Abstract
Purpose of Review
Overweight and obesity are well-established risk factors for type 2 diabetes. However, a substantial number of individuals develop the disease at underweight or normal weight. In this review, we discuss the epidemiology of type 2 diabetes in non-overweight adults; pose questions about etiology, pathophysiology, diagnosis, and prognosis; and examine implications for prevention and treatment.
Recent Findings
In population-based studies, the prevalence of type 2 diabetes ranged from 1.4–10.9%. However, the prevalence of type 2 diabetes in individuals with BMI < 25 kg/m2 ranged from 1.4–8.8%. In countries from Asia and Africa, the proportion of individuals with diabetes who were underweight or normal weight ranged from 24 to 66%, which is considerably higher than the US proportion of 10%. Impairments in insulin secretion, in utero undernutrition, and epigenetic alterations to the genome may play a role in diabetes development in this subgroup.
Summary
A substantial number of individuals with type 2 diabetes, particularly those with recent ancestry from Asia or Africa, are underweight or normal weight. Future research should consist of comprehensive studies of the prevalence of type 2 diabetes in non-overweight individuals; studies aimed at understanding gaps in the mechanisms, etiology, and pathophysiology of diabetes development in underweight or normal weight individuals; and trials assessing the effectiveness of interventions in this population.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance
International Diabetes Federation. IDF diabetes atlas. 8th ed. Brussels: International Diabetes Federation; 2017.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.
Narayan KMV, Boyle JP, Thompson TJ, Gregg EW, Williamson DF. Effect of BMI on lifetime risk for diabetes in the U.S. Diabetes Care. 2007;30(6):1562–6.
Menke A, Rust KF, Fradkin J, Cheng YJ, Cowie CC. Associations between trends in race/ethnicity, aging, and body mass index with diabetes prevalence in the United States: a series of cross-sectional studies. Ann Intern Med. 2014;161(5):328–35.
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes [Internet]. Nature 2006 [cited 2017 Dec 6]. Available from: https://www.nature.com/articles/nature 05482.
Gregg EW, Cheng YJ, Narayan KMV, Thompson TJ, Williamson DF. The relative contributions of different levels of overweight and obesity to the increased prevalence of diabetes in the United States: 1976–2004. Prev Med. 2007;45(5):348–52.
Tulloch JA, Macintosh D. “J”-type diabetes. Lancet. 1961;278(7194):119–21.
De Zoysa VP. Clinical variations of the diabetic syndrome in a tropical country (Ceylon). AMA Arch Intern Med. 1951;88(6):812–8.
Hugh-Jones P. Diabetes in Jamaica. Lancet. 1955;266(6896):891–7.
Tripathy BB, Kar BC. Observations on clinical patterns of diabetes mellitus in India. Diabetes. 1965;14(7):404–12.
Mohan V, Mohan R, Susheela L, Snehalatha C, Bharani G, Mahajan VK, et al. Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile. Diabetologia. 1985;28(4):229–32.
Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362(12):1090–101.
Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA. 2017;317(24):2515–23.
Miyakawa M, Shimizu T, Van Dat N, Thanh P, Thuy PTP, Anh NTH, et al. Prevalence, perception and factors associated with diabetes mellitus among the adult population in central Vietnam: a population-based, cross-sectional seroepidemiological survey. BMC Public Health. 2017;17:298.
Akter S, Rahman MM, Abe SK, Sultana P. Prevalence of diabetes and prediabetes and their risk factors among Bangladeshi adults: a nationwide survey. Bull World Health Organ. 2014;92:204–213A.
• Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK, et al. Prevalence of diabetes and prediabetes in 15 states of India: results from the ICMR–INDIAB population-based cross-sectional study. Lancet Diabetes Endocrinol. 2017;5(8):585–96. This study is the largest nationally representative study of diabetes in India to date.
Binh TQ, Nhung BT. Prevalence and risk factors of type 2 diabetes in middle-aged women in Northern Vietnam. Int J Diabetes Dev Ctries. 2016;36(2):150–7.
