The Daily Burden of Living with Type 1 Diabetes
Living with type 1 diabetes is a 24/7 job — patients must constantly think about how they are managing the disease. Despite significant advances in the treatment of type 1 diabetes, particularly over the past 30 years, including the development of blood glucose (sugar) monitors, insulin analogs, insulin pumps and continuous glucose monitors, glucose control remains a tremendous challenge. In the United States less than 50% of people with type 1 diabetes achieve target-recommended A1c levels. Furthermore, even at target A1c (7%), recent data demonstrates a person with diabetes spends a very significant portion of the day hyperglycemic (too high blood sugar levels) and over an hour every day hypoglycemic (too low blood sugar levels). Hypoglycemia remains the major barrier to normal blood glucose levels and severe episodes still prove fatal.
The Diabetes Control and Complications Trial (DCCT) and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) have demonstrated the association between glucose control and both onset and progression of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. Surprisingly, recent data from the EDIC cohort has shown a strong metabolic memory effect of glucose control and that poor blood glucose control can have negative impact well into the future. The duration of this metabolic memory is unknown and is the focus of intense research. The direct link between sustained elevated glucose and macrovascular disease is not as clear. However, the longer-term follow-up of the EDIC cohort has shown significant benefit of intensive glucose management in reducing cardiovascular events by over 40% and severe events (including nonfatal myocardial infarction, stroke, or death from cardiovascular disease) by approximately 57% based on these study results.
Fortunately, the risk of developing diabetes complications continues to decrease. However, normal blood glucose level control is currently very difficult to achieve and the management of diabetes remains a grueling daily task for the individuals with type 1 diabetes as well as their loved ones. The Treat Research Program at JDRF aims to drive the discovery, development and delivery of devices and drugs that improve glucose control, reduce diabetes burden and improve health-related quality of life, and prevent diabetic complications.
JDRF TREAT Research Goal: Improved Blood Glucose Control and Resisting and Reversing Complications
JDRF’s Treat Research Program has four main areas of focus:
A closed loop artificial pancreas has been a long-sought approach to restore glucose control. A functional automated system was developed in the late 1970′s (the Biostator) that demonstrated considerable efficacy, but due to size was only suitable for in-hospital use. Today, small FDA-approved insulin pumps are being used in combination with small FDA-approved continuous glucose monitors. By adding sophisticated control algorithms, automation of insulin delivery in the home setting appears achievable. JDRF launched a major initiative — the JDRF Artificial Pancreas Project (APP) — in 2005 to accelerate the commercialization of these systems. Preliminary data suggests automation of insulin delivery, and ultimately multi-hormone replacement, will significantly improve glycemic/metabolic control and should ease the burden of diabetes management. JDRF support of the APP focuses on: a) Funding of the JDRF APP Academic Consortium, which is an international group of diabetes clinical experts partnering with leading control algorithm developers (mathematicians and engineers) to test new automation strategies, b) Partnership with industry to commercialize and deliver these approaches to patients, and c) Working with regulatory agencies for clarity on the regulatory pathway to accelerate regulatory approval.
A basic “artificial pancreas” would link continuous blood sugar measurements to an insulin pump with software that would together function more like a normal pancreas.
Treatment of patients with insulin alone is standard practice today. Without diabetes, the body produces many hormones that act in concert with insulin to achieve tight glycemic control and overall metabolic homeostasis. In type 1 diabetes, the functions of many of these hormones are either totally missing or compromised, necessitating the use of excessive compensating doses of insulin — a drug that comes with its own undesirable adverse side effects. This research area aims to discover, develop, and accelerate the delivery of improved therapeutics to control blood glucose levels (i.e. more physiologic insulin profiles, glucagon, amylin, leptin).
JDRF has launched its first Grand Challenge Prize to spur innovation toward the discovery and development of a glucose-responsive insulin drug with transformative potential to treat insulin-dependent diabetes. With the initial $100,000 Challenge prize, JDRF’s ultimate goal is to discover a glucose-responsive insulin drug that would work only when the body needs it. Glucose-responsive insulin would deliver the precise amount of insulin needed in response to circulating glucose levels to control and maintain normal blood glucose levels throughout a daily routine with once-daily or less frequent dosing in people with diabetes. The Challenge is open to the public and more details can be found at the Challenge website.
JDRF is focused on prevention of complications, with approaches independent of glucose, blood pressure and lipid control. Here, continued research is needed to gain a better understanding of the underpinnings of why certain people develop complications while others are afforded some degree of protection. This information will be utilized to exploit this knowledge to develop therapeutics and biomarkers to translate these findings into real solutions for patients. The research focuses on: a) the impact of genes, epigenetics, and gene/environment interaction on development of complications; b) identification and validation of novel targets and pathways; and c) the development of prognostic and predictive biomarkers to aid clinical development and to address the current challenges of the need for large-size complication clinical trials and long clinical trial. The Joslin 50-Year Medalists and its sister cohort, Golden Years, are clinical research studies of individuals with long duration of type 1 diabetes (>50 years) and include many individuals who have remained free of diabetic complications. Studies of this unique and valuable population and other cohorts that have not developed complications after decades of type 1 diabetes, may uncover essential factors that afford protection from the adverse effects of hyperglycemia that can then be applied to drug discovery and to the development of biomarkers to predict risk or stage progression of diabetic complications.
Diabetic eye disease or retinopathy is the leading cause of vision impairment and blindness in people aged 20-74 years. JDRF sees an opportunity to dramatically and tangibly change the status quo in diabetic eye disease through creation of a comprehensive program to serve patient needs for eye care and treatment. The approach includes: a) Screening and diagnostic technologies, b) Novel drugs and their delivery, and c) Access to eye care through regulatory reform and reimbursement strategies. In addition to the need for continued research and development of drugs and their delivery, issues of screening and diagnosis need to be addressed. The current paradigm for diabetic retinopathy screening and diagnosis is not convenient, rapid, or affordable, leading to delay in diagnosis of diabetic eye disease. Also, there are a limited number of retinal specialists to address the burden of diabetic eye disease in a timely manner. In addition, JDRF believe the regulatory process can be accelerated and that new provisions for reimbursement for screening, diagnosis and professional services need to be implemented.