To describe the clinical characteristics and risk factors associated with the progression of COVID-19 in elderly diabetes patients. This was a retrospective cohort study, including elderly COVID-19 patients admitted to Wuhan Huoshenshan Hospital between February 10 and 13, 2020. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. We included 131 elderly COVID-19 patients (50 patients with diabetes). COVID-19 diabetes patients experienced more severe pneumonia and abnormal organ functions than non-diabetes patients (P < 0.05 or P < 0.01). Most function indicators were significantly different between the mild to moderate and severely ill groups in diabetes patients (P < 0.05 or P < 0.01). Python analysis confirmed diabetes was the independent risk factor of COVID-19 progression in elderly patients. All blood glucose (BG) indices went into the risk factor equation. The cut-off values of COVID-19 progression were BG value on admission > 8.0 mmol/L or maximum BG value > 12.0 mmol/L in all elderly patients, and BG value on admission > 5.1 mmol/L or maximum BG value > 5.4 mmol/L in non-diabetes patients. Diabetes is an independent important risk factor, and glucose levels associate closely with COVID-19 progression in elderly patients.

Testosterone is essential for spermatogenesis and the maintenance of secondary sexual characteristics in males. An important transcription factor, LIM‐homeobox gene 9 (Lhx9) is indispensable for testis development and testosterone production; however, post‐translational modifications of Lhx9 are largely unknown. Here, for the first time to our knowledge, we demonstrate that the level of Lhx9 protein increases in human chorionic gonadotropin‐exposed Leydig cells and can be polyubiquitylated. We found that Smad ubiquitylation regulatory factor 1 (Smurf1), an E3 ubiquitin ligase, targets Lhx9 for ubiquitin‐mediated proteasome degradation, thereby negatively modulating its function. Increasing Smurf1 decreases the level of Lhx9 and inhibits the Lhx9 trans‐activation capacity of steroidogenic factor 1 [nuclear receptor subfamily 5, group A, member 1 (NR5A1)]. In contrast, the depletion of Smurf1 leads to increased expression of Lhx9 protein and enhances testosterone biosynthesis‐related gene transcripts [NR5A1, steroidogenic acute regulatory protein, CYP17A1, hydroxy‐δ‐5‐steroid dehydrogenase, hydroxy‐δ‐5‐steroid dehydrogenase isomerase 6, and hydroxysteroid (17‐β) dehydrogenase 3] and testosterone production in Leydig cells. Furthermore, we found that Smurf1 knockout mice exhibit higher levels of Lhx9 protein and steroidogenesis, which leads to increased serum testosterone concentration. These findings reveal that Smurf1 promotes Lhx9 ubiquitylation and is involved in testosterone production in Leydig cells directly. Our results provide new insights into the molecular events that play a role in the homeostasis of testosterone levels and may provide a new target for testosterone regulation.—Hu, F., Zhu, Q., Sun, B., Cui, C., Li, C., Zhang, L. Smad ubiquitylation regulatory factor 1 promotes LIM‐homeobox gene 9 degradation and represses testosterone production in Leydig cells. FASEB J. 32, 4627–4640 (2018). www.fasebj.org

There have been few reports regarding the association between 1 h-PG concentration and type 2 diabetes mellitus (T2DM) in the elderly. This study was performed to assess the efficacy of 1 h-PG and 2 h-PG values in predicting future risk of T2DM in elderly. The study population consisted of 928 male volunteers ≥ 55 years old without diabetes who were involved in a retrospective-prospective cohort study over 20 years with a baseline fasting plasma glucose and OGTT that included measurement of 1 h-PG and 2 h-PG. The predictive capabilities of FPG and 1 h-PG, 2 h-PG values obtained during OGTT alone and added to a clinical prediction model consisting of traditional diabetes risk factors were assessed. Overall, 577 of all the 928 study participants (62%) developed T2DM over the 20-year follow-up. 1 h-PG and 2 h-PG values predicted T2DM and remained independent predictors of T2DM after adjusting for various traditional risk factors [HR = 1.269 (95% CI = 1.214-1.327), P < 0.001; HR = 1.269 (95% CI = 1.179-1.366), P < 0.001, respectively]. C-statistics for 1-h PG (C-statistics 0.794 [95% CI 0.765-0.823]) was significantly greater than that for 2-h PG (C-statistic 0.747 [95% CI 0.716-0.779]) in models adjusting for various traditional risk factors. 1 h-PG had the greatest area under the ROC curve (AUC, 0.766), which was greater than that of 2 h-PG (0.719). 1 h-PG is useful as a predictor of future development of T2DM independently of traditional risk factors in an elderly Chinese male population.