Update on diabetes

Drug Store News, Feb 20, 1989 by Myron Weiner

Update on Diabetes

Myron Weiner, Ph.D. Associate professor of pharmacology and toxicology Department of Pharmacology & Toxicology University of Maryland School of Pharmacy Baltimore, Md. 21201

Feb. 20, 1989, lesson 679-401-89-2

GOAL:

To provide the practicing pharmacist with current pharmacological information on the treatment approaches to the two forms of diabetes mellitus.

OBJECTIVES:

1. Identify the characteristics of the two types of diabetes mellitus, with regard to incidence and pathology. 2. Define the different treatment approaches for the two types of diabetic patients. 3. Describe the mechanism of action of insulin and the oral hypoglycemic agents as well as their adverse effects and pharmacokinetic characteristics. 4. Describe basic differences between insulin preparations and between the six sulfonylureas. 5. Describe new methods for insulin administration, methods for monitoring blood glucose levels and proposed treatment approaches for diabetics.

This continuing education program will attempt to show that pharmacists can serve as vital members of the health care team by providing diabetes mellitus patients with a wealth of knowledge in addition to drugs and supplies.

From a pharmacological viewpoint, for a long time the pharmacist only had to be familiar with four orally-administered compounds and various beef- or pork-derived insulins. Even though there are just two additional oral agents available, and human insulin has been added to the various types of insulin preparations, there is new and important data concerning the appropriate use of the oral agents and insulins, and there are differences between the available drugs which have an impact on diabetic control.

Diabetes mellitus is a disease mainly characterized by increased glucose plasma levels, and diagnosed by a fasting hyperglycemia (plasma glucose level greater than 140 mg/100 ml) or by plasma glucose levels remaining above defined limits (greater than 200 mg/100 ml) over a specified time period during oral glucose tolerance testing (OGTT). Use of the OGTT has declined during the past few years for a number of reasons. The test is only diagnostic if the patient exhibits symptoms of diabetes and gives an indication for diagnostic testing (family history, obesity, etc.), but the fasting plasma glucose level is less than 140 mg/100 ml. Results of the OGTT can, at times, be misinterpreted; strict methodology adherence by testing personnel as well as the patient is important.

In addition to abnormal carbohydrate (glucose) metabolism, diabetes can result in modifications in protein (increased catabolism in muscle) and fat (increased release of free fatty acids from adipose tissue) metabolism.

Insulin (the hormone released from the beta cells of the Islets of Langerhans in the pancreas) primarily controls the relationship between the carbohydrate, fat and protein metabolisms. Insulin increases glucose uptake and utilization by insulin-dependent tissues, i.e., tissues which require insulin for glucose transport across the cell membrane. The two main insulin-dependent tissues are adipose and muscle tissues. Insulin also regulates glucose uptake into the liver and increases its storage as glycogen; in addition, the hormone suppresses the overproduction of glucose by the liver. The effects of insulin require the presence of functioning insulin receptors on cell membranes of these peripheral tissues. If either the insulin receptors themselves or post-receptor events within the cell are abnormal, conditions of hyperglycemia and diabetes can result.

Diabetes mellitus

Diabetes mellitus exists in two forms, an insulin-dependent form (IDDM; Type I) representing 10 percent of the diabetics in the United States, and a noninsulin-dependent form (NIDDM; Type II), existing in the remaining 90 percent of diabetics.

As the name implies, the former requires treatment with insulin to sustain life and to prevent ketoacidosis, while the latter can effectively be treated with oral sulfonylureas but may require insulin to provide adequate glucose control. In most cases, the Type I diabetic is thin, diagnosed as diabetic while under 25 years old, and tests positive for ketones in the urine as well as exhibiting hyperglycemia. This patient lacks insulin production by the pancreas.

The Type II diabetic, on the other hand, is usually obese, diagnosed while over 30 years of age, and not prone to ketoacidosis except under periods of extreme stress. Type II diabetics are often divided into obese and non-obese patients; however, only 10 percent are non-obese. While the NIDDM patient may possess normal, high or low blood levels of insulin, insulin resistance (decreased tissue sensitivity or responsiveness to insulin) is always present. The classic symptoms of diabetes are associated with the Type I diabetic and include polydipsia (excessive thirst), polyuria (increased urination), polyphagia (increased hunger), and weight loss. Type II diabetics may not exhibit these symptoms at the time of diagnosis of the disorder.