The Children's Hospital of Philadelphia

Colin P Hawkes

Type 1 diabetes is a life-long condition that results from the autoimmune destruction of the insulin-producing pancreatic beta cells. These cells play a critical role in detecting fluctuations in blood glucose and responding through insulin secretion. Prior to the discovery of insulin in the early 20th century, this was a uniformly fatal disease. This discovery led to the development of medications and tools for patients to take on the role of the pancreas. Monitoring glucose became possible through frequent capillary glucose sampling(i.e., ‘finger-stick’ checks), and glucose management was achievable with measured subcutaneous insulin injection.

Careful dose calculation is required to reduce the risk of severe hypoglycemia complications, including seizures, coma, or even death. Administering too little insulin results in hyperglycemia, and this can be associated with the life-threatening complication of diabetic ketoacidosis in the short-term. Chronic hyperglycemia can increase the risk of long term complications, including kidney disease, blindness, heart disease, or nerve damage.

In the 100 years since the discovery of insulin, there have been advances in the development of insulin preparations with different profiles of action, but little progress has been made in finding a cure for this onerous disease. However, technological advances have revolutionized the management of this condition in the quest for the Holy Grail of the artificial pancreas.

Continuous subcutaneous insulin infusion therapy with an insulin pump has removed the need for frequent injections for many patients with this disease. A catheter placed beneath the skin allows for insulin to be infused at a programmed rate, with additional manual dose administration when required. These devices were initially large and cumbersome, but have become sleek and robust in the past 20 years. The accompanying software allows for data to be uploaded and trends in diabetes management to be reviewed.

The glucose-sensing role of the pancreas has become possible using continuous glucose monitors (CGMs). A subcutaneous catheter can detect fluctuations in interstitial glucose, and this can provide continuous data to replace intermittent capillary glucose checks. Recent advances have increased the reliability of CGM readings and removed the requirement for frequent calibration of the device. These devices may not even require external placement due to the recent development of implantable CGM devices. An alternative approach to capillary glucose checks has also been developed in the form of a flash monitoring system that will provide a glucose reading on-demand.

"Technology has transformed the clinical care of patients with type 1 diabetes at an exciting rate over the past 20 years"

Although, it appears that the tools for technology to function fully as an ‘artificial pancreas,’ there are challenges that have limited progress in this area. The CGM’s sensor is placed in the interstitial fluid and not in the bloodstream directly.So, there is a delay between glucose concentrations in the blood being reflected in the interstitial fluid. Similarly, the insulin pump delivers insulin to the subcutaneous tissue, and this must subsequently enter the bloodstream. Insulin analogs also do not act as quickly as the body’s insulin does in people without diabetes. These delays in the system have hindered the development of the artificial pancreas, but there have been stepwise approaches toward acheiving this goal.

CGM devices first communicated with insulin pumps allowing the patient to see blood glucose trends on their pump device. Subsequently, algorithms were developed to allow the insulin pump to stop administering insulin when the CGM detected blood glucose is low (i.e., ‘low glucose suspend’). The next step was to develop ‘predictive low glucose suspend’ algorithms that suspended insulin delivery when the CGM trend anticipated low glucose levels before they occurred. The latest devices have taken the next step in administering insulin in response to high glucose trends, but the patient still needs to administer ‘bolus’ insulin at meals. The rapid progress through these steps over the past 15 years have raised expectations that technology will eventually manage type 1 diabetes with minimal patient input.

These technological advances have transformed the clinical care of this patient population. In the past, patients were required to keep diligent log-books, recording capillary blood glucose measurements. These were reviewed at quarterly clinic visits, and dose adjustments were made based on these recordings. The clinician is now often overwhelmed by continuous day-to-day data from uploaded CGM devices, paired with additional data from the insulin pump. Many devices continually upload data to the cloud, so these data can also be reviewed in detail outside of the clinic setting.

As technology advances into the realm of dose adjustment, the intensity of clinician input into the care of patients with this disease is likely to change. Current guidelines recommend that patients attend clinic visits every 3-months to monitor disease management, adjust medication doses, and detect complications. With the availability of uploaded data, telemedicine visits may replace the need for frequent in-person clinic review. Improved diabetes control with technology may also reduce the risk of complications of this disease, possibly permitting less frequent clinical examination. As the role of technology advances to encompass more aspects of algorithm-driven insulin (and possibly glucagon) dosing, the skill-set most required by the patient’s diabetes care provider would increasingly be one of a technician rather than a clinician.

With these advances in technology, there have been massive increases in the cost of diabetes care. This is already putting technological options beyond many children and adults with diabetes both in the United States and throughout the world. As technology continues to improve, the deficit inquality of care received by patients and countries with limited resources will widen further. To address this, there is a need for low-cost and high-quality options that will improve access for all patients to the best available treatment for this disease going forward.

In summary, technology has transformed the clinical care of patients with type 1 diabetes at an exciting rate over the past 20 years. It does not appear to be slowing down and will continue to significantly improve the quality of life and clinical outcomes of patients with this disease. The artificial pancreas, once seen as an unattainable goal, has become a realistic possibility. At that point, the challenge will arise to make this accessible to all patients and the care model for patients with type 1 diabetes is likely to change to reflect the changing needs of this population. 

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