Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects
Abstract
The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10–12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGS), was much reduced in the evening (AM 2.98 ± 0.45, PM 1.86 ± 0.33 min−1 P < 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 ± 0.31 min−1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 ± 0.18 min−1 P > 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 ± 2.9, PM 10.2 ± 1.9 × 10−5 min−1/pM, P < 0.01) and reduced β-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 ± 441, PM 1825 ± 381 pM/10 min, P < 0.05) and the potentiation slope (AM 462 ± 68, PM 267 ± 35 pM/mM, P < 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 ± 0.7, PM 4.9 ± 1.0 × 10−5 min−1/pM). A marginally significant decline in (β-cell responsiveness was observed in the obese group (potentiation slope AM 388 ± 78, PM 233 ± 58 pM/mM, P < 0.05). Glucose tolerance is maintained when the pancreas adequately compensates for prevailing insulin resistance, a relationship described by the disposition index (SI, × Φ1). This product decreased 46% in nonobese subjects from morning to evening (P < 0.05), reflecting the inability of the pancreas to overcome prevailing insulin resistance, and resulting in evening glucose intolerance. No diurnal decline in the disposition index was observed in obese subjects. The diurnal rhythms in insulin sensitivity and secretion in nonobese subjects are not consistent with known rhythms in growth hormone or cortisol, but could be due to the effects of a putative diurnal rhythm of sympathetic activity, which would suppress both insulin sensitivity and secretion in the evening. The absence of a rhythm in the obese could reflect an autonomic or hormonal dysfunction that may be related to body-weight regulation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In healthy nonobese individuals, SI is higher in the morning than 8 to 10 h later.
“In healthy nonobese individuals, SI is higher in the morning than 8 to 10 h later, in the late afternoon or early evening (29).”
From Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss (2014) · cites this paper as [29]
Cited by
Sorted by citations
Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes
Hovorka, R., Canonico, V., Chassin, L. J., Haueter, U., Massi-Benedetti, M., Federici, M. O., Pieber, T. R., Schaller, H. C., Schaupp, L., Vering, T., et al. (2004) · Physiological Measurement · doi:10.1088/0967-3334/25/4/010 · Cited by 1,274 · see citing works
“…known that parameters of the glucoregulatory system differ considerably between subjects (Bergman et al 1989) and also exhibit diurnal variations (Lee et al 1992, Van Cauter et al 1992) although exact quantification of the variation (amplitude and frequency) within a subject is yet to be…”
BackgroundCircadian regulation of glucose, lipid, and energy metabolism in humans
Poggiogalle, E., Jamshed, H., & Peterson, C. M. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.017 · Cited by 716 · see citing works
“[50] Lee A, Ader M, Bray GA, Bergman RN.”
BackgroundInfluentialLeproult, R., Holmbäck, U., & Van Cauter, E. (2014) · Diabetes · doi:10.2337/db13-1546 · Cited by 607 · see citing works
“In healthy nonobese individuals, SI is higher in the morning than 8 to 10 h later, in the late afternoon or early evening (29).”
BackgroundJakubowicz, D., Barnea, M., Wainstein, J., & Froy, O. (2013) · Obesity · doi:10.1002/oby.20460 · Cited by 593 · see citing works
“This is consistent with previous studies that have shown that insulin sensitivity and glucose tolerance decreases progressively throughout the day with insulin sensitivity reaching a nadir in the evening (18,36,37).”
ResultRoles of Circadian Rhythmicity and Sleep in Human Glucose Regulation
Cauter, E. V., Polonsky, K. S., & Scheen, A. J. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.5.0317 · Cited by 611 · see citing works
“Although, in subjects receiving constant glucose infusions, there is an inverse temporal relationship between the 24-h glucose and insulin patterns, on the one hand, and that of plasma cortisol, on the other hand, and the relative amplitudes of both rhythms are significantly correlated (40), the possibility that the 2…”
BackgroundResultInfluentialCircadian Rhythms and Metabolic Syndrome
Maury, E., Ramsey, K. M., & Bass, J. T. (2010) · Circulation Research · doi:10.1161/circresaha.109.208355 · Cited by 502 · see citing works
Hutchison, A. T., Regmi, P., Manoogian, E. N. C., Fleischer, J. G., Wittert, G. A., Panda, S., & Heilbronn, L. K. (2019) · Obesity · doi:10.1002/oby.22449 · Cited by 466 · see citing works
“However, it is well described that glucose tolerance diminishes over the course of the day under natural circadian variation (21,22,25).”
