The term diabetes mellitus is derived from the Greek word for fountain and the Latin word for honey.




Drugs for Diabetes Mellitus

Laura D. Rosenthal DNP, ACNP, FAANP

Diabetes Mellitus: Basic Considerations

The term diabetes mellitus is derived from the Greek word for fountain and the Latin word for honey. The term describes one of the prominent symptoms of untreated diabetes: production of large volumes of glucose-rich urine. Indeed, long ago, the disease we now call diabetes was “diagnosed” by the sweet smell of urine—and, yes, by its sweet taste, too. In this chapter we use the terms diabetes mellitus and diabetes interchangeably.

Diabetes is primarily a disorder of carbohydrate metabolism. Symptoms mainly result from a deficiency of insulin or from cellular resistance to insulin's actions. The principal sign of diabetes is sustained hyperglycemia, which results from impaired glucose uptake by cells and from increased glucose production. When hyperglycemia develops, it can quickly lead to polyuria, polydipsia, ketonuria, and weight loss. Over time, hyperglycemia can lead to heart disease, renal failure, blindness, neuropathy, amputations, impotence, and stroke. There is an often-overlooked point about diabetes: in addition to affecting carbohydrate metabolism, insulin deficiency disrupts metabolism of proteins and lipids. We refer to regulation of blood glucose levels as glycemic control.

In the United States diabetes is the most common endocrine disorder and the seventh leading cause of death by disease. According to the 2011 National Diabetes Fact Sheet, compiled by the Centers for Disease Control and Prevention, about 26 million Americans have diabetes, and nearly one fourth of them have not been diagnosed. Another 79 million or so Americans are estimated to have prediabetes and are at increased risk for developing diabetes in the future.

We need to do a better job of diagnosing diabetes and treating it—and we need to do what we can to reduce the risk for developing the disease in the first place. Unfortunately, the risk for developing diabetes is largely genetic, a factor that can't be modified. Nonetheless, we can still reduce risk significantly by adopting a healthy lifestyle, centered on engaging in physical activity and establishing a healthy diet.

Types of Diabetes Mellitus

There are two main forms of diabetes mellitus: type 1 diabetes mellitus (often abbreviated as T1DM) and type 2 diabetes mellitus (often abbreviated as T2DM). Both forms have similar signs and symptoms. Major differences concern etiology, prevalence, treatments, and outcomes (illness severity and deaths). The distinguishing characteristics of type 1 and type 2 diabetes are shown in Table 46.1 and discussed later. Another important form—gestational diabetes—is discussed later under “Diabetes and Pregnancy.” Although there are additional forms of diabetes, they are relatively rare and will not be discussed specifically here.

TABLE 46.1

Characteristics of Type 1 and Type 2 Diabetes Mellitus

Type of Diabetes Mellitus


Type 1

Type 2

Age of onset

Usually childhood or adolescence

Usually older than 40 years

Speed of onset



Family history

Frequently negative

Frequently positive


Approximately 5% of people with diabetes have type 1 diabetes

90%–95% of people with diabetes have type 2 diabetes


Autoimmune process

Unknown—but there is a strong familial association, suggesting that heredity is a risk factor

Primary defect

Loss of pancreatic beta cells

Insulin resistance and inappropriate insulin secretion

Insulin levels

Reduced early in the disease and completely absent later

Levels may be low (indicating deficiency), normal, or high (indicating resistance)


Insulin replacement is mandatory, along with strict dietary control

Treat with an oral antidiabetic or noninsulin injectable agent and/or insulin, but always in combination with a reduced-calorie diet and appropriate exercise

Blood glucose

Levels fluctuate widely in response to infection, exercise, and changes in caloric intake and insulin dose

Levels are generally more stable than in type 1 diabetes


Polyuria, polydipsia, polyphagia, weight loss

May be asymptomatic initially

Body composition

Usually thin and undernourished at diagnosis

Frequently obese


Common, especially if insulin dosage is insufficient


Type 1 Diabetes

Type 1 diabetes accounts for about 5% of all diabetes cases. Between 1.2 million and 2.4 million Americans have this disorder. In the past, type 1 diabetes was called juvenile-onset diabetes mellitus or insulin-dependent diabetes mellitus (IDDM). These terms have fallen out of favor, however, because type 2 diabetes is becoming more common in children, and many people with type 2 diabetes use insulin to manage their diabetes. Accordingly, the terms juvenile-onset diabetes mellitus and IDDM are no longer clinically useful. Generally, type 1 diabetes develops during childhood or adolescence, and symptom onset is relatively abrupt. That being said, type 1 diabetes can develop during adulthood.

The primary defect in type 1 diabetes is destruction of pancreatic beta cells—the cells responsible for insulin synthesis and release into the bloodstream. Insulin levels are reduced early in the disease and usually fall to zero later. Beta cell destruction is the result of an autoimmune process (i.e., the patient's immune system inappropriately wages war against its own beta cells). The trigger for this immune response is not entirely known, but genetic, environmental, and infectious factors likely play a role.