Hwang J, Shon C. Relationship between socioeconomic status and type 2 diabetes: results from Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012. BMJ Open. 2014;4(8):e005710.
Bailey SL, Ayles H, Beyers N, Godfrey-Faussett P, Muyoyeta M, du Toit E, et al. Diabetes mellitus in Zambia and the Western Cape province of South Africa: prevalence, risk factors, diagnosis and management. Diabetes Res Clin Pract. 2016;118:1–11.
Bahendeka S, Wesonga R, Mutungi G, Muwonge J, Neema S, Guwatudde D. Prevalence and correlates of diabetes mellitus in Uganda: a population-based national survey. Tropical Med Int Health. 2016;21(3):405–16.
Little M, Humphries S, Patel K, Dodd W, Dewey C. Factors associated with glucose tolerance, pre-diabetes, and type 2 diabetes in a rural community of south India: a cross-sectional study. Diabetol Metab Syndr. 2016;8:21.
Hu Y, Teng W, Liu L, Chen K, Liu L, Hua R, et al. Prevalence and risk factors of diabetes and diabetic retinopathy in Liaoning Province, China: a population-based cross-sectional study. PLoS One. 2015 Mar 18;10(3):e0121477.
Uehara A, Kurotani K, Kochi T, Kuwahara K, Eguchi M, Imai T, et al. Prevalence of diabetes and pre-diabetes among workers: Japan Epidemiology Collaboration on Occupational Health Study. Diabetes Res Clin Pract. 2014;106(1):118–27.
Araneta MRG, Kanaya AM, Hsu WC, Chang HK, Grandinetti A, Boyko EJ, et al. Optimum BMI cut points to screen Asian Americans for type 2 diabetes. Diabetes Care. 2015 May 1;38(5):814–20.
McNeely MJ, Boyko EJ. Type 2 diabetes prevalence in Asian Americans: results of a national health survey. Diabetes Care. 2004;27(1):66–9.
Chiu M, Austin PC, Manuel DG, Shah BR, Tu JV. Deriving ethnic-specific BMI cutoff points for assessing diabetes risk. Diabetes Care. 2011;34(8):1741–8.
Hsia DS, Larrivee S, Cefalu WT, Johnson WD. Impact of lowering BMI cut points as recommended in the revised American Diabetes Association’s Standards of Medical Care in Diabetes—2015 on diabetes screening in Asian Americans. Diabetes Care. 2015;38(11):2166–8.
Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Charles MA, Bennett HP. A two-step model for development of non-insulin-dependent diabetes. Am J Med. 1991;90(1):229–35.
Kasuga M. Insulin resistance and pancreatic cell failure. J Clin Invest. 2006;116(7):1756–60.
Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE. Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999;84(1):137–44.
Boyko EJ, Fujimoto WY, Leonetti DL, Newell-Morris L. Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans. Diabetes Care. 2000;23(4):465–71.
Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon K-H, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009;301(20):2129–40.
Tanaka S, Horimai C, Katsukawa F. Ethnic differences in abdominal visceral fat accumulation between Japanese, African-Americans, and Caucasians: a meta-analysis. Acta Diabetol. 2003;40(1):s302–4.
Lear SA, Humphries KH, Kohli S, Chockalingam A, Frohlich JJ, Birmingham CL. Visceral adipose tissue accumulation differs according to ethnic background: results of the Multicultural Community Health Assessment Trial (M-CHAT). Am J Clin Nutr. 2007;86(2):353–9.
Park Y-W, Allison DB, Heymsfield SB, Gallagher D. Larger amounts of visceral adipose tissue in Asian Americans. Obes Res. 2001;9(7):381–7.
Kadowaki T, Sekikawa A, Murata K, Maegawa H, Takamiya T, Okamura T, et al. Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study. Int J Obes. 2006;30(7):1163–5.
Rush E, Plank L, Chandu V, Laulu M, Simmons D, Swinburn B, et al. Body size, body composition, and fat distribution: a comparison of young New Zealand men of European, Pacific Island, and Asian Indian ethnicities. N Z Med J Online Christch. 2004;117(1207):U1203.
Ali MK, Singh K, Kondal D, Devarajan R, Patel SA, Shivashankar R, et al. Effectiveness of a multicomponent quality improvement strategy to improve achievement of diabetes care goals: a randomized, controlled trial. Ann Intern Med. 2016;165(6):399–408.
Sakurai M, Miura K, Takamura T, Ishizaki M, Morikawa Y, Nakamura K, et al. J-shaped relationship between waist circumference and subsequent risk for type 2 diabetes: an 8-year follow-up of relatively lean Japanese individuals. Diabet Med. 2009;26(8):753–9.
Kuwahara K, Honda T, Nakagawa T, Yamamoto S, Hayashi T, Mizoue T. Body mass index trajectory patterns and changes in visceral fat and glucose metabolism before the onset of type 2 diabetes. Sci Rep 2017;7.
Chan WB, Tong PCY, Chow CC, So WY, Ng MCY, Ma RCW, et al. The associations of body mass index, C-peptide and metabolic status in Chinese type 2 diabetic patients. Diabet Med J Br Diabet Assoc. 2004;21(4):349–53.
Wang J, Yan R, Wen J, Kong X, Li H, Zhou P, et al. Association of lower body mass index with increased glycemic variability in patients with newly diagnosed type 2 diabetes: a cross-sectional study in China. Oncotarget 2017;8(42):73133.
Tatsumi Y, Morimoto A, Miyamatsu N, Noda M, Ohno Y, Deura K. Effect of body mass index on insulin secretion or sensitivity and diabetes. Am J Prev Med. 2015;48(2):128–35.
Staimez LR, Deepa M, Ali MK, Mohan V, Hanson RL. The tale of two Indians: a comparison of beta-cell function and insulin resistance between Pima Indians and Asian Indians. In: Diabetes Amer Diabetes Assoc 1701 N BEAUREGARD St, Alexandria, VA 22311–1717 USA; 2014. p. A400–A400.
Staimez LR, Weber MB, Ranjani H, Ali MK, Echouffo-Tcheugui JB, Phillips LS, et al. Evidence of reduced β-cell function in Asian Indians with mild dysglycemia. Diabetes Care. 2013;36(9):2772–8.
Mohan V, Amutha A, Ranjani H, Unnikrishnan R, Datta M, Anjana RM, et al. Associations of β-cell function and insulin resistance with youth-onset type 2 diabetes and prediabetes among Asian Indians. Diabetes Technol Ther. 2013;15(4):315–22.
Gujral UP, Narayan KM, Kahn SE, Kanaya AM. The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: the MASALA study. J Diabetes Complicat. 2014;28(1):45–50.
Gray LJ, Yates T, Davies MJ, Brady E, Webb DR, Sattar N, et al. Defining obesity cut-off points for migrant South Asians. PLoS One. 2011 Oct 19;6(10):e26464.
Ntuk UE, Gill JM, Mackay DF, Sattar N, Pell JP. Ethnic-specific obesity cutoffs for diabetes risk: cross-sectional study of 490,288 UK biobank participants. Diabetes Care. 2014;37(9):2500–7.
L h L. Decreased birthweights in infants after maternal in utero exposure to the Dutch famine of 1944–1945. Paediatr Perinat Epidemiol. 1992;6(2):240–53.
Jensen CB, Storgaard H, Dela F, Holst JJ, Madsbad S, Vaag AA. Early differential defects of insulin secretion and action in 19-year-old Caucasian men who had low birth weight. Diabetes. 2002;51(4):1271–80.
Li C, Johnson MS, Goran MI. Effects of low birth weight on insulin resistance syndrome in Caucasian and African-American children. Diabetes Care. 2001;24(12):2035–42.
Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A. Birth weight and subsequent risk of type 2 diabetes: a meta-analysis. Am J Epidemiol. 2007;165(8):849–57.
Wei J-N, Sung F-C, Li C-Y, Chang C-H, Lin R-S, Lin C-C, et al. Low birth weight and high birth weight infants are both at an increased risk to have type 2 diabetes among schoolchildren in Taiwan. Diabetes Care. 2003;26(2):343–8.
Lumey LH, Khalangot MD, Vaiserman AM. Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932–33: a retrospective cohort study. Lancet Diabetes Endocrinol. 2015;3(10):787–94.
de RSR, Painter RC, Roseboom TJ, Phillips DIW, Osmond C, Barker DJP, et al. Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine. Diabetologia. 2006;49(4):637–43.
de RSR, Painter RC, Phillips DIW, Osmond C, Michels RPJ, Godsland IF, et al. Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care. 2006;29(8):1897–901.
Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009;32(2):335–41.
Li J, Liu S, Li S, Feng R, Na L, Chu X, et al. Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a population-based cohort study of families in Suihua, China. Am J Clin Nutr 2016;ajcn138792.
Norris SA, Osmond C, Gigante D, Kuzawa CW, Ramakrishnan L, Lee NR, et al. Size at birth, weight gain in infancy and childhood, and adult diabetes risk in five low- or middle-income country birth cohorts. Diabetes Care 2011;DC_110456.
Wang T, Huang T, Li Y, Zheng Y, Manson JE, Hu FB, et al. Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study. Diabetologia. 2016;59(9):1920–7.
Kamal SMM, Hassan CH, Alam GM. Dual burden of underweight and overweight among women in Bangladesh: patterns, prevalence and sociodemographic correlates. J Health Popul Nutr. 2015;33(1):92–105.
Biswas T, Garnett SP, Pervin S, Rawal LB. The prevalence of underweight, overweight and obesity in Bangladeshi adults: data from a national survey. PLoS One. 2017;12(5):e0177395.
Min J, Zhao Y, Slivka L, Wang Y. Double burden of diseases worldwide: coexistence of undernutrition and overnutrition-related non-communicable chronic diseases. Obes Rev. 2018;19(1):49–61.
Hanandita W, Tampubolon G. The double burden of malnutrition in Indonesia: social determinants and geographical variations. SSM - Popul Health. 2015;1:16–25.
Tan S-T, Scott W, Panoulas V, Sehmi J, Zhang W, Scott J, et al. Coronary heart disease in Indian Asians. Glob Cardiol Sci Pract. 2014;2014(1):4.
Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009;18(21):4046–53.
Chambers JC, Loh M, Lehne B, Drong A, Kriebel J, Motta V, et al. Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study. Lancet Diabetes Endocrinol 2015;3(7):526–534.
Low birthweight [Internet]. UNICEF DATA. [cited 2018 Mar 5]. Available from: https://data.unicef.org/topic/nutrition/low-birthweight/.
Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini E, et al. Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population. Int J Cardiol. 2012;162(1):20–6.
Logue J, Walker JJ, Leese G, Lindsay R, McKnight J, Morris A, et al. Association between BMI measured within a year after diagnosis of type 2 diabetes and mortality. Diabetes Care. 2013;36(4):887–93.
Carnethon MR, De Chavez PJD, Biggs ML, Lewis CE, Pankow JS, Bertoni AG, et al. Association of weight status with mortality in adults with incident diabetes. JAMA. 2012;308(6):581–90.
Tobias DK, Pan A, Jackson CL, O’reilly EJ, Ding EL, Willett WC, et al. Body-mass index and mortality among adults with incident type 2 diabetes. N Engl J Med. 2014;370(3):233–44.
Yu E, Ley SH, Manson JE, Willett W, Satija A, Hu FB, et al. Weight history and all-cause and cause-specific mortality in three prospective cohort studies. Ann Intern Med. 2017;166(9):613–20.
