that inhibit OCT1.
Alcoholism and chronic pancreatitis have been associated with the development of insulin-deficient diabetes.16 More than 500 individual drugs have been associated with the risk of acute pancreatitis as an adverse effect, yet in only a small percentage of drugs has causality be established.17 Additionally, it is chronic exocrine pancreatic inflammation and damage rather than acute pancreatitis that is more likely to be linked etiologically to diabetes risk. The subject of alcohol and diabetes risk is discussed further in Chapter 10. It is possible that other as yet unidentified environmental toxins may be involved in the pathogenesis of the rare nonautoimmune cases of T1D.
Drugs Associated with Type 2 Diabetes
In contrast to the rarity of drug-associated typical T1D, several commonly used medications have been associated with the development of phenotypical type 2 diabetes (T2D). The latter classification is based loosely on the absence of absolute insulinopenia together with evidence for insulin resistance or related mechanisms for the disruption of glucoregulation. Depending on the severity and acuteness of the perturbation, some patients with drug-related diabetes may present with diabetic ketoacidosis (DKA). The fact that DKA is more characteristic of T1D than T2D may lead physicians to classify such presentations as T1D. Note, however, that ~25% of patients with T2D in the general population present with DKA.18,19 After initial stabilization with insulin therapy and fluid repletion, the majority of such patients respond to oral antidiabetic agents, as is typical of T2D. Therefore, it is more important to stabilize the patient with drug-related hyperglycemic crisis than to be distracted by a quest for an exact classification in the acute setting. In fact, in many instances, the exact mechanism of the medication-related hyperglycemia remains obscure, and the condition is best assigned to the other category.
According to the Centers for Disease Control and Prevention (CDC), the age-adjusted percentage of adults ≥18 years old with diagnosed diabetes who reported having hypertension was 57.1% in 2009.20 Other chronic comorbidities frequently found in people with diabetes include dyslipidemia, degenerative joint disease, chronic obstructive pulmonary disease, sleep apnea, congestive heart failure, affective disorders, and peptic ulcer disease. People with diabetes also are at risk for infections. These various conditions often require chronic or recurrent treatment with a wide array of medications, some of which could affect insulin sensitivity, β-cell function, or other aspects of glucoregulation. Whenever feasible, preference should be given to those agents that are either neutral or beneficial in their effects on carbohydrate and lipid metabolism.
In the chapters that follow, different classes of medications will be discussed with regard to their impact on diabetes risk. These medication classes were selected for discussion based either on 1) their historical association with dysglycemia in clinical practice, 2) extensive utilization for the management of comorbid conditions (e.g., hypertension, dyslipidemia) in patients with diabetes, or 3) existing or emerging reports of possible association with dysglycemia.
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19. Wang ZH, Kihl-Selstam E, Eriksson JW. Ketoacidosis occurs in both type 1 and type 2 diabetes—a population-based study from northern Sweden. Diabet Med 2008;25:867–870
20. Centers for Disease Control. Age-adjusted percentage of adults aged 18 years or older with diagnosed diabetes who have hypertension, United States, 1995–2009. Available from http://www.cdc.gov/diabetes/statistics/comp/fig8.htm. Accessed 23 January 2015
3: Glucocorticoid, Mineralocorticoid, and Immunomodulatory Agents
DOI: 10.2337/9781580406192.03
Glucocorticoid Steroids
In people with diabetes, systemic glucocorticoid steroid therapy impairs glycemic control via multiple mechanisms. Glucocorticoids induce insulin resistance, inhibit peripheral glucose utilization, stimulate lipolysis, and increase hepatic glucose production.1–3 In addition, these steroids inhibit insulin secretion and insulin biosynthesis, stimulate glucagon release, and induce endoplasmic reticulum stress and β-cell apoptosis following
