Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects and Measurements
2.2. Ethics
2.3. Analytical Assays
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Patients
3.2. Impact of Stress Hyperglycemia
3.3. Circulating Osteocalcin as a Marker for Hyperglycemia and Prognosis
3.4. Impact of the Composition of Artificial Nutrition
3.5. Circulating Inflammatory Markers
3.6. Ancillary Analyses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Alkundi, A.; Mahmoud, I.; Musa, A.; Naveed, S.; Alshawwaf, M. Clinical characteristics and outcomes of COVID-19 hospitalized patients with diabetes in the United Kingdom: A retrospective single centre study. Diabetes Res. Clin. Pract. 2020, 165, 108263. [Google Scholar] [CrossRef]
- Wake, D.J.; Gibb, F.W.; Kar, P.; Kennon, B.; Klonoff, D.C.; Rayman, G.; Rutter, M.K.; Sainsbury, C.; Semple, R.K. Endocrinology in the time of COVID-19: Remodelling diabetes services and emerging innovation. Eur. J. Endocrinol. 2020, 183, G67–G77. [Google Scholar] [CrossRef] [PubMed]
- Hussain, A.; Bhowmik, B.; do Vale Moreira, N.C. COVID-19 and diabetes: Knowledge in progress. Diabetes Res. Clin. Pract. 2020, 162, 108142. [Google Scholar] [CrossRef] [PubMed]
- Sardu, C.; D’Onofrio, N.; Balestrieri, M.L.; Barbieri, M.; Rizzo, M.R.; Messina, V.; Maggi, P.; Coppola, N.; Paolisso, G.; Marfella, R. Outcomes in Patients With Hyperglycemia Affected by COVID-19: Can We Do More on Glycemic Control? Diabetes Care 2020, 43, 1408–1415. [Google Scholar] [CrossRef]
- Mantovani, A.; Byrne, C.D.; Zheng, M.H.; Targher, G. Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies. Nutr. Metab. Cardiovasc. Dis. 2020, 30, 1236–1248. [Google Scholar] [CrossRef]
- Singer, P.; Blaser, A.R.; Berger, M.M.; Alhazzani, W.; Calder, P.C.; Casaer, M.P.; Hiesmayr, M.; Mayer, K.; Montejo, J.C.; Pichard, C.; et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin. Nutr. 2019, 38, 48–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Solomon, D.M.; Hollands, J.M.; Pontiggia, L.; Delic, J.J.; Bingham, A.L. Metabolic Complications Occur More Frequently in Older Patients Receiving Parenteral Nutrition. Nutr. Clin. Pract. 2020, 35, 627–633. [Google Scholar] [CrossRef]
- Dungan, K.M.; Braithwaite, S.S.; Preiser, J.C. Stress hyperglycaemia. Lancet 2009, 373, 1798–1807. [Google Scholar] [CrossRef]
- Lheureux, O.; Prevedello, D.; Preiser, J.C. Update on glucose in critical care. Nutrition 2019, 59, 14–20. [Google Scholar] [CrossRef]
- Bilotta, F.L.; Arcidiacono, B.; Messineo, S.; Greco, M.; Chiefari, E.; Britti, D.; Nakanishi, T.; Foti, D.P.; Brunetti, A. Insulin and osteocalcin: Further evidence for a mutual cross-talk. Endocrine 2018, 59, 622–632. [Google Scholar] [CrossRef] [Green Version]
- Gower, B.A.; Pollock, N.K.; Casazza, K.; Clemens, T.L.; Goree, L.L.; Granger, W.M. Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and beta-cell function in overweight adults. J. Clin. Endocrinol. Metab. 2013, 98, E1173–E1180. [Google Scholar] [CrossRef] [Green Version]
