Lipid management, especially with respect to triglyceride (TG) metabolism, in patients with diabetes is not sufficient with current therapeutic agents, and new approaches for improvement are needed. Members of the angiopoietin-like protein (ANGPTL) family, specifically ANGPTL3, 4, and 8, have been reported as factors that inhibit lipoprotein lipase (LPL) activity and affect TGs. The present study investigated the association between lipid and glucose metabolism markers and the mechanism by which these proteins affect lipid metabolism. A total of 84 patients hospitalized for diabetes treatment were evaluated. Lipid and glucose metabolism markers in blood samples collected before breakfast, on the day after hospitalization, were analyzed. ANGPTL8 showed a significant positive correlation with TG values. HDL-C values displayed a significant positive correlation with ANGPTL3 but a negative correlation with ANGPTL4 and ANGPTL8. The results did not indicate a significant correlation among ANGPTL3, 4, and 8 levels. Thus, it is possible that the distribution of these proteins differs among patients. When patients were divided into groups according to the levels of ANGPTL3 and ANGPTL8, those with high levels of both ANGPTL3 and ANGPTL8 also had high levels of TG and small dense LDL-C/LDL-C (%). Multiple regression analysis indicated that low LPL, high ApoC2, high ApoC3, high ApoE, and high ANGPTL8 levels were the determinants of fasting hypertriglyceridemia. By contrast, no clear association was observed between any of the ANGPTLs and glucose metabolism markers, but ANGPTL8 levels were positively correlated with the levels of HOMA2-IR and BMI. Patients with high levels of both ANGPTL3 and ANGPTL8 had the worst lipid profiles. Among ANGPTL3, 4, and 8, ANGPTL8 is more important as a factor determining plasma TG levels. We anticipate that the results of this research will facilitate potential treatments targeting ANGPTL8 in patients with diabetes.

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Background: Diabetes care management aims to not only achieve good glycemic control but also maintain the quality of life (QoL). Basal insulin-treated patients frequently receive bolus insulin as a strengthening therapy; however, concerns exist about QoL due to the increasing number of injections. We examined the glycemic effect and QoL in patients treated with liraglutide (Lira) and insulin degludec/insulin aspart (IDegAsp). Methods: Patients with type 2 diabetes treated with basal-supported oral therapy (BOT) and DPP-4 inhibitor were enrolled in this observational study. Basal insulin was switched to IDegAsp at the same dose and DPP-4 inhibitor to Lira simultaneously; no titration protocol was used. We estimated the clinical and laboratory parameters and assessed the change in QoL within 12 weeks using the diabetes therapy-related QoL (DTR-QoL) questionnaire. The timing of dose up in regard to IDegAsp and Lira was also determined. Results: Fourteen patients were enrolled (male/female: 9/5, age (years): 63.6). The IDegAsp dose ranged from 9.1 to 13.7 U; all patients received 0.9 mg/day of Lira. The combination therapy significantly decreased HbA1c levels (8.7% vs. 7.1%, P=0.02), pre-breakfast glucose level (138.2 mg/dL vs. 108.9 mg/dL, P=0.044), bodyweight (62.9 kg vs. 60.3 kg, P=0.003), and BMI (24.6 vs. 23.5, P=0.004). The total DTR-QoL score at baseline was 61.6 and significantly improved to 73.2 (P=0.004). Significant improvement was also seen in D3 score (hypoglycemia; 63.6 vs. 81.4, P=0.036). D4 score (satisfaction with treatment) showed an increasing trend (59.0 vs. 78.2) and was negatively correlated with HbA1c levels (P=0.049). Conclusion: The change from BOT to the combination therapy of Lira and IDegAsp significantly improved glycemic control and reduced the bodyweight without deteriorating QoL in type 2 diabetes, although the treatment modality changed from one-injection to two-injection therapy. Disclosure M. Harada: None. M. Shinoda: None. R. Sakamoto: None. J. Suzuki: None. K. Takahashi: None. T. Yamakawa: None.

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Metformin monotherapy as first-line treatment for patients with type 2 diabetes (T2D) has been shown to effectively improve blood glucose levels and motivation to undergo treatment and prevent complications. However, no studies have reported its effect when combined with other drugs or compared the effect based on administration time. This study aimed to investigate the effect of metformin administration in Japanese patients with T2D, examine how the introduction line impacts the effect of metformin, and examine the characteristics of patients demonstrating improved blood glucose levels. Data on characteristics of patients who were newly prescribed metformin with no shifting of hypoglycemic agents in the subsequent 24-week observation period, and their age [mean, 56.8 years], body mass index [mean, 27.5 kg/m 2 ], glycated hemoglobin [HbA1c] [mean, 8.1%], and duration of diabetes [mean, 3.0 years] were obtained from the medical records of 201 patients. The changes in HbA1c by introduction line after 24 weeks were -1.59%, -0.91%, -0.89%, and -0.65% in the first, second, third, and fourth induction lines, respectively; earlier introduction more significantly improved blood glucose. The factors significantly associated with HbA1c changes were early introduction, high baseline HbA1c, high estimated glomerular filtration rate, decreased insulin secretion, short estimated duration of diabetes, and increased metformin dose. Furthermore, factors contributing to the largest HbA1c improvement by metformin were high baseline HbA1c and early administration. Metformin is expected to lower blood glucose levels in Japanese patients with T2D, even in those with decreased insulin secretion, due to its early introduction as a first-line drug.