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).     

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory

AimsAs diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to ‘glucose memory’ by evaluating patients’ HbA1c over previous years and their skin autofluorescence (SAF).MethodsIn 334 patients with T2D and HbA1c levels ≤ 8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment].ResultsOur patients were mostly men (58.4%) aged 63 ± 10 years, with a duration of diabetes of 13 ± 10 years and HbA1c = 7.1 ± 0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods ?4 ± 3 months (n = 255), ?16 ± 4 months (n = 152), ?30 ± 4 months (n = 93) and ?62 ± 26 months (n = 105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR = 6.75, 95% CI: 1.90–23.90. Moreover, SAF values were higher in those with DR [2.95 ± 0.67 arbitrary units (AU)] vs 2.65 ± 0.65 AU with no DR (P < 0.01) and were also associated with the oldest previous HbA1c values (P < 0.01).ConclusionOur study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5 years prior to study admission and their SAF values, a marker of glucose memory.     

Serum glycated albumin predicts the progression of diabetic retinopathy—a five year retrospective longitudinal study

AimsTo assess the predictive value of glycated albumin (GA) and other risk factors on a progression of diabetic retinopathy (DR).MethodsIn this retrospective longitudinal study, we enrolled the subjects with type 2 diabetes who had undergone fundus photography twice with a 5-years gap between January 2006 and December 2012, and had been measured consecutively for hemoglobin A1c (HbA1c) and GA levels every 3 or 6 months. The subjects were divided into two groups with or without a progression of DR. The mean HbA1c and mean GA were calculated separately by the sum of all measured values divided by the numbers of values throughout the study period.ResultsOf the 359 subjects, progression group showed significantly higher diabetes duration (8.41 ± 5.72 vs. 6.46 ± 5.77, P < 0.01), baseline HbA1c (9.13 ± 2.71 vs. 8.41 ± 2.32, P < 0.05), fasting plasma glucose (8.71 ± 2.78 vs. 7.94 ± 2.63, P < 0.05), 2 h-postprandial glucose (15.12 ± 11.20 vs.13.14 ± 4.72, P < 0.05), eGFR (114.81 ± 39.15 vs. 103.23 ± 32.18, P < 0.01), mean HbA1c (8.32 ± 1.69 vs. 7.39 ± 1.35, P < 0.01) and mean GA (22.66 ± 5.92 vs. 19.83 ± 5.18, P < 0.01) than non-progression group. The frequencies of subjects with DR progression increased obviously with the increment of baseline HbA1c, mean HbA1c and mean GA according to quartile stratification of the above three glucose parameters. Multivariable binary logistic regression analysis investigated that the factors affected the DR progression were the presence of DR at baseline (OR = 0.391, P = 0.005), mean HbA1c (OR = 1.389, P = 0.021), mean GA (OR = 1.087, P = 0.039) and eGFR (OR = 1.008, P = 0.045). The optimal cut-off values of mean HbA1c and GA to predict DR progression were 7.27% and 21.85%, respectively.ConclusionsThe presence of DR at baseline, poor glycemic control, glycated albumin, and impaired renal function predicted DR progression in patients with type 2 diabetes.     

Screening for diabetic retinopathy in a rural French population with a mobile non-mydriatic camera

AimThe aim of this study was to evaluate the yield of diabetic retinopathy (DR) screening in a rural population using a mobile non-mydriatic camera.MethodsThe 72 least medicalized areas of Burgundy were the target areas. An orthoptist took fundus photographs using a Topcon TRC-NW6S non-mydriatic camera (four fields: posterior pole; nasal; temporal; and upper). Interpretations were done in the Department of Ophthalmology according to the classification of the French Language Association for the Study of Diabetes and Metabolic Diseases (Alfediam).ResultsBetween 2004 and 2006, 1974 diabetics were screened—676 the first year, and 1298 in the second. The rate of non-interpretable photographs was 13%. Of the 1974 screened patients, there were 103 cases of DR (5.2%), comprising 70 mild non-proliferative DR (68%), 21 moderate non-proliferative DR (20.4%) and 12 severe non-proliferative DR (11.6%). The mean age of the patients with a DR was 66.7 ± 10.9 years, with a mean duration of diabetes of 16.5 ± 9.8 years. Only 35 (34%) patients were aware of their HbA_1c, which had a mean value of 7.8% and 19 had visited an ophthalmologist in the year before screening (18.4%). After the initial screening, 90,5% of the patients consulted an ophthalmologist as recommended.ConclusionScreening improved the quality of the ocular follow-up in diabetics in this rural area. However, improvements in management are needed to lower the cost of such a programme.     

