TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus.

Aim of the present study was to investigate the possible involvement of TNF-α signaling pathway and T-lymphocyte activation in DN. Eighty-two diabetic patients [39 male, age 69.5(56-78)years] were divided into three groups, according to Albumin/Creatinine ratio (ACR) levels, Group I (ACR < 30 µg/mg), Group II (ACR 30-300 µg/mg), Group III (ACR > 300 µg/mg). Urinary Tumor Necrosis Factor-α (TNF-α), and serum TNF-α, ΤNF-receptor 1 (TNFR1), TNFR2, B7-1, CD28, Cytoxic T-Lymphocyte-Associated protein-4 (CTLA4), were estimated. There were significant differences between Groups I, II, III regarding the concentration of urinary TNF-α (p < .001), serum TNFR1 (p < .001), serum TNFR2(p < .001), CTLA4 (p < .001) and CD28(p = .034). In multivariate analysis, independent parameters correlated with ACR were serum TNFR1 (p = .003), TNFR2 (p = .012) and urinary TNF-α (p = .015) levels. There was a significant correlation between markers of T-cell activation and TNF-α signaling pathway activation. Activation of TNF-α signaling pathway and T-lymphocytes seem to synergize and participate in the development of DN in type II DM.

Effect of quinapril or losartan alone and in combination on left ventricular systolic and diastolic functions in asymptomatic patients with diabetic autonomic neuropathy.

OBJECTIVE: To investigate the effect of angiotensin converting enzyme inhibition (ACE-I) or angiotensin receptor blockade (ARB), and their combination, on both diabetic autonomic neuropathy (DAN) and left ventricular (LV) diastolic dysfunction (LVDD) in asymptomatic patients with diabetes mellitus (DM). MATERIALS AND METHODS: Sixty-two patients (34 women) with long-term DM (24 with Type 1) and DAN, aged 51.7+/-13.9 years, free of coronary artery disease (CAD) or arterial hypertension (HT) at baseline, were studied for a 12-month period. Diagnosis of DAN was established if two or more of the standard cardiovascular reflex tests (CRT) were abnormal. Patients were randomly allocated to quinapril (20 mg/day), losartan (100 mg/day), or quinapril plus losartan (20 mg/day+100 mg/day). LV systolic and diastolic function was assessed using radionuclide ventriculography (RNV) at baseline and after 12 months of treatment. RESULTS: In all three treatment groups, abnormal CRT values were improved. In the quinapril group, the first third filling fraction (1/3FF, 48.9+/-17.8% vs. 39.2+/-12.9% at baseline, P=.005) was increased and the atrial contribution to ventricular filling (25.1+/-6.3 vs. 30.1+/-7.8, P=.027) was reduced in the losartan group; the peak filling rate (PFR) was improved (3.41+/-.62 vs. 3.11+/-.44 volumes/s, P=.05), and in the combination group, the 1/3FF (39.4+/-11.8% vs. 29.6+/-11.9%, P=.018) was markedly increased, while the time to peak filling (TPF; 147+/-42 vs. 184+/-33 ms, P=.02) and the TPF/filling time (TPF/FT; 32.5+/-6.2% vs. 38.2+/-5.7%, P=.016) were reduced. CONCLUSIONS: Early ACE-I or ARB improve both DAN and LVDD in asymptomatic patients with Type 1 or 2 DM, after 1 year of treatment. Their combination may be slightly better than monotherapies on DAN and LVDD. The clinical importance of these effects should be validated by larger studies.

Insulin pump therapy in adults.

Restoration of the physiological insulin secretion is a current medical challenge and a dream for patients with Diabetes Mellitus. Continuous insulin therapy using pumps was the first step to the development of artificial pancreas. The aim of diabetes treatment is to achieve strict glycemic control in order to avoid the development of long-term diabetic complications while reducing the frequency of hypoglycemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump, offers both a better blood glucose stability as compared to multiple daily injections and a broader flexibility in life mode, and reduces the frequency of severe hypoglycemia. The advantages of the insulin pump (consistency of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Finally, the use of CSII in patients with Diabetes Mellitus type 2 now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients.

Insulin therapy during hospitalization.

Hyperglycemia occurring during hospitalization is a common phenomenon among patients with or without a known history of diabetes mellitus. For several years, hyperglycemia in hospitalized patients had been considered as an accompanying characteristic of the acute disease that resulted in admission. That point of view changed over time mainly because of emerging indications from clinical studies showing that hyperglycemia during hospitalization could aggravate prognosis and increase mortality. Further studies engaged on how hyperglycemia should be treated, yielded results that highlighted the increasing risk of mortality due to hypoglycemia in such efforts and also questioned the initial relation between hyperglycemia during hospitalization and a poor prognosis. Based on the fact that there is still no common ground on what is the best approach on hyperglycemia of hospitalized patients, the best practice remains to follow a different regime with different glycemic goals for different patient groups. In this review, hospitalized patients are divided into three groups; intensive care unit patients (general and cardiac), non-intensive care unit patients (general and cardiac) and peri-operative patients.

Insulin and the heart.

The main role of insulin in the heart under physiological conditions is obviously the regulation of substrate utilization. Indeed, insulin promotes glucose uptake and its utilization via glycolysis. Insulin, promoting glucose as the main cardiac energy substrate, reduces myocardial O(2) consumption and increases cardiac efficiency. Moreover, insulin seems to augment cardiomyocyte contraction, while it affects favorably myocardial relaxation, increases ribosomal biogenesis and protein synthesis, stimulates vascular endothelial growth factor (VEGF) and thereby angiogenesis, suppresses apoptosis, promotes cell survival and finally ameliorates both myocardial microcirculation and coronary artery resistance, leading to increased blood perfusion of myocardium. Thus, insulin acts directly on heart muscle, and this action is mediated principally through PKB/Akt signal pathway. Under pathological conditions, such as type 2 diabetes, myocardial ischaemia, and cardiac hypertrophy, insulin signal transduction pathways and action are clearly modified. In this review we summarize the evidence that the heart is an important target of insulin action and that elimination of these actions is important in disease states.

Effects of improving glycemic control with insulin on leptin, adiponectin, ghrelin and neuropeptidey levels in patients with type 2 diabetes mellitus: a pilot study.

OBJECTIVE: Insulin therapy is associated with weight gain in patients with type 2 diabetes mellitus (T2DM). Several peptides are implicated in appetite control. We evaluated the effects of insulin-induced improved glycaemic control on leptin, adiponectin, ghrelin, neuropeptide Y (NPY) levels and patient characteristics. METHOD: Consecutive T2DM patients (n = 90) were divided into 2 groups: Group A: 45 insulin-naïve uncontrolled (glycosylated haemoglobin A(1c); HbA(1c )>7%) patients on oral hypoglycaemic agents (OHAs) who converted to insulin monotherapy. Group B: 45 well-controlled (HbA(1c )<7%) patients on OHAs. Both groups were monitored at baseline, 3 and 6 months. Males and females were analyzed separately because some hormone levels differ between genders. RESULTS: In both genders, insulin therapy (Group A) was associated with significant (p = 0.003 to <0.001) increases in weight, body mass index and leptin levels and significant decreases in glucose, HbA(1c) and NPY levels. In male insulin-treated patients a significant increase in adiponectin levels (p = 0.008) was observed. There were significant correlations (p = 0.016 to <0.001) between leptin levels, waist circumference and body fat in all patient groups, except group B males. CONCLUSION: Changes in leptin, adiponectin and NPY levels may occur after insulin-induced improved glycaemic control. These changes may be influenced by gender, weight, body fat and HbA(1c).