Diabetes Mellitus
Diabetes mellitus, commonly referred to as diabetes, is a chronic metabolic disorder characterized by impaired regulation of blood glucose levels. This condition stems from genetic predispositions and environmental influences that disrupt insulin synthesis, its cellular action, or both.
Pathophysiology of Diabetes
Diabetes develops when the pancreas fails to produce sufficient insulin—a hormone critical for glucose regulation—or when the body becomes resistant to insulin’s effects. Blood glucose, a primary energy source for cells, requires insulin to facilitate its transport from the bloodstream into tissues. Insulin is produced by pancreatic beta cells, and its dysfunction leads to dysregulated glucose metabolism.
Primary Classifications of Diabetes Mellitus
1. Type 1 Diabetes
- An autoimmune disorder in which the immune system erroneously targets and destroys insulin-producing pancreatic beta cells.
- Management mandates lifelong insulin replacement via injections or pumps, coupled with consistent blood glucose monitoring.
- Without insulin, severe complications like diabetic ketoacidosis (a life-threatening accumulation of ketones in the blood) may arise. Although diet and exercise aid in stabilization, they cannot halt disease progression.
2. Type 2 Diabetes
- Defined by insulin resistance, where cells exhibit a diminished response to insulin, often paired with progressive beta-cell dysfunction.
- Early stages may involve compensatory hyperinsulinemia (excess insulin production). Interventions such as dietary modifications, physical activity, and medications to enhance insulin sensitivity are foundational to management.
- Over time, pancreatic insulin secretion may decline, necessitating advanced therapies, including insulin supplementation.
Related Metabolic Disorders
Diabetes Insipidus: A rare disorder unrelated to glucose metabolism, caused by inadequate antidiuretic hormone (ADH) secretion or renal resistance to ADH. Symptoms include excessive dilute urination and unrelenting thirst.
Gestational Diabetes: Occurs during pregnancy due to hormonal shifts that impair insulin function. Affecting 2–5% of pregnancies, it typically resolves postpartum but substantially elevates maternal susceptibility to Type 2 diabetes (20–35% lifetime risk).
Key Considerations
While “diabetes” often denotes diabetes mellitus, the pathological distinction from diabetes insipidus is critical. Diabetes mellitus remains a global health burden, with Type 2 comprising over 90% of cases. Proactive management strategies are vital to mitigating complications such as cardiovascular disease, neuropathy, and renal failure.
Diabetes in Childhood and Adolescence
Diabetes diagnosed during childhood or adolescence is most commonly Type 1. In allopathic medicine, insulin therapy remains the most effective and essential treatment, a cornerstone supported by extensive medical research. Alternative treatments cannot fully manage Type 1 diabetes, making insulin injections the most reliable and evidence-based option. Administration should always occur under the guidance of a diabetes specialist. Over time, patients learn to understand insulin’s effects on their bodies and, with proper management, can lead healthy, active lives.
Insulin: The Hormone That Regulates Blood Sugar
Insulin, a hormone produced by the pancreas, is released into the bloodstream to regulate blood glucose levels. It enables the body to process blood sugar efficiently. A deficiency in insulin leads to diabetes mellitus, characterized by dangerously elevated blood glucose levels that, over time, damage multiple organs.
Structurally, insulin is initially synthesized as a single polypeptide chain of 110 amino acids. Through enzymatic processing, it splits into two chains: Chain A (21 amino acids) and Chain B (30 amino acids), linked by two disulfide bonds. Chain A contains an additional internal disulfide bond.
Modern insulin is produced using genetically modified *Escherichia coli* bacteria, which pose no harm to humans. Its chemical formula is **C₂₅₇H₃₈₃N₆₅O₇₇S₆**, with a molecular weight of 5808. Each 100 units of insulin typically contains 15 micrograms of zinc.
Insulin was first administered to humans in Canada in 1922. Before 1978, it was derived from pigs (differing from human insulin by one amino acid) or cows (differing by three amino acids). In 1978, scientists developed genetically engineered insulin by inserting human genes into *E. coli*.
Types of Insulin
Four primary types of insulin are used clinically. Most patients combine two types, either manually or via pre-mixed formulations:
1. Rapid-Acting Insulin
- Begins working within 15 minutes of injection, ideal for pre-meal administration.
- Peaks in 30 minutes to 3 hours and remains effective for up to 5 hours.
- Must be paired with long-acting insulin for 24-hour coverage.
- Risk of hypoglycemia if taken without food.
2. Short-Acting Insulin (Regular/R)
- Administered 30–60 minutes before meals.
- Onset in 30–60 minutes, peaks in 2–5 hours, and lasts up to 8 hours.
- Combined with long-acting insulin for sustained control.
3. Intermediate-Acting Insulin (NPH/N)
- Slow onset (1.5–4 hours) with prolonged effects.
- Peaks at 4–12 hours and lasts up to 24 hours.
- Typically injected twice daily.
4. Long-Acting Insulin (e.g., Lantus)
- Begins working within 1 hour and provides steady coverage for 24 hours.
- Usually administered once daily.
Note: Insulin cannot be taken orally due to degradation in the digestive tract. In 2006, Pfizer introduced inhalable insulin, but it was discontinued within a year due to high costs and limited demand.
Insulin Absorption Dynamics
Insulin functions in its monomeric form, but the body stores it as an inactive hexamer (six-molecule complex). Synthetic insulins are engineered to resist hexamer formation, allowing faster action.
Post-meal blood glucose spikes necessitate rapid-acting insulin. Typically, half the daily dose is fast-acting (split across meals), and the other half is long-acting (divided into two 12-hour doses). Adjustments depend on lifestyle, activity, and diet.
Most insulins can be mixed (e.g., 70% Regular and 30% NPH), but glargine (Lantus) cannot be combined with others due to its acidic pH (4.0) compared to regular insulin’s neutral pH (7.0–7.8).
Insulin Dosage Guidelines
Most patients require **0.7–1 unit/kg/day**. For example, a 70 kg individual may need 50–70 units daily. Treatment begins with half the estimated dose, adjusted gradually based on glucose monitoring.
Insulin resistance may necessitate higher doses to maintain target glucose levels.
Insulin and Adjunctive Therapies
Post-1990, oral medications like rosiglitazone, lobeglitazone, and pioglitazone were introduced to enhance insulin sensitivity. However, these drugs correlate with an elevated risk of heart failure, particularly when combined with insulin.
Metformin is often paired with insulin to mitigate therapy-associated weight gain.