Maturity-Onset Diabetes of Youth in Black Americans

Abstract

Twelve of 129 black patients with youth-onset diabetes were identified as having an unusual clinical course, with apparent insulin dependence at the time of presentation followed by absence of dependence months to years later. This atypical form of diabetes was found in at least two generations in 9 of the 12 families of the propositi. Fourteen of the diabetic relatives, as well as the 12 propositi, were studied. Islet-cell autoantibodies were not found in any of the patients, and thyroid microsomal auto-antibodies were found in only one. The frequencies of the insulin-dependent-diabetes-associated antigens HLA-DR3 and DR4 were not increased among the propositi, and diabetes did not cosegregate with HLA haplotypes in the informative families. Insulin secretion, as measured by C-peptide responses to a liquid mixed meal (Sustacal), was intermediate between secretion in nondiabetic controls and that in patients with classic insulin-dependent diabetes. Peripheral-blood monocytes expressed increased numbers of insulin receptors as well as decreased empty-site affinities. The atypical form of diabetes in black Americans can be distinguished from classically defined insulin-dependent diabetes and may be best classified as a form of maturity-onset diabetes of youth.

The Occurrence of Diabetic Ketoacidosis in Adults.

“…And they exhibited type 2 DMclinical course after presenting with DKA.This unusual form of diabetes has been recognized in African-Americans and Japanese (4-7). Winter et al (15) reported that some young Afri- can-Americans mayhave symptomsof insulin deficiency, with or without ketoacidosis, but display clinical and metabolic features of type 2 diabetes. Obesity was present in 50%of their patients.…”

Type 2 Diabetes in the Young: The Evolving Epidemic

“…However, DKA may occur at presentation in subjects who are eventually found to have type 2 diabetes (38); that is, they have elevated C-peptide and an absence of antibodies to islet cells (ICA) or glutamic acid decarboxylase (anti-GAD), and after the initial period of severe metabolic disturbance, they do not require insulin (13). Initial reports were among African-American adults, and an autosomal dominant inheritance was suggested (38,39). Subsequent studies have confirmed that type 2 diabetes often presents with ketosis or DKA and occurs in ϳ40% of African-American children (40,41) with type 2 diabetes, 4% of children with Canadian aboriginal backgrounds (42), and 30% of children with Mexican-American backgrounds (32).…”

The polymorphism Gly574Ser in the transcription factor HNF-1α is not a marker of adult-onset ketosis-prone atypical diabetes in Afro-Caribbean patients

“…amplification of allelic effect in the presence of variants at other loci, is likely to be present further illustrating the complexity. The prevalent Ala allele of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene is associated in many studies with increased insulin sensitivity and a decreased risk of Type 2 diabetes [1]. In line with these observations, we recently showed an association of the Ala/Ala genotype and a decreased propensity to develop the IRS in the Danish Monitoring of trends and determinants in Cardiovascular diseases (MONICA) study population [2].…”

“…To the Editor: Type 1B diabetes or ketosis-prone atypical diabetes (KPAD) is a subtype of diabetes mostly described in patients of sub-Saharan African ancestry and characterized by insulin dependence at the time of presentation, without immunological markers seen in typical Type 1A diabetes (T1D), and frequently followed by absence of insulin requirements as in the case of Type 2 diabetes (T2D) [1,2,3]. The subsequent clinical course of KPAD, which could represent up to 12% of the sub-Saharan African diabetic population, is characterized by an alternance of near normoglycaemic remissions and relapses of insulin dependence without precipitating illness [3,4].…”