This study provides evidence of increased CVD risk associated with hypoglycaemia, especially with serious hypoglycaemia events. While associations were attenuated with non-serious hypoglycaemia, the results were suggestive of a potential increased risk.

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the world. Elevated glucose metabolism in the availability of oxygen, a phenomenon called the Warburg effect, is important for cancer cell growth. Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and is frequently lost in various types of cancer. Here, we demonstrated that expression of FBP1 was downregulated in HCC patient specimens and decreased expression of FBP1 associated with poor prognosis. Low expression of FBP1 correlated with high levels of histone deacetylase 1 (HDAC1) and HDAC2 proteins in HCC patient tissues. Treatment of HCC cells with HDAC inhibitors or knockdown of HDAC1 and/or HDAC2 restored FBP1 expression and inhibited HCC cell growth. HDAC-mediated suppression of FBP1 expression correlated with decreased histone H3 lysine 27 acetylation (H3K27Ac) in the FBP1 enhancer. Restored expression of FBP1 decreased glucose reduction and lactate secretion and inhibited HCC cell growth in vitro and tumor growth in mice. Our data reveal that loss of FBP1 due to histone deacetylation associates with poor prognosis of HCC and restored FBP1 expression by HDAC inhibitors suppresses HCC growth. Our findings suggest that repression of FBP1 by HDACs has important implications for HCC prognosis and treatment.

In the present study, we observed the renal outcomes in a cohort of 1814 Chinese patients with biopsy-proven lupus nephritis (LN) and evaluated the risk factors associated with poor renal prognosis. The 5 -, 10 -, 15 - and 20-year renal survival rates were 93.1%, 87.9%, 81.0% and 68.3%, respectively. Gender, LN duration, mean arterial pressure (MAP), proteinuria, serum creatinine, haemoglobin and pathological classification at the time of biopsy were independent risk factors for end-stage renal disease (ESRD). The long-term renal outcomes of patients with class II LN were unfavorable as opposed to those with class V. Additionally, the time-average proteinuria (TA-Pro) and the time-average mean arterial pressure (TA-MAP) during the follow-up were important risk factors for ESRD, with better predictive values than the baseline proteinuria and MAP. The results underscore the need for proteinuria and blood pressure control during follow-up in patients with LN; proteinuria levels should be controlled at least to < 1.0 g/24 h, and optimally to < 0.5 g/24 h; MAP should not exceed 96.5 mmHg. More attention should be paid to class II LN and emphasis should be placed on recurrence prevention of class II LN.