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Published in: Cardiovascular Diabetology 1/2023

Open Access 01-12-2023 | Obesity | Research

High BMI and the risk for incident type 1 Diabetes Mellitus: a systematic review and meta-analysis of aggregated cohort studies

Authors: Maya Nitecki, Hertzel C. Gerstein, Yulia Balmakov, Eyal Tsur, Vladislav Babushkin, Tomer Michaeli, Arnon Afek, Orit Pinhas-Hamiel, Tali Cukierman-Yaffe, Gilad Twig

Published in: Cardiovascular Diabetology | Issue 1/2023

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Abstract

Background

There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize evidence regarding BMI and the risk of developing type 1 diabetes.

Methods

A systematic review and meta-analysis were conducted to assess the association between BMI and incident type 1 diabetes. Databases were searched up to June 2022. Cohort studies were included reporting the association between overweight and/or obesity, as measured by BMI after age 2 years, with incident type 1 diabetes. Independent reviewers extracted data and assessed study quality. Risk estimates were pooled using a random-effects model.

Results

Ten cohort studies met the inclusion criteria. The seven studies that classified BMI into categories were of high quality and involved 1,690,660 individuals and 1979 incident type 1 diabetes cases. The pooled risk ratio (RR) for type 1 diabetes was 1.35 (95% CI 0.93–1.97) among people with overweight (3 studies); 2.17 (95% CI 1.75–2.69) among people with obesity (5 studies); and 1·87 (95% CI 1.52–2.29) among people with overweight/obesity (two studies merged the categories). These point estimates persisted in sensitivity analyses that addressed the duration of follow-up, variability in baseline risk for incident type 1 diabetes, and potential misclassifications related to exposure or outcome definitions. People with overweight/obesity had a 2.55 (95% CI 1.11–5.86) greater risk for incident type 1 diabetes with positive islet autoantibodies.

