Administration of neutral protamine Hagedorn insulin at bedtime versus with dinner in type 1 diabetes mellitus to avoid nocturnal hypoglycemia and improve control. A randomized, controlled trial.

Abstract

BACKGROUND:

Intensive insulin treatment of type 1 diabetes mellitus increases the risk for nocturnal hypoglycemia.

OBJECTIVE:

To demonstrate that splitting the evening insulin regimen reduces the risk for nocturnal hypoglycemia in intensive treatment of type 1 diabetes mellitus.

DESIGN:

Randomized, open, two-treatment crossover trial in two 4-month periods.

SETTING:

University research center in Italy.

PATIENTS:

22 C-peptide-negative persons with type 1 diabetes mellitus (mean age [+/-SD], 29 +/- 3 years).

INTERVENTIONS:

Each patient was randomly assigned to one of two insulin regimens for 4 months and then switched to the other regimen for another 4 months. The two treatment regimens were 1) mixed treatment--a mixture of human regular and neutral protamine Hagedorn (NPH) insulin administered before dinner and 2) split treatment--human regular insulin administered at dinner and NPH insulin administered at bedtime.

MEASUREMENTS:

Frequency of nocturnal hypoglycemia. Secondary end points were levels of fasting blood glucose and hemoglobin A1c and responses to experimental hypoglycemia.

RESULTS:

During the split-regimen treatment period, patients had fewer episodes of nocturnal hypoglycemia (mean [+/-SE], 0.10 +/- 0.02 episode/patient-day vs. 0.28 +/- 0.04 episode/patient-day; P = 0.002), a lower fasting blood glucose level (mean [+/-SE], 7.6 +/- 0.2 mmol/L vs. 8.3 +/- 0.5 mmol/L [137 +/- 4 mg/dL vs. 160 +/- 8 mg/dL]; P = 0.030), less variable fasting blood glucose levels (SD range, 2.0 +/- 0.4 vs. 3.5 +/- 0.6; P = 0.001), and lower hemoglobin A1c value (mean [+/-SE], 7.0% +/- 0.11% vs. 7.5% +/- 0.15%; P = 0.004) than during the mixed regimen. Responses to experimental hypoglycemia were better preserved with the split regimen than with the mixed regimen.

CONCLUSION:

When the goal of insulin therapy in type 1 diabetes mellitus is near-normoglycemia, splitting the evening insulin treatment regimen into short-acting insulin at dinner and NPH insulin at bedtime reduces the risks for nocturnal hypoglycemia and hypoglycemia unawareness and decreases the hemoglobin A1c value compared with mixing short-acting insulin and NPH insulin at dinner.

• Authors: Carmine G Fanelli, Simone Pampanelli, Francesca Porcellati, Paolo Rossetti, Paolo Brunetti, Geremia B Bolli
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 136 Issue 7 Pg. 504-14 (Apr 02 2002) ISSN: 1539-3704 [Electronic] United States
• PMID: 11926785 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Insulin, Isophane

Topics

• Adult
• Analysis of Variance
• Blood Glucose (metabolism)
• Circadian Rhythm
• Cognition Disorders (etiology)
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (blood, drug therapy)
• Drug Administration Schedule
• Female
• Humans
• Hypoglycemia (prevention & control, psychology)
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Insulin (administration & dosage, adverse effects, blood)
• Insulin, Isophane (administration & dosage, adverse effects)
• Male
• Prospective Studies
• Regression Analysis