The Effect of SGLT2 Inhibitors on Heart Rate Variability and BDNF Levels in Patients With Type 2 Diabetes

NCT ID: NCT05164523

Last Updated: 2023-09-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 64 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2022-12-30

Brief Summary

Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. The aim is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.

Detailed Description

Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Five-year mortality rates of diabetic patients with CAN are significantly higher than those without. Although there are various methods, primarily scintigraphic and pharmacological tests, to evaluate CAN, the practical use of these methods remains limited. In recent years, heart rate recovery (HRR) and heart rate variability (HRV) have been increasingly used as simple, inexpensive, and non-invasive methods to evaluate the status of heart sympathetic and vagus nerve functions. Values obtained as a result of 24-hour rhythm Holter provide the measurement of sympathetic and parasympathetic activity. While a significant relationship was observed between blood glucose levels and HRV in previous studies, no relationship was found between HbA1c levels and HRV.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with growth factor properties. Studies with SGLT2 inhibitors have shown a decrease in HbA1c values, weight loss, and a decrease in both systolic and diastolic blood pressure. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. As a result of these data, these medications are recommended as drugs that should be used in the foreground following metformin, especially in diabetic patients with cardiac and renal diseases. In the study of Shimuz et al. in which the effects of empagliflozin and placebo on heart rate variability were compared in patients with acute myocardial infarction, HRV improved significantly with the use of empagliflozin in the early period. A study examining the effects of empagliflozin use on HRV in patients with type 2 diabetes is still ongoing. Apart from these 2 studies, no study was found in the literature.

The aim of this study is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.

Conditions

Type 2 Diabetes; Heart Rate Variability

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with type 2 diabetes treated with SGLT2 inhibitors

metformin using patients with type 2 diabetes who were recently prescribed an SGLT2 inhibitor

24-hour rhythm Holter

Intervention Type: DIAGNOSTIC_TEST

Before starting their newly prescribed medication, the investigators will apply 24-hour rhythm Holter and repeat it at the end of the trial.

36 item Short Form Survey (SF-36)

Intervention Type: DIAGNOSTIC_TEST

Before starting their newly prescribed medication, the investigators will apply SF-36 survey and repeat it at the end of the trial.

Patients with type 2 diabetes treated with other oral agents

metformin using patients with type 2 diabetes who were recently prescribed a pre-defined antidiabetic medication other than SGLT2 inhibitors

24-hour rhythm Holter

Intervention Type: DIAGNOSTIC_TEST

Before starting their newly prescribed medication, the investigators will apply 24-hour rhythm Holter and repeat it at the end of the trial.

36 item Short Form Survey (SF-36)

Intervention Type: DIAGNOSTIC_TEST

Before starting their newly prescribed medication, the investigators will apply SF-36 survey and repeat it at the end of the trial.

Interventions

24-hour rhythm Holter

Before starting their newly prescribed medication, the investigators will apply 24-hour rhythm Holter and repeat it at the end of the trial.

Intervention Type: DIAGNOSTIC_TEST

36 item Short Form Survey (SF-36)

Before starting their newly prescribed medication, the investigators will apply SF-36 survey and repeat it at the end of the trial.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

SF-36

Eligibility Criteria

Inclusion Criteria

• giving consent
• being 30 years old or older
• HbA1c concentrations between 6.5% and 8%
• using metformin as a single agent for at least 3 months
• diabetes age <10 years

Exclusion Criteria

• having uncontrolled hypothyroidism, hyperthyroidism, or other diseases that may affect cognitive functions
• ketoacidosis or coma
• cerebrovascular disease or psychiatric disorder
• mental retardation, psychosis, dementia, brain trauma, epilepsy and other cerebral diseases
• alcohol or other substance abuse
• hearing loss
• Presence of diseases that will affect cognitive function such as chronic inflammatory diseases and respiratory system diseases
• chronic kidney failure (GFR <45)
• sleep apnea syndrome
• malignancy
• using a sulfonylurea or glinide
• using beta blocker or non-dihydropyridine group calcium antagonists
• diabetic autonomous neuropathy
• atrial fibrillation
• an acute coronary event within the last 3 months

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Goztepe Training and Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ayse N Erbakan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ayse N Erbakan, MD

Role: PRINCIPAL_INVESTIGATOR

Istanbul Medeniyet University Goztepe Research and TRaining Hospital

Locations

Istanbul Medeniyet University Goztepe Research and Training Hospital

Istanbul, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

Heart Rate Variability-BDNF

Identifier Type: -

Identifier Source: org_study_id