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Autophagy is thought to be a key mechanism in maintaining the balance of liver lipid metabolism. However, the relationship between apolipoprotein M (ApoM) and autophagy has not been reported, and the role of ApoM in triglyceride metabolism is still unclear. In this study, we investigated the correlation between ApoM and autophagy and liver triglyceride metabolism in ApoM-knockout animal and cellular models. First, we observed that spontaneous hepatic steatosis developed in the liver of adult ApoM-/- mice, which was presented as the accumulation of large quantities of lipid droplets in hepatocytes under electron microscopy; Oil Red O staining showed significant accumulation of triglycerides. At the molecular level, the expression of lipid synthesis-associated proteins (primarily triglyceride synthesis) as well as acetyl-CoA carboxylase alpha (ACACA), fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP1) was upregulated. Moreover, lipid metabolic disorder and accumulation were accompanied by dysfunction in autophagy, which displayed predominantly as inhibition of the degradation pathway; for example, P62 protein accumulated and key proteins involved in the initiation of autophagy including ATG7, ATG5-12, Beclin1 and the LC3BII/LC3BI ratio were upregulated as a feedback response. When the autophagy dysfunction was ameliorated by the activation of autophagy pathways induced by starvation, the lipid metabolic disorder was corrected to a certain extent. This suggests that the autophagy dysfunction caused by the deficiency of ApoM is an important factor in hepatic steatosis (triglyceride accumulation). ApoM plays a key role in normal autophagy activity in the liver and thereby further regulates the metabolism of liver lipids, particularly triglycerides.

Study objective: This research examined the association of baseline pulmonary function with future quality of life (QOL). Methods: We collected baseline pulmonary function data in 1993 and 1994, and assessed QOL using the Chinese 35-Item Quality of Life Instrument in 2002 in a cohort of 1,356 participants. We used Pearson correlation analysis, multivariate analysis of variance, and multivariate linear regression analysis to assess the relationship between pulmonary function and QOL. Results: The baseline percentage of age- and height-predicted FEV1 (FEV1%) was significantly correlated with the resurvey total QOL score (r 0.126, p < 0.001) and with QOL scores for the general (r 0.074, p 0.006), physical (r 0.085, p 0.002), independence (r 0.178, p < 0.001), and psychological (r 0.064, p 0.018) domains but not with the social and environmental domains after adjusting for age and sex. These associations were weaker for the percentage of age- and height-predicted FVC. Multiple linear regression showed that the above associations were independent of baseline and resurvey smoking status. Inclusion of respiratory symptoms in the model reduced the regression coefficients from 0.82 to 0.41 for the total QOL score and from 1.43 to 0.94 for the independence domain score, for a 10% change in FEV1%. The age- and sex-adjusted mean total QOL scores were 78, 76, 76, and 69, respectively (p < 0.001), for the groups of normal, symptomatic only, impaired pulmonary function only, and both symptomatic and impaired pulmonary function. This trend was also significant for the general, physical, independence, and psychological domain scores. Conclusion: Impaired baseline pulmonary function has a significant negative impact on QOL in later life that is independent of age, sex, height, and smoking status and is largely mediated through the development of chronic respiratory symptoms. (CHEST 2005; 128:2448–2457)

Background The three most commonly used basal insulins in patients with type 2 diabetes are neutral protamine Hagedorn (NPH) insulin and the long-acting insulin analogues glargine and detemir. Although randomised controlled trials have shown equivalent efficacy of these three insulins, inconsistencies in safety exist. We aimed to assess the safety and efficacy of these three basal insulins in real-world clinical setting in the ORBIT (Observational Registry for Basal Insulin Treatment) study. Methods In this multicentre, 6 month, prospective, registry study, patients were recruited between Nov 25, 2011, and Sept 1, 2014, who were aged 18–80 years, with type 2 diabetes that was inadequately controlled (HbA 1C ≥7%, 53 mmol/mol) with oral antidiabetic drugs and who were willing to start treatment with basal insulin were enrolled from 209 hospitals in eight regions of China. Patients who were prescribed any type of insulin in the past 2 years, with clinically significant acute major organ or systemic disease or other condition judged by the investigator that would create difficulty for the 6 month follow-up, or current or planned pregnancy or lactating women were excluded. Type and dose of basal insulin were at the physician's discretion and at the patients' willingness. Assessments were done at baseline (0 month—visit 1), mid-term (3 months—visit 2), and at the end of the study (6 months—visit 3) by investigators during routine practice. During analysis, patients were separated into NPH, glargine, and detemir insulin groups according to their initial prescription of basal insulin. Outcomes included the change in concentration of HbA 1c , hypoglycaemia rate, and bodyweight change in the three groups from baseline to 6 months. Propensity scores with regression adjustment were used to balance the baseline differences among the three groups. Intention-to-treat analysis was used to assess the outcomes. Findings Our findings show that treatment with long-acting insulin analogues is associated with better glycaemic control and less hypoglycaemia and weight gain than treatment with NPH insulin in patients with type 2 diabetes. Interpretation 16 341 patients were analysed in the intention-to-treat group and 9002 were analysed in the per-protocol group. In the intention-to-treat population, there were 11 290 (69%) patients treated with glargine, 2135 (13%) patients treated with detemir, and 18% (2916) patients treated with NPH insulin. After controlling for the baseline and process variables in the propensity score regression, the intention-to-treat analysis showed that the reductions in HbA 1c in the glargine (2%, SD 2·1, p=0·0014) and detemir (2%, 2·1, p=0·0065) groups were higher than that in the NPH group (2%, 2·2). The detemir group had lower weight gain (−0·1 kg, SD 2·9) than the glargine group (0·1 kg, 3·0; p=0·032) and the NPH group (0·3 kg, 3·1; p Funder Sanofi (Shanghai, China).