Conclusion

This systematic review and meta-analysis of high-quality observational cohort studies indicated an association between high BMI and the risk of type 1 diabetes, in a graded manner.
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Literature
3.
go back to reference Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for Islet autoimmunity among monozygotic twins. N Engl J Med. 2008;359:2849–50.PubMedCrossRef Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for Islet autoimmunity among monozygotic twins. N Engl J Med. 2008;359:2849–50.PubMedCrossRef
4.
go back to reference Waldhör T, Schober E, Rami B. Regional distribution of risk for childhood diabetes in Austria and possible association with body mass index. Eur J Pediatr. 2003;162:380–4.PubMedCrossRef Waldhör T, Schober E, Rami B. Regional distribution of risk for childhood diabetes in Austria and possible association with body mass index. Eur J Pediatr. 2003;162:380–4.PubMedCrossRef
5.
go back to reference Knip M, Reunanen A, Virtanen SM, Nuutinen M, Viikari J, Åkerblom HK. Does the secular increase in body mass in children contribute to the increasing incidence of type 1 diabetes? Pediatr Diabetes. 2008;9:46–9.PubMedCrossRef Knip M, Reunanen A, Virtanen SM, Nuutinen M, Viikari J, Åkerblom HK. Does the secular increase in body mass in children contribute to the increasing incidence of type 1 diabetes? Pediatr Diabetes. 2008;9:46–9.PubMedCrossRef
6.
go back to reference Verbeeten KC, Elks CE, Daneman D, Ong KK. Association between childhood obesity and subsequent Type 1 diabetes: a systematic review and meta-analysis. Diabet Med. 2011;28(1):10–8.PubMedCrossRef Verbeeten KC, Elks CE, Daneman D, Ong KK. Association between childhood obesity and subsequent Type 1 diabetes: a systematic review and meta-analysis. Diabet Med. 2011;28(1):10–8.PubMedCrossRef
7.
go back to reference Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. The BMJ: BMJ Publishing Group; 2021. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. The BMJ: BMJ Publishing Group; 2021.
8.
go back to reference Grossman DC, Bibbins-Domingo K, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, et al. Screening for obesity in children and adolescents: us preventive services task force recommendation statement. JAMA. 2017;317:2417–26.PubMedCrossRef Grossman DC, Bibbins-Domingo K, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, et al. Screening for obesity in children and adolescents: us preventive services task force recommendation statement. JAMA. 2017;317:2417–26.PubMedCrossRef
9.
go back to reference Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes—2023. Diabetes Care. 2023;46:S128–39.PubMedCrossRef Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes—2023. Diabetes Care. 2023;46:S128–39.PubMedCrossRef
11.
go back to reference Syn NL, Cummings DE, Wang LZ, Lin DJ, Zhao JJ, Loh M, et al. Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. The Lancet. 2021;397:1830–41.CrossRef Syn NL, Cummings DE, Wang LZ, Lin DJ, Zhao JJ, Loh M, et al. Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. The Lancet. 2021;397:1830–41.CrossRef
12.
go back to reference Nitecki R, Ramirez PT, Frumovitz M, Krause KJ, Tergas AI, Wright JD, et al. Survival after minimally invasive vs open radical hysterectomy for early-stage cervical cancer: a systematic review and meta-analysis. JAMA Oncol. 2020;6(7):1019–27.PubMedCrossRef Nitecki R, Ramirez PT, Frumovitz M, Krause KJ, Tergas AI, Wright JD, et al. Survival after minimally invasive vs open radical hysterectomy for early-stage cervical cancer: a systematic review and meta-analysis. JAMA Oncol. 2020;6(7):1019–27.PubMedCrossRef
13.
go back to reference Michael B, Hedges LV, Higgins JP, T., Rothstein Hannah R. Introduction to Meta-Analysis. Chichester, West Sussex: A John Wiley and Sons Ltd, Publication; 2009. Michael B, Hedges LV, Higgins JP, T., Rothstein Hannah R. Introduction to Meta-Analysis. Chichester, West Sussex: A John Wiley and Sons Ltd, Publication; 2009.
14.
go back to reference Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J Publ Gr. 2003;327(7414):557–60.CrossRef Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J Publ Gr. 2003;327(7414):557–60.CrossRef
15.
go back to reference Zucker I, Zloof Y, Bardugo A, Tsur AM, Lutski M, Cohen Y, et al. Obesity in late adolescence and incident type 1 diabetes in young adulthood. Diabetologia. 2022;65:1473–82.PubMedCrossRef Zucker I, Zloof Y, Bardugo A, Tsur AM, Lutski M, Cohen Y, et al. Obesity in late adolescence and incident type 1 diabetes in young adulthood. Diabetologia. 2022;65:1473–82.PubMedCrossRef
16.
go back to reference Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS. Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes. 2010;59:679–85.PubMedCrossRef Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS. Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes. 2010;59:679–85.PubMedCrossRef
17.
