Late potentials: are they related to cardiovascular complications in children with type 1 diabetes?

INTRODUCTION: The aim of our study was to assess the influence of cardiovascular complications on the occurrence of late ventricular potentials (LP) in children with diabetes mellitus type 1. MATERIALS AND METHODS: 72 children (36 boys and 36 girls), with average course of diabetes type 1 of 6.5+/-2.8 years, were included into the study. Standard physical examination, blood pressure measurements, signal-averaged electrocardiogram (SAECG), autonomic test, 24-h Holter monitoring, and Doppler echo investigations were performed. The control group consisted of 55 sex- and age-matched healthy children. We utilised nonlinear logistic regression analysis to assess the effect of disease duration, albuminuria, insulin demand, cardiac autonomic neuropathy (CAN), heart rate variability (HRV) indices, diabetes complication score, metabolic control, systolic and diastolic blood pressure, left ventricular parameters, and ventricular arrhythmias on LP occurrence. RESULTS: LP was discovered in 12 patients with diabetes and in 1 from the control group (P<.014). Diabetic children with LPs had thicker left ventricular posterior wall (LVPW) and longer diabetes duration time than children without LP (P<.045 and.031, respectively). Nonlinear regression model shows that duration of diabetes, CAN, and LVPW were the strongest independent parameters of LP occurrence (P<.001,.01 and.005, respectively). CONCLUSIONS: Diabetes type 1 is associated not only with increased occurrence of abnormal SAECG but also with LP presence. The disease duration, posterior wall thickness, and CAN are independent predictors of LP appearance in diabetes type 1 children. The presence of cardiovascular complication has no influence on LP occurrence in diabetic children.     

PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy?

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the PPAR family. The endogenous activators of all members of the PPAR family are a variety of fatty acids, which suggests that the PPARs are highly involved in lipid metabolism. In the present paper, the current understanding of the involvement of PPARgamma in adipocyte proliferation and adipose tissue formation is extensively reviewed, and it is stressed that PPARgamma seems to be a major regulator in the differentiation of adipocytes. Thiazoledinediones (TZDs) are a group of PPARgamma-agonists used in the treatment of type 2 diabetes (T2D) since 1997. They are characterized by their ability to decrease insulin resistance, and have been suggested to slow down the progression of insulin resistance. Treatment with TZD requires several weeks of treatment to decrease plasma glucose levels, but in addition they markedly decrease plasma triglycerides and free fatty acids. A major drawback of treatment with TZD is body fat gain, but some evidence suggests that the fat is redistributed in a favourable direction, that is, from visceral to subcutaneous depots. However, the effect of long-term treatment on weight gain following TZD treatment is unknown, and it may be questioned whether the use of these 'adipogenic compounds' is appropriate, considering that excess body fat is almost a prerequisite for the development of type 2 diabetes.     

Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: a new test for monitoring the disease?

PURPOSE: In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress and induction of the stress protein heme oxygenase (HO)-1. Considering that carbon monoxide (CO) is a product of HO activity, we studied the level of exhaled CO as a marker of oxidative stress in diabetes. METHODS: Eight patients with insulin-dependent diabetes mellitus (type 1) (4 men, 4 women; [mean +/- SEM] age, 50 +/- 8 years) were studied, of whom 2 had peripheral neuropathy and 1 had renal failure. Sixteen patients with non-insulin-dependent diabetes mellitus (type 2) (5 men, 11 women; age 63 +/- 8 years) were studied, of whom 2 had peripheral neuropathy. Glycosylated hemoglobin (HbA(1)c) levels were higher (7.4 +/- 0.3%) in patients with type 1 (mean duration of the disease, 20 +/- 5 years) than in type 2 (4.9 +/- 0.4%; p < 0.05; mean duration of the disease, 11 +/- 2 years). All of the patients were lifelong nonsmokers. RESULTS: Levels of exhaled CO were higher in patients with diabetes (type 1, 4.0 +/- 0.7 ppm; type 2, 5.0 +/- 0.4 ppm) when compared to 37 nonsmoking healthy subjects (20 men, 17 women; age, 33 +/- 3 years) (2.9 +/- 0.2 ppm; p < 0.05). There was a positive correlation between exhaled CO levels and the incidence of glycemia in all subjects (r = 0.52, p < 0.05) and the duration of diabetes (r = 0.48, p < 0.05), but there was not a strong correlation with concentrations of HbA(1)c (r = 0.06, p = 0.8). In addition, an oral glucose tolerance test was performed in five healthy nonsmoking volunteers (three men; age, 33 +/- 4 years). The maximal glucose increase (from 3.9 +/- 0.2 to 5.5 +/- 0.1 mmol/L at 15 min; p < 0.05) was associated with a significant increase in exhaled CO concentration (from 3.0 +/- 0.5 to 6.3 +/- 1.0 ppm; p < 0. 05). Both parameters returned to the baseline at 40 min after glucose administration. CONCLUSIONS: Elevated levels of exhaled CO in diabetes may reflect HO-1 induction and oxidative stress. The measurement of CO may be a new tool for disease monitoring.     

What is the role of autoimmunity in type 1 diabetes? A clinical perspective

Despite tremendous research efforts, type 1 diabetes is one of the few remaining autoimmune diseases without any approved immunological treatment. This observation compels us to reconsider the role of autoimmunity in the pathogenesis of this disease. In this commentary, we will review solely human data in an attempt to appreciate, in an unbiased manner, the importance and relevance of the immunological alterations in patients with type 1 diabetes. The aim of this paper is to generate reflection on this topic, rather than a controversy.     

Insulin therapy in type 2 diabetes: what is the evidence?

Aim: To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus Methods: A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. Results: The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long‐acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long‐acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long‐acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal–bolus regimen seems not possible. Some studies showed that rapid‐acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. Conclusion: A once‐daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.     

The prevention of type 2 diabetes: what is the evidence?

The prevalence of diabetes is increasing in epidemic proportion worldwide. Because of the morbidity and mortality associated with the disease, it is becoming a major burden for the health care system. With a better understanding of the pathogenesis of type 2 diabetes, the concept of primary prevention has emerged. A number of studies demonstrated that both lifestyle modification program and pharmacological interventions in subjects with impaired glucose tolerance (IGT) can prevent or delay the progression to diabetes. The Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP) convincingly showed that an intensive lifestyle modification program is highly effective in decreasing the risk of diabetes in a high risk population (risk reduction of 58%). Four other smaller studies have made similar observations. The DPP study showed that metformin can reduced the risk of diabetes by 31% in subjects with IGT. The STOP-NIDDM trial confirmed the efficacy of acarbose in decreasing the risk of diabetes by 36% in similar high risk population. The TRIPOD study showed that troglitazone can reduce the incidence of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that in very obese population on intensive lifestyle modification program, xenical treatment was associated with a 37% reduced incidence of diabetes compared to placebo. Three studies suggested that bariatric surgery in morbidly obese subjects with or without IGT can reduce the incidence of diabetes to near zero. Eight of 10 studies showed that treatment with inhibitors of the renin-angiotensin aldosterone system in high risk population for cardiovascular disease (CVD) were associated with a significant reduction in the subsequent development of diabetes as a secondary outcome. The WOSCOPS study and the HERS study examined the effect of pravastatin and estrogen/progestin respectively on cardiovascular events and observed that these pharmacological interventions were associated with a 30% and 35% reduction in the incidence of diabetes as secondary outcome. There are 3 major trials currently in progress examining the effect of rosiglitazone/ramipril (the DREAM study), nateglinide/valsartan (the NAVIGATOR study) and pioglitazone (the ACT NOW study) on the development of diabetes in IGT subjects as a primary outcome. We also have 3 studies studying the prevention of diabetes as secondary outcomes: the ONTARGET-TRANSCEND study examining telmisartan with or without ramipril, and the ORIGIN study testing glargine insulin/omega 3. The evidence is overwelming-diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This new information now has to be translated in the real world into well defined strategies for screening and treating high risk population. Prevention of the disease is our only chance to alleviate the ever growing burden of diabetes mellitus in the world.     

The benefit of aspirin therapy in type 2 diabetes: what is the evidence?

Many clinical guidelines recommend aspirin therapy for the prevention of cardiovascular events in individuals with type 2 diabetes. However it is unclear whether the level of evidence in guidelines is derived from studies carried out among individuals with diabetes. Medline and Embase databases were searched to retrieve studies published since 1990, evaluating the effect of aspirin on cardiovascular outcomes in subjects with type 2 diabetes. Four studies corresponded to the inclusion criteria. The three clinical trials retrieved could not prove from a statistical point of view, the benefits of aspirin therapy for subjects with type 2 diabetes. Reduction in cardiac mortality was found only in one observational study. Consequently, these findings suggest that the clinical guidelines have based their recommendations upon the expected benefit previously observed in other high-risk populations. Given the lack of hard evidence and the different well-known platelet physiology encountered in patients with diabetes, use of aspirin as a standard treatment at the highest level of evidence in guidelines for subjects with type 2 diabetes should be revisited.