Importance of glycemic control on the course of glomerular filtration rate in type 2 diabetes with hypertension and microalbuminuria under tight blood pressure control

Background and aimsTo evaluate the role of glycemic control on the evolution of glomerular filtration rate (GFR) in type 2 diabetes (T2DM) with mild-moderate hypertension under tight blood pressure control, and to address the current controversy whether diabetic nephropathy worsens, independently of blood pressure, proportionally to HbA1c at any physiological level or only when HbA1c is above a 7.5–8% threshold.Methods and resultsT2DM (N = 127) during early stage diabetic nephropathy characterized by microalbuminuria were followed during a 2 year multicenter study. Individual GFR profiles were accurately obtained by ⁵¹Cr – EDTA bolus injections and analyzed with linear statistical mixed-effects models. GFR at baseline was significantly negatively correlated with age and plasma creatinine concentration (P ≤ 0.0001), and GFR declined, on average, by 4.0 ml/min 1.73 m²/year (P = 0.001). A significant correlation was found between individual GFR decline rate and average systolic (SBP) and diastolic (DBP) blood pressures (−0.254 (0.736) ml/min 1.73 m²/year per mmHg increase in SBP (DBP), P = 0.041 (0.014)) and % of glycated hemoglobin (HbA1c) (−1.78 ml/min 1.73 m²/year per % increase in HbA1c, P = 0.048). This implies a 44% increase/reduction in GFR decline rate for 1% HbA1c increase/reduction around 7.0% (i.e. 5.79 and 2.24 ml/min 1.73 m²/year at 8% and 6% HbA1c, respectively).ConclusionsThis study demonstrates that, despite tight blood pressure control, an accurate glycemic control till very low patterns of HbA1c (from 10–11% to 5–6%) is needed to delay the progression of GFR decay in Mediterranean T2DM in south Europe with microalbuminuria.     

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

PurposeIn this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.MethodsGenomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.ResultsA statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p < 0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015–2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p < 0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024–2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p > 0.05).ConclusionsThis is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.     

Changes over time in the prevalence and quality of care of type 2 diabetes in Italy: the Casale Monferrato surveys, 1988 and 2000

Background and aimsIn this study we assessed the prevalence of diagnosed type 2 diabetes and the quality of care during the period 1988–2000 in an Italian population.Methods and resultsTwo population-based surveys, using similar methods and centralized measurements, were conducted in 1988 and 2000 in a representative Italian area to identify people with known diabetes. The adjusted prevalence (reference, 2001 Italian population) was computed. The age- and sex-adjusted prevalence rates of diabetes in the population of Casale Monferrato were 2.13% (2.05–2.22) in 1988 and 3.07% (2.97–3.17) in 2000. In comparison with diabetic persons recruited in 1988 and independently of age and sex, persons recruited in 2000 had a lower likelihood of having HbA1c ≥7.0% (OR = 0.48; 0.42–0.56), diastolic blood pressure ≥80 mmHg (OR = 0.61; 0.49–0.75), LDL cholesterol ≥2.59 mmol/l (OR = 0.77; 0.63–0.93) and AER ≥20 μg/min (OR = 0.53; 0.45–0.61; they had a higher likelihood of having BMI ≥25 kg/m² (OR = 1.49; 1.2–1.74). However, 45.4% of patients still had HbA1c ≥7.0%, 80% blood pressure ≥130/80 mmHg and 79% LDL-cholesterol values ≥2.59 mmol/l.ConclusionMore than two-thirds of Italians with diabetes are now aged 65 years and more. The quality of control of glycemia, lipids and blood pressure improved and the prevalence of diabetic nephropathy decreased over time, although complete adherence to international guidelines has not yet been achieved.     

