Coronavirus infection (SARS-CoV-2) in obesity and diabetes comorbidities : is heat shock response determinant for the disease complications?

Chronic infammation is involved in the pathogenesis of several metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). With the recent worldwide outbreak of coronavirus disease (SARS-CoV-2), it has been observed that individuals with these metabolic diseases are more likely to develop complications, increasing the severity of the disease and a poorer outcome. Coronavirus infection leads to the activation of adaptive and innate immune responses, resulting in massive infammation (to so called cytokine storm), which in turn can lead to damage to various tissues, septic shock and multiple organ failure. Recent evidence suggests that the common link between metabolic diseases and SARS-CoV-2 is the infammatory response (chronic/low-grade for metabolic diseases and acute/intense in coronavirus infection). However, the ability of the infected individuals to resolve the infammation has not yet been explored. The heat shock response (HSR), an important anti-infammatory pathway, is reduced in patients with metabolic diseases and, consequently, may impair infammation resolution and control in patients with SARS-CoV-2, thus enabling its amplifcation and propagation through all tissues. Herein, we present a new hypothesis that aims to explain the increased severity of SARS-CoV-2 infection in people with metabolic diseases, and the possible benefts of HSR-inducing therapies to improve the infammatory profle in these patients

MRI-based early diagnosis : a diabetic Charcot spine case report

Background: Spinal neuroarthropathy (SNA), also known as Charcot spine, is an uncommon aggressive arthropathy, secondary to loss of proprioceptive and nociceptive feedback from the spine. A diagnosis of SNA is frequently delayed due to the scarcity of symptoms in its early stages, leading to significant neurological deterioration. Therefore, prompt suspicion of the disease is critical to providing better outcomes. This case assembles two rare characteristics of SNA: diabetic aetiology and a precocious time of diagnosis, and aims to highlight the magnetic resonance imaging (MRI) findings that allowed for the diagnosis. Case presentation: A 44-year-old woman, with long-term type 1 diabetes, presented with a two-month history of progressive lumbar pain, difficulty in maintaining an upright position, and discrete trunk forward-leaning. Diabetesrelated vasculopathy and nephropathy were already known, and laboratory test results did not show any new abnormalities. A lumbar MRI revealed extensive signal intensity changes of the L2 and L3 vertebral bodies associated with marginal areas of enhancement and the involvement of regions adjacent to interapophyseal articulations and spinous processes from L2–L3 to L5–S1, in association with degenerative changes of the thoracolumbar spine. These findings were identified by the radiologist as suggestive of SNA. To rule out neoplastic and infectious disease, a bone biopsy at the L2–L3 level was executed. The pathology report revealed intervertebral disc material and fragments of fibrous tissue, with a complete absence of inflammatory cells. It was decided to perform a six-month MRI follow-up, which showed stability of the findings, confirming the hypothesis of Charcot spine. The patient was under clinical and radiological follow-up and did not require surgical fixation at the moment of diagnosis. After 2.5 years from the initial diagnosis, a new MRI revealed progression of the lesions with oedema and enlarged paravertebral soft tissues; these findings are compatible with the patient’s latest complaints of lumbar pain recurrence. Conclusion: To the best of our knowledge, this is the first case report of an MRI-based early diagnosis of diabetic SNA, a rare disease with nonspecific symptoms in its initial stages and a wide spectrum of differential diagnoses. The MRI findings, distinctly the involvement of both anterior and posterior spinal elements, were the key to allowing for the proper diagnosis. A precocious diagnosis, although challenging, is fundamental to providing early intervention and to preventing further neurological impairment

Distinct metabolic profile according to the shape of the oral glucose tolerance test curve is related to whole glucose excursion : a cross-sectional study

