OBJECTIVEDiabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODSIn this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTSThe proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P 5 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P 5 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P 5 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONSC-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death

<div><b>OBJECTIVE:</b> Diabetes is one of the most distinct comorbidities of COVID-19. Here, we described the clinical characteristics and outcomes in diabetic patients with confirmed or clinically diagnosed (with typical lung imaging features and symptoms) COVID-19, and their association with glucose lowering or blood pressure lowering medications.</div><div><br></div><div><b>RESEARCH DESIGN AND METHODS: </b>In this retrospective study involving 904 COVID-19 patients (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between diabetic vs non-diabetic groups, and different medication groups. Logistic regression was used to explore risk factors associated with mortality or poor prognosis.</div><div><br></div><div><b>RESULTS:</b> Proportion of comorbid diabetes is similar between confirmed and clinically diagnosed COVID-19 cases. Risk factors for higher mortality of diabetic patients with COVID-19 were elder age (adjusted OR [aOR] 1.09 [95% CI 1.04, 1.15], per year increase, P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24], mg/dL, P = 0.043). Insulin usage (aOR 3.58 [95%CI 1.37, 9.35], P = 0.009) was associated with poor prognosis. Clinical outcomes of ACE inhibitor or angiotensin II type-I receptor blocker (ACEI/ARB) users were comparable to non-ACEI/ARB users in COVID-19 patients with diabetes and hypertension.</div><div><br></div><div><b>CONCLUSIONS: </b>C-reactive protein may help to identify diabetic patients with greater risk. Elder diabetic patients were prone to COVID-19-related fatality. Attentions need to be paid on insulin-using diabetic patients with COVID-19. ACEI/ARB showed no significant impact on COVID-19 patients with diabetes and hypertension.</div>

<div><b>OBJECTIVE:</b> Diabetes is one of the most distinct comorbidities of COVID-19. Here, we described the clinical characteristics and outcomes in diabetic patients with confirmed or clinically diagnosed (with typical lung imaging features and symptoms) COVID-19, and their association with glucose lowering or blood pressure lowering medications.</div><div><br></div><div><b>RESEARCH DESIGN AND METHODS: </b>In this retrospective study involving 904 COVID-19 patients (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between diabetic vs non-diabetic groups, and different medication groups. Logistic regression was used to explore risk factors associated with mortality or poor prognosis.</div><div><br></div><div><b>RESULTS:</b> Proportion of comorbid diabetes is similar between confirmed and clinically diagnosed COVID-19 cases. Risk factors for higher mortality of diabetic patients with COVID-19 were elder age (adjusted OR [aOR] 1.09 [95% CI 1.04, 1.15], per year increase, P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24], mg/dL, P = 0.043). Insulin usage (aOR 3.58 [95%CI 1.37, 9.35], P = 0.009) was associated with poor prognosis. Clinical outcomes of ACE inhibitor or angiotensin II type-I receptor blocker (ACEI/ARB) users were comparable to non-ACEI/ARB users in COVID-19 patients with diabetes and hypertension.</div><div><br></div><div><b>CONCLUSIONS: </b>C-reactive protein may help to identify diabetic patients with greater risk. Elder diabetic patients were prone to COVID-19-related fatality. Attentions need to be paid on insulin-using diabetic patients with COVID-19. ACEI/ARB showed no significant impact on COVID-19 patients with diabetes and hypertension.</div>

The results suggest that ERG may be a potential hypoglycemic agent for the treatment of T2DM with the probable mechanism of stimulating GLUT4 translocation and expression modulated by the PI3K/Akt pathway and PKC pathway.

Background Patients on dialysis were susceptible to COVID-19 and were prone to severe clinical characteristics after infection; acute kidney injury was related to mortality in COVID-19 cases. Limited is known about the characteristics of COVID-19 patients with end-stage renal disease not requiring renal replacement therapy (RRT). Aim Evaluate clinical characteristics, course and outcomes of COVID-19 patients with chronic kidney disease (CKD) who did not require RRT and those on dialysis. Design A two-center retrospective study. Methods 836 adult patients with COVID-19 (24 CKD not on dialysis; 15 dialysis-dependent CKD) were included. The study includes no patients with renal transplantation. Risk factors were explored. Results CKD not requiring RRT is an independent risk factor for in-hospital death [adjusted OR (aOR) 7.35 (95%CI 2.41-22.44)] and poor prognosis [aOR 3.01 (95%CI 1.23-7.33)]. Compared to COVID-19 cases without CKD, those with CKD not requiring RRT showed similar percentage of initial moderate cases (75.00% vs. 73.65%) but higher incidence of in-hospital neutrophilia (50.00% vs. 27.30%) or death (50.00% vs. 9.03%). The odds ratio of dialysis associated to mortality in CKD patients was 2.00 (95%CI 0.52-7.63), suggesting COVID-19 patients with dialysis-dependent CKD were at greater risk of in-hospital death. For COVID-19 patients with CKD not requiring RRT, statins reduced the risk of neutrophilia [OR 0.10 (95%CI 0.01-0.69)] while diuretics increased the risk of neutrophilia [OR 15.4 (95%CI 1.47-160.97)], although both showed no association to mortality. Conclusion COVID-19 patients with CKD presented high incidence of neutrophilia, poor prognosis and in-hospital death, with dialysis patients being more vulnerable.

No abstract

Key points Diabetic kidney disease (DKD) is a major complication of diabetes. We found that UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase, was upregulated in the renal mesangial and tubular cells of diabetic mice and DKD patients. In cultured renal mesangial and tubular cells, UTX overexpression promoted palmitic acid‐induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects. We found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes and apoptosis; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage. Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal abnormalities in db/db mice, an animal model of type 2 diabetes. These results revealed the possible mechanisms underlying the regulation of histone methylation in DKD and suggest UTX as a potential therapeutic target for DKD. Abstract Diabetic kidney disease (DKD) is a microvascular complication of diabetes and the leading cause of end‐stage kidney disease worldwide without effective therapy available. UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase that removes the di‐ and tri‐methyl groups from histone H3K27, plays important biological roles in gene activation, cell fate control and life span regulation in Caenorhabditis elegans. In the present study, we report upregulated UTX in the kidneys of diabetic mice and DKD patients. Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal dysfunction, abnormal morphology, inflammation, apoptosis and DNA damage in db/db mice, comprising an animal model of type 2 diabetes. In cultured renal mesanglial and tubular cells, UTX overexpression promoted palmitic acid induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects. Mechanistically, we found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage. Collectively, our results suggest UTX as a potential therapeutic target for DKD.

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, co-immunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labelling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 receptor-binding domain and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the receptor-binding domains of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.