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This first article in a three-part series discusses the differences between type 1 and type 2 diabetes,

complications related to diabetes, common treatment options for patients with diabetes and new

treatment options for patients with diabetes.

Barry J. Goldstein, MD, PhD, Professor of Medicine, Director, Division of Endocrinology, Diabetes and

Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA;

and Cindy J. Wordell, PharmD, Thomas Jefferson University Hospitals, Department of Pharmacy,

Philadelphia, PA, served as consultants for this article for the Certified Medical Representatives

Overview of Diabetes

Diabetes mellitus is not a single disease but rather a group of diseases character-ized by hyperglycemia and difficulties in effectively producing or using insu-

lin. The two primary types of diabetes mellitus are type 1 and type 2 diabetes. Overt diabetes, or conditions involving abnormal glucose metabo-lism, can also develop in certain circumstances, such as pregnancy, pancreatic disease or hor-monal imbalances. Many types of drugs can also cause impaired glucose tolerance (IGT) or hyperglycemia. When diabetes develops as a result of another condition, it is referred to as secondary diabetes.

Diabetes typesType 1 diabetes (insulin-dependent diabetes mellitus) is an autoimmune disease characterized by destruction of the insulin-producing cells and a severe deficiency of insulin production. While the onset of overt symptoms is usually sudden, immunologic abnormalities typically occur gradually and precede symptoms by sev-eral years.

Type 1 diabetes is relatively uncommon and

occurs in approximately 5 to 10% of all cases of diabetes mellitus. While type 1 diabetes can occur at any age, the incidence in the United States peaks in the teenage years. It is the second-most common chronic disease in children, after asthma. In most patients with type 1 diabetes, certain gene types are found in a specific chromosomal region that is involved in immunity and cell recognition. Also, there is a strong racial/ethnic association with type 1 diabetes risk. For example, Caucasians are at higher risk for developing type 1 diabetes than certain ethnic minority groups in the United States. Research also indicates that environ-mental factors, such as a virus or chemical exposure, may trigger the immune system to begin destroying cells in individuals with a genetic predisposition.

Type 2 diabetes (noninsulin-dependent diabetes mellitus) is related to inadequate amounts of insulin being secreted, as well as an inability of insulin to carry out its normal functions. These patients tend to be older. Approximately 90 to 95% of all cases of diabetes are due to this type of diabetes; therefore, most diabetes management

Describe the epidemiology and pathology of type 1 diabetes.

Describe the epidemiology and pathology of type 2 diabetes.

Identify the major types of complications related to diabetes.

Discuss common treat-ment options for patients with diabetes.

Describe new treatment options for patients with diabetes.

Learning Objectives

Diabetes: Approaches in Disease Management Part 1

Continuing Education in Pharmaceutical Representative aims to provide reps with information to help them meet the needs of the people they serve and to contribute to reps’ personal and professional development. Every third issue includes a self-assessment quiz covering the previous three Continuing Education articles. The quiz for this article will appear in the December issue. Reps who correctly complete the quiz and return it to the CMR Institute with a nominal handling fee will receive a completion-recognition form showing that they have successfully completed the three-part educational series and earned .25 CEU (2.5 contact hours). The CMR Institute also will send a letter of recognition to reps’ managers upon completion of a quarterly series. A Certificate of Achievement will be awarded to any representative who successfully com-pletes four quizzes or has obtained 1.0 CEU.

Note: The Continuing Education quizzes are not part of CMR Institute’s certification program and do not count as credits toward the CMR® designation.

About the CMR Institute:The Certified Medical Representatives Institute is an independent non-profit educational organization established in 1966 to provide a source of professional development and certification for pharmaceutical representatives. The Institute provides an up-to-date, approved continuing education curriculum designed to expand and enhance internal company training and development in a cost-effective manner. The curricu-lum concentrates on providing a general knowledge base and avoids such areas as selling skills and specific product education.

© 2008 The Certified Medical Representatives Institute Inc., Roanoke, VA 24014. All rights reserved. No part of this article may be reproduced by any method or in any form without written permission from the CMR Institute. Reprints of this article are available from the CMR Institute. Request Continuing Education article DB-1.

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programs focus on type 2 diabetes. The occur-rence of type 2 diabetes is influenced by factors such as:

• Age. Many body processes begin to have decreased functioning with advancing age, including tissue insulin sensitivity.

• Genetic background. Type 2 diabetes has a strong familial correlation; for example, if a mother or father has type 2 diabetes, the chances that a child will develop it are greater than 50%.

• Ethnic group. There is an increased risk of type 2 diabetes in certain ethnic groups, in-cluding American Indians, Hispanic/Latino Americans and African Americans.

