key: cord-0697680-a9xxk7vc authors: Tanji, Yasuhiro; Sawada, Shojiro; Watanabe, Taichi; Mita, Takashi; Kobayashi, Yasutaka; Murakami, Takahisa; Metoki, Hirohito; Akai, Hiroaki title: Impact of COVID-19 pandemic on glycemic control among outpatients with type 2 diabetes in Japan: A hospital-based survey from a country without lockdown date: 2021-04-30 journal: Diabetes Res Clin Pract DOI: 10.1016/j.diabres.2021.108840 sha: 0cc9050947a430a4863c3a6124e6fdf6a6881f2b doc_id: 697680 cord_uid: a9xxk7vc Aims Some studies have reported changes in glycemic control of patients with diabetes mellitus under lockdown. However, no previous study examined the impact of the pandemic on glycemic control in patients with diabetes in countries that did not introduce a lockdown such as Japan. This study aimed to assess changes in glycemic control during the pandemic in patients with type 2 diabetes treated at a Japanese clinic. Methods We conducted a historical cohort study, using electronic medical records of patients with type 2 diabetes who visited our clinic between January 2019 and August 2020. Differences in HbA1c values before and after the outbreak of COVID-19 were the primary outcome, examined using the linear mixed model. Results HbA1c values significantly increased from 7.45% to 7.53% after the state of emergency was introduced (n=1,009). Furthermore, a deterioration in HbA1c values was observed in particular among women, patients aged ≥ 65 years, those with body mass index of ≥ 25 kg/m2, and those that were not using insulin. Conclusions Glycemic control deteriorated in patients with type 2 diabetes during the pandemic even in a country without a national lockdown. The coronavirus disease 2019 (COVID- 19) was first identified in Wuhan, China, in late 2019, before spreading worldwide [1] . The World Health Organization declared the COVID-19 outbreak a pandemic on March 11, 2020 [2] . Subsequently, many countries introduced lockdowns and other types of restrictions to contain the spread of infection. In Japan, the first case of COVID-19 was identified on January 14, 2020; the number of confirmed cases increased rapidly thereafter, and on April 7, 2020, the Japanese government declared a state of emergency, calling on the citizens to remain home and refrain from non-essential outings. This approach was in contrast to that of many other countries, which opted for national lockdowns. Preliminary research has shown that in countries that introduced lockdowns, patients with diabetes mellitus were subject to treatment delays, and discontinuation of care, service, and medicine supply. In fact, the World Health Organization reported that diabetes treatment was partially or completely disrupted in 49% of 155 countries surveyed in May 2020 [3] . Meanwhile, in Japan, diabetes treatment continued as usual, without evidence of treatment delay or discontinuation. Nevertheless, the state of emergency has affected the nation's habits, introducing social distancing, the requirement to wear a mask in public, and remote working. Such large-scale behavioral changes may have affected glycemic control among patients with diabetes mellitus even in the absence of a lockdown. Maintaining good glycemic control during the COVID-19 pandemic is paramount to patients with diabetes mellitus. The deterioration of glycemic control may lead to chronic complications of diabetes mellitus (such as macro-and micro-vascular disease) and increase the risk of infection and associated mortality. In fact, patients with diabetes mellitus have been shown to be at increased risk of morbidity and mortality during the pandemic [4] . Moreover, COVID-19 patients with uncontrolled type 2 diabetes have markedly higher mortality rates than do those with good glycemic control [5] . Previous studies have examined the impact of the COVID-19 pandemic on glycemic control among patients with diabetes mellitus; however, the findings have been inconsistent. For example, a study from Spain reported improved glycemic control in 307 patients with type 1 diabetes after 8 weeks of lockdown compared to before lockdown. These patients were administered multiple daily insulin injections or insulin pump therapy, using continuous glucose monitoring (CGM). This improvement in glycemic control may be due to improved disease self-management under lockdown, made possible by decreased workload, improved diet, and more time for diabetes management [6] . Similar findings were reported in the Netherlands [7] , France [8] , Italy [9, 10] , Greece [11] and by a separate group in Spain [12] . However, these studies included only patients with type 1 diabetes that were using CGM; these patients may have been better placed to manage their disease than were their counterparts, as they could easily monitor their blood glucose levels. However, a study in the UK has shown that glycemic control worsened in patients with type 1 diabetes that were not using CGM [13] . This finding may be accounted for by the restricted availability of insulin or glucostrips under lockdown. Meanwhile, reports on glycemic control in