Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors.

Clausen, Jesper O.; Borch‐Johnsen, Knut; Ibsen, Hans; Bergman, Richard N.; Hougaard, P.; Winther, Kaj; Pedersen, Oluf

doi:10.1172/jci118903

Cited by 251 publications

(226 citation statements)

References 67 publications

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“…Gylvin et al: [21]. s-C-peptide, serum C-peptide; p-glucose, plasma glucose; s-insulin, serum insulin [22] In conclusion, a mutation scanning of the human SOCS3 gene identified no variations associated with Type 1 diabetes mellitus. Homozygosity for a C −920→A promoter polymorphism with a minor allele frequency of 8% was shown to be associated with increased whole-body insulin sensitivity in a population of young healthy unrelated individuals.…”

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confidence: 78%

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Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

et al. 2004

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Aims/hypothesis. Beta cell loss in Type 1 and Type 2 diabetes mellitus may result from apoptosis and necrosis induced by inflammatory mediators. The suppressor of cytokine signalling (SOCS)-3 is a natural inhibitor of cytokine signalling and also influences insulin signalling. SOCS3 could therefore be a candidate gene in the development of Type 1 and Type 2 diabetes mellitus. Methods. Mutation analysis of the SOCS3 gene was performed in 21 patients with Type 1 diabetes mellitus and in seven healthy subjects. An identified promoter variant was examined in (i) 250 families with Type 1 diabetic family members (1097 individuals); (ii) 212 glucose-tolerant first-degree relatives of Type 2 diabetic patients; and (iii) 370 population-based young, healthy subjects who were unrelated. Results. Three mutations were identified in the promoter region, but none in the coding region or the 3′UTR.Two of the three mutations had allele frequencies below 1% whereas the C −920→A substitution had a minor allele frequency of 8%. In the group of young healthy subjects the insulin sensitivity index was higher among homozygous carriers of the A-allele than among heterozygous and wild-type subjects (p=0.027, uncorrected). The same trend was found in the group of first-degree relatives of Type 2 diabetic patients. No association or linkage was found to Type 1 diabetes mellitus. Conclusions/interpretation. Homozygosity for the A-allele of the C −920→A promoter polymorphism of the SOCS3 gene may be associated with increased whole-body insulin sensitivity, but deserves further investigation.

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confidence: 78%

“…A random population-based sample of young, healthy, unrelated Danish subjects (n=370) from Copenhagen. Aged 18 to 32 years, these subjects underwent an IVGTT in combination with an intravenous tolbutamide injection [22].…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

et al. 2004

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“…15 Takemura et al 8 found that higher levels of fitness at baseline were protective against the development of IGT over a 20-year period. The protective effect of fitness was evident even after adjusting for baseline and follow-up BMI.…”

Section: Fitness and Glucose Tolerancementioning

confidence: 99%

Cardiovascular fitness and physical activity in children with and without impaired glucose tolerance

et al. 2005

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Objective: To examine differences in cardiovascular fitness (VO 2max ) and physical activity levels in overweight Hispanic children with normal glucose tolerance (NGT) vs impaired glucose tolerance (IGT). Participants: A total of 173 overweight (BMI percentile 97.073.1) Hispanic children ages 8-13 years with a family history of type 2 diabetes. Methods: VO 2max was measured via a maximal effort treadmill test and open circuit spirometry. Physical activity was determined by questionnaire. Glucose tolerance was established by a 2-h oral glucose challenge (1.75 g of glucose/kg body weight). IGT was defined from an oral glucose tolerance test as a 2-h plasma glucose level X140 and o200 mg/dl. Results: IGT was detected in 46 of the 173 participants (B27%); no cases of type 2 diabetes were identified. No significant differences were found between youth with NGT and those with IGT in absolute VO 2max (2.270.6 vs 2.170.5 l/min), VO 2max adjusted for gender, age, and body composition (2.270.2 vs 2.170.2 l/min), or recreational physical activity levels (8.778.2 vs 6.976.2 h/week). Conclusion: Overweight Hispanic youth with IGT exhibit similar levels of VO 2max and physical activity compared to their NGT counterparts. Longitudinal analyses are necessary to determine whether fitness/activity measures contribute significantly to diabetes risk over time in this group.

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“…The first consisted of 4444 middleaged NGT subjects, 490 subjects with IFG and 678 subjects with IGT, all of whom were from the Inter99 study and were examined by a standard 75-g OGTT with measurements of circulating levels of glucose, insulin and C-peptide at 0, 30 and 120 min. The second was a population-based sample of 358 young healthy subjects, who underwent a tolbutamide-modified IVGTT for measurements of the acute serum insulin and C-peptide responses as described previously [17]. Data on birth length and birthweight of the latter group were obtained from the midwife records stored in the Danish Provincial Archives for Zealand, Lolland-Falster and Bornholm.…”

Section: Subjectsmentioning

confidence: 99%

“…Acute serum insulin and serum C-peptide responses during a tolbutamide-modified IVGTT were calculated as the incremental area under the insulin/C-peptide curve for 0 to 8 min [17,18]. The insulin sensitivity index (S i ) was measured using Bergman's minimal model on data obtained during the IVGTT.…”

Section: Genotyping Of the Ins-vntr Class I And Class Iii Allelesmentioning

confidence: 99%

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

et al. 2004

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Aims/hypothesis. The class III allele of the variablenumber-of-tandem-repeats polymorphism located 5′ of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. Methods. We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middleaged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes.Results. There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middleaged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. Conclusions/interpretation. The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

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Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors.

Cited by 251 publications

References 67 publications

Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

Cardiovascular fitness and physical activity in children with and without impaired glucose tolerance

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

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