Alena Smahelova

Once-daily initiation with biphasic insulin aspart 30 versus insulin glargine in patients with type 2 diabetes inadequately controlled with oral drugs: an open-label, multinational RCT

Abstract Objectives: To assess the efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine, administered once daily in subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs. Research design and methods: In this 26-week, open-labeled, randomized, parallel-group, multinational, treat-to-target trial, 480 insulin-naïve subjects were randomized to receive either BIAsp 30 before dinner or insulin glargine at bedtime, both in combination with metformin and glimepiride. Trial registration: NCT00469092, ClinicalTrials.gov. Results: A total of 433 subjects completed the trial. Estimated mean reduction in HbA1c from baseline to end of treatment was −1.41% with BIAsp 30 and −1.25% with insulin glargine (BIAsp 30 – insulin glargine = −0.16%, 95% CI [−0.30; −0.02], p = 0.029). At the end of treatment, mean HbA1c was 7.1% and 7.3% for BIAsp 30 and insulin glargine, respectively. Significantly lower plasma glucose levels were observed with BIAsp 30 post-dinner (BIAsp 30 – insulin glargine = −0.52 mmol/L, 95% CI [−1.02; −0.03], p = 0.04) and at bedtime (BIAsp 30 – insulin glargine = −0.78 mmol/L, 95% CI [−1.25; −0.31], p < 0.01). The relative risk (RR) of experiencing a nocturnal hypoglycemic episode (00:00–06.00 a.m.) was significantly higher with BIAsp 30 than with insulin glargine (1.1 versus 0.5 episodes/year, RR = 2.41, 95% CI [1.34; 4.34], p = 0.003), but overall hypoglycemia rates were low. There were three major hypoglycemic episodes in each group. Conclusions: With respect to HbA1c, BIAsp 30 fulfilled the statistical criteria for non-inferiority and superiority to insulin glargine and, according to pre-defined criteria, the improvements in HbA1c are considered clinically equivalent. Subjects had an increased risk of minor nocturnal hypoglycemia with BIAsp 30. There were no differences in treatment satisfaction between the two groups.

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial

OBJECTIVE To examine the safety and cardiovascular (CV) effects of saxagliptin in the predefined elderly (≥65 years) and very elderly (≥75 years) subpopulations of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESEARCH DESIGN AND METHODS Individuals ≥40 years (n = 16,492; elderly, n = 8,561; very elderly, n = 2,330) with HbA1c ≥6.5% (47.5 mmol/mol) and ≤12.0% (107.7 mmol/mol) were randomized (1:1) to saxagliptin (5 or 2.5 mg daily) or placebo in a double-blind trial for a median follow-up of 2.1 years. RESULTS The hazard ratio (HR) for the comparison of saxagliptin versus placebo for the primary end point (composite of CV mortality, myocardial infarction, or ischemic stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P = 0.06) and 0.95 for very elderly patients. The HRs for the secondary composite end points in the entire cohort, elderly cohort, and very elderly cohort were similar. Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population, there was no age-based treatment interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very elderly patients vs. those <75 years). Among saxagliptin-treated individuals with baseline HbA1c ≥7.6% (59.6 mmol/mol), the mean change from baseline HbA1c at 2 years was −0.69%, −0.64%, −0.66%, and −0.66% for those ≥65, <65, ≥75, and <75 years old, respectively. The incidence of overall adverse events (AEs) and serious AEs was similar between saxagliptin and placebo in all cohorts; however, hypoglycemic events were higher for saxagliptin versus placebo regardless of age. CONCLUSIONS The SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased irrespective of age category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients.

A case report of the treatment of diabetic foot ulcers using a sodium hyaluronate and iodine complex.

Diabetic foot ulcers are difficult to heal due to defects in local microvasculature and persistent, concomitant infection. Despite the best medical care, amputation is often a management option for this problem. The authors have developed a new and unique system for wound treatment, which is based on a combination of high molecular weight sodium hyaluronate with an iodine complex—Hyiodine® (Contipro C, Dolní Dobrouc, Czech Republic). In this case report, the authors present an observational study on a series of patients with diabetic foot disease with nonhealing wounds treated with Hyiodine. The effect of the HA-iodine complex was studied on 18 patients suffering from complicated foot diabetic wounds. The HA-iodine complex was either spread directly over the wound, or more frequently, gauze was immersed in the HA-iodine complex and then put on/into the wound. Then several layers of dry gauze covered the wound. This dressing was changed every 24 hours. Wound healing was monitored daily, and wound pictures were taken each second week. Clinical improvement was observed in the majority. This suggests that the HA-iodine complex dressing has potential that needs to be developed from controlled studies.

Selected metabolic parameters and the risk for uterine fibroids

To analyze the possible association between insulin resistance and dyslipidemia with uterine fibroids, using objective metabolic measurements.

