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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Type II diabetes ; obesity ; dyslipidaemia ; genetic epidemiology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by environmental factors. Although the familial aggregation of Type II diabetes is acknowledged, there is little data concerning the prevalence of diabetes in the relatives of subjects with diabetes in comparison with the general population, and our objective was to address this question in the defined geographic region of Oxfordshire, England. We studied 139 first degree relatives of 90 probands with Type II diabetes who attended routine diabetes clinics in Oxfordshire and documented the fasting plasma glucose, triglyceride and HDL-cholesterol concentrations and BMI of these subjects. The probands were selected without regard to family history of diabetes. The control population data were derived from two large-scale Oxford community studies which documented the prevalences of known and newly diagnosed diabetes. The prevalences of newly diagnosed and known diabetes were calculated for each group. The mean BMI, and concentrations of fasting glucose, triglyceride and HDL-cholesterol were compared and prevalence ratios for obesity (defined as BMI 〉 30 kg/m2), hyperglycaemia (defined as fasting plasma glucose ≥ 6.1 mmol/l), and dyslipidaemia (defined as triglyceride 〉 2.0 mmol/l, HDL 〈 1.0 mmol/l) were calculated. There was a fourfold higher prevalence of hyperglycaemia in the first degree relatives of subjects with Type II diabetes compared with the control population: the prevalence ratio after adjustment for age, sex and BMI was 4.32 (95 % confidence interval 2.29–8.17). The relatives had a considerably higher fasting plasma glucose concentration than the control population (5.18 ± 0.67 mmol/l (mean ± 1 SD) vs 4.76 ± 1.59 mmol/l, p = 0.0001), and this difference remained statistically significant after adjustment for age, sex and obesity. The relatives were significantly more obese, had higher fasting plasma insulin concentrations and had lower HDL-cholesterol concentrations. In conclusion, there is a strong familial aggregation of hyperglycaemia and obesity in the relatives of subjects with Type II diabetes and these subjects have higher fasting plasma insulin concentrations and lower HDL-cholesterol than the general population. These data indicate the particular relevance of screening the first degree relatives of subjects with Type II diabetes, as intervention strategies which aim to improve the metabolic profile are indicated for a large proportion of these subjects. [Diabetologia (1999) 42: 24–27]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Type II diabetes ; mortality ; cardiovascular disease ; cancer ; population study ; post-challenge hyperglycaemia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The aim of this study was to examine the possible link between isolated post-challenge hyperglycaemia (2-h post-challenge plasma glucose ≥ 11.1 mmol/l, and fasting plasma glucose 〈 7.0 mmol/l) and mortality. Methods. The data from three population based longitudinal studies (in Mauritius, Fiji and Nauru) were pooled and mortality rates were determined in 9179 people who were followed for between 5 and 12 years. Results. There were 595 people with previously diagnosed diabetes, and 799 with newly diagnosed diabetes, of whom 243 (31) had isolated post-challenge hyperglycaemia. In comparison with people without diabetes, people with isolated post-challenge hyperglycaemia had an increased risk of all-cause mortality [Cox proportional hazards ratio (95 % CI): 2.7 (1.8–3.9) – men; 2.0 (1.3–3.3) – women], and of cardiovascular mortality [2.3 (1.2–4.2) – men; 2.6 (1.3–5.1) – women]. In addition, men with isolated post-challenge hyperglycaemia had a high risk of cancer death [8.0 (3.6–17.9)]. Conclusion/interpretation. These data show that isolated post-challenge hyperglycaemia, which can only be identified by the 2-h glucose, is common, and at least doubles the mortality risk. This should be considered in the design of screening programmes that use only fasting glucose [Diabetologia (1999) 42: 1050–1054]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; genetic epidemiology ; genetic linkage.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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) 37: 1231–1240]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; genetic epidemiology ; genetic linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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