Conditions: Type 2 Diabetes Hypertension
Keywords: diabetes, hypertension, free-fatty acids
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: yes

Brief summary:
Insulin resistance has been implicated as the central pathogenetic feature of cardiovascular risk factor cluster that includes hypertension, impaired glucose tolerance, diabetes, dyslipidemia, and hemostatic disorders. Recent evidence suggests that increased levels of free fatty acids (FFA) in obese subjects is a leading candidate in the pathogenesis of insulin resistance (1-4). In our preliminary studies on the effect of FFA on insulin secretion and action (lipotoxicity), we have observed that the infusion of Intralipid/heparin to increase FFA \~ four-fold-baseline levels for 48 hours results in a significant and reproducible raise in systolic and diastolic blood pressure (BP) in obese African American subjects with and without diabetes. The increase in blood pressure is apparent after 12 hours of infusion, reaching a peak increment of 32 mm Hg in systolic and 14 mm Hg in diastolic pressure at 24 hours. These preliminary findings indicate that, in addition to the well-known effect on insulin resistance, sustained elevation of FFA results in the development of an acute metabolic syndrome.

Detailed description:
The FFA-induced hypertension constitutes a useful model with which to examine disease mechanisms and test new therapeutic interventions to correct the different disorders associated with insulin resistance and metabolic syndrome. The effect of FFA on insulin action is well established (4-6); however, the pressor effect of FFA infusion in obese subjects has not been investigated. We hypothesize that observed changes in blood pressure is the result of acute endothelial dysfunction due to increased FFA concentration; and that rosiglitazone, a PPAR gamma receptor agonist, will protect against FFA-induced elevation in blood pressure and endothelial dysfunction in obese subjects.

Arms:
arm 1: Obese, normotensive African-Americans with diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours, then normal saline 0.9% at 40 ml/hr intravenously for 48 hours, and then randomized to rosiglitazone for six weeks followed by Intralipid 20% at 40ml/hr intravenously for 48 hours arm 2: Obese, normotensive African-Americans without diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours

Interventions: intervention 1: Rosiglitazone intervention 2: Normal saline 0.9% intervention 3: Intralipid 20%
Intervention descriptions: intervention 1: Diabetic subjects will be receive rosiglitazone for 6 weeks intervention 2: Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours intervention 3: Intralipid 20% at 40ml/hr intravenously for 48 hours

Protocol document: