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1.
Medicina (Kaunas) ; 58(1)2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-1636386

ABSTRACT

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Diabetes Mellitus, Type 2/drug therapy , Fatty Acids, Nonesterified , Humans
2.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585887

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
4.
Obes Facts ; 15(1): 90-98, 2022.
Article in English | MEDLINE | ID: covidwho-1571513

ABSTRACT

INTRODUCTION: Neuropilin 1 (NRP-1) is a novel co-receptor promoting SARS-CoV-2 infectivity. Animal data indicate a role in trans-endothelial lipid transport and storage. As human data are sparse, we aimed to assess the role of NRP-1 in 2 metabolic active tissues in human obesity and in the context of weight loss-induced short- and long-term metabolic changes. METHODS: After a standardized 12-week weight reduction program, 143 subjects (age >18; body mass index ≥27 kg/m2, 78% female) were randomized to a 12-month lifestyle intervention or a control group using a stratified randomization scheme. This was followed by 6-month follow-up without any intervention. Phenotyping was performed before and after weight loss, after 12-month intervention and after subsequent 6 months of follow-up. Tissue-specific insulin sensitivity was estimated by HOMA-IR (whole body and mostly driven by liver), insulin sensitivity index (ISI)Clamp (predominantly skeletal muscle), and free fatty acid (FFA) suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). NRP-1 mRNA expression was measured in subcutaneous adipose tissue (NRP-1AT) and skeletal muscle (NRP-1SM) before and after weight loss. RESULTS: NRP-1 was highly expressed in adipose tissue (7,893 [7,303-8,536] counts), but neither NRP-1AT nor NRP-1SM were related to estimates of obesity. Higher NRP-1AT was associated with stronger FFASupp (r = -0.343, p = 0.003) and a tendency to higher ISIClamp (r = 0.202, p = 0.085). Weight loss induced a decline of NRP-1AT but not NRP-1SM. This was more pronounced in subjects with stronger reduction of adipose ACE-2 mRNA expression (r = 0.250; p = 0.032) but was not associated with short- and long-term improvement of FFASupp and ISIClamp. CONCLUSION: NRP-1AT is related to adipose insulin sensitivity in obesity. Weight loss-induced decline of NRP-1AT seems not to be involved in metabolic short- and long-term improvements after weight loss. However, weight loss-induced reduction of both NRP-1AT and ACE-2AT indicates a lower susceptibility of adipose tissue for SARS-CoV-2 after body weight reduction.


Subject(s)
COVID-19 , Insulin Resistance , Adipose Tissue , Female , Humans , Male , Neuropilin-1/genetics , Obesity/genetics , RNA, Messenger , SARS-CoV-2 , Weight Loss
5.
Int J Mol Sci ; 22(21)2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488608

ABSTRACT

Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support. Although the origin of chronic fatigue is multifactorial, the MF in illness conditions is intrinsically linked to the occurrence of muscle loss. The sequence of events leading to chronic fatigue can be schematically denoted as: trigger (genetic or pathological) -> molecular outcome within the muscle cell -> muscle wasting -> loss of muscle function -> occurrence of chronic muscle fatigue. The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting, thereby helping us understand how we could prevent or treat this debilitating condition.


Subject(s)
Muscle Fatigue/physiology , Muscle Proteins/metabolism , Muscle, Skeletal/physiology , Autophagy , COVID-19/physiopathology , Critical Illness , Humans , Insulin Resistance , Lysosomes/metabolism , Muscle Fatigue/drug effects , Muscle, Skeletal/physiopathology , Muscular Atrophy/etiology , Sarcopenia/physiopathology
6.
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
7.
Int J Mol Sci ; 22(18)2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1448875

ABSTRACT

The metabolic syndrome (MetS) consists of a cluster of metabolic abnormalities including central obesity, insulin resistance, glucose intolerance, hypertension, and atherogenic dyslipidemia [...].