BackgroundThe Effects of Light at Night on Circadian Clocks and Metabolism
Fonken, L. K., & Nelson, R. J. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1051 · Cited by 468 · see citing works
Insulin Resistance in Short Children with Intrauterine Growth Retardation1
Hofman, P. L., Cutfield, W. S., Robinson, E. M., Bergman, R. N., Menon, R. K., Sperling, M. A., & Gluckman, P. D. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3752 · Cited by 443 · see citing works
Self-citationA Daily Rhythm in Glucose Tolerance
la Fleur, S. E., Kalsbeek, A., Wortel, J., Fekkes, M. L., & Buijs, R. M. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1237 · Cited by 337 · see citing works
“Plasma insulin responses at ZT 14 in SCN-lesioned rats and in SCN-intact rats were not significantly different [interaction (F[5,65] 5 1.”
BackgroundResultInfluentialObesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings1
Hoffman, R. M., Boston, R. C., Stefanovski, D., Kronfeld, D. S., & Harris, P. A. (2003) · Journal of Animal Science · doi:10.2527/2003.8192333x · Cited by 321 · see citing works
“Glucose tolerance was shown to have a diurnal variation in humans (Lee et al., 1992) and appears to have a diurnal variation in horses (Staniar, 2002), so the modified FSIGT were initiated at approximately the same time each morning (0857 with SD of 23 min).”
BackgroundResultDiurnal pattern to insulin secretion and insulin action in healthy individuals
Saad, A., Dalla Man, C., Nandy, D. K., Levine, J. A., Bharucha, A. E., Rizza, R. A., Basu, R., Carter, R. E., Cobelli, C., Kudva, Y. C., et al. (2012) · Diabetes · doi:10.2337/db11-1478 · Cited by 297 · see citing works
“The reverse pattern has been observed in people with type 2 diabetes (6) and obesity (7).”
BackgroundScreening and Diagnosis of Gestational Diabetes Mellitus, Where Do We Stand
Pr, R. (2016) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2016/17588.7689 · Cited by 247 · see citing works
Chronobiology in the endocrine system
Haus, E. L. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.01.001 · Cited by 222 · see citing works
“Also “counter regulatory hormones”, like GH, are likely involved in the reduced insulin sensitivity in the afternoon and evening leading to a reduction in glucose tolerance at that time [366,367].”
BackgroundPlat, L., Leproult, R., L’Hermite-Baleriaux, M., Fery, F., Mockel, J., Polonsky, K. S., & Van Cauter, E. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.9.5978 · Cited by 225 · see citing works
“Comparison between placebo and hydrocortisone at 0500 h (cortisol elevation at normal time of day) Placebo Hydrocortisone P level Basal pretreatment levels (0400–0500 h) Mean glucose level (mmol/L) 6.57 6 0.21 6.87 6 0.26 ns Mean cortisol level (nmol/L) 127 6 22 149 6 30 ns Mean ISR (pmol/min) 316 6 21 290 6 60 ns Mea…”
InfluentialCircadian regulation of metabolism
Bailey, S. M., Udoh, U. S., & Young, M. E. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0200 · Cited by 211 · see citing works
“1974, Lee et al .”
