In vivo and in vitro characterization of insulin resistance in three cases of lipoatrophic diabetes.
Insulin resistance was explored in vivo and in vitro in 3 lipoatrophic diabetic girls (12, 15 and 19 years old = L1, L2 and L3). Patients L1 and L2 were explored with fasting hyperglycaemia (9 mmol/l); patient L3 was normoglycaemic. All had abnormal OGTT with marked hyperinsulinemia. Their basal glucose productions, measured by [6,6(-2)H] glucose constant infusion, were 3.3, 2.6 and 3.4 mg kg-1 min-1, respectively; they did not correlate with fasting plasma glucose. Glucose production in response to a 2 mg kg-1 min- unlabeled glucose infusion, was normally suppressed in L2, but was incompletely suppressed (by 1.5 mg kg-1 min-1) in L1 and L3. The dose-response curve during hyperinsulinemic euglycaemic clamp at 1, 2 and 10 mU kg-1 min-1 insulin infusion was shifted to the right in all three patients. However the maximal glucose disposal rates were close to normal (9 and 9 mg kg-1 min-1) in L1 and L3, while it remained very low (3.6 mg kg-1 min-1 at 10 mU kg-1 min-1 insulin infusion) in L2. The endogenous insulin secretion (plasma C-peptide) was also incompletely suppressed during insulin infusion. Thus, the in vivo insulin resistance of lipoatrophic diabetes concerns not only glucose disposal but also hepatic glucose output and insulin secretion; in addition, the alterations of glucose metabolism were not the same in all subjects. The in vitro studies showed no pre-receptor defect (anti-insulin antibodies, insulin receptor antibodies). Insulin binding to erythrocytes and cultured fibroblasts was normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Robert
J J
JJ
Unité d'Endocrinologie et Diabétologie de l'Enfant, INSERM U 30, Hôpital des Enfants Malades, Paris, France.
Magre
J
J
Reynet
C
C
Darmaun
D
D
Picard
J
J
Capeau
J
J
D000273:Adipose Tissue / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D001284:Atrophy; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002478:Cells, Cultured; D002648:Child; D002784:Cholesterol / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance; D008049:Lipase / Q000097:blood; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000097:blood; D008099:Liver / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D013577:Syndrome; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D014280:Triglycerides; D006003:Glycogen; D002784:Cholesterol; D011972:Receptor, Insulin; D008049:Lipase; D008071:Lipoprotein Lipase; D005947:Glucose