@article {940, title = {Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Apr}, pages = {1319-25}, abstract = {

CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.

OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.

DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.

MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.

RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95\% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.

CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

}, keywords = {Aged, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Multivariate Analysis, Risk Factors, Stroke}, issn = {0021-972X}, doi = {10.1210/jc.2006-1631}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis H and Strickler, Howard D and Rohan, Tom E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {1035, title = {High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly.}, journal = {Am Heart J}, volume = {155}, year = {2008}, month = {2008 Jun}, pages = {1006-12}, abstract = {

BACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.

METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95\% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.

RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95\% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95\% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95\% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.

CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.

}, keywords = {Aged, Aged, 80 and over, Female, Heart Failure, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Predictive Value of Tests, Prospective Studies, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2007.12.031}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {991, title = {Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults.}, journal = {Growth Horm IGF Res}, volume = {18}, year = {2008}, month = {2008 Apr}, pages = {166-73}, abstract = {

Increasing evidence suggests that the insulin-like growth factor (IGF)-axis may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women > or = 65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95\% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95\% CI: 0.26, 0.64; p-trend: <0.01) for IFG. We did not find any significant association between IGF-I and glucose intolerance in this study and the association for IGFBP-3 was less clear. However, low levels of IGF-I and IGFBP-3 were associated with increased levels of markers of inflammation including C-reactive protein and interleukin-6 levels. We conclude that among adults > or = 65 years, low IGFBP-1 levels are associated with increased prevalence of glucose intolerance. We did not confirm prior associations of low IGF-I with glucose intolerance in this cohort of older individuals.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Cross-Sectional Studies, Female, Glucose Intolerance, Humans, Inflammation, Insulin-Like Growth Factor Binding Proteins, Male, Signal Transduction, Somatomedins}, issn = {1096-6374}, doi = {10.1016/j.ghir.2007.08.004}, author = {Rajpathak, Swapnil N and McGinn, Aileen P and Strickler, Howard D and Rohan, Thomas E and Pollak, Michael and Cappola, Anne R and Kuller, Lewis and Xue, XiaoNan and Newman, Anne B and Strotmeyer, Elsa S and Psaty, Bruce M and Kaplan, Robert C} } @article {1021, title = {Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Apr}, pages = {652-60}, abstract = {

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults.

DESIGN: Cohort study.

SETTING/PARTICIPANTS: One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study.

MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality.

RESULTS: Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95\% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95\% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties.

CONCLUSION: In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Enzyme-Linked Immunosorbent Assay, Fasting, Female, Follow-Up Studies, Hand Strength, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Survival Rate, United States, Walking}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01637.x}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Xue, XiaoNan and Kritchevsky, Stephen B and Newman, Anne B and Psaty, Bruce M} } @article {7547, title = {The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.}, journal = {J Clin Endocrinol Metab}, volume = {102}, year = {2017}, month = {2017 Dec 01}, pages = {4541-4547}, 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.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Longitudinal Studies, Male, New England, Prospective Studies, Risk}, issn = {1945-7197}, doi = {10.1210/jc.2017-01273}, author = {Aneke-Nash, Chino S and Xue, XiaoNan and Qi, Qibin and Biggs, Mary L and Cappola, Anne and Kuller, Lewis and Pollak, Michael and Psaty, Bruce M and Siscovick, David and Mukamal, Kenneth and Strickler, Howard D and Kaplan, Robert C} }