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.     

Cardiovascular risk assessment in patients with type 2 diabetes mellitus and metabolic syndrome: Role of biomarkers

ObjectivesMetabolic syndrome (MetS) and type 2 diabetes mellitus (DM) are associated with a high incidence of cardiovascular diseases. The aim of this study was to determine paraoxonase (PON), total sialic acid (TSA), and nitric oxide (NO) levels in addition to conventional risk markers in patients with DM, MetS and DM plus MetS.Material and methodsThe study has been carried out over 78 subjects which divided into four groups; control (n = 18), DM (n = 20), newly diagnosed MetS (n = 20) and DM plus MetS patient groups (n = 20).ResultsBoth insulin and triglyceride concentrations were significantly higher in DM + MetS group than in control and DM groups and serum HDL-C concentrations were significantly lower in DM + MetS group than other groups. Patients with MetS had higher LDL-C, total cholesterol and hsCRP concentrations than in the other groups. Interestingly, in addition to body mass index and waist circumference values, LDL-C, total cholesterol and hsCRP concentrations were decreased in patients who have both DM and MetS. Serum NO and TSA levels were higher in MetS and DM + MetS groups compared to control subjects. Unexpectedly, PON activity has been found lower in control group when compared to other groups.ConclusionsAlthough there is no doubt that association of DM and MetS elevates the risk of cardiovascular disease, occurrence of DM in patients with undiagnosed MetS might be encouraging patients to change their life styles and dietary habits.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Gender and ethnic differences in the prevalence of type 2 diabetes among Asian subgroups in California

AimsTo investigate gender and ethnic type 2 diabetes (DM) prevalences among California Asian subgroups versus other ethnic groups and if risk factors explain these differences.MethodsWe identified the prevalence of DM and associated risk factors, stratified by gender, among Chinese, Filipino, South Asian, Japanese, Korean, Vietnamese, Mexican, Other Hispanic, African-American, Caucasian, and Native American adults in a large survey conducted in 2009 (n = 46,091, projected n = 26.6 million).ResultsThe highest age-adjusted DM prevalence was seen in Native Americans (32.4%), Filipinos (15.8%), and Japanese (11.8%) among men and in Native Americans (16.0%) and African-Americans (13.3%) among women. Caucasian and Mexican men had higher DM prevalences than women. Age and risk factor-adjusted logistic regression showed DM more likely (relative to Caucasians) among women in Koreans (OR = 4.6, p < 0.01), Native Americans (OR = 3.0, p < 0.01), and Other Hispanics (OR 2.9, p < 0.01) and among men in Filipinos (OR = 7.0, p < 0.01), South Asians (OR = 4.7, p < 0.01), and Native Americans (OR = 4.7, p < 0.01). No specific risk factors accounted for the gender differences.ConclusionsEthnic and gender differences in DM prevalence persist, even after adjusting for lifestyle and other risk factors; prevalence is high among certain Asian American subgroups. Different diabetes prevention approaches may be needed across ethnic/gender groups.     

Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: in vitro and in vivo studies

ObjectiveParaoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities.Methods and resultsIn HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL–PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL (p < 0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL.In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL–PON1 arylesterase (150%) and lactonase (94%) activities (p < 0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL (p < 0.01). Similarly, olive oil consumption by healthy subjects increased HDL–PC-18:1 levels, HDL–PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment (p < 0.01).PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 (p < 0.01).ConclusionIntervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.     

Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: Their role in the prediction of vascular complications

Background and objectiveEndothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications.MethodsFifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay.ResultssEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p = 0.02, and p = 0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p = 0.04.ConclusionPatients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM.     

Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease

BackgroundUbiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains unclear. In this study, we examine the diagnostic value of UbA52 as a biomarker in predicting early diabetic kidney disease (DKD) in T2DM patients.MethodsWe used two-step ELISA to test UbA52 level in urine of 3 defined patient groups. Samples from T2DM patients without albuminuria or diabetic retinopathy (DM-WNP; n = 30), T2DM patients with albuminuria and diabetic retinopathy, excluding other renal diseases clinically (DM-NP; n = 30) and healthy controls (n = 30) were analyzed. Spearman's correlation analysis and multiple linear regression model were used to analyze the correlation of urinary UbA52 level with laboratory results regarding kidney function. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of UbA52 in predicting T2DM and early DKD.ResultsUrinary UbA52 level in DM-NP group was 1.75 times and 2.71 times higher than in DN-WNP (p = 0.004) and normal control group (p < 0.001), respectively. The level of urinary UbA52 correlated significantly with serum creatinine (r = 0.468, p < 0.001), GFR (r = −0.300, p = 0.004) and proteinuria (r = 0.484, p < 0.001). Multiple linear regression analysis showed that proteinuria level was independently associated with urinary UbA52 level (β = 0.833, p < 0.001). The area under the ROC of urinary UbA52 in diagnosing T2DM and DKD was 0.751 and 0.755, respectively.ConclusionThe level of urinary UbA52 increased significantly in T2DM patients with DKD. The level of proteinuria is independently associated with urinary UbA52 level. Urinary UbA52 could serve as an early marker in the diagnosis of DKD.ClinicalTrials.gov Identifier: NCT02204280.     

Serum resistin in acute myocardial infarction patients with and without diabetes mellitus

AimHuman resistin is an adipokine, which has been suggested to be an inflammatory marker, with possible links to atherosclerosis and coronary heart disease. Meanwhile, the relationship between serum resistin, insulin resistance, and type 2 diabetes mellitus (T2DM) is still controversial. Therefore, this study aimed to assess serum resistin in patients with acute ST-segment elevation myocardial infarction (STEMI), with and without T2DM.Patients and methodsA total of 55 subjects included in this study, were categorized into three groups: 20 non-diabetic patients with acute STEMI (group I), 20 diabetic patients with acute STEMI (group II), and 15 healthy age and gender-matched controls (group III). Levels of serum lipids, fasting blood glucose (FBG), insulin, troponin I, creatine kinase (CK), lactate dehydrogenase (LDH), and resistin, were estimated.ResultsSerum total cholesterol, low density lipoprotein cholesterol (LDLc), FBG, troponin I, CK (total and MB), LDH, and resistin, were significantly higher in group II, than in group I and group III (p < 0.05). In group II, serum resistin was positively correlated with serum troponin I and TG (r = 0.59, p < 0.05 and r = 0.47, p < 0.05, respectively), but was negatively correlated with high density lipoprotein cholesterol (HDLc) (r = −0.46, p > 0.05). However, in this patients’ group, serum resistin was not correlated with age, gender, body mass index (BMI), total cholesterol, FBG, insulin, CK, LDH, and the calculated homeostasis model for insulin resistance (HOMA-IR) (p > 0.05). As regards group I, serum resistin was not correlated to any of these studied parameters (p > 0.05).ConclusionSerum resistin levels are elevated in patients with acute STEMI. This increase is more evident in patients with T2DM than those without T2DM, denoting higher degrees of inflammation. However, serum resistin is not correlated with age, gender, BMI, and insulin resistance. These data denote that serum resistin concentration might be used as a diagnostic biomarker for acute STEMI. In addition, optimization of the treatment of T2DM could improve cardioprotection.     

Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with β-catenin accumulation

Aimsβ-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear.MethodsColorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1 year (n = 27) and non-DM patients without hyperglycemia (n = 20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n = 6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence.ResultsCompared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group (all p < 0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient = 0.55; p < 0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p < 0.01).ConclusionsEnhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.     

Ferroportin Q248H mutation,hyperferritinemia and atypical type 2 diabetes mellitus in South Kivu

