Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis.

BACKGRUOUND: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. METHODS: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed. RESULTS: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321). CONCLUSION: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018.

BACKGRUOUND: Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate. METHODS: The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed. RESULTS: In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population. CONCLUSION: The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.

Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis.

AIMS: Accumulating evidence suggests that inhibitors of dipeptidyl peptidase-4 (DPP-4), such as sitagliptin, may play an important role in the prevention of non-alcoholic steatohepatitis (NASH). This study was conducted to elucidate whether sitagliptin could prevent steatohepatitis by inhibiting pathways involved in hepatic steatosis, inflammation, and fibrosis. METHODS: C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet with or without supplement with sitagliptin for 5 weeks. Liver and adipose tissue from mice were examined histologically and immunohistochemically to estimate the effect of sitagliptin on the development of NASH. RESULTS: Supplementation with sitagliptin resulted in significant improvement of MCD diet-induced fat accumulation in the liver. In addition, sitagliptin treatment lowered fatty acid uptake, expression of VLDL receptor and hepatic triglyceride content. Sitagliptin also effectively attenuated MCD diet-induced hepatic inflammation, endoplasmic reticulum (ER) stress, and liver injury, as evidenced by reduced proinflammatory cytokine levels, ER stress markers, and TUNEL staining. Expression of CYP2E1 and 4NHE were strongly increased by the MCD diet, but this effect was successfully prevented by sitagliptin treatment. Furthermore, sitagliptin significantly decreased levels of MCD diet-induced fibrosis-associated proteins such as fibronectin and α-SMA in the liver. Inflammatory and atrophic changes of adipose tissue by MCD diet were restored by sitagliptin treatment. CONCLUSIONS: Sitagliptin attenuated MCD diet-induced hepatic steatosis, inflammation, and fibrosis in mice through amelioration of mechanisms responsible for the development of NASH, including CD36 expression, NF-κB activation, ER stress, CYP2E1 expression, and lipid peroxidation. Treatment with sitagliptin may represent an effective approach for the prevention and treatment of NASH.

Alpha-lipoic acid attenuates methionine choline deficient diet-induced steatohepatitis in C57BL/6 mice.

AIMS: Non-alcoholic steatohepatitis (NASH) is a liver disease that causes fat accumulation, inflammation and fibrosis. Increased oxidative stress contributes to hepatic inflammation and fibrosis by upregulation of Cytochrome P450 2E1 (CYP2E1), endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) activity. This study examined whether alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, prevents steatohepatitis through the inhibition of several pathways involved in hepatic inflammation and fibrosis. MAIN METHODS: C57BL/6 mice were fed an MCD diet with or without ALA for 4weeks. Liver sections from mice on control or MCD diets with or without ALA were stained with hematoxylin-eosin, oil red O, and anti-4-HNE antibody. The effects of ALA on methionine-choline deficient MCD-diet induced plasma AST and ALT as well as tissue TBARS were measured. The effects of ALA on CYP2E1 expression, ER stress, MAPK levels, and NF-κB activity in MCD diet-fed mice liver were measured by northern and western blot analysis. KEY FINDINGS: Dietary supplementation with ALA reduced MCD diet-induced hepatic lipid accumulation, hepatic inflammation, TBARS, 4-HNE, and plasma ALT and AST levels. These effects were associated with a reduced expression of CYP2E1 and reduced ER stress and MAPK and NF-κB activity. SIGNIFICANCE: Taken together, the results of the present study indicate that ALA attenuates steatohepatitis through inhibition of several pathways, and provide the possibility that ALA can be used to prevent the development and progression of non-alcoholic fatty liver disease in patients who have strong risk factors for NASH.