patients with type 2 diabetes during the COVID-19 pandemic were mixed. A recent study from India reported that glycemic control worsened in 143 patients with type 2 diabetes after 3 weeks of lockdown [14] . This finding may have been due to psychological stress, and difficulty in obtaining medication and medical advice under lockdown. Similar findings were reported in China [15] , Korea [16] and by another group in India [17] . In contrast, a separate study from India [18] and one from Greece [19] reported that glycemic control improved; nevertheless, it was reported as unchanged in studies from Italy [20, 21] and Turkey [22] . In addition, a French study has shown that glycemia was less well controlled in patients with gestational diabetes mellitus [23], likely due to reduced physical activity, modified dietary habits, and anxiety experienced under lockdown. Overall, these findings suggest that the impact of the COVID-19 pandemic on glycemic control differs depending on the type of diabetes mellitus and the region of the world. However, most previous studies were performed in countries that did impose lockdowns, and no previous study has examined the impact of the pandemic on glycemic control of patients with diabetes in a country that did not impose a lockdown. The present study aimed to evaluate the changes in glycemic control associated with the COVID-19 pandemic in Japanese patients with type 2 diabetes. We performed a historical cohort study that involved reviewing electronic medical records of patients with diabetes mellitus, treated at the Tohoku Medical and Pharmaceutical University Hospital in Sendai, which is a central city in northeast Japan. We included all patients with diabetes mellitus who visited our clinic from January 1, values (< 7.0%, ≥ 7.0%), and insulin use vs. no insulin use. Results were expressed as mean±standard deviation or mean and 95% confidence interval. P-values of < 0.05 were considered indicative of a statistically significant finding. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC, USA). This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Committee of the Tohoku Pharmaceutical University Hospital (2020-2-214). As this was an observational study based on previously collected clinical data, the study was exempt from the informed consent requirement. Instead, relevant information regarding the study was made available to the public and opt-out opportunities were provided. This study included 1,816 patients with diabetes mellitus who visited our clinic between January 1, 2019, and August 31, 2020. We excluded 88 and 97 patients with type 1 or another type of diabetes, respectively. A total of 1,631 patients with type 2 diabetes were included after initial screening; subsequently, we excluded 88, 508, and 26 patients with a history of hospitalization during the observation period, < 180 days of clinical data, and missing clinical data, respectively. Finally, 1,009 patients with type 2 diabetes were included in further analysis (Fig. 1) . Baseline characteristics of the selected patients are presented in Table 1 Table 1 . Additionally, in Japan, self-monitoring of blood glucose (SMBG) is currently reimbursed for patients with diabetes receiving insulin injections. In our study, 91.4% of the patients who were treated with insulin performed SMBG, and they measured their blood glucose level 39.9 ± 16.3 times / month. In contrast, patients who were not treated with insulin did not perform SMBG. The linear mixed model adjusted for age, sex, BMI, insulin use, and year of measurement revealed that HbA1c values were the highest between January and March; subsequently, they fell gradually after April, reaching the lowest values in the period between September and November ( Fig. 2A) . Using a similar model revealed that BMI values were highest in January and then gradually declined, reaching the lowest values in the period from August to October (Fig. 2B ). A model adjusted for sex, age, BMI, insulin use, and month and year of measurement revealed that HbA1c values significantly deteriorated after the state of emergency was declared in Japan (Fig. 3) . Furthermore, HbA1c values significantly increased among women, patients aged ≥ 65 years and those with BMI of ≥ 25 kg/m 2 , as well as those that did not use insulin (Fig. 3) . When we performed stratified analysis based on baseline HbA1c values (< 7.0%, ≥ 7.0%), we observed that HbA1c values significantly increased after the state of emergency in patients with a baseline HbA1c level of < 7.0% (6.42% to 6.60%, p < 0.0001). In contrast, HbA1c values did not change in patients with a baseline HbA1c level of ≥ 7.0% (7.89% to 7.92%, p = 0.342). The group with baseline HbA1c < 7.0% included 24.9% insulin users, while the group with baseline HbA1c ≥ 7.0% included 34.4% insulin users. Meanwhile, BMI in patients with type 2 diabetes was the same before and after the state of emergency was declared (Fig. 4) . Finally, change in BMI was similar in all subgroups (Fig. 4) . In the present study, we investigated the impact of the COVID- 19 reported