Effect of obesity and glycated hemoglobin on oxygen saturation in ambulatory type 2 diabetic individuals: A pilot study

AimsTissue hypoxia is an important contributor to diabetic complications. Glycation of hemoglobin (Hb) and obesity are major determinant of oxygen saturation (SpO2) in blood. Hence, the present study was planned to evaluate the effect of obesity on SpO2 in a wide range of glycated hemoglobin (HbA1c) levels in ambulatory type 2 diabetic patients.Material and methodsA cohort of 60 subjects irrespective of diabetic status were recruited and clustered in group I (HbA1c <6.5) and group II (HbA1c ≥6.5) depending on HbA1c. Anthropometry and routine biochemical parameters were measured. HbA1c (%) were estimated by high performance liquid chromatography (HPLC) respectively. SpO2 (%) levels were measured by pulse oximetry. Pearson correlation, bivariate regression and student ‘t’ test were used for statistical analysis.ResultsBlood concentration of HbA1c was <6.5 in 29 participants and ≥6.5 in 31 participants. Plasma fasting and post prandial glucose, HbA1c as well as Hb levels were significantly (p < 0.50) higher in diabetics as compared to non diabetics. Waist circumference (WC) (r = −400; p = 0.026) and body mass index (BMI) (r = −381; p = 0.034) showed a significant negative correlation with SpO2 in diabetic patients. On adjusting HbA1c in group II, SpO2 was found to independently and inversely associated with WC (p = 0.042) and BMI (p = 0.049).ConclusionsObesity was found to be a strong independent contributor to reduction in oxygen carrying capacity in ambulatory type 2 diabetic subjects. However there is no effect of glycated Hb on SpO2 in the same population.     

Association of endothelial lipase Thr111Ile polymorphism with proliferative retinopathy in type 2 diabetes patients

AimOur previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR.MethodsThis retrospective cohort study was based on a review of the institutional charts of 287 type 2 diabetes patients (mean age = 59.7 years; mean BMI = 29.0 kg/m²; mean HbA_1c = 8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813, p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT).ResultsOn univariate analysis, the minor allele homozygote TT variant was significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared with the major CC homozygote. No significant result was found for the CT heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or proliferative DR. Other associations were not significant.ConclusionMinor allele homozygosity for this EL variant (c.584C>T) could be a significant risk factor for developing severe, sight-threatening disease due to proliferative DR. Further prospective studies of this EL polymorphism in a larger population sample are needed to confirm these results.     

Change in tear protein profile in diabetic retinopathy with duration of diabetes

AimsTo study change in tear protein profile with duration of diabetes and severity of diabetic retinopathy (DR) in type 2 diabetes patients.Materials and methodsTear protein profile was ascertained by SDS PAGE method in 30 patients with DR (group A) and 37 patients without DR (group B).ResultsSix distinct bands of proteins were identified; these proteins are as follows: 91 kDa (P1), 66 kDa (P2), 60 kDa (P3), 30 kDa (P4), 18.4 kDa (P5) and 14.4 kDa (P6). Prevalence of P3 was significant (p = 0.036) in group A, especially in cases with diabetes ≤8 years compared with diabetes >8 years (p = 0.0107). In group B, P2 was significantly prevalent (p < 0.0013) in cases with diabetes ≤8 years compared to diabetes >8 years. Considering the changes in terms of duration of diabetes in general, patients with diabetes of ≤8 years, P3 was significantly prevalent in group A compared to group B (p = 0.004); and when the duration of diabetes is >8 years, P2 was found significantly more in group A compared to group B (p = 0.01). No significant difference in P3 (p = 0.025), P4 (p = 0.2877), P5 (p = 0.4801), P6 (p = 0.0985) was observed in mild to moderate NPDR group compared to severe NPDR to PDR group. P1 and P2 were present only in severe NPDR and PDR.ConclusionVariable protein expression was observed with duration of diabetes and severity of diabetic retinopathy.     

