METHODS: Chinese and Malay men (n = 382) aged 20 years or above residing in the Klang Valley, Malaysia were recruited. Their fasting blood was collected for serum testosterone, sex hormone-binding globulin (SHBG) and 25-hydroxyvitamin D (25(OH)D) assays. Relationship between 25(OH)D and testosterone levels was analyzed using multiple regression analysis. Testosterone and SHBG levels among subjects with different vitamin D status were compared using univariate analysis. Confounders such as age, ethnicity and body mass index (BMI) were adjusted.
RESULTS: 25(OH)D was significantly and positively associated with total testosterone and SHBG levels before and after adjustment for age and ethnicity (p 0.05).
CONCLUSION: 25(OH)D is significantly associated with total testosterone and SHBG in Malaysian men but this association is BMI-dependent.
MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.
RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.
CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.
OBJECTIVE: This study sought to identify demographic, clinical, and genetic factors that may contribute to increased insulin resistance or worsening of glycaemic control in patients with T2DM.
SETTING: This prospective cohort study included 156 patients with T2DM and severe or acute hyperglycaemia who were treated with insulin at any medical ward of the National University of Malaysia Medical Centre.
METHOD: Insulin resistance was determined using the homeostatic model assessment-insulin resistance index. Glycaemic control during the episode of hyperglycaemia was assessed as the degree to which the patient achieved the target glucose levels. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify polymorphisms in insulin receptor substrate (IRS) genes.
MAIN OUTCOME MEASURE: Identification of possible predictors (demographic, clinical, or genetic) for insulin resistance and glycaemic control during severe/acute hyperglycaemia.
RESULTS: A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence interval (CI) 1.2-16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95 % CI 0.6-64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P < 0.05) may indirectly predict worsening of insulin resistance or glycaemic control in patients with severe/acute hyperglycaemia.
CONCLUSION: Clinical and genetic factors contribute to worsening of insulin resistance and glycaemic control during severe/acute hyperglycaemia in patients with T2DM. Early identification of factors that may influence insulin resistance and glycaemic control may help to achieve optimal glycaemic control during severe/acute hyperglycaemia.
METHODS: Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.
RESULTS: Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.
CONCLUSIONS: TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.