Time in Range (TIR) and Time Below Range (TBR) in Insulin-Treated Elderly Patients With Type 2 Diabetes

Prospective observational cohort study. Elderly patients >65 years with type 2 diabetes mellitus (T2DM) on insulin therapy and HbA1c between 7% and 9%, with or without oral agents, will be identified from medical records and invited to participate. Patients will wear a FreeStyle Libre Flash CGM during a 6-week study period.

Using CGM technology, we will assess an efficacy outcome : time in range (TIR) between 70-180 mg/dl and a safety outcome: incidence of hypoglycemia (time below range (TBR) less than 70, 54, and 40 mg/dl in insulin treated older adults with T2DM.

Patients will return to clinic every 2 weeks for new continuous glucose monitoring (CGM) placement, assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.

CGM data will be downloaded every 2 weeks.

Study Overview

• Status: Completed
• Conditions: Continuous Glucose Monitoring
• Intervention / Treatment: Device: Application of the FreeStyle Libre Flash Glucose CGM.; Diagnostic test: InBody 270 multifrequency bioimpedance

Detailed Description

Prospective observational cohort study. Patients over 65 years of age, with TDM2 using insulin with or without the use of associated oral antidiabetic agents and with HbA1c between 7% and 9%, will be identified by medical records at the Hospital da Cruz Vermelha Brasileira-Filial do Paraná and they will be invited to participate in the study by telephone and forwarded to the research center Cline Research Center where the study procedures will be carried out. Patients from the private clinic of neurology and endocrinology Cline will also be invited by telephone. In this way the sample of patients will include patients from the public and private health system.

On the first visit to the research centers, after signing the informed consent form (ICF), patients will be evaluated for the presence of other comorbidities associated with diabetes such as the presence of cardiovascular disease, hypertension and dyslipidemia.

The screening for the presence of sarcopenia will be performed with the application of the SARC-F questionnaire; measuring muscle strength with grip strength; the functional test of getting up from the chair without supporting the arms and walking for 3 meters, turning 180º and returning to sit. The time in which the elderly person performs this task is timed and the time up to 20 seconds is considered normal.

Patients will undergo a complete physical examination and body composition analysis using the InBody 270 multifrequency bioimpedance to calculate the appendicular skeletal musculature.

After the first evaluation at the research centers, patients will be referred to partner laboratories that use the same methodologies for measuring HbA1c, blood count, urea, creatinine, glutamic oxalacetic transaminase (TGO) and glutamic-pyruvic transaminase (TGP), which will be performed only at the initial visit.

During the second visit to the research center, the FreeStyle Libre Flash interstitial glucose sensor will be inserted for the first time in the posterior and upper arm and the patient will be instructed to read the glucose at least 10 times a day, being sure to check glucose for a period longer than 8 hours. The patient should be instructed to return to the research center every 2 weeks to change the sensor until completing the 6-week period.

The patient's travel to the research center will be reimbursed by the study team. The study will be carried out at the Hospital da Cruz Vermelha Brasileira-Filial do Paraná, located in Curitiba in partnership with the independent research center Cline Research Center (CRC). Eligible patients will be randomly selected from clinical outpatients at participating institutions, concomitantly.

• Study Type: Observational
• Enrollment (Actual): 71

Contacts and Locations

Study Locations

• Brazil
  • PR
    • Curitiba, PR, Brazil, 80030480
      • Cline Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Elderly patients >65 years with T2DM on insulin therapy and HbA1c between 7% and 9%, with or without oral agents, will be identified from medical records and invited to participate. Patients will wear a FreeStyle Libre Flash CGM during a 6-week study period.

Description

Inclusion Criteria:

• Age > 65 years
• Known history of type 2 Diabetes Mellitus
• BMI between 18.5 and 35kg/m2
• HbA1c between 7% and 9.0%
• Insulin with or without oral agent treatment for diabetes mellitus

Exclusion Criteria:

• Patients using GLP1 (Glucagon-like peptide-1) agonists
• Patients with eGFR<30 (epidermal growth factor receptor) using (calculated CKD EPI)
• Anemia (Hb<11 grams)
• Chronic liver chronic disease (ALT>3xULN)
• Use of glucocorticoids within 3 months preceding the investigation
• Neoplasia treatment
• Inability by the patient or caretaker to commit to protocol instructions and visit schedule.
• Type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
T2DM Elderly on Insulin CGM; 70 patients with type 2 diabetes > 65 years of age taking insulin as treatment. The sample size was calculated to estimate the minimal number of patients necessary to describe the mean TIR (minutes/day).	Device: Application of the FreeStyle Libre Flash Glucose CGM.; Assessment of glycemic control and hypoglycemia, adherence to therapy and CGM use.; Diagnostic test: InBody 270 multifrequency bioimpedance; analysis of body composition to calculate appendicular skeletal muscle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome is time in range (TIR)	TIR between 70-180 mg/dL in insulin treated in patients older than 65 years.	04-07-2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
-Frequency of hypoglycemia (<70mg/dL, <54mg/dL) to measure Time Bellow Range	percentage of patients with greater than 5%-time below glucose target (<70 mg/dL);; diurnal and nocturnal hypoglycemia;	04-07-2021
-Time in hyperglycemia > 180, 250 mg/dL to measure Time Above Range	percentage of patients with greater than 5%-time glucose above 250mg/dL; percentage of patients with greater than 25%-time glucose above 180mg/dL	04-07-2021
-Adherence to CGM use and sensor utilization for diabetes care management using CGM	-assessing the percentage of captured sensor data	04-07-2021
- Rate of emergency room visits and hospitalization	-changing insulin type and dose to prevent hospitalization	04-07-2021
-Glucose Variability	glycemic variability standard deviation and MAGE(mean amplitude of glycemic excursions); glucose variability will be calculated as % coefficient of variation %CV= (standard deviation (SD)/mean glucose x 100%)	04-07-2021

Collaborators and Investigators

• Sponsor: Cline Research Center
• Collaborators: Abbott Diabetes Care
• Investigators: Principal Investigator: Silmara Leite, MD, PhD, Cline Research Center

Publications and helpful links

Helpful Links

• International Consensus o use of Continuous Glucose Monitoring. Diabetes Care 2017;40:1631-1640
• The physiology of endocrine systems with ageing
• Diabetes in the older patient: heterogeneity requires individualization of therapeutic strategies
• Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial.
• Estimating the mean and variance from the median, range, and the size of a sample.
• A power primer.
• Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range
• The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2020
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 12, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Elderly; Continuous Glucose Monitoring; Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: ADC-OUS-IIS-19-47

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No