Chapter 94: Diabetes Mellitus

KEY CONCEPTS

• Diabetes mellitus (DM) is a metabolic disorder. While there are numerous etiological causes, defects in insulin secretion, insulin action (sensitivity), or both lead to elevations in blood glucose as well as altered fat and protein metabolism.

• DM is a leading cause of eye and kidney disease. Patients with DM are at high risk for CV events, heart failure, and atherosclerotic disease.

• The two most common classifications of DM are type 1 (absolute insulin deficiency) and type 2 (relative insulin deficiency due to β-cell dysfunction coupled with insulin resistance). They differ in clinical presentation, pathophysiology, and treatment approach.

• The prevalence of type 2 DM has doubled worldwide over the last 40 years. This has been attributed to an alarming increase in the prevalence of obesity due to diminished physical activity and increased caloric consumption.

• The diagnosis of diabetes is made using any of the following criteria: (1) fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L); (2) a hemoglobin A1C (A1C) ≥6.5% (0.065; 48 mmol/mol); (3) a random plasma glucose level ≥200 mg/dL (11.1 mmol/L) coupled with classic symptoms of diabetes; or (4) a 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT). A diagnosis using criteria 1-3 requires two abnormal test results from the same sample or in two separate test samples.

• The goals of therapy in DM are to achieve optimal glycemic control (based on age, comorbid conditions, and patient preferences), reduce the onset and progression of diabetes-related complications, aggressively address CV risk factors, and improve quality of life.

• Intensive glycemic control prevents the onset and slows the progression of microvascular complications (eg, neuropathy, retinopathy, and nephropathy).

• Knowledge of the patient’s meal patterns and activity levels, as well as the pharmacologic properties of antihyperglycemic agents, is essential to creating an individualized treatment plan that achieves optimal glycemic control, avoids hypoglycemia, and minimizes adverse effects.

• Metformin has historically been used as the initial treatment for most patients with type DM. However, sodium-glucose transporter-2 (SGLT2) inhibitors and some glucagon-like peptide -1 (GLP-1) receptor agonists have well-established benefits in specific patient populations. Several guidelines now recommend a person-centered approach when selecting the initial treatment taking into consideration cardiovascular and kidney benefits, glucose-lowering efficacy, impact on weight, cost, and adverse effects.

• Type 2 DM often requires the use of multiple therapeutic agents (combination therapy) including oral and injected antihyperglycemics to achieve and maintain optimal glycemic control. A persistent decline in β-cell function over time often necessitates periodic adjustment and changes in therapy.

• Insulin therapy is required in type 1 DM. Intensive basal-bolus insulin therapy, either via multiple daily injections of insulin or continuous subcutaneous insulin infusion therapy (aka an insulin pump), in motivated individuals is more likely to achieve optimal glycemic control. Basal-bolus therapy includes a long-acting ...