Pancreatic β-cell Function is Higher in Morning Versus Intermediate Chronotypes With Obesity

Overview

Journal Obes Sci Pract

Date 2025 Feb 28

PMID 40018087

Authors

Steven K Malin

Mary-Margaret E Remchak

Emily M Heiston

Chiara Fabris

Ankit M Shah

Affiliations

Soon will be listed here.

Abstract

Objectives: People with later chronotypes are at greater T2D risk, yet it is unknown if β-cell function differs among chronotypes. Thus we, assessed β-cell function in morning (MORN) and intermediate (INT) chronotypes with obesity.

Methods: Adults ( = 41, 9M, 55 ± 1.7 y, 36.8 ± 1.0 kg/m) were grouped as MORN or INT per the Morningness-Eveningness Questionnaire. Glucose, insulin, C-peptide, GIP, and GLP-1(active) were collected every 30 min during a 120 min 75g-OGTT. Insulin secretion rates (ISR) were calculated (regularized deconvolution) to assess early (total area under the curve; tAUC) and total-phase (tAUC) glucose-stimulated insulin secretion (GSIS:ISR/Glucose). Skeletal muscle (glucose infusion rate/steady-state insulin) insulin sensitivity and hepatic (HOMA-IR) as well as adipose (Adipose-IR) insulin resistance were assessed during a 120 min euglycemic hyperinsulinemic clamp (40mU/m/min, 90 mg/dL). β-cell function (disposition index (DI): GSIS adjusted insulin sensitivity) was determined. Body composition (DXA) and fitness (VOmax) were also measured.

Results: Age, body composition and VOmax were similar between groups, but INT had reduced muscle insulin sensitivity and higher hepatic and adipose IR ( < 0.05). INT had higher C-peptide tAUC ( = 0.04) and lower hepatic DI (tAUC = 0.05 and tAUC = 0.07, respectively). Early phase hepatic DI correlated with GLP-1 tAUC ( = 0.35, < 0.02) and tAUC ( = -0.40, = 0.04).

Conclusions: β-cell function was higher in MORN versus INT chronotypes. Further work is warranted to discern how chronotype impacts insulin secretion.

Trial Registration: NCT03355469.

References

Cole J, Motivala S, Buysse D, Oxman M, Levin M, Irwin M . Validation of a 3-factor scoring model for the Pittsburgh sleep quality index in older adults. Sleep. 2006; 29(1):112-6. DOI: 10.1093/sleep/29.1.112. View

Remchak M, Heiston E, Ballantyne A, Dotson B, Stewart N, Spaeth A . Insulin Sensitivity and Metabolic Flexibility Parallel Plasma TCA Levels in Early Chronotype With Metabolic Syndrome. J Clin Endocrinol Metab. 2022; 107(8):e3487-e3496. PMC: 9282268. DOI: 10.1210/clinem/dgac233. View

Mason I, Qian J, Adler G, Scheer F . Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetologia. 2020; 63(3):462-472. PMC: 7002226. DOI: 10.1007/s00125-019-05059-6. View

Van Cauter E, Polonsky K, Scheen A . Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr Rev. 1997; 18(5):716-38. DOI: 10.1210/edrv.18.5.0317. View

Jensen M, Nielsen S . Insulin dose response analysis of free fatty acid kinetics. Metabolism. 2006; 56(1):68-76. DOI: 10.1016/j.metabol.2006.08.022. View

Dotson B, Heiston E, Miller S, Malin S . Insulin stimulation reduces aortic wave reflection in adults with metabolic syndrome. Am J Physiol Heart Circ Physiol. 2021; 320(6):H2305-H2312. PMC: 8289357. DOI: 10.1152/ajpheart.00975.2020. View

Malin S, Frick H, Wisseman W, Edwards E, Edwards D, Emerson S . β-Cell function during a high-fat meal in young versus old adults: role of exercise. Am J Physiol Regul Integr Comp Physiol. 2023; 325(2):R164-R171. PMC: 10393366. DOI: 10.1152/ajpregu.00047.2023. View

Lee A, Ader M, Bray G, Bergman R . Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects. Diabetes. 1992; 41(6):750-9. DOI: 10.2337/diab.41.6.750. View

Heiston E, Eichner N, Gilbertson N, Gaitan J, Kranz S, Weltman A . Two weeks of exercise training intensity on appetite regulation in obese adults with prediabetes. J Appl Physiol (1985). 2019; 126(3):746-754. PMC: 6459386. DOI: 10.1152/japplphysiol.00655.2018. View

10.

Minato-Inokawa S, Tsuboi-Kaji A, Honda M, Takeuchi M, Kitaoka K, Kurata M . Associations of alanine aminotransferase/aspartate aminotransferase with insulin resistance and β-cell function in women. Sci Rep. 2023; 13(1):7853. PMC: 10185667. DOI: 10.1038/s41598-023-35001-1. View

11.

Lyssenko V, Nagorny C, Erdos M, Wierup N, Jonsson A, Spegel P . Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2008; 41(1):82-8. PMC: 3725650. DOI: 10.1038/ng.288. View

12.

Utzschneider K, Prigeon R, Faulenbach M, Tong J, Carr D, Boyko E . Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2008; 32(2):335-41. PMC: 2628704. DOI: 10.2337/dc08-1478. View

13.

Newsholme P, Krause M . Nutritional regulation of insulin secretion: implications for diabetes. Clin Biochem Rev. 2012; 33(2):35-47. PMC: 3387883. View

14.

Overberg J, Kalveram L, Keller T, Krude H, Kuhnen P, Wiegand S . Interactions between nocturnal melatonin secretion, metabolism, and sleeping behavior in adolescents with obesity. Int J Obes (Lond). 2022; 46(5):1051-1058. PMC: 9050511. DOI: 10.1038/s41366-022-01077-4. View

15.

Anothaisintawee T, Lertrattananon D, Thamakaison S, Knutson K, Thakkinstian A, Reutrakul S . Later chronotype is associated with higher hemoglobin A1c in prediabetes patients. Chronobiol Int. 2017; 34(3):393-402. DOI: 10.1080/07420528.2017.1279624. View

16.

Fischer D, Lombardi D, Marucci-Wellman H, Roenneberg T . Chronotypes in the US - Influence of age and sex. PLoS One. 2017; 12(6):e0178782. PMC: 5479630. DOI: 10.1371/journal.pone.0178782. View

17.

Roberts H . AFTERNOON GLUCOSE TOLERANCE TESTING: A KEY TO THE PATHOGENESIS, EARLY DIAGNOSIS AND PROGNOSIS OF DIABETOGENIC HYPERINSULINISM. J Am Geriatr Soc. 1964; 12:423-72. DOI: 10.1111/j.1532-5415.1964.tb05730.x. View

18.

Saini C, Petrenko V, Pulimeno P, Giovannoni L, Berney T, Hebrok M . A functional circadian clock is required for proper insulin secretion by human pancreatic islet cells. Diabetes Obes Metab. 2015; 18(4):355-65. DOI: 10.1111/dom.12616. View

19.

Reutrakul S, Hood M, Crowley S, Morgan M, Teodori M, Knutson K . Chronotype is independently associated with glycemic control in type 2 diabetes. Diabetes Care. 2013; 36(9):2523-9. PMC: 3747872. DOI: 10.2337/dc12-2697. View

20.

Boden G, Ruiz J, Urbain J, Chen X . Evidence for a circadian rhythm of insulin secretion. Am J Physiol. 1996; 271(2 Pt 1):E246-52. DOI: 10.1152/ajpendo.1996.271.2.E246. View