Type 2 Diabetes

Type 2 diabetes is the most prevalent form of diabetes, accounting for 90% to 95% of all diagnosed cases. Approximately 22 million Americans have this disease. In the past, type 2 diabetes was called non–insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes mellitus. As discussed previously for type 1 diabetes, these terms are no longer clinically useful because insulin is commonly used by people with type 2 diabetes and type 2 diabetes can occur in all age groups. The disease most commonly begins in middle age and progresses gradually. In contrast to type 1 diabetes, type 2 diabetes carries little risk for ketoacidosis. However, type 2 diabetes does carry the same long-term risks as type 1 diabetes (see later).

Symptoms of type 2 diabetes usually result from a combination of insulin resistance and impaired insulin secretion. In contrast to patients with type 1 diabetes, those with type 2 diabetes are capable of insulin synthesis. In fact, early in the disease, insulin levels tend to be normal or slightly elevated, a state known as hyperinsulinemia. However, although insulin is still produced, its secretion is no longer tightly coupled to plasma glucose content: release of insulin is delayed, and peak output is subnormal. More important, the target tissues of insulin (liver, muscle, adipose tissue) exhibit insulin resistance: for a given blood insulin level, cells in these tissues are less able to take up and metabolize the glucose available to them. Insulin resistance appears to result from three causes: reduced binding of insulin to its receptors, reduced receptor numbers, and reduced receptor responsiveness. Over time, hyperglycemia leads to diminished pancreatic beta cell function, and hence insulin production and secretion eventually decline as the beta cells work harder to overcome insulin resistance within the tissues.

Although the underlying causes of type 2 diabetes are not entirely known, there is a strong familial association, suggesting that genetics play a role. This possibility was reinforced by a study that implicated the gene for insulin receptor substrate-2 (IRS-2), a compound that helps mediate intracellular responses to insulin.

Diabetes and Pregnancy

Before the discovery of insulin, virtually all babies born to mothers with severe diabetes died during infancy. Although insulin therapy has greatly improved outcomes, successful management of the diabetic pregnancy remains a challenge. Three factors contribute to the problem. First, the placenta produces hormones that antagonize insulin's actions. Second, production of cortisol, a hormone that promotes hyperglycemia, increases threefold during pregnancy. Both factors increase the body's need for insulin. And third, because glucose can pass freely from the maternal circulation to the fetal circulation, hyperglycemia in the mother will stimulate excessive secretion of insulin in the fetus. The resultant hyperinsulinism can have multiple adverse effects on the fetus.

Successful management of diabetes during pregnancy demands that proper glucose levels be maintained in both the mother and fetus; failure to do so may be teratogenic or may otherwise harm the fetus. Achieving glucose control requires diligence on the part of the mother and her prescriber. Some experts on diabetes in pregnancy advise that blood glucose levels must be monitored 6 to 7 times a day. Insulin dosage and food intake must be adjusted accordingly.

Gestational diabetes is defined as diabetes that appears in the pregnant patient during pregnancy and then subsides rapidly after delivery. Gestational diabetes is managed in much the same manner as any other diabetic pregnancy: blood glucose should be monitored and then controlled with diet and insulin. In most cases, the diabetic state disappears almost immediately after delivery, permitting discontinuation of insulin. However, if the diabetic state persists beyond parturition, it is no longer considered gestational and should be rediagnosed and treated accordingly.

In women taking an oral drug for type 2 diabetes, current practice is to discontinue the oral drug and switch to insulin. The only exception is the oral agent metformin, which is often satisfactory for managing type 2 diabetes in pregnancy. Women who discontinue oral medications can resume oral therapy after delivery.


Diagnosis of diabetes was once made solely by measuring blood levels of glucose. However, in 2010, the American Diabetes Association (ADA) recommended an alternative test, based on measuring hemoglobin A1c—a test that provides an estimate of glycemic control over the previous 2 to 3 months. For all of these tests, diagnostic values of diabetes are shown in Table 46.2.

TABLE 46.2

Criteria for the Diagnosis of Diabetes Mellitus

Fasting plasma glucose ≥126 mg/dL*


Casual plasma glucose ≥ 200 mg/dL plus symptoms of diabetes


Oral glucose tolerance test (OGTT): 2-hr plasma glucose ≥200 mg/dL‡


Hemoglobin A1c 6.5% or higher

*Fasting is defined as no caloric intake for at least 8 hours.

Casual is defined as any time of day without regard to meals. Classical symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss.

In this OGTT, plasma glucose content is measured 2 hours after ingesting the equivalent of 75 g of anhydrous glucose dissolved in water. The OGTT is not recommended or needed for routine clinical use.

Data from Standards of Medical Care in Diabetes—2014. Diabetes Care 2014;37(Suppl 1):S14-S80.

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