TY - JOUR
T1 - Impaired Diurnal Pattern of Meal Tolerance and Insulin Sensitivity in Type 2 Diabetes
T2 - Implications for Therapy
AU - Yadav, Yogesh
AU - Romeres, Davide
AU - Cobelli, Claudio
AU - Man, Chiara Dalla
AU - Carter, Rickey
AU - Basu, Ananda
AU - Basu, Rita
N1 - Funding Information:
The work received support through funds from the National Institute of Diabetes and Digestive and Kidney Diseases R01 DK029953 to R.B. and R01 DK085516 to A.B. Sample processing performed at Vanderbilt University received support from the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases grants DK059637 (Mouse Metabolic Phenotyping Center) and DK020593 (Diabetes Research and Training Center). Support was received from the Ministero dell’Universit e della Ricerca (MIUR; Italian Minister for Education) under the initiative “Departments of Excellence” (Law 232/2016) to D.R. and C.D.M.
Funding Information:
conduct of the studies, Benjamin Gran (lead technologist), Benjamin Paysour (research technologist), Nirmal Bhandari (research technologist), and David Fulkerson (research technologist) for sample analyses, and Rajia Arbab (research assistant) for technical assistance. Funding. The work received support through funds from the National Institute of Diabetes and Digestive and Kidney Diseases R01 DK029953 to R.B. and R01 DK085516 to A.B. Sample processing performed at Vanderbilt University received support from the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases grants DK059637 (Mouse Metabolic Phenotyping Center) and DK020593 (Diabetes Research and Training Center). Support was received from the Ministero dell’Universit e della Ricerca (MIUR; Italian Minister for Education) under the initiative “Departments of Excellence” (Law 232/2016) to D.R. and C.D.M. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. Y.Y. and D.R. assisted with the study, analyzed data, and helped in the conduct of the study. C.C. and C.D.M. analyzed the data and reviewed the manuscript. R.C. analyzed the data and edited the manuscript. A.B. and R.B. designed and conducted the studies, analyzed data, and wrote the manuscript. R.B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were published in abstract form at the 80th Scientific Sessions of the American Diabetes Association, virtual meeting, 12–16 June 2020, published in Diabetes 2020;69(Suppl. 1):313-OR, and at the 57th EASD Annual Meeting of the European Association for the Study of Diabetes, virtual meeting, 28 September–1 October 2021, published in Diabetologia 2021;64(Suppl. 1):S129–S130.
Publisher Copyright:
© 2023 by the American Diabetes Association.
PY - 2023/2
Y1 - 2023/2
N2 - To assess the diurnal patterns of postprandial glucose tolerance and insulin sensitivity, 19 subjects with type 2 diabetes (8 women; 60 ± 11 years; BMI 32 ± 5 kg/m2) and 19 anthropometrically matched subjects with no diabetes (ND; 11 women; 53 ± 12 years; BMI 29 ± 5 kg/m2) were studied during breakfast (B), lunch (L), and dinner (D) with identical mixed meals (75 g carbohydrates) on 3 consecutive days in a randomized Latin square design. Three stable isotopes of glucose were ustilized to estimate meal fluxes, and mathematical models were used in estimating indices of insulin action and b-cell function. Postmeal glucose excursions were higher at D versus B and at D versus L in type 2 diabetes (P < 0.05), while in ND they were higher at D versus B (P = 0.025) and at L versus B (P = 0.04). The insulin area under the curve was highest at B compared with L and D in type 2 diabetes, while no differences were observed in ND. Disposition index (DI) was higher at B than at L (P < 0.01) and at D (P < 0.001) in ND subjects, whereas DI was low with unchanging pattern across B-L-D in individuals with type 2 diabetes. Furthermore, between-meal differences in β-cell responsivity to glucose (F) and insulin sensitivity (SI) were concurrent with changes in the DI within groups. Fasting and postmeal glucose, insulin, and C-peptide concentrations, along with estimates of endogenous glucose production (EGP), Rd, SI, F, hepatic extraction of insulin, insulin secretion rate, extracted insulin, and DI, were altered in type 2 diabetes compared with ND (P <0.011 for all). The data show a diurnal pattern of postprandial glucose tolerance in overweight otherwise glucosetolerant ND individuals that differs from overweight individuals with type 2 diabetes.
AB - To assess the diurnal patterns of postprandial glucose tolerance and insulin sensitivity, 19 subjects with type 2 diabetes (8 women; 60 ± 11 years; BMI 32 ± 5 kg/m2) and 19 anthropometrically matched subjects with no diabetes (ND; 11 women; 53 ± 12 years; BMI 29 ± 5 kg/m2) were studied during breakfast (B), lunch (L), and dinner (D) with identical mixed meals (75 g carbohydrates) on 3 consecutive days in a randomized Latin square design. Three stable isotopes of glucose were ustilized to estimate meal fluxes, and mathematical models were used in estimating indices of insulin action and b-cell function. Postmeal glucose excursions were higher at D versus B and at D versus L in type 2 diabetes (P < 0.05), while in ND they were higher at D versus B (P = 0.025) and at L versus B (P = 0.04). The insulin area under the curve was highest at B compared with L and D in type 2 diabetes, while no differences were observed in ND. Disposition index (DI) was higher at B than at L (P < 0.01) and at D (P < 0.001) in ND subjects, whereas DI was low with unchanging pattern across B-L-D in individuals with type 2 diabetes. Furthermore, between-meal differences in β-cell responsivity to glucose (F) and insulin sensitivity (SI) were concurrent with changes in the DI within groups. Fasting and postmeal glucose, insulin, and C-peptide concentrations, along with estimates of endogenous glucose production (EGP), Rd, SI, F, hepatic extraction of insulin, insulin secretion rate, extracted insulin, and DI, were altered in type 2 diabetes compared with ND (P <0.011 for all). The data show a diurnal pattern of postprandial glucose tolerance in overweight otherwise glucosetolerant ND individuals that differs from overweight individuals with type 2 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85147045614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147045614&partnerID=8YFLogxK
U2 - 10.2337/db22-0238
DO - 10.2337/db22-0238
M3 - Article
C2 - 36346619
AN - SCOPUS:85147045614
SN - 0012-1797
VL - 72
SP - 223
EP - 232
JO - Diabetes
JF - Diabetes
IS - 2
ER -