Johnny Ludvigsson

Linkoping University

Title: Combination therapy to preserve residual insulin secretion in type 1 diabetes


Johnny Ludvigsson, MD, PhD is a full Professor of Pediatrics, Linköping University. He performed the first immune intervention ever in T1D with plasmapheresis (BMJ 1983) which lead to the discovery of 64kD (Nature 1982), later shown to be GAD. He performed a number of different immune interventios both with GAD-alum (NEJM 2008, NEJM 2012) and AntiCD3 monoclonal antibodies (Lancet 2011). More than 430 scientific publications also on diabetic complications (NEJM 1994), and is the main tutor of >20 PhD students. He was the first pediatrician ever as Honorary member of EASD.


Introduction: Several mechanisms are involved in the pathogenetic process leading to insulin deficiency in Type 1 diabetes (T1D). Overwhelming insulin demand contributes to endoplasmatic reticulum stress, reduced function of the beta cells and increased sensitivity to a toxic immunologic milieu. Increased blood glucose, infections and obesity may contribute to a harmful inflammation. Autoimmunity, primary or secondary, then seems to add the ultimate blow. We therefore perform a pilot-trial where we combine beta cell protection, anti-inflammatory treatment and immune modulation. Patients and design: 60 Patients 10-18 years old with T1D since <4 months, fasting C-peptide >0.12 nmol/l and GADA positive all get intensive insulin treatment and strict blood glucose control to decrease beta cell stress. In addition they are randomized in a double-blind trial into one of four arms: A. Day 1-90 Ibuprofen 400 mg/d + Vitamin D 2000 U/d Day 1-450 + GAD-alum 20 mikrogsc Day 15 and 45. B. The same as A but placebo instead of Ibuprofen. C. The same as C but 40 instead of 20 mikrog GAD-alum. D: Placebo. Results: Only some patients have passed 6 month visit, but so far minimal treatment related adverse events. Several patients low insulin requirement and HbA1c within normal range (<43 mmol/mol). Data will be presented in Nov-2014. Conclusion: Combination of several treatment modalities, which as single therapy have insufficient efficacy, may offer safe alternatives to preserve residual insulin secretion.