The Effect of Canagliflozin on High-Density Lipoprotein Cholesterol and Angiopoietin-Like Protein 3 in Type 2 Diabetes Mellitus.

Background: Diabetes mellitus is often accompanied by dyslipidemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM), have been reported to exert effects on lipid, while the results remain controversial. This study is aimed at exploring the effect of SGLT2 inhibitor canagliflozin on lipid profile. Methods: This study was a single-center, open-label, nonrandomized, prospective study. Metformin (500 mg three times per day) or canagliflozin (100 mg, once daily) was administered for 12 weeks. Fasting blood samples were collected before and 12 weeks after treatment. Serum lipid profile levels and angiopoietin-like protein 3 (ANGPTL3) were determined. In animal experiment, C57BL/6 J mice were divided into three groups including control, STZ + HFD, and STZ + HFD + canagliflozin. Lipid profile and plasma ANGPTL3 level were measured after 12 week's treatment. Moreover, the expression of ANGPTL3 was detected in the liver tissues. Results: There was a decreased trend in low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) after canagliflozin treatment, while canagliflozin significantly increased high-density lipoprotein cholesterol (HDL-c) level and decreased plasma ANGPTL3 level. In addition, the expression of ANGPTL3 in liver tissues decreased obviously in diabetic mice with canagliflozin treatment. Conclusions: Canagliflozin increases HDL-c level and suppresses ANGPTL3 expression in patients with T2DM and diabetic mice. The reduction of ANGPTL3 may contribute to the increase of HDL-c. However, the specific mechanism needs further research. This trial is registered with ChiCTR1900021231.

Relationship of Para and Perirenal Fat and High-Density Lipoprotein and Its Function in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Para and perirenal fat is a fat pad surrounding the kidneys. Recent studies showed the association between para and perirenal fat and cardiovascular diseases including atherosclerosis and hypertension. We aimed to assess the relationship between para-perirenal ultrasonographic fat thickness and serum high-density lipoprotein (HDL) level and cholesterol efflux capacity of HDL in patients with type 2 diabetes mellitus (T2DM). METHODS: We recruited 58 subjects with T2DM and collected anthropometric indices including height, weight, waist circumference, and other clinical data. Para-perirenal ultrasonographic fat thickness (PUFT) was measured via ultrasound. Serum lipid profile and other metabolic indices were determined as well. Correlation analysis and regression analysis were performed to analyze the relationship between PUFT and HDL level and cholesterol efflux capacity in all patients and subgroups. RESULTS: Patients with higher PUFT have lower serum HDL level but increased cholesterol efflux capacity. Further analysis showed that PUFT negatively correlated with the serum HDL level in all patients, with no difference in groups divided by body mass index (BMI). In addition, PUFT was positively correlated with cholesterol efflux capacity in all patients. Multiple stepwise regression analysis showed an independent association of PUFT and serum HDL level and cholesterol efflux capacity. CONCLUSIONS: PUFT is closely correlated with the serum HDL level and cholesterol efflux capacity in patients with T2DM.

Low serum levels of bone turnover markers are associated with the presence and severity of diabetic retinopathy in patients with type 2 diabetes mellitus.

BACKGROUND: Accumulating evidence demonstrates an association of type 2 diabetes mellitus (T2DM) and its microvascular complications with increased fracture risk. In this study, we aimed to evaluate the relationships between serum concentrations of bone turnover markers and the presence and/or severity of diabetic retinopathy (DR) among patients with T2DM. METHODS: A total of 285 patients with T2DM comprising 168 patients without DR and 117 patients with DR were enrolled in the cross-sectional study. In the latter group, patients were further divided into patients of mild and severe DR stages. The biochemical parameters and bone turnover markers were determined in all participants. RESULTS: This study found that serum levels of procollagen type 1 N-terminal propeptide (P1NP), a bone formation marker, and the bone resorption marker serum ß-cross-linked C-telopeptide of type I collagen (ß-CTX) were more decreased in diabetic patients with DR than in those without DR, with differences remaining significant (P < .05) in multivariate linear regression models after adjustments for multiple confounding factors. Osteocalcin and ß-CTX levels were further reduced along with the severity of DR among participants with DR. Moreover, multivariate logistic regression analysis revealed that lower serum levels of P1NP and ß-CTX were associated with higher odds for the presence of DR, while ß-CTX was associated with the severity of DR. CONCLUSION: Our results suggest that the development of DR might be involved in the progression of T2DM-induced deficits in bone formation and resorption or vice versa. Follow-up studies and further research are necessary to validate the associations and elucidate the underlying mechanisms.

