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  • 1
    Electronic Resource
    Electronic Resource
    High prevalence of Type 2 (non-insulin-dependent) diabetes among the offspring of conjugal Type 2 diabetic parents in India (1985)
    Springer
    Diabetologia 28 (1985), S. 907-910 
    Details
    ISSN: 1432-0428
    Keywords: Conjugal diabetes ; India ; Type 2 diabetes ; genetics ; ethnic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of Type 2 (non-insulin-dependent) diabetes among offspring of conjugal Type 2 diabetic parents in India was determined by performing oral glucose tolerance tests. Diabetes was present in 50% of offspring, and 12% had impaired glucose tolerance according to the National Diabetes Data Group criteria. Thus, 62% of all offspring had abnormal glucose tolerance tests. This is the highest prevalence rate for diabetes among offspring of conjugal diabetic parents and might represent an ethnic variation of the genetic factors operating in Indian patients with Type 2 (non-insulin-dependent) diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00703134
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  • 2
    Electronic Resource
    Electronic Resource
    Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile (1985)
    Springer
    Diabetologia 28 (1985), S. 229-232 
    Details
    ISSN: 1432-0428
    Keywords: Tropical pancreatic diabetes ; heterogeneity ; ketosis-resistant ; C-peptide ; microangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 nondiabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p〈0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p〈0.01) and VLDL cholesterol (p〈0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n=11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n=17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n=5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogenous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00282238
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  • 3
    Electronic Resource
    Electronic Resource
    The genetic predisposition to fibrocalculous pancreatic diabetes (1989)
    Springer
    Diabetologia 32 (1989), S. 45-51 
    Details
    ISSN: 1432-0428
    Keywords: Genetics ; insulin gene ; DQβ gene ; fibrocalculous pancreatic diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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 mellitus. 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 Type 2 (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 DRα/DQα/DXα genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQβ gene (DQβ 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 (p 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265403
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  • 4
    Electronic Resource
    Electronic Resource
    Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus amongst South Indians (1993)
    Springer
    Diabetologia 36 (1993), S. 633-641 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin dependent) diabetes mellitus ; glucokinase ; genetics ; linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3′) and GCK(5′)) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5′) marker; however, there were significant differences in allele frequencies at the GCK(3′) marker between the Type 2 diabetic subjects and control subjects (χ 2=11.6, df=3, p=0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z+2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score 〈−2) at a recombination fraction of zero under five of the ten models used and highly unlikely (−2 〈 lod score 〈−1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404073
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  • 5
    Electronic Resource
    Electronic Resource
    Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease (1995)
    Springer
    Diabetologia 38 (1995), S. 481-486 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor substrate-1 ; gene mutations ; non-insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p=0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410287
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  • 6
    Electronic Resource
    Electronic Resource
    Rising prevalence of NIDDM in an urban population in India (1997)
    Springer
    Diabetologia 40 (1997), S. 232-237 
    Details
    ISSN: 1432-0428
    Keywords: Keywords NIDDM ; impaired glucose tolerance ; epidemiology ; India ; urban population.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A survey conducted in 1988–1989, in the city of Madras, South India, showed that the prevalence of diabetes mellitus in adults was 8.2 % and prevalence of impaired glucose tolerance (IGT) was 8.7 %. The present survey was another cross-sectional study conducted 5 years later in the same urban area to study the temporal changes in the prevalence of diabetes and IGT. The two sample populations surveyed were similar in age structure and socioeconomic factors. In the second survey in 1994–1995, a total of 2183 subjects, 1081 men and 1102 women, with a mean age of 40 ± 12 years were tested by an oral glucose tolerance test; fasting and 2-h post-glucose plasma glucose were measured. Anthropometric measurements, details of physical activity and clinical history of diabetes were recorded. Age-standardised prevalence of diabetes had increased to 11.6 % from 8.2 % in 1989 and IGT was 9.1 %, similar to 8.7 % in 1989. Multiple regression analysis showed age, waist : hip ratio, body mass index (BMI) and female sex were correlated to diabetes. Family history of diabetes showed interaction with age and BMI. Prevalence of IGT correlated to age, BMI and waist : hip ratio. This study highlights the rising trend in the prevalence of non-insulin-dependent diabetes (NIDDM) in urban Indians. The persistent high prevalence of IGT may also be a predictor of a further increase in NIDDM in the future. No significant differences in the anthropometric data were noted in this compared to the previous study. [Diabetologia (1997) 40: 232–237]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050668
