There are few reports on the genetic, immunological and nutritional characteristics of insulin-using youth-onset diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) and malnutrition-related diabetes mellitus (MRDM) in Korea. Among 1266 hospitalized Korean diabetics, 29 (2.3%) were IDDM and 84 (6.6%) were MRDM. A diabetes history of first-relatives (28.6%) was more frequently found in the MRDM group than in the IDDM (14.8) and non-insulin-dependent diabetes mellitus (NIDDM) (19.0%) groups. HLA-DR4 was more common among IDDM (54.2%) and MRDM (52.4%) patients than controls (26.3%), and HLA-DR3 was more common among only IDDM patients (29.2%) than controls (10.9%). Conventional islet-cell antibodies were detected in 8 of 15 IDDM patients tested (53.3%) and in 11 of 22 MRDM patients (50.0%). MRDM patients had higher serum basal (1.02 +/- 0.51 ng/ml) and peak (1.44 +/- 0.76 ng/ml) C-peptide concentrations than IDDM patients, but lower concentrations than NIDDM patients. Before the onset of diabetes, the calorie intake of 21 MRDM patients assessed was 63.1% of the daily requirement and the intake of carbohydrate, protein and fat was 71.7%, 55.9% and 39.8%, respectively. In summary, our data suggest that IDDM in Korea is associated with HLA-DR3 or HLA-DR4, indicating a risk for IDDM in Western societies; furthermore, MRDM has a history of undernutrition at the preonset period and is also associated with HLA-DR4. It might be also concluded that MRDM in Korea is another expression of IDDM caused by the shortage of some nutrients for the structural and/or functional maintenance of pancreatic beta-cells.