Bidirectional temporal relationship between obesity and hyperinsulinemia: longitudinal observation from a Chinese cohort

Chao Xu, Guangshuai Zhou, Meng Zhao, Xu Zhang, Li Fang, Qingbo Guan, Haiqing Zhang, Ling Gao, Tao Zhang, Jiajun Zhao, Chao Xu, Guangshuai Zhou, Meng Zhao, Xu Zhang, Li Fang, Qingbo Guan, Haiqing Zhang, Ling Gao, Tao Zhang, Jiajun Zhao

Abstract

Introduction: Although obesity and hyperinsulinemia are closely intercorrelated, their temporal sequence is still uncertain. This study aims to investigate the temporal relationship patterns between obesity measures and hyperinsulinemia in Chinese adults.

Research design and methods: The longitudinal cohort consisted of 2493 participants (860 males and 1633 female, mean age 56.71 years at follow-up) for whom measurements of obesity and hyperinsulinemia measures were collected twice between 2011 and 2014, with an average follow-up time of 3 years. Cross-lagged panel analysis was used to examine the temporal relationship between obesity measures (body mass index (BMI); waist circumference (WC); hip circumference (HC); waist-to-hip ratio (WHR)) and hyperinsulinemia (insulin, homeostasis model assessment of insulin resistance (HOMA-IR), or homeostasis model assessment of beta cell function (HOMA-%β)).

Results: After the adjustment of age, sex, smoking, drinking and follow-up years, in the BMI-insulin model, the path coefficient (β2=0.229; p<0.001) of baseline BMI to follow-up insulin was significantly greater than the path coefficient (β1=0.073; p<0.001) of baseline insulin to follow-up BMI (p<0.001 for β2>β1). In the WHR-insulin model, the path coefficient (β1=0.152; p<0.001) of baseline insulin to follow-up WHR was significantly greater than the path coefficient (β2=0.077; p<0.001) of baseline WHR to follow-up insulin (p=0.007 for β1>β2). In the WC/HC-insulin model, the path coefficients of baseline insulin to follow-up WC or HC (β1s) were also greater than the path coefficients of baseline WC or HC to follow-up insulin (β2s), but the difference between β1s and β2s were not significant. The similar temporal patterns were founded between obesity measures with HOMA-IR or HOMA-%β.

Conclusions: These findings indicate that there is a bidirectional relationship between obesity and hyperinsulinemia, and abdominal obesity measures are more sensitive to hyperinsulinemia measures than BMI.

Trial registration: ClinicalTrials.gov NCT01506869.

Keywords: insulin resistance; longitudinal studies; obesity.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Cross-lagged panel model between obesity measures and insulin, adjusted for age, sex, smoking, drinking and follow-up years. Obesity measures include body mass index (BMI), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR). β1 and β2 are cross-lagged path coefficients; r1 is synchronous correlations; r2 and r3 are tracking correlations.
Figure 2
Figure 2
Yearly rates of change (Δ) of obesity measures and insulin by quartiles of their baseline values in the total sample, with adjustment of age, sex, smoking, drinking and their baseline values. BMI, body mass index; HC, hip circumference; WC, waist circumference; WHR, waist-to-hip ratio.

