R M Agesen1, P L Kristensen2, H Beck-Nielsen3, K Nørgaard4, H Perrild5, J S Christiansen6, T Jensen7, P Hougaard8, H H Parving9, B Thorsteinsson10, L Tarnow11, U Pedersen-Bjergaard10. 1. Department of cardiology, nephrology and endocrinology, Nordsjællands university hospital - Hillerød, Dyrehavevej, 29, 3400 Hillerød, Denmark; Faculty of health and medical sciences, university of Copenhagen, Blegdamsvej, 3B, 2200 København N, Denmark. Electronic address: rikke.agesen@regionh.dk. 2. Department of cardiology, nephrology and endocrinology, Nordsjællands university hospital - Hillerød, Dyrehavevej, 29, 3400 Hillerød, Denmark; Steno diabetes center, Niels Steensens Vej, 2, 2820 Gentofte, Denmark. 3. Department of endocrinology M, Odense university hospital, Søndre boulevard, 29, 5000 Odense C, Denmark; Faculty of health sciences, university of Southern Denmark, J.B. Winsløws Vej, 19, 3, 5000 Odense C, Denmark. 4. Department of endocrinology, Hvidovre university hospital, Kettegårds Alle, 30, 2650 Hvidovre, Denmark. 5. Department of internal medicine, Bispebjerg university hospital, Bispebjerg Bakke, 24, 2400 København NV, Denmark. 6. Department of endocrinology M, Aarhus university hospital, Palle Juul-Jensens boulevard, 99, 8200 Aarhus N, Denmark; Health, university of Aarhus, Nordre Ringgade, 1, 8000 Aarhus C, Denmark. 7. Department of medical endocrinology, Copenhagen university hospital (Rigshospitalet), Blegdamsvej, 9, 2100 København Ø, Denmark. 8. Department of biostatistics, university of Southern Denmark, J.B. Winsløws Vej, 9 B, st.tv., 5000 Odense C, Denmark. 9. Health, university of Aarhus, Nordre Ringgade, 1, 8000 Aarhus C, Denmark; Department of medical endocrinology, Copenhagen university hospital (Rigshospitalet), Blegdamsvej, 9, 2100 København Ø, Denmark. 10. Department of cardiology, nephrology and endocrinology, Nordsjællands university hospital - Hillerød, Dyrehavevej, 29, 3400 Hillerød, Denmark; Faculty of health and medical sciences, university of Copenhagen, Blegdamsvej, 3B, 2200 København N, Denmark. 11. Steno diabetes center, Niels Steensens Vej, 2, 2820 Gentofte, Denmark; Health, university of Aarhus, Nordre Ringgade, 1, 8000 Aarhus C, Denmark; Department of clinical research, Nordsjællands hospital-Hillerød, Dyrehavevej, 29, 3400 Hillerød, Denmark.
Abstract
AIM: Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. METHODS: This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). RESULTS: Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. CONCLUSION: In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.
RCT Entities:
AIM: Insulin analogues reduce the risk of hypoglycaemia compared with humaninsulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. METHODS: This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). RESULTS: Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. CONCLUSION: In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with humaninsulin.
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