Abstract | AIM: METHODS: Twenty-seven insulin-treated men with type 2 diabetes [body mass index 30.8 +/- 2.6 kg/m(2) (mean +/- s.d.), haemoglobin A(1c) 7.6 +/- 1.1%] were enrolled in this randomized, double-blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within-subject and between-subject variabilities), BG, C-peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post-dose. RESULTS: The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC-GIR(total)) with increasing dose [low dose: 647 +/- 580, 882 +/- 634, 571 +/- 647 mg/kg ( insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 +/- 816, 1720 +/- 1109, 1393 +/- 1203 mg/kg and high dose: 2171 +/- 1344, 3119 +/- 1549, 2952 +/- 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within-subject variability was lower for the albumin-bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between-subject variability did not differ between treatments, nor did the effects on BG, C-peptide, FFA, EGP or PGU. CONCLUSIONS:
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Authors | O Klein, J Lynge, L Endahl, B Damholt, L Nosek, T Heise |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 9
Issue 3
Pg. 290-9
(May 2007)
ISSN: 1462-8902 [Print] England |
PMID | 17391154
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Blood Glucose
- C-Peptide
- Fatty Acids, Nonesterified
- Hypoglycemic Agents
- Insulin
- Insulin, Long-Acting
- Lys(B29)-N(epsilon)-lithocholoyl-gamma-Glu des(b30) insulin
- Insulin Glargine
- Insulin Detemir
- Glucose
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Topics |
- Blood Glucose
(analysis)
- C-Peptide
(blood)
- Diabetes Mellitus, Type 2
(drug therapy)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Administration Schedule
- Fatty Acids, Nonesterified
(blood)
- Glucose
(metabolism, pharmacokinetics)
- Glucose Clamp Technique
(methods)
- Humans
- Hypoglycemic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Insulin
(administration & dosage, adverse effects, agonists, analogs & derivatives, pharmacokinetics)
- Insulin Detemir
- Insulin Glargine
- Insulin, Long-Acting
- Male
- Middle Aged
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