The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee’s index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.

This study was designed to investigate the relationship between SIRTs 1 and 4 in peripheral blood leukocytes (PBLs) and human type 2 diabetes mellitus (T2DM). SIRTs 1 and 4 have been confirmed to be associated with homeostasis of glucose/lipid metabolism, but their roles in T2DM are still poorly understood. Peripheral blood and biochemical data were collected from 52 healthy individuals (normal control group, NC group) and 113 cases of T2DM patients. Immunocytochemical staining was used to detect SIRT1 and SIRT4 and reverse transcription polymerase chain reaction (RT-PCR) was used to detect SIRT1 or SIRT4 mRNA levels in PBLs. Immunocytochemical staining showed that SIRT1 is expressed in both nucleus and cytoplasm, and SIRT4 in the cytoplasm of granulocytes and monocytes. No SIRT1 or SIRT4 was found in lymphocytes. RT-PCR showed that SIRT1 and SIRT4 mRNA levels in T2DM group were lower than those in NC group (P<0.01). Correlation analysis showed that there is a negative correlation between SIRTs 1 and 4 and fasting plasma glucose (FPG) (P<0.05) (r= -0.161 and -0.156), a positive correlation between SIRT4 mRNA levels and triglyceride (TG)/lipoprotein a (LPa) levels (P<0.05), and a negative correlation between SIRT4 mRNA levels and high density lipoprotein cholesterol (HDL) (P<0.05). SIRTs 1 and 4 may have a role in the pathogenesis of T2DM and their expression in granulocytes and monocytes may indirectly reflect the homeostasis of glucose/lipid metabolism in T2DM.

Background: Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM. Methods: This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM. Results: Over a median follow-up period of 7.98 (IQR: 5.74–8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05‒1.25), 1.17 (1.07‒1.27), 1.38 (1.26‒1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4‒year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01‒1.29), 1.17 (1.04‒1.32), 1.40 (1.25‒1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28‒1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk. Conclusions: Cumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk.

Background. Some studies have demonstrated that inflammation is highly associated with the prevalence of thyroid nodules (TNs). However, more confounders, such as metabolic diseases, should be adjusted. Methods. A clinical study collecting 2722 subjects was conducted to confirm the association between inflammation and TNs. The underlying mechanism was investigated in combination with bioinformatics analysis. Results. In the clinical study, propensity score matching was used to match metabolic parameters and other confounders, and it is observed that subjects with high inflammation had a higher prevalence of TNs and thyroid-stimulating hormone (TSH) than those with low inflammation. After further matching TNs, it is found that inflammation was positively associated with TSH, which was also demonstrated in a population without TNs. In bioinformatics study, inflammation did not promote TNs formation directly. Instead, it inhibited the synthesis of thyroid hormone, which might be the cause of the elevated TSH coexisting with inflammation. Conclusion. Inflammation promotes the development of TNs disease, probably due to its indirect effect through inhibiting the synthesis of thyroid hormone, which results in the elevation of TSH.