The course and determinants of insulin action in type 1 (insulin-dependent) diabetes mellitus.
The course and determinants of insulin action were investigated in 8 newly diagnosed Type 1 (insulin-dependent) diabetic patients, who were studied every 3 months for one year, and in three groups of 8 patients each with 5, 10 and 20 years diabetes, studied once. Fifteen healthy subjects matched for age, sex and body weight served as control subjects. Dose-response curves were constructed using sequential euglycaemic (5.0 mmol/l) clamps (insulin infusion rates: 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in periods of 2h). After 1/2 month of insulin treatment, insulin responsiveness was normal, but sensitivity was decreased (ED50 70 +/- 7 mU/l (SEM) vs 54 +/- 4 mU/l in control subjects, p less than 0.05). After 6 months, insulin sensitivity was improved (ED50 57 +/- 4 mU/l, p less than 0.01 vs 1/2 month and not significant (NS) vs control subjects); but after 9 and 12 months, it was reduced again, similarly to 0.5 month. Insulin responsiveness remained normal at all time-points. In the three groups of patients with longstanding diabetes, impaired insulin sensitivity with normal responsiveness was noted also (ED50 73 +/- 9 mU/l, p less than 0.02 vs control subjects). At 6, 9 and 12 months, glycaemic control (HbA1) and insulin dose were inverse correlates for insulin action; in patients with longstanding disease, this was noted for HbA1 and body weight, in control subjects for body weight. In conclusion, decreased insulin sensitivity re-develops in Type 1 diabetes within the first year following an initial improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Nijs
H G
HG
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands.
Radder
J K
JK
Frölich
M
M
Krans
H M
HM
D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D019270:Fructosamine; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007330:Insulin Antibodies / Q000032:analysis*; D007332:Insulin Infusion Systems; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D012016:Reference Values
D001323:Autoantibodies; D015415:Biomarkers; D001786:Blood Glucose; D019270:Fructosamine; D006442:Glycated Hemoglobin; D006595:Hexosamines; D007328:Insulin; D007330:Insulin Antibodies; C024211:islet cell antibody