Aims: This meta-analysis was performed to provide an update on the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus (T2DM).
Methods:We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy in patients with T2DM by the end of December 2012, using the key words 'alogliptin', 'dutogliptin', 'linagliptin', 'saxagliptin', 'sitagliptin', 'vildagliptin' and 'metformin'. RCTs were selected for meta-analysis if (1) they were RCTs comparing DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy, (2) duration of treatment was ≥12 weeks and (3) reported data on haemoglobin A1c (HbA1c) change, fasting plasma glucose (FPG) change, weight change, adverse cardiovascular (CV) events, hypoglycaemia or gastrointestinal adverse events (AEs). Conclusions: DPP-4 inhibitors, which are safe and effective in controlling the blood glucose, may possibly decrease the risk of CV events in patients with T2DM. It could be a credible alternative for T2DM patients who, for some reason, cannot use metformin, or are in high risk of CV exposure. High-quality, large sample and long-term follow-up clinical trails are needed to confirm the long-term conclusions.
Purpose To quantitatively evaluate the upper extremity and elbow function with the Mayo Elbow Performance Score (MEPS) in children with transphyseal fracture of the distal humerus (TFDH) treated surgically. Methods During the period between 2005 and 2015, a total of 16 patients (ten male, six female) met the inclusion criteria. Mean age at the time of injury was 18 months (11 to 37) and mean follow-up was 42.3 months (6 to 98). Based on a modified version of Delee’s classification (Group A to C), the clinical and radiographic outcome of TFDH in toddlers treated surgically were retrospectively evaluated. Results Mean humeral-ulnar (HU) angle of the injured and non-injured side was 1.2° (-18° to 14°) and 8.8° (2° to 19°), respectively (p = 0.001). Closed and open reduction showed similar HU angle values (p = 0.682). Mean MEPS score of the injured and non-injured side was 85.5 points (70 to 95) and 95 points (90 to 100), respectively (p = 0.002). No significant association was identified between MEPS score and gender, side, age at trauma, direction of displacement, time from trauma to surgery, presence of ossified capitellum, type of surgery and type of fracture. Conclusion Functional outcome was generally good regardless of surgical procedure performed, closed or open and type of fracture according to modified Delee’s classification. However, a residual cubitus varus was commonly observed among toddlers with transphyseal fractures of the distal humerus. Level of evidence: Level IV – Therapeutic study
Studies of C-peptide cellular effects show that not only the full-length native peptide but also specific C-terminal fragments are biologically active in in vitro systems. In the present study, the effect of five C-peptide fragments and the native peptide on whole-body glucose turnover was studied in streptozotocin diabetic rats using the insulin clamp technique. Insulin was infused intravenously at 18 pmol kg(-1) min(-1) for 90 min and blood glucose concentration was clamped at 8 and 4 mM in diabetic and non-diabetic animals. A steady state was reached during the last 30 min of the study period. Rat C-peptide II and fragments comprising residues 27-31 and 28-31 were effective in augmenting glucose turnover in diabetic rats (+100% to 150%), while no significant effects were seen for segments 1-26, 11-19 and 11-15. The metabolic clearance rate for glucose during infusion of C-peptide or fragments 27-31 and 28-31 in diabetic rats was similar to that seen in non-diabetic animals. We conclude that C-terminal tetra- and pentapeptides, but not fragments from the middle segment of C-peptide, are as effective as the full-length peptide in stimulating whole-body glucose turnover in diabetic rats.
IRX3 genetic variants associate with birth weight, BMI and AST/ALT-related transaminase metabolism, supporting the role of IRX3 as an obesity-associated susceptibility gene.
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