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1.
Eur J Endocrinol ; 185(5): C13-C17, 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1463338

ABSTRACT

In this SARS-COV2-pandemic, diabetes mellitus (DM) soon emerged as one of the most prominent risk factors for a severe course of corona virus disease-2019 (COVID-19) and increased mortality due to hyperglycemia/insulin resistance, obesity, inflammation, altered immune status, and cardiovascular complications. In general, men are at a higher risk of severe or fatal COVID-19 disease irrespective of age, region and despite comparable infection rates in both sexes. In COVID-19, there is also a male predominance among hospitalized patients with diabetes, however, overall, data among patients with diabetes are ambiguous so far. Of note, similar to cardiovascular complications, women with type 2 diabetes (DM2) appear to lose their biological female advantage resulting in comparable death rates to those of men. The complex interplay of biological and behavioral factors, which may put men at greater risk of a severe or fatal course of COVID-19, and gender-related psychosocial factors, which may cause disadvantage to women concerning the infection rates, might explain why sex-disaggregated data among infected patients with diabetes are conflicting. Better knowledge on biological factors leading to functionally different immune responses and of gender-sensitive sociocultural determinants of COVID-19 infection rates may help to optimize prevention and management in the high-risk groups of men and women with diabetes.


Subject(s)
COVID-19/complications , COVID-19/mortality , Diabetes Complications/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus/mortality , Adult , COVID-19 Vaccines/therapeutic use , Female , Humans , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Male , Middle Aged , Pregnancy , Sex Factors , Treatment Outcome
2.
Ghana Med J ; 54(4 Suppl): 52-61, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1436195

ABSTRACT

Introduction: Since the declaration of COVID-19 by the World Health Organisation (WHO) as a global pandemic on 11th March 2020, the number of deaths continue to increase worldwide. Reports on its pathologic manifestations have been published with very few from the Sub-Saharan African region. This article reports autopsies on COVID-19 patients from the Ga-East and the 37 Military Hospitals to provide pathological evidence for better understanding of COVID-19 in Ghana. Methods: Under conditions required for carrying out autopsies on bodies infected with category three infectious agents, with few modifications, complete autopsies were performed on twenty patients with ante-mortem and/or postmortem RT -PCR confirmed positive COVID-19 results, between April and June, 2020. Results: There were equal proportion of males and females. Thirteen (65%) of the patients were 55years or older with the same percentage (65%) having Type II diabetes and/or hypertension. The most significant pathological feature found at autopsy was diffuse alveolar damage. Seventy per cent (14/20) had associated thromboemboli in the lungs, kidneys and the heart. Forty per cent (6/15) of the patients that had negative results for COVID-19 by the nasopharyngeal swab test before death had positive results during postmortem using bronchopulmonary specimen. At autopsy all patients were identified to have pre-existing medical conditions. Conclusion: Diffuse alveolar damage was a key pathological feature of deaths caused by COVID-19 in all cases studied with hypertension and diabetes mellitus being major risk factors. Individuals without co-morbidities were less likely to die or suffer severe disease from SARS-CoV-2. Funding: None declared.


Subject(s)
Autopsy/statistics & numerical data , COVID-19/pathology , Hospitals, Military/statistics & numerical data , Hospitals, Municipal/statistics & numerical data , SARS-CoV-2 , COVID-19/mortality , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Comorbidity , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/virology , Female , Ghana/epidemiology , Humans , Hypertension/mortality , Hypertension/virology , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Alveoli/pathology , Pulmonary Alveoli/virology , Risk Factors
3.
Endocrinol Metab (Seoul) ; 36(4): 904-908, 2021 08.
Article in English | MEDLINE | ID: covidwho-1328154

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Observational Studies as Topic/methods , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Dipeptidyl Peptidase 4/blood , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Mortality/trends
4.
Can J Diabetes ; 45(6): 524-530, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1317699

