Bariatric Surgery for Type 2 Diabetes Mellitus in Patients with BMI <30 kg/m2: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: The role of bariatric surgery in non-obese patients with type 2 diabetes (T2DM) remains unclear, and its use in clinical practice is controversial. We conducted a systemic review and meta-analysis to investigate the metabolic changes after surgical treatment in diabetic patients with body mass index (BMI) <30 kg/m2. METHODS: We conducted a comprehensive search in MEDLINE (PubMed), EMBASE and the Cochrane Library of published articles from January 2000 to April 2013 reporting the clinical outcome changes in various metabolic outcomes in diabetic patients with BMI <30 kg/m2. RESULTS: Ten prospective studies including 290 patients were included in the meta-analysis. Bariatric surgery led to an overall 2.79 kg/m2 [95%CI 2.05~3.53, P<0.00001] reduction in BMI, a 1.88%[95%CI 1.32~2.43, P<0.00001] reduction in glycosylated hemoglobin, a 3.70 mmol/L [95%CI, 1.93~5.47, P<0.00001] reduction in fasting blood glucose, a 6.69 mmol/L [95%CI, 2.29~11.08, P=0.003] reduction in postprandial glucose, anda 3.37 [95%CI 0.55~6.18, P=0.02] reduction in homeostasis model assessment of insulin resistance (HOMA-IR). After surgical treatment, 76.2% of the patients were insulin free, and 61.8% patients were off medication. In total, 90(42.4%), 10(37%) and 34(37.2%) patients had post-surgical HbA1c levels of <6%,<6.5% and<7%, respectively. No deaths were observed in the included studies, and the major complication rate was 6.2%. CONCLUSIONS: Based on the currently available data, bariatric surgery might improve glycemic control and weight loss in a very limited range with a doubled surgical complication rate in drug-refractory T2DM patients with BMI <30 kg/m2. It remains too premature to suggest bariatric surgery for non-obese T2DM patients.

Increased plasma DPP4 activities predict new-onset hyperglycemia in Chinese over a four-year period: possible associations with inflammation.

OBJECTIVE: DPP4, a novel proinflammatory cytokine, is involved in the inflammatory process through its interaction with the IGF-II/M6P receptor. Our objective was to determine whether DPP4 acts as a link between low-grade chronic inflammation and hyperglycemia. DESIGN AND METHODS: A prospective cohort study was conducted with 486 adults (177 men and 309 women) aged 18 to 70years without hyperglycemia examined in 2007 (baseline) and 2011 (follow-up). Circulating DPP4 activity, IGF-II/M6P receptor, and inflammatory markers were measured at baseline and four years later. RESULTS: After a four-year follow-up period, 111 individuals developed hyperglycemia (71 prediabetes and 40 type 2 diabetes). According to the multiple linear regression analysis, the baseline DPP4 activity was an independent predictor of an increase in the IGF-II/M6P receptor, inflammatory markers, and insulin resistance over the four-year period (all P <0.05). In the multivariable-adjusted models, the odds ratio (OR) for incident hyperglycemia comparing the highest and lowest quartiles of DPP4 activity was 2.90 (95% CI 1.47-5.73) after adjustment for confounding risk factors (P=0.002). The incidence of hyperglycemia because of DPP4 activity increased by 9.47%. Furthermore, the plasma DPP4 activity significantly improved the area under the ROC curve for predicting new-onset hyperglycemia based on the information from the baseline levels of the risk factors (P=0.036). CONCLUSIONS: DPP4 activity is an important predictor of the onset of insulin resistance and hyperglycemia in apparently healthy Chinese. This finding may have important implications for understanding the proinflammatory role of DPP-4 in the development and pathogenesis of hyperglycemia.

Increased plasma dipeptidyl peptidase 4 activities predict new-onset microalbuminuria in association with its proinflammatory effects in Chinese without diabetes: a four-year prospective study.

BACKGROUND: Recent evidence supports a protective role of dipeptidyl peptidase 4 (DPP4) inhibitors in lowering microalbuminuria (MAU) in diabetes but till now few studies have investigated the associations between DPP4 activity and MAU in nondiabetic Chinese individuals. This study tested whether DPP4 activity could predict new-onset MAU in Chinese without diabetes. METHODS: This was a 4-year prospective study conducted in Sichuan, China. A total of 664 Chinese women and men aged 18-70 years were studied. Circulating DPP4 activity, inflammatory markers and urinary albumin-to-creatinine ratio (ACR) were measured at baseline and 4 years later. RESULTS: The incidence of MAU during follow-up was 33.1 per 1000 patient-years. At baseline, individuals in the highest quartile of DPP4 activity had higher age, body mass index, waist/hip ratio, systolic blood pressure, diastolic blood pressure, fasting insulin, low-density lipoprotein-cholesterol, interleukin-6, high-sensitivity C-reactive protein, urinary albumin-to-creatinine ratio and lower high-density lipoprotein-cholesterol compared with individuals in the lowest quartile. After a 4-year follow-up, 88 individuals developed MAU. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in inflammatory markers and ACR over a 4-year period (all P < 0.05). In multivariable-adjusted models, the odds ratio for incident MAU comparing the highest with the lowest quartiles of DPP4 activity was 3.48 (95% CI: 1.50-8.09) after adjustment for confounding risk factors (P < 0.01). The incidence of MAU owing to DPP4 activity increased by 18.59%. CONCLUSION: DPP4 activity is an important predictor of the onset of inflammation and MAU in Chinese apparently without diabetes. This finding may have important implications for understanding the proinflammatory role of DPP-4 in the pathogenesis of MAU. TRIAL REGISTRATION NUMBER: #TR-CCH-Chi CTR-CCH-00000361.

