Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes ...mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium-glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.
Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a ...gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.
To examine the association of diabetes stigma with psychological, behavioral, and HbA
outcomes and to investigate moderation effects of self-esteem, self-efficacy, and/or social support.
The national ...Second Diabetes MILES - Australia (MILES-2) survey included adults with type 1 diabetes (
= 959, 41% of whom were male, with mean ± SD age 44 ± 15 years), insulin-treated type 2 diabetes (
= 487, 60% male, age 61 ± 9 years), and non-insulin-treated type 2 diabetes (
= 642, 55% male, age 61 ± 10 years). (Un)adjusted linear regression analyses tested the association between diabetes stigma (Diabetes Stigma Assessment Scale DSAS) and psychological outcomes (depressive symptoms eight-item version of the Patient Health Questionnaire (PHQ-8), anxiety symptoms Generalized Anxiety Disorder 7-item (GAD-7) questionnaire, and diabetes-specific distress 20-item Problem Areas In Diabetes (PAID) scale), behavioral outcomes (healthy diet and physical activity Summary of Diabetes Self-Care Activities (SDSCA)), and self-reported HbA
. Interaction effects tested whether associations varied by self-esteem (Rosenberg Self-Esteem Scale RSES), self-efficacy (Confidence in Diabetes Self-Care CIDS scale), or diabetes-specific social support (Diabetes Support Scale DSS).
Significant positive associations were observed between DSAS and PHQ-8, GAD-7, and PAID across diabetes type/treatment groups (all
< 0.001), whereby each SD increase in DSAS scores was associated with approximately one-half SD deterioration in emotional well-being. Associations between DSAS and SDSCA and HbA
were nonmeaningful. Self-esteem moderated psychological outcomes among participants with type 1 and non-insulin-treated type 2 diabetes and diabetes distress among those with insulin-treated type 2 diabetes. Interaction effects were partially observed for social support but not for self-efficacy.
This study provides evidence of the association between diabetes stigma and depressive/anxiety symptoms and diabetes distress and for the moderating effects of self-esteem and social support among adults with type 1 and type 2 diabetes. Further research is needed to examine associations with objectively measured behavioral and clinical outcomes.
Abstract Background Research suggests that co-morbid diabetes and depression is common; however, the implications for clinical practice remain unclear. This paper reviews the current epidemiological ...evidence on comorbid diabetes and depression, in order to identify the key publications which could both inform practice and identify gaps in knowledge and research. Methods A systematic review was conducted to identify published literature on the epidemiology of diabetes and depression. In order to review evidence on up-to-date knowledge of recent research and innovations in care literature searches for the last five years (August 2006–August 2011) were conducted. To identify relevant literature, electronic databases MEDLINE, Psych-INFO and EMBASE were searched for English language articles in peer-reviewed journals. Results High rates of co-morbidity of depression and diabetes have been reported. The prevalence rate of depression is more than three-times higher in people with type 1 diabetes (12%, range 5.8–43.3% vs. 3.2%, range 2.7–11.4%) and nearly twice as high in people with type 2 diabetes (19.1%, range 6.5–33% vs. 10.7%, range 3.8–19.4%) compared to those without. Women with diabetes and also women without diabetes experience a higher prevalence of depression than men. Reviewed studies provide support for a modest relationship between diabetes and depressive symptoms, but the exact direction of this relationship remains unclear. Limitations Most studies reviewed were cross-sectional and this limits any conclusions about the causal nature and direction of the relationship between diabetes and depression. Variation in measurement methods, lack of longitudinal data and few studies outside Europe and America limit the generalizability of the findings of this review. Conclusions Current research suggests that the risk of developing depression is increased in people with diabetes; however, further studies are required in order to establish the nature of the relationship between depression, glycaemic control and the development of diabetes complications, and make appropriate recommendations for treatment and to support self-management of diabetes.
