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      Relationship between sleep parameters, insulin resistance and age-adjusted insulin like growth factor-1 score in non diabetic older patients

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          Abstract

          Background

          Sleep complaints are prevalent in older patients. Sleepiness, short or long sleep duration and obstructive sleep apnea (OSA) are associated with insulin resistance (IR). These parameters have not yet been considered together in the same study exploring the possible association between IR and sleep in older patients. IR is involved in cardiovascular and metabolic diseases, pathologies which are highly prevalent in older patients. Here we assess, in older non-diabetic patients with sleep complaints, the associations between IR and sleep parameters objectively recorded by polysomnography (PSG) rather than self-report. The Growth Hormone/Insulin like growth factor-1 axis could play a role in the development of IR during sleep disorders. The second objective of this study was to analyze the association between sleep parameters and age-adjusted IGF-1 score, which could explain the association between OSA and IR.

          Methods

          72 non-diabetic older patients, mean age 74.5 ± 7.8 years, were included in this observational study. We evaluated anthropometric measures, subjective and objective sleepiness, polysomnography, Homeostatic Model Assessment for IR (HOMA-IR) and age-adjusted IGF-1 score. A multivariate regression was used to determine factors associated with HOMA-IR.

          Results

          The 47 OSA patients were over-weight but not obese and had higher IR than the non-OSA patients. In multilinear regression analysis, apnea-hypopnea index was independently associated with IR after adjustment for several confounding factors. Neither IGF-1 level nor IGF-1 score were different in the two groups.

          Conclusions

          We demonstrate that in non-diabetic older patients with sleep complaints, OSA is independently associated with IR, regardless of anthropometric measurements and sleep parameters (sleep duration/sleepiness/arousals). Targeting OSA to reduce IR could be useful in the elderly, although further exploration is required.

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          Most cited references27

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          Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.

          Terry Young, Eyal Shahar, F Nieto … (2002)
          Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.
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            Sleep-disordered breathing in community-dwelling elderly.

            S Ancoli-Israel, D Kripke, M R Klauber … (1991)
            These are the final results of a survey of sleep-disordered breathing, which examined objective and subjective information from a large randomly selected elderly sample. We randomly selected 427 elderly people aged 65 yr and over in the city of San Diego, California. Twenty-four percent had an apnea index, AI, greater than or equal to 5 and 62% had a respiratory disturbance index, RDI, greater than or equal to 10. Correlates of sleep-disordered breathing included high relative weight and reports of snoring, breathing cessation at night, nocturnal wandering or confusion, daytime sleepiness and depression. Body mass index, falling asleep at inappropriate times, male gender, no alcohol within 2 hr of bedtime and napping were the best predictors of sleep-disordered breathing. Despite statistical significance, all of the associations between interview variables and apnea indices were small. No combination of demographic variables and symptoms allowed highly reliable prediction of AI or RDI.
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              Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study.

              Manjinder S. Sandhu, Adrian H Heald, J. Gibson … (2002)
              Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance. Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance. At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011). These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.
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                Author and article information

                Contributors
                Bertrand Blondeau: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 6 April 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 4
                Electronic Location Identifier: e0174876
                Affiliations
                [1 ]Assistance Publique-Hôpitaux de Paris (APHP), DHU FAST, Functional Exploration Unit of older patients, Groupe hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France
                [2 ]Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Aging, Paris, France
                [3 ]Università degli Studi di Milano, Milan, Italy
                [4 ]Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, Pitié Salpétrière Hospital, Paris, France
                [5 ]Sorbonne Universités, UPMC Univ Paris 06, Paris, France
                [6 ]INSERM, UMR_S 1138, Centre de recherche des Cordeliers, Paris, France
                [7 ]CNRS, UMR 8256, Biological Adaptation and Aging, Paris, France
                Centre de Recherche des Cordeliers, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: KK.

                • Data curation: SD MD.

                • Formal analysis: KK MD.

                • Investigation: KK SD ALMS.

                • Methodology: KK OB MD.

                • Project administration: KK.

                • Resources: VHNM.

                • Supervision: KK.

                • Validation: KK.

                • Visualization: KK SD OB MD JM.

                • Writing – original draft: KK SD OB MD.

                • Writing – review & editing: KK SD OB MD JM.

                Article
                Publisher ID: PONE-D-16-39012
                DOI: 10.1371/journal.pone.0174876
                PMC ID: 5383056
                PubMed ID: 28384333
                SO-VID: 023c838f-5aab-49fc-82d6-a78d0968b412
                Copyright © © 2017 Damanti et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 29 September 2016
                Date accepted : 16 March 2017
                Page count
                Figures: 1, Tables: 3, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Sleep
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Physiological Processes
                Subject: Sleep
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Sleep Disorders
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Diabetic Endocrinology
                Subject: Insulin
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Hormones
                Subject: Insulin
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Physiology
                Subject: Insulin Resistance
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Insulin Resistance
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Insulin Resistance
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Apnea
                Subject: Sleep Apnea
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Sleep Disorders
                Subject: Sleep Apnea
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Anthropometry
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Anthropometry
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Body Mass Index
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Physiological Parameters
                Subject: Body Weight
                Subject: Body Mass Index
                Subject: Medicine and Health Sciences
                Subject: Clinical Medicine
                Subject: Clinical Neurophysiology
                Subject: Polysomnography
                Custom metadata
                Data Availability All relevant data regarding the results are within the paper. There are restrictions on the availability of data for this study, due to CNIL recommendation (National Commission "Informatics and Liberty" to protect personal data and preserve individual liberties), as the patients did not agree to make public their individual-level data. Anonymized data that support the findings of this study are available from the corresponding author ( kiyoka.kinugawa@ 123456aphp.fr ) upon reasonable request.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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