Porth's Essentials of Pathophysiology, 4e

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Endocrine System

U N I T 9

Impaired insulin secretion Excessive glucagon secretion

Carbohydrate absorption

Pancreas

Intestines

Type 2 Diabetes

Skeletal muscle

Liver

Fat cells

Increased basal hepatic glucose production

Decreased insulin-stimulated glucose uptake

A

Glucose absorption

Hepatic glucose output

α -Glucosidase inhibitors Amylin analogs

Biguanides

Thiazolidinediones

Type 2 Diabetes

Thiazolidinediones

Biguanides

Insulin secretagogues Incretins

Amylin analogs Incretins

Peripheral glucose uptake

FIGURE 33-8. (A) Mechanisms of elevated blood glucose in type 2 diabetes mellitus. (B) Action sites of hypoglycemic agents and mechanisms of lowering blood glucose in type 2 diabetes. The incretins are the dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists.

Major effect Minor effect

Glucagon secretion

Insulin secretion

B

impaired hepatic and renal function who are taking the longer-acting sulfonylureas. The meglitinides (repaglinide) and related drugs (nat- eglinide) are shorter-acting insulin secretagogues (termed glinides) that target post-prandial glucose elevation. These agents, which are rapidly absorbed from the gas- trointestinal tract, are taken shortly before meals. Both drugs can produce hypoglycemia; thus, proper timing of meals in relation to drug administration is essential. Biguanides. Metformin, the only currently available biguanide, inhibits hepatic glucose production and increases the sensitivity of peripheral tissues to the actions of insulin. Secondary benefits of metformin therapy include weight loss and improved lipid profiles. This medication does not stimulate insulin secretion; therefore, it does not produce hypoglycemia. However,

it confers an increased risk for lactic acidosis, and is contraindicated in people with elevated serum creati- nine levels, clinical and laboratory evidence of severe liver disease, or conditions associated with hypoxemia or dehydration. 32 α -Glucosidase Inhibitors. The α -glucosidase inhibitors (acarbose, miglitol) block the action of intestinal brush border enzymes that break down complex carbohy- drates. 32 By delaying the breakdown of complex carbohy- drates, the α -glucosidase inhibitors delay the absorption of carbohydrates from the gut and blunt the postprandial increase in plasma glucose and insulin levels. Although not a problem with monotherapy or combination therapy with a biguanide, hypoglycemia may occur with concur- rent sulfonylurea treatment. If hypoglycemia does occur, it should be treated with glucose (dextrose) and not