Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.

Melatonin improved glucose homeostasis is associated with the reprogrammed gut microbiota and reduced fecal levels of short-chain fatty acids in db/db mice.

Accumulated evidence shows that melatonin possesses the potential to improve lipid metabolism by modifying gut microbiota and glucose metabolism via regulating the melatonin receptor signaling pathway. However, the contribution of melatonin consumption on glucose homeostasis by affecting gut microbiota has not been investigated in diabetes. In the current work, we investigated the effect of melatonin administration on gut microbiota and glucose homeostasis in db/db mice, a type 2 diabetes model with leptin receptor deficiency. Administration of melatonin through drinking water (at 0.25% and 0.50%) for 12 weeks decreased diabetic polydipsia and polyuria, increased insulin sensitivity and impeded glycemia. The accumulated fecal levels of total short-chain fatty acids (SCFAs) and acetic acid are positively correlated with diabetes-related parameters-homeostasis model assessment of insulin resistance (HOMA-IR) index and fasting blood glucose (FBG) level. The reprogramming of gut microbiota structure and abundance and the reduction of fecal levels of SCFAs, including acetic acid, butyric acid, isovaleric acid, caproic acid, and isobutyric acid, by melatonin may be beneficial for enhancing insulin sensitivity and lowering FBG, which were verified by the results of correlation analysis between acetic acid or total SCFAs and HOMA-IR and FBG. In addition, the melatonin downregulated hepatic genes, including fructose-1,6-bisphosphatase 1, forkhead box O1 alpha, thioredoxin-interacting protein, phosphoenolpyruvate carboxy-kinase (PEPCK), PEPCK1 and a glucose-6-phosphatase catalytic subunit, that responsible for gluconeogenesis support the result that melatonin improved glucose metabolism. Overall, results showed that the melatonin supplementation reduced fecal SCFAs level via reprogramming of gut microbiota, and the reduction of fecal SCFAs level is associated with improved glucose homeostasis in db/db mice.

Obesity and COVID-19: insights from two pandemics.

This review article discusses the pathophysiological mechanisms of the development of coronavirus infection in obese patients. It has been shown that obesity is considered as the most important risk factor for the development of many comorbid diseases, including severe forms and deaths as a result of a new coronavirus infection. The higher incidence and severity of a new coronavirus infection in obese patients is based on a complex of factors, the main of which are an increase in cardiovascular risk, including a tendency to thrombosis, a decrease in the efficiency of the respiratory system, impaired immune response, and the presence of chronic inflammatory state. The article discusses non-drug approaches and issues of pharmacological therapy in patients with obesity in the context of a pandemic of a new coronavirus infection. It is shown that the implementation of national quarantine measures has led to an increase in physical inactivity, the level of stress and a change in the eating behavior of the population, closing a vicious circle and contributing to an increase in body weight. For this reason, the efforts of physicians of therapeutic specialties should be directed primarily to increasing resistance to infection among obese patients and combating physical inactivity. The main groups of drugs that can be used to combat lipotoxicity are listed. It was noted that infectious disease doctors and endocrinologists can use those groups of drugs that affect the most vulnerable pathogenetic triggers for the development of obesity and comorbidities: hunger and satiety processes, decreased insulin sensitivity, development of lipotoxicity and chronic inflammation. It has been proven that the range of positive effects of new antihyperglycemic drugs from the groups of type 1 glucagon-like peptide agonists and type 2 sodium-glucose transporter inhibitors, combined with a well-studied efficacy and safety profile, represents a new opportunity for the treatment of obesity in the context of a coronavirus infection pandemic.Copyright © 2022 Authors. All rights reserved.

Obesity and COVID-19: insights from two pandemics.

