Metabolic diseases such as obesity and diabetes have been the most serious social and health problems in the world. Current treatments mainly focus on the disease consequence rather than the cause of metabolic disorders, and it is difficult to curb the global trend of explosive growth of patients. Thus new and more effective prevention and treatment strategies are needed. Genetics and environment influence the process of obesity and diabetes. But the genomic analysis only accounts for 10% to 20% of the metabolic diseases, while environmental factors such as diet and other lifestyle habits play an important role in the onset of metabolic diseases. In recent years, an increasing number of studies have shown that human gut microbiota is closely related to the onset and development of metabolic diseases such as obesity and type 2 diabetes. The rapid progress in this emerging academic field will not only help elucidate the pathogenesis of metabolic disease, but will also provide direction for exploring new therapeutic targets and pathways.

Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion,and potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptidehormones, glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulin releasing polypeptide (GIP). According to the recently finished studies, the review focuses on the physiological actions of incretin, explains the different insulinotropic actions of GLP-1 and GIP in type 2 diabetic patients, and evaluates the clinical features of recently approved therapeutic agents based on incretin action.

Incretin is defined as an intestinal hormone released in response to nutrient ingestion, which potentiates the glucose-induced insulin response. In human body, the incretin's effect is mainly induced by two peptide hormones, glucagon-like peptide-I (GLP-I)and glucose-dependent insulinotropic polypeptide (GIP). In order to fully evaluate the clinical advantages of novel agents based on incretin, this review introduces the islet actions of incretin in brief, and mainly focuses on the extra-islet effect of incretin.

Objective To investigate the clinical characteristics of the familial early onset type 2 diabetes（T2DM）,and the factors affecting the age at diagnosis. Methods 190 probands from early onset T2DM pedigrees （diagnosed before 40 years old） and 103 probands from late onset T2DM （pedigrees） （all patients were diagnosed after 40 years old）were included in this study. The homeostasis model assessment of insulin resistance （HOMA-IR）was used to estimate insulin resistance, HOMA-β cell was used to evaluate basal insulin secretion. The ratio of the incremental insulin (ΔI30) over （incremental） glucose(ΔG30) was calculated after intake of a steamed bread made of 100g flour to （evaluate） the early insulin secretion. Body mass index（BMI）and serum lipid levels were also （determined.） （Results） （1）The early onset group had significantly higher fasting serum insulin （（natural） logarithm transformed, 2.6±0.6 vs 2.4±0.5 μU/ml, P<0.05）, triglycerid （TG, 1.7±2.0 vs 1.4±2.0 mmol/L,P<0.05）,HOMA-IR（natural logarithm transformed, 1.6±0.8 vs 1.3±0.6, P<0.01）and lower high density lipoprotein （HDL-C, 1.2±0.3 vs 1.3±0.3mmol/L,P<0.05） than those in late onset group.（2）Linear regression analyses showed that HOMA-IR, HOMA-β were （independent） risk factors predicting early age of onset. （3）In the early onset type 2 diabetic patients, the subgroup with BMI more than 25 kg/m2 had significant earlier diagnosis age （32±7 vs 34±5 y, P<0.05）, lower level of serum HDL-C （1.1±0.3 vs 1.3±0.3 mmol/L, P<0.01）, higher FIns （（natural） logarithm transformed, 2.8±0.6 vs 2.4±0.6, P<0.01）, higher HOMA-IR （natural （logarithm） transformed, 4.3±0.9 vs 3.9±1.0, P<0.01）and higher TG （1.9±2.0 vs 1.5±2.1 mmol/L, P<0.01）than those with BMI less than 25 kg/m2. Conclusion Compared with late onset familial type 2 diabetic patients,more severe insulin resistance and relative β cell function defect are the important clinical （features） in early onset familial type 2 diabetic patients. The interaction between （insulin resistance） and （β-cell） dysfunction are probably the determinants of onset age of T2DM.

Objective To assess the validity of using fasting plasma glucose （FPG） and HbA1c for the screening of diabetes. Methods 1118 subjects （489 men, 629 women） in Beijing area underwent an oral glucose tolerance test （OGTT） for screening diabetes. HbA1c was examined at the same time. They have never undergone OGTT and controlled plasma glucose levels by any methods. Their average age was 48±12 years. Results Using 1999 WHO criteria, 510 had normal glucose tolerance （NGT）, 35 had impaired fasting glucose（IFG）, 155 had impaired glucose tolerance （IGT）, 52 had IGT and IFG, 366 had diabetes. Using a receiver operating characteristic curve （ROC curve）, the optimal cut-point of FPG related to diabetes diagnosed by OGTT was 6.2mmol/L that was associated with a sensitivity and specificity of 85.0% and 90.4% respectively. Area under the curve was 0.943 （95% CI 0.9270.959）, a positive likelihood ratio （LR） was 8.9, and a negative LR was 0.2. The optimal cut-point of HbA1c related to diabetes diagnosed by OGTT was 6.2%, which was associated with a sensitivity and specificity of 86.6% and 77.5% respectively. Area under the curve was 0.896 （95% CI 0.8760.916）, a positive LR was 3.9, and a negative LR was 0.2. The cut-point of FPG related to IGT diagnosed by OGTT was 5.1 mmol/L, which was associated with a sensitivity and specificity of 65.2% and 68.3% respectively. Area under the curve was 0.729 （95% CI 0.6890.769）, a positive LR was 2.1, and a negative LR was 0.5. The cut-point of HbA1c related to IGT diagnosed by OGTT was 5.7%, which was associated with a sensitivity and specificity of 63.3% and 56.5% respectively. Area under the curve was 0.634 （95% CI 0.5910.677）, a positive LR was 1.5, and a negative LR was 0.7. Conclusions When FPG<7.0 mmol/L and ≥6.2 mmol/L or HbA1c≥6.2%, OGTT was necessary to confirm the diagnosis of diabetes. FPG or HbA1c was not reliable to identify IGT.

