OBJECTIVE -We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA) n microsatellite and a C/T polymorphism at the 5Ј region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) Ն20 g/min and albumin-to-creatinine ratio Ն3.5 mg/ mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA) n and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively. RESULTS -In the whole cohort, patients with diabetic retinopathy (n ϭ 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n ϭ 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The zϩ6 carriers of the (CA) n polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n ϭ 551) (4.3 vs. 9.3%, P ϭ 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 ϫ/Ϭ 7.2 vs. 21.9 ϫ/Ϭ 6.9 g/min, P ϭ 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with Ͻ5 years disease duration. The group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P ϭ 0.03) and T allele (26.4 vs. 18.5%, P ϭ 0.04) and a lower frequency of the zϩ6 allele (1.7 vs. 5.5%, P ϭ 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6, 95% CI 1.20 -5.83, P ϭ 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19 -5.19, P ϭ 0.02) were independent predictors for both diabetic nephropathy and retinopathy.CONCLUSIONS -Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy and diabetic retinopathy. Both the z-2 allele of (CA) n polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications. Diabetes Care 26:2410 -2415, 2003G lycemic control, blood pressure, and disease duration are known predictive factors for the development of diabetic microvascular complications, including nephropathy and retinopathy (1,2). However, not all diabetic patients develop microvascular complications. Family studies in Pima Indian and Caucasian populations suggest genetic influences in the development of these complications (3,4). There is also increasing evidence (5,6) showing that non-Caucasian (including Asian) diabetic patients have a higher risk of renal complications than Caucasian populations. In Hong Kong, up to 50% of type 2 diabetic patients attending ho...

Copper (Cu) is a necessary trace element participated in many physiological processes in plants. But excessive Cu2+ is toxic, which can activate intracellular signals that lead to cellular damage. The mitogen-activated protein kinase (MAPK) cascade is at the center of cell signal transduction and has been reported to be involved in stress-related signaling pathways. ZmMPK3, a kind of MAPKs in maize cells, can be activated by diverse abiotic stresses. In the present study, we investigated the effects of Cu2+ on hydrogen peroxide (H2O2) level, ZmMPK3 activity as well as the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and ascorbic acid peroxidase (APX) using maize leaf as an experimental model. The results demonstrated that acute Cu2+ exposure for 24 hours led to rapid increases of H2O2 level and the increase in ZmMPK3 activity as well as the total activities of antioxidant enzymes SOD, CAT and APX. H2O2 scavenger, dimethylthiourea (DMTU), effectively inhibited the Cu2+-increased H2O2 level and the activity of ZmMPK3 as well as the activities of the antioxidant enzymes SOD, CAT and APX. Pre-treatment with the MAPK inhibitor, PD98059, significantly blocked the Cu2+-increased activities of ZmMPK3, CAT, APX and SOD, but didn’t affect the accumulation of H2O2. Our results suggest that Cu2+ causes oxidative stress to the maize leaves which then activates defense antioxidant enzymes via MAPK pathway. Thus, the signaling pathway is Cu2+—H2O2—ZmMPK3—antioxidant enzymes.

OBJECTIVE -We examined the prevalence of different forms of diabetes in Hong KongChinese patients with familial early-onset type 2 diabetes and compared their clinical features with patients with familial late-onset type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 145 young patients with earlyonset diabetes (age and age at diagnosis Յ40 years) and a family history of diabetes were studied. They were screened for mutations in the genes encoding glucokinase, hepatocyte nuclear factor (HNF)-4␣, and HNF-1␣. The mitochondrial DNA A3 G at nucleotide 3243 (mt3243) and amylin S20G mutations were studied, and antibodies to GAD (anti-GADs) were also examined.RESULTS -The prevalence of putative diabetogenic gene mutations and autoimmune markers were 4% for glucokinase, 0% for HNF-4␣, 5% for HNF-1␣, 3% for mt3243, 2% for amylin S20G, and 4% for anti-GAD. Compared with late-onset patients, the patients with early-onset diabetes had a higher prevalence of a parental history of diabetes and were generally more obese. When classified by obesity indexes (BMI and waist circumference), the obese patients, especially those with early-onset diabetes, had a clustering of cardiovascular risk factors and increased rates of retinopathy and albuminuria.CONCLUSIONS -Genetic factors (up to 14%) and obesity (55%) play more significant roles than autoimmunity (4%) in familial type 2 diabetes in young Chinese patients. The significance of obesity-related genes and other gene-gene and gene-environment interactions in these young patients remains to be determined.