BackgroundThe ferroportin Q248H mutation is relatively common in sub-Saharan Africa. No previous study examined its relationship with atypical diabetes mellitus (DM) in this area.ObjectiveTo determine the potential interactions between ferroportin Q248H mutation, hyperferritinemia and DM in South Kivu (RDC).MethodologyPresence of ferroportin Q248H mutation and iron status were investigated in diabetic patients (n = 179, age (mean) 57.7 years, CRP (median) 0.16 mg/L) and non-diabetic subjects (n = 86, age 44.5 years, CRP 0.07 mg/L) living in the city of Bukavu. Hyperferritinemia was considered for values greater than 200 and 300 μg/L in women and in men, respectively.ResultsThe prevalence of ferroportin Q248H mutation [12.1%] was non-significantly higher in diabetics than non-diabetics [14.0% vs. 8.1%, p = 0.17]. Similarly, hyperferritinemia frequency was higher in diabetic patients with Q248H mutation [44.0% vs. 14.3%, p = 0.16] and in mutation carriers [37.0% vs 16.5%, p = 0.001] than in the control groups, respectively. The association between Q248H mutation and DM was nevertheless not significant [adjusted OR 1.70 (95% CI: 0.52–5.58), p = 0.37], whereas hyperferritinemia [OR 2.72 (1.24–5.98), p = 0.01] showed an independent effect after adjustment for age and metabolic syndrome.ConclusionsThe present work suggests a potential association between abnormal iron metabolism, ferroportin Q248H mutation and atypical DM in Africans, which may be modulated by environmental factors.     

Compare the effects of different visfatin concentration on cardiovascular risk factors,adiponectin and insulin resistance in patients with T2DM

AimThe discovery of new adipokine, visfatin can significantly enhance our knowledge of insulin resistance and diabetes mellitus. We explored the relation of visfatin concentrations to cardiovascular risk factors, adiponectin and insulin resistance criteria in patients with type 2 diabetes mellitus (T2DM).Materials and MethodsFifty-eight patients with T2DM were recruited from the out patients clinic of Shariati Hospital. Laboratory and anthropometric measurements include FBG, OGTT, HbA1c, fasting serum visfatin, insulin and adiponectin, HOMA-IR and hsCRP, weight, height, BMI and WHR were performed in all participants. All of the statistical data were analyzed using the SPSS15 software.ResultsThe log₁₀-transformed (log) plasma visfatin concentration was in significant positive correlation with age (r = 0.286, p = 0.033). Patients were divided in two groups by median log visfatin (0.85 ng/mL): group I had low values and group II had high values. In group I the log visfatin was in significant positive correlation with age (r = 0.436, p = 0.018) and in group II log visfatin was in significant negative correlation with FPG and HbA1c (r > 0.4, p < 0.05).ConclusionIn conclusion high circulating levels of visfatin could be in healthy relations with cardiovascular risk factors, insulin resistance status and adiponectin in diabetic patients.     

The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes

AimsEvidence that pancreatic fat accumulation has a role in obesity, metabolic syndrome and type 2 diabetes mellitus (DM) is emerging. However, data on the influence of pancreatic steatosis on subclinical atherosclerosis are lacking.MethodsWe examined 198 patients with type 2 DM. Pancreatic computed tomography (CT) attenuations were assessed using CT imaging. Obesity was defined as BMI ≥ 25 kg/m² according to the Asian-specific BMI cut-offs. We defined pancreatic steatosis as pancreatic attenuations below median levels.ResultsThe pancreatic attenuations was significantly correlated with age (r = −0.302, p < 0.001), visceral fat area (r = −0.194, p = 0.006) and vascular stiffness (r = −0.242, p = 0.001). In the non-obese group (BMI < 25 kg/m²), pancreatic steatosis was associated with a higher prevalence of carotid artery plaque and vascular stiffness. In the non-obese group, patients with pancreatic steatosis, compared with those without, had an odds ratio (OR) of 3.1 (95% CI 1.2–8.1) for carotid atherosclerosis, after adjusting for age, gender and BMI. However, significant associations between pancreatic steatosis and atherosclerosis were not found in the obese group.ConclusionEctopic fat in the pancreas is strongly associated with carotid atherosclerosis in non-obese subjects with type 2 DM. This finding highlights the importance of pancreatic fat deposits related to a higher risk of cardiovascular disease, especially in non-obese subjects.     