go back to reference So M, O’Rourke C, Ylescupidez A, Bahnson HT, Steck AK, Wentworth JM, et al. Characterising the age-dependent effects of risk factors on type 1 diabetes progression. Diabetologia. 2022;65:684–94.PubMedPubMedCentralCrossRef So M, O’Rourke C, Ylescupidez A, Bahnson HT, Steck AK, Wentworth JM, et al. Characterising the age-dependent effects of risk factors on type 1 diabetes progression. Diabetologia. 2022;65:684–94.PubMedPubMedCentralCrossRef
18.
go back to reference Steck AK, Dong F, Frohnert BI, Waugh K, Hoffman M, Norris JM, et al. Predicting progression to diabetes in islet autoantibody positive children. J Autoimmun. 2018;90:59–63.PubMedPubMedCentralCrossRef Steck AK, Dong F, Frohnert BI, Waugh K, Hoffman M, Norris JM, et al. Predicting progression to diabetes in islet autoantibody positive children. J Autoimmun. 2018;90:59–63.PubMedPubMedCentralCrossRef
19.
go back to reference Viner RM, Hindmarsh PC, Taylor B, Cole TJ. Childhood body mass index (BMI), breastfeeding and risk of Type 1 diabetes: findings from a longitudinal national birth cohort. Diabet Med. 2008;25:1056–61.PubMedCrossRef Viner RM, Hindmarsh PC, Taylor B, Cole TJ. Childhood body mass index (BMI), breastfeeding and risk of Type 1 diabetes: findings from a longitudinal national birth cohort. Diabet Med. 2008;25:1056–61.PubMedCrossRef
20.
go back to reference Tosur M, Geyer SM, Rodriguez H, Libman I, Baidal DA, Redondo MJ. Ethnic differences in progression of islet autoimmunity and type 1 diabetes in relatives at risk. Diabetologia. 2018;61:2043–53.PubMedPubMedCentralCrossRef Tosur M, Geyer SM, Rodriguez H, Libman I, Baidal DA, Redondo MJ. Ethnic differences in progression of islet autoimmunity and type 1 diabetes in relatives at risk. Diabetologia. 2018;61:2043–53.PubMedPubMedCentralCrossRef
21.
go back to reference Nucci AM, Virtanen SM, Cuthbertson D, Ludvigsson J, Einberg U, Huot C, et al. Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk. Diabetologia. 2021;64:826–35.PubMedPubMedCentralCrossRef Nucci AM, Virtanen SM, Cuthbertson D, Ludvigsson J, Einberg U, Huot C, et al. Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk. Diabetologia. 2021;64:826–35.PubMedPubMedCentralCrossRef
22.
go back to reference Meah FA, DiMeglio LA, Greenbaum CJ, Blum JS, Sosenko JM, Pugliese A, et al. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet pathway to prevention participants. Diabetologia. 2016;59:1186–95.PubMedPubMedCentralCrossRef Meah FA, DiMeglio LA, Greenbaum CJ, Blum JS, Sosenko JM, Pugliese A, et al. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet pathway to prevention participants. Diabetologia. 2016;59:1186–95.PubMedPubMedCentralCrossRef
23.
go back to reference Herzog K, Andersson T, Grill V, Hammar N, Malmström H, Talbäck M, et al. Alterations in biomarkers related to glycemia, lipid metabolism, and inflammation up to 20 years before diagnosis of type 1 diabetes in adults: findings from the AMORIS cohort. Diabetes Care. 2022;45:330–8.PubMedCrossRef Herzog K, Andersson T, Grill V, Hammar N, Malmström H, Talbäck M, et al. Alterations in biomarkers related to glycemia, lipid metabolism, and inflammation up to 20 years before diagnosis of type 1 diabetes in adults: findings from the AMORIS cohort. Diabetes Care. 2022;45:330–8.PubMedCrossRef
24.
go back to reference Harpsøe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, et al. Body mass index and risk of autoimmune diseases: a study within the danish national birth cohort. Int J Epidemiol. 2014;43:843–55.PubMedCrossRef Harpsøe MC, Basit S, Andersson M, Nielsen NM, Frisch M, Wohlfahrt J, et al. Body mass index and risk of autoimmune diseases: a study within the danish national birth cohort. Int J Epidemiol. 2014;43:843–55.PubMedCrossRef
25.
go back to reference Carlsson S, Midthjell K, Tesfamarian MY, Grill V. Age, overweight and physical inactivity increase the risk of latent autoimmune diabetes in adults: results from the Nord-Trøndelag health study. Diabetologia. 2007;50:55–8.PubMedCrossRef Carlsson S, Midthjell K, Tesfamarian MY, Grill V. Age, overweight and physical inactivity increase the risk of latent autoimmune diabetes in adults: results from the Nord-Trøndelag health study. Diabetologia. 2007;50:55–8.PubMedCrossRef
26.
go back to reference Soltesz G, Patterson C, Dahlquist G. Worldwide childhood type 1 diabetes incidence ? what can we learn from epidemiology? Pediatr Diabetes. 2007;8:6–14.PubMedCrossRef Soltesz G, Patterson C, Dahlquist G. Worldwide childhood type 1 diabetes incidence ? what can we learn from epidemiology? Pediatr Diabetes. 2007;8:6–14.PubMedCrossRef
27.
go back to reference Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med. 2017;376:1419–29.PubMedPubMedCentralCrossRef Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med. 2017;376:1419–29.PubMedPubMedCentralCrossRef
28.
go back to reference Bruining GJ. Association between infant growth before onset of juvenile type-1 diabetes and autoantibodies to IA-2. Lancet. 2000;356:655–6.PubMedCrossRef Bruining GJ. Association between infant growth before onset of juvenile type-1 diabetes and autoantibodies to IA-2. Lancet. 2000;356:655–6.PubMedCrossRef
29.
