The development of hyperglycaemia in patients with insulin-resistant generalized lipoatrophic syndromes.
Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100 mU/kg.min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.
Robert
J J
JJ
Unit of Pediatric Endocrinology and Diabetology, INSERM U 30, Necker-Enfants Malades Hospital, Paris, France.
Rakotoambinina
B
B
Cochet
I
I
Foussier
V
V
Magre
J
J
Darmaun
D
D
Chevenne
D
D
Capeau
J
J
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002648:Child; D002784:Cholesterol / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008060:Lipodystrophy / Q000097:blood*; D013577:Syndrome; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D002784:Cholesterol; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides