Perinatal famine is associated with excess risk of proliferative retinopathy in patients with type 2 diabetes

Purpose Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopat...

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Published inActa ophthalmologica (Oxford, England) Vol. 100; no. 2; pp. e539 - e545
Main Authors Fedotkina, Olena, Luk, Andrea, Jain, Ruchi, Prasad, Rashmi B., Shungin, Dmitry, Simó‐Servat, Olga, Özgümüs, Türküler, Cherviakova, Liubov, Khalimon, Nadiya, Svietleisha, Tetiana, Buldenko, Tetiana, Kravchenko, Victor, Hernández, Cristina, Jain, Deepak, Simo, Rafael, Artner, Isabella, Nilsson, Peter M., Khalangot, Mykola D., Vaiserman, Alexander M., Chan, Juliana, Vaag, Allan, Lyssenko, Valeriya
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.03.2022
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Summary:Purpose Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long‐term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR). Methods We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932–1933) and the WWII (1941–1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942–1945. Results During the Holodomor and WWII, perinatal famine was associated with a 1.76‐fold (p = 0.019) and 3.02‐fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66‐fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (padditive interaction < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05). Conclusion In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications.
Bibliography:We thank the patients for their diligent and active participation; Anatoliy Lysenko and Valentina Burkhanova for their excellent management and technical assistance; Lars Diaz for analytical support for the statistical analyses of the Ukraine National Diabetes Registry data. We are particularly grateful to Prof. Leif Groop, who provided extensive and useful comments to the manuscript.
Funding: Swedish Research Council (Dnr2015‐03574, Dnr349‐2006‐237), Strategic Research Area Exodiab (Dnr2009‐1039), the Novonordisk Foundation (NNF12OC1016467), Swedish Foundation for Strategic Research (DnrIRC15‐0067), the Steno Diabetes Center Copenhagen, Bergen Research Foundation (BFS811294) and the University of Bergen.
OF did the statistical analyses, RJ, RP, MGR, TU, CH, RS, DJ and IA involved in data interpretation and drafted the manuscript. DS assisted in statistical analyses and acquisition of the data. LC, NK, TS, TB and AMZ developed the study design and collected the data. VK, AV and MDK involved in acquisition of the data. PMN and AAV contributed to the editing of the manuscript. VL conceived and designed the study, planned the analyses, supervised all parts of the study, interpreted the data and wrote the manuscript. All authors contributed to the interpretation of the data and approved the final version of the manuscript.
Role of the funding source: The study sponsor(s) did not participate in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for submitting for publication.
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ISSN:1755-375X
1755-3768
1755-3768
DOI:10.1111/aos.14948