341 Sec 3: Diabetes

Diabetes mellitus

A heterogeneous metabolic disorder characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both

Conceptual definition of diabetes

A failure of glucose homeostasis resulting from impaired hormonal regulation, primarily involving insulin

Glucose homeostasis

The regulation of blood glucose levels within a narrow physiological range across different metabolic states

Chronic hyperglycemia

Persistently elevated blood glucose that defines diabetes and drives symptoms and complications

General epidemiology of diabetes

Diabetes prevalence is increasing globally, strongly associated with aging populations, and frequently underdiagnosed

Public health significance of diabetes

Rising prevalence leads to long-term strain on healthcare systems

Type 1 diabetes (T1D)

An autoimmune disease characterized by immune-mediated destruction of pancreatic beta cells resulting in absolute insulin deficiency

Autoimmune beta-cell destruction

Immune attack against pancreatic beta cells leading to loss of endogenous insulin production

Islet cell autoantibodies

Markers of immune-mediated beta-cell destruction commonly seen in type 1 diabetes

Absolute insulin deficiency

Complete or near-complete absence of endogenous insulin secretion

C-peptide

A marker of endogenous insulin production released in equimolar amounts with insulin

Low C-peptide

Indicates reduced or absent beta-cell insulin secretion

Type 2 diabetes (T2D)

A metabolic disorder characterized by insulin resistance combined with progressive beta-cell dysfunction

Insulin resistance

Reduced responsiveness of peripheral tissues to insulin’s actions

Relative insulin deficiency

Inadequate insulin secretion relative to the degree of insulin resistance

Progressive beta-cell failure

Gradual decline in beta-cell function over time that drives worsening hyperglycemia

Gestational diabetes

Glucose intolerance first recognized during pregnancy

Secondary diabetes

Diabetes resulting from drugs, genetic defects, or other medical conditions

Primary signs of diabetes

Symptoms arising from hyperglycemia such as polydipsia, polyuria, blurred vision, and infections

Polydipsia

Excessive thirst caused by osmotic effects of hyperglycemia

Polyuria

Frequent urination due to glucose-induced osmotic diuresis

Insulin

The primary hormone responsible for lowering blood glucose

Physiologic actions of insulin

Promotes glucose uptake, suppresses hepatic glucose production, enhances glycogen storage, and inhibits lipolysis

Glucagon

A counter-regulatory hormone that raises blood glucose by stimulating hepatic glucose release

Counter-regulatory hormones

Hormones such as glucagon, cortisol, catecholamines, and growth hormone that oppose insulin action

Incretins

Gut-derived hormones that enhance glucose-stimulated insulin secretion

GLP-1

An incretin hormone that increases insulin secretion, suppresses glucagon, and promotes satiety

Fed state metabolism

High insulin and low glucagon suppress endogenous glucose production while dietary glucose supplies energy

Fasting state metabolism

Low insulin and high glucagon maintain blood glucose via glycogenolysis and gluconeogenesis

Starvation state metabolism

Glycogen depletion leads to reliance on gluconeogenesis and fatty acid oxidation, with increased ketone use by the brain

Pathogenesis of type 1 diabetes

Autoimmune beta-cell destruction driven by genetic susceptibility and environmental triggers

Insulitis

Inflammatory infiltration of pancreatic islets seen in type 1 diabetes

Timing of T1D symptoms

Clinical symptoms appear only after significant beta-cell loss (>70%)

Pathogenesis of type 2 diabetes

Combination of insulin resistance and progressive beta-cell dysfunction

Compensatory hyperinsulinemia

Early increase in insulin secretion to overcome insulin resistance

Loss of first-phase insulin secretion

Early defect in beta-cell response seen in type 2 diabetes

Central role of beta cells in diabetes

Failure of beta-cell function is the key event in progression of both T1D and T2D

Primary goals of diabetes therapy

Control hyperglycemia, prevent symptoms, avoid acute complications, and reduce long-term risk

Disease progression in diabetes

Therapeutic needs evolve over time as beta-cell function declines

Interpretation of islet autoantibodies and low C-peptide

Indicates autoimmune beta-cell destruction consistent with type 1 diabetes

Expected pancreatic findings in T1D

Reduced beta-cell mass with immune infiltration of islets

Typical age of onset for T1D

Most commonly childhood or adolescence, though adult-onset autoimmune diabetes can occur

ABCDES3 framework

A conceptual approach to diabetes management emphasizing comprehensive care including glycemic control, blood pressure management, cholesterol control, diabetes education, lifestyle modification, screening and prevention of complications, and psychosocial support