Availability of Type II Diabetic Families for Detection of Diabetes Susceptibility Genes

Cook, J. T. E.; Page, R.; O'Rahilly, Steven; Lévy, Jonathan; Holman, Rury R.; Barrow, B A; Hattersley, Andrew T.; Shaw, J. A. G.; Wainscoat, James S.

doi:10.2337/diab.42.10.1536

Cited by 13 publications

(14 citation statements)

References 21 publications

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“…48, DECEMBER 1999 1 Potential availability of trios (diabetic proband with two living parents) and affected sibling pairs in a population-based questionnaire survey of 5,809 diabetic subjects (>99% U.K. C a u c a s i a n ) Treatment category Type 2 Type 1 A l l I n s u l i n O H A D i e t 24.2%, P < 0.0001) and were more obese than the sibling-pair probands (BMI 32.0 vs. 29.0 k g / m 2 , P < 0.0001; not available for population survey). In the trios in which parental status could be directly tested, no maternal excess was seen, as reported in the two other series in which both parents were available for testing (6,7). In contrast, our reported data in the sibling pairs and population series showed an excess of maternal diabetes, in keeping with other studies that used reported data (8).…”

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confidence: 61%

Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.

et al. 1999

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The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene variants in disease that avoids the problem of population stratification that may confound conventional case/control studies and allows the detection of parent-of-origin effects. Trios have played a major role in defining genes in a number of polygenic conditions, including type 1 diabetes. We assessed the prevalence, clinical characteristics, and suitability for defining type 2 susceptibility genes of European type 2 diabetes trios. In a Caucasian population in the U.K., only 2.5% of type 2 patients had both parents alive. Using a nationwide strategy, we collected 182 trios defined by strict clinical criteria. Immunological and genetic testing resulted in the exclusion of 25 trios as a result of latent autoimmune diabetes (n = 13), inconsistent family relationships (n = 7), and maternally inherited diabetes and deafness (n = 5). The 157 remaining probands had similar treatment requirements to familial type 2 diabetic subjects but presented at a younger age, were more obese, and more frequently had affected parents. Using this resource, we have not found any evidence for linkage disequilibrium between type 2 diabetes and the glucokinase gene markers GCK1 and GCK2 and the chromosome 20 marker D20S197. We conclude that European type 2 diabetes trios are difficult to collect but provide an important additional approach to dissecting the genetics of type 2 diabetes.

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confidence: 61%

Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.

et al. 1999

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“…In a study of the ascertainment of suitable pedigrees from 950 known diabetic patients in Oxfordshire, only 127 (13%) families were available for study [8]. The strategy investigated in this study was based on the identification of probands with a history of gestational diabetes who, on retesting, had evidence of IGT or NIDDM, with subsequent testing of their parents.…”

Section: Discussionmentioning

confidence: 99%

“…Of the 35 potential probands, 40 % of patients and parents were available and willing to be studied as a family, representing 23 % of those with fasting hyperglycaemia. This is a larger yield than that from known diabetic patients in the Oxfordshire study [8], and provides a complementary strategy for the collection of pedigree data suitable for genetic studies. As one might expect that those with a diabetic parent would be more likely to volunteer for the study, this would counteract any potential bias from not being able to study families in which a parent had died from a diabetes-related cause.…”

Section: Discussionmentioning

confidence: 99%

“…The last column shows the number of parents of each proband who, in the study, were found to have either fasting hyperglycaemia or diabetes. I, Insulin; D, diet generation, nuclear families in which both parents of a diabetic patient are alive and available for study [8]. Cook et al [9] recently identified 20 NIDDM patients with nuclear families to ascertain the distribution of NIDDM in the parents, and the apparent pattern of inheritance [9].…”

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Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

et al. 1995

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Summary Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (+ SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5 _< fpg < 7.8 mmol/1) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m 2. The parents were aged 62 (6) years and had BMI 29 (6) kg/m 2 and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level > 2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43 %) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We concludes that the study of women who have had gestational diabetes allows detection of probands with diabetes or impaired glucose tolerance, who have both parents available for study. A substantial proportion had neither parent affected with impaired glucose tolerance or diabetes, similar to the nuclear families of NIDDM patients. The results are in accord with studies of nuclear families of NIDDM patients in suggesting polygenic inheritance or environmental influences rather than autosomal dominant inheritance with high penetrance. [Diabetologia (1995) 25 years, more than 50 % of the women develop diabetes [1]. Approximately 30 % of women who present with NIDDM in middle age have previously been suspected to have diabetes in pregnancy because of hyperglycaemia or glycosuria [2]. Women who have had gestational diabetes present an opportunity to study diabetes at an early stage in its evolution [3]. They are often overweight, and have both impaired beta-cell function and increased insulin resistance [4,5]. These are similar defects to those found in the first degree relatives of NIDDM patients [5][6][7].Studies of inheritance of NIDDM have been restricted because of the difficulty in identifying two

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“…Probands were aged 35 years or older at the time of diagnosis of diabetes. Families with three or more siblings and a quarter of families with two siblings living within the study area were approached to establish whether they were willing to be recruited to the program [13]. The proband assessed the willingness of their siblings to be approached as potential study volunteers, and the research team then contacted those interested.…”

Section: Participants and Methodsmentioning

confidence: 99%

In a randomized trial, outcomes were not affected by intensive follow-up over 1 year

Farmer

Doll

2005

Journal of Clinical Epidemiology

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Availability of Type II Diabetic Families for Detection of Diabetes Susceptibility Genes

Cited by 13 publications

References 21 publications

Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.

Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

In a randomized trial, outcomes were not affected by intensive follow-up over 1 year

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