Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus

Insulin delivery to muscle is rate-limiting for insulin's metabolic action and is regulated by insulin's own action to increase skeletal muscle blood flow and to recruit microvasculature. Microvascular dysfunction has been observed in insulin resistant states. We investigated the relation between insulin's action to recruit microvasculature and its metabolic action in type 1 diabetes. Near euglycaemia was obtained by an overnight insulin infusion during 17 inpatient admissions of participants with type 1 diabetes. This was followed by a 2 h 1 mU kg(-1) min(-1) euglycaemic-hyperinsulinaemic clamp. Microvascular blood volume (MBV) was assessed using contrast-enhanced ultrasound 10 min before and 30 min after starting the clamp. We observed that, after overnight modest hyperinsulinaemia (average approximate to 286 pmol/l), MBV was positively related to the steady-state insulin sensitivity measured during the subsequent clamp (r = 0.62, p = 0.008). The more marked hyperinsulinaemia during the clamp (average steady-state insulin approximate to 900 pmol/l) increased MBV in the more insulin resistant participants within 30 min but not in the insulin sensitive participants. The change in MBV during the clamp was negatively correlated to the insulin sensitivity (r = -0.55, p = 0.022). As a result, MBV after 30 min of marked hyperinsulinaemia was comparable between the insulin sensitive and resistant participants. We conclude that moderate overnight hyperinsulinaemia recruited microvasculature in the more sensitive participants, while higher levels of plasma insulin were needed for more insulin resistant participants. This suggests that microvascular responsiveness to insulin is one determinant of metabolic insulin sensitivity in type 1 diabetes. ClinicalTrials.gov NCT00943787 This study is supported by the NIH/NIDDKRO1 DK 51562 grant and the University of Virginia General Clinical Research Center M01 RR 000847 grant.