Antihypertensive therapy, new-onset diabetes, and cardiovascular disease

Type 2 diabetes mellitus is a worldwide epidemic with considerable health and economic consequences. Diabetes is an important risk factor for cardiovascular disease, which is the leading cause of death in diabetic patients, and decreasing the incidence of diabetes may potentially reduce the burden of cardiovascular disease. This article discusses the clinical trial evidence for modalities associated with a reduction in the risk of new-onset diabetes, with a focus on the role of antihypertensive agents that block the renin–angiotensin system. Lifestyle interventions and the use of antidiabetic, anti-obesity, and lipid-lowering drugs are also reviewed. An unresolved question is whether decreasing the incidence of new-onset diabetes with non-pharmacologic or pharmacologic intervention will also lower the risk of cardiovascular disease. A large ongoing study is investigating whether the treatment with an oral antidiabetic drug or an angiotensin-receptor blocker will reduce the incidence of new-onset diabetes and cardiovascular disease in patients at high risk for developing diabetes

Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats

Background: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. Methods: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/ day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. Results: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. Conclusion: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug

Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options

Incidence of diabetes following ramipril or rosiglitazone withdrawal.

OBJECTIVE: To examine the impact of withdrawing rosiglitazone and ramipril medication on diabetes incidence after closeout of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS: The 3,366 DREAM subjects at trial end who had not developed diabetes while taking double-blind study medication were transferred to single-blind placebo for 2 to 3 months before undergoing an oral glucose tolerance test. Glycemic status was analyzed for the trial plus washout period and for the washout period alone. RESULTS: Following median (interquartile range) 71 (63-86) days drug withdrawal, overall glycemic status remained modestly improved in those allocated ramipril during the trial with an 11% increase in regression to normoglycemia, compared with placebo. In those previously allocated rosiglitazone, glycemic status remained substantially improved with a 49% reduction of new-onset diabetes or death and a 22% increase in regression to normoglycemia, compared with placebo. However, during the washout phase alone the incidence of diabetes or death was identical for those allocated previously to ramipril or placebo, or to rosiglitazone or placebo. CONCLUSIONS: In people allocated to ramipril compared with those not allocated ramipril during the trial, the postwashout normoglycemia incidence was higher. In people allocated to rosiglitazone compared with those not allocated rosiglitazone during the trial, the postwashout incidence of diabetes was significantly lower and the incidence of normoglycemia was higher. During the washout period, diabetes incidence was the same for ramipril versus placebo and for rosiglitazone versus placebo. Rosiglitazone delays disease progression during treatment but the process resumes at the placebo rate when the drug is stopped