Strict nocturnal diabetic control diminishes subsequent glycemic escape during acute insulin withdrawal

Abstract

Five Type 1 (insulin dependent) diabetic patients with no endogenous insulin secretion and very low antiinsulin antibody levels (IBC < 4%) were studied twice. Nocturnal plasma glucose was maintained by intravenous insulin just beyond each extreme of the normal range, either “hypoglycemic”, at 2.71 ± 0.03mmol/L, or “hyperglycemic”, 8.59 ± 0.13mmol/L. Glucose turnover measurements were performed before and after insulin was discontinued the following morning. The steady state plasma glucose concentration achieved during subsequent glycemic escape was significantly lower following nocturnal hypoglycemia, (16.1 ± 0.3 v 20.2 ± 0.03 mmol/L; P < 0.01). The initial rate of rise of plasma glucose was identical in both groups. Free insulin levels, although significantly higher in the hypoglycemic study, before withdrawal, 24.3 ± 6.0 v 13.3 ± 0.8mU/L, ( P < 0.01), fell to similarly low levels 1 hour after insulin withdrawal. Free fatty acid and total ketone concentrations were normalized during hypoglycemia, but remained elevated in the hyperglycemic group. Lactate concentrations were not different in the two studies. During glycemic escape glucose appearance rate (R a) rose faster following hypoglycemia, but similar final rates were achieved in each group. When related to plasma glucose concentration glucose uptake (R d) was normal following hypoglycemia and remained persistently greater than the hyperglycemic group throughout the 5 hours following insulin withdrawal. Plasma cortisol, pancreatic glucagon, and growth hormone levels were not significantly different in the two groups following withdrawal. It is suggested that the persistent normal glucose uptake, following glycemic control that has been sufficient to normalize plasma metabolites, will limit glycemic excursions caused by acute reductions in plasma-free insulin concentration. Therefore nocturnal plasma glucose levels of 8 to 9 mmol/L do not represent adequate metabolic control. Although true normoglycemia is desirable, it must be weighed against the associated potential hazards of hypoglycemia.