High prevalence of Type 2 (non-insulin-dependent) diabetes among the offspring of conjugal Type 2 diabetic parents in India

Viswanathan, M; Mohan, Viswanathan; Snehalatha, Chamukuttan; Ramachandran, Ambady

doi:10.1007/bf00703134

Cited by 89 publications

(28 citation statements)

References 16 publications

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“…About one-third of these patients had evidence of vertical transmission of diabetes through two or more generations and thus presumably had MODY on clinical grounds, although the genetics of MODY was unknown at that time. Due to the earlier onset of type 2 diabetes among Asian Indians, the conventional criteria of age of onset and family history might not differentiate MODY mutation carriers from early-onset type 2 diabetic patients in this age range (3,4). Therefore, examination at the molecular level gains importance.…”

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confidence: 99%

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

et al. 2005

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OBJECTIVE—Among Europeans, mutations in the hepatocyte nuclear factor-1α (HNF1α) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1α gene in different types of diabetes in Asian Indians. RESEARCH DESIGN AND METHODS—Genotyping of Ala98Val was done by the PCR–restriction fragment–length polymorphism method in the following groups: 1) MODY, defined as non–insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups. RESULTS—The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2–like diabetes (groups 1–4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002). CONCLUSIONS—Among Asian Indians, the Ala98Val polymorphism of HNF1α gene is associated with MODY and with earlier age at onset of type 2 diabetes.

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confidence: 99%

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

et al. 2005

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“…Results in FCPD were compared with those found in South Indian subjects who either had Type 1 (insulin-dependent) or Type 2 (non-insulin-dependent) diabetes to investigate a possible genetic link between these diseases and FCPD. The Type 2 diabetic population in South India provided new data in its own right, since genetic polymorphisms linked to this disease has not previously been sought in this ethnic group in which there is a high familial occurrence of diabetes [12].…”

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The genetic predisposition to fibrocalculous pancreatic diabetes

et al. 1989

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Summary. Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes rnellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n=94), patients with Type2 (non-insulin-dependent) diabetes (n=87) and Type 1 (insulin-dependent) diabetes (n = 58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DRc~/DQc~/DXct genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQ[~ gene (DQ[~ T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p = 0.01 ; corrected p value = 0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p = 0.0001 ; corrected p value = 0.0008). In Type 2 diabetes, similar results were obtained with 33% subjects possessing the class 3 allele (t7 value compared to control subjects = 0.0005; corrected p value = 0.004). This study suggests that fibrocalculous pancreatic diabetes has a genetic component in its aetiology. Furthermore, its origin might be related to an individual with part of the genetic predisposition to diabetes (Type 1 or Type 2) who additionally has evidence of chronic calcific pancreatitis.

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“…31 Higher prevalence of "asymptomatic" diabetes among the OCDP was observed on glucose tolerance testing. 32 Using oral glucose tolerance testing, Viswanathan et al 33 noted that 50% of the OCDP had overt diabetes and 12% had impaired glucose tolerance, and that 30% of the diabetic offspring developed the disease before age 40. The potential limitation of this study was that the ascertainment was based on family history.…”

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confidence: 99%

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?

Gunaid

1999

Ann Saudi Med

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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.

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High prevalence of Type 2 (non-insulin-dependent) diabetes among the offspring of conjugal Type 2 diabetic parents in India

Cited by 89 publications

References 16 publications

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

A Prevalent Amino Acid Polymorphism at Codon 98 (Ala98Val) of the Hepatocyte Nuclear Factor-1α Is Associated With Maturity-Onset Diabetes of the Young and Younger Age at Onset of Type 2 Diabetes in Asian Indians

The genetic predisposition to fibrocalculous pancreatic diabetes

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?

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