Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer

Demetrius Albanes, Stephanie J. Weinstein, Margaret E. Wright, Satu Männistö, Paul John Limburg, Kirk Snyder, Jarmo Virtamo

Research output: Contribution to journalArticle

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Abstract

BackgroundThe mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.MethodsWe investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. ResultsInsulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; Ptrend =. 02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; Ptrend =. 02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (Ptrend =. 38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100000 person-years in the highest quartile.ConclusionElevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1272-1279
Number of pages8
JournalJournal of the National Cancer Institute
Volume101
Issue number18
DOIs
StatePublished - Sep 2009

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Insulin Resistance
Prostatic Neoplasms
Insulin
Glucose
Serum
Odds Ratio
Fasting
Confidence Intervals
Homeostasis
Cohort Studies
Logistic Models
Hexokinase
beta Carotene
alpha-Tocopherol
Somatomedins
Prostate
Carcinogenesis
Reference Values
Antibodies
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Albanes, D., Weinstein, S. J., Wright, M. E., Männistö, S., Limburg, P. J., Snyder, K., & Virtamo, J. (2009). Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. Journal of the National Cancer Institute, 101(18), 1272-1279. https://doi.org/10.1093/jnci/djp260

Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. / Albanes, Demetrius; Weinstein, Stephanie J.; Wright, Margaret E.; Männistö, Satu; Limburg, Paul John; Snyder, Kirk; Virtamo, Jarmo.

In: Journal of the National Cancer Institute, Vol. 101, No. 18, 09.2009, p. 1272-1279.

Research output: Contribution to journalArticle

Albanes, D, Weinstein, SJ, Wright, ME, Männistö, S, Limburg, PJ, Snyder, K & Virtamo, J 2009, 'Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer', Journal of the National Cancer Institute, vol. 101, no. 18, pp. 1272-1279. https://doi.org/10.1093/jnci/djp260
Albanes, Demetrius ; Weinstein, Stephanie J. ; Wright, Margaret E. ; Männistö, Satu ; Limburg, Paul John ; Snyder, Kirk ; Virtamo, Jarmo. / Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. In: Journal of the National Cancer Institute. 2009 ; Vol. 101, No. 18. pp. 1272-1279.
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abstract = "BackgroundThe mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.MethodsWe investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. ResultsInsulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8{\%} higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10{\%} and 6{\%} higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95{\%} confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95{\%} CI = 0.86 to 3.56; and OR = 2.55, 95{\%} CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; Ptrend =. 02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95{\%} CI = 1.03 to 4.26; Ptrend =. 02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (Ptrend =. 38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100000 person-years in the highest quartile.ConclusionElevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.",
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AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

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AU - Männistö, Satu

AU - Limburg, Paul John

AU - Snyder, Kirk

AU - Virtamo, Jarmo

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N2 - BackgroundThe mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.MethodsWe investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. ResultsInsulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; Ptrend =. 02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; Ptrend =. 02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (Ptrend =. 38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100000 person-years in the highest quartile.ConclusionElevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

AB - BackgroundThe mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.MethodsWe investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided. ResultsInsulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; Ptrend =. 02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; Ptrend =. 02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (Ptrend =. 38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100000 person-years in the highest quartile.ConclusionElevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

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