Effekte von rtCGM bei Erwachsenen mit Typ-1-Diabetes und Hypoglykämieproblemen, die mit einer multiplen Insulininjektions-Therapie behandelt werden: Ergebnisse der multizentrischen, randomisierten kontrollierten HypoDE-Studie

Fragestellung: Die Wirksamkeit von rtCGM zur Vermeidung von Hypoglykämien bei Patienten mit multiplen Insulininjektionen und Hypoglykämieproblemen wurde bisher nicht untersucht. Ziel dieser Studie war es zu zeigen, dass der Einsatz von rtCGM bei diesen Patienten zu einer Reduktion von hypoglykämischen Glukosewerten führt. Methodik: Die HypoDE-Studie war eine randomisierte, kontrollierte Studie mit 6-Monats Follow-up, die von 12 diabetologischen Schwerpunktpraxen in Deutschland durchgeführt wurde. Studienteilnehmer hatten Typ-1-Diabetes mit einer Hypoglykämiewahrnehmungsstörung und/oder schwere Unterzuckerungen im letzten Jahr. Studienteilnehmer trugen für 28 Tage ein verblindetes rtCGM-System und wurden anschließend entweder auf die Nutzung eines offenen rtCGM-Systems (Dexcom G5) für 26 Wochen (rtCGM-Gruppe), oder die Kontrollgruppe, die weiterhin die Blutzuckermessung nutzte, randomisiert. Zur Follow-up-Phase, Woche 22 – 26, bekam die Kontrollgruppe wieder ein verblindetes rtCGM-System. Primärer Endpunkt war die Verbesserung hypoglykämischer Ereignisse, definiert als Glukosewerte ≤54 mg/dl für 320 Minuten. Als sekundärer Endpunkt wurde die Anzahl schwerer Unterzuckerungen (Fremdhilfe + medizinische Intervention) analysiert. Ergebnisse: Vollständige Daten von 141 Patienten konnten ausgewertet werden. Im Durchschnitt konnte die Anzahl hypoglykämischer Ereignisse in der rtCGM-Gruppe von 10,4 ± 9,6 auf 3,4 ± 4,5 gesenkt werden; in der Kontrollgruppe von 13,5 ± 11,8 auf 13,2 ± 11,5. Die Incidence-Rate-Ratio (IRR) für hypoglykämische Ereignisse war für Teilnehmer der rtCGM-Gruppe um 72% signifikant geringer (IRR 0,28; 95% KI 0,20 – 0,39; p < 0,0001). Die Inzidenzrate schwerer Unterzuckerungen seit Randomisierung war 0,64 pro Patientenjahr in der rtCGM-Gruppe und 1,18 pro Patientenjahr in der Kontrollgruppe (IRR 0,36; 95% KI 0,15 – 0,88; p = 0,0247). Schlussfolgerungen: rtCGM führt bei Patienten mit multiplen Insulininjektionen mit Hypoglykämieproblemen zu einer signifikanten Reduktion von hypoglykämischen Werten sowie schwerer Unterzuckerungen

Can CGM Discriminate Between Type 1 Diabetes Patients With and Without Severe Hypoglycaemia? Results of the Baseline Assessment from the HypoDE Study

severe hypoglycaemia (SH), defined as the need of third party assistance for recovery. Continuous glucose monitoring (CGM) offers valuable data about glycaemic control and hypoglycaemic exposure in these high-risk patients. However, it is unknown to which extent CGM can provide data that enables identifying people who experienced an episode of severe hypoglycaemia in the past year in this high-risk group. Therefore, we analysed baseline data of the HypoDE study to examine the following problems: 1. Is the hypoglycaemic CGM footprint different in people with and without SH? 2. Can CGM data be used to identify people with severe hypoglycaemia in this high-risk group? 3. What is the screening performance of the hypoglycaemic CGM footprint to identify people with SH

Psychological Impact of Severe Hypoglycaemia on Fear of Hypoglycaemia and Diabetes-related Distress: Baseline Assessment in Participants of the HypoDE Study

Hypoglycaemia has long been described as the main limiting factor in intensified insulin therapy. While mild hypoglycaemia can occur several times a week (or even day) and can be handled by the patient her/himself, severe hypoglycaemia, which require the help of others to recover, occur less frequently but are more dramatic for patients. To understand the impact of severe hypoglycaemia (SH) on patients, we analysed the psychological profile of people with type 1 diabetes who had experienced at least one episode of severe hypoglycaemia (SH: third party assistance for recovery) and compared it with patients without a recent SH episode

Kann man durch CGM-Profile Menschen mit Typ 1-Diabetes und einem hohen Risiko für schwere Hypoglykämien identifizieren? Erste Ergebnisse der Baseline-Erhebung der bundesweiten HypoDE-Studie