Objective To investigate the effect of metformin on thyroid hormone and thyrotropin(TSH) in diabetic patients without thyroid hormone replacement.Methods Serum levels of free T3(FT3),free T4(FT4),total T3(TT3),total T4(TT4) and TSH were measured in diabetic patients with or without metformin therapy and the relationship between TSH and metformin was analyzed.Results There were no significant differences in serum FT3(4.65±0.68 vs 4.59±0.67 pmol/L),FT4(17.88±3.26 vs 17.75±2.85pmol/L),TT3(1.79±0.42 vs 1.77±0.38nmol/L),TT4(107.9 ±22.1 vs 109.2±22.1nmol/L) and thyrotropin(ln TSH:0.49±0.83 vs 0.47±0.87 mU/L) between diabetic patients taking and not taking metformin.Conclusions In diabetic patients without thyroid hormone replacement,metformin does not suppress serum TSH

Objective To investigate the insulin dosage and analyze the dosage-impacting factors of intensive insulin treatment in Chinese type 2 diabetic patients.Methods Totally 1025 patients with intensive insulin treatment were included,the insulin dosage and clinical characteristics were taken down and analyzed.Results The mean insulin dosage was 39.30U/day,the insulin dosage per kg of body weight was 0.61U/Kg,among which the dosage of intermediate-acting insulin was 9.79 U/day,occupying 25.24%,while the pre-meal one was 29.51 U/day,occupying 74.76%.According to the insulin dosage per kg of body weight,patients were divided into low dosage group and high dosage one.The result showed significant difference in period of diabetes,BMI,HbA1c,and the highest weight level between the two groups.Correlation analysis showed that the average insulin dosage per kg of body weight was positively correlated with period of diabetes,HbA1c,fasting glucose level and LDL-C,while negatively correlated with BMI,fasting and postprandial C-peptide,the highest body weight level and HDL-C.Conclusions The average insulin dosage for type 2 diabetic patients is 39.30U/day,among which the dosage of intermediate-acting insulin occupies 25% while the pre-meal one occupies 75%.The insulin dosage is positively correlated with period of diabetes and HbA1c,while negatively correlated with BMI and the highest body weight level

Objective To explore the association of serum uric acid level with the different states of glucose metabolism and glomerular filtration rate (GFR) reflected by creatinine clearance rate and to test the hypothesis that increased GFR is one of the determinants of serum uric acid level. Methods 822 subjects with high risk factors for diabetes in Beijing area underwent a 75g oral glucose tolerance test (OGTT) for screening of diabetes. The subjects were divided into three groups:NGT,IGR and DM after OGTT. SUA and Ccr were compared between three groups. The general linear model was employed to test the relationships of the small FPG intervals with SUA and Ccr. Results The correlations of uric acid level with sex,BMI,TG,HbA1c and Ccr remained significant in a multiple regression analysis. After adjusting sex,BMI and TG,the newly diagnosed DM group had the lowest SUA level(P<0.01) and the highest Ccr(P<0.01). When fasting glucose level was stratified by a grade of 1 to 2mmol/L,we found that the correlation between SUA and FPG levels became significant only when FPG was higher than 7.0 mmol/L(P<0.01) and the correlation between Ccr and FPG levels became significant only when FPG was between 6.0 mmol/L and 10.0 mmol/L (P<0.01). Conclusions This study confirms the previous finding that SUA level decreases in diabetes,and provides a supporting evidence that the increased GFR might contribute to the fall of SUA level

[Summary] MS ,which is highly related tothe occurrence of cardiovascular disease and T2DM ,is characterized by glucose and fat metabolic dysregulation ,central obesity ,hypertension and hyperuricemia.11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is regarded as a new therapeutic target for MS.11β‐HSD1 converts inactive glucocorticoid to active glucocorticoid. 11β‐HSD1 knockout improves obesity , hyperlipidemia andhyperglycemia. The inhibition of 11β‐HSD1 alleviates IR in human and rodents ,but the application of 11β‐HSD1 inhibitors is limited by the side effects.

Objective To investigate the effect of metformin on thyroid hormone and thyrotropin(TSH) in diabetic patients without thyroid hormone replacement.Methods Serum levels of free T3(FT3),free T4(FT4),total T3(TT3),total T4(TT4) and TSH were measured in diabetic patients with or without metformin therapy and the relationship between TSH and metformin was analyzed.Results There were no significant differences in serum FT3(4.65?0.68 vs 4.59?0.67 pmol/L),FT4(17.88?3.26 vs 17.75?2.85pmol/L),TT3(1.79?0.42 vs 1.77?0.38nmol/L),TT4(107.9 ?22.1 vs 109.2?22.1nmol/L) and thyrotropin(ln TSH:0.49?0.83 vs 0.47?0.87 mU/L) between diabetic patients taking and not taking metformin.Conclusions In diabetic patients without thyroid hormone replacement,metformin does not suppress serum TSH.