Mapping Genes for NIDDM: Design of the Finland—United States Investigation of NIDDM Genetics (FUSION) Study

Valle, Timo T.; Tuomilehto, Jaakko; Bergman, Richard N.; Ghosh, Soumitra; Hauser, Elizabeth R.; Eriksson, Johan G.; Nylund, Stella J.; Kohtamäki, Kimmo; Toivanen, Liisa; Vidgrén, Gabriele; Tuomilehto‐Wolf, Eva; Ehnholm, Christian; Blaschak, Jillian; Langefeld, Carl D.; Watanabe, Richard M.; Magnuson, Victoria L.; Ally, Delphine S.; Hagopian, William; Ross, Edna H.; Buchanan, Thomas A.; Collins, Francis S.; Boehnke, Michael

doi:10.2337/diacare.21.6.949

Cited by 91 publications

(106 citation statements)

References 13 publications

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“…The ongoing search for genes for Type II diabetes will provide new information about the genetic markers of interest. We will be able to determine whether those subjects with IGT who progress to Type II diabetes share certain susceptibility genes and whether subjects with certain genotypes respond particularly well to intensive lifestyle interventions based on the results of genetic studies currently going on in Finland [31].…”

Section: Methodsmentioning

confidence: 99%

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland

Eriksson¹,

Lindström²,

Valle³

et al. 1999

Diabetologia

329

324

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Aims/hypothesis. The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. Methods. A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. Results. During the first year, weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l, p < 0.001; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. Conclusion/interpretation. The interim results show the efficacy and feasibility of the lifestyle intervention programme. [Diabetologia (1999) 42: 793±801]

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Section: Methodsmentioning

confidence: 99%

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland

Eriksson¹,

Lindström²,

Valle³

et al. 1999

Diabetologia

329

324

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“…The Finland-US Investigation of NID-DM (Type II diabetes mellitus) Genetics (FUSION) Study is an international collaborative effort with the goal of mapping and cloning the genes predisposing to Type II diabetes and intermediate quantitative traits in Finnish subjects [15]. The age at diagnosis of Type II diabetes in index cases from which the families were ascertained ranged from 35±60 years.…”

Section: Methodsmentioning

confidence: 99%

The W64R variant of the β 3 -adrenergic receptor is not associated with Type II diabetes or obesity in a large Finnish sample

et al. 1999

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Obesity affects up to one third of people in Western populations and severe obesity is associated with excess morbidity and mortality [1]. Obesity increases insulin resistance which often predisposes to Type II (non-insulin-dependent) diabetes mellitus even though the mechanisms for this pathway are still notThere is evidence that functional b 3 -adrenergic receptors are present in both human white and brown adipose tissue [6,7] and b 3 -adrenergic receptor agonists have been shown to decrease insulin resistance in both obese diabetic and non-diabetic subjects [8]. Targeted disruption of the b 3 -adrenoceptor gene has given rise to animals that are generally more obese [9,10]. Thus, it is not surprising that a number of studies have focused on the role of b 3 -adrenergic receptor variants in Type II diabetes and obesity. Altered function could promote obesity by increased fat storage in white adipose tissue and decreased thermogenesis in brown adipose tissue. Further, abnormal b 3 -adrenergic receptor activity could result in increased insulin resistance by increasing delivery of non-esterified fatty acids from intra-abdominal fat stores to the portal circulation [11].Recently, a b 3 -adrenergic receptor variant was found to be associated with insulin resistance [12], Diabetologia (1999) 42: 238±244 The W64R variant of the b 3 -adrenergic receptor is not associated with Type II diabetes or obesity in a large Finnish sample

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“…The FUSION study design, recruitment, and phenotyping have been detailed elsewhere (Valle et al 1998), and details regarding genotyping can be found in the companion article by Ghosh et al (2000 [in this issue]). Therefore, in this article we only briefly review recruitment and phenotyping.…”

Section: Subjects and Phenotypingmentioning

confidence: 99%

“…Fasting glucose, insulin, lipids, and resting blood pressure were measured in all study subjects. Fasting C-peptide and glutamic acid decarboxylase antibody (GAD Ab) were measured in diabetic individuals, and these values were used in conjunction with insulin-treatment information to identify possible cases of late-onset type 1 diabetes, as described elsewhere (Valle et al 1998). An oral glucose-tolerance test (OGTT), conforming to World Health Organization (1985) standards, was performed both in all nondiabetic subjects, to determine their glucose-tolerance status, and in diabetic subjects whose affection status could not be readily confirmed, yielding 2-h glucose and insulin measurements in these individuals.…”

Section: Subjects and Phenotypingmentioning

confidence: 99%

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

Watanabe¹,

Ghosh²,

Langefeld³

et al. 2000

Am. J Hum. Genet.

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Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting Cpeptide/glucose: maximum LOD score [MLS] p 3.13 at 53.0 cM) and 13 (body-mass index: MLS p 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS p 3.11 at 21.0 cM), 13 (2-h insulin: MLS p 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS p 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS p 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS p 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS p 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

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Mapping Genes for NIDDM: Design of the Finland—United States Investigation of NIDDM Genetics (FUSION) Study

Abstract: Our work demonstrates the feasibility of collecting a large number of affected sib-pair families with NIDDM to provide data that will enable a whole genome search approach, including linkage analysis.

Cited by 91 publications

References 13 publications

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland

The W64R variant of the β 3 -adrenergic receptor is not associated with Type II diabetes or obesity in a large Finnish sample

The Finland–United States Investigation of Non–Insulin‐Dependent Diabetes Mellitus Genetics (FUSION) Study. II. An Autosomal Genome Scan for Diabetes‐Related Quantitative‐Trait Loci

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