This review article discusses the pathophysiological mechanisms of the development of coronavirus infection in obese patients. It has been shown that obesity is considered as the most important risk factor for the development of many comorbid diseases, including severe forms and deaths as a result of a new coronavirus infection. The higher incidence and severity of a new coronavirus infection in obese patients is based on a complex of factors, the main of which are an increase in cardiovascular risk, including a tendency to thrombosis, a decrease in the efficiency of the respiratory system, impaired immune response, and the presence of chronic inflammatory state. The article discusses non-drug approaches and issues of pharmacological therapy in patients with obesity in the context of a pandemic of a new coronavirus infection. It is shown that the implementation of national quarantine measures has led to an increase in physical inactivity, the level of stress and a change in the eating behavior of the population, closing a vicious circle and contributing to an increase in body weight. For this reason, the efforts of physicians of therapeutic specialties should be directed primarily to increasing resistance to infection among obese patients and combating physical inactivity. The main groups of drugs that can be used to combat lipotoxicity are listed. It was noted that infectious disease doctors and endocrinologists can use those groups of drugs that affect the most vulnerable pathogenetic triggers for the development of obesity and comorbidities: hunger and satiety processes, decreased insulin sensitivity, development of lipotoxicity and chronic inflammation. It has been proven that the range of positive effects of new antihyperglycemic drugs from the groups of type 1 glucagon-like peptide agonists and type 2 sodium-glucose transporter inhibitors, combined with a well-studied efficacy and safety profile, represents a new opportunity for the treatment of obesity in the context of a coronavirus infection pandemic.Copyright © 2022 Authors. All rights reserved.

IDF2022-0635 Can COVID-19 infection provoke new-onset A-beta+ KPD (ketosis-prone diabetes)? - Insights from an Indian prospective study

Background COVID-19 as a trigger for A-beta+ ketosis-prone diabetes (KPD) [1,2] in previously normoglycemic individuals presenting with new-onset DKA, has been sparsely studied. Aim To study prospective changes in insulin secretion and insulin resistance in suspected A-beta+ KPD patients presenting with COVID-associated new-onset DKA. Method 22 previously non-diabetic, antibody-negative patients with new-onset DKA and RT-PCR positive COVID-19 (suspected A-beta + KPD), were followed up for one year. They were compared with 20 Type 1A and 18 Type 2 DM patients, with serial assessments (0,6 and 12 months) of insulin secretion rates (ISR) and multi-tissue insulin resistance (IR). 75-g OGTT with serial glucose, insulin and C-peptide estimation (0,15, 30,45, 60,90,120, 150 and 180 minutes) was used to derive IS, while hepatic and peripheral IR was calculated based on study by Ghani et al. [3]. Results At baseline, ISR in suspected KPD (n = 22) was significantly reduced but similar to Type 1A DM(p = 0.15). Serial ISR demonstrated complete recovery in 17 (77%) patients who became insulin independent at one-year follow-up (remission), while 5(23%) patients continued to require insulin (non-remission). KPD patients showed significant hepatic and peripheral IR at baseline compared to Type 1A DM (p < 0.05). The remission group (n = 17) showed significantly enhanced recovery of hepatic and peripheral insulin sensitivity at 6 and 12 months follow-up (all p < 0.01) compared to the non-remission (n = 5) group, with IR in the latter being comparable to Type 2 DM at follow-up (all p > 0.05). Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were factors associated with poorer recovery of beta-cell secretion amongst the KPD patients. Conclusion This is the first prospective study to demonstrate progressive recovery of p-cell secretion in new-onset A-beta + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM.Copyright © 2023 Elsevier B.V.

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.

Associations of resting and peak fat oxidation with sex hormone profile and blood glucose control in middle-aged women.