Circadian Etiology of Type 2 Diabetes Mellitus
Javeed, N., & Matveyenko, A. V. (2018) · Physiology · doi:10.1152/physiol.00003.2018 · Cited by 205 · see citing works
The effects of nocturnal life on endocrine circadian patterns in healthy adults
Qin, L.-Q., Li, J., Wang, Y., Wang, J., Xu, J.-Y., & Kaneko, T. (2003) · Life Sciences · doi:10.1016/s0024-3205(03)00628-3 · Cited by 192 · see citing works
Kanderian, S. S., WEINZIMER, S. A., Voskanyan, G. R., & Steil, G. M. (2009) · Journal of Diabetes Science and Technology · doi:10.1177/193229680900300508 · Cited by 162 · see citing works
Altered postprandial hormone and metabolic responses in a simulated shift work environment
Ribeiro, D., Hampton, S., Morgan, L., Deacon, S., & Arendt, J. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1580305 · Cited by 155 · see citing works
“Insulin sensitivity is known to be lower during the night than in the day (Van Cauter et al. 1992, Lee et al. 1992, Owens et al. 1996), so it might be expected that it would take a greater amount of insulin to cope with the same amount of glucose when the body clock time was 2130 h (i.e.…”
Insulin-mediated vasodilation: impairment with increased blood pressure and body mass
Feldman, R. D., & Bierbrier, G. S. (1993) · The Lancet · doi:10.1016/0140-6736(93)91708-t · Cited by 144 · see citing works
Impact of Sleep and Sleep Loss on Glucose Homeostasis and Appetite Regulation
Knutson, K. L. (2007) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2007.03.004 · Cited by 139 · see citing works
Al-Naimi, S., Hampton, S. M., Richard, P., Tzung, C., & Morgan, L. M. (2004) · Chronobiology International · doi:10.1081/cbi-200037171 · Cited by 134 · see citing works
“The failure to observe a compensatory rise in plasma insulin at night in response to a raised glucose has been shown to be partly due to a diminished sensitivity of the pancreatic cell to glucose (Lee et al., 1992).”
BackgroundEffects of morning cortisol elevation on insulin secretion and glucose regulation in humans
Plat, L., Byrne, M. M., Sturis, J., Polonsky, K. S., Mockel, J., Fery, F., & Van Cauter, E. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.1.e36 · Cited by 132 · see citing works
Daily Rhythms in Glucose Metabolism: Suprachiasmatic Nucleus Output to Peripheral Tissue
la Fleur, S. (2003) · Journal of neuroendocrinology · doi:10.1046/j.1365-2826.2003.01019.x · Cited by 86 · see citing works
Leung, G. K. W., Huggins, C. E., & Bonham, M. P. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2017.11.010 · Cited by 132 · see citing works
Arends, N. J. T., Boonstra, V., Duivenvoorden, H. J., Hofman, P. L., Cutfield, W. S., & Hokken-Koelega, A. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02171.x · Cited by 132 · see citing works
Diurnal Pattern of Insulin Action in Type 1 Diabetes
Hinshaw, L., Dalla Man, C., Nandy, D. K., Saad, A., Bharucha, A. E., Levine, J. A., Rizza, R. A., Basu, R., Carter, R. E., Cobelli, C., et al. (2013) · Diabetes · doi:10.2337/db12-1759 · Cited by 125 · see citing works
Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism
Morgan, L., Arendt, J., Owens, D., Folkard, S., Hampton, S., Deacon, S., English, J., Ribeiro, D., & Taylor, K. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1570443 · Cited by 124 · see citing works
“…a compensatory rise in plasma insulin in response to the raised glucose has been shown to be partially due to a diminished sensitivity of the pancreatic B cell to glucose (Lee et al. 1992) and also to an increase in the rate of insulin clearance from the plasma at night (Van Cauter et al. 1992).”
BackgroundResultAndriessen, C., Fealy, C. E., Veelen, A., van Beek, S. M. M., Roumans, K. H. M., Connell, N. J., Mevenkamp, J., Moonen‐Kornips, E., Havekes, B., Schrauwen‐Hinderling, V. B., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05752-z · Cited by 122 · see citing works
Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
Depner, C. M., Melanson, E. L., McHill, A. W., & Wright, K. P. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714813115 · Cited by 122 · see citing works
“Previous findings consistently show glucose tolerance decreases across the 24-h day and is under circadian regulation (47, 58).”
