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      The impact of the COVID‐19 pandemic on glycaemic control in people with diabetes: A systematic review and meta‐analysis

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          Abstract

          Aim

          To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID‐19) pandemic and lockdown (LD) on glycaemic control in people with diabetes.

          Materials and Methods

          We searched multiple databases up to 2 February 2021 for studies reporting HbA1c, time in range (TIR), average or fasting glucose, severe hypoglycaemia and diabetic ketoacidosis. Data were pooled using random effects meta‐analysis and are presented as mean difference (MD) with 95% confidence intervals (CI). This review was preregistered on PROSPERO (CRD42020179319).

          Results

          We include 59 studies; 44 (n = 15 464) were included in quantitative syntheses and 15 were narratively synthesized. Pooled data were grouped by diabetes type. Results from 28 studies (n = 5048 type 1 diabetes [T1D] and combined diabetes participants) showed that TIR increased during LD compared with before LD (MD 2.74%, 95% CI 1.80% to 3.69%). Data from 10 studies (n = 1294 T1D participants) showed that TIR increased after LD compared with before LD (MD 5.14%, 95% CI 3.12% to 7.16%). Pooled results from 12 studies (n = 4810 T1D and type 2 diabetes participants) resulted in average glucose decreasing after LD compared with before LD (MD –6.86 mg/dl, 95% CI –8.54 to –5.18). Results for other outcomes, including HbA1c, were not statistically significantly different.

          Conclusions

          The COVID‐19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, although there was insufficient evidence to suggest that this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high‐income countries; more research is needed in less advantaged populations.

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          Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020

