Harrison DM treatment
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"type 1 diabetes mellitus"[MeSH Terms] AND "treatment"[MeSH Terms]
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Treatment of Type 1 Diabetes Mellitus
Harrison's Principles of Internal Medicine, 22nd Edition (2025)
Goals of Treatment
The primary goal is to design an insulin regimen that mimics physiologic insulin secretion. Since individuals with T1DM lack endogenous insulin, two components are essential:
- Basal insulin — regulates glycogen breakdown, gluconeogenesis, lipolysis, and ketogenesis
- Prandial (bolus) insulin — matched to carbohydrate intake and insulin sensitivity
Intensive Glycemic Management
Intensive insulin therapy seeks to achieve normal or near-normal glycemia and requires:
- Continuous patient education
- Comprehensive glucose and nutrition monitoring
- Variable insulin regimens matched to carbohydrate intake and exercise
Insulin Delivery Methods
| Method | Description |
|---|---|
| MDI (Multiple Daily Injections) | Basal + bolus injections; standard approach |
| CSII (Continuous Subcutaneous Insulin Infusion / Insulin Pump) | Manual entry to adjust basal rate or bolus |
| Sensor-Augmented System | Pump + CGM; suspends insulin when glucose is low or predicted to fall |
| AID (Automated Insulin Delivery) | Pump + CGM + algorithm; automatically increases/decreases basal rate in real time; some deliver correction boluses |
AID systems are not fully closed-loop — patients must still input carbohydrate intake and expected activity. DIY approaches from the T1DM community exist but are not FDA-approved.
Insulin Preparations
Insulins are classified by onset and duration:
| Preparation | Onset (h) | Peak (h) | Duration (h) |
|---|---|---|---|
| Rapid-acting (Aspart, Glulisine, Lispro) | <0.25 | 0.5–1.5 | 3–5 |
| Inhaled human insulin | <0.25 | 1–2 | 3 |
| Short-acting (Regular) | 0.5–1.0 | 2–3 | 4–8 |
| Intermediate-acting (NPH) | 2–4 | 4–10 | 10–16 |
| Long-acting (Glargine) | 2–4 | Minimal | 20–24 |
| Ultralong-acting (Degludec) | 1–9 | Minimal | ~42 |
Key points:
- Rapid-acting analogues (aspart, lispro, glulisine) are preferred over regular insulin for prandial coverage — their shorter duration reduces post-meal hypoglycemia.
- Insulin glargine and degludec are preferred long-acting options (minimal peak, reduced nocturnal hypoglycemia vs. NPH).
- U-500 Regular insulin is used in severe insulin resistance.
- U-300 glargine has longer duration than standard U-100 glargine.
Typical Regimens
Basal-Bolus Regimen (MDI)
- Basal: Once-daily glargine or degludec (covers overnight and between-meal glucose)
- Bolus: Rapid-acting insulin (lispro, aspart, or glulisine) with each meal, dosed by carbohydrate counting and correction factor
Insulin Pump (CSII)
- Uses rapid-acting insulin exclusively
- Programmable basal rates + patient-directed boluses
- Advanced systems suspend delivery during predicted hypoglycemia
Continuous Glucose Monitoring (CGM)
- Strongly encouraged at diagnosis, including in newly diagnosed patients
- Enables real-time adjustments and hypoglycemia detection
Benefits of Intensive Therapy
- Reduction in acute metabolic complications (DKA)
- Reduction in chronic microvascular complications (retinopathy, nephropathy, neuropathy)
- Greater patient sense of control and well-being
- Flexibility in meal timing and exercise
- During pregnancy: reduces fetal malformations and morbidity
Intensive management is not appropriate for all individuals at all times — care must be individualized (some patients prefer MDI + CGM over continuous pump attachment).
Adjunctive / Emerging Therapies
Recent evidence supports GLP-1 receptor agonists as adjunctive therapy to insulin in T1DM:
- A 2024 meta-analysis (PMID 39344842) showed GLP-1RAs significantly improve HbA1c and CGM metrics when added to insulin in adults with T1DM.
- Fully automated insulin delivery systems (closed-loop AID): a 2025 systematic review (PMID 40432359) confirms superior glycemic outcomes vs. open-loop systems.
- Hybrid closed-loop systems: network meta-analysis (PMID 39298688) shows variable efficacy across commercial AID systems.
Cost Considerations
Harrison's 22E specifically flags insulin cost as a major challenge. Recent U.S. federal and state legislation has begun addressing this, but insulin affordability remains a critical issue in T1DM care.
Source: Harrison's Principles of Internal Medicine, 22nd Edition (2025), Chapter 416 — Diabetes Mellitus
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