Association between metformin and physical activity with glucose control in adults with type 2 diabetes

Abdalhk, Diana; Riddell, Michael C.; Swayze, Sarah; Kuk, Jennifer L.

doi:10.1002/edm2.206

Cited by 3 publications

References 22 publications

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N-of-1 analysis of circadian data reveals potential for precision chrono-medicine approach of concomitant exercise and metformin recommendations

Lyons,

Peña Carrillo,

Dasar

et al. 2024

Preprint

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The integration of chrono-medicine into disease management has potential for cost-effective improvements, particularly in type 2 diabetes care. While both exercise and metformin are effective in lowering glycaemia, their combined effect is non-additive. Individual circadian rhythms suggest that personalised timing of interventions may optimise outcomes. This study aims to investigate the heterogeneity in response to the timing of exercise and metformin intake using an n-of-1 approach within a randomised crossover trial, thereby exploring the potential for individualised chrono-medicine strategies. A previously published 16-week randomised crossover study was conducted to explore the potential therapeutic effects of prescribed moderate exercise timings in participants undergoing metformin monotherapy. Physical activity, heart rate, sleep, and glucose levels were tracked using wearable technology and continuous glucose monitors. Data were collected during baseline, and throughout the intervention periods. Analysis focused on individual responses to the timing of exercise and metformin intake. Morning exercise significantly lowered 24-hour post-exercise blood glucose levels compare to evening exercise. Both exercise timings reduced mean blood glucose levels, but morning exercise had a greater effect (mean difference: -0.63 mmol/L, p<0.001) than evening exercise (mean difference: -0.34 mmol/L, p=0.016). Individual responses varied, with some participants displaying a substantial reduction in glucose levels in response to morning or evening exercise, while others did not benefit from either exercise intervention. Pre-breakfast metformin intake significantly lowered area under the curve (AUC) glucose values in response to morning exercise compared to post-breakfast, an effect not observed with evening exercise. Morning exercise combined with pre-breakfast metformin intake is the most effective strategy for lowering blood glucose levels in the greatest number of participants with type 2 diabetes. However, individual response heterogeneity suggests that chrono-medicine approaches must be personalised. Further research is needed to understand the underlying mechanisms of individual variability in response to exercise and medication timing.

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N-of-1 analysis of circadian data reveals potential for precision chrono-medicine approach of concomitant exercise and metformin recommendations

Lyons,

Peña Carrillo,

Dasar

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Morning exercise and pre‐breakfast metformin interact to reduce glycaemia in people with type 2 diabetes: a randomized crossover trial

Carrillo,

Cope,

Gurel

et al. 2024

The Journal of Physiology

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Exercise is recommended in the treatment of type 2 diabetes and can improve insulin sensitivity. However, previous evidence suggests that exercise at different times of the day in people with type 2 diabetes may have opposing outcomes on glycaemia. Metformin is the most commonly prescribed initial pharmacological intervention in type 2 diabetes, and may alter adaptions to exercise. It is unknown if there is an interaction between metformin and diurnal exercise outcomes. We aimed to investigate glycaemic outcomes of moderate intensity morning vs. evening exercise in people with type 2 diabetes being prescribed metformin monotherapy. In this study, nine males and nine females with type 2 diabetes undergoing metformin monotherapy (age 61 ± 8.2 years, mean ± SD) completed a 16‐week crossover trial including 2‐week baseline recording, 6 weeks randomly assigned to a morning exercise (07.00–10.00 h) or evening exercise (16.00–19.00 h) and a 2‐week wash‐out period. Exercise arms consisted of 30 min of walking at 70% of estimated max heart rate every other day. Glucose levels were measured with continuous glucose monitors and activity measured by wrist‐worn monitors. Food‐intake was recorded by 4‐day food diaries during baseline, first and last 2 weeks of each exercise arm. There was no difference in exercise intensity, total caloric intake or total physical activity between morning and evening arms. As primary outcomes, acute (24 h) glucose area under the curve (AUC), was lower (P = 0.02) after acute morning exercise (180.6 ± 68.4 mmol/l) compared to baseline (210.3 ± 76.7 mmol/l); and there were no differences identified for glucose (mmol/l) between baseline, morning and evening exercise at any specific time point when data were analysed with two‐way ANOVA. As secondary outcomes, acute glucose AUC was significantly lower (P = 0.01) in participants taking metformin before breakfast (152.5 ± 29.95 mmol/l) compared with participants taking metformin after breakfast (227.2 ± 61.51 mmol/l) only during the morning exercise arm; and during weeks 5–6 of the exercise protocol, glucose AUC was significantly lower (P = 0.04) for participants taking metformin before breakfast (168.8 ± 15.8 mmol/l), rather than after breakfast (224.5 ± 52.0 mmol/l), only during morning exercise. Our data reveal morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. This beneficial effect upon glucose levels of combined morning exercise and pre‐breakfast metformin persisted through the final 2 weeks of the trial. Our findings suggest that morning moderate intensity exercise combined with pre‐breakfast metformin intake may benefit the management of glycaemia in people with type 2 diabetes. imageKey points Morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. Morning exercise combined with pre‐breakfast metformin persistently reduced glucose compared to morning exercise combined with post‐breakfast metformin through the final week (week 6) of the intervention. Our study suggests it may be possible to make simple changes to the time that people with type 2 diabetes take metformin and perform exercise to improve their blood glucose.

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Relationship Between Blood Glucose and Hemoglobin A1c Levels and Urinary Incontinence in Women

Liu

Mao

et al. 2021

IJGM

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Objective The purpose of this study was to evaluate the associations between blood glucose and hemoglobin A1c (HbA1c) levels with the degree of stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) in women. Methods We conducted a cross-sectional study of female participants in the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2012. Univariate and multivariate logistic regressions were used to assess the relationship between blood glucose and HbA1c levels and the degree of SUI and UUI. Results A total of 3821 participants were enrolled in the study, of whom 2421 (63.4%) had no SUI, 1133 (29.7%) had monthly SUI, 267 (7.0%) had weekly SUI; 2883 (75.5%) had no UUI, 735 (19.2%) had monthly UUI, 203 (5.3%) had weekly UUI. The levels of blood glucose and HbA1c were positively correlated with SUI and UUI, and increased with increasing degree of UUI. Multivariate logistic regression showed that there was a positive association between blood HbA1c level and degree of SUI. Conclusion Our study found that blood glucose and HbA1c levels can be used as indicators of SUI and UUI severity in women.

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Association between metformin and physical activity with glucose control in adults with type 2 diabetes

Cited by 3 publications

References 22 publications

N-of-1 analysis of circadian data reveals potential for precision chrono-medicine approach of concomitant exercise and metformin recommendations

N-of-1 analysis of circadian data reveals potential for precision chrono-medicine approach of concomitant exercise and metformin recommendations

Morning exercise and pre‐breakfast metformin interact to reduce glycaemia in people with type 2 diabetes: a randomized crossover trial

Relationship Between Blood Glucose and Hemoglobin A1c Levels and Urinary Incontinence in Women

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