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Diabetes Technology and Devices Transform the Lives of People with Diabetes

Published:April 28, 2015DOI:https://doi.org/10.1016/j.jcjd.2015.04.003
      Advances in diabetes treatment and technology over the past several decades have fundamentally transformed the lives of millions of people with diabetes mellitus globally. It is timely to choose diabetes technology and devices as the theme for this issue of Canadian Journal of Diabetes. To gain a better appreciation of the significant contributions made by the astounding scientific and medical advances in diabetes technology and devices, it would be of interest to our readers to recap a brief history of diabetes and its management.
      Diabetes is not a modern-day disease; the first suspected case of diabetes was recognized by the Egyptians more than 3500 years ago, dating to 1550 BCE. The Greek physician Aretaeus (81 to 133 AD) described a disease with symptoms of constant thirst, excessive urination and loss of weight and coined the condition diabetes, meaning flowing through. Historical documents reveal that Indian, Persian, Chinese, Japanese and Korean physicians were aware of the condition, but its cause remained elusive. During medieval times, urine samples were often used to diagnose various diseases. The word mellitus, meaning honey or sweet, was added by Thomas Willis in 1675 after discovering the sweetness of urine in his patients with diabetes. It was not until the early 19th century that glucose was identified as the sugar present in the urine samples of patients with diabetes. In earlier times, a diagnosis of diabetes was akin to a death sentence.
      The discovery of insulin by Banting, Best and McLeod in 1921, and the first injection of a crude beef pancreatic extract prepared by Collip, given to 14-year-old Leonard Thompson in 1922, heralded the lifesaving treatment of diabetes (
      • Bliss M.
      The discovery of insulin.
      ). Although insulin injections became successful in combating diabetes, many cases were unresponsive to this form of treatment. Himsworth was the first to distinguish between the 2 types of diabetes—insulin sensitive and insulin insensitive—in 1936, and they have now been reclassified as type 1 and type 2 diabetes, respectively (
      • Reaven G.M.
      Why syndrome X? From Harold Himsworth to the insulin resistance syndrome.
      ). Oral medications that stimulate the pancreas to develop more insulin were developed in the 1950s, and they appeared to be more effective than insulin in patients with insulin-insensitive diabetes. However, the cause of insulin-insensitive diabetes was not known until the development of the radioimmunoassay of insulin by Yalow and Berson in 1960, at which time patients with this form of diabetes were found to have higher than normal insulin levels, rather than insulin deficiency (
      • Reaven G.M.
      Why syndrome X? From Harold Himsworth to the insulin resistance syndrome.
      ). Shortly thereafter, distinct and separate treatment paradigms started to emerge for juvenile-onset, insulin-dependent and maturity-onset non-insulin-dependent diabetes, the diagnoses of which were based mainly on the ages of the patients’ diagnoses and the clinical presentations. In the 1960s, diabetes management improved significantly with the development of urine test strips, which made detecting sugar easier and simplified the process of managing blood sugar levels.
      Nonetheless, when I started my internship in Boston in 1975, I was struck by the fact that so many young people with insulin-dependent diabetes were admitted to the hospital for management of severe macrovascular complications: myocardial infarctions in their 30s and 40s, strokes, foot ulcers and gangrene requiring amputations, and renal failure requiring dialysis. Patients monitored their glycemic control using only urine tests, mostly with Clinitest tablets and, later, with urine test strips. Ketones were also measured in urine specimens using tablets and, later, dipsticks. The Harvard-affiliated hospitals were known at the time for providing state-of-the-art management of inpatients with diabetes by being the first to introduce blood glucose monitoring. The house staff members were trained to perform urine glucose and ketone testing and to write daily insulin orders based on the results of finger-tip or ear-lobe capillary blood sugar levels obtained by a large team of laboratory technicians who attended the hospital wards once or twice daily. Patients admitted for diabetic ketoacidosis were given large doses of intravenous as well as intramuscular short-acting beef-pork or pork insulin. Patients with insulin-dependent diabetes were discharged on a mixture of animal-sourced insulins, short-acting regular and longer acting neutral protamine Hagedorn (NPH), Lente, or protamine zinc insulin (PZI) injections once or twice daily. Some patients with diabetes were sent home on insulin and oral sulfonylurea agents. Diabetes management was largely the responsibility of the prescribing physicians, who would regularly monitor their patients by urine and blood glucose measurements. Diabetes technology was largely nonexistent except in research laboratories across the continent.
      Dextrostix, the first blood glucose test strip, was first developed in 1965 by Ames Laboratory. At about the same time, BoehringerMannheim developed a competitive blood glucose strip, the ChemstripbG, which was easier to use and stimulated the development of glucose metres (
      • Clarke S.F.
      • Foster J.R.
      A history of blood glucose metres and their role in self-monitoring of diabetes mellitus.
      ). Large portable glucose metres were created in 1969 and, in subsequent years, were reduced to the size of handheld calculators. Nonetheless, they were inconvenient, expensive and out of reach for most patients with diabetes. In the early 1970s, glycated hemoglobin measurement was gaining acceptance as an index for assessing the relationship between glycemic control and the risk for vascular complications. It was not until 1980 to 1981 that the Glucometer, the first portable glucose metre, became available to consumers. The metres are simple to use, produce accurate results and allow patients to monitor their blood sugar levels at home, at work and anywhere else. Diabetes management has transitioned from primary care practitioners and diabetes educators to self-management by the patients themselves and has resulted in dramatically improved glycemic control for a majority of patients. Enormous progress has been made in glucose metres over the past 4 decades; many metres now have more sophisticated data-handling capabilities and can be downloaded by a cable or infrared to a computer that has diabetes management software to display the test results. Some metres allow entry of additional data throughout the day, such as insulin doses, amounts of carbohydrates eaten and exercise. Since the late 1980s, self-monitoring of blood glucose (SMBG) using sophisticated portable glucose metres has become an essential tool and is truly the game-changer in diabetes self-managing today.
      The discovery of biosensors in the early 1980s greatly facilitated the development of continuous glucose monitoring (CGM) systems, which use a tiny sensor inserted under the skin to check glucose levels in tissue fluid. A transmitter sends information about glucose levels via radio waves from the sensor to a pager-like wireless monitor. CGM systems are more expensive than conventional glucose monitoring, but they may enable better glucose control. These devices provide real-time measurements of glucose levels, with glucose levels displayed at 5-minute or 1-minute intervals, and users can set alarms to alert them when glucose levels are too low or too high. CGM systems are used by about 10% of patients with type 1 diabetes.
      The next wave of SMBG and CGM systems is the development of noninvasive metres and the coupling of them with insulin-delivery devices and mobile applications to provide a more seamless tool to improve real-life diabetes outcomes. The U.S. Food and Drug Administration recently approved the marketing of the first set of mobile medical apps that allow people with diabetes to share data automatically and securely from a CGM system with other people in real time by using an Apple mobile device such as an iPhone (