Diabetes and cardiovascular risk factor controls in Thai type 2 diabetes with no history of cardiovascular complications; situation and compliance to diabetes management guideline in Thailand

BackgroundCardiovascular complication is one of the most important issues causing morbidity and death in diabetic patients. Primary prevention is a key to prevent this complication.AimsThe objective was to study the situations of diabetes and cardiovascular risk factor controls in Thai type 2 diabetic patients who had no history of cardiovascular complication at a university hospital in Thailand after the Thai diabetes management guideline was recently launched.MethodsThe study was a cross-sectional survey in type 2 diabetes patients with no history of cardiovascular disease. Seven hundred and fourteen patients were enrolled in the study and 54.3% were females. The data were collected retrospectively from out-patient medical records and an electronic data base for the patients who were followed up at the hospital during January–December 2010. The most recent laboratory values were utilized in the analysis.Results70%–90% of all patients were checked for HbA1c and lipid profiles (LDL-C, total cholesterol, triglycerides) at least once a year. It was observed that only 28% of the patients had HbA1c < 6.5%. Furthermore, the percentages of the patients who had blood pressure < 130/80 mmHg, and who had LDL-C < 100 mg/dL were 28% and 41%, respectively.ConclusionEven though the practice guideline has been launched since 2008, diabetes, hypertension and dyslipidemia were still poorly controlled. Further study is recommended to identify factors influencing these outcomes as well as the policy of diabetic care in Thailand is needed to be seriously implemented.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

Evaluation of trace elements and Malondialdehyde levels in type II diabetes mellitus

BackgroundThere are so many factors contributing to the pathophysiology of type II DM, some of these factors are trace elements and Malondialdehyde (MDA). Their increase or decrease may affect control of diabetes and delay the complications.AimZinc (Zn), copper (Cu), magnesium (Mg), chromium (Cr), selenium (Se) and MDA were studied in this work to clarify their role in the pathogenesis and complications of type II DM aiming at preventing or delaying its complications.Materials and methodsThe present study was conducted on 50 patients with type II DM divided into 2 groups: group I (controlled diabetic patients), n = 20 and group II which comprised 30 uncontrolled diabetic patients complicated with diabetic nephropathy, neuropathy and retinopathy. Their results were compared to 15 age and sex matched healthy group. Patients and controls were subjected to full history taking, complete clinical examination and laboratory investigations which included measuring fasting serum glucose, cholesterol, triglycerides, HDL-c and LDL-c. HbA1c was measured by column chromatography. MDA was assayed using colorimetric technique. The trace elements were measured in blood by means of atomic absorption spectrometer.ResultsThe mean levels of Zn, Mg, Se were significantly lower in the diabetic groups than the control group (P < 0.001), while MDA was significantly higher in the diabetic groups (P < 0.001). MDA showed significant positive correlation with HbA1c (r = 0.301), cholesterol (r = 0.394), triglycerides (0.315) and LDL-c (r = 0.354) and negative correlation with HDL-c (r = ?0.315). Significant negative correlation was found between each of Zn, Mg and Se and each of HbA1c and cholesterol. Copper positively correlated with HbA1c, cholesterol and LDL-c. MDA positively correlated with copper (r = 0.307) and negatively correlated with Zn, Mg and Se (r = ?0.356, ?0.282, ?0.513, respectively).ConclusionTrace elements and MDA could have a role as cofactors in the pathogenesis of type II DM. They could be used as markers to evaluate the glycemic control as well as showing the lipid status of diabetic patients. Trace elements supplementations as zinc, magnesium and selenium might have utility in the treatment of the complex disorder in type II DM and may help in control of blood glucose and lipid levels, thus preventing or delaying serious clinical events in these patients.     

Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 27)

