03082nas a2200409 4500008004100000022001400041245012400055210006900179260001300248300001000261490000700271520181300278653000902091653001802100653001902118653003002137653001102167653001102178653004902189653004902238653003302287653000902320653002602329100002502355700002902380700002602409700002102435700002402456700002802480700002002508700002102528700002002549700002002569700002502589700002202614856003602636 2015 eng d a1532-541500aChanges in insulin-like growth factor-I and its binding proteins are associated with diabetes mellitus in older adults.0 aChanges in insulinlike growth factorI and its binding proteins a c2015 May a902-90 v633 a

OBJECTIVES: To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period.

DESIGN: Retrospective analysis of a cohort study.

SETTING: Participants were recruited from North Carolina, California, Maryland, and Pennsylvania.

PARTICIPANTS: Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N=897).

MEASUREMENTS: Plasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06).

RESULTS: At baseline, mean age was 76.3±3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3% for IGF-I, 59.7% for IGFBP-1, -13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: -3.7% for IGF-I, 25.6% for IGFBP-1, -6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up.

CONCLUSION: Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality.

10aAged10aBlood Glucose10aCohort Studies10aDiabetes Mellitus, Type 210aFemale10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aRetrospective Studies1 aAneke-Nash, Chino, S1 aParrinello, Christina, M1 aRajpathak, Swapnil, N1 aRohan, Thomas, E1 aStrotmeyer, Elsa, S1 aKritchevsky, Stephen, B1 aPsaty, Bruce, M1 aBůzková, Petra1 aKizer, Jorge, R1 aNewman, Anne, B1 aStrickler, Howard, D1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/673702547nas a2200229 4500008004100000022001400041245016500055210006900220260001300289300000900302490000700311520179200318100002502110700002702135700002102162700001402183700001702197700002002214700002502234700002202259856003602281 2016 eng d a1532-223800aAgreement between circulating IGF-I, IGFBP-1 and IGFBP-3 levels measured by current assays versus unavailable assays previously used in epidemiological studies.0 aAgreement between circulating IGFI IGFBP1 and IGFBP3 levels meas c2016 Feb a11-60 v263 a

OBJECTIVE: Levels of insulin-like growth factor (IGF) proteins are associated with the risk of cancer and mortality. IGF assays produced by Diagnostic Systems Laboratories (DSL) were widely used in epidemiological studies, were not calibrated against recommended standards and are no longer commercially available.

DESIGN: In a split sample study among 1471 adults participating in the Cardiovascular Health Study, we compared values obtained using DSL assays with alternative assays for serum IGF-I (Immunodiagnostic Systems, IDS), IGFBP-1 (American Laboratory Products Company, ALPCO) and IGFBP-3 (IDS).

RESULTS: Results were compared using kernel density estimation plots, quartile analysis with weighted kappa statistics and linear regression models to assess the concordance of data from the different assays. Participants had a mean age of 77years. Results between alternative assays were strongly correlated (IGF-I, r=0.93 for DSL versus IDS; log-IGFBP-1, r=0.90 for DSL versus ALPCO; IGFBP-3, r=0.92 for DSL versus IDS). Cross tabulations showed that participants were usually in the same quartile categories regardless of the assay used (overall agreement, 74% for IGF-I, 64% for IGFBP-1, 71% for IGFBP-3). Weighted kappa also showed substantial agreement between assays (kw, 0.78 for IGF-I, 0.69 for IGFBP-1, 0.76 for IGFBP-3). Regressions of levels obtained with DSL assays (denoted X) to alternative assays were, IGF-I: 0.52X+15.2ng/ml, log-IGFBP-1: 1.01X-1.73ng/ml IGFBP-3: 0.87X+791.1ng/ml. Serum values of IGF-I, IGFBP-1 and IGFBP-3 measured using alternative assays are moderately correlated.

CONCLUSIONS: Care is needed in the interpretation of data sets involving IGF analytes if assay methodologies are not uniform.

1 aAneke-Nash, Chino, S1 aDominguez-Islas, Clara1 aBůzková, Petra1 aQi, Qibin1 aXue, XiaoNan1 aPollak, Michael1 aStrickler, Howard, D1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/695203488nas a2200481 4500008004100000022001400041245014400055210006900199260001600268300001400284490000800298520209000306653000902396653002202405653001502427653001802442653002802460653001902488653002202507653001102529653001102540653001402551653004902565653003302614653002502647653000902672653001602681653002402697653000902721100002502730700001702755700001402772700001902786700001802805700001802823700002002841700002002861700002102881700002102902700002502923700002202948856003602970 2017 eng d a1945-719700aThe Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.0 aAssociation Between IGFI and IGFBP3 and Incident Diabetes in an  c2017 Dec 01 a4541-45470 v1023 a

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.

10aAged10aAged, 80 and over10aBiomarkers10aBlood Glucose10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aHumans10aIncidence10aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aLongitudinal Studies10aMale10aNew England10aProspective Studies10aRisk1 aAneke-Nash, Chino, S1 aXue, XiaoNan1 aQi, Qibin1 aBiggs, Mary, L1 aCappola, Anne1 aKuller, Lewis1 aPollak, Michael1 aPsaty, Bruce, M1 aSiscovick, David1 aMukamal, Kenneth1 aStrickler, Howard, D1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/7547