The study group.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)69703-1.pdf

Epidemic obesity and type 2 diabetes in Asia

Iodine-deficiency disorders

Oxidative stress results from a cell or tissue failing to detoxify the free radicals that are produced during metabolic activity. Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism. This review explores the concept that diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia cause oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy. Proteins that are damaged by oxidative stress have decreased biological activity leading to loss of energy metabolism, cell signaling, transport, and, ultimately, to cell death. Examination of the data from animal and cell culture models of diabetes, as well as clinical trials of antioxidants, strongly implicates hyperglycemia-induced oxidative stress in diabetic neuropathy. We conclude that striving for superior antioxidative therapies remains essential for the prevention of neuropathy in diabetic patients.

/pdf/oxidative-stress-in-the-pathogenesis-of-diabetic-neuropathy-3e2r3aiuth.pdf

Oxidative stress in the pathogenesis of diabetic neuropathy.

IL-10, IL-6, and TNF-α: Central factors in the altered cytokine network of uremia—The good, the bad, and the ugly

1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.

Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.

Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

Objective— To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake. Research Design and Methods— The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects ≥ 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT. Results— The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5–14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, ≥ 40 yr of age, an income > M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes. Conclusions— Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.

Prevalence of NIDDM and impaired glucose tolerance in aborigines and malays in Malaysia and their relationship to sociodemographic, health, and nutritional factors

Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p < 0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p < 0.01), but an increase in E-selectin levels (p < 0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p < 0.05) and IL-6 levels (p < 0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.

Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia.

This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.

/pdf/tocotrienols-rich-diet-decreases-advanced-glycosylation-end-2w9l4loh4d.pdf

Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats.

B. A K Khalid

Papers

Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.

Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

Prevalence of NIDDM and impaired glucose tolerance in aborigines and malays in Malaysia and their relationship to sociodemographic, health, and nutritional factors

Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia.

Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats.