Objective: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. Research design and methods: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO₂/FiO₂≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). Results: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. Conclusion: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.

Type 2 diabetes (T2D) is a high-risk factor for Alzheimer’s disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight. Capsaicin-containing standard chow was also introduced to non-diabetic rats (NC+CAP). Blood glucose and insulin were monitored. The phosphorylation level of tau at individual sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blots. The results revealed that the levels of phosphorylated tau protein at sites Ser199, Ser202 and Ser396 in hippocampus of T2D+CAP group were decreased significantly, but these phospho-sites in T2D+PF group didn’t show such improvements compared with T2D group. There were almost no changes in non-diabetic rats on capsaicin diet (NC+CAP) compared with the non-diabetic rats with normal chow (NC). Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either. These results demonstrated that dietary capsaicin appears to prevent the hyperphosphorylation of AD-associated tau protein by increasing the activity of PI3K/AKT and inhibiting GSK-3β in hippocampus of T2D rats, which supported that dietary capsaicin might have a potential use for the prevention of AD in T2D.

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

With the aging world population, the prevalence of aging‐related disorders is on the rise. Diseases such as Alzheimer's, type 2 diabetes mellitus (T2DM), Parkinson's, atherosclerosis, hypertension, and osteoarthritis are age‐related, and most of these diseases are comorbidities or risk factors for AD; however, our understandings of molecular events that regulate the occurrence of these diseases are still not fully understood. Brain and muscle Arnt‐like protein‐1 (Bmal1) is an irreplaceable clock gene that governs multiple important physiological processes. Continuous research of Bmal1 in AD and associated aging‐related diseases is ongoing, and this review picks relevant studies on a detailed account of its role and mechanisms in these diseases. Oxidative stress and inflammation turned out to be common mechanisms by which Bmal1 deficiency promotes AD and associated aging‐related diseases, and other Bmal1‐dependent mechanisms remain to be identified. Promising therapeutic strategies involved in the regulation of Bmal1 are provided, including melatonin, natural compounds, metformin, d‐Ser2‐oxyntomodulin, and other interventions, such as exercise, time‐restricted feeding, and adiponectin. The establishment of the signaling pathway network for Bmal1 in aging‐related diseases will lead to advances in the comprehension of the molecular and cellular mechanisms, shedding light on novel treatments for aging‐related diseases and promoting aging‐associated brain health.

Backgrounds: The aim of the research was to investigate the factors contributing to cognitive dysfunction in type 2 diabetic patients, to distinguish the complex relationship between diabetic retinopathy (DR) and different cognitive status. Methods: Two hundred and ninety-seven type 2 diabetes mellitus (T2DM) patients were enrolled in our study. We adopted the Clinical Dementia Rating (CDR), Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA) to evaluate the cognitive function. Firstly, cognition status was classified into dementia and non-dementia according to MMSE and CDR. Patients with non-dementia were further classified into mild cognitive impairment (MCI) and normal cognition status based on MOCA. The factors contributing to cognitive dysfunction were analyzed. Results: Among the 297 T2DM subjects, 47 were enrolled in the dementia group and 174 in the MCI group according to a battery of cognitive function tests, presenting a prevalence of 15.8% and 58.6% respectively. After adjustment for age, sex, and education level, waist circumference and DR were risk factors for dementia (OR: 1.057, P=0.011; OR: 2.197, P=0.040). Low-density lipoprotein cholesterol (LDL-C) was a risk factor for MCI (OR: 1.635, P=0.047), while age at T2DM onset and moderate drinking were protective factors for MCI (OR: 0.936, P=0.044; OR: 0.289, P=0.004). Conclusions: MCI is common in T2DM patients. Waist circumference and DR are risk factors of dementia, LDL-C is a risk factor for MCI, and moderate drinking and age at T2DM onset are protective factors for MCI. DR is unrelated to MCI in T2DM.