          On March 18, 2020, this report was posted online as an MMWR Early Release. Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries ( 1 ). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic ( 2 ). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19–associated illness and death than are younger persons ( 3 ). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years ( 3 ). In this report, COVID-19 cases in the United States that occurred during February 12–March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities ( 4 ). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups. Data from cases reported from 49 states, the District of Columbia, and three U.S. territories ( 5 ) to CDC during February 12–March 16 were analyzed. Cases among persons repatriated to the United States from Wuhan, China and from Japan (including patients repatriated from cruise ships) were excluded. States and jurisdictions voluntarily reported data on laboratory-confirmed cases of COVID-19 using previously developed data collection forms ( 6 ). The cases described in this report include both COVID-19 cases confirmed by state or local public health laboratories as well as those with a positive test at the state or local public health laboratories and confirmation at CDC. No data on serious underlying health conditions were available. Data on these cases are preliminary and are missing for some key characteristics of interest, including hospitalization status (1,514), ICU admission (2,253), death (2,001), and age (386). Because of these missing data, the percentages of hospitalizations, ICU admissions, and deaths (case-fatality percentages) were estimated as a range. The lower bound of these percentages was estimated by using all cases within each age group as denominators. The corresponding upper bound of these percentages was estimated by using only cases with known information on each outcome as denominators. As of March 16, a total of 4,226 COVID-19 cases had been reported in the United States, with reports increasing to 500 or more cases per day beginning March 14 (Figure 1). Among 2,449 patients with known age, 6% were aged ≥85, 25% were aged 65–84 years, 18% each were aged 55–64 years and 45–54 years, and 29% were aged 20–44 years (Figure 2). Only 5% of cases occurred in persons aged 0–19 years. FIGURE 1 Number of new coronavirus disease 2019 (COVID-19) cases reported daily*,† (N = 4,226) — United States, February 12–March 16, 2020 * Includes both COVID-19 cases confirmed by state or local public health laboratories, as well as those testing positive at the state or local public health laboratories and confirmed at CDC. † Cases identified before February 28 were aggregated and reported during March 1–3. The figure is a histogram, an epidemiologic curve showing 4,226 coronavirus disease 2019 (COVID-19) cases, by date of case report, in the United States during February 12–March 16, 2020. Figure 2 Coronavirus disease 2019 (COVID-19) hospitalizations,* intensive care unit (ICU) admissions, † and deaths, § by age group — United States, February 12– March 16, 2020 * Hospitalization status missing or unknown for 1,514 cases. † ICU status missing or unknown for 2,253 cases. § Illness outcome or death missing or unknown for 2,001 cases. The figure is a bar chart showing the number of coronavirus disease 2019 (COVID-19) hospitalizations, intensive care unit admissions, and deaths, by age group, in the United States during February 12– March 16, 2020. Among 508 (12%) patients known to have been hospitalized, 9% were aged ≥85 years, 36% were aged 65–84 years, 17% were aged 55–64 years, 18% were 45–54 years, and 20% were aged 20–44 years. Less than 1% of hospitalizations were among persons aged ≤19 years (Figure 2). The percentage of persons hospitalized increased with age, from 2%–3% among persons aged ≤19 years, to ≥31% among adults aged ≥85 years. (Table). TABLE Hospitalization, intensive care unit (ICU) admission, and case–fatality percentages for reported COVID–19 cases, by age group —United States, February 12–March 16, 2020 Age group (yrs) (no. of cases) %* Hospitalization ICU admission Case-fatality 0–19 (123) 1.6–2.5 0 0 20–44 (705) 14.3–20.8 2.0–4.2 0.1–0.2 45–54 (429) 21.2–28.3 5.4–10.4 0.5–0.8 55–64 (429) 20.5–30.1 4.7–11.2 1.4–2.6 65–74 (409) 28.6–43.5 8.1–18.8 2.7–4.9 75–84 (210) 30.5–58.7 10.5–31.0 4.3–10.5 ≥85 (144) 31.3–70.3 6.3–29.0 10.4–27.3 Total (2,449) 20.7–31.4 4.9–11.5 1.8–3.4 * Lower bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group; upper bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group with known hospitalization status, ICU admission status, or death. Among 121 patients known to have been admitted to an ICU, 7% of cases were reported among adults ≥85 years, 46% among adults aged 65–84 years, 36% among adults aged 45–64 years, and 12% among adults aged 20–44 years (Figure 2). No ICU admissions were reported among persons aged ≤19 years. Percentages of ICU admissions were lowest among adults aged 20–44 years (2%–4%) and highest among adults aged 75–84 years (11%–31%) (Table). Among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years (Table) (Figure 2). Discussion Since February 12, 4,226 COVID-19 cases were reported in the United States; 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. These findings are similar to data from China, which indicated >80% of deaths occurred among persons aged ≥60 years ( 3 ). These preliminary data also demonstrate that severe illness leading to hospitalization, including ICU admission and death, can occur in adults of any age with COVID-19. In contrast, persons aged ≤19 years appear to have milder COVID-19 illness, with almost no hospitalizations or deaths reported to date in the United States in this age group. Given the spread of COVID-19 in many U.S. communities, CDC continues to update current recommendations and develop new resources and guidance, including for adults aged ≥65 years as well as those involved in their care ( 7 , 8 ). Approximately 49 million U.S. persons are aged ≥65 years ( 9 ), and many of these adults, who are at risk for severe COVID-19–associated illness, might depend on services and support to maintain their health and independence. To prepare for potential COVID-19 illness among persons at high risk, family members and caregivers of older adults should know what medications they are taking and ensure that food and required medical supplies are available. Long-term care facilities should be particularly vigilant to prevent the introduction and spread of COVID-19 ( 10 ). In addition, clinicians who care for adults should be aware that COVID-19 can result in severe disease among persons of all ages. Persons with suspected or confirmed COVID-19 should monitor their symptoms and call their provider for guidance if symptoms worsen or seek emergency care for persistent severe symptoms. Additional guidance is available for health care providers on CDC’s website (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html). This report describes the current epidemiology of COVID-19 in the United States, using preliminary data. The findings in this report are subject to at least five limitations. First, data were missing for key variables of interest. Data on age and outcomes, including hospitalization, ICU admission, and death, were missing for 9%–53% of cases, which likely resulted in an underestimation of these outcomes. Second, further time for follow-up is needed to ascertain outcomes among active cases. Third, the initial approach to testing was to identify patients among those with travel histories or persons with more severe disease, and these data might overestimate the prevalence of severe disease. Fourth, data on other risk factors, including serious underlying health conditions that could increase risk for complications and severe illness, were unavailable at the time of this analysis. Finally, limited testing to date underscores the importance of ongoing surveillance of COVID-19 cases. Additional investigation will increase the understanding about persons who are at risk for severe illness and death from COVID-19 and inform clinical guidance and community-based mitigation measures.* The risk for serious disease and death in COVID-19 cases among persons in the United States increases with age. Social distancing is recommended for all ages to slow the spread of the virus, protect the health care system, and help protect vulnerable older adults. Further, older adults should maintain adequate supplies of nonperishable foods and at least a 30-day supply of necessary medications, take precautions to keep space between themselves and others, stay away from those who are sick, avoid crowds as much as possible, avoid cruise travel and nonessential air travel, and stay home as much as possible to further reduce the risk of being exposed ( 7 ). Persons of all ages and communities can take actions to help slow the spread of COVID-19 and protect older adults. † Summary What is already known about this topic? Early data from China suggest that a majority of coronavirus disease 2019 (COVID-19) deaths have occurred among adults aged ≥60 years and among persons with serious underlying health conditions. What is added by this report? This first preliminary description of outcomes among patients with COVID-19 in the United States indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years. What are the implications for public health practice? COVID-19 can result in severe disease, including hospitalization, admission to an intensive care unit, and death, especially among older adults. Everyone can take actions, such as social distancing, to help slow the spread of COVID-19 and protect older adults from severe illness.
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            Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study

            Summary Background Although diabetes has been associated with COVID-19-related mortality, the absolute and relative risks for type 1 and type 2 diabetes are unknown. We assessed the independent effects of diabetes status, by type, on in-hospital death in England in patients with COVID-19 during the period from March 1 to May 11, 2020. Methods We did a whole-population study assessing risks of in-hospital death with COVID-19 between March 1 and May 11, 2020. We included all individuals registered with a general practice in England who were alive on Feb 16, 2020. We used multivariable logistic regression to examine the effect of diabetes status, by type, on in-hospital death with COVID-19, adjusting for demographic factors and cardiovascular comorbidities. Because of the absence of data on total numbers of people infected with COVID-19 during the observation period, we calculated mortality rates for the population as a whole, rather than the population who were infected. Findings Of the 61 414 470 individuals who were alive and registered with a general practice on Feb 16, 2020, 263 830 (0·4%) had a recorded diagnosis of type 1 diabetes, 2 864 670 (4·7%) had a diagnosis of type 2 diabetes, 41 750 (0·1%) had other types of diabetes, and 58 244 220 (94·8%) had no diabetes. 23 698 in-hospital COVID-19-related deaths occurred during the study period. A third occurred in people with diabetes: 7434 (31·4%) in people with type 2 diabetes, 364 (1·5%) in those with type 1 diabetes, and 69 (0·3%) in people with other types of diabetes. Unadjusted mortality rates per 100 000 people over the 72-day period were 27 (95% CI 27–28) for those without diabetes, 138 (124–153) for those with type 1 diabetes, and 260 (254–265) for those with type 2 diabetes. Adjusted for age, sex, deprivation, ethnicity, and geographical region, compared with people without diabetes, the odds ratios (ORs) for in-hospital COVID-19-related death were 3·51 (95% CI 3·16–3·90) in people with type 1 diabetes and 2·03 (1·97–2·09) in people with type 2 diabetes. These effects were attenuated to ORs of 2·86 (2·58–3·18) for type 1 diabetes and 1·80 (1·75–1·86) for type 2 diabetes when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease, or heart failure. Interpretation The results of this nationwide analysis in England show that type 1 and type 2 diabetes were both independently associated with a significant increased odds of in-hospital death with COVID-19. Funding None.
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              Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study

              Summary Background Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. Methods We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. Findings Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017–19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48–53 mmol/mol (6·5–7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50–3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47–1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48–53 mmol/mol (HR 1·22 [95% CI 1·15–1·30, p<0·0001] for 59–74 mmol/mol [7·6–8·9%] and 1·36 [1·24–1·50, p<0·0001] for 75–85 mmol/mol [9·0–9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0–29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60–3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53–3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11–2·56, p<0·0001) and 1·60 (1·47–1·75, p<0·0001). Interpretation Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. Funding None.
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                Author and article information

                Contributors
                llom1@leicester.ac.uk
                Journal
                Diabetes Obes Metab
                Diabetes Obes Metab
                10.1111/(ISSN)1463-1326
                DOM
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                1462-8902
                1463-1326
                20 June 2022
                September 2022
                20 June 2022
                : 24
                : 9 ( doiID: 10.1111/dom.v24.9 )
                : 1850-1860
                Affiliations
                [ 1 ] Diabetes Research Centre University of Leicester Leicester UK
                [ 2 ] Nuffield Department of Primary Care Health Sciences University of Oxford Oxford UK
                [ 3 ] Medical Sciences Division University of Oxford Oxford UK
                [ 4 ] Freelance Systematic Reviewer Warwickshire UK
                Author notes
                [*] [* ] Correspondence

                Lauren L. O'Mahoney, PhD, Diabetes Research Centre, University of Leicester, Leicester, UK.

                Email: llom1@ 123456leicester.ac.uk

                Author information
                https://orcid.org/0000-0002-2786-3290
                https://orcid.org/0000-0002-0410-5788
                https://orcid.org/0000-0003-0947-3640
                https://orcid.org/0000-0002-2849-6672
                https://orcid.org/0000-0003-2332-5185
                https://orcid.org/0000-0002-0946-3904
                https://orcid.org/0000-0002-5104-6629
                https://orcid.org/0000-0002-9091-7853
                https://orcid.org/0000-0002-9683-2295
                https://orcid.org/0000-0003-1832-3679
                https://orcid.org/0000-0001-6843-8568
                https://orcid.org/0000-0003-2343-7099
                https://orcid.org/0000-0001-9898-3049
                Article
                DOM14771
                10.1111/dom.14771
                9347483
                35603919
                d89416b8-b269-469e-9815-2f9b0d18152e
                © 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 04 May 2022
                : 29 March 2022
                : 17 May 2022
                Page count
                Figures: 4, Tables: 1, Pages: 11, Words: 6761
                Funding
                Funded by: National Institute for Health Research, Applied Research Collaboration Oxford
                Funded by: NIHR Applied Research Collaboration East Midlands
                Funded by: Thames Valley at Oxford Health NHS Foundation Trust
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                September 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:03.08.2022

                Endocrinology & Diabetes
                continuous glucose monitoring,systematic review,type 1 diabetes,type 2 diabetes

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