Diabetic Neuropathy – Top USMLE Diseases

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance, as well as relative insulin deficiency. Genetically determined causes of diabetes (e.g., maturity-onset diabetes of the young and late autoimmune diabetes in adults) are being increasingly recognized, but they make up a small portion of cases. There is no definitive cure for DM. The objective of management is the prevention of complications, which may include coronary artery disease, CKD, retinopathy, and neuropathy. Long-term monitoring and maintenance of optimal blood glucose levels are key to preventing complications. Treatment is specific to the type of diabetes, with glycemic control as the goal in all types; insulin replacement is essential in type 1, and a healthy diet, lifestyle changes, and medications are important in type 2.

Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non–iodine-deficient regions. Primary hypothyroidism occurs with thyroid gland disorders, while the central type arises from pituitary and hypothalamic conditions. Thyroid hormones are integral in metabolic processes and in the development of the brain and other organs. Congenital hypothyroidism can result in significant mental disability due to the loss of thyroid hormones. The features of acquired hypothyroidism also reflect the effects of slowed organ function, such as fatigue, bradycardia, cold intolerance, and exertional dyspnea. Diagnosis is by thyroid function testing. Elevated thyroid stimulating hormone and low free thyroxine (T4) levels are noted. Treatment is with synthetic T4.

Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma, which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and free T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin secretion (type 1 DM), insulin resistance (type 2 DM), or both (latent autoimmune diabetes in adults (LADA)). The goal of diabetes management is to prevent chronic serious and potentially disabling complications due to damage to various organs. Adequate long-term control of blood glucose is crucial in the prevention of complications. Macrovascular complications include heart disease, stroke, peripheral vascular disease, and CKD in various stages, including end-stage renal disease that requires dialysis. Microvascular disease can cause retinopathy, neuropathy, or symptomatic cardiac disease, which are not seen during stress testing or angiogram that are used to diagnose large vessel diseases.

Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. The clinical presentation varies by etiology as well as classification of the polyneuropathy, but generally manifests as sensorimotor disturbances (pain, paresthesia, numbness, weakness, and loss of coordination and balance), which have a gradual onset and progressive course. Distal nerves are affected most commonly, but the disease process may progress proximally with time or progression of the underlying etiologic disease entity. Diagnosis is made clinically, but laboratory studies, electrodiagnostic testing, and/or nerve biopsy may be required in some cases. Management varies depending on the etiology.

Non-insulinotropic diabetes medications are used to treat type 2 diabetes by methods other than increasing insulin secretion. This group of medications includes the biguanides, thiazolidinediones, alpha-glucosidase inhibitors, sodium–glucose transport protein 2 inhibitors, and amylin analogs. Mechanisms of action vary, but they can include increasing peripheral insulin sensitivity, reducing glucagon release, inhibiting gluconeogenesis, slowing glucose absorption, and increasing satiety. Metformin is the initial medication of choice; others may be used as an alternative monotherapy or as adjunctive therapy. Most of these medications are not associated with severe hypoglycemia, except for amylin analogs or when medications are used in conjunction with other hypoglycemic agents.

Insulinotropic diabetes medications treat type 2 diabetes mellitus by increasing insulin secretion, which results in decreased glucose levels. The group of medications includes sulfonylureas, meglitinides, glucagon-like peptide-1 (GLP-1) receptor agonists, and DPP-4 inhibitors. The agents are usually used in combination with other therapies for diabetes management. Sulfonylureas and meglitinides are associated with weight gain, while GLP-1 agonists may provide the added benefit of weight loss. Other side effects vary between the drug classes. None of the medications should be used in the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. There are several forms of insulin, and they differ in their time of onset, peak effect, and duration. Insulin can be classified as fast acting, short acting, intermediate acting, or long acting. A combination of classes can be used to maintain glucose control throughout the day. Common adverse effects include hypoglycemia, weight gain after initiation of an insulin regimen, and local injection site changes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of

Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma, which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and unbound T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non–iodine-deficient regions. Primary hypothyroidism occurs with thyroid gland disorders, while the central type arises from pituitary and hypothalamic conditions. Thyroid hormones are integral in metabolic processes and in the development of the brain and other organs. Congenital hypothyroidism can result in significant mental disability due to the loss of thyroid hormones. The features of acquired hypothyroidism also reflect the effects of slowed organ function, such as fatigue, bradycardia, cold intolerance, and exertional dyspnea. Diagnosis is by thyroid function testing. Elevated thyroid stimulating hormone and low free thyroxine (T4) levels are noted. Treatment is with synthetic T4.