Coronary revascularization in diabetic patients: off-pump versus on-pump surgery.

BACKGROUND: Coronary artery bypass grafting (CABG) is a well-established procedure for treating diabetic patients with multivessel disease, but extracorporeal circulation and cardioplegia-induced cardiac arrest introduce a severe burden to these patients. The present study investigated if off-pump CABG decreases 30-day mortality and mid-term mortality in diabetic patients in comparison with conventional CABG. METHODS: From February 2009 through October 2011, data from 355 consecutive adult diabetic patients undergoing off-pump CABG and 502 patients undergoing on-pump CABG were prospectively recorded. Data analysis was performed by propensity score (PS)-adjusted logistic regression analysis and PS-adjusted Cox regression analysis. The primary endpoint was 30-day mortality. Secondary endpoints were major complications and mortality on follow-up. RESULTS: Off-pump CABG was associated with a significantly lower 30-day mortality rate (0.3% vs 4.2%; adjusted odds ratio [OR] = 0.09 [95% confidence interval (CI):0.01 to 0.70] p = 0.021) than on-pump CABG. Results coincided with a lower rate of postoperative neurologic complications in patients undergoing off-pump CABG (1.7% vs 5.4%; adjusted OR = 0.31 [95% CI: 0.12 to 0.77] p = 0.012) and a less frequent need for hemofiltration in these patients (3.4% vs 10.4%; adjusted OR = 0.30 [95% CI: 0.14 to 0.64] p = 0.002). The off-pump technique decreased the 6-month mortality rate (2.3% vs 8.8%; adjusted hazard ratio = 0.27 [95% CI: 0.12 to 0.61] p = 0.002) and also the 1-year mortality rate (4.0% vs 10.6%; adjusted hazard ratio = 0.40 [95% CI: 0.22 to 0.75] p = 0.004) significantly. CONCLUSIONS: Our data indicate that in terms of postoperative complications and early and mid-term survival, off-pump CABG is superior to the on-pump technique in diabetic patients.

Predicting the optimal basal insulin infusion pattern in children and adolescents on insulin pumps.

OBJECTIVE: We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII). RESEARCH DESIGN AND METHODS: We used the German/Austrian DPV-Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients <20 years of age (November 2009). A total of 1,248 individuals from our previous study were excluded (dataset 1), resulting in 6,063 CSII patients (dataset 2) (mean age 10.6 ± 4.3 years). Only the most recent basal insulin infusion rates (BRs) were considered. BR patterns were identified and corresponding patients sorted by unsupervised clustering. Logistic regression analysis was applied to calculate the probabilities for each BR pattern. Equations were based on both independent datasets separately, and probabilities for BR patterns were cross-validated using typical test patients. RESULTS: Of the 6,063 children, 5,903 clustered in one of four major circadian BR patterns, confirming our previous study. The oldest age-group (mean age 12.8 years) was represented by 2,490 patients (42.18%) with a biphasic dawn-dusk pattern (BC). A broad single insulin maximum at 9-10 p.m. (F) was unveiled by 853 patients (14.45%) (mean age 6.3 years). Logistic regression analysis revealed that age, to a lesser extent duration of diabetes, and partly sex predicted BR patterns. Cross-validation revealed almost identical probabilities for BR patterns BC and F in the two datasets but some variation in the remaining two BR patterns. CONCLUSIONS: Reconfirmation of four key BR patterns in two very large independent cohorts supports that these patterns are realistic approximations of the circadian distribution of insulin needs in children with type 1 diabetes. Prediction of an optimal pattern a priori can improve initiation and clinical follow-up of CSII in children and adolescents. In addition, these BR patterns represent valuable information for insulin-infusion algorithms in closed-loop CSII.

Clinical and forensic examinations of glycaemic marker methylglyoxal by means of high performance liquid chromatography-tandem mass spectrometry.

