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Insulin degludec is associated with less frequent and milder hypoglycemia in insulin-deficient patients with type 1 diabetes compared with insulin glargine or detemir

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Abstract

Introduction

The aim of this study was to determine the efficacy of insulin degludec (IDeg) relative to insulin glargine (IGlar) or insulin detemir (IDet) in glycemic control, as evaluated by continuous glucose monitoring (CGM) in insulin-deficient patients with type 1 diabetes.

Methods

We studied 28 outpatients treated with IGlar or IDet (IGlar/IDet). Basal insulin was switched to IDeg when glycemic control was considered unstable, as judged by the dawn phenomenon or nocturnal hypoglycemia. Whole-day CGM data were also divided into daytime and nighttime data.

Results

The dawn phenomenon or nocturnal hypoglycemia under IGlar/IDet treatment was observed in all patients. Among 26 patients who completed the study, there were no significant differences in parameters representing glycemic variability, hyperglycemia, mean glycemic control, and HbA1c or insulin therapy-related quality of life at the night score. Measures of hypoglycemia [whole-day %Low and area under the curve (AUC) below 70] were significantly lower under IDeg treatment than under IGlar/IDet treatment (%Low, 9.6 ± 11.5 vs. 14.7 ± 14.9%, p = 0.045; AUC below 70, 85.5 ± 126.0 vs. 145.0 ± 178.6 mg/dl h, p = 0.030). Dividing patients into two groups according to percentage or degree of hypoglycemia under IGlar/IDet treatment, the whole-day, daytime and nighttime %Low in the high-percentage groups and AUC below 70 in the high-degree groups were significantly ameliorated, respectively (p < 0.05).

Conclusion

Patients with unstable glycemic control under IGlar/IDet treatment did not improve glycemic control upon switching to IDeg, but the frequency and the degree of hypoglycemia was reduced in insulin-deficient outpatients with type 1 diabetes, especially in those suffering from severe hypoglycemia.

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References

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012;35(Suppl 1):S64–71.

    Article  Google Scholar 

  2. Sartore G, Chilelli NC, Burlina S, Di Stefano P, Piarulli F, Fedele D, Mosca A, Lapolla A. The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM). Acta Diabetol. 2012;49(Suppl 1):S153–60.

    Article  PubMed  Google Scholar 

  3. Kuenen JC, Borg R, Kuik DJ, Zheng H, Schoenfeld D, Diamant M, Nathan DM, Heine RJ, ADAG Study Group. Does glucose variability influence the relationship between mean plasma glucose and HbA1c levels in type 1 and type 2 diabetic patients? Diabetes Care. 2011;34:1843–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50:1140–7.

    Article  Google Scholar 

  5. Šoupal J, Škrha J Jr, Fajmon M, Horová E, Mráz M, Škrha J, Prázný M. Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control. Diabetes Technol Ther. 2014;16:198–203.

    Article  PubMed  Google Scholar 

  6. Kondos GT, Hoff JA, Sevrukov A, Daviglus ML, Garside DB, Devries SS, Chomka EV, Liu K. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation. 2003;107:2571–6.

    Article  PubMed  Google Scholar 

  7. Snell-Bergeon JK, Roman R, Rodbard D, Garg S, Maahs DM, Schauer IE, Bergman BC, Kinney GL, Rewers M. Glycaemic variability is associated with coronary artery calcium in men with type 1 diabetes: the coronary artery calcification in type 1 diabetes study. Diabet Med. 2010;27:1436–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301:1565–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lin CH, Sheu WH. Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med. 2013;273:102–10.

    Article  PubMed  Google Scholar 

  10. Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care. 2015;38:316–22.

    Article  PubMed  Google Scholar 

  11. Lung TW, Petrie D, Herman WH, Palmer AJ, Svensson AM, Eliasson B, Clarke PM. Severe hypoglycemia and mortality after cardiovascular events for type 1 diabetic patients in Sweden. Diabetes Care. 2014;37:2974–81.