Backgroundde Araújo, M. C. P. M., Haber, E. P., Carpinelli, Â. R., & Cipolla‐Neto, J. (2002) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2002.02925.x · Cited by 116 · see citing works
Ramsey, K. M., Marcheva, B., Kohsaka, A., & Bass, J. T. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093546 · Cited by 122 · see citing works
“The cyclical nature of glucose tolerance has been ascribed to a circadian effect on insulin sensitivity of the peripheral tissues (13, 85, 88, 166) as well as to a relative decrease in insulin secretion during the evening hours (19, 29, 88, 103).”
Knutson, K. L., Wu, D., Patel, S. R., Loredo, J. S., Redline, S. S., Cai, J., Gallo, L. C., Mossavar‐Rahmani, Y., Ramos, A. R., Teng, Y., et al. (2017) · SLEEP · doi:10.1093/sleep/zsx014 · Cited by 113 · see citing works
Bromocriptine: old drug, new formulation and new indication
Holt, R. I. G., Barnett, A. H., & Bailey, C. J. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01304.x · Cited by 110 · see citing works
“In lean individuals without diabetes, glucose tolerance is better in the morning and deteriorates by evening, associated with a decrease in insulin sensitivity and a reduction in islet β-cell responsiveness to glucose [16].”
BackgroundThe hypothalamic clock and its control of glucose homeostasis
Kalsbeek, A., Yi, C., la Fleur, S. E., & Fliers, E. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.02.005 · Cited by 106 · see citing works
Henriksen, J. E., ALFORD, F. P., Handberg, A., Vaag, A. A., Ward, G. M., Kalfas, A., & Beck‐Nielsen, H. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117436 · Cited by 106 · see citing works
Hwu, C., Kwok, C., Lai, T.-Y., Shih, K., Lee, T.-S., Hsiao, L.-C., Lee, S.-H., Fang, V. S., & Ho, L.-T. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4311 · Cited by 105 · see citing works
Morgan, L. M., Aspostolakou, F., Wright, J., & Gama, R. (1999) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/000456329903600407 · Cited by 101 · see citing works
Almoosawi, S., Prynne, C. J., Hardy, R., & Stephen, A. M. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.103 · Cited by 100 · see citing works
Coupled network of the circadian clocks: a driving force of rhythmic physiology
Finger, A., Dibner, C., & Kramer, A. (2020) · FEBS Letters · doi:10.1002/1873-3468.13898 · Cited by 99 · see citing works
Leproult, R., Reeth, O. V., Byrne, M. M., Sturis, J., & Cauter, E. V. (1997) · Journal of Biological Rhythms · doi:10.1177/074873049701200306 · Cited by 94 · see citing works
How to measure insulin action in vivo
Scheen, A. J., Paquot, N., Castillo, M. J., & Lefèbvre, P. J. (1994) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610100206 · Cited by 89 · see citing works
Metabolic and Glycemic Sequelae of Sleep Disturbances in Children and Adults
Koren, D., O’Sullivan, K. L., & Mokhlesi, B. (2014) · Current Diabetes Reports · doi:10.1007/s11892-014-0562-5 · Cited by 91 · see citing works
Complex physiology and clinical implications of time-restricted eating
Petersen, M. C., Gallop, M. R., Ramos, S. F., Zarrinpar, A., Broussard, J. L., Chondronikola, M., Chaix, A., & Klein, S. (2022) · Physiological Reviews · doi:10.1152/physrev.00006.2022 · Cited by 91 · see citing works
Biochemical measures in a population-based study: effect of fasting duration and time of day
Emberson, J., Whincup, P. H., Walker, M., et al. (2002) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/000456302320314511 · Cited by 86 · see citing works
Wong, X., Singh-Levett, I., Hollingsworth, L., Shaw, G. M., Hann, C. E., Lotz, T., Lin, J., Wong, O. S. W., & Chase, J. G. (2006) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2006.8.174 · Cited by 84 · see citing works
The role of the circadian clock system in nutrition and metabolism
Cagampang, F. R. A., & Bruce, K. D. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512002139 · Cited by 83 · see citing works
“Daily rhythms in glucose tolerance have also been reported, with a lower plasma glucose response to bolus glucose administration in the morning compared with responses in the evening (145,146) .”
