Poor glycemic control induces hypertension in diabetes mellitus

We conducted this study to test the hypothesis that hypertension is a primary consequence of poor glycemic control per se very early in insulin-dependent diabetes mellitus. Sprague-Dawley rats (n=15) were instrumented with artery and vein catheters, placed in metabolic cages, and sodium intake was clamped throughout the study. Mean arterial pressure was measured 24 h/d. After a precontrol period, streptozotocin (70 mg/kg IV) was administered, and 15 hours later a continuous intravenous insulin infusion was begun at 4 U/rat per day. The insulin infusion was titrated on an individual rat basis to maintain good glycemic control, and after this 7-day control period, blood glucose, urinary sodium excretion, and mean arterial pressure were not different from precontrol values, averaging 8.8+/-0.6 mmol/L, 2.8+/-0.2 mmol/d, and 103+/-2 mm Hg, respectively, for control days 5 through 7. Subsequently, a 4-day period of poor glycemic control was initiated by reducing the insulin infusion rate. Blood glucose, urinary sodium excretion, and mean arterial pressure began to increase on day 1; for diabetes days 3 and 4, they averaged 23.4+/-1.0 mmol/L, 3.6+/-0.1 mmol/d, and 110+/-2 mm Hg, respectively. All were significantly elevated. When insulin treatment was restored, all variables returned to control levels during the next 4 days. A second 4-day diabetic period yielded similar results. These results indicate that elevated blood pressure is a primary consequence of poor glycemic control in insulin-dependent diabetes, occurring before renal injury has had time to develop, and therefore, may be a factor contributing to the initiation of end-organ injury.