Understanding Diabetes Mellitus: Types, Diagnosis, and Pathogenesis

Posted on Feb 22, 2025 in Medicine

Understanding Diabetes Mellitus

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Chronic hyperglycemia is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

Types of Diabetes Mellitus

  • Type 1 Diabetes Mellitus
  • Type 2 Diabetes Mellitus
  • Other specific types of Diabetes
  • Gestational Diabetes
  • Glucose intolerance and impaired fasting glycemia

Type 1 Diabetes Mellitus

Type 1 diabetes is characterized by the destruction of beta cells, leading to absolute insulin deficiency and often ketoacidosis.

Autoimmune Diabetes

85-95% of cases show antibody positive markers such as anti-islet cell antibodies (ICAs), anti-GAD antibodies (glutamic acid decarboxylase), and anti-IA2 and IA2 tyrosine phosphatase antibodies.

Idiopathic Diabetes

This type shows no association with markers of autoimmunity. It is often diagnosed when 90% of beta cells have been destroyed or damaged. 80% of cases occur in individuals under 30 years of age and is characterized by a tendency to ketosis. It accounts for less than 10% of diabetes cases.

Other Types of Diabetes

  • Genetic defects
  • Endocrinopathies
  • Pancreatic disease
  • Drugs
  • Infectious agents

Gestational Diabetes

Gestational diabetes is impaired glucose regulation that appears during pregnancy. It may disappear after pregnancy or persist as glucose intolerance or clinical diabetes.

Impaired Glucose Tolerance

Impaired glucose tolerance is an abnormal response to an oral glucose load. It is associated with an increased prevalence of cardiovascular disease and a risk of developing clinical diabetes (5-10% per year).

Impaired Fasting Glycemia

Impaired fasting glycemia is characterized by fasting blood glucose levels between 110 and 125 mg/dL. Identification of this condition suggests an oral glucose tolerance test for final classification.

Diagnosis

Diagnosis of diabetes mellitus can be made based on the following criteria:

  • Random blood glucose > 200 mg/dL, plus classic symptoms (polyuria, polydipsia, weight loss)
  • Two or more fasting blood glucose levels > 126 mg/dL
  • 75g OGTT > 200 mg/dL

Impaired Glucose Tolerance

  • Fasting blood glucose levels < 126 mg/dL
  • 75g OGTT at 120 minutes: 140 and 199 mg/dL

Impaired Fasting Blood Glucose Levels

  • 110 and 125 mg/dL

Pathogenesis of Type 1 Diabetes Mellitus

Impaired response of the fast phase of insulin secretion predicts the onset of irreversible disease. Evolution leads to insulinopenia, with C-peptide levels < 1 ng/mL.

Diabetes Mellitus Type 2

Type 2 diabetes is characterized by insulin resistance and relative (not absolute) insulin deficiency. It is most common in obese individuals, with or without abdominal obesity, and has a strong genetic predisposition. Insulin levels may be normal or elevated, and there is no tendency to ketoacidosis. Patients typically respond to diet and oral hypoglycemic agents.

Pathogenesis of Type 2 Diabetes Mellitus

Progressive worsening of metabolic control occurs over time, with increasing insulin resistance and declining insulin secretion, despite hyperinsulinemia.

Metabolic Changes in Acute Insulin Deficiency

  1. Reduced glucose uptake by muscle and adipose tissue
  2. Reduction of glycogen synthesis in the liver and muscle
  3. Reduction of anaerobic and aerobic glycolysis in insulin-dependent tissues
  4. Increased hepatic production of glucose results in hyperglycemia, a key sign of this condition.
  5. Increased oxidative stress

Lipid Metabolism

  1. Reduction of triglyceride synthesis.
  2. Increased catabolism of triglycerides in adipose tissue and transport of fatty acids into the liver.
  3. Activation of hepatic ketogenesis: interaction of insulin deficiency and increased activity of glucagon. Glucagon plays a pivotal role in the synthesis and activation of acyl carnitine transferase, promotes the synthesis of carnitine in the liver and, in conjunction with insulin deficiency, reduces malonyl CoA which is the main system restrainer.
  4. Decreased lipoprotein lipase activity in the peripheral system, either by default of their synthesis, translocation, and activation, leading to reduced catabolism of triglyceride-rich lipoproteins.