ABSTRACT

OBJECTIVES: Patients with diabetes are potentially at higher risk of mortality due to coronavirus disease-2019 (COVID-19). In this study, we aimed to compare the outcomes and severity of pulmonary involvement in COVID-19 patients with and without diabetes. METHODS: In this cohort study, we recruited patients with diabetes who were hospitalized due to COVID-19 during the period from February 2020 to May 2020. Hospitalized individuals without diabetes were enrolled as control subjects. All patients were followed for 90 days and clinical findings and patients' outcomes were reported. RESULTS: Over a period of 4 months, 127 patients with diabetes and 127 individuals without diabetes with a diagnosis of COVID-19 were recruited. Their mean age was 65.70±12.51 years. Mortality was higher in the group with diabetes (22.8% vs 15.0%; p=0.109), although not significantly. More severe pulmonary involvement (p=0.015), extended hospital stay (p<0.001) and greater need for invasive ventilation (p=0.029) were reported in this population. Stepwise logistic regression revealed that diabetes was not independently associated with mortality (p=0.092). Older age (odds ratio [OR], 1.054; p=0.003), aggravated pulmonary involvement on admission (OR, 1.149; p=0.001), presence of comorbidities (OR, 1.290; p=0.020) and hypothyroidism (OR, 6.576; p=0.021) were associated with mortality. Diabetic foot infection had a strong positive correlation with mortality (OR, 49.819; p=0.016), whereas insulin therapy had a negative correlation (OR, 0.242; p=0.045). CONCLUSIONS: The mortality rate due to COVID-19 did not differ significantly between patients with or without diabetes. Older age, macrovascular complications and presence of comorbidities could increase mortality in people with diabetes. Insulin therapy during hospitalization could attenuate the detrimental effects of hyperglycemia and improve prognosis of patients with COVID-19 and diabetes.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/mortality , Hospitalization/trends , Respiration Disorders/mortality , Severity of Illness Index , Adult , Aged , COVID-19/diagnostic imaging , COVID-19/therapy , Cohort Studies , Diabetes Mellitus, Type 2/diagnostic imaging , Diabetes Mellitus, Type 2/therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mortality/trends , Respiration Disorders/diagnostic imaging , Respiration Disorders/therapy
6.
Endocrinol Diabetes Metab ; 4(4): e00287, 2021 10.
Article in English | MEDLINE | ID: covidwho-1306644

ABSTRACT

INTRODUCTION: To investigate type 2 diabetes as a risk factor for COVID-19 death following hospital admission in Kuwait. METHODS: A retrospective cohort study using data from a central hospital that cared for all hospitalized COVID-19 patients in Kuwait. We investigated the association between type 2 diabetes, with COVID-19 mortality using multiply imputed logistic regression and calculated the population attributable fraction. RESULTS: A total of 5333 patients were admitted with COVID-19, of whom 244 died (4.6%). Diabetes prevalence was 24.8%, but 53.7% of those who died had diabetes. After adjusting for age, sex, ethnicity and other comorbidities, diabetes was associated with death (OR 1.70 [95% CI 1.23, 2.34]) and admission to the intensive care unit more than 3 days after initial admission (OR 1.78 [95% CI 1.17, 2.70]). Assuming causality, the population attributable fraction for type 2 diabetes in COVID-19 death was 19.6% (95% CI 10.8, 35.6). CONCLUSION: Type 2 diabetes is a strong risk factor for COVID-19 death in the Middle East. Given the high prevalence of type 2 diabetes in the Middle East, as well as many Western countries, the public health implications are considerable.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/mortality , Adult , Aged , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Female , Hospital Mortality , Hospitalization , Humans , Inpatients , Intensive Care Units , Kuwait/epidemiology , Male , Middle Aged , Prevalence , Retrospective Studies , Risk
7.
BMC Endocr Disord ; 21(1): 144, 2021 Jul 03.
Article in English | MEDLINE | ID: covidwho-1295459

