03693nas a2200421 4500008004100000022001400041245007800055210006900133260001600202300001200218490000600230520248800236653000902724653002802733653001902761653002802780653001102808653002502819653001902844653001102863653004902874653004902923653003302972653000903005653002103014653001003035653002903045653001703074653001803091100001603109700001403125700001803139700001803157700002103175700001703196700002203213856003603235 2013 eng d a1550-939700aSleep and insulin-like growth factors in the Cardiovascular Health Study.0 aSleep and insulinlike growth factors in the Cardiovascular Healt c2013 Dec 15 a1245-510 v93 a

STUDY OBJECTIVES: Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population.

DESIGN SETTING: Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS).

PATIENTS OR PARTICIPANTS: 1,233 elderly participants from the CHS and SHHS.

MEASUREMENTS AND RESULTS: The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p < 0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p < 0.01). As expected, slow wave sleep was better preserved in females compared to males (22% total sleep time vs. 9% total sleep time, p < 0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] ≥ 5/h) was more prevalent in males compared to females (60% vs. 46%, p < 0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI ≥ 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI ≥ 5 and < 15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts.

10aAged10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aSex Distribution10aSleep10aSleep Apnea, Obstructive10aSomatomedins10aUnited States1 aShah, Neomi1 aRice, Tom1 aTracy, Daniel1 aRohan, Thomas1 aBůzková, Petra1 aNewman, Anne1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/618902680nas a2200289 4500008004100000022001400041245011600055210006900171260001600240300001500256520179300271100002202064700002202086700002202108700002702130700002102157700002202178700001802200700002002218700001802238700002002256700001802276700002302294700002002317700001702337856003602354 2016 eng d a1945-719700aInsulinlike growth factor binding protein-1 and ghrelin predict health outcomes among older adults: CHS cohort.0 aInsulinlike growth factor binding protein1 and ghrelin predict h c2016 Nov 07 ajc201627793 a

CONTEXT: Multiple diseases may explain the association of the growth hormone / insulinlike growth factor-I (GH/IGF-I) axis with longevity.

OBJECTIVE: To relate circulating GH/IGF-I system protein levels with major health events.

DESIGN: Cohort study Setting: Four US communities Participants: Adults (n=2268) 65 years and older free of diabetes and cardiovascular disease.

MEASUREMENTS: We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiologic covariates.

RESULTS: During 13,930 person-years of follow-up, 48.1% individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-h ghrelin were associated with a 27% higher (95% CI: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-h IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite endpoint. Similarly, higher mortality was significantly associated with higher fasting and 2-h ghrelin level, and with 2-h IGFBP-1 level. When examined together, 2-h post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels.

CONCLUSIONS: Circulating IGFBP-1 and ghrelin measured during an OGTT predict major health events and death in older adults, which may explain the influence of the GH-IGF-axis on lifespan and health.

1 aKaplan, Robert, C1 aStrizich, Garrett1 aAneke-Nash, Chino1 aDominguez-Islas, Clara1 aBůzková, Petra1 aStrickler, Howard1 aRohan, Thomas1 aPollak, Michael1 aKuller, Lewis1 aKizer, Jorge, R1 aCappola, Anne1 aLi, Christopher, I1 aPsaty, Bruce, M1 aNewman, Anne uhttps://chs-nhlbi.org/node/7258