transitioning to a healthy diet and lowering their alcohol intake [28] . These findings suggest that behavioral management, including dietary habits, physical activity, medication and insulin adjustment, work routine, stress levels, and social relationships may affect glycemic control in patients with diabetes mellitus. However, the present study did not account for these behavioral parameters, which is a limitation of the present study. In stratified analyses, we identified four subgroups particularly vulnerable to the worsening of glycemic control during the COVID-19 pandemic. First, HbA1c values significantly increased among women but not among men with diabetes mellitus. A recent study conducted in Japan reported that psychological distress associated with the COVID-19 pandemic was significantly larger among women than among men [29] . Women tend to be more affected by the social and economic consequences of a pandemic than do men [30] . In fact, a study of patients with diabetes mellitus in Denmark reported that women had more COVID-19-specific diabetes-related worries, suggesting getting infected may have greater consequences for women than it does for men with diabetes [31] . In the present study, women may have experienced worsened glycemic control due to high psychological stress associated with the pandemic. [35, 36] . Thus, in the present study, patients with BMI of ≥ 25 kg/m 2 may have experienced the worsening of glycemic control due to changes in their dietary patterns. Fourth, HbA1c values significantly increased in patients that were not receiving insulin treatment but not in those that were receiving such treatment. In Japan, SMBG or flash glucose monitoring (FGM) are currently reimbursed for patients with type 1 and 2 diabetes receiving daily insulin injections. These patients can monitor their glucose levels, using SMBG or FGM at home and adjust their insulin doses, dietary intake, and physical activity, as required. In contrast, SMBG or FGM are not reimbursed for patients with type 2 diabetes not treated with insulin. Thus, patients with type 2 diabetes receiving insulin treatment, most of whom use SMBG or FGM, may have been better placed to self-manage their disease than were their counterparts. We further divided the subjects into two groups based on their baseline HbA1c level and observed the subsequent changes. The group with baseline HbA1c < 7.0% received less treatment with insulin than the group with baseline HbA1c ≥ 7.0%. The former group showed a significant increase in HbA1c after a state of emergency was introduced, while the latter group showed no change in HbA1c. As mentioned above, SMBG is reimbursed for insulin users in Japan. Thus, the group with baseline HbA1c ≥ 7.0% which includes many insulin users, could self-monitor blood glucose levels unlike the group with baseline HbA1c < 7.0%. Thus, the high HbA1c group may have been less susceptible to worsening blood glucose control during the COVID-19 pandemic. On the other hand, it is necessary to consider the "regression toward the mean", which is observed when the baseline value is divided into two parts, and subsequent changes are observed. In the present study, BMI values remained unchanged after the state of emergency was introduced. Herein, we analyzed data collected until August 2020; therefore, the lack of change in BMI may be due to the short observation period. Previous studies on the impact of the COVID-19 pandemic on body weight in patients with diabetes mellitus were inconsistent, reporting an increase [7] , no change [18, [21] [22] [23] , and a decrease [19] . These previous studies also had short observation periods. This study has some limitations. First, this was a single-center retrospective study; however, the sample size was much larger than those of the previous studies [6, 7, 9-15, 18-20, 22 This study included 1,816 patients with diabetes mellitus who visited our clinic between January 1, 2019, and August 31, 2020. Finally, 1,009 patients with type 2 diabetes were included in further analysis. HbA1c values and their 95% confidence intervals for each month were calculated, using the mixed linear model adjusted for age, sex, body mass index, insulin use, and year of measurement. Body mass index (BMI) values and their 95% confidence intervals for each month were calculated, using the mixed linear model adjusted for age, sex, HbA1c levels, insulin use, and year of measurement.  Lockdowns against COVID-19 have affected glycemic control in patients with diabetes.  Glycemic control deteriorated also in patients in countries without lockdowns.  Pandemic-related behavioral changes of a population affected glycemic control.  The effect was greatest among women, older adults, and patients with obesity.  The effect was little among patients receiving insulin treatment. 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Population health management Abbreviations: BMI, body mass index We would like to thank Editage (www.editage.com) for English language editing. The authors declare that they have no competing interests.