The pathogenesis of type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Earlier studies reported that increased levels of pancreatic fat may lead to the development of β-cell dysfunction and insulin resistance. The present study aimed to demonstrate the relationship between pancreatic fat content (PFC) and insulin secretion and insulin resistance in Chinese subjects with T2DM. Seventy-eight T2DM subjects and 35 non-diabetic volunteers were recruited in this study. All subjects were subjected to an oral glucose tolerance test (OGTT). We also measured PFC and liver fat content (LFC) by three-point Dixon method (3p-Dixon), and we examined the relations between PFC and OGTT-derived parameters. T2DM subjects had higher PFC than non-diabetic subjects (p < 0.01). PFC was correlated with body mass index (BMI), liver fat content (LFC) and age in two groups, however, it was only positively associated with insulin secretion, insulin resistance, early-and late-phase insulin secretion in male T2DM subjects, but not in non-diabetic and female T2DM subjects. After adjusting for BMI, LFC and age, the association still existed (all p < 0.05). Furthermore, the relationship was more obvious in male T2DM subjects with a shorter course of disease. PFC was associated with β-cell dysfunction and insulin resistance in subjects with T2DM and was more obvious in male T2DM subjects with shorter duration of diabetes. Therefore, PFC might represent a potential risk factor for the development of T2DM.

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Purpose: Pyrotinib (PTN) is primarily metabolized by cytochrome P450 (CYP)3A4 isozyme. Rifampicin (RIF) is a strong CYP3A4 inducer. Thus, the effect of oral RIF on PTN pharmacokinetics (PK) was evaluated to provide dose recommendation when co-administered.Method: This phase I, open-label study investigated the effects of steady-state RIF administration on single-dose PK of PTN, in 18 healthy participants who received PTN 400 mg single doses on days 1 and 13, and were administrated with RIF 600 mg qd on days 6-16. Each dose for RIF was administrated on an empty stomach, PTN were administrated orally in the morning 30 min after the start of the standard meal. Serial PK samples for PTN were collected on day 1 and day 13. Plasma PTN PK parameters were determined with non-compartmental analysis. Geometric least-squares mean ratios (GMRs) and 90% confidence intervals (CIs) were generated by the mixed-effected model for within-subject treatment comparisons. Safety assessments were performed throughout the study.Results: Eighteen subjects were enrolled and 15 completed the study. RIF significantly reduced PTN exposure: GMRs (90 % CI) for PTN + RIF versus PTN alone were 0.04 (0.034,0.049), 0.04 (0.037,0.054), and 0.11 (0.09,0.124) for area under the curve from time zero to time of last quantifiable concentration (AUC0-t), area under the curve from time zero to infinity (AUC0-∞ ), and maximum observed plasma concentration(Cmax), respectively. PTN alone and co-administered with RIF was well tolerated.Conclusion: Concurrent administration of PTN and RIF was associated with significantly decreased systemic exposure to PTN. The findings suggest that concomitant strong CYP3A4 inducers should be avoided during PTN treatment. Concurrent administration of PTN and RIF was well tolerated.