Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice.

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.

Predictive factors of thyroid cancer in patients with Graves' disease.

BACKGROUND: The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. METHODS: This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. RESULTS: Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. CONCLUSIONS: Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

[Association between side effects of oral anti-diabetic drugs and self-reported mental health and quality of life among patients with type 2 diabetes].

OBJECTIVE: To examine the association between the side effects of oral anti-diabetic drugs (OAD) and self-reported mental health and quality of life among patients with type 2 diabetes mellitus (T2DM). METHODS: An observational, cross-sectional multicenter study with a retrospective medical chart review was conducted at 16 medical centers from around China. The T2DM patients were followed-up and treated with OAD alone prior to the index visit from January to September 2007. All subjects were ≥30 years old at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Health-related quality of life was measured by the EuroQol-5D (EQ-5D) and Hypoglycemia Fear Survey (HFS)-II. RESULTS: The symptoms of hypoglycemia were reported by 41.8% (n=203) of participants, and 19.2% (n=93) experienced weight gain. For those reporting hypoglycemia, the scores were higher for HFS-II [7.00 (2.00-19.00) vs 0.00 (0.00-7.00), P<0.01] and lower for EQ-5D (0.90±0.12 vs 0.93±0.13, P=0.003) than those without hypoglycemic symptoms. According to the multivariate linear regression analysis, the symptoms of hypoglycemia were positively correlated with HFS-II (ß=5.78, P<0.01) and negatively with EQ-5D (ß=-0.04, P<0.05) after adjusting for patient and disease characteristics. CONCLUSION: There is a high possibility of hypoglycemic risks among T2DM patients on OAD therapy. The self-reported hypoglycemia is associated with health-related quality of life and hypoglycemic fear. They may have an impact on the long-term prognosis.

Association between peroxisome proliferator-activated receptor-gamma coactivator-1alpha gene polymorphisms and type 2 diabetes in southern Chinese population: role of altered interaction with myocyte enhancer factor 2C.

BACKGROUND: Some single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1alpha and type 2 diabetes in the southern Chinese population and to determine whether the common variants: Gly482Ser and Thr394Thr, in the PGC-1alpha gene have any impacts on interaction with myocyte enhancer factor (MEF) 2C. METHODS: The SNPs in all exons of the PGC-1alpha gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1alpha gene alter the interaction with MEF2C. RESULTS: Three frequent SNPs (Thr394Thr, Gly482Ser and Thr528Thr) were found in exons of the PGC-1alpha gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls (40.1% vs 29.3%, P < 0.01). Even in controls, the 482Ser (A) carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly (G) carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr (A) had a synergic effect on the interaction between 482Ser variant and MEF2C. CONCLUSIONS: The results suggested that the 482Ser variant of PGC-1alpha conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants (Gly482Ser, Thr394Thr) in the PGC-1alpha gene and MEF2C.