Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics

A novel RNA betacoronavirus causing coronavirus disease 2019 (Covid-19) has now been declared pandemic disease by WHO. Guo et al published the first report of biochemical features in patients with diabetes and the further risk that this disease can determine to the progression of Covid-19. Among different cytokines found significantly higher in patients with diabetes compared to those without, Interleukin-6 (IL-6), which is already increased in conditions of chronic inflammation, may play a more deleterious role in Covid-19 infection. Targeting the overexpression of Il-6 effects with a monoclonal antibody against IL-6 receptor or using Janus Kinase inhibitors may be particularly helpful for treatment of Covid-19 pneumonia in diabetes

The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

Purpose: Angiotensin converting enzyme 2 (ACE2) is the door for SARS-CoV-2, expressed in critical metabolic tissues. So, it is rational that the new virus causes pleiotropic alterations in glucose metabolism, resulting in the complication of pre-existing diabetes’s pathophysiology or creating new disease mechanisms. However, it seems that less attention has been paid to this issue. This review aimed to highlight the importance of long-term consequences and pleiotropic alterations in glucose metabolism following COVID-19 and emphasize the need for basic and clinical research in metabolism and endocrinology. Results: SARS-CoV-2 shifts cellular metabolism from oxidative phosphorylation to glycolysis, which leads to a decrease in ATP generation. Together with metabolic imbalance, the impaired immune system elevates the susceptibility of patients with diabetes to this deadly virus. SARS-CoV-2-induced metabolic alterations in immune cells can result in hyper inflammation and a cytokine storm. Metabolic dysfunction may affect therapies against SARS-CoV-2 infection. The effective control of metabolic complications could prove useful therapeutic targets for combating COVID-19. It is also necessary to understand the long-term consequences that will affect patients with diabetes who survived COVID-19. Conclusions: Since the pathophysiology of COVID-19 is still mostly unknown, identifying the metabolic mechanisms contributing to its progression is essential to provide specific ways to prevent and improve this dangerous virus’s detrimental effects. The findings show that the new virus may induce new-onset diabetes with uncertain metabolic and clinical features, supporting a potential role of COVID-19 in the development of diabetes

Use of DPP4 inhibitors in Italy does not correlate with diabetes prevalence among COVID-19 deaths

In a nationwide study of 3,818 charts from patients with fatal COVID-19, we found that geographical differences in Dipeptidyl peptidase 4 (DPP4) inhibitors use did not correlate with diabetes prevalence among COVID-19 deaths, thus not supporting the hypothesis of a clinically relevant involvement of DPP4 in COVID-19 development and progression

Zinc Transporter 8 Antibodies Complement GAD and IA-2 Antibodies in the Identification and Characterization of Adult-Onset Autoimmune Diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4

OBJECTIVE: Zinc transporter 8 (ZnT8) is an islet beta-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes. RESEARCH DESIGN AND METHODS: ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH(2)-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study. RESULTS: ZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH(2) were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all P(trend) < 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P < 0.001). CONCLUSIONS: ZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes

Transaminase abnormalities and adaptations of the liver lobule manifest at specific cut-offs of steatosis

There is little documented evidence suggesting that liver fat is responsible for liver injury in the absence of other disease processes. We investigated the relationships between liver fat, aminotransferases and hepatic architecture in liver biopsies with simple steatosis. We identified 136 biopsies with simple steatosis from the Royal Free Hospital Archives with both clinical data and sufficient material. Digital image analysis was employed to measure fat proportionate area (mFPA). Hepatocyte area (HA) and lobule radius (LR) were also measured. There were significant increases in ALT (p &lt; 0.001) and AST (p = 0.013) with increased fat content and evidence to suggest both 5% and 20% mFPA as a cut-off for raised ALT. In liver with increased fat content there were significant increases in HA (p &lt; 0.001). LR also increased as mFPA increased to 10% (p &lt; 0.001), at which point the lobule ceased to expand further and was counterbalanced with a decrease in the number of hepatocytes per lobule (p = 0.029). Consequently there are mechanisms of adaption in the liver architecture to accommodate the accumulation of fat and these are accompanied by significant increases in transaminases. These results support the generally accepted cut-off of 5% fat for steatosis and indicate 20% as a threshold of more severe liver injury

Dietary Fat, Sugar Consumption, and Cardiorespiratory Fitness in Patients With Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is associated with obesity and, indirectly, with unhealthy diet. The role of dietary components in HFpEF is, however, largely unknown. In this study, the authors showed that in obese HFpEF patients, consumption of unsaturated fatty acids (UFA), was associated with better cardiorespiratory fitness, and UFA consumption correlated with better diastolic function and with greater fat-free mass. Similarly, mice fed with a high-fat diet rich in UFA and low in sugars had preserved myocardial function and reduced weight gain. Randomized clinical trials increasing dietary UFA consumption and reducing sugar consumption are warranted to confirm and expand our findings

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS

Aims: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6&nbsp;months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. Methods: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. Results: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00–pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p &lt; 0.05). Conclusions: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. Clinical trial registration: EudraCT 2015-001167-3

Pasta consumption and connected dietary habits: Associations with glucose control, adiposity measures, and cardiovascular risk factors in people with type 2 diabetes—TOSCA.IT study

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors