Purpose of Review
Increased risk of type 2 diabetes mellitus (T2D) among individuals with overweight or obesity is well-established; however, questions remain about the temporal dynamics of weight change (gain or loss) on the natural course of T2D in this at-risk population. Existing epidemiologic evidence is limited to studies that discretely sample and assess excess weight and T2D risk at different ages with limited follow-up, yet changes in weight may have time-varying and possibly non-linear effects on T2D risk. Predicting the impact of weight change on the risk of T2D is key to informing primary prevention. We critically review the relationship between weight change, trajectory groups (i.e., distinct weight change patterns), and T2D risk among individuals with excess weight in recently published T2D prevention randomized controlled trials (RCTs) and longitudinal cohort studies.
Overall, weight trajectory groups have been shown to differ by age of onset, sex, and patterns of insulin resistance or beta-cell function biomarkers. Lifestyle (diet and physical activity), pharmacological, and surgical interventions can modify an individual’s weight trajectory. Adolescence is a critical etiologically relevant window during which onset of excess weight may be associated with higher risk of T2D. Changes in insulin resistance and beta-cell function biomarkers are distinct but related correlates of weight trajectory groups that evolve contemporaneously over time. These multi-trajectory markers are differentially associated with T2D risk.
T2D risk may differ by the age of onset and duration of excess body weight, and the type of weight loss intervention. A better understanding of the changes in weight, insulin sensitivity, and beta-cell function as distinct but related correlates of T2D risk that evolve contemporaneously over time has important implications for designing and targeting primary prevention efforts.
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Conflict of Interest
Arthur H. Owora reports grants to his institution from Eli Lilly & Co., Inc, Merck & Co., Inc, Soleno Therapeutics, Inc., and the National Institutes of Health, outside the submitted work.
Dr. Allison reports personal fees from Alkermes, Inc.; personal fees from Amin, Talati, Wasserman (Glanbia); other from Big Sky Health, Inc.; personal fees from Biofortis Innovation Services/Merieux NutriSciences; grants and personal fees from California Walnut Commission; personal fees from Clark Hill PLC; other from International Life Sciences Institute of North America (ILSI); personal fees from Kaleido Biosciences and from Law Offices of Ronald Marron; personal fees from Medpace/Gelesis; personal fees from Nestec/Nestle; personal fees from Novo Nordisk Fonden; personal fees from Sports Research Corporation; personal fees from Tomasik, Kostin, & Kasserman; other from Northarvest Bean Grower’s Association; grants from Alliance for Potato Research and Education; other from Almond Board; grants from American Egg Board; grants and personal fees from Arnold Ventures; grants from Dairy Management, Inc.; grants from Eli Lilly and Co.; grants from Herbalife International; grants from Mars, Incorporated; grants and other from Mondelez; grants from National Cattlemen’s Beef Association; grants and other from Peanut Institute; grants from Reckitt Bencksier Group PLC; grants from Soleno Therapeutics; grants from USDA; and grants from National Institutes of Health, outside the submitted work.
Xuan Zhang reports grants to his institution from Eli Lilly & Co., Inc, and National Institutes of Health, outside the submitted work.
Nana A. Gletsu-Miller reports grants to her institution from Eli Lilly & Co., Inc, and National Institutes of Health, outside the submitted work.
Kishore M. Gadde reports grants to his institution from AstraZeneca, BioKier, Indiana University Foundation, and National Institutes of Health, outside the submitted work.
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Owora, A.H., Allison, D.B., Zhang, X. et al. Risk of Type 2 Diabetes Among Individuals with Excess Weight: Weight Trajectory Effects. Curr Diab Rep 22, 471–479 (2022). https://doi.org/10.1007/s11892-022-01486-9