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1.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-2160403

ABSTRACT

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Gastric Inhibitory Polypeptide/administration & dosage , Glucagon-Like Peptides/administration & dosage , Hypoglycemic Agents/administration & dosage , Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Gastric Inhibitory Polypeptide/adverse effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/adverse effects , Glycated Hemoglobin A/analysis , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Injections, Subcutaneous , Male , Metformin/therapeutic use , Middle Aged , Nausea/chemically induced , Weight Loss/drug effects
2.
Front Endocrinol (Lausanne) ; 12: 777130, 2021.
Article in English | MEDLINE | ID: covidwho-1662576

ABSTRACT

Objective: To identify clinical and biochemical characteristics associated with 7- & 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19. Research Design and Methods: We conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome. Results: We analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p < 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (<70 years) had a greater risk of death [OR 2.74 (1.31-5.76)]. BMI, microvascular and macrovascular complications, HbA1c, and random non-fasting blood glucose on admission were not associated with mortality. On multivariate analysis, CRP and age remained associated with the primary outcome [OR 3.44 (2.17, 5.44)] allowing for a validated predictive model for death by day 7. Conclusions: Higher CRP and advanced age were associated with and predictive of death by day 7. However, BMI, presence of diabetes complications, and glycaemic control were not. A high proportion of these patients required insulin infusion warranting increased input from the inpatient diabetes teams.


Subject(s)
Biomarkers/blood , COVID-19/complications , Diabetes Mellitus, Type 2/mortality , Receptors, Immunologic/blood , SARS-CoV-2/isolation & purification , Age Factors , Aged , Aged, 80 and over , Blood Glucose/analysis , COVID-19/transmission , COVID-19/virology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/virology , Female , Follow-Up Studies , Glycated Hemoglobin A/analysis , Hospitalization , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , United Kingdom/epidemiology
3.
PLoS Med ; 18(11): e1003828, 2021 11.
Article in English | MEDLINE | ID: covidwho-1596033

ABSTRACT

BACKGROUND: Clinical pathways are changing to incorporate support and appropriate follow-up for people to achieve remission of type 2 diabetes, but there is limited understanding of the prevalence of remission in current practice or patient characteristics associated with remission. METHODS AND FINDINGS: We carried out a cross-sectional study estimating the prevalence of remission of type 2 diabetes in all adults in Scotland aged ≥30 years diagnosed with type 2 diabetes and alive on December 31, 2019. Remission of type 2 diabetes was assessed between January 1, 2019 and December 31, 2019. We defined remission as all HbA1c values <48 mmol/mol in the absence of glucose-lowering therapy (GLT) for a continuous duration of ≥365 days before the date of the last recorded HbA1c in 2019. Multivariable logistic regression in complete and multiply imputed datasets was used to examine characteristics associated with remission. Our cohort consisted of 162,316 individuals, all of whom had at least 1 HbA1c ≥48 mmol/mol (6.5%) at or after diagnosis of diabetes and at least 1 HbA1c recorded in 2019 (78.5% of the eligible population). Over half (56%) of our cohort was aged 65 years or over in 2019, and 64% had had type 2 diabetes for at least 6 years. Our cohort was predominantly of white ethnicity (74%), and ethnicity data were missing for 19% of the cohort. Median body mass index (BMI) at diagnosis was 32.3 kg/m2. A total of 7,710 people (4.8% [95% confidence interval [CI] 4.7 to 4.9]) were in remission of type 2 diabetes. Factors associated with remission were older age (odds ratio [OR] 1.48 [95% CI 1.34 to 1.62] P < 0.001) for people aged ≥75 years compared to 45 to 54 year group), HbA1c <48 mmol/mol at diagnosis (OR 1.31 [95% CI 1.24 to 1.39] P < 0.001) compared to 48 to 52 mmol/mol), no previous history of GLT (OR 14.6 [95% CI 13.7 to 15.5] P < 0.001), weight loss from diagnosis to 2019 (OR 4.45 [95% CI 3.89 to 5.10] P < 0.001) for ≥15 kg of weight loss compared to 0 to 4.9 kg weight gain), and previous bariatric surgery (OR 11.9 [95% CI 9.41 to 15.1] P < 0.001). Limitations of the study include the use of a limited subset of possible definitions of remission of type 2 diabetes, missing data, and inability to identify self-funded bariatric surgery. CONCLUSIONS: In this study, we found that 4.8% of people with type 2 diabetes who had at least 1 HbA1c ≥48 mmol/mol (6.5%) after diagnosis of diabetes and had at least 1 HbA1c recorded in 2019 had evidence of type 2 diabetes remission. Guidelines are required for management and follow-up of this group and may differ depending on whether weight loss and remission of diabetes were intentional or unintentional. Our findings can be used to evaluate the impact of future initiatives on the prevalence of type 2 diabetes remission.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Female , Glycated Hemoglobin A/metabolism , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prevalence , Remission Induction , Scotland/epidemiology
4.
Cardiovasc Diabetol ; 20(1): 218, 2021 11 06.
Article in English | MEDLINE | ID: covidwho-1503722

