Types of Diabetes and Insulin Therapy

Types of Diabetes

• Two main types: Type 1 and Type 2
• Type 1: Autoimmune destruction of pancreatic beta cells, leading to no insulin production. Typically develops before 30, with a prevalence of about 5%. Symptoms include weight loss, frequent urination (polyuria), increased thirst (polydipsia), and increased hunger (polyphagia). Can present with diabetic ketoacidosis (DKA), including dehydration, abdominal pain, vomiting, and decreased consciousness. Management is lifelong insulin therapy.
• Type 2: Genetic predisposition combined with environmental factors (e.g., poor diet, lack of exercise, stress). Reduced tissue sensitivity to insulin causes high blood sugar (hyperglycemia). The pancreas initially produces more insulin, but over time, beta cells become impaired and die, failing to keep up with the body's needs. Management includes lifestyle changes such as healthy diet, regular exercise, stress management to prevent further insulin resistance.

Insulin Therapy

• Insulin is a protein, requiring injection or IV administration.
• Various types based on duration of action:
  • Rapid-acting (e.g., lispro, aspart): Used immediately before meals or with insulin pumps.
  • Short-acting (e.g., Regular): Used before meals.
  • Intermediate-acting (e.g., NPH): Used to control blood sugar between meals.
  • Long-acting (e.g., glargine, detemir): Provides basal insulin levels.
  • Premixed insulins (e.g., 70/30): Combinations of intermediate and short-acting insulins.
• Insulin pump: Delivers basal and bolus insulin continuously, mimicking natural insulin release. Advantages include more accurate glucose control, reduced injections, and improved HbA1c levels. Disadvantages associated with the pump are weight gain, the risk of DKA if catheter dislodges, and the cost.
• Insulin inhaler: Delivers powdered insulin via inhalation, with faster absorption than injected insulin. Contraindicated in patients with asthma or COPD due to risk of acute bronchospasm; thorough medical history, exam and spirometry are crucial before starting inhaled insulin.
• Insulin administration sites: Abdomen, outer arms, outer thighs, and buttocks, with consistent rotation crucial.
• Insulin adjustments should be cautious in Type 1 diabetes, given the absence of endogenous insulin production.

Complications of Insulin Therapy

• Hypoglycemia: Most significant risk, requires careful monitoring, especially when combining insulin with other medications.
• Hypokalemia: Possible complication.
• Lipohypertrophy: Abnormal fat accumulation at injection sites due to repeated injections.

Other Diabetic Medications (Type 2)

• Agents to manage Type 2 diabetes aim to increase insulin action, stimulate insulin release, or reduce glucose production.
  • Sulfonylureas and Meglitinides: Stimulate insulin secretion from the pancreas.
  • Biguanides (Metformin): Inhibit glucose production by the liver, increase insulin sensitivity in target tissues, and do not lead to weight gain.
    • Risks: Lactic acidosis, gastrointestinal issues (diarrhea), and decreased vitamin B12/folic acid.
    • Monitoring: Periodic kidney function tests (eGFR).
  • Thiazolidinediones: Increase insulin sensitivity in muscle, fat, and liver; fat redistribution may assist in reducing insulin resistance.
  • Alpha-glucosidase Inhibitors: Slow carbohydrate digestion & absorption in the gut. Side effects include flatulence, diarrhea.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors: Increase glucose excretion in urine, potentially lower blood pressure, and reduce cardiovascular and kidney risk. Potential risks: lower limb amputation, DKA and urinary tract infections. (Note: the warnings re. limb amputation are no longer a black box warning).
  • Non-insulin injectables:
    • GLP-1 agonists: Mimic incretin hormones, stimulating insulin release, inhibiting glucagon release, and slowing gastric emptying. Potential risks including thyroid cancer.

Metformin (Biguanide)

• Initial drug of choice for type 2 diabetes, unless contraindicated or poorly tolerated.
• Works by lowering glucose production in the liver, reducing gut absorption, and enhancing insulin sensitivity without inducing hypoglycemia.
• Benefits include no weight gain, effective in lowering blood glucose, helps reduce cardiovascular risk, and can improve gut microbiome composition.
• Risks: Lactic acidosis, gastrointestinal side effects (e.g., diarrhea), and vitamin deficiencies (e.g., B12).
• Important to avoid alcohol, and hold metformin for 48 hours before IV contrast procedures.

Thiazolidinediones (Glitazones)

• Increase insulin sensitivity in muscle, fat, and to a lesser extent, the liver.
• May redistribute fat from the visceral to subcutaneous compartment.
• Risks: Risk or exacerbation of heart failure, and liver injury

Meglitinides (e.g. Repaglinide)

• Stimulate insulin release. Used for erratic meal schedules.
• Side effects include digestive issues (bloating, cramping, diarrhea).

Alpha-glucosidase Inhibitors (e.g., Acarbose)

• Slow carbohydrate digestion and absorption in the gut, primarily affecting postprandial blood glucose.
• Side effects include gastrointestinal issues (flatulence, diarrhea); most commonly mild and tolerable.
• Often used in combination with other medications.

Sodium-glucose co-transporter 2 (SGLT2) Inhibitors ("Gliflozins")

• Inhibits kidney re-absorption of glucose.
• Protection of heart and kidneys, noted in type 2 diabetes.
• Increased risk of lower limb amputation and DKA, although the Black Box Warning on amputation is no longer a black box warning.

Non-Insulin Injectable Hypoglycemic Agents

• GLP-1 agonists: Mimic incretin hormones, stimulating insulin release, inhibiting glucagon release, and slowing gastric emptying. Potential risks for thyroid cancer.
• Amylin analogs: Slow gastric emptying, suppress glucagon secretion, and promote satiety,

Pregnancy & Diabetes

• Pregestational Diabetes: Managing blood glucose levels before conception reduces risks for congenital anomalies or miscarriages in the fetus. Consider medication safety during pregnancy.
• Gestational Diabetes: Increased risk of complications for the fetus. Close blood glucose control is crucial to reduce perinatal outcomes (e.g., large for gestational age, congenital heart defects). Medications, such as insulin and metformin, may be necessary.

Lactation & Diabetes

• Successful breastfeeding is achievable with diabetes.
• Euglycemia crucial for lactation and normal insulin levels.
• Insulin NPH and regular human insulin are typically considered safe with breastfeeding; cautious approach needed for newer insulins.