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Reversal of Insulin Resistance in Type 1 Diabetes following Initiation of Insulin Treatment

The biological action and pharmacokinetics of insulin were assessed in nine type 1 (insulin‐dependent) diabetic patients before and after 3 months conventional insulin treatment, and in seven age and weight‐matched non‐diabetic controls, by means of the euglycaemic insulin clamp technique. The mean (± S.E.) metabolic clearance rate of insulin, when infused at 1 mU/kg/min, was similar in untreated and treated diabetic patients and in controls (22.7 ± 2.0, 19.3 ± 3.8, and 22.9 ± 3.3 ml/kg/min) but, when infused at 6 mU/kg/min, was greater (p<0.01 and <0.01) in untreated patients (18.0 ± 2.5 ml/kg/min) than in treated patients (11.5 ± 1.4 ml/kg/min) and controls (12.7 ± 1.3 ml/kg/min). Insulin‐mediated glucose disposal was reduced (p<0.01 and <0.01) at insulin infusion rates 1 and 6 mU/kg/min in untreated patients (18.5 ± 1.9 and 33.8 ± 4.5 μmol/kg/min) when compared with controls (35.8 ± 3.4 and 62.0 ± 4.7 μmol/kg/min) and was improved (p<0.01 and <0.01) following insulin treatment (36.1 ± 4.6 and 64.8 ± 4.2 μmol/kg/min). Daily insulin requirement fell by 33% following 3 months insulin treatment with improvement in mean HbA, from 16.3 ± 0.7 to 8.2 ± 0.4%, but without significant increase in endogenous insulin secretion. The ‘honeymoon phenomenon’, which has traditionally been attributed exclusively to resurrection of endogenous insulin release, may also be related to normalization of insulin action following institution of insulin treatment.