From ATLANTA Medicine, Vol. 85, No. 4
Diabetes is not going away. As America becomes more sedentary and more overweight, and as developing countries “ westernize” their diets, the incidence of diabetes – especially Type II – is skyrocketing.
While the incidence of the disease is increasing at an alarming rate, we are continuing to advance our knowledge into the pathophysiology of both Type I and Type II diabetes, leading to new forms of therapy. Our technology to detect and monitor these diseases has advanced as well. Hopefully our advances in pathophysiology, treatment and technology will both prevent future cases of diabetes as well as make the lives of those who have diabetes healthier and happier.
Right now the incidence of diabetes in the U.S. is about one in 10, and there are dire predictions that unless we do something to change our course, one in three Americans may have diabetes by the year 2050. Diabetes and obesity are closely linked, so as the incidence of obesity goes up the incidence of diabetes goes up.
Unfortunately, this starts at an early age. When I was growing up in the 1960s, the overweight child was the exception. Now in America’s elementary school, every third desk is occupied by an overweight child. Today, in children under the age of 12 presenting with diabetes, the likelihood that it will be Type II Diabetes instead of Type I is 45 percent.
To combat these rising rates, we must educate both parents and children about proper nutrition and exercise. These skills are just as important as any other life skills to ensure that the life expectancy of future generations is just as high as or higher than it is right now.
Due to the efforts of such great researchers like Dr. Ralph De Fronzo, our knowledge of the pathophysiology of Type II diabetes, the most prevalent form, has increased dramatically. Researchers have been peeling away the layers of the onion to get to the core defects of the disease so that we develop specific treatments to target each of these core defects.
In the early 1990s, Dr. De Fronzo outlined the triumvirate of insulin resistance, impaired insulin secretion and increased hepatic glucose output as the basic pathophysiology behind Type II diabetes. However, new research has led Dr. De Fronzo to expand from the triumvirate to the ominous octet.
This means eight separate areas can be targeted therapy. 1) The pancreatic beta cell because of decreased insulin secretion. 2) The pancreatic alpha cell because increased glucagon secretion. 3) Incretin hormones because Type II diabetics are to some degree both incretin deficient and incretin resistant. 4) The kidney because it is responsible for reabsorption of glucose from the urine. 5) The sympathetic nervous system because increased sympathetic tone increases blood glucose. 6) The muscles because insulin resistance decreases glucose uptake in the muscles. 7) The liver because of increased hepatic glucose output and lastly 8) Adipose tissue because increased lipolysis is toxic to the beta cell and increases insulin resistance.
The ominous octet is just our latest stopping point in understanding Type II diabetes, but our understanding of this disease is ever widening.
When I started practice more than 25 years ago, human insulin had just recently become widely commercially available and the sulfonylureas were the only class of oral agents available in the U.S. Now there are five new analog insulins, three rapid acting, two long acting and an inhaled form of human insulin on the way.
The classes of oral agents have expanded from one to nine. In addition to the sulfonylureas, we now have biguanides like metformin that decrease hepatic glucose output, thiazolidinedione like pioglitazone that increase insulin sensitivity in muscle and fat, nateglinides that increase insulin secretion, alpha-glucosidase inhibitors that block carbohydrate absorption in the gut, GLP-1 agonists that give pharmacologic levels of activation of the incretin GLP-1 receptors, DPP-4 inhibitors that decrease the enzymatic degradation of GLP-1, dopamine agonists that decrease sympathetic tone, and the latest class of new anti-diabetic therapy, the SGLT2 transport blockers that decrease the kidney’s ability to reabsorb glucose. Each one of these therapies targets a specific arm of Dr. De Fronzo’s ominous octet. (See page xx for more on how Dr. Jonathan Ownby puts these agents to appropriate clinical use.)
In the 1980s, home glucose monitors were the size of cassette tape recorders, required a large hanging drop of blood to produce a glucose reading and the test time was two minutes. Insulin pumps were in their infancy, with Auto-Syringes, nicknamed the “blue brick” due to its large size and weight, that could give only a single basal insulin rate.
Now glucose monitors fit in the palm of your hand and require less than 0.5 microliters of blood. There are even smart monitors that can spot trends in blood glucose and can be programmed to calculate insulin doses. Insulin pumps are smaller and smarter. Basal insulin requirements can now be programmed hourly. The pumps can be programmed to calculate mealtime insulin when the patient feeds in their glucose and carbohydrate data.
There are now continuous glucose sensing devices that give a glucose reading every five minutes in real time to help patients on insulin pumps and multiple daily insulin injections avoid lows and combat highs to achieve better control. (See page xx for Dr. Chris Newton’s view on the latest in these technology advances and how to apply them to your patients.)
The incidence of diabetes is advancing, and we are trying to keep pace with advancing our knowledge, technology and treatment strategies. However, all of these advancements will fall short of their potential unless we have educated patients. Education is still the cornerstone of diabetic therapy because the more our patients know about what diabetes is and the more they know about how treat it, the more adherent our patients will be. Our most sophisticated therapies will be ineffective unless we give our patients the tools to implement healthy lifestyles that incorporate diet, weight loss and exercise.