Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect.

Abstract

Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) revealed a severe impairment in insulin secretion, which was present also in those normoglycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with IDDM by lack of glutamic acid decarboxylase antibodies (GAD-Ab). Taken

Genetic testing for maturity onset diabetes of the young: uptake, attitudes and comparison with hereditary non-polyposis colorectal cancer

“…The study included two Finnish extended pedigrees with the Pro291fsinsC mutation in the HNF-1α gene identified in the Botnia study, which is a population-based study aiming at the identification of genes increasing susceptibility to type 2 diabetes [26]. During 2002-2003, we offered the family members genetic counselling and the possibility to obtain their earlier screened gene test result if they were either affected with diabetes or had a 50% risk of having inherited the mutation.…”

“…MODY3 is characterised by a low renal threshold for glucose and a poor insulin response to glucose [17,18]. The beta cells are, however, able to secrete insulin in response to other secretagogues [19].…”

“…The beta cells are, however, able to secrete insulin in response to other secretagogues [19]. This, in conjunction with particularly good insulin sensitivity [17,18], results frequently in hypoglycaemia in patients treated with either oral hypoglycaemic agents or insulin. The degree of insulin deficiency and the age at diagnosis of MODY3 diabetes can vary widely even within the same family [17].…”

“…This, in conjunction with particularly good insulin sensitivity [17,18], results frequently in hypoglycaemia in patients treated with either oral hypoglycaemic agents or insulin. The degree of insulin deficiency and the age at diagnosis of MODY3 diabetes can vary widely even within the same family [17]. Most patients are eventually treated with insulin or oral hypoglycaemic agents but treatment with diet is often sufficient in the early stages.…”

The genetic variant of lactase persistence C (−13910) T as a risk factor for type I and II diabetes in the Finnish population

“…We randomly selected 495 type II diabetes patients from Western Finland and 120 from Eastern Finland participating in the Botnia study and 446 control subjects from Western Finland (Groop et al, 1996) classified according to the revised WHO criteria (Alberti & Zimmet, 1998). Families with maturity-onset diabetes of the young or mitochondrial diabetes were excluded after DNA analysis (Lehto et al, 1997). Spouses without first-or second-degree family history of diabetes were chosen as control subjects.…”