Familial Clustering of Type II Diabetes Mellitus (Dm) Diagnosed Under the Age of 40 Yars in Yemen: Is it Early-Onset Type II dm or Maturity-Onset Diabetes of the Young?

Abstract

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), full-siblings (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 (≥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 non-consanguineous 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 non-consanguineous and consanguineous nondiabetic parents was characteristically lower (14% for each). Maturity-onset 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 earlyonset 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.

Clinical phenotyping of newly diagnosed type 2 diabetes in Yemen

“…These findings may suggest a strong familial burden of T2D in Eastern Mediterranean populations as compared with native Swedish population. In Yemen, 26 we have previously noted that the development of early-onset T2D among the offspring was more likely associated with a consanguineous and/or conjugal parents with diabetes. An increasing level of FH burden was associated with reduced beta-cell function both in immigrant Iraqis in Sweden25 and in Botnia Finish population 24.…”

Diabetic retinopathy, visual impairment and ocular status among patients with diabetes mellitus in Yemen: A hospital-based study

“…Eye complications of DM in the Yemeni population are expected to be high because familial clustering and high rate of consanguinity are the genetic risk factors for DM which are reported to exist in the Yemeni population. [1516] In addition, acquired factors like hypertension, obesity and hyperlipidemia are also reported to be common in this population. [910] A study in Yemen in 1997 had shown a rate of 45% micro-vascular complications in diabetic patients.…”

“…This could explain the DR rate of 8.9% reported in the Ishfahan province of Iran. [15] A study in Lebanon that had 112 diabetic patients and retinopathy evaluation was conducted by using direct and indirect ophthalmoscopes reported 17% prevalence of DR.[16] In a study of diabetic patients in a hospital of Cairo, the prevalence of DR in diabetics was 42. 2%.…”

Epidemiology of Diabetes Mellitus in Al-Baidha Governorate, Yemen

“…These results might support evidence that the genetic factors play an important role in the pathogenesis of diabetes mellitus in some Yemeni patients. Gunaid in a study on 191 Yemeni patients with type II diabetes showed a considerable familial clustering of type II DM (14). Bone-Tamir and others reported that Yemeni Jews who have unusually high incidence of diabetes differ by gene clustering from all other Jews (15).…”