Background: The shapes of the plasma glucose concentration curve during the oral glucose tolerance test are related to different metabolic risk profiles and future risk of type 2 DM. We sought to further analyze the relationship between the specific shapes and hyperglycemic states, the metabolic syndrome and hormones involved in carbohydrate and lipid metabolism, and to isolate the effect of the shape by adjusting for the area under the glucose curve. Methods: One hundred twenty one adult participants underwent a 2-h oral glucose tolerance test and were assigned to either the monophasic (n = 97) or the biphasic (n = 24) group based upon the rise and fall of their plasma glucose concentration. We evaluated anthropometric measures, blood pressure, lipid profile, high-sensitivity C-reactive protein, glycated hemoglobin, insulin sensitivity, beta-cell function, C-peptide, glucagon, adiponectin and pancreatic polypeptide. Results: Subjects with monophasic curves had higher fasting and 2-h plasma glucose levels, while presenting lower insulin sensitivity, beta-cell function, HDL cholesterol, adiponectin and pancreatic polypeptide levels. Prediabetes and metabolic syndrome had a higher prevalence in this group. Glycated hemoglobin, total cholesterol, triglycerides, highsensitivity C-reactive protein and glucagon were not significantly different between groups. After adjusting for the area under the glucose curve, only the differences in the 1-h and 2-h plasma glucose concentrations and HDL cholesterol levels between the monophasic and biphasic groups remained statistically significant. Conclusions: Rates and intensity of metabolic dysfunction are higher in subjects with monophasic curves, who have lower insulin sensitivity and beta-cell function and a higher prevalence of prediabetes and metabolic syndrome. These differences, however, seem to be dependent on the area under the glucose curve

Effect of transcranial direct current stimulation associated with hypocaloric diet on weight loss and metabolic profile in overweight or obesity : study protocol for a double-blind, randomized controlled clinical trial

Background: Dietary interventions have limited success in promoting sustainable weight loss; new treatments allowing better compliance with hypocaloric diets should be developed. The aim of this trial is to describe the effects of a protocol combining repetitive active transcranial direct current stimulation (tDCS) with a hypocaloric diet on weight loss and food consumption in overweight or obese adults. Methods/design: Overweight or obese adults between 20 and 50 years of age with stable weight over the last 4 months will be selected for a 4-week randomized clinical trial of fixed-dose tDCS (20 sessions; 5 consecutive weekdays/wk, 2 mA, 20 minutes) over the right dorsolateral prefrontal cortex associated with a weight loss diet. The subjects will be randomly assigned in a 1:1 ratio and stratified by sex to active tDCS + diet or sham tDCS + diet. The study will be conducted at the Endocrine and Metabolism Unit of the Hospital de Clínicas de Porto Alegre, Brazil. The primary outcome is weight loss. Energy and macronutrient consumption, as well as adherence to the diet, will be assessed using 3-day weighed dietary records. Changes in blood glucose and plasma insulin will be assessed, and participants will complete self-report questionnaires to assess changes in mood and food behavior. All analyses will be done on a per-protocol and intention-to-treat basis. Discussion: This study explores the potential role of tDCS as an adjunctive treatment with a hypocaloric diet for obesity management

Metabolic efects of antihyperglycemic agents and mortality : meta-analysis of randomized controlled trials

The efects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their efects on intermediate factors might explain these diferences. This systematic review explores the relationship between metabolic factors, mechanism of action, and mortality efects of antihyperglycemic medications in type 2 diabetes. Randomized trials assessing the efects of antihyperglycemic medications on all-cause or cardiovascular mortality in type 2 diabetes were included. Myocardial infarction, stroke, and heart failure were secondary outcomes. The efects of medications on HbA1c, severe hypoglycemia (SH), body weight, systolic blood pressure (SBP), and mechanism of action were evaluated. Meta-analyses and meta-regressions were performed grouping studies according to the above-cited factors. All-cause mortality was lower for medications that reduced HbA1c, SH, body weight, and SBP. Decreased cardiovascular mortality was associated with lower HbA1c, SH, SBP. Myocardial infarction and stroke were also associated with favorable metabolic profle. These fndings were not confrmed in meta-regression models. Medications associated with lower SH, body weight and SBP had a lower risk of heart failure. In conclusion, medications with better metabolic profle were associated with reduced all-cause and cardiovascular mortality. These fndings are based on indirect comparisons and must be applied cautiously