    Article  CAS  PubMed  Google Scholar 

  12. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35:1897–901.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cox DJ, Ford D, Gonder-Frederick L, Clarke W, Mazze R, Weinger K, Ritterband L. Driving mishaps among individuals with type 1 diabetes: a prospective study. Diabetes Care. 2009;32:2177–80.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yagasaki H, Kobayashi K, Saitou T, Nagamine K, Mitsui Y, Mochizuki M, Kobayashi K, Cho H, Ohyama K, Amemiya S, Nakazawa S. Nocturnal blood glucose and IGFBP-1 changes in type 1 diabetes: differences in the dawn phenomenon between insulin regimens. Exp Clin Endocrinol Diabetes. 2010;118:195–9.

    Article  CAS  PubMed  Google Scholar 

  15. Frier BM. How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev. 2008;24:87–92.

    Article  PubMed  Google Scholar 

  16. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012;29:2104–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Haahr H, Heise T. A review of the pharmacological properties of insulin degludec and their clinical relevance. Clin Pharmacokinet. 2014;53:787–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14:859–64.

    Article  CAS  PubMed  Google Scholar 

  19. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Francisco AM, Pei H, Bode B, BEGIN Basal-Bolus Type 1 Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to target non-inferiority trial. Lancet. 2012;379:1489–97.

    Article  CAS  PubMed  Google Scholar 

  20. Hirsch IB, Bode B, Courreges JP, Dykiel P, Franek E, Hermansen K, King A, Mersebach H, Davies M. Insulin degludec/insulin aspart administered once daily at any meal, with insulin aspart at other meals versus a standard basal-bolus regimen in patients with type 1 diabetes: a 26-week, phase 3, randomized, open-label, treat-to-target trial. Diabetes Care. 2012;35:2174–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Iwamoto Y, Clauson P, Nishida T, Kaku K. Insulin degludec in Japanese patients with type 1 diabetes mellitus: a randomized controlled trial. J Diabetes Investig. 2013;4:62–8.

    Article  CAS  PubMed  Google Scholar 

  22. Nakamura T, Sakaguchi K, So A, Nakajima S, Takabe M, Komada H, Okuno Y, Hirota Y, Nakamura T, Iida K, Kajikawa M, Nagata M, Ogawa W, Seino S. Effects of insulin degludec and insulin glargine on day-to-day fasting plasma glucose variability in individuals with type 1 diabetes: a multicentre, randomised, crossover study. Diabetologia. 2015;58:2013–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Poolsup N, Suksomboon N, Kyaw AM. Systematic review and meta-analysis of the effectiveness of continuous glucose monitoring (CGM) on glucose control in diabetes. Diabetol Metab Syndr. 2013;5:39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, Hanafusa T, Haneda M, Ueki K, Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig. 2010;1:212–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ishii H, Furuya M, Iburi T, Yamagami K, Ishibashi R, Tsujii S. Insulin therapy related QOL at night (ITR-QOLN). J Jpn Diabetes Soc. 2008;51:593–600 (Japanese).

    Google Scholar 

  26. Yasuda H, Sanada M, Kitada K, Terashima T, Kim H, Sakaue Y, Fujitani M, Kawai H, Maeda K, Kashiwagi A. Rationale and usefulness of newly devised abbreviated diagnostic criteria and staging for diabetic polyneuropathy. Diabetes Res Clin Pract. 2007;77(Suppl 1):S178–83.

    Article  CAS  PubMed  Google Scholar 

  27. Service FJ, O’Brien PC, Rizza RA. Measurements of glucose control. Diabetes Care. 1987;10:225–37.

    Article  CAS  PubMed  Google Scholar 

  28. Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970;19:644–55.

    Article  CAS  PubMed  Google Scholar 

  29. Schlichtkrull J, Munck O, Jersild M. The M valve, an index of blood-sugar control in diabetics. Acta Med Scand. 1965;177:95–102.

    Article  CAS  PubMed  Google Scholar 

  30. Molnar GD, Taylor WF, Ho MM. Day-to-day variation of continuously monitored glycemia: a further measure of diabetic instability. Diabetologia. 1972;8:342–8.