A genome-wide association study of gestational diabetes mellitus in Chinese women.

BACKGROUND: Recently, gestational diabetes mellitus (GDM) exhibits an obvious trend of increase in pregnant mothers and usually causes several abnormities or diseases for the offspring. Although several studies have been reported for potential molecular mechanisms, relevant genes or mutated sites have not been intensively investigated in China. MATERIALS AND METHODS: In the present study, 218 pregnant mothers (GDM group: 103 individuals and control group: 115 individuals) in China were enrolled to conduct genome-wide association study (GWAS) and pathway analyses for the purpose of related genes associated with GDM in China. RESULTS: Our results identified 23 SNPs exhibiting closely association with GDM using multiple tests. Annotation of these 23 SNPs identified four genes (SYNPR, CDH18, CTIF, and PTGIS), which suggests that the four genes may associate with GDM. GO enrichment and KEGG pathway analysis showed that gene SYNPR, CDH18, and PTGIS were enriched or located into the pathways or process associated with glycometabolism (e.g. insulin resistance and glucose tolerance), which further indicates that the three genes may associate with the GDM. CONCLUSION: The identification of these potential genes associating with GDM enriched the potential molecular mechanisms of GDM in Asia and will provide abundant stocks for subsequent clinical verifications for better understanding the molecular mechanisms, diagnosis, drug development and clinical treatment of GDM.

The Composition of Gut Microbiota in Patients Bearing Hashimoto's Thyroiditis with Euthyroidism and Hypothyroidism.

AIMS: Hashimoto's thyroiditis (HT), a type of autoimmune disease, occurs due to genetic predisposition and environmental factors. It is well known that thyroid function may affect the gut microbiota. However, the composition of gut microbiota in HT patients with different thyroid function status has been less highlighted. Therefore, we focused on the alterations in the composition of gut microbiota in HT patients with euthyroidism and hypothyroidism. METHODS: We performed a cross-sectional study, including 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls. Fecal samples were collected, and microbiota was examined by using 16S RNA ribosomal RNA gene sequencing. Then, we analyzed the possible pathways in relation to the enriched bacteria by linear discriminant analysis (LDA) effect size (LEfSe). RESULTS: Compared with the controls, bacterial richness and diversity were significantly lower in patients with HT, especially in hypothyroidism. Moreover, Lachnospiraceae_incertae_sedis, Lactonifactor, Alistipes, and Subdoligranulum were more enriched in HT patients with euthyroidism, while Phascolarctobacterium was more abundant in those with hypothyroidism. Further analysis suggested that Phascolarctobacterium was negatively related to several pathways, including environmental information processing and metabolism. CONCLUSION: In summary, our study demonstrated the altered composition of gut microbiota in HT patients with different thyroid function status. Moreover, Phascolarctobacterium may be involved in the development of HT.

CD26/DPP4 levels in peripheral blood and T cells in Hashimoto's thyroiditis with normal thyroid function.

