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      Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis

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          Abstract

          Introduction

          and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications.

          Materials and methods

          A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications.

          Results

          The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections.

          Conclusion

          The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.

          Highlights

          • •

            A lockdown of India in an attempt to preventing the spread of the virus may adversely impact both diabetes control as well as its associated complications by putting a restriction on the available resources and changes in lifestyle.

          • •

            This is probably the first study to highlight that there is an increment in both the HBA1c as well as diabetes-related complications with increasing duration of a lockdown.

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          SARS-CoV-2: virus dynamics and host response

          Yu Chen, Lanjuan Li (2020)
          Since December, 2019, coronavirus disease 2019 (COVID-19) has affected more than 100 000 patients globally. 1 COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a case-fatality rate of 2·3%, with higher rates among elderly patients and patients with comorbidities. 2 Person-to-person transmission is efficient, with multiple clusters reported. Clinically, patients with COVID-19 present with respiratory symptoms, which is very similar to the presentation of other respiratory virus infections. Radiologically, COVID-19 is characterised by multifocal ground-glass opacities, even for patients with mild disease. 3 Knowledge of virus dynamics and host response are essential for formulating strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19. However, a systematic study on these aspects has not been done. In The Lancet Infectious Diseases, Kelvin To and colleagues 4 report the viral load and antibody profiles of a cohort of 23 patients admitted to hospital with COVID-19. In these patients, the viral load peaked during the first week of illness then gradually declined over the second week. Viral load was also shown to correlate with age. Furthermore, both IgG and IgM antibodies started to increase on around day 10 after symptom onset, and most patients had seroconversion within the first 3 weeks. Finally, the IgG and IgM antibody level against the SARS-CoV-2 internal nucleoprotein and the surface spike receptor binding domain correlated with neutralising activity. These findings have several practical implications. First, the high viral load during the early phase of illness suggests that patients could be most infectious during this period, and it might account for the high transmissibility of SARS-CoV-2. Furthermore, the high viral load on presentation suggests that SARS-CoV-2 could be susceptible to emergence of antiviral resistance. Second, age was associated with viral load in this study, which could explain the high degree of severe disease in older patients with SARS-CoV-2.5, 6 The high viral load in elderly patients is associated not only with low immunity but also with high expression of the ACE2 receptor (the cell-entry receptor for SARS-CoV-2) in older adults. 7 The timing of antibody seroconversion is crucial for determining the optimum timepoints for collecting serum specimens for antibody testing for diagnosis. Furthermore, this information is important for immunologists to choose the best timepoints for obtaining peripheral blood B cells for development of therapeutic monoclonal antibodies. 8 The major strength of the study by To and colleagues is the systematic analysis of the serial viral load and antibody profile for up to 4 weeks, which provides insights into viral and host interactions during the acute and convalescent phases. Another notable aspect is that self-collected posterior oropharyngeal saliva samples were used, instead of nasopharyngeal specimens, for viral load monitoring. Collection of nasopharyngeal specimens is an invasive procedure, and it is uncomfortable for the patient and poses an infection risk to health-care workers. Self-collected saliva is much more acceptable to patients and is safer for health-care workers. This study clearly shows the feasibility of using saliva for viral load monitoring. The information provided by To and colleagues is solid scientific evidence on COVID-19 for clinicians and scientists. Nonetheless, many questions are still outstanding on the viral characteristics and host response during infection. SARS-CoV-2 has been detected in faeces, blood, and urine samples,9, 10 and it is important to ascertain viral load dynamics in such samples, for prevention and control of the pandemic. Furthermore, the relation between viral load and disease severity needs to be further clarified. Studies with a larger sample size are needed to understand how different factors can affect viral load or antibody response. For example, immunocompromised patients might have higher viral load, prolonged viral shedding, and impaired antibody response. Future studies in the paediatric population are vital, because children seem to have much milder disease than in adults. Finally, a more detailed understanding of the innate and adaptive immune response against SARS-CoV-2 is important for understanding the pathogenesis and for designing vaccines. © 2020 Flickr-Ben (busy) 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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            Impact of a Natural Disaster on Diabetes

            Vivian A. Fonseca, Hayden Smith, Nitesh D. Kuhadiya … (2009)
            OBJECTIVE To examine the impact of Hurricane Katrina on the health of individuals with diabetes. RESEARCH DESIGN AND METHODS This was an observational study in 1,795 adults with an A1C measurement 6 months before and 6−16 months after Hurricane Katrina in three health care systems: private (Tulane University Hospital and Clinic [TUHC]), state (Medical Center of Louisiana at New Orleans [MCLNO]), and Veterans Affairs (VA). Glycemic control (A1C), blood pressure, and lipids before the hurricane were compared with the patients' first measurement thereafter. The CORE Diabetes Model was used to project life expectancy and health economic impact. RESULTS Mean predisaster A1C levels differed between MCLNO and VA patients (mean 7.7 vs. 7.3%, P < 0.001) and increased significantly among MCLNO patients to 8.3% (P < 0.001) but not among VA and TUHC patients. Mean systolic blood pressure increased in all three systems (130–137.6 mmHg for TUHC and 130.7–143.7 for VA, P < 0.001; 132–136 for MCLNO, P = 0.008). Mean LDL cholesterol increased in the VA (97.1–104.3 mg/dl) and TUHC patients (103.4–115.5; P < 0.001). Hurricane Katrina increased modeled direct, indirect, and total health care costs and also reduced life expectancy as well as quality-adjusted life expectancy, with the economic impact being quite substantial because of the large population size affected. We estimate a lifetime cost of USD $504 million for the adult population affected, with the largest economic impact seen among MCLNO patients. CONCLUSIONS A major disaster had a significant effect on diabetes management and exacerbated existing disparities. These effects may have a lasting impact on both health and economic implications.
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              Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study

              Viswanathan Mohan, Siddharth Shah, Shashank R. Joshi … (2014)
              Objectives: DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India. Materials and Methods: This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The patients’ and physicians’ perceptions about diabetes management were recorded using a questionnaire. Results: A total of 6168 subjects with diabetes (95.8% type 2), mean age 51.9 ± 12.4 years and mean duration of diabetes, 6.9 ± 6.4 years were included. Mean HbA1c was 8.9 ± 2.1% and the mean fasting (FPG), post prandial (PPG) and random (RBG) plasma glucose levels were 148 ± 50 mg/dl 205 ± 66 mg/dl and 193 ± 68mg/dl respectively. Neuropathy was the most common complication (41.4%); other complications were: Foot (32.7%), eye (19.7%), cardiovascular (6.8%) and nephropathy (6.2%). The number of diabetic complications increased with mean duration of diabetes. Most (93.2%) of the patients were on oral anti-diabetic drugs (OADs) and 35.2% were on insulin (±OADs). More than 15% physicians felt that the greatest barrier to insulin therapy from patient's perspective were pain and fear of using injectable modality; 5.2% felt that the greatest barrier to insulin therapy from physician's perspective was the treatment cost; 4.8% felt that the major barriers to achieve optimum diabetic care in practice was loss to follow-up followed by lack of counselling (3.9%) and treatment compliance (3.6%). Conclusion: DiabCare India 2011 has shown that type 2 diabetes sets in early in Indians and glycaemic control is often sub-optimal in these patients. These results indicate a need for more structured intervention at an early stage of the disease and need for increased awareness on benefits of good glycaemic control. It cannot be overemphasized that the status of diabetes care in India needs to be further improved. (ClinTrials.gov identifier: NCT01351922)
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                Author and article information

                Contributors
                Samit Ghosal
                Journal
                Journal ID (nlm-ta): Diabetes Metab Syndr
                Journal ID (iso-abbrev): Diabetes Metab Syndr
                Title: Diabetes & Metabolic Syndrome
                Publisher: Published by Elsevier Ltd on behalf of Diabetes India.
                ISSN (Print): 1871-4021
                ISSN (Electronic): 1878-0334
                Publication date PMC-release: 10 April 2020
                Publication date (Electronic): 10 April 2020
                Affiliations
                [a ]Nightingale Hospital, Kolkata, India
                [b ]AMRI Hospitals, Kolkata, India
                [c ]Milan Majumder, Biostatistician, Pune, India
                [d ]Fortis CDOC Hospital for Diabetes and Allied Sciences, New Delhi, India
                [e ]Diabetes Foundation (India), National Diabetes Obesity and Cholesterol Foundation (NDOC), New Delhi, India
                Author notes
                [∗ ]Corresponding author. ramdasghosal@ 123456gmail.com
                Article
                Publisher ID: S1871-4021(20)30054-0
                DOI: 10.1016/j.dsx.2020.03.014
                PMC ID: 7146694
                PubMed ID: 32298984
                SO-VID: 5772cb21-1eb4-46f3-af75-7d7b651d6d8e
                Copyright © © 2020 Published by Elsevier Ltd on behalf of Diabetes India.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 30 March 2020
                Date accepted : 30 March 2020
                Categories
                Subject: Article

                Keywords: diabetes,lockdown,disaster,multivariate regression analysis,complications
                Data availability:
                Keywords: diabetes, lockdown, disaster, multivariate regression analysis, complications

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