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

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftDiabetes Technology and Therapeutics
Vol/bind20
Udgave nummer3
Sider (fra-til)247-256
ISSN1520-9156
DOI
StatusUdgivet - mar. 2018

Fingeraftryk

Hypoglycemia
Insulin
Blood Glucose Self-Monitoring
Hypoglycemic Agents
Insulin Aspart
Confidence Intervals
Clinical Trials

Citer dette

Agesen, Rikke Mette ; Kristensen, Peter Lommer ; Beck-Nielsen, Henning ; Nørgaard, Kirsten ; Perrild, Hans ; Jensen, Tonny ; Parving, Hans Henrik ; Thorsteinsson, Birger ; Tarnow, Lise ; Pedersen-Bjergaard, Ulrik. / 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. I: Diabetes Technology and Therapeutics. 2018 ; Bind 20, Nr. 3. s. 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 = "CGM, HypoAna trial, Insulin analogs, Non-severe hypoglycemia, Randomized controlled trial, Type 1 diabetes, Humans, Insulin Aspart/administration & dosage, Middle Aged, Male, Hypoglycemic Agents/administration & dosage, Diabetes Mellitus, Type 1/blood, Insulin Detemir/administration & dosage, Blood Glucose/analysis, Blood Glucose Self-Monitoring, Adult, Female, Aged, Hypoglycemia/blood",
author = "Agesen, {Rikke Mette} and Kristensen, {Peter Lommer} and Henning Beck-Nielsen and Kirsten N{\o}rgaard and Hans Perrild and Tonny Jensen and Parving, {Hans Henrik} and Birger Thorsteinsson and Lise Tarnow and Ulrik Pedersen-Bjergaard",
year = "2018",
month = "3",
doi = "10.1089/dia.2017.0372",
language = "English",
volume = "20",
pages = "247--256",
journal = "Diabetes Technology & Therapeutics",
issn = "1520-9156",
publisher = "Mary Ann Liebert Incorporated",
number = "3",

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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; Nørgaard, Kirsten; Perrild, Hans; Jensen, Tonny; Parving, Hans Henrik; Thorsteinsson, Birger; Tarnow, Lise; Pedersen-Bjergaard, Ulrik.

I: Diabetes Technology and Therapeutics, Bind 20, Nr. 3, 03.2018, s. 247-256.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

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

PY - 2018/3

Y1 - 2018/3

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.

KW - CGM

KW - HypoAna trial

KW - Insulin analogs

KW - Non-severe hypoglycemia

KW - Randomized controlled trial

KW - Type 1 diabetes

KW - Humans

KW - Insulin Aspart/administration & dosage

KW - Middle Aged

KW - Male

KW - Hypoglycemic Agents/administration & dosage

KW - Diabetes Mellitus, Type 1/blood

KW - Insulin Detemir/administration & dosage

KW - Blood Glucose/analysis

KW - Blood Glucose Self-Monitoring

KW - Adult

KW - Female

KW - Aged

KW - Hypoglycemia/blood

U2 - 10.1089/dia.2017.0372

DO - 10.1089/dia.2017.0372

M3 - Journal article

C2 - 29565719

AN - SCOPUS:85044448497

VL - 20

SP - 247

EP - 256

JO - Diabetes Technology & Therapeutics

JF - Diabetes Technology & Therapeutics

SN - 1520-9156

IS - 3

ER -