HLA-DQ associations distinguish insulin-resistant and insulin-sensitive variants of NIDDM in black Americans

• Published in: Diabetes care Vol. 16; no. 2; pp. 429 - 433
• Main Authors: BANERJI, M. A, NORIN, A. J, CHAIKEN, R. L, LEBOVITZ, H. E
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-02-1993
• Subjects: Alleles; Biological and medical sciences; Black or African American; Black People; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; HLA-DQ Antigens - analysis; HLA-DQ Antigens - genetics; Humans; Infusions, Intravenous; Insulin - administration & dosage; Insulin - pharmacology; Insulin Resistance - genetics; Insulin Resistance - immunology; Medical sciences; Middle Aged; New York; New York; Endocrinopathy; Human; HLA-DQ-Locus; HLA-System; American; Major histocompatibility system; Inheritance; Etiopathogenesis; Clinical form; Negroid; Exploration; Non insulin dependent diabetes
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.16.2.429

HLA-DQ associations distinguish insulin-resistant and insulin-sensitive variants of NIDDM in black Americans.
M A Banerji ,
A J Norin ,
R L Chaiken and
H E Lebovitz
Department of Medicine, SUNY Health Science Center, Brooklyn 11203.
Abstract
OBJECTIVE--NIDDM in black Americans exists as two variants: one with a primary defect in insulin action (insulin-resistant
variant) and the other with normal insulin action and a primary defect in insulin secretion (insulin-sensitive variant). The
objective of this study was to determine whether these two variants were genetically distinct from each other and from normal
control subjects as determined by HLA typing. RESEARCH DESIGN AND METHODS--Insulin action was measured with the euglycemic
insulin clamp with a 1 mU.kg-1.min-1 insulin infusion with [3-3H]glucose. A glucose disposal of < 278 mumol.kg-1.min-1 was
considered insulin resistant, and a value greater than this was considered insulin sensitive. The study population consisted
of 21 insulin-resistant and 25 insulin-sensitive black NIDDM patients and 89 normal, nondiabetic black control subjects from
an urban hospital. HLA typing was performed with serological methods. RESULTS--The frequency of HLA-DQW7 in the insulin-resistant
population (76%) was significantly greater than that in the insulin-sensitive population (32%, corrected P < 0.018) and the
normal control population (21%, corrected P < 0.001). The frequency of HLA-DQW6 was increased in the insulin-sensitive population
(76%), corrected P < 0.023, as compared with the normal control subjects (33%). The relative risk of HLA-DQW7 in identifying
insulin-resistant NIDDM patients compared with control subjects was 7. CONCLUSIONS--At least one component that differentiates
insulin-resistant and insulin-sensitive NIDDM in black Americans is under different genetic control. One or more loci responsible
for insulin-resistant and insulin-sensitive NIDDM are likely to be in linkage disequilibrium with the DQ locus of the human
MHC region of chromosome 6.