Increased plasma DPP4 activity is predictive of prediabetes and type 2 diabetes onset in Chinese over a four-year period: result from the China National Diabetes and Metabolic Disorders Study.

CONTEXT: The significance of associations between prediabetes, type 2 diabetes, and dipeptidyl peptidase-4 (DPP4) activity in a Chinese population is not clear. OBJECTIVE: The objective of the study was to determine whether DPP4 activity and active glucagon-like peptide-1 (GLP-1) were predictive of the onset of prediabetes and type 2 diabetes. DESIGN, SETTING, AND PATIENTS: This was a 4-year follow-up study conducted in Sichuan, China. A total of 474 Chinese women and men aged 18-70 years were studied. MAIN OUTCOME MEASURES: All subjects were divided into 3 groups (normal glucose tolerance, prediabetes, and type 2 diabetes) on the basis of their glucose metabolism status after 4 years. The DPP4 activity, active GLP-1, and glucagon were measured at baseline and 4 years later. RESULTS: The baseline DPP4 activity was significantly higher in subjects who had progressed to prediabetes or type 2 diabetes compared with subjects who remained normoglycemic (P < .01). In a multiple linear regression analysis, baseline DPP4 activity and active GLP-1 were independent predictors of an increase in insulin resistance over a 4-year period (P < .05). Cox proportional hazards models revealed that DPP4 activity independently predicted the risk of developing prediabetes [relative risk 2.77 (95% confidence interval 1.38-5.55), P < .01] and type 2 diabetes [5.10 (95% confidence interval 1.48-17.61), P < .05] after adjustment for confounding risk factors. CONCLUSIONS: DPP4 activity is an important predictor of the onset of insulin resistance, prediabetes, and type 2 diabetes in apparently healthy Chinese individuals. This finding may have important implications for understanding the etiology of diabetes.

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats.

Silybin has been previously reported to possess anti-inflammatory properties, raising the possibility that it may reduce vascular damage in diabetic retinopathy. Present study was designed to investigate this potential effect of silybin and its underlying mechanisms in experimental diabetic retinopathy. Diabetes was induced with streptozotocin (STZ) plus high-fat diet in Sprague-Dawley rats, and silybin was administrated for 22 weeks after the induction of diabetes. Histochemical and immunofluorescence techniques were used to assess the obliterated retinal capillaries, leukostasis, and level of retinal intercellular adhesion molecule-1 (ICAM-1). Western blot was performed to quantitate the expression of retinal ICAM-1. Results showed that silybin treatment significantly prevented the development of obliterated retinal capillaries in diabetes, compared with vehicle treatment. In addition, leukostasis and level of the retinal ICAM-1 were found to decrease considerably in silybin-treated diabetic groups. In conclusion, these results indicate that silybin reduces obliterated retinal capillaries in experimental diabetes, and the recovered retinal vascular leukostasis and level of ICAM-1 at least partly contributes to the preventive effect of silybin.

Increased plasma DPP4 activity is an independent predictor of the onset of metabolic syndrome in Chinese over 4 years: result from the China National Diabetes and Metabolic Disorders Study.

AIMS: To determine whether fasting plasma Dipeptidyl Peptidase 4 (DPP4) activity and active Glucagon-Like Peptide-1 (GLP-1) were predictive of the onset of metabolic syndrome. METHODS: A prospective cohort study was conducted of 2042 adults (863 men and 1,179 women) aged 18-70 years without metabolic syndrome examined in 2007(baseline) and 2011(follow-up). Baseline plasma DPP4 activity was determined as the rate of cleavage of 7-amino-4- methylcoumarin (AMC) from the synthetic substrate H-glycyl-prolyl-AMC and active GLP-1 was determined by enzymoimmunoassay. RESULTS: During an average of 4 years of follow-up, 131 men (15.2%) and 174 women (14.8%) developed metabolic syndrome. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in insulin resistance over a 4-year period (P<0.01). In multivariable-adjusted models, the odds ratio (OR) for incident metabolic syndrome comparing the highest with the lowest quartiles of DPP4 activity and active GLP-1 were 2.82, 0.45 for men and 2.48, 0.36 for women respectively. Furthermore, plasma DPP4 activity significantly improved the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components (Both P<0.01). CONCLUSIONS: DPP4 activity is an important predictor of the onset of insulin resistance and metabolic syndrome in apparently healthy Chinese men and women. This finding may have important implications for understanding the aetiology of metabolic syndrome. TRIAL REGISTRATION: #TR-CCH-Chi CTR-CCH-00000361.