Statins ; A double weapon in treating dyslipidemic osteoporotic menopausal type 2 diabetics

Recent reports have been suggested the possible role of 3-hydroxy-3 methyl gluteryl Coenzyme A [HMG-C0A] reductase inhibitors to represent an entirely new approach in treating osteoporosis by stimulating the proliferation and differentiation of osteoblasts, the specialized cells that create new bone formation. Also, statins have been reported to prevent bone resorption through blocking an early step in mevalonate pathway and so preventing prenylation, a step that is required for osteoclasts function. The aim of the present work was to study the effect of HMG-CoA reductase inhibitors [statins]; simvastatin and pravastatin, on bone mineral density [BMD] of dyslipidemic postmenopausal females with type 2 diabetes mellitus and having osteoporosis. Thirty postmenopausal dyslipidemic type 2 diabetic females above 50 years with no history of any disease or drugs that affect bone metabolism were included in this study and classified into 2 groups; I] included 15 patients received 40mg daily of simvastatin and II] included 15 patients received 40mg daily of pravastatin both for 3 months. Each patient was subjected to full history taking, complete clinical examination, laboratory investigations including, fasting and post-prandial plasma glucose, glycosylated haemoglobin, alanine aminotransferase [ALT], serum cholesterol and triglycerides, serum calcium [total and ionized] and phosphorus. Serum osteocalcin, biochemical marker of bone formation, was measured by immunometric assay and urinary deoxypyridinoline [DPD], biochemical marker of bone resorption was measured by competitive immunoassays. Dual energy X-ray absorptiometry [DEXA] was used to assess BMD of forearm [peripheral site] and L2-L3 lumbar vertebrae [axial site]. The results of the present work can be summarized as follows; the serum levels of osteocalcin and the BMD revealed significant increase and the urinary levels of DPD revealed significant decrease after 3 months of simvastatin in group I. A mild change in osteocalcin, urinary DPD and BMD had been noticed after 3 months of pravastatin in group II, yet it did not reach a statistical significant level. Also, there was significant reduction of serum cholesterol and triglycerides levels after 3 months therapy of either simvastatin or pravastatin and none of the patients showed any abnormal change in ALT levels supporting the safety of these drugs regarding their effect on the liver. Our results suggest the beneficial unexpected role of lipophyllic statins, simvastatin, in prevention and treatment of osteoporosis. Further studies are needed to reach the best effective dose and mode of administration of statin in preventing and treating osteoporosis. Also, the possibility of using statins in combination with other currently used drugs in this domain

Erythropoitin level in diabetics with and without autonomic neuropathy: relation to anaemia and metabolic control

Anaemia is a frequently noted complication of diabetes. There are several causes for anaemia in diabetes, however, in some diabetic anaemic patients the cause of their anaemia was not clearly explained despite differential hematological studies. This study aimed to measure the level of erythropoietin [EPO] in diabetic anaemic patients with and without autonomic neuropathy, and to compare this level with non-diabetic anaemic patients as control. We therefore studied the clinical and biochemical characteristics of 40 diabetic patients with anaemia of uncertain cause and patients were subdivided into two groups: those complicated with autonomic neuropathy [Group I, n=20], and those without autonomic neuropathy [Group II, n=20]. In addition, we enrolled 20 non-diabetic patients with similar degree of anaemia [Group Ill, n=20] in order to compare the serum EPO responsiveness to anaemia. The haemoglobin levels of diabetic patients correlated with creatinine clearance [r=0.34, p=0.009], but showed no relation to age, sex, duration of diabetes, or glycosylated haemoglobin percentage. The serum EPO concentrations of Group I patients [11.41 +/- 2.58 mIU/ml] were significantly lower than those of Group II[29.92 +/- 6.27 mIU/ml], and Group Ill [38.66 +/- 12.90 mIU/mI]. We concluded that the relatively low serum EPO levels of Group I patients could be the cause of their anaemia, and that the autonomic neuropathy complicating this group of diabetic anaemia patients could be the cause of this blunted EPO responsiveness to anaemia

Correlation of bone mineral density with peripheral neuropathy in patients with insulin dependent diabetes mellitus