ResultMarjot, T., Tomlinson, J., Hodson, L., & Ray, D. W. (2023) · Gut · doi:10.1136/gutjnl-2023-329998 · Cited by 87 · see citing works
“50 51 As a result, the ability to appropriately store and metabolise dietary glucose and lipid intake is progressively impaired throughout the day.”
BackgroundCircadian desynchrony and glucose metabolism
Speksnijder, E. M., Bisschop, P. H. L. T., Siegelaar, S. E., Stenvers, D. J., & Kalsbeek, A. (2024) · Journal of Pineal Research · doi:10.1111/jpi.12956 · Cited by 98 · see citing works
“136”
The Roles of Time of Day and Sleep Quality in Modulating Glucose Regulation: Clinical Implications
Scheen, A. J., & Cauter, E. V. (1998) · Hormone Research in Paediatrics · doi:10.1159/000023170 · Cited by 79 · see citing works
Circadian clock, diurnal glucose metabolic rhythm, and dawn phenomenon
Peng, F., Li, X., Xiao, F., Zhao, R., & Sun, Z. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.03.010 · Cited by 84 · see citing works
Leung, G. K. W., Huggins, C. E., Ware, R. S., & Bonham, M. P. (2019) · Chronobiology International · doi:10.1080/07420528.2019.1683856 · Cited by 82 · see citing works
“The higher postprandial glucose response at night (compared to the day) reported in the current meta-analysis may be caused by a reduction in insulin sensitivity (Lee et al. 1992; Morgan et al. 1999; Saad et al. 2012).”
BackgroundYoshino, J., Almeda-Valdes, P., Patterson, B. W., Okunade, A. L., Imai, S.-I., Mittendorfer, B., & Klein, S. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1579 · Cited by 75 · see citing works
Mealtime: A circadian disruptor and determinant of energy balance?
Ruddick-Collins, L. C., Morgan, P. J., & Johnstone, A. M. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12886 · Cited by 74 · see citing works
Berry, D. C., Croniger, C. M., Ghyselinck, N. B., & Noy, N. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00775-12 · Cited by 72 · see citing works
Nutrition and the circadian timing system
Stenvers, D. J., Jonkers‐Schuitema, C. F., Fliers, E., Bisschop, P. H. L. T., & Kalsbeek, A. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59427-3.00020-4 · Cited by 70 · see citing works
Sturis, J., Scheen, A. J., Leproult, R., Polonsky, K. S., & Cauter, E. V. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117817 · Cited by 69 · see citing works
“and in the face of glucose and insulin infusions at constant mean rates confirms the findings of previous studies showing that reduced insulin sensitivity later in the day is a major cause of the reduction in glucose tolerance (41, 42).”
ResultA Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease
Peng, X., Fan, R., Xie, L., Shi, X., Dong, K., Zhang, S., Tao, J., Xu, W., Ma, D., Chen, J., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010504 · Cited by 68 · see citing works
“These diurnal oscillations in glucose tolerance may be partially due to the diurnal rhythms of β-cell responsiveness, secretion and the clearance of insulin because blood insulin levels and insulin sensibility also follow circadian rhythms [23,29,30].”
BackgroundCauter, E. V., Polonsky, K. S., Blackman, J. D., Roland, D., Sturis, J., Byrne, M. M., & Scheen, A. J. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.6.7989487 · Cited by 69 · see citing works
Circadian Clocks Make Metabolism Run
Sinturel, F., Petrenko, V., & Dibner, C. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.018 · Cited by 64 · see citing works
Glycemic control is impaired in the evening in prediabetes through multiple diurnal rhythms
Sonnier, T. J., Rood, J., Gimble, J. M., & Peterson, C. M. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.04.001 · Cited by 62 · see citing works
Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer’s subjects?