ABSTRACT

BACKGROUND: Although obesity, defined by body mass index (BMI), has been associated with a higher risk of hospitalisation and more severe course of illness in Covid-19 positive patients amongst the British population, it is unclear if this translates into increased mortality. Furthermore, given that BMI is an insensitive indicator of adiposity, the effect of adipose volume on Covid-19 outcomes is also unknown. METHODS: We used the UK Biobank repository, which contains clinical and anthropometric data and is linked to Public Health England Covid-19 healthcare records, to address our research question. We performed age- and sex- adjusted logistic regression and Chi-squared test to compute the odds for Covid-19-related mortality as a consequence of increasing BMI, and other more sensitive indices of adiposity such as waist:hip ratio (WHR) and percent body fat, as well as concomitant cardiometabolic illness. RESULTS: 13,502 participants were tested for Covid-19 (mean age 70 ± 8 years, 48.9% male). 1582 tested positive (mean age 68 ± 9 years, 52.8% male), of which 305 died (mean age 75 ± 6 years, 65.5% male). Increasing adiposity was associated with higher odds for Covid-19-related mortality. For every unit increase in BMI, WHR and body fat, the odds of death amongst Covid19-positive participants increased by 1.04 (95% CI 1.01-1.07), 10.71 (95% CI 1.57-73.06) and 1.03 (95% CI 1.01-1.05), respectively (all p < 0.05). Referenced to Covid-19 positive participants with a normal weight (BMI 18.5-25 kg/m2), Covid-19 positive participants with BMI > 35 kg/m2 had significantly higher odds of Covid-19-related death (OR 1.70, 95% CI 1.06-2.74, p < 0.05). Covid-19-positive participants with metabolic (diabetes, hypertension, dyslipidaemia) or cardiovascular morbidity (atrial fibrillation, angina) also had higher odds of death. CONCLUSIONS: Anthropometric indices that are more sensitive to adipose volume and its distribution than BMI, as well as concurrent cardiometabolic illness, are associated with higher odds of Covid-19-related mortality amongst the UK Biobank cohort that tested positive for the infection. These results suggest adipose volume may contribute to adverse Covid-19-related outcomes associated with obesity.


Subject(s)
Adiposity/physiology , COVID-19/mortality , Cardiovascular Diseases/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , Aged , Aged, 80 and over , Biological Specimen Banks/statistics & numerical data , Body Mass Index , COVID-19/complications , COVID-19/pathology , Cardiometabolic Risk Factors , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Cohort Studies , Databases, Factual , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/mortality , Female , Hospital Mortality , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/mortality , Middle Aged , Morbidity , Mortality , Obesity/complications , Obesity/mortality , Risk Factors , SARS-CoV-2/physiology , United Kingdom/epidemiology
8.
Am J Public Health ; 111(8): 1518-1522, 2021 08.
Article in English | MEDLINE | ID: covidwho-1286893

ABSTRACT

Objectives. To examine the disease-specific excess deaths during the COVID-19 pandemic in the United States. Methods. We used weekly death data from the National Center for Health Statistics to analyze the trajectories of excess deaths from specific diseases in the United States during the COVID-19 pandemic, at the national level and in 4 states, from the first to 52nd week of 2020. We used the average weekly number of deaths in the previous 6 years (2014-2019) as baseline. Results. Compared with the same week at baseline, the trajectory of number of excess deaths from cardiovascular disease (CVD) was highly parallel to the trajectory of the number of excess deaths related to COVID-19. The number of excess deaths from diabetes mellitus, influenza and respiratory diseases, and malignant neoplasms remained relatively stable over time. Conclusions. The parallel trajectory of excess mortality from CVD and COVID-19 over time reflects the fact that essential health services for noncommunicable diseases were reduced or disrupted during the COVID-19 pandemic, and the severer the pandemic, the heavier the impact.


Subject(s)
COVID-19/mortality , Cause of Death/trends , Mortality/trends , COVID-19 Testing/statistics & numerical data , Cardiovascular Diseases/mortality , Comorbidity , Diabetes Mellitus, Type 2/mortality , Humans , Influenza, Human/mortality , Pneumonia/mortality , Risk Factors , United States/epidemiology
9.
Magnes Res ; 34(1): 20-31, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1282349

