Hyperglycemia increases muscle blood flow and alters endothelial function in adolescents with type 1 diabetes

Abstract

Alterations of blood flow and endothelial function precede development of complications in type 1 diabetes. The effects of hyperglycemia on vascular function in early type 1 diabetes are poorly understood. To investigate the effect of hyperglycemia on forearm vascular resistance (FVR) and endothelial function in adolescents with type 1 diabetes, FVR was measured before and after 5 minutes of upper arm arterial occlusion using venous occlusion plethysmography in (1) fasted state, (2) euglycemic state (~90 mg/dL; using 40 mU/m(2)/min insulin infusion), and (3) hyperglycemic state (~200 mg/dL) in 11 adolescents with type 1 diabetes. Endothelial function was assessed by the change in FVR following occlusion. Seven subjects returned for a repeat study with hyperglycemia replaced by euglycemia. Preocclusion FVR decreased from euglycemia to hyperglycemia (P = 0.003). Postocclusion fall in FVR during hyperglycemia was less than during euglycemia (P = 0.002). These findings were not reproduced when hyperglycemia was replaced with a second euglycemia. These results demonstrate that acute hyperglycemia causes vasodilation and alters endothelial function in adolescents with type 1 diabetes. In addition they have implications for future studies of endothelial function in type 1 diabetes and provide insight into the etiology of macrovascular and microvascular complications of type 1 diabetes.

Figure 1

Serum glucose values during hyperinsulinemic hyperglycemia insulin clamp (solid circle) and the euglycemia control clamp (X). Fasting glucose values are indicated by the vertical line. The average time to achieve euglycemia was 57 ± 11 minutes during the hyperglycemia clamp and 70 ± 17 minutes during the euglycemia control clamp. During euglycemia study, normal saline was given to match volume of dextrose 20% given during hyperglycemia study.

Figure 2

Preocclusion forearm blood flow (FBF, (a)), forearm vascular resistance (FVR) (c) and changes in FBF and FVR from pre- to postocclusion (b,d) fasting and during hyperinsulinemic clamp with euglycemia followed by hyperglycemia. FBF measured in mL per minute per 100 mL of forearm tissue volume; FVR determined by MAP (mean arterial pressure)/FBF. Eugly : euglycemic period, Hyper : hyperglycemic period. Lines indicate between group differences.

Figure 3

Preocclusion forearm blood flow (FBF, (a)), forearm vascular resistance (FVR) (c) and changes in FBF and FVR from pre- to post-occlusion (b,d) fasting and during hyperinsulinemic clamp with euglycemia periods 1 and 2. FBF measured in mL per minute per 100 mL of forearm tissue volume; FVR determined by MAP (mean arterial pressure)/FBF. Eugly 1 : first euglycemic period, Eugly 2 : second euglycemic period. Lines indicate between group differences.

Figure 4

Forearm vascular resistance (FVR) during common euglycemic period followed by either hyperglycemia (solid bars) or second euglycemia period (open bars) with continuous insulin infusion throughout. During euglycemia study, normal saline was given during second euglycemic period to match volume of dextrose 20% given during hyperglycemia study. The fall in FVR during hyperlycemia was significantly different from the lack of change during euglycemia (P = 0.042).