Chapter 173: Diabetes Mellitus

ETIOLOGY AND PREVALENCE

Diabetes mellitus (DM) comprises a group of metabolic disorders that share the common feature of hyperglycemia. DM is currently classified on the basis of the pathogenic process that leads to hyperglycemia. Type 1 DM is characterized by insulin deficiency and a tendency to develop ketosis, whereas type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and excessive hepatic glucose production. Other specific types include DM caused by genetic defects (maturity-onset diabetes of the young [MODY] and other rare monogenic disorders), diseases of the exocrine pancreas (chronic pancreatitis, cystic fibrosis, hemochromatosis), endocrinopathies (acromegaly, Cushing’s syndrome, glucagonoma, pheochromocytoma, hyperthyroidism), drugs (nicotinic acid, glucocorticoids, thiazides, protease inhibitors), and pregnancy (gestational DM). The phenotype of these monogenetic and secondary types of DM typically resembles type 2 DM; its severity depends on the degree of beta cell dysfunction and prevailing insulin resistance. Type 1 DM usually results from autoimmune destruction of pancreatic beta cells; it is also known as juvenile-onset diabetes because its peak incidence is in children and adolescents.

The prevalence of DM is increasing rapidly; type 2 DM frequency in particular is rising in parallel with the epidemic of obesity (Chap. 172). Between 1985 and 2013, the worldwide prevalence of DM has risen more than 10-fold, from 30 million to 382 million cases. In the United States, DM prevalence at greater than 8% of the population, increasing with age. A significant portion of persons with DM are undiagnosed.

DM is attended by serious morbidity and significant mortality; it is the fifth leading cause of death worldwide.

DIAGNOSIS

Criteria for the diagnosis of DM include one of the following:

• Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL)

• Symptoms of diabetes plus a random blood glucose concentration ≥11.1 mmol/L (≥200 mg/dL)

• 2-h plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during a 75-g oral glucose tolerance test.

• Hemoglobin A_1c >6.5%

These criteria should be confirmed by repeat testing on a different day, unless unequivocal hyperglycemia is present.

Two intermediate categories also have been designated:

• Impaired fasting glucose (IFG) for a fasting plasma glucose level of 5.6–6.9 mmol/L (100–125 mg/dL)

• Impaired glucose tolerance (IGT) for plasma glucose levels of 7.8–11.1 mmol/L (140–199 mg/dL) 2 h after a 75-g oral glucose load

Individuals with IFG or IGT do not have DM, but are at substantial risk for developing type 2 DM and cardiovascular disease in the future.

Screening with a fasting plasma glucose level is recommended every 3 years for individuals over the age of 45, as well as for younger individuals who are overweight (body mass index ≥25 kg/m²) and have one or more additional risk factors (Table 173-1).