Exercise and PPARGC1A rs8192678 in Older Adults With Type 2 Diabetes and Cognitive Impairment (Association Be)

Association Between PPARGC1A rs8192678 Polymorphism and the Effects of a 12-Week Combined Aerobic and Resistance Exercise Intervention in Older Adults With Type 2 Diabetes Mellitus and Cognitive Impairment

This completed single-arm interventional study evaluated changes in metabolic control, cognitive function, and health-related physical fitness following a 12-week combined aerobic and resistance exercise program in older adults with type 2 diabetes mellitus and cognitive impairment. The study also explored whether the magnitude of response to exercise differed according to PPARGC1A rs8192678 genotype.

A total of 75 participants were genotyped, and 45 participants were included in a balanced genotype-stratified cohort, consisting of 15 participants with the CC genotype, 15 with the CT genotype, and 15 with the TT genotype. All participants received the same exercise intervention and were assessed at baseline and at Week 12.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Behavioral: Combined aerobic and resistance exercise

Detailed Description

This was a completed, retrospectively registered, single-arm exercise intervention study with prespecified genotype-stratified analyses. The study examined whether PPARGC1A rs8192678 genotype was associated with interindividual variation in response to a standardized combined aerobic and resistance exercise program in older adults with type 2 diabetes mellitus and cognitive impairment.

PPARGC1A rs8192678 genotyping was performed on peripheral blood DNA using Kompetitive Allele-Specific Polymerase Chain Reaction (KASP). Genotype was used as an analytical stratification factor and did not determine intervention assignment. From 75 genotyped participants, a balanced cohort of 45 participants was included, comprising 15 participants with each of the CC, CT, and TT genotypes.

All participants received the same 12-week exercise intervention. Aerobic exercise consisted of group-based aerobics performed four times per week. Aerobic exercise duration progressed from 20 minutes per session during Weeks 1-4 to 30 minutes during Weeks 5-8 and 40 minutes during Weeks 9-12. Exercise intensity progressed from 50%-60% of age-predicted maximum heart rate during Weeks 1-6 to 60%-70% during Weeks 7-12. Maximum heart rate was estimated using the equation: 207 - 0.7 × age.

Resistance exercise using elastic bands was performed twice per week. Resistance exercise duration progressed from 20 minutes during Weeks 1-4 to 30 minutes during Weeks 5-8 and 40 minutes during Weeks 9-12. Intensity progressed from 40%-50% of estimated one-repetition maximum during Weeks 1-6 to 50%-60% during Weeks 7-12. One-repetition maximum was estimated from a 10-15 repetition-maximum test using the Brzycki equation: estimated 1RM = load/[1.0278 - (0.0278 × number of repetitions)].

Exercise sessions included a 5-10-minute warm-up and cool-down period. Heart-rate monitors, supervised instruction, standardized exercise demonstrations, and safety monitoring were used to maintain the prescribed intensity and intervention quality. Measurements were obtained before the intervention and after 12 weeks. The main analysis assessed within-participant change from baseline, and exploratory analyses compared changes among genotype groups. For variables with significant baseline differences, analysis of covariance was performed using the baseline value as a covariate.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Sport University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with type 2 diabetes mellitus.
2. No regular exercise training during the previous six months.
3. Aged 65 to 79 years.
4. Self-reported memory decline and Montreal Cognitive Assessment score <26.
5. Stable antidiabetic medication use and stable dietary control.
6. Participant or family member provided informed consent.

Exclusion Criteria:

1. Diabetic ketoacidosis within the previous three months.
2. Visual or hearing impairment or other conditions affecting cognitive assessment.
3. Fracture, limb disability, or other motor disorders affecting exercise participation.
4. History of psychiatric disorders.
5. History of stroke, brain tumor, hypothyroidism, or other diseases that may affect cognitive function.
6. Poor compliance or failure to follow the prescribed diet or exercise requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combined Aerobic and Resistance Exercise; Participants received a 12-week combined aerobic and resistance exercise program, including aerobic exercise four times per week and elastic-band resistance exercise twice per week. Exercise intensity and duration were progressively increased during the intervention.