The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects

ObjectiveTo investigate how VEGF-634G/C and VEGF-460C/T SNPs are related to diabetic retinopathy (DR) in Han Chinese subjects from the Shijiazhuang region of China.MethodsTotally 376 DM cases were divided into non-proliferative diabetic retinopathy (NPDR) group (n = 124), proliferative diabetic retinopathy (PDR) group (n = 108), and diabetes without retinopathy (DWR) group (n = 144). PCR/LDRwas utilised to detect and assess the genotypes and allele distribution frequencies at the VEGF-634G/C and VEGF-460C/T loci in each group.ResultsThe differences between NPDR, PDR and DWR groups were not significant in genotypes and allele distribution frequencies at VEGF-634G/C locus (P > 0.05). But there were significant differences between NPDR and DWR groups in genotypes (P = 0.013) and allele distribution frequencies (P = 0.002) at VEGF-460C/T locus, at which CT + CC genotypes were associated with a reduced risk of developing NPDR. There were no significant differences in genotypes (P = 0.759) or allele distribution frequencies (P = 0.433) at VEGF-460C/T locus between PDR and DWR groups.ConclusionsAmong Chinese Han individuals with type-2 DM, polymorphism − 634G/C of the VEGF gene was not correlated with NPDR or PDR; however, polymorphism-460C/T of the VEGF gene was correlated with NPDR, and C allele was associated with lower NPDR risk than T allele.     

Altered fibrin-clot properties are associated with retinopathy in type 2 diabetes mellitus

AimThe development and progression of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) have been associated with poor glycaemic control, long disease duration and other clinical features. However, the pathogenesis of the complication is still poorly understood. As the formation of dense fibrin clots resistant to lysis has been described in diabetes patients, this study tested the hypothesis that altered clot structure and function are associated with DR in T2DM patients.MethodsThe study included 101 T2DM subjects without DR (NDR) and 60 with DR. Plasma fibrin-clot permeation was assessed using a pressure-driven system, and expressed as the permeation coefficient (K_s), indicating pore size, and as the time required for a 50% decrease in clot turbidity (t_50%) as a marker of susceptibility to fibrinolysis. All patients underwent ophthalmological examination. Clinical and biochemical co-variables were also measured. Determinants of DR were identified using stepwise, multivariable, logistic-regression analyses.ResultsPatients with DR had lower clot permeability (K_s: 6.15 ± 1.18 vs. 7.53 ± 1.24 10^?9 cm²; P < 0.0001) and slower fibrin-clot lysis (t_50%: 10.12 ± 1.24 vs. 9.12 ± 1.4 min; P < 0.0001) than NDR subjects. Logistic analysis revealed associations between DR and K_s, t_50%, fasting glucose and diabetes duration, as well as insulin treatment and statin non-use (P < 0.05). After adjusting for these variables as well as for age and gender, associations between K_s and t_50% with DR proved to be significant.ConclusionFormation of compact fibrin clots and impaired clot lysis are both associated with DR in T2DM patients. However, it is unclear whether these abnormalities lead to the development of DR or merely constitute a marker of its presence.     

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

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

Does insulin resistance in type 2 diabetes alter vitamin D status?

