Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial

Rikke Mette Agesen; Peter Lommer Kristensen; Henning Beck-Nielsen; Kirsten Nørgaard; Hans Perrild; Tonny Jensen; Hans-Henrik Parving; Birger Thorsteinsson; Lise Tarnow; Ulrik Pedersen-Bjergaard

doi:10.1089/dia.2017.0372

Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial

Rikke Mette Agesen, Peter Lommer Kristensen, Henning Beck-Nielsen, Kirsten Nørgaard, Hans Perrild, Tonny Jensen, Hans-Henrik Parving, Birger Thorsteinsson, Lise Tarnow, Ulrik Pedersen-Bjergaard

9 Citations (Scopus)

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.

Original language	English
Journal	Diabetes Technology & Therapeutics
Volume	20
Issue number	3
Pages (from-to)	247-256
Number of pages	10
ISSN	1520-9156
DOIs	https://doi.org/10.1089/dia.2017.0372
Publication status	Published - Mar 2018

Keywords

Adult
Aged
Blood Glucose/analysis
Blood Glucose Self-Monitoring
Diabetes Mellitus, Type 1/blood
Female
Humans
Hypoglycemia/blood
Hypoglycemic Agents/administration & dosage
Insulin Aspart/administration & dosage
Insulin Detemir/administration & dosage
Male
Middle Aged

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Agesen, R. M., Kristensen, P. L., Beck-Nielsen, H., Nørgaard, K., Perrild, H., Jensen, T., Parving, H.-H., Thorsteinsson, B., Tarnow, L., & Pedersen-Bjergaard, U. (2018). Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial. Diabetes Technology & Therapeutics, 20(3), 247-256. https://doi.org/10.1089/dia.2017.0372

Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial. / Agesen, Rikke Mette; Kristensen, Peter Lommer; Beck-Nielsen, Henning et al.
In: Diabetes Technology & Therapeutics, Vol. 20, No. 3, 03.2018, p. 247-256.

Research output: Contribution to journal › Journal article › Research › peer-review

Agesen, RM, Kristensen, PL, Beck-Nielsen, H, Nørgaard, K , Perrild, H, Jensen, T, Parving, H-H, Thorsteinsson, B, Tarnow, L & Pedersen-Bjergaard, U 2018, 'Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial', Diabetes Technology & Therapeutics, vol. 20, no. 3, pp. 247-256. https://doi.org/10.1089/dia.2017.0372

Agesen RM, Kristensen PL, Beck-Nielsen H, Nørgaard K , Perrild H, Jensen T et al. Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial. Diabetes Technology & Therapeutics. 2018 Mar;20(3):247-256. doi: 10.1089/dia.2017.0372

Agesen, Rikke Mette ; Kristensen, Peter Lommer ; Beck-Nielsen, Henning et al. / Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia : Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial. In: Diabetes Technology & Therapeutics. 2018 ; Vol. 20, No. 3. pp. 247-256.

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title = "Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia: Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial",

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.",

keywords = "Adult, Aged, Blood Glucose/analysis, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1/blood, Female, Humans, Hypoglycemia/blood, Hypoglycemic Agents/administration & dosage, Insulin Aspart/administration & dosage, Insulin Detemir/administration & dosage, Male, Middle Aged",

author = "Agesen, {Rikke Mette} and Kristensen, {Peter Lommer} and Henning Beck-Nielsen and Kirsten N{\o}rgaard and Hans Perrild and Tonny Jensen and Hans-Henrik Parving and Birger Thorsteinsson and Lise Tarnow and Ulrik Pedersen-Bjergaard",

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T1 - Effect of Insulin Analogs on Frequency of Non-Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Severe Hypoglycemia

T2 - Much Higher Rates Detected by Continuous Glucose Monitoring than by Self-Monitoring of Blood Glucose-The HypoAna Trial

AU - Agesen, Rikke Mette

AU - Kristensen, Peter Lommer

AU - Beck-Nielsen, Henning

AU - Nørgaard, Kirsten

AU - Perrild, Hans

AU - Jensen, Tonny

AU - Parving, Hans-Henrik

AU - Thorsteinsson, Birger

AU - Tarnow, Lise

AU - Pedersen-Bjergaard, Ulrik

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N2 - 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.

AB - 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.

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KW - Aged

KW - Blood Glucose/analysis

KW - Blood Glucose Self-Monitoring

KW - Diabetes Mellitus, Type 1/blood

KW - Female

KW - Humans

KW - Hypoglycemia/blood

KW - Hypoglycemic Agents/administration & dosage

KW - Insulin Aspart/administration & dosage

KW - Insulin Detemir/administration & dosage

KW - Male

KW - Middle Aged

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