Associations of Cumulative Adulthood, Childhood and Life-long Insulin with Adulthood Retinal Microvasculature

Oskari Repo; Markus Juonala; Suvi P Rovio; Juha Mykkänen; Jaakko Nevalainen; Mika Kähönen; Terho Lehtimäki; Tomi P Laitinen; Jorma Viikari; Olli Raitakari; Robyn Tapp; Katja Pahkala

doi:10.1210/clinem/dgae865

Associations of Cumulative Adulthood, Childhood and Life-long Insulin with Adulthood Retinal Microvasculature

Oskari Repo, Markus Juonala, Suvi P Rovio, Juha Mykkänen, Jaakko Nevalainen, Mika Kähönen, Terho Lehtimäki, Tomi P Laitinen, Jorma Viikari, Olli Raitakari, Robyn Tapp, Katja Pahkala

Centre for Intelligent Healthcare

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Abstract

CONTEXT: Exogenous insulin is reported to have both vasodilatory and vasoconstrictive effects on the microvasculature. Little is known about the associations of long-term endogenous insulin exposure with microvasculature.

OBJECTIVE: To 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.

METHODS: We analyzed data derived from the longitudinal Cardiovascular Risk in Young Finns Study (YFS). 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 34-49 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 life-long AUCs.

RESULTS: Higher adulthood, childhood and life-long 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.

CONCLUSIONS: Cumulative childhood, adulthood and life-long insulin are associated with decreased retinal arteriolar diameter in adulthood in a population of participants without diabetes, independently of conventional cardiovascular risk factors.

Original language	English
Pages (from-to)	e3085–e3092
Number of pages	8
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	110
Issue number	9
Early online date	11 Dec 2024
DOIs	https://doi.org/10.1210/clinem/dgae865
Publication status	Published - 1 Sept 2025

Bibliographical note

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Funding

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; Yrj\u00F6 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).

Funders	Funder number
Tampereen Tuberkuloosisäätiö
Paavo Nurmen Säätiö
Jane ja Aatos Erkon Säätiö
Signe ja Ane Gyllenbergin Säätiö
Suomen Kulttuurirahasto
Suomen kliinisen kemian yhdistys
Juho Vainion Säätiö
Emil Aaltosen Säätiö
Diabetestutkimussäätiö
Syöpäsäätiö
Sydäntutkimussäätiö
Tampere University Hospital
Yrjö Jahnssonin Säätiö
Sigrid Juséliuksen Säätiö
Horizon Europe	848146, 755320
Turku University Hospital	X51001
Research Council of Finland	126925, 322098, 129378, 121584, 117797, 141071, 356405, 286284, 134309, 124282
European Research Council	742927

Keywords

insulin
microvascular changes
arterioles
retina
lifespan

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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dgae865 (1)Final published version, 551 KBLicence: CC BY

Cite this

Repo, O., Juonala, M., Rovio, S. P., Mykkänen, J., Nevalainen, J., Kähönen, M., Lehtimäki, T., Laitinen, T. P., Viikari, J., Raitakari, O., Tapp, R., & Pahkala, K. (2025). Associations of Cumulative Adulthood, Childhood and Life-long Insulin with Adulthood Retinal Microvasculature. Journal of Clinical Endocrinology and Metabolism, 110(9), e3085–e3092. https://doi.org/10.1210/clinem/dgae865

Repo, O, Juonala, M, Rovio, SP, Mykkänen, J, Nevalainen, J, Kähönen, M, Lehtimäki, T, Laitinen, TP, Viikari, J, Raitakari, O, Tapp, R & Pahkala, K 2025, 'Associations of Cumulative Adulthood, Childhood and Life-long Insulin with Adulthood Retinal Microvasculature', Journal of Clinical Endocrinology and Metabolism, vol. 110, no. 9, pp. e3085–e3092. https://doi.org/10.1210/clinem/dgae865

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abstract = "CONTEXT: Exogenous insulin is reported to have both vasodilatory and vasoconstrictive effects on the microvasculature. Little is known about the associations of long-term endogenous insulin exposure with microvasculature.OBJECTIVE: To 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.METHODS: We analyzed data derived from the longitudinal Cardiovascular Risk in Young Finns Study (YFS). 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 34-49 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 life-long AUCs.RESULTS: Higher adulthood, childhood and life-long 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.CONCLUSIONS: Cumulative childhood, adulthood and life-long 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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AU - Juonala, Markus

AU - Rovio, Suvi P

AU - Mykkänen, Juha

AU - Nevalainen, Jaakko

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Laitinen, Tomi P

AU - Viikari, Jorma

AU - Raitakari, Olli

AU - Tapp, Robyn

AU - Pahkala, Katja

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PY - 2025/9/1

Y1 - 2025/9/1

N2 - CONTEXT: Exogenous insulin is reported to have both vasodilatory and vasoconstrictive effects on the microvasculature. Little is known about the associations of long-term endogenous insulin exposure with microvasculature.OBJECTIVE: To 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.METHODS: We analyzed data derived from the longitudinal Cardiovascular Risk in Young Finns Study (YFS). 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 34-49 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 life-long AUCs.RESULTS: Higher adulthood, childhood and life-long 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.CONCLUSIONS: Cumulative childhood, adulthood and life-long 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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Associations of Cumulative Adulthood, Childhood and Life-long Insulin with Adulthood Retinal Microvasculature

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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