Diabetes Mellitus Overview

Diabetes Mellitus (DM)

• Chronic multisystem disease characterized by high blood sugar (hyperglycemia) from abnormal insulin production or use.
• A significant global health problem, affecting approximately 34.2 million people (10.5% of the population) in the US. An estimated 7.3 million people remain undiagnosed.
• The 7th leading cause of death in the US.
• Prediabetes affects 88 million US adults.

Etiology and Pathophysiology

• Causes of DM are often a combination of genetic, autoimmune, and environmental factors (e.g., viruses, weight).
• Primarily involves abnormal glucose metabolism due to insufficient or absent insulin, or impaired insulin use.
• Four main types of DM: Type 1, Type 2, Maturity-onset diabetes of the young (MODY), Gestational DM, and other specific types.

Normal Glucose and Insulin Metabolism

• Insulin, a hormone produced by the pancreas's beta cells, regulates glucose levels.
• Insulin is released continuously, and its release increases after eating.
• Normal blood glucose levels range from 74-106 mg/dL (4.1-5.9 mmol/L).
• Daily insulin production in an adult is typically 40-50 units (or 0.6 units/kg body weight).
• Insulin facilitates glucose transport into cells for energy production.
• Excess glucose is stored as glycogen in the liver and muscles.
• Insulin's role as an anabolic (storage) hormone is crucial. During fasting, counterregulatory hormones (like glucagon and cortisol) help maintain glucose in circulation.
• Some tissues (brain, liver, blood cells) don't directly rely on insulin.
• Insulin signaling depends on presence of receptors for many cells

Type 1 Diabetes

• Accounts for 5-10% of diabetes cases.
• Primarily affects people under 40, although it can affect people of any age.
• An autoimmune disorder where the body attacks insulin-producing beta cells in the pancreas.
• Genetic predisposition and viral exposure may contribute.
• Development of symptoms is often rapid, leading to severe hyperglycemia or diabetic ketoacidosis (DKA).
• Characterized by classic symptoms: excessive thirst, frequent urination, and extreme hunger.
• Requires exogenous (external) insulin for survival.
• "Honeymoon period" is possible for newly diagnosed patients with temporary remission.
• Eventually requires lifelong insulin treatment as beta cells are destroyed

Type 2 Diabetes

• Accounts for 90-95% of diabetes cases.
• Associated with a variety of risk factors, including: family history, obesity, and advancing age (increasing incidence in children as well).
• Ethnic background is increasingly a factor.
• Characterized by both impaired insulin secretion and insulin resistance.
• Patients usually produce some insulin.
• Develops gradually, often without obvious symptoms for years. Many are diagnosed during routine tests or unrelated medical care.
• Often diagnosed after significant beta cell loss (~50% to 80% lost). People usually have had the condition for six and a half years before diagnosis.

Genetic Links

• Type 1 DM genetic predisposition linked to human leukocyte antigens (HLAs).
• Specific HLA types (DR3 and DR4) increase type 1 diabetes risk.
• Idiopathic diabetes (a type 1 sub-type) is strongly inherited without autoimmunity.
• Latent autoimmune diabetes in adults (LADA) is a slower, autoimmune form of type 1 diabetes

Type 2 Pathophysiology

• Several metabolic factors contribute to type 2.
  • Reduced insulin sensitivity (resistance): Insulin receptors are ineffective, insufficient, or both, causing high blood sugar.
  • Decrease in insulin production by the pancreatic beta cells (compensatory): The cells overproduce insulin initially to compensate for resistance but eventually fatigue or lose beta cell mass.
  • Unregulated glucose production by the liver
  • Adipokines (hormones released by fat tissue) may play a role in insulin resistance and chronic inflammation.
    • Adiponectin and leptin are two adipokines of importance.
  • The role of the brain, kidneys, and gut are currently under study regarding how they contribute.
• Individuals with metabolic syndrome (high blood sugar, abdominal obesity, high blood pressure, high triglycerides, and low HDL levels) are at higher risk.