Double-Blind Crossover Trial of Isophane (NPH)- and Lente-Based Insulin Regimens

Abstract

Isophane (NPH) and lente insulin preparations have been the basis of insulin-injection regimens for many decades but were never formally compared. After a 2-mo run-in period, 82 patients were randomized to NPH (Protaphane) or lente (Monotard) insulin preparations given together with Actrapid as a twice-daily injection regimen in a double-blind study. Patients were seen monthly and crossed over after 5 mo of treatment. Control as assessed by glycosylated hemoglobin (NPH 9.2 +/- 0.1%, lente 9.3 +/- 0.1%, mean +/- SE) and fructosamine (1.55 +/- 0.02 and 1.57 +/- 0.02 mM) concentrations was identical for the two regimens as were home-collected laboratory-measured fasting blood glucose (BG) (NPH 8.8 +/- 0.5 mM, lente 9.0 +/- 0.5 mM) and mean BG (8.2 +/- 0.3 and 7.6 +/- 0.3 mM) concentrations. For both regimens, the major control problem was the BG concentration before and after breakfast. Total insulin dosage was similar (NPH 56.3 +/- 0.6 U/day, lente 57.2 +/- 0.6 U/day) with no tendency for a difference in the evening intermediate-acting dose (NPH 17.0 +/- 0.3 U/day, lente 17.0 +/- 0.3 U/day) to counter fasting hyperglycemia. Serum lipid concentrations and body weight confirmed the equivalence of control. Hypoglycemic events were recorded in personal diaries and graded by predetermined criteria. Self-treated, relative-assisted, and hospital/doctor-treated hypoglycemic events did not differ in frequency. We conclude that lente- and NPH-based twice-daily human insulin regimens give indistinguishable metabolic control.

Clinical Pharmacology of Human Insulin

“…In a crossover, randomized double-blind trial of 82 IDDM patients, the use of human lente (Monotard HM, Novo/Nordisk) or NPH insulin, given twice daily in combination with regular human insulin, resulted in comparable metabolic control (71). With both regimens, the major problem was elevated blood glucose concentrations before breakfast (NPH insulin versus lente insulin: 8.8 ± 0.5 vs. 9.0 ± 0.5 mM, NS).…”

Split-Mixed Insulin Regimen With Human Ultralente Before Supper and NPH (Isophane) Before Breakfast in Children and Adolescents With IDDM

“…Diabetes Care 14:1100-106, 1991 H yperglycemia before and after breakfast occurs in most patients with insulin-dependent diabetes mellitus (IDDM) treated with twice-daily subcutaneous insulin regimens (1,2). Mean fasting blood glucose was significantly lower on ultralente (9.6 ± 1 .…”

Intensive insulin therapy in clinical practice

“…Levels of blood glucose control comparable with those reported in the DCCT will not be achievable for any population-based cohort of people with insulin-dependent diabetes in the long-term, unless other means of motivation or self-discipline are found. Nevertheless less intense studies achieve mean glycated haemoglobin levels of around 7.4 %Hb (HbA 1 c , DCCT standardized) [20,21], while the normal clinic median in our own service is around 7.9-8.0 %Hb, varying slightly year by year.…”

“…Re-education course Self-monitoring of blood glucose (4-7 times daily) Adjustment of insulin doses to meet targets Supplemental insulin injections Telephone contact (1-7 times a week) Group hospitalization and out-patient visits Family counselling Clinic visits every 1-2 weeks lin regimens (intensive, pump, pen-injector, different extended-acting insulin preparations), many of them using the same patients or pool of patients [20,21]. The blood glucose control achieved in those studies was measured by glycated haemoglobin concentration as HbA 1 , and when normalized to the DCCT HbA 1 c assay the average results translate as 7.4 % Hb, just a little higher than the 7.1 % Hb achieved in that more intensive study.…”