Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges.

Both diabetes mellitus (DM) and tuberculosis (TB) are prevalent all across in India. TB-DM comorbidity has emerged as a syndemic and needs more attention in India considering gaps in screening, clinical care, and research. This paper is intended to review published literature on TB and DM in India to understand the burden of the dual epidemic and its trajectory and to obtain perspectives on the gaps, constraints, and challenges in care and treatment of this dual epidemic. A literature search was carried out on PubMed, Scopus, and Google Scholar, using the key words 'Tuberculosis' OR 'TB' AND 'Diabetes' OR 'Diabetes Mellitus' AND 'India', focusing on the research published between the year 2000 to 2022. The prevalence of DM is high in patients with TB. Quantitative data on the epidemiological situation of TB/DM in India such as incidence, prevalence, mortality, and management are lacking. During the last 2 years convergence of TB-DM syndemic with the COVID-19 pandemic has increased cases with uncontrolled DM but also made coordinated control of TB-DM operationally difficult and of low effectiveness. Research regarding TB-DM comorbidity is required in the context of epidemiology and management. Detection and bidirectional screening are aggressively warranted. Management of DM in those with TB-DM comorbidity needs more efforts, including training and supervision of frontline workers.

Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis.

BACKGROUND: Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. METHODS: We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. RESULTS: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04). CONCLUSIONS: AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.

An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19.

BACKGROUND AND AIMS: Molnupiravir is a newer oral antiviral drug that has recently received emergency use authorization (EUA) in USA, UK and India. We aim to conduct an update on our previous systematic review to provide practical clinical guideline for using molnupiravir in patients with COVID-19. METHODS: We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar until January 5, 2022, using key MeSH keywords. RESULTS: Final result of phase 3 study in 1433 non-hospitalized COVID-19 patients showed a significant reduction in composite risk of hospital admission or death (absolute risk difference, -3.0% [95% confidence interval {CI}, -5.9 to -0.1%]; 1-sided P = 0.02) although with a non-significant 31% relative risk reduction (RRR). RRR for death alone was 89% (95% CI, 14 to 99; P-value not reported). Number needed to treat to prevent 1 death or 1 hospitalization or death composite appears to be closely competitive to other agents having EUA in people with COVID-19. However, cost-wise molnupiravir is comparatively cheaper compared to all other agents. CONCLUSION: Molnupiravir could be a useful agent in non-pregnant unvaccinated adults with COVID-19 who are at increased risk of severity including hospitalization. However, it is effective only when used within 5-days of onset of symptoms. A 5-days course seems to be safe without any obvious short-term side effects.

Molnupiravir in COVID-19: A systematic review of literature.

BACKGROUND AND AIMS: Molnupiravir is a newer oral antiviral drug that has recently been tested in COVID-19. We aim to conduct a systematic review of literature to find out the efficacy and safety of molnupiravir in patients with COVID-19. METHODS: We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar from inception until October 15, 2021, using MeSH keywords. Ongoing trials of molnupiravir in COVID-19 were additionally searched from the ClinicalTrials.Gov and ctri.nic.in/Clinicaltrials. We retrieved all the available granular details of phase 1 to 3 studies of molnupiravir in COVID-19. Subsequently we reviewed the results narratively. RESULTS: Two phase 1 double-blind, randomized, placebo-controlled (DBRPC) studies of molnupiravir showed that 1600 mg daily dose is safe and tolerable, without any serious adverse events up to 5.5 days. One phase 2 DBPRC study found significantly lower time to clearance (RNA negativity) with molnupiravir 800 mg twice daily compared to the placebo (log-rank p value = 0.013) in mild to moderate COVID-19. Interim report of one phase 3 DBRPC study in non-hospitalized COVID-19 found a significant reduction in the risk of hospital admission or death by 50% (p = 0.0012). However, no significant benefit was observed with molnupiravir in the later stage of moderate to severe COVID-19. CONCLUSION: Molnupiravir is first oral antiviral drug to demonstrate a significant benefit in reducing hospitalization or death in mild COVID-19 and could be an important weapon in the battle against SARS-CoV-2. However, its role in moderate to severe COVID-19 is questionable and more studies are needed.

COVID-19 associated mucormycosis: A Descriptive Multisite Study from India.

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.

High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: A case-control study.

