What is the role of insulin in diabetes management?

Insulin: The Cornerstone of Diabetes Management

Insulin is essential therapy for all individuals with type 1 diabetes and becomes necessary for most people with type 2 diabetes when oral medications and lifestyle modifications fail to achieve glycemic targets. 1, 2

Role in Type 1 Diabetes

Insulin is the primary and life-sustaining treatment for type 1 diabetes, where absent or near-absent β-cell function makes exogenous insulin replacement absolutely necessary 1, 3. Without insulin, patients with type 1 diabetes face severe metabolic decompensation including hyperglycemia, ketoacidosis, and tissue catabolism that can be life-threatening 1.

Intensive Insulin Regimens Are Standard

Most people with type 1 diabetes should be treated with multiple daily injections (MDI) of basal and prandial insulin (3-4 injections daily) or continuous subcutaneous insulin infusion (CSII) via pump therapy. 1

• The landmark DCCT demonstrated that intensive insulin therapy reduced A1C to approximately 7% and led to 50% reductions in microvascular complications over 6 years, with sustained benefits extending 20 years beyond the active treatment period 1.
• Total daily insulin requirements typically range from 0.4 to 1.0 units/kg/day, with approximately 50% administered as basal insulin and 50% as prandial insulin divided among meals 1, 4.
• For metabolically stable patients, 0.5 units/kg/day is the typical starting point 1, 4.

Modern Insulin Analogs Reduce Hypoglycemia

Insulin analogs should be used preferentially over human insulins in type 1 diabetes to minimize hypoglycemia risk while maintaining glycemic control. 1

• Rapid-acting analogs (lispro, aspart, glulisine) provide better postprandial glucose control than regular human insulin and should be dosed 0-15 minutes before meals 1, 3.
• Long-acting basal analogs (glargine, detemir, degludec) have flatter, more constant activity profiles with less nocturnal hypoglycemia compared to NPH insulin 1.
• The DCCT, conducted with human insulins, showed intensive therapy was associated with 62 episodes of severe hypoglycemia per 100 patient-years, but modern analogs have significantly reduced this risk 1.

Technology Integration Improves Outcomes

Early use of continuous glucose monitoring (CGM) is recommended for adults with type 1 diabetes to improve glycemic outcomes, quality of life, and minimize hypoglycemia. 1

• Automated insulin delivery systems should be considered for all adults with type 1 diabetes 1.
• Sensor-augmented pump therapy with threshold suspend features reduces nocturnal hypoglycemia without increasing A1C 1.

Role in Type 2 Diabetes

Insulin becomes necessary in type 2 diabetes when oral medications and other therapies fail to achieve glycemic targets, or when patients present with severe hyperglycemia 2, 5.

Clear Indications for Insulin Initiation

Insulin should be started in type 2 diabetes when A1C remains >7% despite optimal oral medications (typically metformin plus additional agents), or immediately in patients with severe hyperglycemia. 2, 5

Specific scenarios requiring immediate insulin initiation include:

• A1C ≥10-12% with symptomatic or catabolic features (weight loss, ketosis) 1, 2, 5
• Blood glucose ≥300-350 mg/dL 2, 5
• Acute illness, surgery, or pregnancy 3
• Glucose toxicity requiring rapid metabolic correction 3

Basal Insulin Is the Preferred Starting Point

The recommended initial insulin regimen for type 2 diabetes is once-daily basal insulin (glargine, detemir, degludec, or NPH) at 10 units daily or 0.1-0.2 units/kg/day, combined with metformin. 4, 2, 5

• Long-acting analogs are preferred over NPH insulin because they cause less nocturnal hypoglycemia and have more predictable pharmacokinetics 5.
• Metformin should be continued unless contraindicated, as it reduces insulin requirements, limits weight gain, and provides complementary glucose-lowering effects 1, 4.
• For patients with more severe hyperglycemia (A1C ≥9%), consider higher starting doses of 0.3-0.4 units/kg/day 4, 5.

