Associations of common genetic variants with age-related changes in fasting and postload glucose: Evidence from 18 years of follow-up of the whitehall II cohort

Anders C. Jensen, Adam Barker, Meena Kumari, Eric J. Brunner, Mika Kivimäki, Aroon D. Hingorani, Nicholas J. Wareham, A. Tabák, Daniel R. Witte, Claudia Langenberg

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Abstract

OBJECTIVE - In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. RESEARCH DESIGN AND METHODS - We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI. RESULTS - The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023-0.034) difference (P = 2.76 × 10-21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047-0.105) per genetic score point (P = 3.1 × 10-7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003-0.009) per genetic score point per year (age interaction P = 3.0 × 10-5), resulting in diverging age trajectories by genetic score. CONCLUSIONS - Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.

Original languageEnglish
Pages (from-to)1617-1623
Number of pages7
JournalDiabetes
Volume60
Issue number5
DOIs
Publication statusPublished - May 2011

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Fasting
Glucose
Glucose Tolerance Test
Single Nucleotide Polymorphism
Research Design
Genotype

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Jensen, A. C., Barker, A., Kumari, M., Brunner, E. J., Kivimäki, M., Hingorani, A. D., ... Langenberg, C. (2011). Associations of common genetic variants with age-related changes in fasting and postload glucose: Evidence from 18 years of follow-up of the whitehall II cohort. Diabetes, 60(5), 1617-1623. https://doi.org/10.2337/db10-1393

Associations of common genetic variants with age-related changes in fasting and postload glucose : Evidence from 18 years of follow-up of the whitehall II cohort. / Jensen, Anders C.; Barker, Adam; Kumari, Meena; Brunner, Eric J.; Kivimäki, Mika; Hingorani, Aroon D.; Wareham, Nicholas J.; Tabák, A.; Witte, Daniel R.; Langenberg, Claudia.

In: Diabetes, Vol. 60, No. 5, 05.2011, p. 1617-1623.

Research output: Contribution to journalArticle

Jensen, AC, Barker, A, Kumari, M, Brunner, EJ, Kivimäki, M, Hingorani, AD, Wareham, NJ, Tabák, A, Witte, DR & Langenberg, C 2011, 'Associations of common genetic variants with age-related changes in fasting and postload glucose: Evidence from 18 years of follow-up of the whitehall II cohort', Diabetes, vol. 60, no. 5, pp. 1617-1623. https://doi.org/10.2337/db10-1393
Jensen, Anders C. ; Barker, Adam ; Kumari, Meena ; Brunner, Eric J. ; Kivimäki, Mika ; Hingorani, Aroon D. ; Wareham, Nicholas J. ; Tabák, A. ; Witte, Daniel R. ; Langenberg, Claudia. / Associations of common genetic variants with age-related changes in fasting and postload glucose : Evidence from 18 years of follow-up of the whitehall II cohort. In: Diabetes. 2011 ; Vol. 60, No. 5. pp. 1617-1623.
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abstract = "OBJECTIVE - In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. RESEARCH DESIGN AND METHODS - We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI. RESULTS - The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95{\%} CI 0.023-0.034) difference (P = 2.76 × 10-21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047-0.105) per genetic score point (P = 3.1 × 10-7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003-0.009) per genetic score point per year (age interaction P = 3.0 × 10-5), resulting in diverging age trajectories by genetic score. CONCLUSIONS - Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.",
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T2 - Evidence from 18 years of follow-up of the whitehall II cohort

AU - Jensen, Anders C.

AU - Barker, Adam

AU - Kumari, Meena

AU - Brunner, Eric J.

AU - Kivimäki, Mika

AU - Hingorani, Aroon D.

AU - Wareham, Nicholas J.

AU - Tabák, A.

AU - Witte, Daniel R.

AU - Langenberg, Claudia

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N2 - OBJECTIVE - In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. RESEARCH DESIGN AND METHODS - We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI. RESULTS - The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023-0.034) difference (P = 2.76 × 10-21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047-0.105) per genetic score point (P = 3.1 × 10-7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003-0.009) per genetic score point per year (age interaction P = 3.0 × 10-5), resulting in diverging age trajectories by genetic score. CONCLUSIONS - Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.

AB - OBJECTIVE - In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. RESEARCH DESIGN AND METHODS - We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI. RESULTS - The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023-0.034) difference (P = 2.76 × 10-21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047-0.105) per genetic score point (P = 3.1 × 10-7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003-0.009) per genetic score point per year (age interaction P = 3.0 × 10-5), resulting in diverging age trajectories by genetic score. CONCLUSIONS - Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose.

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