      U.S. Food and Drug Administration. FDA permits marketing of first system of mobile medical apps for continuous glucose monitoring. FDA 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm431385.htm. Accessed March 6, 2015.

      ).
      In parallel with the development of portable glucose monitors, insulin delivery systems have also made great strides since 1970, when insulin pumps were developed to mimic the body’s normal release of insulin. Today, the insulin pumps deliver accurate amounts of insulin subcutaneously and are light and portable, allowing for comfortable wearing on a daily basis. Advances in recent years include the low glucose insulin-suspend (LGS) pumps, long-term continuous subcutaneous insulin infusion (CSII) and CSII in type 2 diabetes to improve glycemic control while minimizing hypoglycemia.
      For individuals living with type 1 diabetes, monitoring blood glucose has classically been accomplished in an open-loop fashion through the utilization of a continuous glucose monitor (CGM), a finger-stick method or both. A closed-loop artificial pancreas system, which requires CGM, an insulin pump and a control algorithm that calculates insulin dosing based on the input from the CGM, has the potential to significantly reduce the burdens of patients with type 1 diabetes. The concept of a closed-loop system that responds automatically to changing blood glucose concentrations by modulating insulin delivery in patients with type 1 diabetes has been around for several decades, but significant advances in technologic and algorithmic capabilities have brought the closed-loop system a step closer to reality. In the future, an artificial pancreas system will not only monitor glucose levels in the body but will also automatically adjust the delivery of insulin to reduce hyperglycemia and minimize the incidence of hypoglycemia with little or no input from the patient. However, formidable challenges such as adaptation (with possible individualization) of algorithms based on changes in physiologic parametres remain before such a system can be safely used in free-living situations.
      In addition to diabetes technology and devices and the development of new oral and injectable medications, newer insulins have also improved glycemic control without increasing the risk for weight gain and hypoglycemia or other long-term safety issues. Taken together, there have been several important advances in diabetes management since the turn of the 20th century. The first major game changer was the discovery of insulin, followed some 50-plus years later by the introduction of SMBG and, more recently, the development of new diabetes technologies and devices as well as the availability of new medications and insulins. These exciting developments have transformed not only the management of diabetes but, more important, the lives and the quality of lives of people affected by diabetes. I hope our readers find the various original research articles, reviews and perspectives in practice and commentaries in this theme issue to be informative and educational.
      The future of diabetes is indeed very bright and exciting despite the increasing global prevalence of both type 1 and type 2 diabetes. I remain optimistic that a world with fewer people with diabetes and healthier people with diabetes is within reach in our generation.

      References

        • Bliss M.
        The discovery of insulin.
        The University of Chicago Press, Chicago1982
        • Reaven G.M.
        Why syndrome X? From Harold Himsworth to the insulin resistance syndrome.
        Cell Metab. 2005; 1: 9-14
        • Clarke S.F.
        • Foster J.R.
        A history of blood glucose metres and their role in self-monitoring of diabetes mellitus.
        Br J Biomed Sci. 2012; 69: 83-93
      1. U.S. Food and Drug Administration. FDA permits marketing of first system of mobile medical apps for continuous glucose monitoring. FDA 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm431385.htm. Accessed March 6, 2015.