Correlation between HCV viraemia and splenic volume in chronic HCV infected patients: An Egyptian study

Background and Study aimsAs HCV lymphotropism was ascertained, this study was carried out to verify the possible involvement of the spleen in HCV-related chronic hepatitis.Patients and MethodsA cross-sectional study was conducted on 97 HCV infected patients attending for treatment with interferon, categorised as follows; before treatment (group I, n = 49), non-responders (group II, n = 18), responders (group III, n = 18) and group IV (n = 12) including patients with HCV RNA below detection limit after 24 weeks of treatment. A control group of healthy blood donors (n = 19) was enrolled in our study. Conventional ultrasonography was carried out on all participants. Splenic volume was measured and compared between the groups, and its relationship to HCV RNA concentration was investigated.ResultsIt was found that the splenic volume of patients of both groups I and II is significantly greater than that of the control group (p-values : 0.004 and 0.009, respectively) and, of patients of both groups III and IV. The latter are not significantly greater than that of the control group (p-value: 0.8 and 0.6, respectively). A significant positive relationship was detected between the splenic volume and the HCV RNA concentration in group I (r = 0.56, p-value = 0.00) but this is insignificant in group II. There is no significant relationship between the splenic longitudinal diameter and the HCV RNA concentration in any of the studied groups.ConclusionThe splenic volume positively correlated with HCV RNA concentration in HCV positive patients, but this become insignificant in non-responders to interferon therapy. The successful response to interferon therapy matches with near normal splenic volume whilst non-responders to Interferon therapy matches with increased splenic volume. The change in the viral load leads to a corresponding change in the splenic volume and does not affect the splenic longitudinal diameter.     

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.     

An exploratory trial of basal and prandial insulin initiation and titration for type 2 diabetes in primary care with adjunct retrospective continuous glucose monitoring: INITIATION study

AimsTo evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator – Registered Nurse (CDE-RN) support.MethodsInsulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation.ResultsNinety-two patients mean age (range) 59 (28–77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p = 0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002).ConclusionsInsulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition.Trial registration ACTRN12610000797077.     

Apolipoprotein E genotype predicts cardiovascular endpoints in dialysis patients with type 2 diabetes mellitus

ObjectiveCardiovascular disease (CVD) is the leading cause of death in patients with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Lipid metabolism is influenced by environmental and genetic factors. Among the latter, the apolipoprotein E (apoE) genotype is known to be associated with CVD risk and thus may affect cardiovascular outcome.Methods and resultsBased on the German Diabetes and Dialysis Study evaluating 1255 T2DM patients on haemodialysis (HD) (median follow-up 4 years), the impact of the apoE genotype (available for 1177 patients) on pre-specified, centrally adjudicated endpoints was investigated: all-cause mortality (n = 558), combined cardiovascular events (CVE: cardiac death, MI, stroke; n = 442), and cardiac death (n = 218). Patients with at least one ?4 allele (?4+) showed a 30% increased risk for CVE (HR 1.299, 95%CI 1.045–1.615, p = 0.018) and a 36% increased risk for cardiac death (HR 1.362, 95%CI 1.002–1.852, p = 0.048) compared to patients with no ?4 allele. Consistently, addition of ?4+ to a multivariate ROC model for risk prediction of CVE including atorvastatin treatment, history of cardiovascular disease, dialysis and lipoprotein parameters, hsCRP, and NT-pro-BNP increased the area under the curve from 0.666 (95%CI 0.634–0.698) to 0.671 (95%CI 0.639–0.702), p = 0.013.ConclusionsThe presence of the ?4 allele increases the risk for CVE and cardiac death in patients with T2DM and ESRD. Whether treatment strategies guided by apoE genotype will improve outcome needs to be evaluated in the future.     

Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes

ObjectiveOur objective was to examine the role of hypertriglyceridemia on the capacity of HDL to facilitate ABCA-1 mediated cholesterol efflux in type 2 diabetes (T2DM).MethodsHDL mediated cholesterol efflux through the ABCA-1 transporter was measured using BHK cell lines in samples of 71 participants with T2DM in the presence or absence of high triglyceride levels (TG). Additionally, HDL mediated efflux was measured in 13 diabetic and non-diabetic participants fasting and four hours after a high-fat test challenge.ResultsHDL mediated cholesterol efflux function was increased in participants with T2DM with hypertriglyceridemia when compared to participants with T2DM without hypertriglyceridemia (efflux ratio mean ± standard deviation (SD), T2DM + TG: 1.17 ± 0.25 vs. T2DM − TG: 1.03 ± 0.19, p = 0.0098). In the fat challenge study, we observed a significant increase in ABCA-1 mediated cholesterol efflux capacity following an ingestion of high-fat test meal by participants in both groups of T2DM (n = 6, efflux ratio, mean ± SD, pre: 0.86 ± 0.4 vs. post: 1.34 ± 0.6, p = 0.01) and non-diabetic participants (n = 7, efflux ratio mean ± SD pre: 1.24 ± 0.31 vs. post: 1.39 ± 0.42, p = 0.04) that was partly explained by the difference in CETP activity (r = 0.6, p = 0.03).ConclusionOur study suggests that high triglyceride levels facilitate ABCA-1 mediated efflux function of HDL in part by activating CETP.     

