Genetic factors in diabetes mellitus studied by the oral glucose tolerance test.

Thompson, G. S.

doi:10.1136/jmg.2.4.221

Cited by 29 publications

(7 citation statements)

References 10 publications

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“…This is theoretically advantageous as there is a continuous distribution of plasma glucose values in the Caucasian population [7], and subjects with impaired glucose tolerance have an increased risk of progression to NIDDM [34][35][36][37]. The likelihood of single locus models was significantly improved by considering the FPG diathesis by COMDS in addition to affection status using POINTER or COMDS.…”

Section: Discussionmentioning

confidence: 90%

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Segregation analysis of NIDDM in Caucasian families

et al. 1994

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Summary Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypotheses, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4 %. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity. [Diabetologia (1994[Diabetologia ( ) 37: 1231[Diabetologia ( -1240 Key words Non-insulin-dependent diabetes mellitus, genetic epidemiology, genetic linkage.Non-insulin-dependent diabetes mellitus (NIDDM) is a common metabolic disorder with considerable morbidity and mortality. Despite evidence for a substantial genetic component, the mode of inheritance and the molecular basis of this inheritance remain un-

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Section: Discussionmentioning

confidence: 90%

“…An alternative explanation may be that the rate of transition from normality to disease in these populations is rapid, perhaps due to the deleterious effects of hyperglycaemia. Bimodality has not been described in the Caucasian population [7] but has been reported in the first-degree relatives of Caucasian NIDDM subjects [8].…”

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confidence: 99%

Segregation analysis of NIDDM in Caucasian families

et al. 1994

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“…This survey offers no assistance in resolving the conflict between the single gene and multifactorial hypotheses of the genetic factors in diabetes (Harris, 1950;Steinberg, 1959;Simpson, 1964;Thompson, 1965); in either event it is the prevalence of the genes in each of the two populations which is manifest as the frequency of clinical diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…pregnancy, infection, steroid medication, or obesity (Jackson, 1955). This underlying defect is, in turn, regarded as due to the effect of an abnormal genetic constitution whether this is in a single gene (Harris, 1950;Steinberg, 1959) or to the combined effects of a number of genes working in concert (Simpson, 1964;Thompson, 1965).…”

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confidence: 99%

Diabetes in wales.

Ashley¹

1967

Journal of Medical Genetics

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“…Several authors have studied glucose tolerance and insulin response in relatives of diabetic patients using oral as well as intravenous or cortisone-primed glucose tolerance tests (Thompson 1965, Burkeholder et al 1967, Navarrete & Torres 1967, Kahn et al 1969. The conclusions drawn have usually been that abnormalities in glucose tolerance as well as in insulin response occur with a significantly increased frequency in these subjects.…”

Section: No Of Observations Variablementioning

confidence: 99%

Significance of genetic factors for the plasma insulin response to glucose in healthy subjects

Lindsten¹,

Cerasi

Luft

et al. 1976

Clinical Genetics

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The intravenous glucose tolerance and plasma insulin response to glucose infusion were analysed in a twin and family material, comprising 279 healthy subjects. The relation between the blood glucose and plasma insulin values was studied by an analysis of the principal eigenvalues. The variables obtained were corrected for sex, age and weight, and standardized with regard to mean and variance. The results showed that at least four of the variables have appreciable familial correlations, corresponding to a heritability (h-") varying between 0.38 and 0.72. These correlations could not be accounted for by common environment alone. Thus, the beta cell function in normal man, as measured by a glucose challenge test, appears to be genetically regulated.

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Genetic factors in diabetes mellitus studied by the oral glucose tolerance test.

Cited by 29 publications

References 10 publications

Segregation analysis of NIDDM in Caucasian families

Segregation analysis of NIDDM in Caucasian families

Diabetes in wales.

Significance of genetic factors for the plasma insulin response to glucose in healthy subjects

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