Subject(s)
Metabolic Syndrome/metabolism , Obesity/metabolism , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Humans , Insulin Resistance/physiology , Metabolic Syndrome/physiopathology , Obesity/physiopathology
8.
Am J Clin Nutr ; 114(5): 1655-1665, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1349771

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) serves protective functions in metabolic, cardiovascular, renal, and pulmonary diseases and is linked to COVID-19 pathology. The correlates of temporal changes in soluble ACE2 (sACE2) remain understudied. OBJECTIVES: We explored the associations of sACE2 with metabolic health and proteome dynamics during a weight loss diet intervention. METHODS: We analyzed 457 healthy individuals (mean ± SD age: 39.8 ± 6.6 y) with BMI 28-40 kg/m2 in the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study. Biochemical markers of metabolic health and 236 proteins were measured by Olink CVDII, CVDIII, and Inflammation I arrays at baseline and at 6 mo during the dietary intervention. We determined clinical and routine biochemical correlates of the diet-induced change in sACE2 (ΔsACE2) using stepwise linear regression. We combined feature selection models and multivariable-adjusted linear regression to identify protein dynamics associated with ΔsACE2. RESULTS: sACE2 decreased on average at 6 mo during the diet intervention. Stronger decline in sACE2 during the diet intervention was independently associated with female sex, lower HOMA-IR and LDL cholesterol at baseline, and a stronger decline in HOMA-IR, triglycerides, HDL cholesterol, and fat mass. Participants with decreasing HOMA-IR (OR: 1.97; 95% CI: 1.28, 3.03) and triglycerides (OR: 2.71; 95% CI: 1.72, 4.26) had significantly higher odds for a decrease in sACE2 during the diet intervention than those without (P ≤ 0.0073). Feature selection models linked ΔsACE2 to changes in α-1-microglobulin/bikunin precursor, E-selectin, hydroxyacid oxidase 1, kidney injury molecule 1, tyrosine-protein kinase Mer, placental growth factor, thrombomodulin, and TNF receptor superfamily member 10B. ΔsACE2 remained associated with these protein changes in multivariable-adjusted linear regression. CONCLUSIONS: Decrease in sACE2 during a weight loss diet intervention was associated with improvements in metabolic health, fat mass, and markers of angiotensin peptide metabolism, hepatic and vascular injury, renal function, chronic inflammation, and oxidative stress. Our findings may improve the risk stratification, prevention, and management of cardiometabolic complications.This trial was registered at clinicaltrials.gov as NCT01826591.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Body Composition , COVID-19/metabolism , Diet, Reducing , Obesity/metabolism , Proteome/metabolism , Weight Loss/physiology , Adipose Tissue/metabolism , Adult , Biomarkers/blood , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Inflammation , Insulin Resistance , Male , Middle Aged , Obesity/diet therapy , Oxidative Stress , Pandemics , SARS-CoV-2 , Triglycerides/blood , Weight Reduction Programs
9.
J Endocrinol ; 249(1): 57-70, 2021 04.
Article in English | MEDLINE | ID: covidwho-1314460

ABSTRACT

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study's aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.


Subject(s)
Granulosa Cells/physiology , Heat-Shock Proteins/physiology , Polycystic Ovary Syndrome/physiopathology , Serpins/physiology , Adult , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Fertilization in Vitro , Follicular Fluid/chemistry , France , Gene Expression , Granulosa Cells/chemistry , Granulosa Cells/drug effects , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Humans , Infertility, Female/therapy , Insulin Resistance/physiology , Obesity/metabolism , Ovary/chemistry , Ovary/metabolism , RNA, Messenger/analysis , Serpins/genetics , Serpins/pharmacology , Steroids/biosynthesis
10.
Islets ; 13(3-4): 66-79, 2021 07 04.
Article in English | MEDLINE | ID: covidwho-1310869

ABSTRACT

The link between COVID-19 infection and diabetes has been explored in several studies since the start of the pandemic, with associations between comorbid diabetes and poorer prognosis in patients infected with the virus and reports of diabetic ketoacidosis occurring with COVID-19 infection. As such, significant interest has been generated surrounding mechanisms by which the virus may exert effects on the pancreatic ß cells. In this review, we consider possible routes by which SARS-CoV-2 may impact ß cells. Specifically, we outline data that either support or argue against the idea of direct infection and injury of ß cells by SARS-CoV-2. We also discuss ß cell damage due to a "bystander" effect in which infection with the virus leads to damage to surrounding tissues that are essential for ß cell survival and function, such as the pancreatic microvasculature and exocrine tissue. Studies elucidating the provocation of a cytokine storm following COVID-19 infection and potential impacts of systemic inflammation and increases in insulin resistance on ß cells are also reviewed. Finally, we summarize the existing clinical data surrounding diabetes incidence since the start of the COVID-19 pandemic.


