Associations of Cumulative Adulthood, Childhood and Lifelong Insulin With Adulthood Retinal Microvasculature
: Repo, Oskari; Juonala, Markus; Rovio, Suvi P.; Mykkänen, Juha; Nevalainen, Jaakko; Kähönen, Mika; Lehtimäki, Terho; Laitinen, Tomi P.; Viikari, Jorma; Raitakari, Olli; Tapp, Robyn; Pahkala, Katja
Publisher: ENDOCRINE SOC
: WASHINGTON
: 2024
: Journal of Clinical Endocrinology and Metabolism
: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
: J CLIN ENDOCR METAB
: 8
: 0021-972X
: 1945-7197
DOI: https://doi.org/10.1210/clinem/dgae865
: https://doi.org/10.1210/clinem/dgae865
: https://research.utu.fi/converis/portal/detail/Publication/477705826
Context
Exogenous insulin is reported to have both vasodilatory and vasoconstrictive effects on microvasculature. Little is known about the associations of long-term endogenous insulin exposure with microvasculature.
ObjectiveTo test the hypothesis that long-term exposure to high insulin levels in childhood and adulthood is associated with adverse changes in retinal microvasculature in adulthood in a population without diabetes.
MethodsWe analyzed data derived from the longitudinal Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980, and participants were followed for 31 years from childhood to adulthood with frequent follow-up visits. Fundus photos were taken in 2011, and microvascular outcome measures were derived in participants at the age of 34 to 49 years (n = 1684). After exclusion of individuals with diabetes or missing insulin measures, 1166 participants formed the population of the present study. Cumulative exposure as the area under the curve (AUC) for adulthood (10-year exposure between 2001 and 2011) and childhood (exposure between ages 6-18 years) insulin and other cardiovascular risk factors were determined. Additionally, adulthood and childhood cumulative AUCs were summarized to construct lifelong AUCs.
ResultsHigher adulthood, childhood, and lifelong exposure for cumulative insulin was associated with decreased retinal arteriolar diameter when adjusted for age and sex and further for cumulative conventional cardiovascular risk factors.
ConclusionCumulative childhood, adulthood, and lifelong insulin are associated with decreased retinal arteriolar diameter in adulthood in a population of participants without diabetes, independently of conventional cardiovascular risk factors.
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The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278), and the Jane and Aatos Erkko Foundation. K.P. is supported by an Academy of Finland research fellowship (322112).
