Skip to main content
Erschienen in: Wiener klinische Wochenschrift 7-8/2014

01.04.2014 | original article

Comparison of glucose variability assessed by a continuous glucose-monitoring system in patients with type 2 diabetes mellitus switched from NPH insulin to insulin glargine: The COBIN2 study

verfasst von: Denisa Janickova Zdarska, Milan Kvapil, Zdenek Rusavy, Michal Krcma, Jan Broz, Bohumila Krivska, Pavla Kadlecova

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 7-8/2014

Einloggen, um Zugang zu erhalten

Summary

Backround

Glucose variability combined with glycosylated hemoglobin (HbA1c) assessments more reliably represents the level of glycemic control. The study was aimed to compare blood glucose variability with insulin glargine vs. neutral protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a continuous glucose-monitoring system (CGMS), in patients treated with basal insulin using stable dose of oral antidiabetic agents and HbA1c in the range of 4.5–8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2–9.4 % Diabetes Control and Complications Trial (DCCT) units].

Methods

This was a multicenter, prospective, open-label, single-arm study in patients (N = 116) treated for ≥ 2 months with NPH and metformin combined with sulfonylurea or glinide. Glucose variability was measured after a 4-week NPH treatment phase and after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L · h)]. Differences (glargine–NPH) in AUC within 24 h in the glucose ranges of ≤ 3.3, ≤ 3.9, 7.5–3.9 (margins excluding), ≥ 7.5, ≥ 10, and ≥ 15 mmol/L were evaluated. Circadian fluctuation of glucose was assessed by M-value (log-transformation of the deviation from an arbitrary standard).

Results

AUCs of glucose in the lowest ranges (≤ 3.3 and ≤ 3.9 mmol/L) did not change significantly after treatment with glargine. Those in the higher ranges (≥ 7.5, ≥ 10, and ≥ 15 mmol/L) were significantly lower (p < 0.001 for all ranges), whereas AUC of glucose in the normal range (3.9–7.5 mmol/L) was significantly higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation of glucose assessed by M-value showed a significant decrease after glargine treatment (p < 0.003). No significant differences in hypoglycemia confirmed by glucose value ≤ 3.3 mmol/L were found between treatment phases. This trial is registered at ClinicalTrials.gov, NCT00659477.

