Type 2 Diabetes Mellitus Outcomes Research Articles

Diabetes and obesity: therapeutic targeting and risk reduction – a complex interplay

Obesity is a major risk factor for the development of diabetes and predisposes individuals to hypertension and dyslipidaemia. Together these pathologies increase the risk for cardiovascular disease (CVD), the major cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). Worsening trends in obesity and T2DM raise a serious conundrum, namely, how to control blood glucose, blood pressure, and lipids when many antidiabetic agents cause weight gain and thereby exacerbate other cardiovascular risk factors associated with T2DM. Further, evidence suggests that some established antihypertensive agents may worsen glucose intolerance. Many patients who are obese, hypertensive, and/or hyperlipidaemic fail to achieve blood pressure, lipid and glycaemic goals, and this failure may in part be explained by physician reluctance to utilize complex combination regimens for fear of off-target effects. Thus, a clear need exists for clinicians to understand the risks and benefits of different pharmacologic, and indeed non-pharmacologic, options in order to maximize treatment outcomes. While intensive lifestyle modification remains an elusive gold standard, newer diabetes targets, including the incretin axis, may offer greater cardiovascular risk reduction than other antidiabetes therapies, although definitive clinical trial data are needed. The glucagon-like peptide-1 (GLP-1) receptor agonists exenatide and liraglutide and the dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin effectively lower HbA1c; exenatide and liraglutide reduce weight and blood pressure and improve lipid profiles. Sitagliptin and vildagliptin are weight neutral but also appear to improve lipid profiles. Integration of incretin therapies into the therapeutic armamentarium is a promising approach to improving outcomes in T2DM, and perhaps even in reducing complications of T2DM, such as co-morbid hypertension and dyslipidaemia. Additional long-term studies, including CVD end-point studies, will be necessary to determine the appropriate places for incretin-based therapies in treatment algorithms.

Closing the gap between clinical research and clinical practice: can outcome studies with thiazolidinediones improve our understanding of type 2 diabetes?

Recent clinical research has provided a wealth of information to support optimal management strategies in type 2 diabetes mellitus (T2DM). In particular, outcome studies appropriately have had an increasingly important impact on clinical decision-making. Additional, new data are required, however, to close the current gaps in clinical knowledge and improve patient outcomes in T2DM. These outcome studies are particularly important in assessing the long-term benefit of newer agents for which data are available for short-term glycaemic control, effects on lipids and some data on non-traditional cardiovascular risk markers, but outcome data for harder end points relevant to the natural history of T2DM, particularly beta-cell function, are lacking. Outcome studies such as ADOPT and DREAM are investigating the impact of thiazolidinediones (TZDs) on beta-cell function and disease progression in T2DM and impaired glucose tolerance, respectively, the results of which are eagerly anticipated. The primary focus of this article is on TZD outcome studies evaluating beta-cell function and disease progression.

Modulating LDL cholesterol and glucose in patients with type 2 diabetes mellitus: targeting the bile acid pathway

Individuals with type 2 diabetes mellitus (T2DM) have a number of potentially modifiable risk factors, including dyslipidemia, hypertension, and hyperglycemia, that contribute to coronary artery disease risk. Elevated low-density lipoprotein cholesterol (LDL-C) is a major contributor to coronary artery disease, and clinical trials have demonstrated significant macrovascular benefits associated with lowering LDL-C in individuals with T2DM, even in those with only a modest LDL-C elevation. Intensive glycemic control has been shown to reduce microvascular complications associated with T2DM. Therefore, it is important to treat both dyslipidemia and hyperglycemia to reduce complications. In this paper, the effect of elevated LDL-C and glucose concentrations on T2DM outcomes is reviewed. Lipid and glucose homeostasis are linked in part through bile acid pathways. Recent clinical trials demonstrate that bile acid sequestrants, which significantly reduce LDL-C, can also significantly reduce glucose levels in patients with T2DM. These findings supported recent Food and Drug Administration approval of the bile acid sequestrant colesevelam HCl for reducing glycemia in patients with T2DM. A multitargeted therapeutic approach using a bile acid sequestrant to improve both cholesterol and glucose management in patients with T2DM may be clinically beneficial.

Pregnancy Outcome in the Psammomys obesus Gerbil on Low- and High-Energy Diets

Introduction: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy. Methods: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning. Results: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1–3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring. Conclusion: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.