ABSTRACT

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR <60 mL/min per 1.73 m2). T2D patients had lower eGFR and serum magnesium levels when compared to non-diabetics (59.7 ± 32.8 vs. 78.4 ± 33.8 mL/min per 1.73 m2, P = 0.008 and 1.9 ± 0.3 vs. 2.1 ± 0.3 mEq/L, P = 0.012). Survival was worse in T2D patients with eGFR levels less than 60 mL/min per 1.73 m2 as estimated by Kaplan-Meier analyses (log-rank test <0.0001). The Cox model for T2D patients showed that eGFR (HR 0.970, 95% CI 0.949 to 0.991, P = 0.005) and magnesium (HR 8.025, 95% CI 1.226 to 52.512, P = 0.030) were associated with significantly increased risk of death. Reduced eGFR and magnesium levels were associated with increased mortality in our population. These results suggest that early assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce morbidity and mortality among Latin American COVID-19 patients with T2D.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Kidney/physiopathology , Magnesium/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Diabetic Nephropathies/blood , Diabetic Nephropathies/complications , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/mortality , Female , Glomerular Filtration Rate/physiology , Hospital Mortality , Humans , Kidney/metabolism , Male , Middle Aged , Prognosis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Retrospective Studies , SARS-CoV-2/physiology , Survival Analysis
10.
J Cardiovasc Pharmacol ; 78(1): e12-e19, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1232234

ABSTRACT

ABSTRACT: Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19 (coronavirus disease 2019). Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, exerts direct cardioprotective and nephroprotective effects. DARE-19 (Dapagliflozin in Respiratory Failure in Patients With COVID-19), an ongoing clinical trial, is designed to investigate the impact of dapagliflozin on COVID-19 progression. This article discusses the potential favorable impact of dapagliflozin on COVID-19 and its complications.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Benzhydryl Compounds/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Clinical Trials, Phase III as Topic , Comorbidity , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Disease Progression , Glucosides/adverse effects , Humans , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Treatment Outcome
11.
Front Endocrinol (Lausanne) ; 12: 652765, 2021.
Article in English | MEDLINE | ID: covidwho-1177968

ABSTRACT

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.


Subject(s)
COVID-19/complications , COVID-19/mortality , Health Status , Metabolic Diseases/complications , Metabolic Diseases/mortality , Aged , Aged, 80 and over , Blood Glucose , Blood Pressure , Databases, Factual , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Dyslipidemias/complications , Dyslipidemias/mortality , Female , Humans , Hypertension/complications , Hypertension/mortality , Male , Middle Aged , United Kingdom/epidemiology , Waist Circumference
12.
Front Endocrinol (Lausanne) ; 12: 596518, 2021.
Article in English | MEDLINE | ID: covidwho-1156116

ABSTRACT

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.


Subject(s)
COVID-19/immunology , Diabetes Mellitus, Type 2/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , COVID-19/blood , COVID-19/complications , COVID-19/mortality , China/epidemiology , Cytokines/analysis , Cytokines/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Female , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Hyperglycemia/immunology , Hyperglycemia/mortality , Immune System/metabolism , Immune System/pathology , Killer Cells, Natural/pathology , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/complications , Lymphopenia/immunology , Lymphopenia/mortality , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Th1 Cells/pathology , Th2 Cells/pathology
13.
Diabetes Res Clin Pract ; 174: 108753, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1135307

ABSTRACT

AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for severe COVID-19. Our aim was to compare the clinical outcomes of patients with and without T2DM during the first hit of COVID-19 in Istanbul. METHODS: A retrospective population-based study was conducted including all consecutive adult symptomatic COVID-19 cases. Patients were confirmed with rt-PCR; treated and monitored in accordance with standard protocols. The primary endpoints were hospitalization and 30-day mortality. RESULTS: Of the 93,571 patients, 22.6% had T2DM, with older age and higher BMI. Propensity Score matched evaluation resulted in significantly higher rates of hospitalization (1.5-fold), 30-day mortality (1.6-fold), and pneumonia (1.4-fold). They revealed more severe laboratory deviations, comorbidities, and frequent drug usage than the Non-DM group. In T2DM age, pneumonia, hypertension, obesity, and insulin-based therapies were associated with an increased likelihood of hospitalization; whereas age, male gender, lymphopenia, obesity, and insulin treatment were considerably associated with higher odds of death. CONCLUSIONS: COVID-19 patients with T2DM had worse clinical outcomes with higher hospitalization and 30-day mortality rates than those without diabetes. Compared to most territories of the world, COVID-19 mortality was much lower in Istanbul, which may be associated with accessible healthcare provision and the younger structure of the population.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/mortality , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Turkey/epidemiology
14.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1129733