ABSTRACT

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Disease Management , Heart Failure/epidemiology , Mass Screening/methods , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin A/metabolism , Heart Failure/blood , Heart Failure/diagnosis , Humans , Mass Screening/trends , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis
5.
Endocrinol Metab (Seoul) ; 36(5): 1142-1146, 2021 10.
Article in English | MEDLINE | ID: covidwho-1485221

ABSTRACT

It has been suggested that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on glycemic control in patients with type 2 diabetes mellitus (T2DM). However, no study has examined yearly trends in glycated hemoglobin (HbA1c) levels after the start of the COVID-19 outbreak. Here, we performed a retrospective analysis of HbA1c concentrations during the early period of the COVID-19 outbreak (COVID-19 cohort) and then compared the yearly trend in the mean HbA1c level, along with fluctuations in HbA1c levels, with those during previous years (non-COVID-19 cohorts). We observed that the mean HbA1c level in patients with T2DM increased during the first 6 months of the COVID-19 outbreak. After 6 months, HbA1c levels in the COVID-19 cohort returned to levels seen in the non-COVID-19 cohorts. The data suggest that vulnerable patients with T2DM should be monitored closely during the early period of a pandemic to ensure they receive appropriate care.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/blood , Glycated Hemoglobin A/analysis , Glycemic Control/trends , Adult , Blood Glucose/analysis , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Disease Outbreaks/statistics & numerical data , Female , Humans , Male , Retrospective Studies , SARS-CoV-2/genetics , Time Factors
6.
Pharmacol Res ; 169: 105665, 2021 07.
Article in English | MEDLINE | ID: covidwho-1433725

ABSTRACT

Previous studies have reported that vitamin C supplementation may decrease lipid profile in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the influence of vitamin C supplementation on lipid profile in patients with T2DM. Studies examining the effects of vitamin C supplementation on lipid profile in patients with T2DM, published up to November 2020, were identified through PubMed, SCOPUS, and Embase databases. 15 studies, including 872 participants, were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI). Findings from 15 studies indicated that vitamin C supplementation significantly decreased Triglyceride (TG) (WMD: -16.48 mg/dl, 95% CI (-31.89, -1.08), P < 0.001) and total cholesterol (TC) (WMD: -13.00 mg/dl, 95% CI (-23.10, -2.91), P < 0.001) in patients with T2DM. However, vitamin C supplementation failed to improve LDL and HDL. The meta-regression analysis suggested that lipid profile improvement was affected by duration of vitamin C treatment. Dose-response analysis showed that vitamin C supplementation changed LDL significantly based on vitamin C dose. According to our findings, vitamin C supplementation significantly improved lipid profile via decreases in TG and TC. However, vitamin C failed to affect LDL and HDL in diabetic populations. It appears that vitamin C supplementation is more beneficial to lipid profile in long-term vs. short term interventions.


Subject(s)
Ascorbic Acid/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Lipids/blood , Ascorbic Acid/administration & dosage , Ascorbic Acid/pharmacology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Dietary Supplements , Dose-Response Relationship, Drug , Humans , Lipid Metabolism/drug effects
7.
Front Immunol ; 12: 720363, 2021.
Article in English | MEDLINE | ID: covidwho-1376702

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Humans , Inflammation/blood , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/complications , Stroke/blood , Virus Diseases
8.
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
10.
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
11.
Nutr Diabetes ; 11(1): 21, 2021 06 23.
Article in English | MEDLINE | ID: covidwho-1281687

ABSTRACT

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.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Blood Glucose , COVID-19/blood , Communicable Disease Control , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Humans , Pandemics
12.
Mol Metab ; 53: 101262, 2021 11.
Article in English | MEDLINE | ID: covidwho-1253402