The postmortem determination of hyperglycaemic coma is quite difficult because of the lack of morphological findings and the difficult interpretation of biochemical parameters. Methylglyoxal (MG) is a reactive oxoaldehyde, which is mainly derived from glycolysis. An electrospray ionisation liquid chromatography-tandem mass spectrometric procedure for the determination of methylglyoxal in human serum and postmortem blood was developed. It involves protein precipitation with perchloric acid and a derivatisation step with 2,3-diaminonaphthalene. The assay was validated according to international guidelines. Serum samples from diabetics obtained at a diabetes clinic and from non-diabetics were used to assess data about reference concentrations in human serum. The assay showed linearity within the physiological concentrations in serum (5-500 ng/ml). Intraday imprecision at three concentrations was 10.3, 9.2 and 8.3 %, and interday imprecision was 15.3, 14.2 and 9.4 %; the limit of detection was 1.3 ng/ml, and limit of quantification, 3.2 ng/ml. One hundred and eighteen clinical (100 diabetics, 18 non-diabetics) and 98 forensic samples (84 non-diabetics, 14 in a status of hyperglycaemic coma) were measured. During life, diabetics showed significantly (p < 0.001) higher serum concentrations of MG than non-diabetics. After death, concentrations of MG increased significantly (p < 0.001). However, there was no correlation between the sum formula of Traub in vitreous humour and MG femoral blood concentrations (R = 0.237). This indicates that MG concentrations in the deceased cannot distinguish deaths due to a hyperglycaemic coma from other causes of death.

Liraglutide and DPP-4 inhibitors - side effects comparative clinical study.

The objective of this study was to monitor the side effects of the GLP-1 receptor agonist liraglutide in comparison to those of DPP-4 inhibitors (sitagliptin and vildagliptin), in order to determine their safety, tolerability and therapeutic efficiency. The study was carried out in the "Heart and Diabetes Center NRW" and included overweight patients with type 2 diabetes whose therapeutic regimen was switched to liraglutide or DPP-4 inhibitors. A validated questionnaire method was used to monitor the side effects during the hospitalization period, then again at 3, and 6 months after the beginning of the therapy. The therapy with liraglutide was associated with more side effects than the one with DPP-4 inhibitors. In general, side effects were declining with time, thus only few patients stopped therapy. The incretin therapy turned out to be a safe and effective therapeutic option for patients with type 2 diabetes mellitus.

Simultaneous determination and validated quantification of human insulin and its synthetic analogues in human blood serum by immunoaffinity purification and liquid chromatography-mass spectrometry.

Possible fatal complications of human insulin and its synthetic analogues like hypoglycemia require precise classification and quantitative determination of these drugs both for clinical purposes as well as for forensic toxicologists. A procedure was developed for the identification and quantification of human insulin and different long-acting as well as short-acting synthetic insulins in human blood serum specimens. After an immunoaffinity purification step and separation by liquid chromatography, the insulins were characterized by their five- or sixfold protonated molecule ions and diagnostic product ions. Clinical samples of 207 diabetic and 50 non-diabetic patients after the administration of human insulin or oral antidiabetics and forensic samples were analyzed for human/synthetic insulin concentrations. The method was validated according to international guidelines. Limits of detection of the insulins ranged between 1.3 and 2.8 µU/ml. Recoveries ranged between 33.2 % and 51.7 %. Precision data was in accordance with international guidelines. Clinical samples showed concentrations of human insulin lower than 301 µU/ml. Our liquid chromatography tandem mass spectrometry procedure allows unambiguous identification and quantification of the intact human insulin and its intact synthetic analogues Humalog®, Novolog®, Apidra®, Lantus®, and Levemir® in human blood serum in clinical and overdose cases. The assay could be successfully tested in patients with diabetes mellitus on therapy with insulins or oral antidiabetics.

Clinical and forensic examinations of glycemic marker 1,5-anhydroglucitol by means of high performance liquid chromatography tandem mass spectrometry.

Postmortem diagnosis of diabetes and a diabetic coma can be difficult because of the lack of characteristic morphological findings. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, competes with glucose for reabsorption in the kidneys. Therefore, diabetics with a permanent hyperglycemia show significantly lower serum concentrations of 1,5-AG than non-diabetics. A liquid chromatography-mass spectrometric method for the determination of 1,5-AG in serum and postmortem blood was developed and validated according to international guidelines. Linearity was given between 1 µg/ml and 50 µg/ml. Recovery rates ranged between 70.8% and 89.8%, the limit of quantification of the procedure was 0.20 µg/ml, limit of quantification was 0.55 µg/ml. Serum of 199 diabetics and 116 non-diabetics and femoral blood of 31 diabetic and 27 non-diabetic deceased was measured. Average concentrations were significantly (p<0.001) higher in non-diabetics compared to diabetics ante and postmortem. Seven of the diabetics may have died because of a hyperglycemic coma indicated by a sum formula of Traub>450 mg/dl. 1,5-AG average concentrations in these deceased were not significantly different to diabetics which did not die because of a diabetic coma. Concentrations of 1,5-AG give a hint for not well controlled diabetes antemortem and postmortem and can be assumed as an additional and alternative information postmortem to the measurement of HbA1c or fructosamine.