Type 1 and type 2 diabetes are characterized by chronic inflammation; both diseases involve pancreatic islet inflammation, while systemic low-grade inflammation is a feature of obesity and type 2 ...diabetes. Long-term activation of the innate immune system impairs insulin secretion and action, and inflammation also contributes to macrovascular and microvascular complications of diabetes. However, despite strong preclinical evidence and proof-of-principle clinical trials demonstrating that targeting inflammatory pathways can prevent cardiovascular disease and other complications in patients with diabetes, there are still no approved treatments for diabetes that target innate immune mediators. Here, we review recent advances in our understanding of the inflammatory pathogenesis of type 1 and type 2 diabetes from a translational angle and point out the critical gaps in knowledge that need to be addressed to guide drug development.
Summary
Diabetes (DM) as well as obesity, due to their increasing incidence, were recognized as epidemic by the World Health Organization. Obesity is involved not only in the aetiopathogenesis of the ...most common worldwide type of DM—type 2 diabetes—but also in the development of its complications. There is also increasing scientific evidence regarding the role of obesity and overweight in type 1 diabetes. Weight gain may be considered as a complication of insulin treatment but also reveals significant pathophysiological impact on various stages of the disease. Another very important aspect related to DM as well as obesity is the microbiome, which is highly variable. The function of the gut microflora, its interaction with the whole organism, and its role in the development of obesity and type 1 diabetes as well as type 2 diabetes are still not fully understood and subject of ongoing investigations. This review presents a summary of recently published results concerning the relation of obesity/overweight and DM as well as their associations with the microbiome.
The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The ...Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.
We investigated non‐alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes (T1D), and in insulin‐naïve and insulin‐treated patients with type ...2 diabetes (T2D). Baseline data from patients who had liver fat content (LFC) evaluated by magnetic resonance imaging in four phase 3 studies of basal insulin peglispro (BIL) were analysed. Associations of NAFLD with clinical characteristics, glycaemic control and diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC ≥ 6%) was low in T1D (8.8%) but high in T2D, with greater prevalence in insulin‐naïve (75.6%) vs insulin‐treated (61.7%) T2D patients. LFC (mean ± SD) was higher in T2D patients (insulin‐naïve, 13.0% ± 8.4%; insulin‐treated, 10.2% ± 7.8%) than in T1D patients (3.2% ± 3.2%). In T2D, NAFLD was associated with several markers of insulin resistance. In all three populations, there was an absence of association of HbA1c with LFC, but insulin doses were higher in patients with NAFLD.
End organ injury in diabetes mellitus (DM) is driven by microvascular compromise (including diabetic retinopathy and nephropathy). Cognitive impairment is a well-known complication of DM types 1 and ...2; however, its mechanism(s) is(are) not known. We hypothesized that blood-brain barrier (BBB) compromise plays a key role in cognitive decline in DM. Using a DM type 1 model (streptozotocin injected C57BL/6 mice) and type 2 model (leptin knockout obese db/db mice), we showed enhanced BBB permeability and memory loss (Y maze, water maze) that are associated with hyperglycemia. Gene profiling in isolated microvessels from DM type 1 animals demonstrated deregulated expression of 54 genes related to angiogenesis, inflammation, vasoconstriction/vasodilation, and platelet activation pathways by at least 2-fold (including eNOS, TNFα, TGFβ1, VCAM-1, E-selectin, several chemokines, and MMP9). Further, the magnitude of gene expression was linked to degree of cognitive decline in DM type 1 animals. Gene analysis in brain microvessels of DM type 2 db/db animals showed alterations of similar genes as in DM 1 model, some to an even greater extent. Neuropathologic analyses of brain tissue derived from DM mice showed microglial activation, expression of ICAM-1, and attenuated coverage of pericytes compared to controls. There was a significant upregulation of inflammatory genes in brain tissue in both DM models. Taken together, our findings indicate that BBB compromise in DM in vivo models and its association with memory deficits, gene alterations in brain endothelium, and neuroinflammation. Prevention of BBB injury may be a new therapeutic approach to prevent cognitive demise in DM.
Abstract Background Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic ...hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. Aim This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. Results Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. Conclusion It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients.
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