PurposeThe aims of this study were to report the prevalence of various microvascular complications and to identify the various clinical and biochemical characteristics related to these complications in subjects with newly diagnosed type II diabetes.MethodsOf the 5999 subjects enumerated, 1414 subjects with diabetes (both known and newly diagnosed) were analyzed for the study. Among the diabetic subjects, 248 (17.5%) were newly diagnosed with diabetes and the remaining had history of diabetes. All subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography), neuropathy (vibration pressure threshold), and nephropathy (microalbuminuria).ResultsThe prevalence of any form of microvascular complication was 30.2% (95% confidence interval [CI] = 24.5–35.9). The prevalence of diabetic retinopathy was 4.8%, and that of diabetic nephropathy and neuropathy was 10.5%. The risk factors for developing any form of microvascular complication were increasing age (odds ratio [OR] = 1.07, 95% CI = 1.04–1.11, P < .0001), increasing systolic blood pressure (OR = 1.03, 95% CI = 1.01–1.06, P = .001), and increasing hemoglobin (OR = 1.39, 95% CI = 1.09–1.79, P = .011). The risk factors for diabetic retinopathy and diabetic nephropathy were increasing systolic blood pressure (OR = 1.06 [P = .001] for retinopathy and OR = 1.04 [P = .012] for nephropathy) and increasing hemoglobin (OR = 2.20 [P = .007] for retinopathy and OR = 1.57 [P = .023] for nephropathy). The risk factor for diabetic neuropathy was increasing age (OR = 1.12, P < .0001).ConclusionsNearly one third of the newly diagnosed type II diabetes subjects had some form of microvascular complication; nephropathy, and neuropathy being commoner than retinopathy.     

Visit-to-visit variability in systolic blood pressure predicts development and progression of diabetic nephropathy,but not retinopathy,in patients with type 2 diabetes

ObjectiveTo investigate whether visit-to-visit variability in systolic blood pressure (SBP) can predict development and progression of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus (T2DM).MethodsFrom 1995 through 1996, 664 T2DM patients visited our hospital for the first time and were subsequently examined 4 times or more and at least once annually.At first visit, 326 had normoalbuminuria, 644 had an estimated glomerular filtration rate (eGFR) of ≥ 45 ml/min/1.73 m², 526 had no diabetic retinopathy and 609 had no severe non-proliferative diabetic retinopathy (NPDR). They were followed through June 2012, at the latest.ResultsNinety patients developed microalbuminuria, 76 showed decrease of eGFR to < 45 ml/min/1.73 m², 113 developed mild–moderate NPDR and 50 progression to severe NPDR. The unadjusted, age- and sex-adjusted and multivariate-adjusted hazard ratios for development and progression of nephropathy, but not retinopathy, increased across tertiles of the standard deviation (SD) of SBP. Both the SD and coefficient of variation (CV) of SBP were significant predictors of development and progression of nephropathy, but not retinopathy, independently of mean SBP.ConclusionVisit-to-visit SBP variability is an independent predictor of development and progression of diabetic nephropathy, but not retinopathy, in T2DM patients.     

Dry eye and its correlation to diabetes microvascular complications in people with type 2 diabetes mellitus

AimsThis study was performed to investigate the correlation between dry eye disease and diabetes microvascular complications.MethodsIn this study 243 people with type 2 diabetes were enrolled. Tear osmolarity was measured using tear lab osmolarity system. All of the participants were evaluated for diabetes microvascular complications. The Michigan neuropathy screening instrument was used for detection of peripheral neuropathy, and the albumin/creatinine ratio in a spot urine sample was considered to diagnose diabetic nephropathy.ResultsThe prevalence of dry eye disease was 27.7%. The mean value for tear osmolarity was 301.97 ± 13.52 mOsm/L. We found a significant correlation between dry eye disease and diabetic retinopathy (P = 0.01). However no significant correlation was found between dry eye disease, diabetic neuropathy, and diabetic nephropathy.Dry eye disease was more prevalent in people with proliferative diabetic retinopathy and/or clinically significant macular edema (0.006). In a binary logistic regression analysis model, there was a significant correlation between dry eye disease and retinopathy (OR = 2.29, CI = 1.16–4.52, P = 0.016). In addition, both dry eye and retinopathy had significant correlation with HbA1C.ConclusionsDry eye disease is common in people with type 2 diabetes, especially in those with diabetic retinopathy. In addition, it is more prevalent in people who suffer from advanced stages of diabetic retinopathy.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Type 1 diabetes in Cheshire: cardiometabolic risk factor trends (2004-2009)