Menschen mit einem Typ 1 Diabetes und einer Hypoglykämiewahrnehmungsstörung haben ein erhöhtes Risiko für schwere Hypoglykämien (definiert als Hypoglykämie zu deren Behandlung die Hilfe Dritter notwendig ist). In dieser Untersuchung soll geklärt werden, inwieweit in einer solchen Hochrisikogruppe mit Hilfe von Glukosedaten der kontinuierlichen Glukosemessung (CGM), Personen identifiziert werden können, die im letzten Jahr eine schwere Unterzuckerung erlitten haben. Es wurden Baseline-Daten der HypoDE Studie analysiert, um die folgenden Fragen zu beantworten: 1) Sind die CGM Glukoseprofile von Menschen mit und ohne schwere Hypoglykämien unterschiedlich? 2) Können die CGM-Profile genutzt werden, um Personen mit schweren Hypoglykämien in dieser Hochrisikogruppe zu identifizieren? 3) Wie sind die Screeningeigenschaften von CGM Glukoseprofilen zur Identifikation von Personen mit schweren Hypoglykämien

People with Type 1 Diabetes and Increased Hypoglycemia Frequency have a Higher Risk for Nocturnal Hypoglycemia During the Second Half of the Night

Based on the baseline data of a multi-center randomized CGM trial (HypoDE), we analyzed the glucose recordings of participants with an increased hypoglycemia frequency. All 126 participants had type 1 diabetes and were on an MDI insulin therapy (age 46.5±11.5 yrs., 36.5% female, HbA1c 7.5±1.0%, hypoglycemia unawareness score 5.0±1.1). Each participant used a blinded CGM system (DexCom Gen 4) for 28 days. The percentage of glucose readings ≤70 mg/dl over a 24h period (6 am to 10 am; 10 am to 2 pm, 2 pm to 6 pm, 6 pm to 10 pm, 10 pm to 2 am, and 2 am to 6 am) were analyzed. During the whole day, on average 7.6% of all 288 glucose readings per patients were ≤70 mg/dl. From morning to evening, 192 of ≤70 mg/dl readings were between 7.0% and 7.3%. In the early night, this percentage was lower than during the late night, in which the percentage of ≤70 mg/dl values rose to >10% (p<0.001). A similar pattern could be observed for mean glucose values during these intervals (figure). Since study participants were at higher risk for hypoglycemia, they appear to have an elevated bedtime glucose in order to avoid nocturnal hypoglycemia. This worked well during the first half of the night; however, during the second half of the night the hypoglycemia risk increased considerably. A modification of nocturnal basal insulin supply should be considered in this high risk group

Clinical and Psychological Characteristics of People with Type 1 Diabetes and a High Risk of Hypoglycemic Events

For the HypoDE study people with type 1 diabetes treated by MDI with a high risk of hypoglycemic events were recruited. Baseline data of 126 study participants were analyzed (age 46.5±11.6 yrs., 36.5% female, HbA1c 7.5±1.0%). They reported 4.5±9.2 episodes of severe hypoglycemia per year (third party assistance for recovery required) and 1.0±2.4 episodes of hypoglycemic episodes with coma or seizure per year prior to study participation. This corresponds to 700%, respectively 600% more hypoglycemic episodes than observed in the DCCT 0.64,respectively 0.16 episodes per year). Blinded CGM recordings for 28 days during the run-in phase of the study revealed that the participants had 12.7±11.8 hypoglycemic events per 28 days (= glucose reading ≤55 mg/dl for at least 20 min). They spent 109 min per day at glucose levels ≤70 mg/dl and 34 min per day ≤50 mg/dl. This corresponds to 32.5%, respectively 55% more time in this range that the adult participants in the JDRF CGM-trial. The hypoglycemia unawareness score of the participants was 5.0±1.1 (out of a maximum score of 7); 95.2% yielded a score ≥4, which is used as a cut-off score for hypoglycemia unawareness. In the Hypoglycemia Fear Survey, HypoDE participants achieved a score of 32.3±15.5 and a Diabetes Distress Scale mean item score of 2.5±1.2. Both scores were higher than those which could be expected in a sample of people with type 1 diabetes, not specifically selected by hypoglycemia problems. In summary, these data suggest that HypoDE participants represent patients with a high risk of clinical as well as biochemical hypoglycemic events. Compared to the “typical” patient with type 1 diabetes, these subjects reported a high amount of hypoglycemia worries and diabetes-related distress

Identifying people at risk for severe hypoglycemia by CGM in a sample of people with reduced hypoglycemia awareness

It is well known that people with type 1 diabetes (pw1d) and hypoglycemia unawareness have an increased risk for severe hypoglycemia (SH); however, it is unknown if continuous glucose monitoring (CGM)helps to prospectively evaluate the risk of SH in such patients. We analyzed CGM recordings of 126 participants on MDI in the HypoDE study with hypoglycemia unawareness wearing blinded CGM (DexCom Gen 4) for 28 days (age 46.5±11.5 yrs. 36.5% female, HbA1c 7.5±1.0%, unawareness score 5.0±1.1). From these subjects, 65 (51.6%) reported occurrence of SH in the last year prior to study start. In a high-risk group of pw1d and hypoglycemia unawareness, CGM data on the exposure regarding hypoglycemic glucose values or number of hypoglycemic events ≤55 mg/dl predict the occurrence of SH. ROC analyses suggested meaningful cut-off values for the duration of hypoglycemic episodes, respectively the number of hypoglycemic events. These cut-off values can facilitate the identification of people with an elevated risk for SH even in a hypoglycemic high-risk group with reasonable sensitivity and specificity