BACKGROUND: Post COVID-19 syndrome (PCS) has emerged as a major roadblock in the recovery of patients infected with SARS-CoV-2. Amongst many symptoms like myalgia, headache, cough, breathlessness; fatigue is is most prevalent and makes the patient severely debilitated. Research on PCS, in particular fatigue, in patients with diabetes has not been done. METHODOLOGY: In this prospective study, we included patients with type 2 diabetes (T2D) who had COVID-19 (mild to moderate severity), and matched T2D patients who did not suffer from COVID-19. Demography, anthropometry, glycemic measures, treatment, and details of COVID-19 were recorded. Symptoms were scored using Chalder Fatigue Scale (reported as fatigue score, FS) and handgrip strength (in kg) was recorded by Jamar Hydraulic Hand Dynamometer. RESULTS: A total of 108 patients were included (cases, 52, controls, 56). Both groups were matched for age, duration of diabetes, BMI, TSH, serum albumin and vitamin D levels. T2D patients who had COVID-19 showed significantly more fatigue when compared with patients who did not have COVID-19 but both groups had comparable handgrip strength. Furthermore, patients with T2D with previous COVID-19 infection and who had FS > 4 have had significant higher inflammation markers during acute illness, and post COVID-19, had increased post prandial blood glucose levels, lost more weight, had reduced physical activity and showed significantly lower handgrip strength as compared to those with FS < 4. CONCLUSION: Patients with T2D who had COVID-19 infection as compared to those without had significantly more fatigue after the acute illness, and those with higher FS had reduced handgrip strength indicating sarcopenia, even after careful matching for common contributory factors to fatigue at baseline. Rehabilitation of those with FS>4 after acute infection would require careful attention to nutrition, glycemic control and graduated physical activity protocol.

Management of diabetes mellitus through teleconsultation during COVID-19 and similar scenarios - Guidelines from Indian Council of Medical Research (ICMR) expert group.

INTRODUCTION: Emergence of COVID-19 pandemic has led to increased use of telemedicine in health care delivery. Telemedicine facilitates long-term clinical care for monitoring and prevention of complications of diabetes mellitus. GUIDELINES: Precise indications for teleconsultation, clinical care services which can be provided, and good clinical practices to be followed during teleconsultation are explained. Guidance on risk assessment and health education for diabetes risk factors, counselling for blood glucose monitoring, treatment compliance, and prevention of complications are described. CONCLUSION: The guidelines will help physicians in adopting teleconsultation for management of diabetes mellitus, facilitate access to diabetes care and improve health outcomes.

Diabetes and COVID19: a bidirectional relationship.

The advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body's stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

Diabetes Mellitus and COVID-19: Review Article.

BACKGROUND AND AIMS: We aim to cover most of the current evidence on the mutual effect of diabetes & COVID-19 infection on each other and the management of the COVID-19 patients with diabetes. METHODS: We utilized databases to review the current evidence related to diabetes mellitus and COVID-19. RESULTS: We discussed the most recent evidence of diabetes milieus and COVID-19 regarding risk factors, management, complications, and telemedicine. CONCLUSION: Diabetes mellitus is associated with a significant risk of complications, extended hospital stays, and mortality in COVID-19 infected patients.

Post COVID-19 Syndrome ("Long COVID") and Diabetes: Challenges in Diagnosis and Management.

BACKGROUND AND AIMS: Post Covid-19 syndrome (PCS) is a major cause of morbidity. In this article we intend to review the association and consequences of PCS and diabetes. METHODS: We reviewed all studies on "Long Covid", "Post COVID-19 Syndrome" and diabetes in PubMed and Google Scholar. RESULTS: The symptoms of PCS can be due to organ dysfunction, effects of hospitalisation and drugs, or unrelated to these. Type 2 diabetes mellitus has a bidirectional relationship with COVID-19. Presence of diabetes also influences PCS via various pathophysiological mechanisms. COVID-19 can add to or exacerbate tachycardia, sarcopenia (and muscle fatigue), and microvascular dysfunction (and organ damage) in patients with diabetes. CONCLUSION: PCS in patients with diabetes could be detrimental in multiple ways. Strict control of diabetes and other comorbidities, supervised rehabilitation and physical exercise, and optimal nutrition could help in reducing and managing PCS.

Absence of Case of Mucormycosis (March 2020-May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit.

AIMS: With a sudden increase in cases of mucormycosis seen in Covid -19 patients, we conducted a retrospective analysis of all admitted patients in a tertiary care covid-19 hospital looking at incidence of mucormycosis. METHODS: Intensive care unit daily rounds data stored in an electronic format was retrieved by one of the consultants, looking for incidence of mucormycosis, diabetes mellitus, adherence to protocol for steroid use, glycemic control and use of monoclonal antibodies. Also, patients follow up data base of post covid Outpatients Department was searched for cases of mucormycosis. RESULTS: A total of 5248 patients were admitted between March 2020 to May 2021, of which 1027 were in ICU and 4221 in wards. Of the 1027 patients admitted in Intensive care unit, 915 received steroids and 417 had diabetes as existing co-morbidity. No case of mucormycosis was reported during the stay in the hospital and during immediate outpatient department follow up. The low dose steroids were administered as per state government protocol for treating COVID 19, a nurse driven strict glycemic control regime (blood glucose level was maintained between 140 and 180 mg/dl through the admission in ICU and was achieved consistently in 842 (82%) patients, followed along with minimal use of other immunomodulatory like monoclonal antibodies. CONCLUSION: A strict adherence to protocol of low dose steroids coupled with strict glycemic control helped in eliminating the risk and incidence of mucormycosis in a tertiary care dedicated covid-19 hospital.

Diabetes and COVID19: a bidirectional relationship.

The advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body's stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

Impact of the vitamin D deficiency on COVID-19 infection and mortality in Asian countries.