ABSTRACT

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic ß-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Metformin/pharmacology , Autophagy/drug effects , COVID-19/complications , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/mortality , Gastrointestinal Microbiome/drug effects , Humans , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Intracellular Signaling Peptides and Proteins/drug effects , Intracellular Signaling Peptides and Proteins/metabolism
15.
J Diabetes ; 12(12): 895-908, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1096641

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus. Diabetes (mostly type 2 diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that patients with diabetes and COVID-19 are at an increased risk for developing severe complications including acute respiratory distress syndrome, multi-organ failure, and death. Here we explore potential mechanistic links that could explain the observed higher morbidity and mortality in this patient population. Patients with T2DM have an underlying increased level of inflammation associated with obesity and insulin resistance in addition to other comorbidities including hypertension, obesity, cardiovascular disease, dyslipidemia, and being older. We review evidence that T2DM with hyperglycemia are among factors that lead to elevated expression of angiotensin-converting enzyme 2 (ACE2) in lungs and other tissues; ACE2 is the cellular "receptor" and port of viral entry. The preexisting chronic inflammation with augmented inflammatory response to the infection and the increasing viral load leads to extreme systemic immune response ("cytokine storm") that is strongly associated with increased severity of COVID-19. Based on the available evidence, it is recommended by a panel of experts that safe but stringent control of blood glucose, blood pressure, and lipids be carried out in patients with T2DM, measures that could potentially serve to decrease the severity of COVID-19 should these patients contract the viral infection. Once the infection occurs, then attention should be directed to proper glycemic control with use of insulin and frequent monitoring of blood glucose levels.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/mortality , Inflammation/physiopathology , Insulin Resistance , Obesity/physiopathology , SARS-CoV-2/isolation & purification , COVID-19/complications , COVID-19/virology , China/epidemiology , Diabetes Mellitus, Type 2/virology , Humans , Morbidity , Prognosis , Survival Rate
16.
BMJ Open Diabetes Res Care ; 9(1)2021 02.
Article in English | MEDLINE | ID: covidwho-1088231

ABSTRACT

INTRODUCTION: Diabetes and hyperglycemia are risk factors for critical COVID-19 outcomes; however, the impact of pre-diabetes and previously unidentified cases of diabetes remains undefined. Here, we profiled hospitalized patients with undiagnosed type 2 diabetes and pre-diabetes to evaluate its impact on adverse COVID-19 outcomes. We also explored the role of de novo and intrahospital hyperglycemia in mediating critical COVID-19 outcomes. RESEARCH DESIGN AND METHODS: Prospective cohort of 317 hospitalized COVID-19 cases from a Mexico City reference center. Type 2 diabetes was defined as previous diagnosis or treatment with diabetes medication, undiagnosed diabetes and pre-diabetes using glycosylated hemoglobin (HbA1c) American Diabetes Association (ADA) criteria and de novo or intrahospital hyperglycemia as fasting plasma glucose (FPG) ≥140 mg/dL. Logistic and Cox proportional regression models were used to model risk for COVID-19 outcomes. RESULTS: Overall, 159 cases (50.2%) had type 2 diabetes and 125 had pre-diabetes (39.4%), while 31.4% of patients with type 2 diabetes were previously undiagnosed. Among 20.0% of pre-diabetes cases and 6.1% of normal-range HbA1c had de novo hyperglycemia. FPG was the better predictor for critical COVID-19 compared with HbA1c. Undiagnosed type 2 diabetes (OR: 5.76, 95% CI 1.46 to 27.11) and pre-diabetes (OR: 4.15, 95% CI 1.29 to 16.75) conferred increased risk of severe COVID-19. De novo/intrahospital hyperglycemia predicted critical COVID-19 outcomes independent of diabetes status. CONCLUSIONS: Undiagnosed type 2 diabetes, pre-diabetes and de novo hyperglycemia are risk factors for critical COVID-19. HbA1c must be measured early to adequately assess individual risk considering the large rates of undiagnosed type 2 diabetes in Mexico.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/blood , Prediabetic State/blood , Undiagnosed Diseases/complications , Adult , Blood Glucose/analysis , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/mortality , Fasting/blood , Female , Glycated Hemoglobin A/analysis , Hospitalization/statistics & numerical data , Humans , Male , Mexico/epidemiology , Middle Aged , Prediabetic State/epidemiology , Prediabetic State/mortality , Prospective Studies , Risk Factors , SARS-CoV-2/genetics , Severity of Illness Index , Undiagnosed Diseases/epidemiology
17.
Diabetes Care ; 44(1): 50-57, 2021 01.
Article in English | MEDLINE | ID: covidwho-1067598