Guidelines [Internet]. [cited 2018 Mar 18]. Available from: https://www.idf.org/e-library/guidelines/128-idf-clinical-practice-recommendations-for-managing-type-2-diabetes-in-primary-care.html
Siu AL. Screening for abnormal blood glucose and type 2 diabetes mellitus: U.S. Preventive Services Task Force recommendation statement screening for abnormal blood glucose and type 2 diabetes mellitus. Ann Intern Med. 2015;163(11):861–8.
Katulanda P, Hill NR, Stratton I, Sheriff R, De Silva SDN, Matthews DR. Development and validation of a diabetes risk score for screening undiagnosed diabetes in Sri Lanka (SLDRISK). BMC Endocr Disord. 2016;16:42.
Nanri A, Nakagawa T, Kuwahara K, Yamamoto S, Honda T, Okazaki H, et al. Development of risk score for predicting 3-year incidence of type 2 diabetes: Japan Epidemiology Collaboration on Occupational Health Study. PLoS One. 2015;10(11):e0142779.
Organization WH. Screening for type 2 diabetes: report of a World Health Organization and International Diabetes Federation meeting. 2003
Group TDPP (DPP) R. The diabetes prevention program (DPP): description of lifestyle intervention. Diabetes Care. 2002;25(12):2165–71.
Lindström J, Louheranta A, Mannelin M, Rastas M, Salminen V, Eriksson J, et al. The Finnish Diabetes Prevention Study (DPS). Diabetes Care. 2003;26(12):3230–6.
Eriksson K-F, Lindgärde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise: the 6-year Malmö feasibility study. Diabetologia. 1991;34(12):891–8.
Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V, et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006;49(2):289–97.
Li G, Zhang P, Wang J, Gregg EW, Yang W, Gong Q, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371(9626):1783–9.
Sakane N, Sato J, Tsushita K, Tsujii S, Kotani K, Tsuzaki K, et al. Prevention of type 2 diabetes in a primary healthcare setting: three-year results of lifestyle intervention in Japanese subjects with impaired glucose tolerance. BMC Public Health. 2011 Jan 17;11:40.
Balagopal P, Kamalamma N, Patel TG, Misra R. A community-based diabetes prevention and management education program in a rural village in India. Diabetes Care. 2008;31(6):1097–104.
Balagopal P, Kamalamma N, Patel TG, Misra R. A community-based participatory diabetes prevention and management intervention in rural India using community health workers. Diabetes Educ. 2012;38(6):822–34.
Bailey CJ. Metformin: historical overview. Diabetologia. 2017 Sep 1;60(9):1566–76.
•• van Raalte DH, Verchere CB. Improving glycaemic control in type 2 diabetes: stimulate insulin secretion or provide beta-cell rest? Diabetes Obes Metab. 2017;19(9):1205–13. This review presents the evidence for improving glycemic control either by stimulating insulin secretion or promoting beta-cell rest. This is something that is of importance but has not been heavily discussed in the literature thusfar.
Boyko EJ, Gerstein HC, Mohan V, Yusuf S, Sheridan P, Anand S, et al. Effects of ethnicity on diabetes incidence and prevention: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabet Med. 2010;27(11):1226–32.
Acknowledgments
We thank Dr. Tran Quang Binh, Dr. Silver Bahendeka, Dr. David Guwatudde, and Dr. R.M Anjana and the team at the Madras Diabetes Research Foundation for contributing additional data for our review article.
Funding
Mary Beth Weber and K.M. Venkat Narayan were supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK111024.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Unjali P. Gujral, Mary Beth Weber, Lisa R. Staimez, and K.M. Venkat Narayan declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Diabetes Epidemiology
Rights and permissions
About this article
Cite this article
Gujral, U.P., Weber, M.B., Staimez, L.R. et al. Diabetes Among Non-Overweight Individuals: an Emerging Public Health Challenge. Curr Diab Rep 18, 60 (2018). https://doi.org/10.1007/s11892-018-1017-1
Published:
DOI: https://doi.org/10.1007/s11892-018-1017-1