ABSTRACT

OBJECTIVE: Obesity, in particular visceral obesity, and insulin resistance emerged as major risk factors for severe coronavirus disease 2019 (COVID-19), which is strongly associated with hemostatic alterations. Because obesity and insulin resistance predispose to thrombotic diseases, we investigated the relationship between hemostatic alterations and body fat distribution in participants at risk for type 2 diabetes. SUBJECTS: Body fat distribution (visceral and subcutaneous abdominal adipose tissue) and liver fat content of 150 participants - with impaired glucose tolerance and/or impaired fasting glucose - were determined using magnetic resonance imaging and spectroscopy. Participants underwent precise metabolic characterization and major hemostasis parameters were analyzed. RESULTS: Procoagulant factors (FII, FVII, FVIII, and FIX) and anticoagulant proteins (antithrombin, protein C, and protein S) were significantly associated with body fat distribution. In patients with fatty liver, fibrinogen (298 mg/dl vs. 264 mg/dl, p = 0.0182), FVII (99% vs. 90%, p = 0.0049), FVIII (114% vs. 90%, p = 0.0098), protein C (124% vs. 111%, p = 0.0006), and protein S (109% vs. 89%, p < 0.0001) were higher than in controls. In contrast, antithrombin (97% vs. 102%, p = 0.0025) was higher in control patients. In multivariate analyses controlling for insulin sensitivity, body fat compartments, and genotype variants (PNPLA3I148MM/MI/TM6SF2E167kK/kE), only protein C and protein S remained significantly increased in fatty liver. CONCLUSIONS: Body fat distribution is significantly associated with alterations of procoagulant and anticoagulant parameters. Liver fat plays a key role in the regulation of protein C and protein S, suggesting a potential counteracting mechanism to the prothrombotic state in subjects with prediabetes and fatty liver.


Subject(s)
Body Fat Distribution , COVID-19/complications , Diabetes Mellitus, Type 2/epidemiology , Fatty Liver/epidemiology , Hemostasis/physiology , Aged , COVID-19/blood , COVID-19/physiopathology , Cohort Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Fatty Liver/blood , Fatty Liver/diagnosis , Fatty Liver/physiopathology , Female , Humans , Insulin Resistance/physiology , Liver/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Protein C/analysis , Protein C/metabolism , Protein S/analysis , Protein S/metabolism , Randomized Controlled Trials as Topic , Risk Factors , SARS-CoV-2/pathogenicity
13.
Int J Mol Sci ; 22(10)2021 May 17.
Article in English | MEDLINE | ID: covidwho-1234744

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , Diabetes Complications/blood , Diabetes Mellitus, Type 2/blood , MicroRNAs/blood , Adult , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Biomarkers/blood , Body Mass Index , COVID-19/blood , COVID-19/complications , COVID-19/genetics , Diabetes Complications/genetics , Diabetes Complications/virology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/virology , Down-Regulation , Female , Gene Expression Regulation/genetics , Humans , Male , MicroRNAs/genetics , Middle Aged , Obesity/blood , Obesity/genetics
14.
Diabetes Res Clin Pract ; 176: 108840, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1209298

ABSTRACT

AIMS: Some studies have reported changes in glycemic control of patients with diabetes mellitus under lockdown. However, no previous study examined the impact of the pandemic on glycemic control in patients with diabetes in countries that did not introduce a lockdown such as Japan. This study aimed to assess changes in glycemic control during the pandemic in patients with type 2 diabetes treated at a Japanese clinic. METHODS: We conducted a historical cohort study, using electronic medical records of patients with type 2 diabetes who visited our clinic between January 2019 and August 2020. Differences in HbA1c values before and after the outbreak of COVID-19 were the primary outcome, examined using the linear mixed model. RESULTS: HbA1c values significantly increased from 7.45% to 7.53% after the state of emergency was introduced (n = 1,009). Furthermore, a deterioration in HbA1c values was observed in particular among women, patients aged ≥ 65 years, those with body mass index of ≥ 25 kg/m2, and those that were not using insulin. CONCLUSIONS: Glycemic control deteriorated in patients with type 2 diabetes during the pandemic even in a country without a national lockdown.