AIMS: Exploring the CD26 expression in peripheral blood and T cells in Hashimoto's thyroiditis with normal thyroid function. And evaluating the association between CD26 expression and TGAb and TPOAb levels. METHODS: We collected peripheral blood and thyroid tissues from healthy controls and HT patients. Then we measured circulating CD26 level via ELISA and membrane-bound CD26 on Th and Tc cells via flow cytometry. Immunochemistry is used to evaluate CD26 expression in thyroid tissue. Moreover, we analyzed the correlation between serum CD26 and autoantibodies and CD26 on T cells. RESULTS: Compared with healthy controls, CD26 expression in serum and thyroid tissues were obviously lower in HT patients with normal thyroid function. And serum CD26 level was negatively related with TGAb. While no correlation was seen between membrane-bound CD26 and autoantibodies. There was no relation between serum CD26 and CD26 expression on T cells. CONCLUSIONS: Taken together, our results show that the level of serum CD26 was associated with TGAb in HT patients with normal thyroid function.

Selective sensitivity of the gut microbiome to iron chelators in polybacterial abdominal sepsis.

Iron chelation has been proposed as a potential therapy for polybacterial abdominal sepsis. Treatment with iron chelation is known to be able to attenuate bacterial growth. It is hypothesized that the different types of bacteria will exhibit variations in their sensitivity to iron chelation based on differences in their iron metabolism. Bacteria with weaker iron access systems might have their growth reduced initially, but stronger species may also be suppressed. Gram-positive and Gram-negative bacteria are known to possess different iron acquisition systems, which may affect their response to iron chelation. Bacteria which can produce siderophores are at a particular advantage for iron acquisition. Novel iron chelators, which do not act as xenosiderophores, may be effective in depriving these bacteria of iron. This has implications for the treatment of polybacterial sepsis, which might be enhanced if the sensitivity to iron chelation of the primary causative agents is known.

A NOVEL COMPOUND HETEROZYGOUS VARIANT OF SLC12A3 GENE IN A PEDIGREE WITH GITELMAN SYNDROME CO-EXISTENT WITH THYROID DYSFUNCTION.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive disorder characterized by salt wasting and hypokalemia resulting from mutations in the SLC12A3 (solute carrier family 12 member 3) gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. To date, more than 488 mutations of the SLC12A3 gene have been discovered in patients with GS. In this study, we reported a GS pedigree complicated by thyroid diseases or thyroid dysfunction. METHODS: Sanger sequencing and next-generation sequencing analysis were performed to determine the SLC12A3 gene mutations in a GS pedigree including the 16-year old male patient with GS and his family members within 3 generations. Chemiluminescence immunoassays were used to detect thyroid hormone and antibody concentrations. RESULTS: Genetic analysis of the SLC12A3 gene identified 2 mutations in the 16-year old male patient with GS concomitant with Graves disease (GD) and his younger sister accompanied by abnormal thyroid function. Additionally, one mutation site (c.1456G>A) in SLC12A3 gene was found in his father, paternal uncle and elder female cousin, who were complicated by subclinical hypothyroidism or autoantibody against thyroid. The other mutation site (c.2102_2107 delACAAGA) in SLC12A3 gene, a novel mutated variant of SLC12A3 gene, was carried by his mother and maternal grandfather. CONCLUSION: Two mutation sites were documented in the pedigree with GS, and one has not been reported before. Moreover, we found a mutation at nucleotide c.1456 G>A in the SLC12A3 gene that may affect thyroid function. However, further studies are needed to explore the underlying molecular mechanisms. ABBREVIATIONS: FT3 = free triiodothyronine; FT4 = free tetraiodothyronine; GD = Graves disease; GS = Gitelman syndrome; SLC12A3 = solute carrier family 12 member 3; TGAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; TT3 = total triiodothyronine; TT4 = total tetraiodothyronine.

The Prevalence and Associated Risk Factors of Impaired Glucose Regulation in Chinese Adults: A Population-Based Cross-Sectional Study.

The goal of this study was to determine the prevalence and associated risk factors of impaired glucose regulation (IGR) in the population of Tongzhou, China, and to provide scientific basis for preventive interventions. In the study, the overall age-standardized prevalence of IGR (16.0%) in Tongzhou residents was higher than that in the national population (15.0%). There was no significant geographic difference in prevalence of IGR between urban and rural males. Older age, elevated blood pressure, high serum lipids, overweight, and central obesity were significantly associated with increased risk of IGR.