ISPAD roving reporters 2020

Abstract

Type 1 diabetes (T1D) progresses through stages. Those at increased genetic risk progress to alterations in immune regulation leading to an imbalance between T regulatory and T effector cells and the development of pancreatic autoantibodies. In the next stage individuals with T1D have asymptomatic abnormal glucose tolerance, which then progresses to symptomatic clinical diabetes, and finally long-standing T1D. All individuals with stage 1 T1D, characterized by at least two pancreatic autoantibodies, will progress to clinical T1D over 15–20 years. Teplizumab, a monoclonal antibody that binds CD3 on the T-cell receptor, has been shown to delay the onset of Stage 3 clinical T1D in patients with autoantibodies and abnormal oral glucose tolerance test (OGTT). Ongoing TrialNet studies are focusing on the use of hydroxychloroquine and abatacept to intercede in the progression of T1D. However, to date, prevention and cure of T1D have remained elusive and no therapies have produced robust, durable effects on inducing immune tolerance or preserving insulin secretion. Suboptimal glycemic control, weight gain, and severe hypoglycemia are areas of unmet clinical need in T1D care. Severe hypoglycemia is associated with decreased quality of life, fear of hypoglycemia and resulting suboptimal control, cognitive decline, and increased mortality. Despite these risks, approximately half of people with T1D do not fill prescriptions for glucagon and 50% of trained caregivers failed to administer intramuscular glucagon in a simulated episode of severe hypoglycemia. In studies, nasal glucagon 3 mg successfully raised blood glucose values in all patients and was successfully administered by 94% of trained caregivers and 93% of untrained acquaintances. Glucagon-like peptide-1 (GLP-1) agonists are typically prescribed for Type 2 diabetes (T2D), however evidence showing reduced postprandial hyperglycemia and hepatic glucose output suggests the potential use of these agents as adjunctive therapy in T1D. In adults with T1D, the use of liraglutide resulted in sustained hemoglobin A1c (A1c) reductions of approximately 0.5% and up to 4 kg of weight loss. Despite these potential benefits, use has been limited by increased rates of hypoglycemia and ketotic hyperglycemia. Similarly, sodium glucose co-transporter 2 inhibitors (SGLT2i), which inhibit renal glucose reabsorption, have been associated with improvements in A1c and blood pressure, weight loss, and decreased urine microalbumin levels. Despite these potential benefits, their use in T1D has been limited by a 2– 4 fold greater risk for diabetic ketoacidosis (DKA). SYMPOSIUM 1: DIABETES PREVENTION