Subject(s)
Blood Glucose/metabolism , COVID-19/blood , COVID-19/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Glycemic Control/methods , Aged , COVID-19/virology , Cohort Studies , Female , Humans , Japan/epidemiology , Male , Outpatients , Pandemics , SARS-CoV-2/isolation & purification , Surveys and Questionnaires
15.
J Clin Endocrinol Metab ; 106(5): e2025-e2034, 2021 04 23.
Article in English | MEDLINE | ID: covidwho-1199961

ABSTRACT

PURPOSE: Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess. METHODS: This retrospective study focused on adult convalescent outpatients with SARS-CoV-2 positive serology during the COVID-19 pandemic at NewYork Presbyterian/Weill Cornell. Data collected for descriptive and correlative analysis included SARS-COV-2 immunoglobin G (IgG) levels and history of MetS comorbidities from April 17, 2020 to May 20, 2020. Additional data, including SARS-CoV-2 IgG levels, body mass index (BMI), hemoglobin A1c (HbA1c) and lipid levels were collected and analyzed for a second cohort from May 21, 2020 to June 21, 2020. SARS-CoV-2 neutralizing antibodies were measured in a subset of the study cohort. RESULTS: SARS-CoV-2 IgG levels were significantly higher in convalescent individuals with MetS comorbidities. When adjusted for age, sex, race, and time duration from symptom onset to testing, increased SARS-CoV-2 IgG levels remained significantly associated with obesity (P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with HbA1c ≥6.5% compared to those with HbA1c <5.7% (P = 0.0197) and remained significant on multivariable analysis (P = 0.0104). A positive correlation was noted between BMI and antibody levels [95% confidence interval: 0.37 (0.20-0.52) P < 0.0001]. Neutralizing antibody titers were higher in COVID-19 individuals with BMI ≥ 30 (P = 0.0055). CONCLUSION: Postconvalescent SARS-CoV-2 IgG and neutralizing antibodies are elevated in obese patients, and a positive correlation exists between BMI and antibody levels.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Metabolic Syndrome/immunology , Adult , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/virology , Female , Humans , Immunoglobulin G/blood , Male , Metabolic Syndrome/blood , Metabolic Syndrome/virology , Middle Aged , Obesity/blood , Obesity/immunology , Obesity/virology , Retrospective Studies
16.
Front Endocrinol (Lausanne) ; 12: 651009, 2021.
Article in English | MEDLINE | ID: covidwho-1190304

ABSTRACT

Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelet Disorders/etiology , Blood Platelets/chemistry , Blood Proteins/analysis , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Hypoglycemia/blood , Hypoglycemia/complications , Aged , COVID-19/complications , Case-Control Studies , Female , Glucose Clamp Technique , Humans , Lipids/blood , Male , Middle Aged , Platelet Activation , Thromboembolism/blood , Thromboembolism/etiology
17.
Diabetes Res Clin Pract ; 173: 108674, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1188452

ABSTRACT

OBJECTIVES: The DAR Global survey of Ramadan-fasting during the COVID-19 pandemic aimed to describe the characteristics and care in participants with type 2 diabetes (T2D) with a specific comparison between those <65 years and ≥65 years. METHODS: Participants were consented to answer a physician-administered questionnaire following Ramadan 2020. Impact of COVID-19 on the decision of fasting, intentions to fast and duration of Ramadan and Shawal fasting, hypoglycaemia and hyperglycaemia events were assessed. Specific analysis comparing age categories of <65 years and ≥65 years were performed. RESULTS: Among the 5865 participants, 22.5% were ≥65 years old. Concern for COVID-19 affected fasting decision for 7.6% (≥65 years) vs 5.4% (<65 years). More participants ≥65 years old did not fast (28.8% vs 12.7%, <65 years). Of the 83.6%, participants fulfilling Ramadan-fasting, 94.8% fasted ≥15 days and 12.6% had to break fast due to diabetes-related illness. The average number of days fasting within and post-Ramadan were 27 and 6 days respectively, regardless of age. Hypoglycaemia and hyperglycaemia occurred in 15.7% and 16.3% of participants respectively, with 6.5% and 7.4% requiring hospital care respectively. SMBG was performed in 73.8% of participants and 43.5% received Ramadan-focused education. CONCLUSION: During the COVID-19 pandemic, universally high rates of Ramadan-fasting were observed regardless of fasting risk level. Glycemic complications occurred frequently with older adults requiring higher rates of acute hospital care. Risk stratification is essential followed by pre-Ramadan interventions, Ramadan-focused diabetes education and self-monitoring to reduce and prevent complications, with particular emphasis in older adults.