Blood and tissue glucose level in critically ill patients: a comparison of different methods of measuring interstitial glucose levels

Sir: Tight glycemic control in critically ill patients may significantly decrease their mortality and morbidity. Mini-invasive techniques for continuous glucose monitoring [the Guardian Real Time (RT) continuous glucose monitoring system and the microdialysis technique] are promising methods for glucose management but clinical trials evaluating the correlation with plasma glucose levels in critically ill patients are missing. To investigate whether the glucose values obtained by the Guardian RT system and microdialysis could be used instead of blood glucose sampling in mechanically ventilated, critically ill patients we performed a prospective study in which we enrolled 15 patients aged 18 and over, admitted to a multidisciplinary ICU and the preliminary results we presented at the 28th International Symposium on Intensive Care and Emergency Medicine and Euroanasthesia 2008 Congress [1, 2]. A microdialysis catheter (CMA 60, 0.5 9 30 mm membrane, 20 kDa cut-off, CMA Microdialysis, Solna, Sweden), inserted into the subcutaneous adipose tissue in the abdominal area was constantly perfused with normal saline at a flow rate of 0.3 lL/min. The dialysate was collected in hourly fractions. A sensor of the Guardian RT system, Medtronic, Inc. (NYSE: MDT), was inserted simultaneously subcutaneously in the abdominal area opposite to the microdialysis catheter. Arterial blood samples were collected from the arterial catheter in hourly fractions (at the time of microvial replacement), analyzed for plasma glucose in the Central Laboratory and paired with the microdialysis and Guardian RT values recorded at the time of microvial replacement. Experiment ran for 24 h. Two hundred and thirty-six arterial blood samples, microdialysate and Guardian glucose readings were analyzed. The data were described as the median ± IQR (interquartile range) and the Pearson coefficient of correlation and the Bland Altman plot were calculated. The P values \0.05 were considered as statistically significant. The median arterial plasma glucose level was 6.2 (5.1; 7.8) mmol/L. The median Guardian RT glucose level was 5.75 (4.5; 7.2) mmol/L and the median microdialysis glucose level was 3.8 (2.5; 5.2) mmol/L. The correlation coefficient between arterial plasma glucose and the microdialysis interstitial glucose level was r = 0.7044. The correlation coefficient between arterial plasma glucose and Guardian RT readings was r = 0.6938. This was confirmed by the Bland Altman plot with broad limits of agreement. According to the observed, clinically unacceptable broad limits of agreement, microdialysis and the Guardian RT system could not be considered equivalent to blood glucose measurement and our findings do not support their use for the tight glycemic control management in mechanically ventilated, critically ill patients.

Urinary Neopterin in Patients with Diabetes Mellitus and Foot Ulcers

Abstract Increased urinary or serum concentrations of neopterin have been reported in disorders associated with systemic immune activation, e.g. viral infections, cancer, or autoimmune diseases, but the data on neopterin concentrations in patients with diabetes mellitus are limited. The aim of the present study was to investigate urinary neopterin concentrations in patients with diabetes mellitus and with or without diabetic foot. Urinary neopterin was determined by high-performance liquid chromatography in 51 patients with diabetes mellitus, including 19 patients with diabetic foot, and 18 healthy controls. Neopterin concentrations were significantly increased in patients with diabetes mellitus compared to controls (mean ± standard deviation; 221 ± 149 vs. 139 ± 66 μmol/mol creatinine; Mann-Whitney U test, p = 0.003). Urinary neopterin concentrations in patients with or without diabetic foot were identical (224 ± 113 vs. 219 ± 169 μmol/mol creatinine). No significant difference was also observed between patients with type 1 and type 2 diabetes mellitus, between patients treated with insulin compared to patients not treated with insulin, patients with or without diabetic retinopathy, with or without diabetic neuropathy, with or without diabetic nephropathy, with or without ischemic heart disease, with or without ischemic disease of lower extremities, and with or without ischemic cerebrovascular disease. Atrend of higher neopterin concentrations was observed in patients with any complication of diabetes compared to no complications (234 ± 164 vs. 176 ± 73 μmol/mol creatinine), and compared to controls, urinary neopterin was significantly increased only in patients with complications. No significant correlation was observed between urinary neopterin and glycosylated hemoglobin (rs = - 0.14, p = 0.39) or the duration of diabetes (rs = 0.25, p = 0.09). In conclusion, present results demonstrate that urinary neopterin is increased in patients with diabetes mellitus. No differences were observed in urinary neopterin concentrations based on type of diabetes, therapy or presence of diabetic foot, and urinary neopterin did not correlate with the glycosylated hemoglobin levels or duration of diabetes. Increased urinary neopterin concentrations in patients with diabetes mellitus is associated with the presence of complications and may reflect systemic immune activation associated with atherosclerosis.