Prevention of type 2 diabetes: Role of the renin-angiotensin-aldosterone system and antihypertensive therapy

PURPOSE: To review the association between hypertension and insulin resistance, and investigate the effects of renin-angiotensin-aldosterone system (RAAS) inhibition on insulin sensitivity. EPIDEMIOLOGY: Hypertension and diabetes are established risk factors for cardiovascular disease (CVD). In the United States, CVD accounts for 39% of all deaths and affects an estimated 20% of the population. Hypertension is associated with insulin resistance and often occurs in patients with type 2 diabetes mellitus (DM2). The metabolic syndrome is an important clinical clustering of risk factors that suggests overlap between the disease pathways involved in hypertension and diabetes. REVIEW SUMMARY: Early recognition of metabolic syndrome components and intervention is important to reduce adverse cardiovascular outcomes. The risk factors that cluster in this syndrome probably share a common pathway. Inhibition of the RAAS reduces the risk of new-onset DM2. Clinical trials reveal that different classes of antihypertensive agents have different effects on development of new-onset DM2. Thiazide diuretics and β-blockers are associated with increased risk of DM2 whereas agents that block the RAAS may increase insulin sensitivity and significantly reduce the risk of DM2. RAAS-inhibiting agents may produce this beneficial effect through diverse mechanisms, including the effects of these agents on skeletal muscle, adipocyte differentiation, insulin signaling pathways, and protection of pancreatic islet cells. TYPE OF AVAILABLE EVIDENCE: Prospective cohort studies, randomized controlled trials, nationally recognized treatment guidelines, systematic reviews. GRADE OF AVAILABLE EVIDENCE: Good. CONCLUSION: The effects of antihypertensive agents on improving insulin sensitivity and reducing risk of new-onset DM2 should be considered as part of an overall CVD prevention strategy, with RAAS-inhibiting agents demonstrating the most benefit in decreasing the development of new-onset DM2.