ABSTRACT

OBJECTIVE: To describe the relationship between type 2 diabetes and all-cause mortality among adults with coronavirus disease 2019 (COVID-19) in the critical care setting. RESEARCH DESIGN AND METHODS: This was a nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between 1 March 2020 and 27 July 2020. Cox proportional hazards models were used to estimate 30-day in-hospital all-cause mortality associated with type 2 diabetes, with adjustment for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease). RESULTS: A total of 19,256 COVID-19-related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70 years) and 5,447 ICU (mean age 58 years) admissions. Of those admitted, 3,524 (18.3%) had type 2 diabetes and 5,077 (26.4%) died during the study period. Patients with type 2 diabetes were at increased risk of death (adjusted hazard ratio [aHR] 1.23 [95% CI 1.14, 1.32]), and this result was consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with higher age (age 18-49 years aHR 1.50 [95% CI 1.05, 2.15], age 50-64 years 1.29 [1.10, 1.51], and age ≥65 years 1.18 [1.09, 1.29]; P value for age-type 2 diabetes interaction = 0.002). CONCLUSIONS: Type 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.


Subject(s)
COVID-19/complications , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Comorbidity , Critical Care/statistics & numerical data , England/epidemiology , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Kidney Failure, Chronic/complications , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
18.
Diabetes Metab ; 47(2): 101202, 2021 03.
Article in English | MEDLINE | ID: covidwho-1064995

ABSTRACT

AIM: Patients with type 2 diabetes mellitus (T2DM) represent a high-risk population for both cardiovascular diseases and severe coronavirus disease 2019 (COVID-19). Recent studies have reported interactions between statin treatment and COVID-19-related outcomes. The study reported here specifically assessed the association between routine statin use and COVID-19-related outcomes in inpatients with T2DM. METHODS: The Coronavirus-SARS-CoV-2 and Diabetes Outcomes (CORONADO) study was a nationwide observational study aiming to describe the phenotypic characteristics and prognosis of T2DM patients with COVID-19 admitted to 68 French hospitals between 10 March and 10 April 2020. The composite primary outcome comprised tracheal intubation and/or death within 7 and 28 days of admission. The association between statin use and outcomes was estimated by logistic regression analysis after applying inverse probability of treatment weighting (IPTW) using a propensity score-weighting approach. RESULTS: Of the 2449 patients with T2DM (881 women, 1568 men; aged 70.9 ± 12.5 years) suitable for analysis, 1192 (49%) were using statin treatment before admission. In unadjusted analyses, patients using statins had rates of the primary outcome similar to those of non-users within both 7 (29.8% vs 27.0%, respectively; P = 0.1338) and 28 days (36.2% vs 33.8%, respectively; P = 0.2191) of admission. However, mortality rates were significantly higher in statin users within 7 (12.8% vs 9.8%, respectively; P = 0.02) and 28 days (23.9% vs 18.2%, respectively; P < 0.001). After applying IPTW, significant associations were observed with statin use and the primary outcome within 7 days (OR [95% CI]: 1.38 [1.04-1.83]) and with death within both 7 (OR [95% CI]: 1.74 [1.13-2.65]) and 28 days (OR [95% CI]: 1.46 [1.08-1.95]). CONCLUSION: Routine statin treatment is significantly associated with increased mortality in T2DM patients hospitalized for COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Female , Humans , Inpatients , Male , SARS-CoV-2
19.
Comput Biol Med ; 130: 104219, 2021 03.
Article in English | MEDLINE | ID: covidwho-1032696