Femminella, G. D., Livingston, N. R., Raza, S., van der Doef, T. F., Frangou, E., Love, S., Busza, G., Calsolaro, V., Carver, S., Holmes, C., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00784-w · Cited by 61 · see citing works
Kessler, K., Hornemann, S., Petzke, K. J., Kemper, M., Kramer, A., Pfeiffer, A. F. H., Pivovarova, O., & Rudovich, N. (2017) · Scientific Reports · doi:10.1038/srep44170 · Cited by 60 · see citing works
Richter, E. A., Bilan, P. J., & Klip, A. (2025) · Physiological Reviews · doi:10.1152/physrev.00033.2024 · Cited by 64 · see citing works
Qian, J., Yeh, B., Rakshit, K., Colwell, C. S., & Matveyenko, A. V. (2015) · Endocrinology · doi:10.1210/en.2015-1516 · Cited by 59 · see citing works
Syncing Exercise With Meals and Circadian Clocks
Heden, T. D., & Kanaley, J. A. (2018) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000172 · Cited by 57 · see citing works
The euglycemic hyperinsulinemic clamp examination: variability and reproducibility
L. Bokemark, A. F. (2000) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365510050185010 · Cited by 56 · see citing works
Watanabe, R. M., Azen, C., Roy, S., Perlman, J. A., & Bergman, R. N. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.5.7962320 · Cited by 55 · see citing works
Self-citationHansen, J., Timmers, S., Moonen‐Kornips, E., Duez, H., Staels, B., Hesselink, M. K. C., & Schrauwen, P. (2016) · Scientific Reports · doi:10.1038/srep35047 · Cited by 54 · see citing works
Diurnal postprandial responses to low and high glycaemic index mixed meals
Gibbs, M. A., Harrington, D., Starkey, S., Williams, P., & Hampton, S. M. (2013) · Clinical Nutrition · doi:10.1016/j.clnu.2013.09.018 · Cited by 53 · see citing works
Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease
Versteeg, R. I., Serlie, M. J. M., Kalsbeek, A., & la Fleur, S. E. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.067 · Cited by 54 · see citing works
The Hypothalamic‐Pituitary‐Adrenal Axis in Obesity
Chalew, S. A., Nagel, H., & Shore, S. (1995) · Obesity Research · doi:10.1002/j.1550-8528.1995.tb00163.x · Cited by 52 · see citing works
Ercan, N., Gannon, M. C., & Nuttall, F. Q. (1994) · Diabetes Care · doi:10.2337/diacare.17.12.1453 · Cited by 53 · see citing works
Gu, N., Park, M. K., Kim, T., Bahng, M. Y., Cho, S., Yoon, S. H., Cho, J., Jang, I., Yu, K., & Lim, K. S. (2014) · Drug Design Development and Therapy · doi:10.2147/dddt.s65678 · Cited by 53 · see citing works
Basse, A. L., Dalbram, E., Larsson, L., Gerhart-Hines, Z., Zierath, J. R., & Treebak, J. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01198 · Cited by 52 · see citing works
Modeling of 24-Hour Glucose and Insulin Profiles of Patients With Type 2 Diabetes
Jauslin, P. M., Frey, N., & Karlsson, M. O. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010362536 · Cited by 51 · see citing works
Diurnal variations in myocardial metabolism
Bray, M. S., & Young, M. E. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn054 · Cited by 52 · see citing works
Diurnal variation in lipoprotein lipase activity
Arasaradnam, M., Morgan, L., Wright, J., & Gama, R. (2002) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1258/0004563021901883 · Cited by 49 · see citing works
Nutrient timing and metabolic regulation
Smith, H. A., & Betts, J. A. (2022) · The Journal of Physiology · doi:10.1113/jp280756 · Cited by 54 · see citing works
“Specifically, a combination of animal and human studies suggests that a net shift in fatty acid metabolism from oxidation towards lipogenesis occurs throughout the day, with circadian regulation of intestinal triglyceride absorption, acylcarnitines, mitochondrial oxidative capacity, very-low-density lipoprotein secret…”
BackgroundAder, M., Garvey, W. T., Phillips, L. S., Nemeroff, C. B., Gharabawi, G. M., Mahmoud, R. A., Greenspan, A. J., Berry, S. A., Musselman, D. L., Morein, J., et al. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2008.01.004 · Cited by 48 · see citing works
“First-phase insulin response (AIRG) was calculated as incremental insulin area from 0 to 10 min and glucose tolerance (KG) as the negative slope of the natural log of glucose versus time from 10 to 19 min (Lee et al., 1992).”