AimsData on changes of vitamin D due to insulin resistance are conflicting. We assessed vitamin D concentrations and parameters of glycemia and mineral homeostasis in patients with insulin resistant type 2 diabetes and in matched normal controls.MethodsSixty-nine patients with type 2 diabetes and 60 matched normal control subjects were studied. After an overnight fast, blood was collected for measuring the parameters of glycemia (glucose, insulin and HbA1c), mineral profile (corrected calcium, phosphate and alkaline phosphatase), total 25(OH) vitamin D and parathyroid hormone (PTH) levels.ResultsPatients had significantly elevated fasting glucose (P = 0.0001), insulin (P = 0.0003) and HbA1c (P = 0.0005) than the controls had. They had significantly raised calculated insulin resistance compared with control subjects (P = 0.0001). Patients and controls had similar levels of serum corrected calcium and ALP, whereas serum phosphate was significantly lower in the patients compared with controls (P = 0.001).Patients and controls had similar levels of 25(OH)D, but the levels of 25(OH)D in both were in the deficiency range. Intact PTH was similar in the patients and controls. Levels of 25(OH)D did not demonstrate any relation with fasting insulin, insulin resistance, or HbA1c, but correlated negatively with intact PTH (r = ?0.4, P = 0.02).ConclusionThis study demonstrated prevalent vitamin D deficiency in insulin resistant type 2 diabetic and normal subjects. Insulin resistance did not influence the status of vitamin D.     

Late afternoon blood pressure increase is associated with diabetic retinopathy in normotensive type 2 diabetes mellitus patients

AimsTo identify if the variability of blood pressure (BP) is associated with diabetic retinopathy (DR) in normotensive type 2 DM patients.MethodsSixty-five normotensive type 2 DM patients that had 24-h ambulatory BP monitoring (ABPM) were grouped according any degree of DR.ResultsFourteen (21%) patients had DR. Office BP and 24-h BP parameters did not differ between groups. At late afternoon period, patients with DR had higher increment in both systolic (11.3 ± 12.7 mmHg vs. 1.0 ± 11.4 mmHg, P = 0.006) and diastolic (6.7 ± 8.6 mmHg vs. ?0.73 ± 10.0 mmHg, P = 0.017) BP levels than those without. Multivariate logistic analyses were performed with DR as a dependent variable. Each 1 mmHg increment in systolic BP at the late afternoon period was associated with a 10.2% increase in DR prevalence [OR 1.102 (CI 95% 1.011–1.202, P = 0.027)], after adjustments for A1C test, DM duration, age, albuminuria and current smoking.ConclusionsIn conclusion, in normotensive type 2 DM patients, BP increase at late afternoon is associated to DR independently from confounder factors or other ABPM parameters.     

Severe hypoglycaemia is a major predictor of incident diabetic retinopathy in Japanese patients with type 2 diabetes

AimHypoglycaemia is a common complication in diabetes patients. However, its relationship with retinopathy has not been well documented in patients with type 2 diabetes (T2D). This study aimed to investigate the associations between hypoglycaemia and the incidence and progression of diabetic retinopathy (DR).MethodsIn this longitudinal cohort study, which was part of the Japan Diabetes Complications Study (JDCS), adult patients with T2D were recruited at 59 diabetes clinics across Japan. Their history of hypoglycaemia was assessed by standardized self-reported questionnaires. Severe hypoglycaemia was defined as having at least one episode with coma requiring an outpatients visit or hospitalization. Adjusted hazard ratios (HRs) for incidence and progression of DR over 8 years of follow-up were determined.ResultsOf 1221 patients without DR, 127 (10.4%) had experienced non-severe hypoglycaemia within the previous year, whereas 10 (0.8%) reported severe hypoglycaemia episodes. During the 8-year follow-up involving 8492 person-years, 329 patients developed DR. In 410 patients with prevalent DR, the adjusted HRs for incident DR were 4.35 (95% CI: 1.98–9.56; P < 0.01) and, for progression of DR, 2.29 (95% CI: 0.45–11.78; P = 0.32) with severe hypoglycaemia.ConclusionHaving a history of severe hypoglycaemia was one of the strongest predictors of incident DR in patients with T2D, with a fourfold increased risk. Identifying patients with greater risks of DR based on their history of hypoglycaemia may help to personalize risk evaluation in patients with diabetes.     