Myeloperoxidase and paraoxonase-1 in type 2 diabetic patients

Background and aimsReduced high density lipoproteins (HDL) and increased oxidative stress are features of type 2 diabetes. Myeloperoxidase is an oxidative enzyme partly associated with HDL and causing HDL dysfunction. It is an independent risk factor for cardiovascular disease. Paraoxonase-1 is an HDL-associated enzyme that protects against cardiovascular disease and is reduced in diabetes. The present study examined if serum myeloperoxidase was (i) increased in type 2 diabetes, (ii) correlated with paraoxonase-1 activity.Methods and resultsThe study was based on cross-sectional analyses of serum myeloperoxidase and paraoxonase-1 in type 2 diabetic patients and non-diabetic participants, with and without cardiovascular disease.Serum myeloperoxidase concentrations were not increased in type 2 diabetic patients without cardiovascular disease compared to non-diabetic controls. They were significantly higher in type 2 patients and non-diabetic patients with angiographically confirmed coronary disease. HDL-associated myeloperoxidase was correlated with serum myeloperoxidase (r = 0.80, p < 0.001) but not HDL-cholesterol (r = 0.08) or apolipoprotein AI (r = 0.08). Multivariate analyses showed serum myeloperoxidase to be an independent determinant of paraoxonase activities (arylesterase, p = 0.024; paraoxonase, p = 0.026).ConclusionsMyeloperoxidase is an independent, negative determinant of paraoxonase-1 activity, which may be one mechanism by which it promotes HDL dysfunction and increases cardiovascular risk. Increased serum myeloperoxidase is not a feature of type 2 diabetes in the absence of overt cardiovascular disease. The level of HDL-associated myeloperoxidase is determined by the serum concentration of the enzyme suggesting that, in the context of reduced HDL concentrations in diabetic patients, myeloperoxidase may have a greater impact on HDL function.     

Comparative effects of pioglitazone and metformin on oxidative stress markers in newly diagnosed type 2 diabetes patients: A randomized clinical trial

AimsRecent studies have suggested that pioglitazone exerts anti-oxidant properties which may countervail oxidative stress (OS). We aimed to elucidate the effects of pioglitazone on OS modulation and to compare its effects with metformin.MethodsData from the randomized clinical trial (registration no.NCT01521624) were used. Newly diagnosed type 2 diabetes patients were assigned to pioglitazone 30 mg daily (n = 30), metformin 1000 mg daily (n = 50), or no medication (n = 49). Recommendations for exercise and dietary modifications were provided for three groups. Serum concentrations of advanced oxidation protein products(AOPP), advanced glycation end products(AGE), ferritin reducing ability of plasma(FRAP), and enzymatic activities of paraoxonase(PON), lecithin-cholesterol asyltransferase(LCAT), and lipoprotein lipase(LPL) were measured at baseline and after three months.ResultsIn comparison with no medication, pioglitazone proved to be superior in OS amelioration (p < 0.05 in all analyses). Compared with metformin, both medications were equally effective in decrement of AOPP and AGE, along with increment of PON (p = 0.688, 0.140, and 0.273, respectively). FRAP concentrations increased significantly with metformin (p = 0.012). On the other hand, pioglitazone yielded better efficacy in restoration of LCAT and LPL enzymatic activities (p = 0.037, and < 0.001, respectively).ConclusionsSimilar to metformin, three months treatment with Pioglitazone is beneficial in terms of OS alleviation and anti-oxidant capacity restoration.