AimsIn the context of changes in the last 10 years in treatment strategies for type 1 diabetes we evaluated longitudinal trends in cardiometabolic risk factor profiles in a population from North-West England.MethodsWe retrospectively examined longitudinal case records for the period for 291 adult patients followed up between 2004 and 2009 (age range 16–85). Data search was performed through the EMIS^® software provider using data held in primary care.ResultsLongitudinal analysis of individually followed patients indicated a mean 0.4% reduction in HbA1c from 8.3% (67 mmol/mol) at baseline (p = 0.002). The proportion of patients with an HbA1c ≥10% (86 mmol/mol) at baseline had a significant reduction over time from 14.0% to 9.5% (χ² = 9.4, p = 0.002). BMI remained unchanged (28.3 vs 28.4 kg/m²). However total cholesterol fell by 12.5% from 4.8 mM to 4.2 mM, (p < 0.0001) with a corresponding 23% reduction in LDL-cholesterol from 3.0 mm to 2.3 mM (p < 0.0001). There was a significant fall in diastolic BP (78–74 mmHg, p = 0.0016). In a mixed longitudinal regression model, HbA1c was associated with LDL-C (β = 0.28, p < 0.001) and age (β = 0.02, p = 0.001), independent of BMI, gender and systolic BP.DiscussionIn spite of intensive work to improve glycaemic control in type 1 diabetes, mean HbA1c remains above target for many people in our area, highlighting the difficulty of achieving glycaemic targets in type 1 diabetes. The significant reduction in diastolic BP, LDL and total cholesterol may have long-term benefit in cardiovascular event rate reduction.     

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.     

Higher HDL cholesterol levels are associated with a lower incidence of chronic kidney disease in patients with type 2 diabetes

Background and aimsType 2 diabetes is one of the most important risk factor for the development of chronic kidney disease (CKD). Recently, it has been shown that lower high-density lipoprotein cholesterol (HDL-C) levels predicted the development of microalbuminuria in type 2 diabetic individuals. We have prospectively assessed the effects of plasma HDL-C levels on the incidence of CKD in a large cohort of type 2 diabetic patients.Methods and resultsWe followed 1987 type 2 diabetic outpatients with normal or near-normal kidney function at baseline for 5 years for the occurrence of incident CKD defined as glomerular filtration rate ≤ 60 mL/min/1.73 m² (as estimated by the abbreviated Modified Diet and Renal Disease Study equation). Cox proportional hazards models were used to examine the independent relationship between plasma HDL-C levels and incident CKD. During a median follow-up of 5 years, 11.8% (n = 234) of participants developed incident CKD. In multivariate regression analysis, higher HDL-C levels were associated with a lower risk of incident CKD (multiple-adjusted hazard ratio 0.76; 95% coefficient intervals 0.61–0.96; p = 0.025) independently of age, gender, body mass index, hypertension, smoking history, diabetes duration, hemoglobin A1c, plasma triglycerides, LDL-cholesterol, presence of diabetic retinopathy, baseline albuminuria, and current use of medications (anti-hypertensive, anti-platelet, lipid-lowering and hypoglycemic drugs).ConclusionsHigher plasma levels of HDL-C are associated with a lower risk of incident CKD in a large cohort of type 2 diabetic adults independently of numerous confounding factors.     

Retrospective comparative analysis of metabolic control and early complications in familial and sporadic type 1 diabetes patients

BackgroundGenetic susceptibility and lifestyle are associated with glycemic control and diabetic complications in type 1 diabetes (T1D).ObjectivesTo investigate metabolic control and occurrence of acute and microvascular complications among familial and sporadic T1D patients.Patients and MethodsRetrieved from our institutional registry of new T1D cases for the years 1979–2008 were 226 familial patients belonging to 121 families (58 parent–offspring, 63 sib-pairs) and 226 sporadic cases matched for age, gender, and year of diagnosis. Extracted from medical files were clinical course and therapeutic regimen.ResultsMean age at diagnosis of diabetes of the cohort was 10.8 ± 5.7 years. Throughout follow-up (11.1 ± 8.7 years) mean HbA1c values were significantly higher in familial than in sporadic cases (8.18% ± 1.15% vs. 7.85% ± 1.15%, p = 0.005). Diabetic ketoacidosis (DKA) rates were higher in familial than sporadic cases (2.8 vs. 1.9 events per 100 patient-years; incidence rate ratio (IRR) = 1.5, 95% CI [1.03, 2.22, p = 0.03]). Severe hypoglycemia events per 100 patient-years were comparable in familial and sporadic groups (3.7 vs. 4.0 events); sib-pairs had higher rates than parent–offspring (4.8 vs. 2.4 events; (IRR) = 2, 95% CI [1.03, 3.25, p = 0.03]). The percentage of patients with microvascular complications was similar in the familial (21.7%) and sporadic (26.7%) groups. In both familial and sporadic cases the most significant predictor for metabolic control and microvascular complications was diabetes duration; a higher mean HbA1c level was the predictor for DKA events.ConclusionsThe worse metabolic control and increased rate of DKA in familial T1D patients as compared to those in the sporadic T1D patients warrant intensified surveillance in this population.     

