Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study

Hong, Yuling; Weisnagel, S. John; Rice, Treva; Sun, Guohua; Mandel, SA; Gu, C. Charles; Rankinen, Tuomo; Gagnon, Jacques; Leon, AS; Skinner, J. S.; Jh, Wilmore; Bergman, Richard N.; Bouchard, Claude; Rao, D. C.

doi:10.1034/j.1399-0004.2001.600104.x

Cited by 40 publications

(35 citation statements)

References 52 publications

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“…The heritability of first-and second-phase insulin secretion in response to glucose was 52% and 77% respectively. For the first phase our results fit neatly in the 35% to 76% range of heritability estimates previously reported using the IVGTT test [6,11,[15][16][17]. However, previous heritability estimates (28% and 58%) of second-phase insulin secretion in response to IVGTT were considerably lower [11,17] than those found in our hyperglycaemic clamp.…”

Section: Discussionsupporting

confidence: 88%

“…In twin studies, the genetic contribution to beta cell function has been tested mostly by examining surrogate measurements of insulin secretion derived from fasting blood levels or in response to oral glucose. In five studies using IVGTT, heritability estimates of the acute insulin response to glucose ranged from 35% to 76% [6,11,[15][16][17]. The heritability of the second-phase insulin response to glucose in an IVGTT has been investigated in two of these studies only [11,17] and was estimated to be 28% and 58%.…”

Section: Introductionmentioning

confidence: 99%

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Genetic influences on the insulin response of the beta cell to different secretagogues

Simonis-Bik

Eekhoff

Moor³

et al. 2009

Diabetologia

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Aims/hypothesis The aim of the present study was to estimate the heritability of the beta cell insulin response to glucose and to glucose combined with glucagon-like peptide-1 (GLP-1) or with GLP-1 plus arginine. Methods This was a twin-family study that included 54 families from the Netherlands Twin Register. The participants were healthy twin pairs and their siblings of the same sex, aged 20 to 50 years. Insulin response of the beta cell was assessed by a modified hyperglycaemic clamp with additional GLP-1 and arginine. Insulin sensitivity index (ISI) was assessed by the euglycaemic-hyperinsulinaemic clamp. Multivariate structural equation modelling was used to obtain heritabilities and the genetic factors underlying individual differences in BMI, ISI and secretory responses of the beta cell. Results The heritability of insulin levels in response to glucose was 52% and 77% for the first and second phase, respectively, 53% in response to glucose+GLP-1 and 80% in response to an additional arginine bolus. Insulin responses to the administration of glucose, glucose+GLP-1 and glucose + GLP-1 + arginine were highly correlated (0.62

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Genetic influences on the insulin response of the beta cell to different secretagogues

Simonis-Bik

Eekhoff

Moor³

et al. 2009

Diabetologia

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“…The heritability of fasting serum insulin and glucose concentrations remained highly significant even after controlling for the effects of significant covariates. The marked heritability of fasting serum glucose and insulin concentrations appears consistent with other reports in Framingham [6,7], Amish [8], and HERITAGE families [9]. Additionally, the genome scans in AAs and EAs provided suggestive evidence that genes regulating fasting serum insulin concentrations and insulin sensitivity (HOMA) were present on chromosomes 19, 7, 5, 4 and 2, and genes regulating fasting glucose concentration were present on chromosomes 2, 5, 9, 13 and 18.…”

Section: Discussionsupporting

confidence: 88%

“…In non-hypertensive populations, an adjusted h 2 value of 0.34 for fasting serum glucose [6] and 0.46 for fasting serum insulin concentrations [7] were reported in the Framingham Offspring Study. Similar high familial correlations for these prediabetic measures were reported in Amish families [8], the HERITAGE FAMILY study [9], and Caucasian twins [3]. Elevated serum insulin and glucose concentrations represent an increased risk of developing overt type 2 diabetes mellitus, with increased rates of cardiovascular morbidity and mortality [10].…”

