Familial clustering of type II diabetes mellitus (DM) diagnosed under the age of 40 years in Yemen: Is it early-onset type II DM or maturity-onset diabetes of the young?

BACKGROUND

Clinical presentation of type II diabetes mellitus (DM) has frequently been observed at an early age in developing countries, probably as a result of genetic, epidemiological and demographic factors. This study aimed to investigate the pattern of familial clustering of type II DM in patients who developed clinical diabetes before the age of 40 years.

PATIENTS AND METHOD

The study involved family pedigrees, clinical assessments and laboratory investigations of 191 patients with type II DM, and 260 age-matched randomly selected non-diabetic controls.

RESULTS

The prevalence of type II DM was found to be statistically higher among parents (P<0.0001), fullsiblings (P<0.0001), half-siblings (P<0.001), uncles (P<0.01) and aunts (P<0.001) of the index patients, as compared to the corresponding relatives of nondiabetic controls. The odds ratio of the family history index (FHI), in association with type II DM in probands who had no family history of diabetes (FHI=0.0), was significantly negative (OR=0.34; 95% CI 0.23, 0.52; P<0.0001). At an FHI level of 0.5-1.0, there was a slight nonsignificant increase in odds ratio for diabetes (OR=1.53; 95% CI 0.95, 2.45; P=0.08). A higher level of FHI (A(3)1.5) was associated with a significant increase in odds ratio for diabetes (OR=3.75; 95% CI 2.13, 6.64; P<0.0001). The age-corrected relative risk of type II DM for the offspring of diabetic parents was found to be progressively increasing from a nonconsanguineous diabetic father (22%) or mother (26.5%), to nonconsanguineous conjugal diabetic parents (27%) and to the offspring of consanguineous single or conjugal diabetic parents (37.5%). On the contrary, the age-corrected relative risk for the offspring of nonconsanguineous and consanguineous nondiabetic parents was characteristically lower (14% for each). Maturityonset diabetes of the young (MODY) was suspected in 10 probands (5%), and early-onset type II DM in the offspring of conjugal diabetic parents in 16 probands (9%). The remaining 165 probands (86%) were unclassified due to lack of specific classification criteria.

CONCLUSION

The considerable familial clustering of type II DM diagnosed under the age of 40 years in this study population reflects the presence of a strong genetic component in its etiology. In addition, the development of early-onset type II DM was more likely associated with a consanguineous and/or conjugal diabetic parents and probably MODY subtype among a substantial number of patients. Epidemiological and demographic factors might have been implicated, especially in those with negative parental diabetic history.