rotein glycation, insulin sensitivity and pancreatic beta cell function in high-risk, non-diabetic, first degree relatives of patients with type 2 diabetes.

Insulin resistance and impaired beta cell function are widely recognized as features of type 2 diabetes. But it is still debated whether insulin resistance or beta cell dysfunction constitutes the primary abnormality. This study was done to evaluate the impact of family history of type 2 diabetes on insulin resistance, beta cell function and glycation of proteins. A total of 30 healthy subjects with a positive family history of type 2 diabetes and thirty two healthy age-matched subjects without any family history of type 2 diabetes were enrolled in this study. Fasting glucose, post prandial glucose, fasting plasma insulin, fructosamine and glycated hemoglobin were evaluated in both the study groups. The mean fasting glucose, fasting Insulin and HOMA-IR were significantly higher among the first-degree relatives of type 2 diabetics, but there was no alteration in HOMA-B. The levels of both glycated hemoglobin and fructosamine were significantly increased in the test group when compared with controls. In conclusion the results from the present study suggest that Indian subjects with family history of type 2 diabetes are associated with insulin resistance and enhanced glycation of proteins, but with no evidence of beta cell defect.

Altered oxidant-antioxidant status in non-obese men with moderate essential hypertension.

BACKGROUND: Although a wide number of experimental evidences are available regarding oxidant-antioxidant disturbance in hypertension, clinical data supporting it is lacking in men in early stages of hypertension. AIMS: The objective of the study was to evaluate oxidative status and antioxidant activities in males with stage I essential hypertension. MATERIALS AND METHODS: Thirty hypertensives and 21 normotensives were included in the study. Protein carbonyl, reduced glutathione, glutathione peroxidase, catalase and fasting glucose were assessed in both the groups. STATISTICAL ANALYSIS: Results were analyzed by student's 't' test and linear regression analysis test. RESULTS: Plasma protein carbonyl and glutathione peroxidase were significantly increased and catalase and GSH were significantly reduced in the hypertensive group compared to normotensive subjects. There was a significant negative correlation between glutathione peroxidase and catalase in the test group. CONCLUSIONS: The data from the present study indicates an alteration in oxidant-antioxidant status in non-obese men in early stages of essential hypertension.

Increased glycated hemoglobin level in non-diabetic nephrotic children is associated with oxidative stress.

Glycation and lipid peroxidation are spontaneous reactions believed to contribute to the pathogenesis of nephrotic syndrome. Possible interrelations of glycated hemoglobin with reduced glutathione and malondialdehyde were evaluated in nephrotic syndrome patients. Eighteen nephrotic syndrome patients and 15 healthy controls were enrolled for this study. Glycated hemoglobin, reduced glutathione, malondialdehyde and fasting glucose were analyzed for their correlation in both the groups. In nephrotic syndrome patients, while glycated hemoglobin and malondialdehyde levels were found to be significantly increased, glutathione levels decreased significantly when compared with controls. Glycated hemoglobin was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. Erythrocytes depleted of glutathione, by pre-treatment with 1-chloro-2, 4-dinitrobenezene, were found to have higher glycated hemoglobin levels when compared with erythrocytes incubated with glucose alone. These data suggest that glycated hemoglobin levels are closely associated with malondialdehyde and glutathione in nephrotic syndrome patients.

Antioxidant response to oxidative stress induced by smoking.

Oxygen free radicals have been hypothesized to play a pivotal role in the deleterious effects of smoking on health. The present study was undertaken to examine the oxidant and antioxidant system among smokers and nonsmokers. Fourteen smokers and 11 nonsmokers were enrolled for this study. The protein carbonyl levels in smokers were found to be significantly higher than in nonsmokers. The levels of plasma ascorbic acid, free sulfhydryl group, and erythrocyte reduced glutathione were lower in smokers compared to nonsmokers. In smokers the erythrocyte activities of both glutathione peroxidase and catalase were decreased when compared to that in nonsmokers. The data from the study reemphasizes the presence of oxidative stress in smokers. The concomitant decrease in the activities of both catalase and glutathione peroxidase found in the erythrocytes of smokers raises rational grounds for expressing concern over the increased susceptibility towards oxidative stress in these subjects.

Nonenzymatic glycation of plasma proteins in smokers.

Glycation is known to play a key role in complications of many pathophysiological processes. The present study was carried out to assess whether there are abnormalities of nonenzymatic glycation of proteins in smokers. Fourteen current smokers and 10 healthy nonsmokers were enrolled for the present study. Fasting plasma glucose, insulin, fructosamine and total plasma glycated proteins were evaluated. A significant rise in the mean levels of fructosamine and total plasma glycated proteins were found in smokers when compared with controls. Significant difference in insulin values was observed between these two groups. When Pearson's correlation analysis was performed, no significant correlation was found between fasting plasma glucose with either fructosamine or total plasma glycated protein levels. These data suggest an increased glycation of proteins in smokers independent of glucose concentration.