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset Type 1 and Type 2 Diabetes

AimTo assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y).MethodsT1DM-Y(n = 150) and T2DM-Y(n = 150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR.ResultsThe prevalence of any DR was 53.3% [95% CI 45.3–61.3] in T1DM-Y (duration of diabetes: 12.4 ±7.4years) and 52.7% [44.7–60.7] in T2DM-Y (11.8 ± 8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42–2.79], waist circumference [1.28 per 5 cm;1.05–1.56] and microalbuminuria [2.39 per 50 μg;1.07–5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61–3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18–2.02], Glycated hemoglobin [1.37 per %;1.07–1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15–2.05;] were associated with DR in T2DM-Y.ConclusionOver half of the people with young-onset diabetes, regardless of type, have retinopathy within 10–12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR.     

Status of serum magnesium in type 2 diabetes mellitus with particular reference to serum triacylglycerol levels

Magnesium (Mg) is the fourth most abundant cation in the body and the second most common intracellular cation. The association between hypomagnesemia and insulin resistance (IR) in diabetes mellitus has been documented earlier. However, we wanted to study whether the extracellular status of magnesium (Mg) could be a biochemical mediator between hypertriacylglycerolemia and diabetes mellitus.AimsTo find out the probable association among HbA1c, triacylglycerol (TG) and magnesium levels – a predictor of vascular complications in T₂DM.Materials and methodsThirty patients who had attended the diabetic clinics during the period of this study were included. All the samples were analysed for glucose, TG, Mg, and HbA1c. For statistical analysis, SPSS 17 package was used.ResultsSerum TG (236.67*, 195.06) and HbA1C (9.97*, 8.57) levels were independently compared between the two groups and were significantly high in group A subjects (Mg < 1.2 mg/dl) as compared to group B subjects (Mg > 1.2 mg/dl) (*p-value < 0.05), respectively.Discussion and conclusionHypertriacylglycerolemia was pronounced in type 2 diabetes mellitus patients with accompanying hypomagnesemia. This compared well with that of the glycemic control. Low Mg levels, high TG levels in association with enhanced HbA1c levels could thus serve as a reliable biochemical indicator of insulin status and action without resorting to the usage of criteria for insulin sensitivity and resistance.     

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.     

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan—A 3-year prospective study

AimsTo explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM).MethodsA 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR.ResultsFundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p < 0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9–6.9 mg/dl) and 4th (≥7.0 mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30–5.08 and 1.92–7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl).ConclusionsSUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.     

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.     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

V-shaped relationship between HbA1c and all-cause mortality in the elderly with type 2 diabetes

PurposeThe optimal glycemic target for elderly patients with diabetes has not been established. The purpose of this study was to elucidate relationship between HbA1c and mortality in elderly patients with diabetes.SubjectsThree hundred consecutive elderly (≥ 65 yrs) patients with type 2 diabetes mellitus admitted for control of hyperglycemia between 2002 and 2010 were registered. Upon mortality survey at the end of 2012, 201 (70%) of them were traceable (men/women 121/80, mean age 71 yrs, duration of diabetes 11 yrs and HbA1c 9.9%). The analysis took account of the following baseline information: gender, age, duration of diabetes, HbA1c, body mass index, systolic blood pressure, eGFR, urinary albumin excretion, serum lipid levels and use of insulin and oral hypoglycemic agents. The follow-up HbA1c was also recorded.ResultsThe mean follow-up period was 5.7 yrs and 45 of the patients have died. The mortality hazard as a function of the baseline HbA1c quartile was significantly V-shaped with the nadir in quartile 2 (HbA1c 8.5–9.4%) (P = 0.02), and this relationship remained significant after adjustment for the confounders such as estimated glomerular filtration rate and insulin use. The follow-up HbA1c was 7.7 ± 1.6% and not significantly related to mortality.Discussion/ConclusionThere was a V-shaped relationship between baseline HbA1c and all-cause mortality in elderly patients with insufficiently controlled glycemia. The nadir was in Q2 in which the HbA1c value was 8.5–9.4%. No significant relationship was found between the follow-up HbA1c and mortality. Further studies are needed to clarify the relationship between HbA1c and mortality in the elderly.