Subject(s)
Insulin-Secreting Cells/physiology , SARS-CoV-2/physiology , Bystander Effect/physiology , COVID-19/complications , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/physiopathology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/virology , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Diabetes Mellitus/virology , Humans , Inflammation/complications , Inflammation/metabolism , Inflammation/virology , Insulin Resistance/physiology , Insulin-Secreting Cells/virology , Pandemics , SARS-CoV-2/pathogenicity
11.
BMC Pregnancy Childbirth ; 21(1): 427, 2021 Jun 16.
Article in English | MEDLINE | ID: covidwho-1277922

ABSTRACT

BACKGROUND: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals. CASE PRESENTATIONS: We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery. CONCLUSION: We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.


Subject(s)
COVID-19/diagnosis , Ketosis/diagnosis , Pregnancy Complications/diagnosis , Starvation/complications , COVID-19/complications , Female , Fluid Therapy/methods , Humans , Insulin Resistance , Ketosis/complications , Ketosis/therapy , Maternal-Fetal Exchange , Pregnancy , Pregnancy Complications/therapy , SARS-CoV-2 , Starvation/therapy
12.
Immunology ; 164(3): 467-475, 2021 11.
Article in English | MEDLINE | ID: covidwho-1266332

ABSTRACT

A number of mechanisms have been proposed to explain the well-established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID-19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune-related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID-19 infections.


Subject(s)
Blood Glucose/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 1/metabolism , Insulin/metabolism , Lymphocytes/metabolism , SARS-CoV-2/pathogenicity , Animals , Biomarkers/blood , COVID-19/immunology , COVID-19/physiopathology , COVID-19/virology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/physiopathology , Host-Pathogen Interactions , Humans , Immune Checkpoint Proteins/metabolism , Insulin Resistance , Lymphocytes/immunology , Lymphocytes/virology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, Insulin/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
13.
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
14.
Immunopharmacol Immunotoxicol ; 43(3): 265-270, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1246577

ABSTRACT

Understanding the exact role of current drugs in Covid-19 disease is essential in the era of global pandemics. Metformin which prescribed as the first-line treatment of type 2 diabetes has beneficial effects on Sars-cov2 infection. These effects are including regulation of immune system, Renin-Angiotensin System and Dipeptidyl Peptidase 4 function in Covid-19 infection. It also activates ACE2, the main receptor of Sars-cov2, in the epithelial cells of respiratory tissue through AMPK signaling and subsequently decreases the rate of viral adhesion. Metformin also declines the adherence of Sars-cov2 to DPP4 (the other receptor of the virus) on T cells. Hence, regulatory effects of metformin on membranous ACE2, and DPP4 can modulate immune reaction against Sars-cov2. Also, immunometabolic effects of metformin on inflammatory cells impair hyper-reactive immune response against the virus through reduction of glycolysis and propagation of mitochondrial oxidation. Metformin also decreases platelet aggravation and risk of thrombosis. In this article, we argue that metformin has beneficial effects on Covid-19 infection in patients with type 2 diabetes and insulin resistance. This opinion should be investigated in future clinical trials.


Subject(s)
COVID-19/drug therapy , Diabetes Mellitus, Type 2 , Drug Repositioning , Insulin Resistance , Metformin/therapeutic use , SARS-CoV-2 , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans
15.
Nat Metab ; 3(6): 774-785, 2021 06.
Article in English | MEDLINE | ID: covidwho-1243313

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.