Section: Introductionsupporting

confidence: 61%

Genome-wide scans for heritability of fasting serum insulin and glucose concentrations in hypertensive families

et al. 2005

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Aims/hypothesis: The heritability of fasting serum insulin and glucose concentrations in non-diabetic members of multiplex hypertensive families is unknown. Methods: We calculated the familial aggregation of fasting serum glucose and insulin concentrations and performed a genome-wide scan to assess whether quantitative trait loci contribute to these phenotypes in 2,412 non-diabetic individuals from 1,030 families enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) in the Family Blood Pressure Program. Results: The heritability (±SE) of fasting serum insulin was 0.47±0.085 in European Americans and 0.28±0.08 in African Americans (p<0.0001 for both), after adjusting for age, sex, and BMI. A genomewide scan for fasting serum insulin yielded a maximum log of the odds (LOD) score of 2.36 on chromosome 5 at 20 cM (p=0.0004) in European Americans, and an LOD score of 2.28 on chromosome 19 at 11 cM (p=0.0004) in African Americans. The heritability of fasting serum glucose was 0.5109±0.08 in the former and 0.29±0.09 in the latter (p<0.0003 for both) after adjusting for age, sex and BMI. A genome-wide scan for fasting serum glucose revealed a maximum LOD score of 2.07 on chromosome 5 at 26 cM (p=0.0009) in European Americans. Conclusions/ interpretation: These analyses demonstrate the marked heritability of fasting serum insulin and glucose concentrations in families enriched for the presence of members with hypertension. They suggest that genes associated with fasting serum insulin concentration are present on chromosomes 19 and 5, and that genes associated with fasting serum glucose concentration are on chromosome 5, in families enriched for hypertension.

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“…In addition, it is important to appreciate that other factors are known to play key roles in determining b-cell function. Approximately, 25% of the variability in DI appears to be related to genetic factors 34,35 and specific fat depots (ie, intrahepatic) may be intimately related to b-cell function, 36 so additional research in these areas is warranted.…”

Section: Body Fatmentioning

confidence: 99%

Insulin sensitivity, insulin secretion and β-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

et al. 2005

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OBJECTIVE:To examine cross-sectional differences in insulin sensitivity, insulin secretion and b-cell function during puberty in overweight Hispanic boys and girls with a family history of type 2 diabetes. STUDY DESIGN AND PARTICIPANTS: This cross-sectional, observational study included 214 8-13-y-old Hispanic children with a BMI percentile Z85th percentile and family history of type 2 diabetes. METHODS AND ANALYSES: Participants underwent a physical examination, body composition measures, oral glucose tolerance test (OGTT), and frequently-sampled intravenous glucose tolerance test. Unadjusted and adjusted general linear models (GLM) tested whether insulin/glucose dynamics differed by Tanner stage and gender. RESULTS: Unadjusted group comparisons showed that fasting insulin increased whereas insulin sensitivity (SI) and the disposition index (DI) (a measure of pancreatic b-cell function) decreased across Tanner stage groups (all Po0.05). No differences in the acute insulin response to glucose (AIRg), fasting glucose or 2-h glucose were found. After adjusting for covariates, there was no independent effect of Tanner stage on SI (P ¼ 0.9) or AIRg (P ¼ 0.2), but DI was slightly lower in later Tanner stages suggesting decreased b-cell function in the more mature groups (P ¼ 0.10). CONCLUSIONS: Overweight Hispanic children with a family history of type 2 diabetes may represent a unique population given that pubertal insulin resistance was not evident once analyses controlled for body composition. Longitudinal analyses are required to determine whether the slightly diminished b-cell function in later Tanner stages plays a role in the development of type 2 diabetes.

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Familial resemblance for glucose and insulin metabolism indices derived from an intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family Study

Cited by 40 publications

References 52 publications

Genetic influences on the insulin response of the beta cell to different secretagogues

Genetic influences on the insulin response of the beta cell to different secretagogues

Genome-wide scans for heritability of fasting serum insulin and glucose concentrations in hypertensive families

Insulin sensitivity, insulin secretion and β-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

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