Behavioral: Combined aerobic and resistance exercise; A 12-week combined exercise program including aerobics and elastic-band resistance training. Aerobic exercise was performed four times per week, with intensity progressing from 50%-60% HRmax during weeks 1-6 to 60%-70% HRmax during weeks 7-12. Resistance exercise was performed twice per week using elastic bands, with intensity progressing from 40%-50% 1RM during weeks 1-6 to 50%-60% 1RM during weeks 7-12. Exercise duration gradually increased from 20 minutes to 40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycated Hemoglobin at 12 Weeks	Change in glycated hemoglobin percentage from baseline to the end of the 12-week exercise intervention.	Baseline and 12 weeks
Change From Baseline in Fasting Plasma Glucose at 12 Weeks	Change in fasting plasma glucose concentration from baseline to the end of the 12-week exercise intervention.	Baseline and 12 weeks
Change From Baseline in Montreal Cognitive Assessment Total Score at 12 Weeks	Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). The instrument contains 12 tasks covering eight cognitive domains. The total score is reported on a scale ranging from 0 to 30 points. In accordance with the study protocol, 1 point was added for participants with 12 or fewer years of education. Higher scores indicate better cognitive function. Change from baseline was calculated as the Week 12 score minus the baseline score; a positive change indicates improvement in cognitive function.	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Insulin at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Total Cholesterol at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Triglycerides at 12 Weeks		Baseline and 12 weeks
Change From Baseline in High-Density Lipoprotein Cholesterol at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Low-Density Lipoprotein Cholesterol at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Body Weight at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Muscle Mass at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Body Mass Index at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Body Fat Percentage at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Vital Capacity Measured Using a GMCS-FHL3 Vital Capacity Tester at 12 Weeks	Vital capacity was measured in milliliters using a GMCS-FHL3 vital capacity tester manufactured by Beijing Xindong Huateng Sports Equipment Co., Ltd. Participants were tested in a standing position. After taking several deep breaths, each participant inhaled maximally and then exhaled continuously and completely through the mouthpiece without taking an additional breath. Two trials were performed, and the highest recorded value was used for analysis. Higher values indicate better respiratory function. Change from baseline was calculated as the Week 12 value minus the baseline value; a positive change indicates improvement.	Baseline and 12 weeks
Change From Baseline in Relative Handgrip Strength, Calculated as Maximum Handgrip Strength Divided by Body Weight, at 12 Weeks	Maximum handgrip strength was measured in kilograms using a GMCS-WCS3 digital handgrip dynamometer manufactured by Beijing Xindong Huateng Sports Equipment Co., Ltd. Participants were assessed while standing upright with the tested arm naturally extended beside the body without touching the trunk. Each hand was tested twice, and the highest value obtained across the four trials was used. Relative handgrip strength was calculated as maximum handgrip strength in kilograms divided by body weight in kilograms and was reported as a dimensionless kg/kg ratio. This is a continuous physiological ratio rather than a bounded questionnaire scale. Its theoretical minimum is 0, and it has no fixed maximum. Higher values indicate greater handgrip strength relative to body weight. Change from baseline was calculated as the Week 12 ratio minus the baseline ratio; a positive change indicates improvement.	Baseline and 12 weeks
Change From Baseline in Sit-and-Reach Performance at 12 Weeks		Baseline and 12 weeks
Change From Baseline in 30-Second Sit-to-Stand Performance at 12 Weeks		Baseline and 12 weeks
Change From Baseline in One-Legged Standing With Eyes Closed at 12 Weeks		Baseline and 12 weeks
Change From Baseline in Choice Reaction Time at 12 Weeks		Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Harbin Sport University
• Investigators: Principal Investigator: Nijia Meng, Associate Professor, Harbin Sport University; Study Director: Xichao Zhang, Harbin Sport University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Aerobic exercise; Type 2 diabetes mellitus; Cognitive impairment; Montreal Cognitive Assessment; adults; Resistance exercise; Genetic polymorphism; Older; Exercise intervention; Health-related physical fitness; Glycolipid metabolism; PPARGC1A; rs8192678
• Additional Relevant MeSH Terms: Endocrine System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Glucose Metabolism Disorders; Diabetes Mellitus; Cognition Disorders; Nutritional and Metabolic Diseases; Cognitive Dysfunction; Diabetes Mellitus, Type 2
• Other Study ID Numbers: HSU-2025115-PPARGC1A-T2DMCI

Drug and device information, study documents

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