Systematic Dose Titration Achieves Targets

Basal insulin should be titrated by 2-4 units every 3 days based on fasting glucose until reaching target of 80-130 mg/dL. 4, 2, 5

• Increase by 2 units every 3 days if fasting glucose is 140-179 mg/dL 4.
• Increase by 4 units every 3 days if fasting glucose is ≥180 mg/dL 4.
• If hypoglycemia occurs, reduce the dose by 10-20% immediately 4, 2.
• Daily fasting blood glucose monitoring is essential during titration 4, 2.

Recognizing When to Advance Beyond Basal Insulin

When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day, adding prandial insulin or a GLP-1 receptor agonist is more appropriate than continuing to escalate basal insulin alone. 1, 4, 5

This critical threshold prevents "overbasalization," characterized by:

• Basal insulin dose >0.5 units/kg/day 4
• Bedtime-to-morning glucose differential ≥50 mg/dL 4
• Hypoglycemia episodes 4
• High glucose variability 4

If after 3-6 months of basal insulin optimization, fasting glucose reaches target but A1C remains above goal, add prandial insulin or a GLP-1 receptor agonist. 4, 5

• Start with 4 units of rapid-acting insulin before the largest meal, or 10% of the current basal dose 4.
• GLP-1 receptor agonists are preferred if weight gain or hypoglycemia are concerns 5.
• Titrate prandial insulin by 1-2 units or 10-15% every 3 days based on postprandial glucose readings 4.

Mechanism of Action

Insulin's primary activity is regulation of glucose metabolism through multiple pathways 6:

• Stimulates peripheral glucose uptake, especially by skeletal muscle and fat 6
• Inhibits hepatic glucose production (the main action of basal insulin) 4, 6
• Inhibits lipolysis and proteolysis 6
• Enhances protein synthesis 6

Basal insulin suppresses hepatic glucose production overnight and between meals, preventing plasma glucose from rising threefold to around 12 mmol/L. 7

Prandial insulin promotes glucose storage in skeletal muscle and controls postprandial glucose excursions over approximately 4 hours. 7

Critical Pitfalls to Avoid

Never delay insulin initiation in patients not achieving glycemic goals with oral medications, as this prolongs exposure to hyperglycemia and increases complication risk. 4, 2, 5

Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to overbasalization with increased hypoglycemia risk and suboptimal control. 4, 5

Avoid using sliding-scale insulin alone as primary therapy, especially in type 1 diabetes—scheduled basal-bolus regimens are superior. 1, 5

Do not abruptly discontinue oral medications when starting insulin; continue metformin unless contraindicated, but discontinue sulfonylureas when advancing beyond basal-only insulin to prevent hypoglycemia. 4, 3

Essential Patient Education

All insulin users require comprehensive education on 1, 2:

• Recognition and treatment of hypoglycemia (treat at glucose ≤70 mg/dL with 15 grams of fast-acting carbohydrate) 4
• Proper insulin injection technique and site rotation to prevent lipohypertrophy 4, 3
• Self-monitoring of blood glucose 4, 2
• Matching prandial insulin doses to carbohydrate intake, premeal glucose, and anticipated activity 1
• "Sick day" management rules 4, 2
• Insulin storage and handling 4

Glucagon should be prescribed for all individuals taking insulin, and family members should know its location and how to administer it. 1

Special Populations

Hospitalized Patients

In critical care settings, continuous intravenous insulin infusion is the preferred method, with glucose targets of 140-180 mg/dL for most patients 1.

For non-critically ill hospitalized patients, scheduled subcutaneous basal-bolus insulin regimens are preferred over sliding-scale insulin alone 1.

Geriatric Patients

Conservative dosing is essential in older adults to avoid hypoglycemia, which may be difficult to recognize in this population 6.

Renal or Hepatic Impairment

Frequent glucose monitoring and dose adjustments may be necessary, as kidney and liver impairment can affect insulin clearance and increase hypoglycemia risk 6.