- Iglesias, P.; Arrieta, F.; Pinera, M.; Botella-Carretero, J.I.; Balsa, J.A.; Zamarrón, I.; Menacho, M.; Díez, J.J.; Muñoz, T.; Vázquez, C. Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance. Clin. Endocrinol. 2011, 75, 184–188. [Google Scholar] [CrossRef]
- American Diabetes Association. 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019, 42, S173–S181. [Google Scholar] [CrossRef] [Green Version]
- Barazzoni, R.; Bischoff, S.C.; Breda, J.; Wickramasinghe, K.; Krznarić, Z.; Nitzan, D.; Pirlich, M.; Singer, P. ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection. Clin. Nutr. 2020, 39, 1631–1638. [Google Scholar] [CrossRef]
- Zoch, M.L.; Clemens, T.L.; Riddle, R.C. New insights into the biology of osteocalcin. Bone 2016, 82, 42–49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Janghorbani, M.; Feskanich, D.; Willett, W.C.; Hu, F. Prospective study of diabetes and risk of hip fracture: The Nurses’ Health Study. Diabetes Care 2006, 29, 1573–1578. [Google Scholar] [CrossRef] [Green Version]
- Starup-Linde, J.; Frost, M.; Vestergaard, P.; Abrahamsen, B. Epidemiology of Fractures in Diabetes. Calcif. Tissue Int. 2017, 100, 109–121. [Google Scholar] [CrossRef] [PubMed]
- Li, T.; Wang, L.; Wang, H.; Gao, Y.; Hu, X.; Li, X.; Zhang, S.; Xu, Y.; Wei, W. Characteristics of laboratory indexes in COVID-19 patients with non-severe symptoms in Hefei City, China: Diagnostic value in organ injuries. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 2447–2455. [Google Scholar] [CrossRef]
- Liu, D.-M.; Guo, X.-Z.; Tong, H.-J.; Tao, B.; Sun, L.-H.; Zhao, H.-Y.; Ning, G.; Liu, J.-M. Association between osteocalcin and glucose metabolism: A meta-analysis. Osteoporos. Int. 2015, 26, 2823–2833. [Google Scholar] [CrossRef] [PubMed]
- Riddle, M.C.; Buse, J.B.; Franks, P.W.; Knowler, W.C.; Ratner, R.E.; Selvin, E.; Wexler, D.J.; Kahn, S.E. COVID-19 in People with Diabetes: Urgently Needed Lessons From Early Reports. Diabetes Care 2020, 43, 1378–1381. [Google Scholar] [CrossRef]
- Hartmann-Boyce, J.; Morris, E.; Goyder, C.; Kinton, J.; Perring, J.; Nunan, D.; Mahtani, K.; Buse, J.B.; Del Prato, S.; Ji, L.; et al. Diabetes and COVID-19: Risks, Management, and Learnings from Other National Disasters. Diabetes Care 2020, 43, 1695–1703. [Google Scholar] [CrossRef]
- Targher, G.; Mantovani, A.; Wang, X.-B.; Yan, H.-D.; Sun, Q.-F.; Pan, K.-H.; Byrne, C.D.; Zheng, K.I.; Chen, Y.-P.; Eslam, M.; et al. Patients with diabetes are at higher risk for severe illness from COVID-19. Diabetes Metab. 2020, 46, 335–337. [Google Scholar] [CrossRef]
- Wang, S.; Ma, P.; Zhang, S.; Song, S.; Wang, Z.; Ma, Y.; Xu, J.; Wu, F.; Duan, L.; Yin, Z.; et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: A multi-centre retrospective study. Diabetologia 2020, 63, 2102–2111. [Google Scholar] [CrossRef] [PubMed]
- Xiu, F.; Stanojcic, M.; Diao, L.; Jeschke, M.G. Stress hyperglycemia, insulin treatment, and innate immune cells. Int. J. Endocrinol. 2014, 2014, 486403. [Google Scholar] [CrossRef] [Green Version]
- Krenitsky, J. Glucose control in the intensive care unit: A nutrition support perspective. Nutr. Clin. Pract. 2011, 26, 31–43. [Google Scholar] [CrossRef]