MethodSelf-citationFritz, J., Phillips, A., Hunt, L., Imam, A., Reid, K., Perreira, K., Mossavar-Rahmani, Y., Daviglus, M., Sotres-Alvarez, D., Zee, P., et al. (2020) · Sleep · doi:10.1093/sleep/zsaa218 · Cited by 36 · see citing works
Rovira‐Llopis, S., Luna-Marco, C., Perea‐Galera, L., Bañuls, C., Morillas, C., & Víctor, V. M. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09853-x · Cited by 48 · see citing works
“…out that, compared to control lean subjects, people who have metabolic problems also develop alterations at the circadian cycle level in terms of the rhythmicity of metabolic processes, such as mitochondrial oxidative capacity [14], glucose homeostasis [15] and oxidation of substrates [14, 16].”
BackgroundPedrini, M. T., Niederwanger, A., Kranebitter, M., Tautermann, C. S., Ciardi, C., Tatarczyk, T., & Patsch, J. R. (2006) · Diabetologia · doi:10.1007/s00125-006-0262-z · Cited by 43 · see citing works
“In most studies, it has been observed that glucose tolerance is decreased in the afternoon or evening compared with the morning [37–39]; decreased glucose tolerance, in these studies, was shown to result from decreased insulin secretion [38–40], decreased insulin sensitivity [41, 42] or both [37, 43].”
BackgroundCircadian variation of the pancreatic islet transcriptome
Rakshit, K., Qian, J., Ernst, J., & Matveyenko, A. V. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00019.2016 · Cited by 40 · see citing works
“Moreover, metabolic abnormalities associated with T2DM have also been shown to impair circadian control of insulin secretion (22).”
BackgroundEffects of aging on glucose regulation during wakefulness and sleep
Frank, S. A., Roland, D. C., Sturis, J., Byrne, M. M., Refetoff, S., Polonsky, K. S., & Cauter, E. V. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.6.e1006 · Cited by 38 · see citing works
Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men
Burdge, G. C., Jones, A. E., Frye, S., Goodson, L., & Wootton, S. A. (2003) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1601722 · Cited by 38 · see citing works
Knutsson, A., Karlsson, B., Örnkloo, K., Landström, U., Lennernäs, M. A. ‐., & Eriksson, K. (2002) · Nutrition and Health · doi:10.1177/026010600201600207 · Cited by 36 · see citing works
Circadian regulation of cellular physiology
Peek, C. B., Ramsey, K. M., Levine, D. C., Marcheva, B., Perelis, M., & Bass, J. (2015) · Methods in Enzymology · doi:10.1016/bs.mie.2014.10.006 · Cited by 35 · see citing works
Scrimgeour, K., Gresham, M., Giles, L. R., Thomson, P. C., WYNN, P. C., & Newman, R. E. (2008) · Journal of Endocrinology · doi:10.1677/joe-07-0627 · Cited by 35 · see citing works
“For example, humans have a higher glucose output and insulin requirement in the early morning hours (Carroll & Nestel 1973, Lee et al. 1992), whereas rodents have higher concentrations of glucose and insulin in the dark period compared with the light period (Pauly & Scheving 1967), which may be…”
BackgroundInsulin resistance in healthy prepubertal twins
Jefferies, C., Hofman, P. L., Knoblauch, H., Luft, F. C., Robinson, E. M., & Cutfield, W. S. (2004) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2004.01.059 · Cited by 35 · see citing works
An Endocrinologist's Guide to the Clock
Prasai, M., Pernicova, I., Grant, P. J., & SCOTT, E. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2449 · Cited by 34 · see citing works
Predominantly night-time feeding and maternal glycaemic levels during pregnancy
Loy, S. L., Cheng, T. S., Colega, M., Cheung, Y. B., Godfrey, K. M., Gluckman, P. D., Kwek, K. Y. C., Saw, S., Chong, Y. S., Padmapriya, N., et al. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516000441 · Cited by 34 · see citing works
“It was suggested that the marked suppression of insulin sensitivity in the morning in obese subjects may lead to failure for detection with further reduction in insulin sensitivity((29)).”