The onset and severity of type 2 diabetes is greatly influenced by lifestyle factors, particularly diet and exercise, with obese patients at greater risk. In addition, a group of metabolic factors clustered together may identify individuals at in-creased risk for developing coronary artery diseases, stroke and type 2 diabetes. The condi-tions are collectively called “metabolic syndrome,” which is defined as the presence of three or more of the following:

• Large waist circumference (>40 inches for men, >35 inches for women)

• Elevated fasting glucose• Elevated blood pressure• Elevated triglyceride level• Low HDL “good” cholesterolIt is believed that with metabolic syndrome,

insulin loses its ability to effectively trigger the ab-sorption of glucose from the blood by the body’s cells. Blood glucose levels remain high after meals, triggering additional insulin secretion. The result-ing high levels of both glucose and insulin are linked with physiologic changes, such as:

• Damage to artery linings, which may lead to heart disease and stroke

• Renal changes, which may lead to high blood pressure, heart disease and stroke

• Increased triglyceride levels, which may increase the risk of developing cardiovascular disease

• Increased risk of blood clot formation, which can block arteries and cause heart attacks and strokes

• Decreased insulin production, which can signal the start of type 2 diabetes

Serious complicationsLong-term complications are the primary causes of death for patients with diabetes. The incidences of cardiovascular disease and stroke are especially high in patients with diabetes. Typically, diabetic complications are categorized as macrovascular and microvascular.

Macrovascular complications. These involve the large blood vessels and include heart disease,

stroke and peripheral vascular disease, which can in turn lead to gangrene, ulcers and amputation. The process begins when fat and other substances are deposited on the inner walls of large blood vessels, a process greatly accelerated by diabetes. This causes the vessels to narrow and harden, decreasing blood flow to organs and lower extrem-ities. Macrovascular diseases are divided into sub-types according to the vessels they affect:

• Coronary artery disease affects major arteries supplying the heart.

• Cerebrovascular disease affects blood vessels supplying the brain.

• Peripheral vascular disease affects the large blood vessels that supply other areas of the body, most often the legs.

Microvascular complications. These involve small blood vessels and occur primarily in three organ systems:

• Diabetic retinopathy involves degenerative changes in the capillaries of the eye, which can lead to internal bleeding and edema, retinal detachment and blindness. It is the leading cause of new adult-onset blindness in the U.S.

• In developed countries, peripheral neuropathy is the most common long-term complication of diabetes, resulting from the destruction of nerve fibers and damage to nerve cell functions brought about by abnormal glucose metabolism.

• Nephropathy refers to kidney disease. Damage to the kidneys can result in life-threatening accumulation of toxic waste products in the blood. Diabetic nephropathy is the leading cause of chronic renal failure in the U.S.

Hypertension and hyperlipidemia are common conditions for patients with diabetes. Hyper- tension (high blood pressure) is the major risk factor for congestive heart failure, occurring in 75% of those with diabetes. Hyperlipidemia (high lipid—or fat—levels in the blood) is associated with the development of atherosclerosis and coronary artery disease.

Type 1 signs and symptoms

Common signs (objective indications observed by a clinician or someone other than the patient) for type 1 diabetes include:

•Hyperglycemia(abnormallyhighbloodglucoselevels)•Glucosuria(abnormalpresenceofsugar,usuallyglucose,

intheurine)•Ketoacidosis(accumulationofacidintheblood)

Common symptoms (subjective reports by a patient of a feeling or experience) of type 1 diabetes include:

•Polyuria(excessiveurination)•Polydipsia(excessivethirst)•Polyphagia(excessivecravingforfood,especiallysweets)•Weightloss•Fatigue

October 2008 | www.pharmrep.com Pharmaceutical Representative 33

In addition, a number of infections are found almost exclusively in people with diabetes, espe-cially within the respiratory tract, urinary tract and soft tissues (particularly in the foot). Other complications that can result from diabetes include erectile dysfunction and periodontitis.

Treatment of diabetesOne of the primary ways to treat diabetes is through nutrition. For type 1, nutrition plans should be designed to integrate with insulin ther-apy, while for type 2, nutrition plans should focus on maintaining glucose, lipid and blood pressure goals. Other treatment options include:

• Exercise, which can help with losing weight and/or maintaining normal weight

• Oral agents, including insulin-secretion enhancers and insulin-sensitizers

• Insulin therapy, which may be prandial (administered at mealtimes) or basal (after mealtimes)

• Non-insulin injectable agents, including hormone analogs, which can be administered in addition to insulin

• Incretin-based agents, also injectable, which are based on hormones that enhance glucose-dependent insulin secretion

Each patient’s treatment plan should be individu-alized according to age, weight, physical condition, presence of high blood pressure, high cholesterol levels, etc. There are, however, some general thera-peutic guidelines depending on the type of diabetes that is diagnosed.

