[Swiss journey through the clinical and genetic characteristics of diabetes in young patients].
The aim of this study is to understand better the genetic causes of type II diabetes and the phenotypic consequences of the genetic changes. We first investigated the relative prevalence of the different forms of diabetes in young adults and their clinical features. 51 non-obese patients were identified in whom diabetes had been diagnosed before age 40; cases of typical insulin-dependent type I diabetes were excluded. A search for mutations of the glucokinase and HNF-1 alpha genes and for mitochondrial DNA was made, anti-islet and anti-GAD antibodies were determined and HLA class II genotyping was performed. Patients were subdivided on clinical grounds into a MODY (maturity onset diabetes of the young) group (n = 19) and a non-MODY group (n = 32). MODY is a form of diabetes which has an autosomal dominant inheritance for which 3 genes have already been implicated (MODY1, HNF-4 gene; MODY2, glucokinase gene, and MODY3, HNF-1 alpha gene). In the MODY group we identified 3 patients with MODY2, 1 with MODY3, 1 with the 3243 mitochondrial mutation and a further patient with autoimmune diabetes. In the non-MODY group we found 5 patients with autoimmune diabetes and 1 with MODY2. No clinical parameter was helpful in classifying patients in one of these subclasses of diabetes; however, glucagon stimulated C-peptide was useful in discriminating between MODY2 patients and the others. Young and lean non-insulin-dependent diabetic patients thus constitute a very heterogeneous group, though presenting similar clinical features. In the second study we analyzed hepatic glucose metabolism in patients with a mutation of the glucokinase gene expressed in both liver and islet beta cells. We found that endogenous glucose production is inadequately inhibited by hyperglycemia, a fact which contributes to the pathogenesis of hyperglycemia in these patients.
Dussoix
P
P
Clinique de médecine II, Hôpitaux universitaires de Genève.
Tappy
L
L
Philippe
J
J
D000328:Adult; D001327:Autoimmune Diseases / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005941:Glucokinase / Q000235:genetics; D006801:Humans; D007515:Islets of Langerhans / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013557:Switzerland
D001786:Blood Glucose; D005941:Glucokinase
Voyage helvétique à travers les caractéristiques cliniques et génétiques du diabète du sujet jeune.