BACKGROUND AND AIMS: COVID-19 is a pandemic that has affected beyond 100 million and caused nearly 3 million deaths globally. Vitamin D is a known risk factor for COVID-19. Therefore, we aimed to investigate the association of prevalence of vitamin D deficiency and mean vitamin D level with COVID-19 infection and mortality in Asia, predicting with other confounding factors such as median age, obesity, and diabetes. METHODS: COVID-19 infections and mortalities among the Asian countries were retrieved from the Worldometer website. Information on prevalence of vitamin D deficiency and mean vitamin D values in each Asian country was retrieved through literature searching on PubMed® and Google scholar. The associations between COVID-19 infections and mortalities with prevalence of vitamin D deficiency and mean vitamin D level were explored with correlation coefficients. As a predictive analysis, multiple linear regression was carried out with all confounders. RESULTS: Positive correlations were observed for prevalence of vitamin D deficiency with COVID-19 infections (r = 0.55; p = 0.01; R2 = 0.31) and mortalities (r = 0.50; p = 0.01; R2 = 0.25). Moreover, the associations for the COVID-19 infections and mortalities improved to r = 0.76 (p = 0.002; R2 = 0.58) and r = 0.65 (p = 0.03; R2 = 0.42), respectively, after predicting with confounding factors. Similarly, mean vitamin D level had a significant negative correlation with COVID-19 infections (r = -0.77; p = 0.04; R2 = 0.59) and mortalities (r = -0.80; p = 0.03; R2 = 0.63) when combining with confounders. CONCLUSION: Prevalence of vitamin D deficiency is significantly positively associated whereas the mean vitamin D level is significantly negatively associated with both infection and mortality rate of COVID-19 among Asian countries upon predicting with all confounders.

Steroid use during COVID-19 infection and hyperglycemia - What a physician should know.

BACKGROUND AND AIMS: The COVID-19 pandemic continues to challenge us. Despite several strides in management, steroids remain the mainstay for treating moderate to severe disease and with it arises challenges such as hyperglycemia. The review aims to enhance awareness amongst physicians on steroid use and hyperglycemia. METHODS: An advisory document describing various strategies for hyperglycemia management was prepared in the public interest by DiabetesIndia. RESULTS: The review provides awareness on steroids and hyperglycemia, adverse outcomes of elevated blood glucose levels and, advice at the time of discharge. CONCLUSIONS: The article emphasizes enhancing awareness on effective management of hyperglycemia during COVID-19.

Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India.

BACKGROUND AND AIMS: There are increasing case reports of rhino-orbital mucormycosis in people with coronavirus disease 2019 (COVID-19), especially from India. Diabetes mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. We aim to conduct a systematic review of literature to find out the patient's characteristics having mucormycosis and COVID-19. METHODS: We searched the electronic database of PubMed and Google Scholar from inception until May 13, 2021 using keywords. We retrieved all the granular details of case reports/series of patients with mucormycosis, and COVID-19 reported world-wide. Subsequently we analyzed the patient characteristics, associated comorbidities, location of mucormycosis, use of steroids and its outcome in people with COVID-19. RESULTS: Overall, 101 cases of mucormycosis in people with COVID-19 have been reported, of which 82 cases were from India and 19 from the rest of the world. Mucormycosis was predominantly seen in males (78.9%), both in people who were active (59.4%) or recovered (40.6%) from COVID-19. Pre-existing diabetes mellitus (DM) was present in 80% of cases, while concomitant diabetic ketoacidosis (DKA) was present in 14.9%. Corticosteroid intake for the treatment of COVID-19 was recorded in 76.3% of cases. Mucormycosis involving nose and sinuses (88.9%) was most common followed by rhino-orbital (56.7%). Mortality was noted in 30.7% of the cases. CONCLUSION: An unholy trinity of diabetes, rampant use of corticosteroid in a background of COVID-19 appears to increase mucormycosis. All efforts should be made to maintain optimal glucose and only judicious use of corticosteroids in patients with COVID-19.

Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility in New Delhi, India.

BACKGROUND AND AIMS: Vaccinations for COVID19 are now open to all adults in India. However, spread of COVID19 infection continues unabated. We aimed to ascertain number of breakthrough COVID19 infections after vaccinations in a chronic care, diabetes-centric healthcare facility. METHODS: We reviewed rigorously maintained data of vaccinations, health status, symptoms of COVID19 & RT-PCR testing of all staff (doctors, nurses, paramedical workers, and other staff) in our health care facility from January 16, 2021 till date. RESULTS: Out of 123 employees, 113 were vaccinated (Covaxin, 28, Covishield, 85). Second dose was completed in 107 (94.7%) and first dose in 6 persons (5.3%). Symptomatic COVD19 infections occurred in 19 persons (16.9%) post any dose of vaccine. Symptomatic breakthrough infections > 14 days after second dose occurred in 15 persons (13.3%). Except one (required hospitalization), all 14 had mild COVID19 disease. CONCLUSIONS: We report mild symptomatic breakthrough infections as seen in our health care facility. Research in breakthrough infections in India should be extended to other institutions and community to obtain larger data.