References

    1. Li Y, Zhang T, Han T, et al. . Impact of cigarette smoking on the relationship between body mass index and insulin: longitudinal observation from the Bogalusa heart study. Diabetes Obes Metab 2018;20:1578–84. 10.1111/dom.13259
    1. Zhang T, Zhang H, Li Y, et al. . Temporal relationship between childhood body mass index and insulin and its impact on adult hypertension: the Bogalusa heart study. Hypertension 2016;68:818–23. 10.1161/HYPERTENSIONAHA.116.07991
    1. Pennings N, Jaber J, Ahiawodzi P. Ten-Year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation. Diabetes Metab Res Rev 2018;34:e2986. 10.1002/dmrr.2986
    1. Astley CM, Todd JN, Salem RM, et al. . Genetic evidence that Carbohydrate-Stimulated insulin secretion leads to obesity. Clin Chem 2018;64:192–200. 10.1373/clinchem.2017.280727
    1. Kim AY, Park YJ, Pan X, et al. . Obesity-Induced DNA hypermethylation of the adiponectin gene mediates insulin resistance. Nat Commun 2015;6:7585. 10.1038/ncomms8585
    1. Pal M, Febbraio MA, Lancaster GI. The roles of c-Jun NH2-terminal kinases (JNKs) in obesity and insulin resistance. J Physiol 2016;594:267–79. 10.1113/JP271457
    1. Ying W, Lee YS, Dong Y, et al. . Expansion of Islet-Resident macrophages leads to inflammation affecting β cell proliferation and function in obesity. Cell Metab 2019;29:457–74. 10.1016/j.cmet.2018.12.003
    1. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–6. 10.1038/nature05482
    1. Fleury C, Neverova M, Collins S, et al. . Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 1997;15:269–72. 10.1038/ng0397-269
    1. Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Diabetes Obes Metab 2011;13:1008–19. 10.1111/j.1463-1326.2011.01433.x
    1. Hodish I. Insulin therapy, weight gain and prognosis. Diabetes Obes Metab 2018;20:2085–92. 10.1111/dom.13367
    1. Alemzadeh R, Langley G, Upchurch L, et al. . Beneficial effect of diazoxide in obese hyperinsulinemic adults. J Clin Endocrinol Metab 1998;83:1911–5. 10.1210/jc.83.6.1911
    1. Thomas SH, Wisher MH, Brandenburg D, et al. . Insulin action on adipocytes. Evidence that the anti-lipolytic and lipogenic effects of insulin are mediated by the same receptor. Biochem J 1979;184:355–60. 10.1042/bj1840355
    1. Choi SM, Tucker DF, Gross DN, et al. . Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway. Mol Cell Biol 2010;30:5009–20. 10.1128/MCB.00797-10
    1. Tokarz VL, MacDonald PE, Klip A. The cell biology of systemic insulin function. J Cell Biol 2018;217:2273–89. 10.1083/jcb.201802095
    1. Odeleye OE, de Courten M, Pettitt DJ, et al. . Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. Diabetes 1997;46:1341–5. 10.2337/diab.46.8.1341
    1. Morrison JA, Glueck CJ, Wang P. Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls. Metabolism 2010;59:718–27. 10.1016/j.metabol.2009.09.016
    1. Hoag S, Marshall JA, Jones RH, et al. . High fasting insulin levels associated with lower rates of weight gain in persons with normal glucose tolerance: the San Luis Valley diabetes study. Int J Obes Relat Metab Disord 1995;19:175–80.
    1. Després J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006;444:881–7. 10.1038/nature05488
    1. Ross R, Neeland IJ, Yamashita S, et al. . Waist circumference as a vital sign in clinical practice: a consensus statement from the IAS and ICCR Working group on visceral obesity. Nat Rev Endocrinol 2020;16:177–89. 10.1038/s41574-019-0310-7
    1. Ohlson LO, Larsson B, Svärdsudd K, et al. . The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes 1985;34:1055–8. 10.2337/diab.34.10.1055
    1. Wahrenberg H, Hertel K, Leijonhufvud B-M, et al. . Use of waist circumference to predict insulin resistance: retrospective study. BMJ 2005;330:1363–4. 10.1136/
    1. Page MM, Skovsø S, Cen H, et al. . Reducing insulin via conditional partial gene ablation in adults reverses diet-induced weight gain. Faseb J 2018;32:1196–206. 10.1096/fj.201700518R
    1. Bi Y, Lu J, Wang W, et al. . Cohort profile: risk evaluation of cancers in Chinese diabetic individuals: a longitudinal (reaction) study. J Diabetes 2014;6:147–57. 10.1111/1753-0407.12108
    1. Rogosa D. A critique of cross-lagged correlation. Psychol Bull 1980;88:245–58. 10.1037/0033-2909.88.2.245
    1. Jöreskog KG. Modeling development: using covariance structure models in longitudinal research. Eur Child Adolesc Psychiatry 1996;5 Suppl 1:8–10. 10.1007/BF00538536
    1. Dale CE, Fatemifar G, Palmer TM, et al. . Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis. Circulation 2017;135:2373–88. 10.1161/CIRCULATIONAHA.116.026560
    1. Chen G, Liu C, Yao J, et al. . Overweight, obesity, and their associations with insulin resistance and β-cell function among Chinese: a cross-sectional study in China. Metabolism 2010;59:1823–32. 10.1016/j.metabol.2010.06.009
    1. Velasquez-Mieyer PA, Cowan PA, Arheart KL, et al. . Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults. Int J Obes Relat Metab Disord 2003;27:219–26. 10.1038/sj.ijo.802227
    1. Lustig RH, Greenway F, Velasquez-Mieyer P, et al. . A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion. Int J Obes 2006;30:331–41. 10.1038/sj.ijo.0803074
    1. Mehran AE, Templeman NM, Brigidi GS, et al. . Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab 2012;16:723–37. 10.1016/j.cmet.2012.10.019
    1. Templeman NM, Skovsø S, Page MM, et al. . A causal role for hyperinsulinemia in obesity. J Endocrinol 2017;232:R173–83. 10.1530/JOE-16-0449
    1. Page MM, Johnson JD. Mild suppression of hyperinsulinemia to treat obesity and insulin resistance. Trends Endocrinol Metab 2018;29:389–99. 10.1016/j.tem.2018.03.018
    1. Neel JV. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? 1962. Bull World Health Organ 1999;77:694–703.
    1. Han JC, Rutledge MS, Kozlosky M, et al. . Insulin resistance, hyperinsulinemia, and energy intake in overweight children. J Pediatr 2008;152:612–7. 10.1016/j.jpeds.2007.12.036
    1. Lemay A, Turcot L, Déchêne F, et al. . Hyperinsulinemia in nonobese women reporting a moderate weight gain at the beginning of menopause: a useful early measure of susceptibility to insulin resistance. Menopause 2010;17:321–5. 10.1097/gme.0b013e3181b7c521
    1. Zhang DL, Du Q, Djemli A, et al. . Cord blood insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin, and their associations with insulin sensitivity, β-cell function and adiposity in infancy. Diabet Med 2018;35:1412–9. 10.1111/dme.13671

Source: PubMed

3
Iratkozz fel