Inheritance of diabetes mellitus

Jonathan (Jon) Zonana, D. L. Rimoin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Familial aggregation of diabetes mellitus has been recognized for centuries; yet the exact contribution of genetic factors to the cause of the disease remains unclear. Studies based on clinical histories and questionnaires clearly demonstrate an increased prevalence of a positive family history for patients with over those without diabetes. Moreover, numerous studies, using both clinical and glucose tolerance testing criteria, have confirmed an increased prevalence of diabetes or abnormal glucose tolerance in specified relatives of patients over similar relatives of controls. Either genetic or environmental factors (or both), however, may be responsible for familial aggregation of a disease. In an attempt to distinguish between these variables, classic twin studies examining concordance rates for diabetes in monozygotic (identical) versus dizygotic (fraternal) twins have been performed. These studies revealed a 45 to 96% concordance of diabetes or glucose intolerance in monozygotic twins in contrast to a 3 to 37% concordance rate in dizygotic twins, indicating a distinct genetic contribution to the cause of diabetes. Although genetic factors appear to be of importance in diabetes, the mode (or modes) of genetic transmission is still unknown. Genetic analysis by numerous different investigators have resulted in conflicting conclusions implicating practically every mode of inheritance, including simple autosomal recessive inheritance, simple autosomal dominant inheritance with incomplete penetrance and multifactorial or polygenic inheritance (i.e., the interaction of multiple gene loci with environmental factors). It is now clear that none of these postulated mechanisms satisfactorily explain the pattern of inheritance in all cases of diabetes. Nevertheless, the autosomal recessive hypothesis has been accepted by many diabetologists; this false assumption has resulted in numerous errors in the design and interpretation of subsequent studies. For example, many research efforts aimed at identifying persons with prediabetes (i.e., persons who are clinically and chemically normal but in whom overt diabetes will subsequently develop) have labeled all identical twins of diabetic patients and all offspring of 2 diabetic patients as having 'genetic prediabetes', on the assumption of autosomal recessive inheritance. Although there is an increased risk of diabetes in these 2 groups, it does not begin to approach the 100% predicted with simple autosomal recessive inheritance. Furthermore, many diabetic patients have received inaccurate genetic counseling based on the false assumption that diabetes is a simple recessive trait.

Original languageEnglish (US)
Pages (from-to)603-605
Number of pages3
JournalNew England Journal of Medicine
Volume295
Issue number11
StatePublished - 1976
Externally publishedYes

Fingerprint

Diabetes Mellitus
Dizygotic Twins
Multifactorial Inheritance
Prediabetic State
Monozygotic Twins
Glucose
Inheritance Patterns
Twin Studies
Glucose Intolerance
Penetrance
Genetic Counseling
Research Personnel
Research
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Inheritance of diabetes mellitus. / Zonana, Jonathan (Jon); Rimoin, D. L.

In: New England Journal of Medicine, Vol. 295, No. 11, 1976, p. 603-605.

Research output: Contribution to journalArticle

Zonana, JJ & Rimoin, DL 1976, 'Inheritance of diabetes mellitus', New England Journal of Medicine, vol. 295, no. 11, pp. 603-605.
Zonana, Jonathan (Jon) ; Rimoin, D. L. / Inheritance of diabetes mellitus. In: New England Journal of Medicine. 1976 ; Vol. 295, No. 11. pp. 603-605.
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