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


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.
Banerji
M A
MA
Department of Medicine, SUNY Health Science Center, Brooklyn 11203.
Norin
A J
AJ
Chaiken
R L
RL
Lebovitz
H E
HE
D000483:Alleles; D044383:Black People; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009518:New York; D001741:Black or African American
D001786:Blood Glucose; D006683:HLA-DQ Antigens; C069546:HLA-DQ7 antigen; D007328:Insulin