Physical Activity and Inflammatory Markers in Prediabetes

A systematic review and meta-analysis of randomized controlled trials examines how some inflammatory markers may be affected by physical activity.

Prediabetes is when the blood glucose level is more than a normal range but less than the range to confirm type 2 diabetes (T2DM). Prediabetes inflammatory stages are associated with an increased level of adipokines and pro-inflammatory cytokines. A pro-inflammatory state in prediabetes occurs predominantly because of the increase in insulin resistance. Physical activity is considered the first-line treatment for many disease states, and it is the first-line therapeutic strategy to treat prediabetes.  Previous studies have analyzed the impact of physical activity on glycemic levels and the resulting reduction in aggravation of prediabetes to T2D. The effect of lifestyle interventions like physical activity on different inflammatory markers has been documented in long-term clinical trials. A systematic review and meta-analysis were conducted to strengthen the evidence on the impact of physical activity promotion on inflammatory markers in prediabetes. 

Physical activity interventions that were provided for patients diagnosed with prediabetes in randomized controlled trials were included in this review. The study included 1,906 prediabetic individuals diagnosed by either the ADA criteria or WHO, both male and female, 20 to 70 years of age. Individuals diagnosed with T2D and standard glucose tolerance were excluded from the study. Studies published in languages other than English and animal studies were excluded from search filters. Outcome measures that were considered included adiponectin, leptin, C-reactive protein interleukin-6, and tumor necrosis factor-α. Electronic search and manual search techniques using keywords and subject headings for prediabetes, physical activity, and inflammatory markers were used to identify eligible primary studies. The studies included interventions in the form of physical activity promotion, including supervised activity sessions or home-based physical activity. Other activities included any multiple or single forms of physical activity administered in the scheduled activity, supervised training, and weight-loss interventions. Dietary advice, counseling, and lifestyle modification were also included. Any pharmacological intervention along with physical activity was excluded. The studies considered physical activity with no interventions and usual care. For assessing the risk of bias in included studies, one author resolved disagreements, and another two evaluated the risk of bias included in the studies. Nine studies were included in the review. 

The search retrieved electronic and manual searches of 1,688 citations, and 1,245 records were screened after duplicate removal. Physical activities and diet were encouraged in two studies, and another two encouraged scheduled activities of 140 hours. One study promoted weight loss through physical activities and dietary modifications. Other physical activity interventions included ≥ 30 min/day of moderate to vigorous exercise, Nordic walking, walking plus resistance exercise, and physical activity promotions with and without a pedometer. The interventions were three months, six months, one year, and five years. The control group was advised on the benefits of exercise, diabetes risk, consequences, and symptoms. The comparison included eight studies comparing physical activity without or with dietary or lifestyle modifications versus usual care. One study compared physical activity without or with dietary or lifestyle change versus no intervention. 

Four studies measured adiponectin levels after three months, four months, and one year of intervention; adiponectin was not affected by physical activity (95% CI -0.42 to 0.93). Leptin levels were measured in five studies after three months, four months, one year, and one study after five years of intervention. Leptin levels in individuals with prediabetes were reduced by physical activity (95% CI -3.81 to -0.42). C-reactive protein (CRP) was measured in four studies after one year and one study after five years of intervention. Physical activity did not affect CRP levels in patients with prediabetes (95% CI -0.33 to 0.23). Interleukin- 6 (IL-6) was measured after one year, four months, and one study after three months of interventions in five studies (95% CI -0.25 to -0.04). Tumor necrosis factor-α (TNF-α) after three months, four months, and one year of interventions in three studies. TNF-α in individuals with prediabetes was not affected by physical activity (95% CI -2.56 to 3.89). Physical activity without or with dietary or lifestyle modification versus no intervention provided two outcomes for adiponectin and leptin. Physical activity only reduced leptin levels in individuals with prediabetes, and the interventions did not affect adiponectin. 

The effect of exercise on pro-inflammatory cytokines has been inconsistent. The results suggested that physical activity may reduce the level of leptin and IL-6. The effect on other pro-inflammatory cytokines in patients with prediabetes is uncertain. 

Practice Pearls: 

• The results show that physical activity may reduce the level of leptin and IL-6. 
• Adiponectin was not affected by physical activity  
• The effect of exercise on other pro-inflammatory cytokines in patients with prediabetes is uncertain.  

Jadhav, Radhika Aditya. et al. Effect of physical activity promotion on adiponectin, leptin and other inflammatory markers in prediabetes: a systematic review and meta‑analysis of randomized controlled trials. Acta Diabetologica; April 2021. 

Author: Brenda Oppong, PharmD Candidate, LECOM School of Pharmacy