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.     

Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction

AimsTo evaluate the effects of adding glucagon-like peptide-1 (GLP-1) analogue therapy to insulin on glycated hemoglobin (HbA1c), weight, insulin dosage, treatment satisfaction, and risk of hypoglycaemia.MethodsType 2 diabetes patients with insulin therapy receiving a GLP-1 analogue at 4 Swedish centers were studied. Hypoglycemia was evaluated using glucometers and patient self-report. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to evaluate treatment satisfaction.ResultsAmong 65 patients studied, 4 discontinued therapy, none due to hypoglycemia, and there were no suspected severe adverse events. Among 61 patients who remained on therapy over a mean of 7.0 months, 40 were treated with liraglutide and 21 with exenatide. HbA1c decreased from a mean of 8.9% (82.4 mmol/mol) to 7.9% (71.9 mmol/mol) (p < 0.001), weight decreased from 111.1 kg to 104.0 kg (p < 0.001) and insulin doses were reduced from 91.1 U to 52.2 U (p < 0.001). There was one patient with severe hypoglycemia. The mean number of asymptomatic hypoglycemia per patient and month, reported for the last month (0.085 below 4.0 mmol/l and 0 below 3.0 mmol/l) and documented symptomatic hypoglycemia (0.24 below 4.0 mmol/l and 0.068 below 3.0 mmol/l) was low. The DTSQc showed higher treatment satisfaction than with the previous regimen of 11.9 (scale ?18 to +18 points, p < 0.001).ConclusionsThe addition of GLP-1 analogues to insulin in patients with type 2 diabetes is associated with reductions in HbA1c, weight, and insulin dose, along with a low risk of hypoglycemia and high treatment satisfaction.     

KCNJ11 gene E23K variant and therapeutic response to sulfonylureas

AimsPotassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K_ATP) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant.Patients and methodsOne hundred and one patients with type 2 diabetes who failed to achieve HbA1c < 7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis.ResultsAfter 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04 ± 0.10 vs. 0.79 ± 0.12%, p = 0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01–0.32, p = 0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n = 55).ConclusionsCarriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.     

Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients

Background and aimData on oxidative stress in type 2 diabetic patients with diabetic nephropathy is scant. The objective of this study was to investigate possible associations between total oxidant status (TOS) and the severity of diabetic nephropathy in type 2 diabetic patients by using a novel automated measurement method.Methods and resultsThirty-six patients with diabetic nephropathy (group 1), 25 diabetic patients without nephropathy (group 2) and 30 controls (group 3) were enrolled. Serum total antioxidant capacity (TAC), TOS levels and oxidative stress index (OSI) were determined. The severity of the disease was determined with microalbuminuria levels. TAC was lower, while TOS and OSI were higher in group 1 than in group 3 (P < 0.01, P < 0.001, P < 0.001; respectively). There were no statistically significant differences between group 2 and group 3 with respect to TAC, TOS and OSI (all P > 0.05). Group 1 had higher TOS and OSI than group 2 (both P < 0.05), but there was no statistically significant difference with respect to TAC. Significant correlations were observed between microalbuminuria levels, and TAC, TOS and OSI levels (r = −0.616, P < 0.001; r = 0.488, P < 0.01; r = 0.567, P < 0.001; respectively).ConclusionOur results suggest that oxidative stress is increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy and this increase seems to be related to the severity of microalbuminuria levels.