Medline, China National Knowledge Infrastructure, Web of Science and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with DMI. Data were obtained from 11 case-control studies that included 2,737 DMI patients and 2,435 diabetic control subjects. In the overall analysis, the CCL5-403 G/A and CCL5-28 C/G gene polymorphisms were not significantly associated with the risk of DMI. However, CCR5-59029 G/A was an independent risk factor of DMI in a dominant model (OR 1.77, 95% CI 1.06-2.97). Subgroup analysis showed that the risk of the CCR5 59029A-positive genotype was significant in Asians (OR 2.08, 95% CI 1.68-2.57). In addition, the CCR5 59029A-positive genotype was associated with increased risk of albuminuria. There were no associations of CCL5 gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism in CCR5 might affect individual susceptibility for DMI.

Genetics and diabetic microangiopathy

Human vital organ systems may be affected by diabetic microvascular complications (DMC), lead to public health difficulty. Recent evidence shows genetic factors provide to the genetic and structural variants, and/or variability in disease severity play important roles in the development of DMC among the patients with similar risk factors. Several genetic loci have discovered that figure the risk of DMC as detected by genetic linkage studies. Genetic variants demonstrate for susceptibility to DMC as detected by genetic association studies. Copy number variation and interactions of gene Χ environment have been discovered by compelling analysis of structural variants. Mitochondrial DNA also acts a definite role in the development of DMC. Sequencing technologies have light important horizon on detecting rare and common genetic loci. This review focuses on the common science of the genetic context of DMC. Finally, recognition of genes or genetic loci and structural variants providing to risk of or guarding from DMC will help intuition the underlying mechanism of DMC, with conclusive suggestions for the evolvement of new medicine for diabetes mellitus complications.