Conclusions

As monitored by CGMS, switching from NPH to glargine with active titration shifted glucose from abnormally high to normal levels with reduced fluctuation and without increased risk of hypoglycemia.
Literatur
1.
Zurück zum Zitat Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005;19(3):178–81.PubMedCrossRef Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications. 2005;19(3):178–81.PubMedCrossRef
2.
Zurück zum Zitat Danielson P, Truedsson L, Eriksson KF, Norgren L. Inflammatory markers and IL-6 polymorphism in peripheral disease with and without diabetes mellitus. Vasc Med. 2005;10(3):191–8.CrossRef Danielson P, Truedsson L, Eriksson KF, Norgren L. Inflammatory markers and IL-6 polymorphism in peripheral disease with and without diabetes mellitus. Vasc Med. 2005;10(3):191–8.CrossRef
3.
Zurück zum Zitat Cohen MP, Shea E, Chen S, Shearman CW. Glycated albumin increases oxidative stress, activates NF-kappa B and extracellular signal-regulated kinase (ERK), and stimulates ERK-dependent transforming growth factor-beta 1 production in macrophage RAW cells. J Lab Clin Med. 2003;141(4):242–9.PubMedCrossRef Cohen MP, Shea E, Chen S, Shearman CW. Glycated albumin increases oxidative stress, activates NF-kappa B and extracellular signal-regulated kinase (ERK), and stimulates ERK-dependent transforming growth factor-beta 1 production in macrophage RAW cells. J Lab Clin Med. 2003;141(4):242–9.PubMedCrossRef
4.
Zurück zum Zitat Taguchi T, Brownlee M.  The biochemical mechanisms of diabetic tissue damage. In: Pickup J, Williams G, editors. Textbook of diabetes. 3rd ed. Oxford: Blackwell Science; 2003. Taguchi T, Brownlee M.  The biochemical mechanisms of diabetic tissue damage. In: Pickup J, Williams G, editors. Textbook of diabetes. 3rd ed. Oxford: Blackwell Science; 2003.
5.
Zurück zum Zitat Qualiaro L, Piconi L, Assalone R, Martinelli L, Motz E, Ceriello A. Intermitent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role o protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52:2795–804.CrossRef Qualiaro L, Piconi L, Assalone R, Martinelli L, Motz E, Ceriello A. Intermitent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role o protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52:2795–804.CrossRef
6.
Zurück zum Zitat Hanefeld M, Fischer S, Julius U, et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia. 1996;39(12):1577–83.PubMedCrossRef Hanefeld M, Fischer S, Julius U, et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia. 1996;39(12):1577–83.PubMedCrossRef
7.
Zurück zum Zitat Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49(12):2142–8.PubMedCrossRef Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49(12):2142–8.PubMedCrossRef
8.
Zurück zum Zitat Owens D, Coates P, Luzio S, Tinbergen JP, Kurzhals R. Pharmacokinetics of 125I-labeled  insulin glarginee (HOE 901) in healthy men. Diabetes Care. 2000;23(6):813–9.PubMedCrossRef Owens D, Coates P, Luzio S, Tinbergen JP, Kurzhals R. Pharmacokinetics of 125I-labeled  insulin glarginee (HOE 901) in healthy men. Diabetes Care. 2000;23(6):813–9.PubMedCrossRef
9.
Zurück zum Zitat Yki-Järvinen H, Dressler A, Zieman M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care. 2000;23(8):1130–6.PubMedCrossRef Yki-Järvinen H, Dressler A, Zieman M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care. 2000;23(8):1130–6.PubMedCrossRef
10.
Zurück zum Zitat Kovatchev B, Anderson S, Heinemann L, Willim C. Comparison of the numerical and clinical accuracy of four continuous glucose monitors. Diabetes Care. 2008;31:1160–4.PubMedCrossRef Kovatchev B, Anderson S, Heinemann L, Willim C. Comparison of the numerical and clinical accuracy of four continuous glucose monitors. Diabetes Care. 2008;31:1160–4.PubMedCrossRef
11.
Zurück zum Zitat Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–53. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–53.
12.
Zurück zum Zitat Stettler C, Allemann S, Jüni P, Cull CA, Holman RR, et al. Glycemic control and macrovascular disease in type 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J. 2006;152:27–38.PubMedCrossRef Stettler C, Allemann S, Jüni P, Cull CA, Holman RR, et al. Glycemic control and macrovascular disease in type 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J. 2006;152:27–38.PubMedCrossRef
13.
Zurück zum Zitat Monnier L, Colette C, Owens DR. Integrating glycaemic variability in the glycaemic disorder of type 2 diabetes: a move towards a unified glucose tetrat concept. Diabetes Metab Res Rev. 2009;25(5):393–402.PubMedCrossRef Monnier L, Colette C, Owens DR. Integrating glycaemic variability in the glycaemic disorder of type 2 diabetes: a move towards a unified glucose tetrat concept. Diabetes Metab Res Rev. 2009;25(5):393–402.PubMedCrossRef
14.
Zurück zum Zitat Buscemi S, Re A, Batsis JA, et al. Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in type 2 diabetes. Diabet Med. 2010;27(8):872–8.PubMedCrossRef Buscemi S, Re A, Batsis JA, et al. Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in type 2 diabetes. Diabet Med. 2010;27(8):872–8.PubMedCrossRef
15.
Zurück zum Zitat Ceriello A. Hyperglycaemia and the vessel wall: the pathophysiological aspects on the atherosclerotic burden in patients with diabetes. Eur J Cardiovasc Prev Rehabil. 2010;17(Suppl. 1):S15–9.PubMedCrossRef Ceriello A. Hyperglycaemia and the vessel wall: the pathophysiological aspects on the atherosclerotic burden in patients with diabetes. Eur J Cardiovasc Prev Rehabil. 2010;17(Suppl. 1):S15–9.PubMedCrossRef
16.
Zurück zum Zitat Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev. 2008;24:353–63.PubMedCrossRef Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev. 2008;24:353–63.PubMedCrossRef
17.
Zurück zum Zitat Hahn, GJ, Meeker WQ. Statistical intervals: a guide for practitioners. New York: John Wiley & Sons; 1991.CrossRef Hahn, GJ, Meeker WQ. Statistical intervals: a guide for practitioners. New York: John Wiley & Sons; 1991.CrossRef
Metadaten
Titel
Comparison of glucose variability assessed by a continuous glucose-monitoring system in patients with type 2 diabetes mellitus switched from NPH insulin to insulin glargine: The COBIN2 study
verfasst von
Denisa Janickova Zdarska
Milan Kvapil
Zdenek Rusavy
Michal Krcma
Jan Broz
Bohumila Krivska
Pavla Kadlecova
Publikationsdatum
01.04.2014
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 7-8/2014
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-014-0508-6

Weitere Artikel der Ausgabe 7-8/2014

Wiener klinische Wochenschrift 7-8/2014 Zur Ausgabe

mitteilungen der österreichischen gesellschaft für innere medizin

Österreichische Gesellschaft für Hypertonie (ÖGH)

gesellschaft der ärzte in wien

gesellschaft der ärzte in wien