ABSTRACT

Comorbidities in COVID-19 patients often lead to more severe outcomes. The disease-specific molecular events, which may induce susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are being investigated. To assess this, we retrieved array-based gene expression datasets from patients of 30 frequently occurring acute, chronic, or infectious diseases. Comparative analyses of the datasets were performed after quantile normalization and log2 transformation. Among the 78 host genes prominently implicated in COVID-19 infection, ACE2 (receptor for SARS-CoV-2) was positively regulated in several cases, namely, leukemia, psoriasis, lung cancer, non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension (PAH). FURIN was positively regulated in some cases, such as leukemia, psoriasis, NAFLD, lung cancer, and type II diabetes (T2D), while TMPRSS2 was positively regulated in only 3 cases, namely, leukemia, lung cancer, and T2D. Genes encoding various interferons, cytokines, chemokines, and mediators of JAK-STAT pathway were positively regulated in leukemia, NAFLD, and T2D cases. Among the 161 genes that are positively regulated in the lungs of COVID-19 patients, 99-111 genes in leukemia (including various studied subtypes), 77 genes in NAFLD, and 48 genes in psoriasis were also positively regulated. Because of the high similarity in gene expression patterns, the patients of leukemia, NAFLD, T2D, psoriasis, and PAH may need additional preventive care against acquiring SARS-CoV-2 infections. Further, two genes CARBONIC ANHYDRASE 11 (CA11) and CLUSTERIN (CLU) were positively regulated in the lungs of patients infected with either SARS-CoV-2, or SARS-CoV or Middle East Respiratory Syndrome Coronavirus (MERS-CoV).


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/metabolism , Diabetes Mellitus, Type 2/metabolism , Neoplasm Proteins/metabolism , Neoplasms/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Psoriasis/metabolism , Pulmonary Arterial Hypertension/metabolism , SARS-CoV-2/metabolism , COVID-19/mortality , Comorbidity , Diabetes Mellitus, Type 2/mortality , Gene Expression Regulation, Neoplastic , Gene Expression Regulation, Viral , Humans , Neoplasms/mortality , Non-alcoholic Fatty Liver Disease/mortality , Psoriasis/mortality , Pulmonary Arterial Hypertension/mortality , Signal Transduction
20.
Front Immunol ; 11: 576818, 2020.
Article in English | MEDLINE | ID: covidwho-993354

ABSTRACT

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), known as a highly contagious disease, currently affecting more than 200 countries worldwide. The main feature of SARS-CoV-2 that distinguishes it from other viruses is the speed of transmission combined with higher risk of mortality from acute respiratory distress syndrome (ARDS). People with diabetes mellitus (DM), severe obesity, cardiovascular disease, and hypertension are more likely to get infected and are at a higher risk of mortality from COVID-19. Among elderly patients who are at higher risk of death from COVID-19, 26.8% have DM. Although the reasons for this increased risk are yet to be determined, several factors may contribute to type-2 DM patients' increased susceptibility to infections. A possible factor that may play a role in increasing the risk in people affected by diabetes and/or obesity is the impaired innate and adaptive immune response, characterized by a state of chronic and low-grade inflammation that can lead to abrupt systemic metabolic alteration. SARS patients previously diagnosed with diabetes or hyperglycemia had higher mortality and morbidity rates when compared with patients who were under metabolic control. Similarly, obese individuals are at higher risk of developing complications from SARS-CoV-2. In this review, we will explore the current and evolving insights pertinent to the metabolic impact of coronavirus infections with special attention to the main pathways and mechanisms that are linked to the pathophysiology and treatment of diabetes.


Subject(s)
Adaptive Immunity , Diabetes Complications , Immunity, Innate , Obesity , Respiratory Distress Syndrome , Age Factors , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Diabetes Complications/immunology , Diabetes Complications/mortality , Diabetes Complications/therapy , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/therapy , Humans , Obesity/immunology , Obesity/mortality , Obesity/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , SARS-CoV-2
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