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Adv Exp Med Biol. 1985;189:65-87.

Heterogeneity within type II and MODY diabetes.


The heterogeneity within Type II diabetes (NIDDM) and within Maturity-Onset type Diabetes of Young people (MODY), a subset of NIDDM which is inherited in an autosomal dominant fashion, is discussed. Aspects of the definition and phenotypic expression of MODY are reviewed. Within NIDDM there are differences in patterns of inheritance between subgroups. HLA antigen associations are not found in most NIDDM populations but exist in three specific population groups with Type II diabetes. Within NIDDM and within MODY there are differences in the magnitude of insulin responses to glucose, differences in target tissue responsiveness to insulin in vivo, and differences in receptor and post-receptor effects of insulin. Structurally abnormal variant and biologically defective insulin molecules have been found in some Type II diabetic patients and in members of certain MODY families. The presence or absence of obesity may mark heterogeneous groups of Type II diabetic patients, in addition to the importance of obesity in uncovering an insulin secretory defect by causing insulin resistance. There is heterogeneity in susceptibility to vascular disease within NIDDM and MODY. The natural history of carbohydrate metabolism and of insulin secretory responses to glucose in early Type I diabetes and in MODY with low insulin secretory responses are illustrated and similarities and dissimilarities compared and contrasted. Failure to recognize young patients with MODY may contribute to incorrect diagnosis, management, and assignment of prognosis of this form of diabetes in the young by many practicing physicians. The recognition that Type I or insulin-dependent diabetes (IDDM) and Type II or noninsulin-dependent (NIDDM) differ from each other not only phenotypically but also in etiology and pathogenesis led the National Diabetes Data Group (NDDG) to devise the present nomenclature and classification of diabetes mellitus. These were adopted by the World Health Organization. As suggested by the NDDG report, the classification should be reexamined periodically to reflect improved understanding of the disease, to stimulate further research, and to be of help to practicing physicians.

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