Free insulin, C-peptide and glucagon profiles in insulin dependent diabetes mellitus

Glucose and hormone profiles, including plasma levels of glucagon, GH, total insulin, free immunoreactive and biologically active insulin were determined by hourly sampling in two groups of insulin dependent diabetics. The five patients in Group I were recently diagnosed and still had residual beta-cell function. The other six in Group II had disease of longer duration, had developed insulin antibodies, and were non-secretors of C-peptide. All patients were studied while receiving their usual maintenance doses of Semilente monocomponent insulin (Novo). Daily insulin requirements were 25.6 +/- 4 U in Group I and 52.2 +/- 7 U in Group II. The glucose profiles were similar in the periprandial periods but over the whole 24-hour period control was more unstable in the patients of Group II and during the period 2400-0200 h plasma glucose fell to low levels (minimum plasma glucose 1.5-3.0 mmol/l). Free insulin levels rose to peak levels over a similar time course but then fell more slowly in the Group II subjects. These patients had higher free, biologically active insulin and lower glucagon levels which were coincident in time with the early morning hypoglycaemia. These observations suggest that raised free insulin levels in the setting of an impaired counter-regulatory glucagon response are one of the factors contributing to glucose instability in long-standing diabetics.