BACKGROUND AND AIMS: Menopause may reduce fat oxidation. We investigated whether sex hormone profile explains resting fat oxidation (RFO) or peak fat oxidation (PFO) during incremental cycling in middle-aged women. Secondarily, we studied associations of RFO and PFO with glucose regulation. METHOD AND RESULTS: We measured RFO and PFO of 42 women (age 52-58 years) with indirect calorimetry. Seven participants were pre- or perimenopausal, 26 were postmenopausal, and nine were postmenopausal hormone therapy users. Serum estradiol (E2), follicle-stimulating hormone, progesterone, and testosterone levels were quantified with immunoassays. Insulin sensitivity (Matsuda index) and glucose tolerance (area under the curve) were determined by glucose tolerance testing. Body composition was assessed with dual-energy X-ray absorptiometry; physical activity with self-report and accelerometry; and diet, with food diaries. Menopausal status or sex hormone levels were not associated with the fat oxidation outcomes. RFO determinants were fat mass (ß = 0.44, P = 0.006) and preceding energy intake (ß = -0.40, P = 0.019). Cardiorespiratory fitness (ß = 0.59, P = 0.002), lean mass (ß = 0.49, P = 0.002) and physical activity (self-reported ß = 0.37, P = 0.020; accelerometer-measured ß = 0.35, P = 0.024) explained PFO. RFO and PFO were not related to insulin sensitivity. Higher RFO was associated with poorer glucose tolerance (ß = 0.52, P = 0.002). CONCLUSION: Among studied middle-aged women, sex hormone profile did not explain RFO or PFO, and higher fat oxidation capacity did not indicate better glucose control.

Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness.

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW.

Effects of Weight Loss on Adipose and Muscular Neuropilin 1 mRNA Expression in Obesity: Potential Implication in SARS-CoV-2 Infections?

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.

MLR-1023 Treatment in Mice and Humans Induces a Thermogenic Program, and Menthol Potentiates the Effect.

A glucose-lowering medication that acts by a different mechanism than metformin, or other approved diabetes medications, can supplement monotherapies when patients fail to meet blood glucose goals. We examined the actions underlying the effects of an insulin sensitizer, tolimidone (MLR-1023) and investigated its effects on body weight. Diet-induced obesity (CD1/ICR) and type 2 diabetes (db/db) mouse models were used to study the effect of MLR-1023 on metabolic outcomes and to explore its synergy with menthol. We also examined the efficacy of MLR-1023 alone in a clinical trial (NCT02317796), as well as in combination with menthol in human adipocytes. MLR-1023 produced weight loss in humans in four weeks, and in mice fed a high-fat diet it reduced weight gain and fat mass without affecting food intake. In human adipocytes from obese donors, the upregulation of Uncoupling Protein 1, Glucose (UCP)1, adiponectin, Glucose Transporter Type 4 (GLUT4), Adipose Triglyceride Lipase (ATGL), Carnitine palmitoyltransferase 1 beta (CPT1ß), and Transient Receptor Potential Melastin (TRPM8) mRNA expression suggested the induction of thermogenesis. The TRPM8 agonist, menthol, potentiated the effect of MLR-1023 on the upregulation of genes for energy expenditure and insulin sensitivity in human adipocytes, and reduced fasting blood glucose in mice. The amplification of the thermogenic program by MLR-1023 and menthol in the absence of adrenergic activation will likely be well-tolerated, and bears investigation in a clinical trial.

Vanadium as potential therapeutic agent for COVID-19: A focus on its antiviral, antiinflamatory, and antihyperglycemic effects.

An increasing evidence suggests that vanadium compounds are novel potential drugs in the treatment of diabetes, atherosclerosis, and cancer. Vanadium has also demonstrated activities against RNA viruses and is a promising candidate for treating acute respiratory diseases. The antidiabetic, antihypertensive, lipid-lowering, cardioprotective, antineoplastic, antiviral, and other potential effects of vanadium are summarized here. Given the beneficial antihyperglycemic and antiinflammatory effects as well as the potential mechanistic link between the COVID-19 and diabetes, vanadium compounds could be considered as a complement to the prescribed treatment of COVID-19. Thus, further clinical trials are warranted to confirm these favorable effects of vanadium treatment in COVID-19 patients, which appear not to be studied yet.

Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

BACKGROUND & AIMS: Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS: 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS: ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS: Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.