- Simpson, F.; Doig, G.S. Parenteral vs. enteral nutrition in the critically ill patient: A meta-analysis of trials using the intention to treat principle. Intensive Care Med. 2005, 31, 12–23. [Google Scholar] [CrossRef]
- Doig, G.S.; Simpson, F. CALORIES trial offers confirmatory evidence that parenteral nutrition does not cause infectious complications in critically ill patients. Evid. Based Med. 2015, 20, 60. [Google Scholar] [CrossRef] [PubMed]
- Reignier, J.; Boisrame-Helms, J.; Brisard, L.; Lascarrou, J.-B.; Hssain, A.A.; Anguel, N.; Argaud, L.; Asehnoune, K.; Asfar, P.; Bellec, F.; et al. Enteral versus parenteral early nutrition in ventilated adults with shock: A randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet 2018, 391, 133–143. [Google Scholar] [CrossRef]
- Heidegger, C.P.; Darmon, P.; Pichard, C. Enteral vs. parenteral nutrition for the critically ill patient: A combined support should be preferred. Curr. Opin. Crit. Care 2008, 14, 408–414. [Google Scholar] [CrossRef] [PubMed]
Patients with COVID-19 (n = 23) | Non-COVID-19 Patients (n = 26) | p | |
---|---|---|---|
Male sex (n, %) | 19 (83) | 14 (54) | 0.039 |
Age (y) | 64 ± 9 | 71 ± 8 | 0.005 |
Time to ICU admission (days) | 8.1 ± 12.2 | 4.0 ± 6.7 | 0.158 |
Glucose metabolism | |||
Previous diabetes mellitus (n, %) | 6 (23) | 6 (26) | 0.806 |
HbA1c (%) | 6.0 ± 0.9 | 6.0 ± 0.8 | 0.977 |
Glycemia at ICU admission (mg/dl) | 148 ± 62 | 129 ± 41 | 0.207 |
Mean glycemia 1 week at ICU (mg/dl) | 136 ± 37 | 128 ± 39 | 0.523 |
Patients with stress hyperglycemia (n, %) * | 10 (48) | 12 (46) | 0.920 |
Patients with insulin infusion therapy (n, %) | 14 (61) | 7 (27) | 0.022 |
Artificial nutrition | |||
Time on TPN (days) | 15.7 ± 9.6 | 7.2 ± 10.1 | 0.004 |
Time on EN (days) | 10.0 ± 12.9 | 2.1 ± 4.3 | 0.010 |
Mean energy delivered (kcal/day) | 1222 ± 180 | 900 ± 329 | <0.001 |
Mean glucose delivered (g/day) | 141 ± 15 | 137 ± 29 | 0.600 |
Metabolic and inflammatory markers | |||
Osteocalcin (µg/L) | 7.0 ± 3.5 | 12.9 ± 7.0 | <0.001 |
Creatinine (mg/dl) | 1.0 ± 0.6 | 1.3 ± 1.3 | 0.309 |
CRP (mg/L) | 181 ± 129 | 161 ± 105 | 0.652 |
Procalcitonin (ng/mL) | 1.0 ± 2.2 | 2.4 ± 3.5 | 0.156 |
D-dimer (µg/mL) | 3791 ± 5403 | - | - |
IL-6 (pg/mL) | 280 ± 400 | - | - |
IL-12 (pg/mL) | 0.8 ± 1.1 | - | - |
Prognostic parameters | |||
ICU stay (days) | 24 ± 16 | 9 ± 13 | <0.001 |
Total hospital stay (days) | 46 ± 19 | 32 ± 39 | 0.138 |
Mortality (n, %) | 8 (35) | 7 (27) | 0.551 |
Patients with Stress Hyperglycemia (n = 22) | Patients without Stress Hyperglycemia (n = 27) | p | |
---|---|---|---|
COVID-19 diagnosis (n, %) | 10 (46) | 13 (48) | 0.851 |
Male sex (n, %) | 14 (64) | 19 (70) | 0.617 |
Age (y) | 69 ± 9 | 67 ± 10 | 0.574 |
Glucose metabolism | |||
Previous diabetes mellitus (n, %) | 9 (41) | 3 (11) | 0.022 |
HbA1c (%) | 6.4 ± 0.9 | 5.7 ± 0.7 | 0.013 |
Glycemia at ICU admission (mg/dl) | 162 ± 44 | 118 ± 42 | 0.003 |
Mean glycemia 1-week at ICU (mg/dl) | 161 ± 29 | 112 ± 26 | <0.001 |
Artificial nutrition | |||
Time on TPN (days) | 14.7 ± 11.8 | 8.3 ± 8.9 | 0.035 |
Time on EN (days) | 8.6 ± 12.6 | 3.5 ± 6.8 | 0.075 |
Mean energy delivered (kcal/day) | 1185 ± 296 | 941 ± 287 | 0.006 |
