HLA-DQ A1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction.

HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.

Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control.

We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (p<0.005), 1.2+/-1.3% (p<0.0005) and 1.3+/-1.4% (p<0.0005) at week 4, at week 8 and week 12, respectively. Subjects who continued their existing combination treatment of sulphonylurea, metformin+/-acarbose also showed a significant reduction in HbA(1c) (p<0.05). Although effective in reducing glycemic parameters, there was no reduction in CRP levels in either treatment group. The treatment regimen consisting of rosiglitazone and glimepiride significantly lowered hs-CRP by -2.6 (3.9) mg/L (p<0.05) at week 12 in spite of no improvement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.

New coronary risk factors: is there a difference between diabetic patients with microalbuminuria compared to those without microalbuminuria?

Diabetes mellitus is an important risk factor for the development of coronary artery disease. The presence of microalbuminuria, which indicates renal involvement in diabetic patients, influences the progression of coronary artery disease. New coronary risk factors such as C-reactive protein (CRP), Lipoprotein a [Lp (a)] and fibrinogen are increasingly being recognized as important cardiovascular prognostic factors. These new coronary risk factors could account for the worse cardiovascular prognosis in diabetic patients with microalbuminuria. Our cross sectional study was to compare the prevalence of elevated CRP and the levels of Lp (a) and fibrinogen between diabetic patients with microalbuminuria and those without microalbuminuria. Diabetic patients with overt coronary artery disease were excluded from the study. A total of 108 patients were recruited of which 57 patients had microalbuminuria and 51 were without microalbuminuria. There was no difference in the number of patients with elevated CRP between these two groups. There were also no significant differences in the mean values of Lp (a) and fibrinogen between diabetic patients with and without microalbuminuria. The inflammatory marker CRP and coagulopathy markers i.e. Lp (a) and fibrinogen seem not to be perturbed in diabetic patients with microalbuminuria.

Effect of Tai Chi exercise on DNA damage, antioxidant enzymes, and oxidative stress in middle-age adults.

BACKGROUND: The biochemical mechanisms involving oxidative stress to explain the relationship between exercise and healthy aging are still unclear. METHODS: Tai Chi participants and matched sedentary volunteers age 45 and above were enrolled. Glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities; levels of DNA damage using the comet assay; and malondialdehyde (MDA) and advanced glycation end products (AGE) were determined at 0, 6, and 12 months. RESULTS: Tai Chi subjects had decreased normal and increased mildly damaged DNA with elevated GPx activity after 6 months (n=25). Plasma MDA and AGE concentrations decreased significantly after 12 months (n=15) accompanied by increased SOD activity. This may be attributed to the hormesis effect, whereby mild induction of oxidative stress at the first 6 months of exercise resulted in stimulation of antioxidant defenses. These parameters were unchanged in the sedentary subjects in the first 6 months (n=27) except for elevated SOD activity. After 12 months, the sedentary subjects (n=17) had decreased normal DNA and increased severely damaged DNA with unaltered MDA and AGE levels while SOD and GPx activities were significantly elevated. CONCLUSION: Regular Tai Chi exercise stimulated endogenous antioxidant enzymes and reduced oxidative damage markers.