Fotios Iliadis

The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus:

Background Diabetes mellitus (DM) and chronic inflammation are strongly related to increased cardiovascular risk. The purpose of this study was to evaluate whether an aerobic training programme would ameliorate inflammatory and anti-inflammatory markers in patients with type 2 DM. Design Interventional study. Methods A total of 60 overweight individuals with type 2 DM, but without vascular complications, were randomly assigned to either a 6-month aerobic exercise training programme (four times/week, 45-60 min/session), designated as exercise group, or to the control group. All participants were on an oral antidiabetic regimen and none was receiving lipid-lowering medications. Anthropometric parameters, cardiorespiratory fitness, glycaemic and lipid profiles, high sensitivity C-reactive protein (hs CRP), adiponectin, interleukin (IL)-10, IL-18, tumour necrosis factor (TNF)-a, insulin, reciprocal index of homoeostasis model assessment (HOMA-IR), body fat and blood pressure (BP) were measured at baseline and at the end of the study. Results In comparison with baseline and control group, exercise-treated patients improved glucose control, lipid profile, exercise capacity (Vo2 peak) and exhibited decreased insulin resistance and systolic BP considerably (P < 0.05). Plasma adiponectin, TNF-α and body weight changed slightly across treatment (P > 0.05), whereas diastolic BP and fat mass tended to decrease (P = 0.071 and 0.061, respectively). Exercise training reduced hs CRP (from 0.48 ± 0.16 to 0.29 ± 0.2 mg/dl; P = 0.04) and IL-18 (from 315.19 ± 122.76 to 203.77 ± 96.02 pg/ml; P = 0.02). Moreover, exercise provided anti-inflammatory protection through IL-10 increment (P = 0.039) and IL-18/IL-10 ratio downregulation (P = 0.014). In multiple regression analysis, alteration in IL-18 was independently correlated with hs CRP and Vo2 peak changes (P < 0.05). Conclusion Aerobic exercise training without significant weight loss improves metabolic profile and exerts anti-inflammatory effects in patients with type 2 DM. Eur J Cardiovasc Prev Rehabil 14: 837-843

Neuropeptide Y and alpha-melanocyte-stimulating hormone: interaction in obesity and possible role in the development of hypertension

Aim:  Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha‐melanocyte‐stimulating hormone (a‐MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity.

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.

Exercise training ameliorates the effects of rosiglitazone on traditional and novel cardiovascular risk factors in patients with type 2 diabetes mellitus

The aim of the study was to investigate the effects of rosiglitazone and/or exercise training on novel cardiovascular risk factors in patients with type 2 diabetes mellitus. One hundred overweight/obese type 2 diabetes mellitus patients, with inadequate glycemic control (hemoglobin A(1c) >7%) despite combined treatment with gliclazide plus metformin, were randomized using a 2 x 2 factorial design to 4 equivalent (n = 25) groups, as follows: (1) CO: maintenance of habitual activities, (2) RSG: add-on therapy with rosiglitazone (8 mg/d), (3) EX: adjunctive exercise training, and (4) RSG + EX: supplementary administration of rosiglitazone (8 mg/d) plus exercise training. No participant had diabetic vascular complications or was receiving lipid-lowering therapy. Anthropometric parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein (apo) A-I, apo B, interleukin (IL)-10, IL-18, insulin resistance, and blood pressure were measured before and after 12 months of intervention (P < .05). Both RSG and EX groups significantly reduced glycemic indexes, insulin resistance, blood pressure, and IL-18, whereas they significantly increased high-density lipoprotein, cardiorespiratory capacity, and IL-10, compared with CO group (P < .05). Besides this, exercise-treated patients conferred a remarkable down-regulation in the rest of lipid parameters (total cholesterol, low-density lipoprotein cholesterol, triglycerides, apo B) and body fat content (P < .05) in comparison with CO group. On the other hand, RSG group rather than CO group considerably increased apo A-I levels and body mass index (P < .05). Notably, the combined treatment group yielded pronounced beneficial changes in glycemic indexes, lipid profile, insulin resistance, blood pressure, IL-10, IL-18, apo A-I, and apo B (vs CO group, P < .05). Furthermore, the addition of exercise to rosiglitazone treatment counteracted the drug-related negative effects on body weight, low-density lipoprotein, and total cholesterol. Rosiglitazone plus exercise training elicited additive effects on body composition, glycemic control, and traditional and novel cardiovascular risk factors in type 2 diabetes mellitus patients, indicating complementary effects.

