Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

M L Hribal; I Presta; T Procopio; M A Marini; A Stancáková; J Kuusisto; F Andreozzi; A Hammarstedt; P-A Jansson; N Grarup; T Hansen; M Walker; N Stefan; A Fritsche; H U Häring; O Pedersen; U Smith; M Laakso; G Sesti; EUGENE2 Consortium

doi:10.1007/s00125-010-2038-8

Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

M L Hribal, I Presta, T Procopio, M A Marini, A Stancáková, J Kuusisto, F Andreozzi, A Hammarstedt, P-A Jansson, N Grarup, T Hansen, M Walker, N Stefan, A Fritsche, H U Häring, O Pedersen, U Smith, M Laakso, G Sesti, EUGENE2 Consortium

Endocrinology and Metabolism

20 Citations (Scopus)

Abstract

Aims/hypothesis: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. Methods: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. Results: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p=0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p=0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). Conclusions/ interpretation: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.

Original language	English
Journal	Diabetologia
Volume	54
Issue number	4
Pages (from-to)	795-802
Number of pages	8
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-010-2038-8
Publication status	Published - Apr 2011

Keywords

Adult
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16
Diabetes Mellitus, Type 2
Female
Genetic Predisposition to Disease
Humans
Insulin
Insulin Resistance
Male
Middle Aged
Polymorphism, Genetic
Sequence Analysis, DNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-010-2038-8

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Hribal, M. L., Presta, I., Procopio, T., Marini, M. A., Stancáková, A., Kuusisto, J., Andreozzi, F., Hammarstedt, A., Jansson, P-A., Grarup, N., Hansen, T., Walker, M., Stefan, N., Fritsche, A., Häring, H. U., Pedersen, O., Smith, U., Laakso, M., Sesti, G., & EUGENE2 Consortium (2011). Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B. Diabetologia, 54(4), 795-802. https://doi.org/10.1007/s00125-010-2038-8

Hribal, ML, Presta, I, Procopio, T, Marini, MA, Stancáková, A, Kuusisto, J, Andreozzi, F, Hammarstedt, A, Jansson, P-A, Grarup, N , Hansen, T, Walker, M, Stefan, N, Fritsche, A, Häring, HU, Pedersen, O, Smith, U, Laakso, M, Sesti, G & EUGENE2 Consortium 2011, 'Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B', Diabetologia, vol. 54, no. 4, pp. 795-802. https://doi.org/10.1007/s00125-010-2038-8

@article{684a240d60ee4193a33d5e7585135861,

title = "Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B",

abstract = "Aims/hypothesis: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. Methods: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. Results: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p=0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p=0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). Conclusions/ interpretation: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.",

keywords = "Adult, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Polymorphism, Genetic, Sequence Analysis, DNA",

author = "Hribal, {M L} and I Presta and T Procopio and Marini, {M A} and A Stanc{\'a}kov{\'a} and J Kuusisto and F Andreozzi and A Hammarstedt and P-A Jansson and N Grarup and T Hansen and M Walker and N Stefan and A Fritsche and H{\"a}ring, {H U} and O Pedersen and U Smith and M Laakso and G Sesti and {EUGENE2 Consortium}",

year = "2011",

month = apr,

doi = "10.1007/s00125-010-2038-8",

language = "English",

volume = "54",

pages = "795--802",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

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TY - JOUR

T1 - Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

AU - Hribal, M L

AU - Presta, I

AU - Procopio, T

AU - Marini, M A

AU - Stancáková, A

AU - Kuusisto, J

AU - Andreozzi, F

AU - Hammarstedt, A

AU - Jansson, P-A

AU - Grarup, N

AU - Hansen, T

AU - Walker, M

AU - Stefan, N

AU - Fritsche, A

AU - Häring, H U

AU - Pedersen, O

AU - Smith, U

AU - Laakso, M

AU - Sesti, G

AU - EUGENE2 Consortium

PY - 2011/4

Y1 - 2011/4

N2 - Aims/hypothesis: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. Methods: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. Results: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p=0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p=0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). Conclusions/ interpretation: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.

AB - Aims/hypothesis: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. Methods: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. Results: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p=0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p=0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). Conclusions/ interpretation: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.

KW - Adult

KW - Cyclin-Dependent Kinase Inhibitor p15

KW - Cyclin-Dependent Kinase Inhibitor p16

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Male

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Sequence Analysis, DNA

U2 - 10.1007/s00125-010-2038-8

DO - 10.1007/s00125-010-2038-8

M3 - Journal article

C2 - 21234743

SN - 0012-186X

VL - 54

SP - 795

EP - 802

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -

Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

Abstract

Keywords

UN SDGs

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