An evaluation of thyroid hormone status and oxidative stress in undialyzed chronic renal failure patients.

Chronic renal failure (CRF) patients on prolonged dialysis have been found to have significant alteration in their thyroid status, but little is known about the same in undialyzed CRF patients. Oxidative stress has been implicated as the key player in altering the levels of thyroid hormone in euthyroid sick syndrome. This study was performed to evaluate the levels of oxidative stress and thyroid status in undialyzed CRF patients. A case control study was performed on 20 undialyzed CRF patients and 20 control subjects. There was a significant decrease in the levels of T3, T4, total protein and albumin levels in CRF patients when compared to control. There was a significant increase in the level of malondialdehyde and total antioxidant status in CRF patients when compared with control subjects. The present study confirms oxidative stress along with altered thyroid status in CRF patients.

Effect of smoking on lipid profile and lipid peroxidation in normal subjects.

The aim of the present study was to assess the association between smoking and the alteration in plasma concentration of lipid profile and lipid peroxides. Fourteen smokers and 11 age matched control were enrolled. Plasma levels of fasting cholesterol, triglycerides, lipoprotein cholesterol and malondialdehyde were estimated. In smokers the levels of total cholesterol, LDL cholesterol, Non-HDL cholesterol and MDA were significantly elevated when compared with the controls. The atherogenic index as indicated by various risk ratios were also found to be increased in smokers as compared to controls. These findings indicate that current smokers are at a pro- atherogenic state and as in other countries, in India smokers require particular attention in terms of public health interventions.

Assessment of luteal rescue and desensitization of macaque corpus luteum brought about by human chorionic gonadotrophin and deglycosylated human chorionic gonadotrophin treatment.

The objective of the current study was to investigate the mechanism by which the corpus luteum (CL) of the monkey undergoes desensitization to luteinizing hormone following exposure to increasing concentration of human chorionic gonadotrophin (hCG) as it occurs in pregnancy. Female bonnet monkeys were injected (im) increasing doses of hCG or dghCG beginning from day 6 or 12 of the luteal phase for either 10 or 4 or 2 days. The day of oestrogen surge was considered as day '0' of luteal phase. Luteal cells obtained from CL of these animals were incubated with hCG (2 and 200 pg/ml) or dbcAMP (2.5, 25 and 100 μM) for 3h at 37°C and progesterone secreted was estimated. Corpora lutea of normal cycling monkeys on day 10/16/22 of the luteal phase were used as controls. In addition the in vivo response to CG and deglycosylated hCG (dghCG) was assessed by determining serum steroid profiles following their administration. hCG (from 15-90 IU) but not dghCG (15-90 IU) treatment in vivo significantly (P < 0·05) elevated serum progesterone and oestradiol levels. Serum progesterone, however, could not be maintained at a elevated level by continuous treatment with hCG (from day 6-15), the progesterone level declining beyond day 13 of luteal phase. Administering low doses of hCG (15-90 IU/day) from day 6-9 or high doses (600 IU/day) on days 8 and 9 of the luteal phase resulted in significant increase (about 10-fold over corresponding control P < 0·005) in the ability of luteal cells to synthesize progesterone (incubated controls) in vitro. The luteal cells of the treated animals responded to dbcAMP (P < 0·05) but not to hCC added in vitro. The in vitro response of luteal cells to added hCG was inhibited by 0, 50 and 100% if the animals were injected with low (15-90 IU) or medium (100 IU) between day 6-9 of luteal phase and high (600 IU on day 8 and 9 of luteal phase) doses of dghCG respectively; such treatment had no effect on responsivity of the cells to dbcAMP. The luteal cell responsiveness to dbcAMP in vitro was also blocked if hCG was administered for 10 days beginning day 6 of the luteal phase. Though short term hCG treatment during late luteal phase (from days 12-15) had no effect on luteal function, 10 day treatment beginning day 12 of luteal phase resulted in regain of in vitro responsiveness to both hCG (P < 0·05) and dbcAMP (P < 0·05) suggesting that luteal rescue can occur even at this late stage. In conclusion, desensitization of the CL to hCG appears to be governed by the dose/period for which it is exposed to hCG/dghCG. That desensitization is due to receptor occupancy is brought out by the fact that (i) this can be achieved by giving a larger dose of hCG over a 2 day period instead of a lower dose of the hormone for a longer (4 to 10 days) period and (ii) the effect can largely be reproduced by using dghCG instead of hCG to block the receptor sites. It appears that to achieve desensitization to dbcAMP also it is necessary to expose the luteal cell to relatively high dose of hCG for more than 4 days.