Mean glucose delivered (g/day) | 147 ± 24 | 132 ± 20 | 0.026 |
Metabolic and inflammatory markers | |||
Osteocalcin (µg/L) | 8.2 ± 5.3 | 12.3 ± 7.0 | 0.034 |
CRP (mg/L) | 170 ± 102 | 180 ± 144 | 0.808 |
Procalcitonin (ng/mL) | 1.8 ± 3.2 | 0.8 ± 1.5 | 0.314 |
Prognostic parameters | |||
ICU stay (days) | 23 ± 17 | 11 ± 13 | 0.007 |
Total hospital stay (days) | 47 ± 39 | 31 ± 23 | 0.090 |
Mortality (n, %) | 5 (19) | 10 (45) | 0.085 |
COVID-19 with Stress Hyperglycemia (n = 10) | COVID-19 without Stress Hyperglycemia (n = 13) | Non-COVID-19 with Stress Hyperglycemia (n = 12) | Non-COVID-19 without Stress Hyperglycemia (n = 14) | p for COVID-19 Effect | p for Hyperglycemia | p for Interaction | |
---|---|---|---|---|---|---|---|
Male sex (n, %) | 9 (90) | 10 (77) | 5 (42) | 9 (64) | 0.031 | 0.678 | |
Age (y) | 65 ± 8 | 63 ± 10 | 72 ± 9 | 71 ± 8 | 0.006 | 0.595 | 0.878 |
ICU stay (days) | 30 ± 17 | 20 ± 14 | 17 ± 15 | 2 ± 2 | <0.001 | 0.002 | 0.172 |
Total hospital stay (days) | 47 ± 20 | 46 ± 19 | 47 ± 52 | 20 ± 20 | 0.263 | 0.110 | 0.255 |
Mortality (n, %) | 5 (50) | 3 (23) | 5 (42) | 2 (14) | 0.391 | 0.120 | |
Osteocalcin (µg/L) | 6.2 ± 4.2 | 6.9 ± 4.3 | 9.8 ± 6.3 | 15.7 ± 6.2 | 0.001 | 0.027 | 0.172 |
CRP (mg/L) | 192 ± 98 | 173 ± 153 | 146 ± 108 | 230 ± 82 | 0.926 | 0.560 | 0.354 |
Procalcitonin (ng/mL) | 1.2 ± 2.9 | 0.7 ± 1.5 | 2.4 ± 3.7 | 1.3 ± 0.7 | 0.373 | 0.816 | 0.904 |
Patients with insulin infusion (n, %) | 8 (80) | 6 (46) | 7 (58) | 0 (0) | 0.040 | 0.041 | |
Time on TPN (days) | 16.4 ± 11.5 | 15.2 ± 8.4 | 13.3 ± 12.5 | 2.0 ± 1.3 | 0.003 | 0.020 | 0.060 |
Time on EN (days) | 13.5 ± 17.0 | 7.2 ± 8.3 | 4.6 ± 5.5 | 1.0 ± 0.5 | 0.004 | 0.045 | 0.750 |
Mean energy delivered (kcal/day) | 1274 ± 135 | 1182 ± 205 | 1109 ± 373 | 717 ± 121 | <0.001 | 0.001 | 0.029 |
Mean glucose delivered (g/day) | 140 ± 16 | 141 ± 15 | 153 ± 29 | 124 ± 21 | 0.721 | 0.029 | 0.015 |
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Arrieta, F.; Martinez-Vaello, V.; Bengoa, N.; Rosillo, M.; de Pablo, A.; Voguel, C.; Pintor, R.; Belanger-Quintana, A.; Mateo-Lobo, R.; Candela, A.; et al. Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition. Nutrients 2021, 13, 3010. https://doi.org/10.3390/nu13093010
Arrieta F, Martinez-Vaello V, Bengoa N, Rosillo M, de Pablo A, Voguel C, Pintor R, Belanger-Quintana A, Mateo-Lobo R, Candela A, et al. Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition. Nutrients. 2021; 13(9):3010. https://doi.org/10.3390/nu13093010
Chicago/Turabian StyleArrieta, Francisco, Victoria Martinez-Vaello, Nuria Bengoa, Marta Rosillo, Angélica de Pablo, Cristina Voguel, Rosario Pintor, Amaya Belanger-Quintana, Raquel Mateo-Lobo, Angel Candela, and et al. 2021. "Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition" Nutrients 13, no. 9: 3010. https://doi.org/10.3390/nu13093010
APA StyleArrieta, F., Martinez-Vaello, V., Bengoa, N., Rosillo, M., de Pablo, A., Voguel, C., Pintor, R., Belanger-Quintana, A., Mateo-Lobo, R., Candela, A., & Botella-Carretero, J. I. (2021). Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition. Nutrients, 13(9), 3010. https://doi.org/10.3390/nu13093010