Subject(s)
Blood Glucose/metabolism , COVID-19/blood , Hyperglycemia/metabolism , COVID-19/complications , COVID-19/virology , Cohort Studies , Humans , Hyperglycemia/complications , Insulin Resistance , Insulin-Secreting Cells/pathology , SARS-CoV-2/isolation & purification
16.
Nat Rev Endocrinol ; 17(4): 192, 2021 04.
Article in English | MEDLINE | ID: covidwho-1241968
17.
Endocr Pract ; 27(8): 834-841, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1196706

ABSTRACT

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge. METHODS: This 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index. RESULTS: Fasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 µg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index. CONCLUSION: Our study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.


Subject(s)
COVID-19 , Diabetes Mellitus , Insulin Resistance , Adult , Blood Glucose , Humans , Insulin , Male , Prospective Studies , SARS-CoV-2 , Triglycerides
18.
Cells ; 10(4)2021 04 17.
Article in English | MEDLINE | ID: covidwho-1194614

ABSTRACT

Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.


Subject(s)
COVID-19/complications , Obesity/complications , Animals , COVID-19/immunology , COVID-19/pathology , Chronic Disease , Humans , Immunity , Inflammation/complications , Inflammation/immunology , Inflammation/pathology , Insulin Resistance , Obesity/immunology , Obesity/pathology , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Severity of Illness Index , Unfolded Protein Response , Virus Internalization
19.
Prim Care Diabetes ; 15(4): 629-634, 2021 08.
Article in English | MEDLINE | ID: covidwho-1174449

ABSTRACT

BACKGROUND: The epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes. METHODS: An online search of all published literature was done via PubMed and Google Scholar using the MeSH terms "COVID-19," "SARS-CoV-2," "coronavirus," "insulin resistance," and "diabetes." Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed. RESULTS: Current data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection. CONCLUSION: Patients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Insulin Resistance , Metabolic Syndrome/epidemiology , COVID-19/metabolism , COVID-19/virology , Comorbidity , Diabetes Mellitus/metabolism , Host-Pathogen Interactions , Humans , Metabolic Syndrome/metabolism , Metabolic Syndrome/virology , Prognosis , Renin-Angiotensin System , Risk Assessment , Risk Factors , SARS-CoV-2/pathogenicity
20.
Clin Appl Thromb Hemost ; 27: 1076029621996445, 2021.
Article in English | MEDLINE | ID: covidwho-1148196

ABSTRACT

BACKGROUND: To investigate the factors associated with elevated fibrinogen (Fbg) levels in COVID-19 patients with and without diabetes (DM) and impaired fasting glucose (IFG). METHODS: According to whether or not their glucose metabolism was impaired, COVID-19 patients were subdivided into 2 groups: 1) with DM and IFG, 2) control group. Their demographic data, medical history, signs and symptoms, laboratory results, and final clinical results were analyzed retrospectively. RESULTS: 28 patients (16.3%) died during hospitalization, including 21 (29.2%) in group 1 and 7 (7.0%) in group 2 (P < 0.001). Fbg levels in groups 1 and 2 were higher than the normal range, at 5.6 g/L (IQR 4.5-7.2 g/L) and 5.0 g/L (IQR 4.0-6.1 g/L), respectively (P = 0.009). Serum ferritin levels, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), triglycerides (TG) were significantly increased in group 1 compared to those in the control. TG levels were 1.3 mmol/L in the control, while that in group 1 was 1.8 mmol/L. Multiple linear regression showed that the predicting factors of Fbg in the control group were serum ferritin and CRP, R2 = 0.295; in group 1, serum ferritin, CRP, and TG, R2 = 0.473. CONCLUSIONS: Fbg in all COVID-19 patients is related to serum ferritin and CRP involved in inflammation. Furthermore, in COVID-19 patients with insulin resistance, Fbg is linearly positively correlated with TG. This suggests that regulation of TG, insulin resistance, and inflammation may reduce hypercoagulability in COVID-19 patients, especially those with insulin resistance.


Subject(s)
Blood Glucose/analysis , COVID-19/blood , Diabetes Mellitus/blood , Fasting/blood , Fibrinogen/analysis , Insulin Resistance , Thrombophilia/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Coagulation , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/virology , Diabetes Mellitus/diagnosis , Female , Ferritins/blood , Humans , Inflammation Mediators/blood , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Thrombophilia/virology , Triglycerides/blood , Up-Regulation , Young Adult
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