PMC

Kaplan–Meier survival curves in AMI patients with and without hyperglycemia. A All-cause mortality. Significant pairwise differences were found for MINOCA with and without hyperglycemia (p < 0.01), MIOCA with and without hyperglycemia (p < 0.001); MIOCA with hyperglycemia and MINOCA without hyperglycemia, (p < 0.05), MINOCA with hyperglycemia and MIOCA without hyperglycemia (p < 0.001), B cardiovascular mortality MIOCA with hyperglycemia and MINOCA without hyperglycemia (p = 0.011), MINOCA with hyperglycemia and MIOCA without hyperglycemia (p < 0.01), MINOCA with and without hyperglycemia (p = 0.0011), MIOCA with and without hyperglycemia (p < 0.001)

GATA4 improves endothelial function and is involved in protection of endothelial function by simvastatin. (A) NO levels in HUVECs with and without GATA4 overexpression. ^%P<0.05 control vs. hyperglycemia; *P<0.01 hyperglycaemia vs. hyperglycaemia + GATA4 overexpression. (B) Western blotting results demonstrating that NOX4 expression in HUVECs exposed to normoglycemic conditions as well as hyperglycemic conditions with or without simvastatin treatment; **P<0.01, hyperglycemia vs. control group; ^##P<0.01, hyperglycemia + simvastatin vs. hyperglycemia group. (C) NO levels in the supernatant of HUVECs exposed to control culture, hyperglycemia, hyperglycemia + simvastatin and hyperglycemia + simvastatin + GATA4-siRNA. (D) Migration analysis in HUVECs exposed to control culture, hyperglycemia, hyperglycemia + simvastatin and hyperglycemia + simvastatin + GATA4-siRNA. (C and D) ^%P<0.05, hyperglycemia vs. control group; ^#P<0.05, hyperglycemia + simvastatin vs. hyperglycemia group; ^!P>0.05 hyperglycemia + simvastatin vs. hyperglycemia + simvastatin + control siRNA; ^$P<0.05 hyperglycemia + simvastatin + control siRNA vs. hyperglycemia + simvastatin + GATA4-siRNA; ^&P<0.05, hyperglycemia + simvastatin + GATA4-siRNA vs. hyperglycemia + simvastatin group. GATA4, GATA-binding protein 4; HUVECs, human umbilical vein endothelial cells; NO, nitric oxide; NOX4, NADPH oxidase 4; siRNA, small interfering RNA.

(A) Blood glucose levels in 3-month-old APP/PS1 mice (n = 6–8 mice/group) during fasted baseline and hyperglycemic clamp. (B) ISF glucose levels increased from 0.158 ± 0.004 to 0.306 ± 0.011 mmol/l during hyperglycemia in 3-month-old APP/PS1 mice (n = 6–8 mice/group). (C) Hyperglycemia increased ISF Aβ levels by 24.5% ± 3.8% in 3-month-old APP/PS1 mice during and after clamp (n = 6–7 mice/group). (D) ISF Aβ correlates with ISF glucose during hyperglycemia (n = 6 mice, Pearson’s r = 0.6032; P < 0.01). (E) ISF glucose levels increased from 0.153 ± 0.003 to 0.397 ± 0.0149 mmol/l during hyperglycemia in 18-month-old APP/PS1 mice (n = 6–7 mice/group). (F) Hyperglycemia increased ISF Aβ levels by 38.8% ± 5.3% in 18-month-old APP/PS1 mice, during and after glucose clamps (n = 6–7 mice/group). (G) Hyperglycemia increases ISF lactate, a marker of neuronal activity (n = 7 mice/group). (H) Compound E decreases ISF Aβ during hyperglycemia and does not alter ISF Aβ half-life, demonstrating hyperglycemia alters Aβ production, not Aβ clearance. Data represent mean ± SEM. Significance denoted *P < 0.05, **P < 0.01, and ***P < 0.001 using 2-way ANOVA (C and F) or Student’s t tests (A, B, E, G, and H).

A: Risk-adjusted Cox regression analysis curves showing survival from severe disease through 18 days for patients with COVID-19 stratified by hyperglycemia vs. normoglycemia. B: Risk-adjusted Cox regression analysis curves showing survival from severe disease through 18 days for patients with COVID-19 stratified by with diabetes vs. no diabetes. C: Risk-adjusted Cox regression analysis curves showing survival from severe disease through 18 days for patients with hyperglycemia and COVID-19 stratified by insulin infusion vs. no insulin infusion treatment. D: Kaplan-Meier analysis showing survival from severe disease through 18 days for patients with hyperglycemia and no diabetes, hyperglycemia and diabetes, no hyperglycemia but with diabetes, and no hyperglycemia and no diabetes. HR, hazard ratio.