Individual Response Variation in the Effects of Weight Loss and Exercise on Insulin Sensitivity and Cardiometabolic Risk in Older Adults

Abstract

Weight loss induced by decreased energy intake (diet) or exercise generally has favorable effects on insulin sensitivity and cardiometabolic risk. The variation in these responses to diet-induced weight loss with or without exercise, particularly in older obese adults, is less clear. The objectives of our study were to (1) examine the effect of weight loss with or without exercise on the variability of responses in insulin sensitivity and cardiometabolic risk factors and (2) to explore whether baseline phenotypic characteristics are associated with response. Sedentary older obese (BMI 36.3 ± 5.0 kg/m 2) adults (68.6 ± 4.7 years) were randomized to one of 3 groups: health education control (HED); diet-induced weight loss (WL); or weight loss and exercise (WL + EX) for 6 months. Composite Z-scores were calculated for changes in insulin sensitivity (C_IS: rate of glucose disposal/insulin at steady state during hyperinsulinemic euglycemic clamp, HOMA-IR, and HbA1C) and cardiometabolic risk (C_CMR: waist circumference, triglycerides, and fasting glucose). Baseline measures included body composition (MRI), cardiorespiratory fitness, in vivo mitochondrial function (ATPmax; P-MRS), and muscle fiber type. WL + EX groups had a greater proportion of High Responders in both C_IS and C_CMR compared to HED and WL only (all p < 0.05). Pre-intervention measures of insulin (r = 0.60) and HOMA-IR (r = 0.56) were associated with change in insulin sensitivity (C_IS) in the WL group (p < 0.05). Pre-intervention measures of glucose (r = 0.55), triglycerides (r = 0.53), and VLDL (r = 0.53) were associated with change in cardiometabolic risk (C_CMR) in the WL group (p < 0.05), whereas triglycerides (r = 0.59) and VLDL (r = 0.59) were associated with C_CMR (all p < 0.05) in WL + EX. Thus, the addition of exercise to diet-induced weight loss increases the proportion of older obese adults who improve insulin sensitivity and cardiometabolic risk. Additionally, individuals with poorer metabolic status are more likely to experience greater improvements in cardiometabolic risk during weight loss with or without exercise.

Sodium-Glucose Co-Transporter-2 Inhibitors in Non-Diabetic Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis

“…Additionally, the discontinuation rate was high due to some safety issues. Thirdly, This meta-analysis showed SGLT2 inhibitors can reduce average 1.42kg body weight in adults with overweight or obesity but not diabetes, but the clinical and prognostic benefit of weight change were limited base on the previous studies (34)(35)(36). Thus, larger sample sizes with longer durations of observation are needed to clarify the long-term benefits and risks of SGLT2 inhibitors in the treatment of adults with overweight or obesity but not diabetes.…”

Outcomes addressed in randomized controlled lifestyle intervention trials in community‐dwelling older people with (sarcopenic) obesity—An evidence map

“…Of 57,721 unique records, 109 articles of 54 studies were included in the evidence map as they provided information on outcomes assessed (Figure 1 and Table S4). 34–87 The unique accession numbers from all database searches are available upon request.…”

“…The “Healthy Aging Index” reported by Shaver et al (2018) (reported at baseline and after 6 months of intervention) comprises biomarkers plus a cognitive function measure 90 . The cardiometabolic risk factor z score reported by Brennan et al (2020) comprised anthropometric, body composition, and biomarkers outcomes 40 . Muscle quality comprised functional and body composition outcomes.…”

Interindividual Variability in Fat Mass Response to a 1-Year Randomized Controlled Trial With Different Exercise Intensities in Type 2 Diabetes: Implications on Glycemic Control and Vascular Function

“…In an era of personalized lifestyle-based medicine and with an increase in the number of interventions focused on the interindividual variability of several cardiometabolic risk factors in response to exercise ( Alvarez et al, 2017 ; Solomon, 2018 ; Brennan et al, 2019 ; Ross et al, 2019 ; Hetherington-Rauth et al, 2020a ; Brennan et al, 2020b ), there is a clear need to have a control group to differentiate the inevitable within-subject random variability due to biological error and the technical error of measurement from the variability resulting from the exercise intervention. A major strength of the D2FIT study was its long-term RCT design in individuals with T2DM, which follows the recent consensus statement recommendations, highlighting the importance of using a control group ( Ross et al, 2019 ; Padilla et al, 2021 ).…”