Type I & II Diabetes Mellitus

Type I Diabetes Mellitus

• Accounts for ~10% of diabetes cases
• Onset is usually before age 25, but can occur at any age
• Risk factors include genetic predisposition like HLA types, family history, and autoimmune triggers caused by viruses or environmental factors
• Autoimmune destruction of pancreatic β-cells leads to absolute insulin deficiency
  • Type 1A is immune-mediated
  • Type 1B is idiopathic
• The onset is acute, with symptoms including polyuria, polydipsia, weight loss, and fatigue
• Often presents with diabetic ketoacidosis (DKA)
• Long-term complications include microvascular issues like retinopathy, nephropathy, and neuropathy, as well as macrovascular complications like cardiovascular disease (CVD)
• There is a high risk of DKA

Type II Diabetes Mellitus

• Accounts for ~90% of diabetes cases
• Prevalence is increasing due to obesity and sedentary lifestyles
• Risk factors include age over 40, obesity, sedentary lifestyle, family history, ethnicity, and metabolic syndrome
• Insulin resistance in peripheral tissues and impaired β-cell function leads to relative insulin deficiency
• Onset is often insidious, with symptoms including fatigue, recurrent infections, and blurred vision
• May be asymptomatic initially. DKA is less common, but HHNKS may occur
• Complications are the same as in Type I diabetes
• Chronic hyperglycemia contributes to oxidative stress, AGE formation, and polyol pathway activation
• Macrovascular events are a high risk

Gestational Diabetes Mellitus (GDM)

• Occurs in ~3–20% of pregnancies, varying by population
• Risk factors include obesity, advanced maternal age, previous GDM, family history, and ethnic background
• Pregnancy hormones like hPL, estrogen, and cortisol cause insulin resistance and β-cell dysfunction
• Usually resolves postpartum
• Symptoms are usually asymptomatic, but may include increased thirst or urination
• Diagnosed via routine prenatal screening (OGTT)
• Risks to the fetus include macrosomia and neonatal hypoglycemia
• Maternal complications include preeclampsia and future T2DM
• 30–50% of women develop T2DM later in life

Relationship Between Metabolic Syndrome and Type II Diabetes Mellitus

• Metabolic Syndrome is a cluster of conditions that increase the risk of developing T2DM and cardiovascular disease
• Diagnosis requires at least 3 out of 5 criteria:
  • Elevated waist circumference that indicates central obesity
  • Elevated triglycerides
  • Reduced HDL cholesterol
  • Elevated blood pressure
  • Elevated fasting plasma glucose
• Insulin resistance is central to both conditions
• In metabolic syndrome, insulin-sensitive tissues, like the liver, muscle, and fat, have reduced responsiveness to insulin
• Obesity, particularly visceral fat, contributes via:
  • Increased free fatty acids and lipotoxicity, which leads to β-cell dysfunction
  • Proinflammatory cytokines like TNF-α and IL-6, which leads to insulin resistance
  • Dysregulated adipokines, with decreased adiponectin and increased leptin, leading to metabolic disturbances
• Hyperglycemia and insulin resistance progress to T2DM, when β-cells can no longer compensate
• Metabolic syndrome predicts T2DM and cardiovascular disease
• Effective prevention of T2DM in those with metabolic syndrome includes lifestyle changes like diet and exercise, and sometimes pharmacological intervention, such as with metformin or antihypertensives
• Management must address all components to reduce long-term risks