BackgroundResultDiurnal Variations in Cardiovascular Function and Glucose Regulation in Normotensive Humans
Biston, P., Cauter, E. V., Ofek, G., Linkowski, P., Polonsky, K. S., & Degaute, J.-P. (1996) · Hypertension · doi:10.1161/01.hyp.28.5.863 · Cited by 34 · see citing works
The hypothalamic clock and its control of glucose homeostasis
Kalsbeek, A., Ruiter, M., la Fleur, S. E., Cailotto, C., Kreier, F., & Buijs, R. M. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53017-1 · Cited by 33 · see citing works
Gyuk, P., Vassányi, I., & Kósa, I. (2019) · Journal of Healthcare Engineering · doi:10.1155/2019/8605206 · Cited by 29 · see citing works
“Both insulin sensitivity and secretion is supposed to change in the evening [33], but diabetics may also experience differences between early morning and afternoon hours.”
BackgroundWhat is bipolar disorder? A disease model of dysregulated energy expenditure
Mansur, R. B., Lee, Y. L., McIntyre, R. S., & Brietzke, E. M. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.006 · Cited by 33 · see citing works
Haldar, S., Egli, L., Castro, C. A. D., Tay, S. L., Koh, M. X. N., Darimont, C., Macé, K., & Henry, C. J. (2020) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2019-001099 · Cited by 31 · see citing works
The islet circadian clock: entrainment mechanisms, function and role in glucose homeostasis
Rakshit, K. P., Qian, J., Colwell, C. S., & Matveyenko, A. V. (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12523 · Cited by 33 · see citing works
“Finally, it is important to note that circadian rhythms in insulin secretion are disrupted in states associated with metabolic disease such as obesity and T2DM [30,33], implying an intriguing possibility that loss of circadian rhythmicity in insulin secretion may serve as an early biomarker of β-cell dysfunction in T2…”
BackgroundAlteration of postprandial glucose and insulin concentrations with meal frequency and composition
Kanaley, J. A., Heden, T. D., Liu, Y., & Fairchild, T. J. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114514002128 · Cited by 31 · see citing works
“However, in obese subjects, this circadian variation is believed to be absent((29)), which is supported by our data.”
- Authors
- Lee, A., Ader, M., Bray, G. A., & Bergman, R. N.
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1992-06-01
- Volume
- 41
- Issue
- 6
- Pages
- 750-759
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2025050665
- Cited by
- 193
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK029867, DK27619, DK29867)
- National Center for Research Resources (RR00425, M01RR000425)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- diurnal variation, glucose tolerance, insulin sensitivity, insulin secretion, obesity, glucose effectiveness, first-phase insulin response, circadian rhythm, glucose tolerance test, insulin sensitivity index
- MeSH terms
- Insulin Secretion, Adult, Arginine, Body Weight, Circadian Rhythm, Female, Glucose Tolerance Test, Humans, Insulin, Male, Obesity, Reference Values, Tolbutamide, Body Mass Index
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
