key: cord-0831291-6sdnx0u2 authors: Zhan, Kegang; Zhang, Xiaohua; Wang, Bin; Jiang, Zheng; Fang, Xiaoyu; Yang, Sha; Jia, Hong; Li, Li; Cao, Guoqiang; Zhang, Kejun; Ma, Xiangyu title: Short and long-term prognosis of glycemic control in COVID-19 patients with type 2 diabetes date: 2022-01-30 journal: QJM DOI: 10.1093/qjmed/hcac020 sha: 8fe2d6c70a3df3e1ca2761d49139393b136a5134 doc_id: 831291 cord_uid: 6sdnx0u2 BACKGROUND AND AIM: To systematically evaluate the associations between glycemic control and short- to long-term outcomes in coronavirus disease 2019 (COVID-19) patients with type 2 diabetes (T2D). DESIGN AND METHODS: A multi-center prospective cohort study including 574 COVID-19 patients with T2D were conducted in Wuhan, China. All patients were followed-up 1 year after hospital discharge using a uniformed questionnaire including self-reported symptoms, and the chronic obstructive pulmonary disease (COPD) assessment test (CAT) items. RESULTS: Of the 574 patients, 443 (77.2%) had well-controlled blood glucose. Glycemic control was significantly associated with decreased risk of death (OR: 0.24, 95% CI: 0.10-0.57), ICU admission (OR: 0.22, 95% CI: 0.10-0.49), invasive mechanical ventilation (OR: 0.25, 95% CI: 0.08-0.72), disease progression (OR: 0.25, 95% CI: 0.11-0.55), and composite outcome (OR: 0.26, 95% CI: 0.14-0.49). The top five long-term sequelae include fatigue (31.5%), sweating (21.2%), chest tightness (15.1%), anxiety (12.2%), myalgia (10.6%), and short breath (6.4%). Glycemic control was associated with decreased risk of respiratory sequelae (OR: 0.42, 95% CI: 0.18-0.99, P = 0.048). CONCLUSIONS: Glycemic control was significantly associated with short-term outcomes in COVID-19 patients with T2D, and showed a significant association with long-term respiratory sequelae. The management and control of blood glucose has a positive impact on prognosis of COVID-19. Type 2 diabetes (T2D) has been identified as the second most common comorbidity of 59 coronavirus disease 2019 , and patients with T2D are at increased risk of 60 severe COVID-19 complications and worse prognosis (1) (2) (3) . In a multicenter national 61 study in China, T2D was present in 8.2% of patients, and the severe group had a higher 62 proportion of T2D (23.7% vs 6.8%) (4). Living systematic review and meta-analyses 63 showed that diabetes was independently associated with increased risk of in-hospital 64 severity and death of COVID-19 (5, 6). To date, no study has yet systematically evaluated whether glycemic control contributes 67 to short-term prognosis of COVID-19, as well as the long-term outcomes of survivors of 68 COVID-19 with T2D. Current evidence focused on the comparisons between pre-existing 69 T2D groups and control group to explore the risk factor ordinarily (2, 3, 5). However, 70 T2D is a highly complex and heterogeneous disease, for which studies have found that 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 year after discharge were the primary indicator of long-term outcomes. Post-sequelae 119 includes any one of systemic sequelae, respiratory sequelae, cardiovascular sequelae, 120 neurological sequelae and digestive sequelae, while emerging sequelae was defined as 121 symptoms that were not observed during hospitalization but were reported in follow-up. Meanwhile, CAT was commonly used to assess symptom burden of COVID-19 patients, 123 and CAT scores ≥ 10 was recommended as the threshold for maintenance treatment in 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 9 147 Baseline characteristics 149 A total of 574 COVID-19 patients with T2D were included in this study (Table 1 150 presented the baseline characteristics). Of them, 443 (77.2%) had well-controlled blood 0.14-0.49), after adjusted for disease severity at admission, age and sex (Table 2) . Survival curve also showed that there was a significant difference in terms of survival 168 rate between two groups (P<0.001) (Figure 3 ). We also explored the risk factors of the 169 short-term composite outcome using a multivariate logistic regression model, and Associations of glycemic control with long-term outcomes of COVID-19 176 Patients included in this study were further followed-up one year after hospital discharge. Table 2 , and Figure 5 ). The median of CAT score was 2 (0-5) in all 189 patients, while a total of 26 patients (8.4%) had CAT scores ≥10 (Table 4) . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 193 sequelae, respiratory sequelae, digestive sequelae, emerging sequelae, and CAT score ≥ 194 10. We found glycemic control was associated with decreased risk of respiratory sequelae 195 (OR: 0.42, 95% CI: 0.18-0.99, P=0.048) (Table 5) , and blood glucose levels was 196 significantly associated with increased risk of respiratory sequelae (OR for per unit: 1.11, 197 95% CI: 1.02-1.21, P=0.017) (Supplementary Table 3 ). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 12 209 Discussion 210 In this prospective cohort study, we systematically evaluated the associations between 211 glycemic control and short-to long-term outcomes of COVID-19 patients with T2D. Of 212 the 574 patients, 443 (77.2%) had well-controlled blood glucose. For short-term 213 outcomes, glycemic control was significantly associated with decreased risk of death, 214 ICU admission, invasive mechanical ventilation, disease progression, and composite 215 outcome. For long-term outcomes, glycemic control was significantly associated with 216 decreased risk of respiratory sequelae. Taken together, our study verified that glycemic 217 control was significantly associated with short-term outcomes in COVID-19 patients 218 with T2D, and showed a significant association with long-term respiratory sequelae. inhibitors, and sulfonylureas were associated with reduced risks of the COVID-19-related 228 mortality, while insulin and DPP4 inhibitors were associated with increases in risk (23). A study conducted in Wuhan, China also reported that insulin treatment was associated 230 with increased mortality in COVID-19 patients with T2D (24). However, another study in 231 Wuhan found metformin was associated with increased incidence of acidosis, and not 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 13 232 was not associated with increased 28-day all-cause mortality (8). A study in Korea 233 impacted that DPP-4i in monotherapy or combination with renin-angiotensin system 234 blockers shown protective effects against severe/lethal cases (25). Even some research 235 reported that there is no significant association between poor prognosis and glucose- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 14 255 patients, potentially high glycosylated angiotensin-converting enzyme 2 (ACE2) in 256 various organs may also increase SARS-CoV-2 viral binding sites, leading to a higher 257 propensity for COVID-19 infection and higher disease severity (32). In addition to short-term outcomes, we also followed-up the long-term outcomes of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 15 278 data analyses, which could introduce unexpected confounding if another parameter, 279 unmeasured but correlated to blood glucose concentration, were the actual driver of the 280 shown effect. Third, long-term outcomes may have been influenced by a severer short-281 term outcome, and the glycemic control status might vary after hospital discharge. In conclusion, our study provides valuable clues that glycemic control was significantly 288 associated with short -term outcomes in COVID-19 patients with T2D, and showed a 289 significant association with long-term respiratory sequelae. 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