Rikke Mette Agesen1,2, Peter Lommer Kristensen1,3, Henning Beck-Nielsen4,5, Kirsten Nørgaard6, Hans Perrild7, Tonny Jensen8, Hans-Henrik Parving8,9, Birger Thorsteinsson1,2, Lise Tarnow3,9,10, Ulrik Pedersen-Bjergaard1,2. 1. 1 Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital-Hillerød , Hillerød, Denmark . 2. 2 Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark . 3. 3 Clinical Research Unit, Steno Diabetes Center , Gentofte, Denmark . 4. 4 Department of Endocrinology M, Odense University Hospital , Odense, Denmark . 5. 5 Faculty of Health Sciences, University of Southern Denmark , Odense, Denmark . 6. 6 Department of Endocrinology, Hvidovre Hospital , Hvidovre, Denmark . 7. 7 Department of Internal Medicine, Bispebjerg Hospital , Copenhagen, Denmark . 8. 8 Department of Medical Endocrinology, Copenhagen University Hospital (Rigshospitalet) , Copenhagen, Denmark . 9. 9 Health, University of Aarhus , Aarhus, Denmark . 10. 10 Department of Clinical Research, Nordsjællands Hospital-Hillerød , Hillerød, Denmark .
Abstract
BACKGROUND: Hypoglycemia is an increasingly important endpoint in clinical diabetes trials. The assessment of hypoglycemia should therefore be as complete as possible. Blinded continuous glucose monitoring (CGM) provides an improved opportunity to capture asymptomatic and nocturnal events. Here we report results from the HypoAna trial comparing all-analog-insulin therapy (aspart/detemir) with all-human-insulin therapy (neutral protamine Hagedorn/regular) on non-severe hypoglycemia (symptomatic and asymptomatic hypoglycemia) as assessed by blinded CGM and compared with data obtained by self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes and recurrent severe hypoglycemia. METHODS: Fifty-three patients completed a substudy of 4 × 3 days of blinded CGM. CGM traces were reviewed for hypoglycemic events lasting 15 min or longer. RESULTS: At the threshold ≤3.9 mmol/L, the per-protocol analysis demonstrated a 40% rate reduction (95% confidence interval [CI] 20%-60%; P = 0.002) in nocturnal non-severe hypoglycemia during analog treatment, mainly due to a 40% rate reduction (95% CI 0%-70%; P = 0.03) of nocturnal asymptomatic hypoglycemia. Similar nonsignificant trends were seen at the glucose threshold ≤3.0 mmol/L. Overall CGM-detected that nocturnal asymptomatic hypoglycemia ≤3.9 mmol/L was ∼17 times more frequent than SMBG-detected episodes (52 vs. 3 events/patient-year). This translates into a time needed to treat one patient with insulin analogs to prevent one episode that is 34 times shorter using CGM data than SMBG data (1.4 vs. 47 weeks). CONCLUSIONS: Capturing hypoglycemic events by the conventional method of SMBG in patients with impaired awareness reveals only a limited number of events. Blinded CGM can provide more complete data, particularly in terms of asymptomatic and nocturnal events.
BACKGROUND:Hypoglycemia is an increasingly important endpoint in clinical diabetes trials. The assessment of hypoglycemia should therefore be as complete as possible. Blinded continuous glucose monitoring (CGM) provides an improved opportunity to capture asymptomatic and nocturnal events. Here we report results from the HypoAna trial comparing all-analog-insulin therapy (aspart/detemir) with all-human-insulin therapy (neutral protamine Hagedorn/regular) on non-severe hypoglycemia (symptomatic and asymptomatic hypoglycemia) as assessed by blinded CGM and compared with data obtained by self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes and recurrent severe hypoglycemia. METHODS: Fifty-three patients completed a substudy of 4 × 3 days of blinded CGM. CGM traces were reviewed for hypoglycemic events lasting 15 min or longer. RESULTS: At the threshold ≤3.9 mmol/L, the per-protocol analysis demonstrated a 40% rate reduction (95% confidence interval [CI] 20%-60%; P = 0.002) in nocturnal non-severe hypoglycemia during analog treatment, mainly due to a 40% rate reduction (95% CI 0%-70%; P = 0.03) of nocturnal asymptomatic hypoglycemia. Similar nonsignificant trends were seen at the glucose threshold ≤3.0 mmol/L. Overall CGM-detected that nocturnal asymptomatic hypoglycemia ≤3.9 mmol/L was ∼17 times more frequent than SMBG-detected episodes (52 vs. 3 events/patient-year). This translates into a time needed to treat one patient with insulin analogs to prevent one episode that is 34 times shorter using CGM data than SMBG data (1.4 vs. 47 weeks). CONCLUSIONS: Capturing hypoglycemic events by the conventional method of SMBG in patients with impaired awareness reveals only a limited number of events. Blinded CGM can provide more complete data, particularly in terms of asymptomatic and nocturnal events.
Authors: Marie M Henriksen; Henrik U Andersen; Birger Thorsteinsson; Ulrik Pedersen-Bjergaard Journal: Diabetologia Date: 2021-01-14 Impact factor: 10.122
Authors: Ulrik Pedersen-Bjergaard; Rikke M Agesen; Julie M B Brøsen; Amra C Alibegovic; Henrik U Andersen; Henning Beck-Nielsen; Peter Gustenhoff; Troels K Hansen; Christoffer Hedetoft; Tonny J Jensen; Claus B Juhl; Andreas K Jensen; Susanne S Lerche; Kirsten Nørgaard; Hans-Henrik Parving; Anne L Sørensen; Lise Tarnow; Birger Thorsteinsson Journal: Diabetes Obes Metab Date: 2021-11-02 Impact factor: 6.408