Maturity‐onset diabetes of the young (MODY)

Department of Internal Medicine (Division of Endocrinology and Metabolism), University of Michigan Medical Center, Ann Arbor, Michigan 48109
Diabetes / Metabolism Reviews 11/1989; 5(7):579 - 606. DOI: 10.1002/dmr.5610050705
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    ABSTRACT: The alarming increase in the prevalence of obesity in children in the United States and globally raises major concerns about its future adverse impact on public health. One outcome of this disturbing trend that is already evident is the rapidly increasing incidence of type 2 diabetes at all ages. This disease, once thought to be nonexistent in children, is increasing coincident with obesity. This article addresses the role that obesity plays in type 2 diabetes and also explores its effects on other types of diabetes that occur in childhood. The new challenges for physicians who formulate a differential diagnosis of diabetes in children are discussed. Also examined are modifications of traditional diabetes treatment that can be helpful in combating the insulin resistance associated with obesity and that use medications that are not traditionally used in this age group. Cases are presented to illustrate certain points. An underlying thesis suggests that specific classification may not be as important to the clinician as the understanding of pathophysiologic factors that contribute to hyperglycemia in individual patients. Recommendations are offered to the practitioner for diagnosing and treating the obese child or adolescent with diabetes.
    PEDIATRICS 03/2008; 121(2):361-8. DOI:10.1542/peds.2007-1234 · 5.30 Impact Factor
  • Nutrition 03/1997; 13(2):95-9. DOI:10.1016/S0899-9007(96)00398-X · 3.05 Impact Factor
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    ABSTRACT: Hepatocyte nuclear factor 4α (HNF4A) is a member of the nuclear receptor family of ligand-activated transcription factors. HNF4A mutations cause hyperinsulinaemic hypoglycaemia in early life and maturity-onset diabetes of the young. Regular screening of HNF4A mutation carriers using the oral glucose tolerance test has been recommended to diagnose diabetes mellitus at an early stage. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are incretin hormones, responsible for up to 70% of the secreted insulin after a meal in healthy individuals. We describe, for the first time, gradual alteration of glucose homeostasis in a patient with HNF4A mutation after resolution of hyperinsulinaemic hypoglycaemia, on serial oral glucose tolerance testing. We also measured the incretin response to a mixed meal in our patient. Our patient was born with macrosomia and developed hyperinsulinaemic hypoglycaemia in the neonatal period. Molecular genetic analysis confirmed HNF4A mutation (p.M116I, c.317G>A) as an underlying cause of hyperinsulinaemic hypoglycaemia. Serial oral glucose tolerance testing, after the resolution of hyperinsulinaemic hypoglycaemia, confirmed the diagnosis of maturity-onset diabetes of the young at the age of 10 years. Interestingly, the intravenous glucose tolerance test revealed normal glucose disappearance rate and first-phase insulin secretion. Incretin hormones showed a suboptimal rise in response to the mixed meal, potentially explaining the discrepancy between the oral glucose tolerance test and the intravenous glucose tolerance test. Maturity-onset diabetes of the young can develop as early as the first decade of life in persons with an HNF4A mutation. Impaired incretin response might be contributory in the early stages of HNF4A maturity-onset diabetes of the young. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 12/2013; 31(3). DOI:10.1111/dme.12369 · 3.06 Impact Factor