The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study

Chino S. Aneke-Nash, Xiaonan (Nan) Xue, Qibin Qi, Mary L. Biggs, Anne Cappola, Lewis Kuller, Michael Pollak, Bruce M. Psaty, David Siscovick, Kenneth Mukamal, Howard Strickler, Robert C. Kaplan

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Abstract

Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.

Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.

Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.

Setting: General community.

Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.

Interventions: Not applicable.

Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.

Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.

Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

Original languageEnglish (US)
Pages (from-to)4541-4547
Number of pages7
JournalThe Journal of clinical endocrinology and metabolism
Volume102
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Insulin-Like Growth Factor Binding Protein 3
Medical problems
Insulin-Like Growth Factor I
Health
Population
Glucose
Inpatients
Outpatients
Medicaid
Statistical Models
International Classification of Diseases
Medicare
Plasmas
Fasting
Homeostasis
Outcome Assessment (Health Care)
Pharmacology
Confidence Intervals
Insulin
Hazards

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study. / Aneke-Nash, Chino S.; Xue, Xiaonan (Nan); Qi, Qibin; Biggs, Mary L.; Cappola, Anne; Kuller, Lewis; Pollak, Michael; Psaty, Bruce M.; Siscovick, David; Mukamal, Kenneth; Strickler, Howard; Kaplan, Robert C.

In: The Journal of clinical endocrinology and metabolism, Vol. 102, No. 12, 01.12.2017, p. 4541-4547.

Research output: Contribution to journalArticle

Aneke-Nash, Chino S. ; Xue, Xiaonan (Nan) ; Qi, Qibin ; Biggs, Mary L. ; Cappola, Anne ; Kuller, Lewis ; Pollak, Michael ; Psaty, Bruce M. ; Siscovick, David ; Mukamal, Kenneth ; Strickler, Howard ; Kaplan, Robert C. / The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study. In: The Journal of clinical endocrinology and metabolism. 2017 ; Vol. 102, No. 12. pp. 4541-4547.
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abstract = "Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.Setting: General community.Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.Interventions: Not applicable.Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95{\%} confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.",
author = "Aneke-Nash, {Chino S.} and Xue, {Xiaonan (Nan)} and Qibin Qi and Biggs, {Mary L.} and Anne Cappola and Lewis Kuller and Michael Pollak and Psaty, {Bruce M.} and David Siscovick and Kenneth Mukamal and Howard Strickler and Kaplan, {Robert C.}",
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AU - Aneke-Nash, Chino S.

AU - Xue, Xiaonan (Nan)

AU - Qi, Qibin

AU - Biggs, Mary L.

AU - Cappola, Anne

AU - Kuller, Lewis

AU - Pollak, Michael

AU - Psaty, Bruce M.

AU - Siscovick, David

AU - Mukamal, Kenneth

AU - Strickler, Howard

AU - Kaplan, Robert C.

PY - 2017/12/1

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N2 - Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.Setting: General community.Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.Interventions: Not applicable.Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

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