RESUMO
Diabetes mellitus imposes a tremendous burden on health economies mainly because of its devastating complications. A long duration of metabolic disturbances can cause vascular damage leading to both macro and micro vascular complications. There is an increasing evidence that atherosclerosis is accompanied by inflammation. Our aim in this study is to prove that a low grade inflammation accompany the diabetes mellitus and this inflammatory process is correlated to diabetic control and diabetic complications. Our study was done on 100 elderly diabetic patients whose total white blood cell count was in the normal range. Their age ranged from 65-85years with mean age of them is 68.1 years, half of them were males and the other half were females. They undergo full clinical examination and laboratory investigations including total white blood cell count, serum Creatine protein level, albumin level in urine. glycosylated haemoglobin in addition to other routine laboratory investigations. The patients were divided into 5 quintiles according to the distribution of the total white blood cell count and serum C-reactive protein level. We found a highly significant positive correlation [P value <0.0001] of the total white blood cell count and serum C-reactive protein level to the diabetes duration, body mass index, systolic and diastolic blood pressure, fasting and post prandial blood glucose levels, glycosylated haemoglobin, total cholesterol, low density lipoprotein-cholesterol, serum creatinine and albuminuria and a highly significant negative Correlation with the high density Iipoprotein-cholesterol [P value<0.0001]. We found also a highly significant positive correlation of the total white blood cell Count and serum C-reactive protein level with diabetic micro and macro vascular complications [P value<0.0001]. Moreover, there is an increased risk of macro and micro vascular complications with progressive quintiles of both white blood cell count and serum C-reactive protein level. The odds ratio for the group 5 of the total white blood cell count in comparison to group 1and2 equals 7.35 [confidence Interval= 3.12-9.31] for macro vascular complications and it equals 7.19 [confidence interval= 4.12-9.19] for micro vascular complications. The odds ratio for groups 3,4and 5 of the serum C-reactive protein level equals 9.31[confidence interval= 6.19-18.1] in comparison to groups 1 and 2 for macro vascular complications and it equals 7.31 [confidence interval= 5.19-15.9] for micro vascular complications. We found also an increased risk for smokers to develop both macro and micro vascular complications of diabetes mellitus , odds ratio equals 6.87[confidence interval= 2.14-22.06] and 3 [confidence interval=1.07-8.38] respectively compared with non smokers in the lowest quintile
RESUMO
Background: The development of cachexia is a particular predictor of adverse prognosis in chronic heart failure [CHF]. Less is known about anabolic metabolism in CHF. Leptin -the hormone product of obesity gene has been shown to inhibit food intake, increase energy expenditure and fat oxidation. Insulin sensitivity and secretion is related to leptin. Leptin has been reported also to stimulate proliferation of CD4 T cells and increases cytokine production. The study aimed to investigate leptin. Insulin sensitivity and tumor necrosis factor-alpha [TNF-alpha] in chronic heart failure with and without cachexia
Methods: We studied 31 male patients with CHF, mean age [59.87 +/- 6.91 years], mean New York Heart Association Functional Class [2.52 +/- 0.81], mean left ventricular ejection fraction [LVEF] [0.33+0.08] and 13 male healthy control subjects, mean age [59.87 +/- 6.91]. Of the CHF patients, 14 were cachectic [cCHF] with non-oedematous weight loss >7.5% over at least6 months and 17 non-cachectic. Serum insulin was measured by enzyme immunoassay, insulin sensitivity was assessed by intravenous glucose tolerance. Serum leptin and TNF were meas ured using commercially available ELISA kit
Results: Compared with the healthy control subjects, patients had elevated levels of leptin, fasting insulin and TNF-alpha [P<0.001], with reduced insulin sensitivity [P<0.001]. Both ncCHF and cCHF subgroups had higher leptin and TNF levels than the control group [P<0.001]. The cCHF subgroup-compared with ncCHF subgroup-showed reduced leptin and fasting insulin levels [P<0.001 and P<0.01] respectively and elevated TNF-alpha levels [P<0.001]. In both patients and control subjects there was a positive correlation between leptin and fasting insulin levels [r=0.59, P<0.001 and r=0.54, P<0.05] respectively. The relative risk of incidence of cCHF in NYHA Functional class [I and II] versus NYHA Functional class [III and IV] was 0.427 [P<0.05]
Conclusion: CHF is hyperleptinaemic state and is associated with decreased insulin sensitivity and elevated fasting plasma insulin levels. The state of cardiac cachexia is associated with higher TNF-alpha levels and more worse NYHA Functional Class. Leptin and TNF-alpha may be valid targets for novel therapeutic interventions in patients with CHF