go back to reference Hyppönen E, Virtanen SM, Kenward MG, Knip M, Åkerblom HK. Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care. 2000;23:1755–60.PubMedCrossRef Hyppönen E, Virtanen SM, Kenward MG, Knip M, Åkerblom HK. Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care. 2000;23:1755–60.PubMedCrossRef
30.
go back to reference Ferrara CT, Geyer SM, Evans-Molina C, Libman IM, Becker DJ, Wentworth JM, et al. The role of age and excess body mass index in progression to type 1 diabetes in at-risk adults. J Clin Endocrinol Metab. 2017;102:4596–603.PubMedPubMedCentralCrossRef Ferrara CT, Geyer SM, Evans-Molina C, Libman IM, Becker DJ, Wentworth JM, et al. The role of age and excess body mass index in progression to type 1 diabetes in at-risk adults. J Clin Endocrinol Metab. 2017;102:4596–603.PubMedPubMedCentralCrossRef
31.
go back to reference Ferrara CT, Geyer SM, Liu YF, Evans-Molina C, Libman IM, Besser R, et al. Excess BMI in childhood: a modifiable risk factor for type 1 diabetes development? Diabetes Care. 2017;40:698–701.PubMedPubMedCentralCrossRef Ferrara CT, Geyer SM, Liu YF, Evans-Molina C, Libman IM, Besser R, et al. Excess BMI in childhood: a modifiable risk factor for type 1 diabetes development? Diabetes Care. 2017;40:698–701.PubMedPubMedCentralCrossRef
33.
go back to reference Gao M, Piernas C, Astbury NM, Hippisley-Cox J, O’Rahilly S, Aveyard P, et al. Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 2021;9:350–9.PubMedPubMedCentralCrossRef Gao M, Piernas C, Astbury NM, Hippisley-Cox J, O’Rahilly S, Aveyard P, et al. Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. 2021;9:350–9.PubMedPubMedCentralCrossRef
34.
go back to reference Ludvigsson J. Why diabetes incidence increases—a unifying theory. Ann N Y Acad Sci. 2006;1079:374–82.PubMedCrossRef Ludvigsson J. Why diabetes incidence increases—a unifying theory. Ann N Y Acad Sci. 2006;1079:374–82.PubMedCrossRef
35.
go back to reference Cnop M, Foufelle F, Velloso LA. Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med. 2012;18(1):59–68.PubMedCrossRef Cnop M, Foufelle F, Velloso LA. Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med. 2012;18(1):59–68.PubMedCrossRef
38.
go back to reference Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: Not a passive bystander. Autoimmun Rev. 2014;13:981–1000.PubMedCrossRef Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: Not a passive bystander. Autoimmun Rev. 2014;13:981–1000.PubMedCrossRef
40.
go back to reference Matarese G, Sanna V, Lechler RI, Sarvetnick N, Fontana S, Zappacosta S, et al. Leptin accelerates autoimmune diabetes in female NOD mice. Diabetes. 2002;51:1356–61.PubMedCrossRef Matarese G, Sanna V, Lechler RI, Sarvetnick N, Fontana S, Zappacosta S, et al. Leptin accelerates autoimmune diabetes in female NOD mice. Diabetes. 2002;51:1356–61.PubMedCrossRef
41.
go back to reference Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler MB. Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 2010;285:33623–31.PubMedPubMedCentralCrossRef Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler MB. Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 2010;285:33623–31.PubMedPubMedCentralCrossRef
42.
go back to reference Steck AK, Armstrong TK, Babu SR, Eisenbarth GS. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes. 2011;60:1045–9.PubMedPubMedCentralCrossRef Steck AK, Armstrong TK, Babu SR, Eisenbarth GS. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes. 2011;60:1045–9.PubMedPubMedCentralCrossRef
43.
go back to reference Ward ZJ, Long MW, Resch SC, Giles CM, Cradock AL, Gortmaker SL. Simulation of growth trajectories of childhood obesity into adulthood. N Engl J Med. 2017;377:2145–53.PubMedPubMedCentralCrossRef Ward ZJ, Long MW, Resch SC, Giles CM, Cradock AL, Gortmaker SL. Simulation of growth trajectories of childhood obesity into adulthood. N Engl J Med. 2017;377:2145–53.PubMedPubMedCentralCrossRef
44.
go back to reference Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. 2019;381:2440–50.PubMedCrossRef Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. 2019;381:2440–50.PubMedCrossRef
45.
go back to reference Van der Schueren B, Ellis D, Faradji RN, Al-Ozairi E, Rosen J, Mathieu C. Obesity in people living with type 1 diabetes. Lancet Diabetes Endocrinol. 2021;9(11):776–85.PubMedCrossRef Van der Schueren B, Ellis D, Faradji RN, Al-Ozairi E, Rosen J, Mathieu C. Obesity in people living with type 1 diabetes. Lancet Diabetes Endocrinol. 2021;9(11):776–85.PubMedCrossRef
46.
47.
go back to reference Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381:603–13.PubMedPubMedCentralCrossRef Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381:603–13.PubMedPubMedCentralCrossRef
Metadata
Title
High BMI and the risk for incident type 1 Diabetes Mellitus: a systematic review and meta-analysis of aggregated cohort studies
Authors
Maya Nitecki
Hertzel C. Gerstein
Yulia Balmakov
Eyal Tsur
Vladislav Babushkin
Tomer Michaeli
Arnon Afek
Orit Pinhas-Hamiel
Tali Cukierman-Yaffe
Gilad Twig
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2023
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-023-02007-y

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