The potential of colchicine for lowering the risk of cardiovascular events in type 1 diabetes.

In type 1 diabetes, average life expectancy is reduced by ˃10 years as compared with outside of diabetes. Residual cardiovascular risk defines high cardiovascular event rate despite modern, guideline-recommended standard of care of established risk factors like hypertension, dyslipidaemia, and glycaemic control, and it adds importantly to these lost years of life in type 1 diabetes due to atherosclerotic cardiovascular diseases like myocardial infarction and ischaemic stroke. With a growing understanding of inflammation as an important driver of atherosclerotic cardiovascular disease, residual inflammatory risk is a novel and common risk factor and a promising target for lowering residual cardiovascular risk in type 1 diabetes. Interestingly, the inexpensive anti-inflammatory agent colchicine reduced the risk of major adverse cardiovascular events by 25% in cardiovascular outcome trials in the secondary prevention of atherosclerotic cardiovascular disease. Here, we summarize the role of inflammation as a driver of atherosclerosis and review current evidence linking inflammation and atherosclerotic cardiovascular disease in type 1 diabetes. Also, we provide an overview of the evidence base for targeting residual inflammatory risk with colchicine for lowering residual cardiovascular risk in type 1 diabetes.

Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial.

INTRODUCTION: Persons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment of the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin therapy in persons with type 1 diabetes will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia. The present article describes a protocol developed to test this hypothesis. METHODS AND ANALYSIS: One-hundred adult persons with type 1 diabetes for more than 1 year, insufficient glycaemic control (glycated haemoglobin A1c (HbA1c) between 58 and 86 mmol/mol) and body mass index >22.0 kg/m2 will be randomised to either exenatide 10 µg three times per day (at meal times) or placebo as add-on therapy to regular basal-bolus insulin treatment for 26 weeks. Primary endpoint is change in HbA1c between the two groups at end of treatment. Secondary endpoints include change in glycaemic excursions (assessed by continuous glucose monitoring); insulin dose; hypoglycaemic and adverse events; body weight, lean body and fat mass; dietary patterns; quality of life and treatment satisfaction; cardiovascular-disease risk profile; metabolomics; and arginine-tested plasma glucose, glucagon and C-peptide levels. ETHICS AND DISSEMINATION: The study is approved by the Danish Medicines Agency, the Regional Scientific Ethics Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Positive, negative as well as inconclusive results will be sought disseminated at scientific meetings and in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT03017352.

A Systematic Review on Insulin Overdose Cases: Clinical Course, Complications and Treatment Options.

A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications besides hypoglycaemia following large insulin overdoses is not readily apparent from the literature. A systematic search, compilation and review of case reports on insulin overdoses, published 1986-2017, was performed in PubMed, EMBASE, Cochrane and PROSPERO databases. Of 1523 published articles, 45 cases of insulin overdoses were included with a total median insulin dose of 900 international units (IU) (range 26-4800 IU). Hospitalization occurred in 44 cases with a median hospitalization duration of 94 hr (range 12-721 hr), and one-third (n = 15) admitted to the intensive care unit. First-line treatment was IV glucose treatment in 95% of cases. Treatment options besides IV glucose that were reported beneficial included glucagon IV or intramuscular (IM), octreotide IV or IM, surgical excision, hydrocortisone IV and oral intake of complex carbohydrates. Prevalent complications were intermittent cerebral impairment (73%), hypokalaemia (49%), other electrolyte disturbances (42%), and hepatic disturbances (7%) and cardiac toxicity (e.g. cardiac arrhythmia) (9%). Long-term consequences were one case of lasting hypoglycaemic encephalopathy and one death. In conclusion, following large insulin overdoses, in-hospital admission and treatment with IV glucose may be needed for up to a week. Monitoring of electrolytes and hepatic and cardiac functions seems important. Several experimental treatment options may be considered in addition to glucose administration. With appropriate pre- and in-hospital treatment, cases with severe hypoglycaemia and neurologic complications may have a favourable outcome.

Prophylactic antibiotics at the time of tracheotomy lowers the incidence of pneumonia.

INTRODUCTION: Nosocomial pneumonia in relation to tracheotomy is a well-known complication. The aim of the present study was to study prophylactic antibiotics at the time of tracheotomy as a protective factor against nosocomial pneumonia. METHODS: A retrospective follow-up study was conducted on otorhinolaryngeal cancer patients requiring a surgical tracheotomy over a four-year period. Data were extracted from a digital record system. The inclusion criteria included a cancer diagnosis in the otorhinolaryngeal area; and the tracheotomy had to be the primary operation. A total of 88 patients were eligible for inclusion, forming a group without antibiotics (n = 53) treatment and a group with antibiotics (n = 35) treatment. RESULTS: In the group without antibiotics, 67% (n = 34) developed pneumonia (not including aspirational) versus 44% (n = 14) in the group with antibiotics (p = 0.04). The 30-day mortality was 10% (n = 9), and the one-year mortality was 58% (n = 42) for the total population, with no statistically significant differences between the groups. Pneumonia after tracheotomy prolonged the hospitalisation time regardless of grouping. In the group without antibiotics, the median was seven days for patients without pneumonia compared with 12.5 days for patients with pneumonia (p < 0.01). Within the group with antibiotics, the median was ten days for the patients without pneumonia versus 16 days for those with pneumonia (p = 0.02). CONCLUSION: The present study indicates that prophylactic antibiotics administration at the time of tracheotomy lowers the incidence of pneumonia in otorhinolaryngeal cancer patients. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.