Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy.

OBJECTIVES: The present study aimed to evaluate the role of hyperlipidemia in increased formation of advanced lipoxidation end products (ALEs) and to evaluate whether there is any relationship between ALEs generation and erythrocyte glucose-6-phosphate dehydrogenase (G6PD) activity in cases of mild nonproliferative diabetic retinopathy (MNPDR). METHODS: In this study, we enrolled 100 patients with type 2 diabetes and MNPDR, 100 subjects with type 2 diabetes but without retinopathy (DNR) and 90 normal individuals without diabetes as healthy controls (HCs). Erythrocyte nicotinamide dinucleotide phosphate (NADPH), G6PD activity, serum total cholesterol, low- and high-density lipoprotein (LDL, HDL) and triglyceride levels were determined by photometric assay. Serum malondialdehyde (MDA) protein adduct and hexanoyl-lysine (HEL) were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: A robust linear relationship was observed between MDA protein adduct and LDL or cholesterol or triglyceride levels, and HEL and LDL or cholesterol or triglyceride levels in subjects with MNPDR (p=0.0001). A significant inverse association was observed between erythrocyte G6PD activity and serum MDA protein adductor HEL levels in subjects with MNPDR (p=0.0001). CONCLUSIONS: Hyperlipidemia is an important factor that is associated with increased ALEs formation in persons with MNPDR. Increased ALEs generation was associated with decreased G6PD activity and low NADPH levels in cases of MNPDR, suggesting their detrimental role in the occurrence of early NPDR.

Metabolic profiles and treatment gaps in young-onset type 2 diabetes in Asia (the JADE programme): a cross-sectional study of a prospective cohort.

BACKGROUND: The prevalence of diabetes is increasing in young adults in Asia, but little is known about metabolic control or the burden of associated complications in this population. We assessed the prevalence of young-onset versus late-onset type 2 diabetes, and associated risk factors and complication burdens, in the Joint Asia Diabetes Evaluation (JADE) cohort. METHODS: JADE is an ongoing prospective cohort study. We enrolled adults with type 2 diabetes from 245 outpatient clinics in nine Asian countries or regions. We classified patients as having young-onset diabetes if they were diagnosed before the age of 40 years, and as having late-onset diabetes if they were diagnosed at 40 years or older. Data for participants' first JADE assessment was extracted for cross-sectional analysis. We compared clinical characteristics, metabolic risk factors, and the prevalence of complications between participants with young-onset diabetes and late-onset diabetes. FINDINGS: Between Nov 1, 2007, and Dec 21, 2012, we enrolled 41,029 patients (15,341 from Hong Kong, 9107 from India, 7712 from Philippines, 5646 from China, 1751 from South Korea, 705 from Vietnam, 385 from Singapore, 275 from Thailand, 107 from Taiwan). 7481 patients (18%) had young-onset diabetes, with age at diagnosis of mean 32·9 years [SD 5·7] versus 53·9 years [9·0] with late-onset diabetes (n=33,548). Those with young-onset diabetes had longer disease duration (median 10 years [IQR 3-18]) than those with late-onset diabetes (5 years [2-11]). Fewer patients with young-onset diabetes achieved HbA1c concentrations lower than 7% compared to those with late-onset diabetes (27% vs 42%; p<0·0001) Patients with young-onset diabetes had higher mean concentrations of HbA1c (mean 8·32% [SD 2·03] vs 7·69% [1·82]; p<0·0001), LDL cholesterol (2·78 mmol/L [0·96] vs 2·74 [0·93]; p=0·009), and a higher prevalence of retinopathy (1363 [20%] vs 5714 (18%); p=0·011) than those with late-onset diabetes, but were less likely to receive statins (2347 [31%] vs 12,441 [37%]; p<0·0001) and renin-angiotensin-system inhibitors (1868 [25%] vs 9665 [29%]; p=0·006). INTERPRETATION: In clinic-based settings across Asia, one in five adult patients had young-onset diabetes. Compared with patients with late-onset diabetes, metabolic control in those with young-onset diabetes was poor, and fewer received organ-protective drugs. Given the risk conferred by long-term suboptimum metabolic control, our findings suggest an impending epidemic of young-onset diabetic complications. FUNDING: The Asia Diabetes Foundation (ADF) and Merck.

Blood pressure control and acceptability of perindopril and its fixed dose combinations with amlodipine or indapamide, in younger patients with hypertension.

OBJECTIVE: Recent hypertension guidelines recommend initiation of treatment with a fixed dose combination of two drugs for more effective and quicker blood pressure control. Few of these have been assessed for efficacy and acceptability. This study examines the short term blood pressure control and acceptability of perindopril, with or without its fixed dose combinations (FDC) with amlodipine and Indapamide in younger patients. METHODS: In a multicentre prospective observational study, patients with stage 1 hypertension were prescribed perindopril 4 mg per day. Those with stage 2 or 3 hypertension were prescribed a single tablet per day of 4 mg perindopril and 5 mg amlodipine (COVERSYL AM), or 4 mg perindopril and 1.25 mg indapamide (COVERSYL PLUS)for 45 days. The primary outcomes were the frequency of patients achieving blood pressure control and the adverse effect of pedal edema. RESULTS: Of 426 patients, with a mean age of 45 years, distributed throughout India, and an average (SD) baseline systolic/diastolic blood pressure of 157.2 (13.5)/98.6 (7.4), 303 (71.1%) achieved blood pressure control. Mean (SD) SBP/DBP decreased from baseline by 26.9 (12.6), and DBP by 15.4 (7.2) mm Hg. Few patients discontinued treatment, and the frequency of cough that interfered with sleep and ankle edema was low. CONCLUSION: In patients requiring combination antihypertensive treatment, the regimen of perindopril alone or its FDC with Indapamide or amlodipine reduces blood pressure effectively, resulting in high rates of blood pressure control over the short term, with a low frequency of side effects including cough and pedal edema.