Purpose: To identify the population susceptible to reactive hypoglycemia and explain the possible reasons for their susceptibility. Methods: Ninety-four patients were divided into normal weight, overweight and obese groups before a 75-gram prolonged oral glucose tolerance test (POGTT). The incidence of reactive hypoglycemia (blood glucose ≤3.1 mmol/L or 55 mg/dL at points of 0-4 hours) was compared among three groups, and blood glucose and insulin levels were monitored simultaneously from 0-4 hours to assess the level of insulin resistance and insulin sensitivity. Furthermore, the degree of insulin resistance among three groups and within each subgroup (whether hypoglycemia events occurred) was compared. Results: Among the three groups, the incidence of hypoglycemia was significantly different at 3 (P=0.033) and 4 hours (P=0.020). At 4 hours, the incidence of reactive hypoglycemia in the obese group was approximately 3 times that in the normal weight group. The insulin level in obese group at 4 hours was nearly 4 times higher than that in normal group, and the same result also exists in the same subgroup of different groups. In addition, the hypoglycemia subgroup of obese group had higher insulin level than non-hypoglycemia (P=0.000). The homeostasis model assessment of insulin resistance index increased with increasing BMI among the three groups (P=0.000), while the Matsuda index decreased (P=0.000). The comparison of the homeostasis model assessment of insulin resistance index between subgroups in each group showed that the P values were 0.021, 0.038 and 0.085, successively, and the P values for the Matsuda index were 0.019, 0.013 and 0.119, respectively. Conclusion: Obese people has higher rate of reactive hypoglycemia than other groups in POGTT, in which insulin resistance may play an important role. But patients who are evaluated for reactive hypoglycemia need to be observed for at least 3 or 4 hours.

Circular RNAs (circRNAs) participate in development of malignancies through its active role as a “miRNA sponge.” Their roles in type 1 diabetes mellitus (T1DM) pathogenesis are elusive. Here, the important role of circRNAs in T1DM was explored. circRNA profiling was performed for isolated CD4+ T cells from blood of T1DM and healthy volunteers. There were 257 differentially expressed circRNAs. Only three upregulated DEcircRNAs (hsa_circ_0000324, hsa_circ_0001853, and hsa_circ_0068797) were consistent with the GEO database. Through KEGG analyses, it was found that the three DEcircRNAs were associated with 11 miRNAs and 8 immune-related target genes (mRNA). Further analysis found that four miRNAs, two circRNAs, and four mRNAs were associated with nine circRNA-miRNA-mRNA networks. This confirmed the requirements of sponge mechanisms. The qRT-PCR analysis revealed that circRNA000324/miRNA675-5p/MAPK14 and circRNA000324/miRNA-675-5p/SYK may be potential mechanisms in regulation of differentiation and proliferation of CD4+ T cell in patients with T1DM. Therefore, targeting circRNA to regulate cellular immune responses by regulating CD4+ T cell differentiation may be a new strategy for the treatment of T1DM.

Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.