Subject(s)
Aging/physiology , COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Fasting/physiology , Islam , Adult , Age Factors , Aged , Aged, 80 and over , Blood Glucose/analysis , Blood Glucose/metabolism , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Female , Health Knowledge, Attitudes, Practice , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Pandemics , SARS-CoV-2/physiology , Surveys and Questionnaires
18.
Diabetes Technol Ther ; 23(8): 537-545, 2021 08.
Article in English | MEDLINE | ID: covidwho-1171321

ABSTRACT

Background: The COVID-19 pandemic has impacted the conduct of clinic visits. We conducted a study to evaluate two academic laboratories' fingerstick capillary blood collection kits suitable for home use for laboratory measurement of HbA1c. Methods: Four clinical sites recruited 240 participants (aged 4-80 years, HbA1c 5.1%-13.5%). Capillary blood samples were obtained by the participant or parent using collection kits from two laboratories (University of Minnesota Advanced Research and Diagnostic Laboratory (ARDL) and Children's Mercy Hospital Laboratory (CMH)) and mailed under varying shipping conditions by United States Postal Service to the laboratories. Comparisons were made between HbA1c measurements from capillary samples and contemporaneously obtained venous samples. The primary outcome was percentage of capillary HbA1c values within 5% of the corresponding venous values. Results: HbA1c values were within 5% of venous values for 96% of ARDL kit specimens shipped with a cold pack and 98% without a cold pack and 99% and 99%, respectively, for the CMH kits. R2 values were 0.98, 0.99, 0.99, and 0.99, respectively. Results appeared similar across HbA1c levels and for pediatric and adult participants. Usability survey scores were high. Conclusions: Capillary blood collection kits, suitable for home use, from two academic laboratories, were demonstrated to be easy to use and provided results that are comparable with those obtained from venous specimens. Based on these results, there is strong evidence that HbA1c measurements from capillary specimens obtained with these specific kits can be used interchangeably with HbA1c measurements from venous specimens for clinical research and clinical care.


Subject(s)
Blood Specimen Collection/instrumentation , COVID-19 , Capillaries , Diabetes Mellitus/blood , Glycated Hemoglobin A/analysis , SARS-CoV-2 , Adolescent , Adult , Aged , Child , Child, Preschool , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Male , Middle Aged , Specimen Handling/methods , Veins
19.
Expert Rev Endocrinol Metab ; 16(3): 147-153, 2021 05.
Article in English | MEDLINE | ID: covidwho-1165207

ABSTRACT

Objectives: Changes in hematological parameters are becoming evident as important early markers of COVID-19. Type 2 Diabetes Mellitus (T2DM) has been shown to be associated with increased severity of COVID-19. In this study, we aim to explore the various hematological variables in COVID-19 positive patients with T2DM, so as to act early and improve patient outcomes.Methods: Medical e-records of seventy adult patients with T2DM who were COVID-19 positive have been analyzed in this retrospective cohort study. Demographic, clinical and laboratory parameters for these patients were examined.Results: Of the seventy patients with T2DM, 48.88% had poorly controlled diabetes. 70.69% were pyrexial, 56.25% were tachycardic and 38.58% were asymptomatic on presentation. Amongst the hematological parameters, anemia was seen in 10% of males and 15.38% of females. 20% had a high red-blood-cell-distribution-width (RDW). 7.27% had thrombocytosis and 3.64% had thrombocytopenia. 73.3% had a high platelet-distribution-width (PDW) and 44.44% had an increased mean-platelet-volume (MPV). 16.36% were neutropenic and 16.67% had lymphocytopenia.Conclusion: Diabetic COVID-19 positive patients have been shown to have prominent manifestations of the hemopoietic-system with varied hematological profiles. Recognizing the implications of these variables early in primary-care, can help clinicians aid management decisions and dictate early referral to secondary-care services, to help improve prognosis.


Subject(s)
COVID-19/blood , Diabetes Mellitus, Type 2/blood , Hematologic Diseases/blood , Primary Health Care/trends , Adult , Anemia/blood , Anemia/diagnosis , Anemia/epidemiology , Biomarkers/blood , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Erythrocyte Indices/physiology , Female , Hematologic Diseases/diagnosis , Hematologic Diseases/epidemiology , Humans , Male , Mean Platelet Volume/methods , Mean Platelet Volume/trends , Middle Aged , Platelet Count/methods , Platelet Count/trends , Primary Health Care/methods , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology
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