Cardiorespiratory capacity is associated with favourable cardiovascular risk profile in patients with Type 2 diabetes

OBJECTIVE The aim of this study was to examine the interaction between cardiorespiratory capacity and cardiovascular risk factors in patients with Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN/METHODS A total of 92 patients with T2DM (40 men, 52 women) performed a symptom-limited exercise test on ergocycle, with continuous gas exchange measurement. All patients were overweight or obese (body mass index >25 kg/m(2)), with poor glycemic control (hemoglobin A(1c) >7%), but free from overt diabetic vascular complications. Anthropometric parameters, blood pressure (BP), cardiorespiratory fitness, glycemic and lipid profile, fibrinogen, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein (hsCRP), insulin resistance, and 24-h urinary albumin excretion (UAE) were measured. Based on the median Vo(2) peak value, participants were placed into low fitness (LF, n=46) or moderate fitness group (MF, n=46). RESULTS In univariate analysis, exercise capacity correlated with systolic (r=-0.349) and diastolic BP (r=-0.441), waist circumference (r=-0.345), total cholesterol (r=-0.348), high-density lipoprotein (HDL) (r=0.362), UAE (r=-0.486), homeostasis model assessment (HOMA-IR) (r=-0.467), uric acid (r=-0.316), and hsCRP (r=-0.217, only in women subgroup) (P<.05). With the exception of the latter three variables, the above associations remained significant after controlling for age and sex in multiple regression analysis (P<.05). Compared to LF group, patients in MF group showed significantly higher levels of HDL and lower levels of BP, waist circumference, hsCRP, and HOMA-IR (P<.05). In addition to this, UAE tended to be lower in fit patients (P=.054). CONCLUSIONS Low cardiorespiratory fitness seems to be independently associated with most traditional and emerging cardiovascular risk factors in patients with T2DM. Even a moderate increase of cardiorespiratory fitness exerts beneficial effects on cardiovascular risk profile.

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.

Is the Anti-Hypertensive Effect of Dietary Supplements via Aldehydes Reduction Evidence Based? A Systematic Review

Growing evidence indicates that insulin resistance and oxidative stress are involved in the pathogenesis of essential hypertension. In insulin-resistant states, like obesity and type 2 diabetes, altered glucose metabolism may lead to increased formation of methylglyoxal and other ketoaldehydes. Animal studies have shown that increased levels of endogenous aldehydes may lead to hypertension and oxidative stress. In animal models, the administration of vitamin C, vitamin B6 or alpha-lipoic acid reduced tissue levels of aldehydes, prevented oxidative stress, and lowered blood pressure. The purpose of this review article is to critically evaluate the available evidence for the role of dietary supplements in hypertension treatment.

Beneficial effects of rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus

Aim  Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients.

TNF-α and microalbuminuria in patients with type 2 diabetes mellitus.

Aim. Recent evidence suggests that chronic subclinical inflammation plays a key role in the pathogenesis and progression of diabetic nephropathy. Aim of the present study was to investigate possible correlation between the presence and degree of microalbuminuria and markers of inflammation in patients with type 2 diabetes mellitus (DM). Patients-Methods. Eighty patients were enrolled and clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was calculated in first-morning urine samples. Serum and urinary tumor necrosis factor-α (TNF-α) levels were determined by ELISA. Results. Forty-five patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria. Patients with microalbuminuria were older, with higher glycosylated hemoglobin levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and cardiovascular disease and were on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was significantly correlated with the presence of cardiovascular disease, hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF-α levels but had a strong correlation with urinary TNF-α levels. Conclusions. In patients with type 2 DM, urinary, but not serum, TNF-α levels are associated with the presence and severity of microalbuminuria.

Initiative for a new diabetes therapeutic approach in a Mediterranean country: the INDEED study

ABSTRACT Aim: To assess the efficacy of a strategy to improve vascular risk management in patients with type 2 diabetes mellitus (T2DM). Methods: This was a pilot best practice implementation enhancement programme that enrolled 578 patients with T2DM. A baseline visit was followed by a concerted effort from previously trained physicians to improve adherence to lifestyle advice and optimise drug treatment for all vascular risk factors. The patients were followed-up for 6 months. The UKPDS risk engine was used to estimate vascular risk in patients without established coronary heart disease (CHD) (n = 279). Results: There was an improvement in compliance to lifestyle measures and increased prescription of evidence-based medication. In patients without established CHD there was a 37% reduction in estimated risk for CHD, 44% for fatal CHD, 10% for stroke and 25% for fatal stroke (p ≤ 0.003 for all comparisons vs. baseline). There was also a substantial increase in the proportion of patients with established CHD who achieved their vascular risk factor targets. Conclusions: This is the first study to increase the adherence to multiple interventions in patients with T2DM in both primary care and hospital settings. Education of physicians and patients, distribution of guidelines/brochures, and the completion of a one-page form, motivated both physicians and patients to achieve multiple vascular risk factor goals.