For patients with type 1 diabetes, insulin therapy is a requirement. In addition, coordinating insulin doses with diet and exercise is essential for patients with type 1 diabetes to maintain their appropriate weight and blood glucose levels and for normal growth and development. Other inject-able agents are now also available for type 1 dia-betics, such as pramlintide acetate, which helps lower blood sugar levels, especially the unhealthy rise in glucose that occurs right after eating. Oral antidiabetic agents, however, offer no benefit to patients with type 1 diabetes and are not used in its treatment.

The management of type 2 diabetes involves a combination of managed nutrition, exercise,

Lackofinsulinpreventsglucosefromenteringfatandmusclecells,soglucoseaccumulatesinbloodwhilethesecellsstarve

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weight reduction as necessary and the use of oral glucose-lowering agents, insulin injections and/ or injection of other non-insulin glucoregulatory agents. Cardiovascular risk factors, such as hypertension, smoking and dyslipidemia, are also addressed in the treatment plan.

The actual treatment approach chosen must take into account factors such as the patient’s abil-ity to understand and adhere to a treatment plan, the risk for developing severe hyperglycemia and the presence of other risk factors, such as concom-itant diseases or advanced age. In addition, type 2 diabetes is a progressive disease, and all treatments may have decreasing effect over time. Consequently, patients must receive continual monitoring for blood sugar control with revision of initial therapy as necessary.

The future of treatment Research is ongoing to provide new treatment options for patients with type 1 and type 2 diabetes. Areas of research include improved methods of insulin administration, pancreatic and -cell transplantation, and the use of stem cells and cells from the spleen.

Because patients typically inject insulin subcuta-neously one or more times each day, scientists have been investigating newer alternatives to standard insulin injections. These new treatment options include:

• Insulin pumps, about the size of a pager, con-tain a supply of insulin that passes through a thin tube into a fine needle inserted beneath the skin. The pump delivers a continuous basal dose of insulin throughout the day.

• Insulin pens allow the patient to load a cartridge filled with insulin into a reusable pen, or pre-filled, disposable pens can be purchased. The patient dials the insulin dose on the pen and pushes a plunger to inject the needle.

• Oral insulin sprays cross the buccal membranes of the mouth to deliver insulin into the blood-stream without entering the lungs.

• Implantable insulin pumps, about the size of a hockey puck, are surgically placed in the ab-dominal cavity and operated by remote control.

• The “artificial pancreas” consists of a continu-ous glucose monitor connected to an insulin pump. The insulin pump is placed in the abdo-men, and the glucose sensor is inserted into the superior vena cava. An electrical wire connects the two components.

• At some point, a single injection of DNA, con-taining an insulin gene, may trigger production of insulin. Animal studies have shown promise.

These are not the only new treatment options under investigation, however. Scientists are exam-ining a range of more experimental treatment options, including:

• Pancreas and -cell transplantation. This pro-cedure involves transplanting a healthy pan-creas or pancreatic tissue into patients with type 1 diabetes. Clinical outcomes so far have been impressive.

• -cell growth and stimulation. Genetic therapy may someday enable researchers to produce healthy -cells to replace dysfunctional -cells.

• Stem cells. Stem cells, which have the ability to differentiate into any cell within the body, have been successfully used to reverse diabe-tes in mice. Scientists are hopeful that a similar technique could be used to allow human stem cells to be used to replace the abnormal islet cells found in patients with type 2 diabetes.

• Cells from the spleen. Research on cells other than stem cells has indicated that cells from the spleen (those that lack the CD45 molecule) can transform into insulin-producing cells. In the future, it may be possible to use this tech-nology to reverse the onset of type 1 diabetes.

Thenextarticle in theserieswill focusondiabetesmanagement

guidelines.

Article Summary• Diabetes mellitus is not a single disease but rather a group of

diseases characterized by hyperglycemia and difficulties in effec-tively producing or using insulin. There are two primary types of diabetes.

–Type1diabetesisanautoimmunediseasecharacterizedbydestructionoftheinsulin-producingcellsandaseveredeficien-cyofinsulinproduction

–Type2diabetesisrelatedtoinadequateamountsofinsulinbeingsecreted,aswellasaninabilityofinsulintocarryoutitsnormalfunctions

• Long-term complications are the primary causes of death for patients with diabetes.

–Incidencesofcardiovasculardiseaseandstrokeareespeciallyhighinpatientswithdiabetes

–Diabeticcomplicationsaretypicallycategorizedasmacrovascu-larandmicrovascular

• The main categories of treatment options for patients with dia-betes include nutrition, exercise, oral agents, insulin therapy and non-insulin injectable agents, including incretin-based agents.

–Patients’treatmentplansshouldbeindividualized;however,therearegeneraltherapeuticguidelinesforeachtypeofdiabetes

• Scientists have been investigating newer treatment alternatives for type 1 and type 2 diabetes, including improved methods of insulin administration, pancreatic and -cell transplantation, and the use of stem cells and cells from the spleen.

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