    Article  CAS  PubMed  Google Scholar 

  31. Wójcicki JM. ‘‘J’’-index. A new proposition of the assessment of current glucose control in diabetic patients. Horm Metab Res. 1995;27:41–2.

    Article  PubMed  Google Scholar 

  32. McCall AL, Cox DJ, Crean J, Gloster M, Kovatchev BP. A novel analytical method for assessing glucose variability: using CGMS in type 1 diabetes mellitus. Diabetes Technol Ther. 2006;8:644–53.

    Article  CAS  PubMed  Google Scholar 

  33. Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke W. Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care. 1998;21:1870–5.

    Article  CAS  PubMed  Google Scholar 

  34. Kashiwagi A, Kasuga M, Araki E, Oka Y, Hanafusa T, Ito H, Tominaga M, Oikawa S, Noda M, Kawamura T, Sanke T, Namba M, Hashiramoto M, Sasahara T, Nishio Y, Kuwa K, Ueki K, Takei I, Umemoto M, Murakami M, Yamakado M, Yatomi Y, Ohashi H, Committee on the Standardization of Diabetes Mellitus-Related Laboratory Testing of Japan Diabetes Society. International clinical harmonization of glycated hemoglobin in Japan: from Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Investig. 2012;3:39–40.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kusunoki Y, Katsuno T, Miyakoshi K, Ikawa T, Nakae R, Ochi F, Tokuda M, Akagami T, Murai K, Miuchi M, Hamaguchi T, Miyagawa J, Namba M. Effects of switching from insulin glargine or detemir to insulin degludec in patients with type 1 diabetes mellitus. Diabetes Ther. 2013;4:461–72.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Komuro M, Inoue G, Tabata M, Yamada Y, Atsuda K, Matsubara H, Irie J, Uchida J, Nakajima C, Izumi H, Shimada M, Yamada S. Insulin degludec requires lower bolus insulin doses than does insulin glargine in Japanese diabetic patients with insulin-dependent state. J Diabetes Sci Technol. 2015;9:632–8.

    Article  CAS  PubMed  Google Scholar 

  37. Schiaffini R, Ciampalini P, Fierabracci A, Spera S, Borrelli P, Bottazzo GF, Crinò A. The continuous glucose monitoring system (CGMS) in type 1 diabetic children is the way to reduce hypoglycemic risk. Diabetes Metab Res Rev. 2002;18:324–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Shiro Fukuda (Department of Metabolic Medicine, Graduate School of Medicine, Osaka University) for his technical assistance.

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Authors and Affiliations

  1. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamadaoka, Suita, 565-0871, Japan

    Shingo Iwasaki, Junji Kozawa, Takekazu Kimura, Kenji Fukui, Hiromi Iwahashi, Akihisa Imagawa & Iichiro Shimomura

  2. Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Suita, Japan

    Takekazu Kimura & Hiromi Iwahashi

  3. Department of Community Medicine, Graduate School of Medicine, Osaka University, Suita, Japan

    Kenji Fukui

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  1. Shingo Iwasaki
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Correspondence to Akihisa Imagawa.

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Conflict of interest

I.S. received honoraria from Novo Nordisk as a speaker and received research funding from Sanofi and Eli Lilly. H.I. received research funding from Novo Nordisk and belongs to the department endowed by the companies including Novo Nordisk. None of the other authors have any conflicts of interest associated with this research.

Ethical standard

This study was carried out in accordance with the Declaration of Helsinki of 1964 and later versions and approved by the ethics committee of Osaka University (approval no. 13089).

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Written informed consent was obtained from all participants before enrollment.

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Iwasaki, S., Kozawa, J., Kimura, T. et al. Insulin degludec is associated with less frequent and milder hypoglycemia in insulin-deficient patients with type 1 diabetes compared with insulin glargine or detemir. Diabetol Int 8, 228–236 (2017). https://doi.org/10.1007/s13340-017-0303-5

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