The lancet. Diabetes & endocrinology
-
Lancet Diabetes Endocrinol · Dec 2013
Randomized Controlled Trial Multicenter StudyTargeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial.
Type 1 diabetes results from autoimmune targeting of the pancreatic β cells, likely mediated by effector memory T (Tem) cells. CD2, a T cell surface protein highly expressed on Tem cells, is targeted by the fusion protein alefacept, depleting Tem cells and central memory T (Tcm) cells. We postulated that alefacept would arrest autoimmunity and preserve residual β cells in patients newly diagnosed with type 1 diabetes. ⋯ Although the primary outcome was not met, at 12 months, alefacept preserved the 4 h C-peptide AUC, lowered insulin use, and reduced hypoglycaemic events, suggesting efficacy. Safety and tolerability were similar in the alefacept and placebo groups. Alefacept could be useful to preserve β-cell function in patients with new-onset type 1 diabetes.
-
Lancet Diabetes Endocrinol · Dec 2013
Randomized Controlled Trial Multicenter StudyAntithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial.
Type 1 diabetes results from T-cell-mediated destruction of β cells. Findings from preclinical studies and pilot clinical trials suggest that antithymocyte globulin (ATG) might be effective for reducing this autoimmune response. We assessed the safety and efficacy of rabbit ATG in preserving islet function in participants with recent-onset type 1 diabetes, and report here our 12-month results. ⋯ Our findings suggest that a brief course of ATG does not result in preservation of β-cell function 12 months later in patients with new-onset type 1 diabetes. Generalised T-cell depletion in the absence of specific depletion of effector memory T cells and preservation of regulatory T cells seems to be an ineffective treatment for type 1 diabetes.
-
Lancet Diabetes Endocrinol · Dec 2013
Meta Analysis Comparative StudyComparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials.
The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. ⋯ In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.
-
Lancet Diabetes Endocrinol · Dec 2013
Randomized Controlled Trial Multicenter StudyEfficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study.
Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperphosphataemia. Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications. We aimed to test the efficacy, safety, and tolerability of once-daily recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) in adults with hypoparathyroidism. ⋯ 50 μg, 75 μg, or 100 μg per day of rhPTH(1-84), administered subcutaneously in the outpatient setting, is efficacious and well tolerated as a PTH replacement therapy for patients with hypoparathyroidism.
-
Lancet Diabetes Endocrinol · Dec 2013
Randomized Controlled TrialLow-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial.
An improper balance of regulatory/effector T (Treg/Teff) cells is central to the development of autoimmune diseases, including type 1 diabetes. We previously showed that low-dose interleukin 2 (IL2) induced Treg cell expansion and activation and clinical improvement in patients with hepatitis-C-virus-induced vasculitis. We aimed to establish which low doses of IL2 would be safe and induce Treg cells in patients with type 1 diabetes, considering that: (1) type 1 diabetes might be linked to alteration of the IL2/IL2R activation pathway; (2) activation of pathogenic Teff cells by IL2 could exacerbate disease; and (3) the safety of low-dose IL2 is not known in type 1 diabetes. ⋯ We have defined a well-tolerated and immunologically effective dose range of IL2 for application to type 1 diabetes therapy and prevention, which could be relevant to other disorders in which a Treg cell increase would be desirable.