Preliminary Report on the Genetics of Diabetes among the Pima Indians

Steinberg, Arthur G.; Rushforth, Norman B.; Bennett, Peter H.; Burch, Thomas A.; Miller, Max

doi:10.1016/b978-0-12-027361-4.50008-9

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…A bimodal curve showing two distinct distributions of plasma glucose concentrations, instead of a single skewed distribution, is compatible with a genetic condition (diabetes) manifest by hyperglycemia and a second population without diabetes (without hyperglycemia). Subsequently, bimodality was reported in other populations with a high prevalence of diabetes, including Nauruans from Micronesia (2), Samoans (3), Asian Indians who had migrated to South Africa (4), and Mexican Americans who were ϳ50% white (5). The diversity of populations with glucose bimodality suggests that this may be a universal phenomenon, readily detected in populations with a high prevalence of diabetes.…”

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confidence: 99%

Bimodality of 2-h Plasma Glucose Distributions in Whites

et al. 2005

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OBJECTIVE -Several studies have shown a bimodal curve in the distribution of glucose in populations with a high prevalence of type 2 diabetes, but bimodality has not been reported among whites of Northern European ancestry. It is not clear whether this difference reflects the lower prevalence of diabetes, obscuring a second mode, or implies a more fundamental difference between whites and nonwhites. We investigate this issue by studying glucose distributions in older white patients. RESEARCH DESIGN AND METHODS-A study of diabetes was conducted among older community-dwelling white residents of a suburban Southern California community between 1984 and 1987. Two-hour plasma glucose data were collected from 2,326 older white men and women aged 23-92. To investigate bimodality of glucose distributions, we fit unimodal and bimodal normal models to 2-h plasma glucose concentrations transformed by the Box-Cox family of transformations.RESULTS -We found that the bimodal normal mixture model fit the data significantly better than the unimodal skewed distribution model for both sexes and all age-groups except those Ն80 years. The cut points separating the two modes were generally within the 11.1-to 13.6-mmol/l range.CONCLUSIONS -The bimodality of glucose distributions among whites, combined with previous findings, indicates that this phenomenon may be universal. A smaller second mode in our study compared with other studies suggests that whites have diabetes susceptibility but may require more obesity to demonstrate it. With increasing obesity in the U.S., the predicted epidemic of diabetes may affect all ethnic groups including whites. Diabetes Care 28:1451-1456, 2005A bimodal distribution of plasma glucose concentrations in a population was first described in a 1971 study on Pima Indians, who have the highest prevalence of type 2 diabetes in the world (1). A bimodal curve showing two distinct distributions of plasma glucose concentrations, instead of a single skewed distribution, is compatible with a genetic condition (diabetes) manifest by hyperglycemia and a second population without diabetes (without hyperglycemia). Subsequently, bimodality was reported in other populations with a high prevalence of diabetes, including Nauruans from Micronesia (2), Samoans (3), Asian Indians who had migrated to South Africa (4), and Mexican Americans who were ϳ50% white (5). The diversity of populations with glucose bimodality suggests that this may be a universal phenomenon, readily detected in populations with a high prevalence of diabetes. To our knowledge, no studies have reported a bimodal glucose distribution among whites of Northern European ancestry, suggesting either genetic/environmental differences or a prevalence of diabetes too low to detect a second mode (6,7).We hypothesized that statistically significant bimodality might be detectable in older white patients because the prevalence of diabetes increases to nearly 20% in old age (8) and because most genetically susceptible people might be expected to develop diabetes if ...

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Bimodality of 2-h Plasma Glucose Distributions in Whites

et al. 2005

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“…Obesity by itself explained an additional 4 % of the variance of fasting blood glucose. Since obesity is a major explanatory variable for fasting blood glucose and is present in a majority of diabetics [Pi-Sunyer, 19821, we speculate that divergent results from previous studies of family resemblance of fasting blood sugar [Elston et al, 1974;Steinberg et al, 1970;Mimura et al, 1964;Williams et al, 19831 might have been accounted for in part by differential degrees of obesity in the population studied. Different methodologies and data adjustments may also partly account for the discrepancies.…”

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confidence: 76%

The Cincinnati lipid research clinic family study: Analysis of commingling and family resemblance for fasting blood glucose

Laskarzewski

Rao

Glueck

et al. 1984

Genetic Epidemiology

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Our specific aim in this study was to investigate commingling and family resemblance for fasting blood glucose in 160 randomly selected white families from the Princeton School District Lipid Research Clinics Family Study. Adjustment of fasting blood glucose for the influence of age, sex, and the use of oral contraceptives and construction of indices were performed simultaneously using multiple regression methods. Path analysis was carried out, constructing an environmental index based on special diet usage, hematocrit, and obesity, which was also adjusted for the influences of age and sex. Commingling analysis and segregation analysis using the mixed model were also performed. Nearly 16% of the variance of fasting blood glucose was accounted for by age and sex. Obesity itself, which constituted the index, explained an additional 4% of the variance of fasting blood glucose. Significant genetic heritability for fasting blood glucose was documented by both path analysis and segregation analysis. In aggregate, we conclude that though there was a major familial vector accounting for within-family aggregation of blood glucose, it was probably generated by a multifactorial component as compared to a major locus. Under the most parsimonious model, path analysis estimated the genetic and cultural heritabilities as h2 = .39 +/- .08 and c2 = .06 +/- .03., respectively.

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“…The burden of certain diseases often falls disproportionately on members of potentially vulnerable populations. For example, Pima Indians have an exceptionally high burden of type 2 diabetes, 7 and African Americans are more likely to experience kidney disease than are Americans of European descent. 8,9 Sometimes, the nature of a specific disease (eg, schizophrenia) may cause significant cognitive or functional disability, 10e12 which potentially renders an individual vulnerable.…”

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confidence: 99%