Hypertension and Insulin Resistance

Abstract

Diminished tissue sensitivity to the metabolic actions of insulin is a characteristic feature of various pathological conditions termed the “cardiometabolic syndrome.”1–3 Factors that contribute to the complex interaction of genetic and environmental factors required for impaired insulin signaling include obesity, inactivity, and aging. Recent research has underscored the importance of heightened activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, oxidative stress, inflammation, and mitochondrial functional abnormalities in promoting insulin resistance.1–3 In addition to the negative effects of these factors on insulin metabolic signaling in conventionally insulin-sensitive tissue, such as skeletal muscle, there is a contemporaneous negative effect on metabolic signaling in cardiovascular tissue. These negative effects include reduced insulin stimulation of endothelial cell NO production and increased NO destruction with resulting endothelial dysfunction and hypertension.1,2 Indeed, both pharmacological and nonpharmacological strategies to improve insulin metabolic signaling generally also improve endothelial function and lower blood pressure. In this regard, the current report from Ruggenenti et al4 is an important translational contribution that provides a potential mechanism by which oral provision of a critical mitochondrial substrate, l-carnitine, can correct insulin resistance and lower blood pressure through improvements in mitochondrial free fatty acid use. This investigative team prospectively studied 2 cohorts of insulin-resistant subjects with the presence of other cardiometabolic risk factors, such as body mass index >25 kg/m2 and hypertension. Eligible subjects underwent a euglycemic, hyperinsulinemic clamp to determine glucose disposal rate (GDR) and were divided into those with and without a …