To investigate whether peripheral neuropathy [PN], as part of the microangiopathic complex, can affect bone mineral density [BMD] of the axial skeleton in patients with type 1 diabetes. Three studied groups where examined. Group 1 comprised 15 males with type 1 diabetes and severe PN with a mean duration of diabetes of 11.07 +/- 2.31 years and an HbA1c% of 9.40+ 1.01.Group2 comprised 15 males type 1 diabetic patients with absent or mild PN matched to patients of group 1 regarding age, weight, and duration of diabetes. Group3 comprised 15 control subjects. BMD was measured by dual energy x-ray absorptiometry [DEXA] of the axial skeleton. In group 1, BMD was significantly reduced in the axial skeleton compared with an expected Z score of 0 [spine, -1.26 +/- 0.52]. To a lesser exlent, but still significantly, group 2 also showed reduced BMD values [spine, -0.54 +/- 0.16],whereas group 3 had normal BMD values [spine, -0.19 +/- 0.23]. Group 1 had lower mean BMD level than group 2 and group 3 at the measured sites which was statistically significant [analysis of variance, P< 0.001]. No significant differences in physical activity levels or serum calcium, serum phosphorus, alkaline phosphatase, were demonstrated between the two patient groups. The present results suggest that in patients with type 1 diabetes PN may be an independent risk factor for reduced BMD in the axial skeleton

Tumor Necrosis factor - alpha, leptin and insulin resistance [peripheral sensitivity] in type 2 diabetes

Aim: Insulin resistance appears to play a pivotal role in the pathogenesis of type 2 diabetes and other chronic diseases including hypertension, cardiovascular disease and hyperlipidemia. Alterations in tumour necrosis factor-alpha [TNF-alpha] and leptin are suggested to be primary metabolic abnormalities leading to insulin resistance. The main aim of this work was to evaluate the serum level of TNF-alpha and leptin in type 2 diabetes mellitus and to correlate these levels with the degree of insulin resistance. Subjects and We studied 40 type 2 diabetic patients and 20 healthy controls. All patients and controls were subjected to history taking, clinical examination and laboratory studies including oral glucose tolerance curve with estimation of serum glucose and insulin, plasma TNF-alpha, serum leptin, lipid profile, serum uric acid and micro-albuminuria. Insulin sensitivity index [SI] was calculated. We found that serum TNF-alpha, serum leptin, total cholesterol, triglycerides, LDL-C, uric acid and micro-albumin were significantly higher in the diabetic group than in the healthy control subjects [P<0.05]. TNF-alpha and leptin were negatively correlated with the degree of insulin sensitivity. Conclusions: We concluded that both TNF-alpha and leptin may play an important role in insulin resistance syndrome in type 2 diabetes

study of diastolic function in insulin dependent diabetic patients in relation to metabolic control and diabetic microangiopathy

Left ventricular diastolic function was assessed in insulin-dependent diabetic patients in relation to metabolic control and microangiopathy in the absence of cardiac manifestations. According to the degree of control and the presence of microangiopathy, three groups of patients were presented: Group 1 with poor control and with evidence of microangiopathy, group 2 with good control and without microangiopathy and group 3 with poor control and without microangiopathy. Group 1 showed marked reduction in diastolic function in the form of increase in peak [A], decrease in peak E/peak A, prolongation of filling rate and an increase in atrial contribution to left ventricular filling. Group 2 patients showed no effect in diastolic function as compared with the control group. Group 3 showed no difference in diastolic function as compared with the controls

study of systolic function in insulin dependent diabetic patients in relation to metabolic control and diabetic microangiopathy

Left ventricular systolic function was assessed in insulin- dependent diabetic patients in relation to metabolic control and microangiopathy in the absence of cardiac manifestations. According to the degree of control and the presence of microangiopathy, The patients were classified into three groups: Group 1 with poor control and with evidence of microangiopathy, group 2 with good control and without microangiopathy and group 3 with poor control and without microangiopathy. Group 1 showed marked reduction in systolic function in the form of decrease in ejection fraction, fractional shortening, prolongation of pre-ejection period [PEP] and PEP/left ventricular ejection index, and increase in septal thickness, which was correlated with the degree of increase in blood pressure. Patients included in group 2 showed no effect in systolic function as compared with control group. Group 3 showed only increase in cardiac output, ejection fraction and functional shortening compared to the control group