Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials.

BACKGROUND: Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved ß-cell function in recent-onset type 1 diabetes. METHODS: We did two randomised, placebo-controlled trials in two groups of patients with recent-onset type 1 diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0·2 nM. Patients in the canakinumab trial were aged 6-45 years and those in the anakinra trial were aged 18-35 years. Patients in the canakinumab trial were enrolled at 12 sites in the USA and Canada and those in the anakinra trial were enrolled at 14 sites across Europe. Participants were randomly assigned by computer-generated blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300 mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo daily for 9 months. Participants and carers were masked to treatment assignment. The primary endpoint was baseline-adjusted 2-h area under curve C-peptide response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9 months (anakinra trial). Analyses were by intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and EudraCT number 2007-007146-34. FINDINGS: Patients were enrolled in the canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No interim analyses were done. 45 canakinumab-treated and 21 placebo-treated patients in the canakinumab trial and 25 anakinra-treated and 26 placebo-treated patients in the anakinra trial were included in the primary analyses. The difference in C peptide area under curve between the canakinumab and placebo groups at 12 months was 0·01 nmol/L (95% CI -0·11 to 0·14; p=0·86), and between the anakinra and the placebo groups at 9 months was 0·02 nmol/L (-0·09 to 0·15; p=0·71). The number and severity of adverse events did not differ between groups in the canakinumab trial. In the anakinra trial, patients in the anakinra group had significantly higher grades of adverse events than the placebo group (p=0·018), which was mainly because of a higher number of injection site reactions in the anakinra group. INTERPRETATION: Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes. Interleukin-1 blockade might be more effective in combination with treatments that target adaptive immunity in organ-specific autoimmune disorders. FUNDING: National Institutes of Health and Juvenile Diabetes Research Foundation.

Diabetes prevalence and quality of diabetes care among Lebanese or Turkish immigrants compared to a native Danish population.

OBJECTIVES: To describe Type 2 diabetes prevalence and care among Turkish (T) and Lebanese (L) immigrants as compared to native Danes (DK) in the county of Aarhus. METHOD: Data from The National Health Service Registry, The Regional Laboratory Database and The Danish National Hospital Registry were collected from 2000 through 2003 to identify and describe known diabetes in a background population of 244.426 citizens in the age group of 40-70 years living in the County of Aarhus. RESULTS: The age-standardised prevalence of Type 2 diabetes was 3.6% (DK), 18.9% (L) and 19.8% (T). In 2003, HbA1c was measured at least once in 84% (DK), 87% (L) and 83% (T) of the patients. In 2003, 72% (DK), 53% (L) and 51% (T) had an HbA1c <8% (p<0.05) and less than 50% of all groups had a total-cholesterol <5.0 mmol/l. In 39% (DK), 35% (L) and 37% (T) of the patients, no examination for retinopathy was registered during the period of 2000-2003. A cardiovascular diagnosis was registered in 27% (DK), 32% (L) and 33% (T) of the patients (p=NS). CONCLUSION: Compared to native Danes, Lebanese and Turkish immigrants had a much higher prevalence of Type 2 diabetes and worse glycaemic regulation. The routine monitoring of diabetes care for native Danes, Lebanese or Turkish immigrants were similar. Overall, diabetes care is not satisfactory neither for native Danes, nor Lebanese or Turkish immigrants.

[Diabetic ketoacedosis]. / Diabetisk ketoacidose.

The diagnosis of diabetic ketoacedosis (DKA) may be based upon simple biochemical findings. Measurement of b-hydroxybutyrate in blood may replace semi-quantitative measurement of acetoacetic acid in urine. A list of criteria of graduating severity is suggested for the selection of patients to be treated in intensive care units. During treatment, intensive rehydration with sodium chloride for a longer period may induce metabolic acidosis. Terminating a regimen of intravenous insulin infusion requires knowledge of the difference in the duration of action of intravenous versus subcutaneous insulin.

[Myocardial necrosis with late occurrence of ventricular tachyarrythmia secondary to diabetic ketoacidosis]. / Myokardienekrose med sen forekomst af ventrikulaer takyarytmi sekundaert til diabetisk ketoacidose.

We present a case of a 27-year-old woman with diabetic ketoacidosis, who developed myocardial necrosis with raised troponin T, CKMB, universal ST-segment elevations and ventricular tachyarrythmia 27 hours after admission. At that time the initial electrolyte disturbances and ketoacidosis had been resolved. Coronary angiography was normal, but echocardiography showed impaired left ventricle function, with an ejection fraction of 45%. At the three-month follow-up echocardiography was normal. The mechanism of myocardial necrosis secondary to metabolic derangements remains unknown.