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  • 7
    Electronic Resource
    Electronic Resource
    Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians (1997)
    Springer
    Diabetologia 40 (1997), S. 971-975 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Vitamin D receptor ; genotype ; insulin-dependent diabetes ; genetic susceptibility ; South India.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vitamin D has important immunomodulatory properties and prevents development of diabetes mellitus in an animal model of insulin-dependent diabetes (IDDM). We have studied the vitamin D receptor locus as a candidate for genetic susceptibility to IDDM in Southern Indian families. We found evidence for an association of one particular vitamin D receptor allele with IDDM susceptibility in this community. Ninety-three South Indian families consisting of available parents and an affected offspring were genotyped for three vitamin D receptor polymorphisms using the restriction enzymes TaqI, ApaI and BsmI as well as an adjacent microsatellite located to 12q14 (D12S85). Transmission disequilibrium testing analysis was used to assess preferential transmission of polymorphic markers and haplotypes with IDDM. There was significant excess transmission of vitamin D receptor alleles containing the BsmI restriction site to affected offspring in these families (p = 0.016). No association was found between D12S85 and IDDM. This study suggests that a polymorphism within or close to the vitamin D receptor gene may modify susceptibility to IDDM in this ethnic group. [Diabetologia (1997) 40: 971–975]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050776
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  • 8
    Electronic Resource
    Electronic Resource
    An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes (1999)
    Springer
    Diabetologia 42 (1999), S. 688-692 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Uncoupling protein genes ; obesity ; leptin ; polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. Methods. Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. Results. In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p 〈 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). Conclusion/interpretation. We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin. [Diabetologia (1999) 42: 688–693]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051216
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  • 9
    Electronic Resource
    Electronic Resource
    Family studies of non-insulin-dependent diabetes mellitus in South Indians (1994)
    Springer
    Diabetologia 37 (1994), S. 1221-1230 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; segregation analysis ; South India ; family studies ; polygenes ; major gene ; heritability ; diathesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70%) diabetic and 11 of 128 (9%) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and nontransmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in non-diabetic family members (diathesis) was included, ii) support for segregation of a diallelic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d=0.8) and a disease-predisposing allele frequency of 14%. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399796
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  • 10
    Electronic Resource
    Electronic Resource
    Family studies of non-insulin-dependent diabetes mellitus in South Indians (1994)
    Springer
    Diabetologia 37 (1994), S. 1221-1230 
    Details
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; segregation analysis ; South India ; family studies ; polygenes ; major gene ; heritability ; diathesis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Though a genetic basis for non-insulin-dependent diabetes mellitus (NIDDM) is clear, the likely mode of inheritance is not known. The segregation of NIDDM was studied in 64 nuclear South Indian pedigrees (449 individuals) ascertained through an affected proband having both parents and more than 1 sibling alive and available for oral glucose tolerance testing. A high proportion of parents were found to be of abnormal glucose tolerance [89 of 128 (70 %) diabetic and 11 of 128 (9 %) impaired]. Complex segregation analysis was performed using (1) POINTER which implements the mixed model and distinguishes major gene, multifactorial and non-transmitted environmental contributions to affection and (2) COMDS which implements an oligogenic model with major gene, modifier gene and environmental contributions to a) affection and b) diathesis (an ordered polychotomy amongst non-affected family members, based on 2-h plasma glucose level). Using POINTER, there was no formal support for a major gene and the most parsimonious solutions were achieved with multifactorial models. Using COMDS, we found i) significant improvements in models when information on glucose levels in non-diabetic family members (diathesis) was included, ii) support for segregation of a diallelic gene as well as background familial resemblance, and iii) under the best-supported model, this diallelic locus featured incomplete dominance (d = 0.8) and a disease-predisposing allele frequency of 14 %. In South Indians, segregation of NIDDM is inadequately described by simple major gene models: more complex models provide more satisfactory descriptions. This finding, if applicable in other populations, has important implications for the search for diabetes-susceptibility genes. [Diabetologia (1994) 37: 1221–1230]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399796
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