Hypertension in diabetes

In individuals in whom pancreatic β-cell function is intact, resistance to insulin action in terms of insulin stimulated glucose uptake results in compensatory hyperinsulinemia (HI). Thus insulin resistance (IR) and HI are inexorbaly linked. Initially, it was proposed that HI resulted in blood pressure (BP) elevation by stimulation of sympathetic nervous system activity and renal reabsorption of sodium, and that HI resulted in dyslipidemia by stimulation of hepatic synthesis & sceretion of very low density lipoproteins (VLDL) and triglycerides (TG). This constuct would imply that increased circulating levels of insulin have adverse consequences. This suggests insulin therapy be avoided in insulin resistant states. Yet, intensive insulin therapy corrects dyslipidemia without aggravation of BP elevation. Accumulating evidence suggests that HI is not responsible for BP elevation and dyslipidemia in the IR syndrome. Rather, IR per se results in these abnormalities. Resistance to insulinʹs vasodilitory effects results in blood pressure elevation. Resistance to insulinʹs effect of inhibiting adiposycte lipolysis results in increased delivery of free fatty acids as substrate for hepatic synthesis and secretion of VLDLs and TGs. Thus, generalized IR accounts for these abnormalities, rather than specific IR for glucose uptake. This has profund therapeutic implications, including effects on insulin sensitivity of various anti-hypertensive strategies.