Molecular and Genetic Medicine

The Unholy Alliance between Obesity, Type-2 Diabetes, the Sympathetic Nervous System, and Hypertension in Young/Middle-Aged Subjects

Abstract

JM Cruickshank

There is an obesity/type-2 diabetes (DM2)/hypertension epidemic in developed countries around the world. The purpose of this review is to examine the interrelationships between obesity, DM2 and hypertension in young/middleaged subjects, highlighting the importance of raised sympathetic nerve activity and treatment implications. Central obesity is associated with insulin-resistance, and high plasma insulin and leptin levels. Insulin and leptin act upon the mid-brain, resulting in increased sympathetic nerve activity and blood pressure. Chronically raised sympathetic nerve activity, independent of blood pressure, is a powerful predictor of myocardial infarction in the middle-aged. Weight-loss, via life-style change or bariatric surgery, results in blood pressure reduction. Anti-hypertensive agents that increase sympathetic nerve activity, e.g. diuretics, dihydropyridine calcium antagonists, and angiotensin receptor blockers (ARBs), do not reduce (and may increase) the risk of myocardial infarction in younger/middleaged subjects with hypertension and DM2. Beta-1 blockade, which is effective in regressing and stabilising coronary atheromataous plaque, is preferable to ACE-inhibition, and is the first-line treatment of choice.