Phenotypic Responses to a Lifestyle Intervention Do Not Account for Inter-Individual Variability in Glucose Tolerance for Individuals at High Risk of Type 2 Diabetes

Abstract

Background: Lifestyle interventions have been shown to delay or prevent the onset of type 2 diabetes among high risk adults. A better understanding of the variability in physiological responses would support the matching of individuals with the best type of intervention in future prevention programmes, in order to optimize risk reduction. The purpose of this study was to determine if phenotypic characteristics at baseline or following a 12 weeks lifestyle intervention could explain the inter-individual variability in change in glucose tolerance in individuals with high risk for type 2 diabetes. Methods: In total, 285 subjects with normal glucose tolerance (NGT, FINDRISC score > 12), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were recruited for a 12 weeks lifestyle intervention. Glucose tolerance, insulin sensitivity, anthropometric characteristics and aerobic fitness were measured. Variability of responses was examined by grouping participants by baseline glycemic status, by cluster analysis based on the change in glucose tolerance and by Principal Component Analysis (PCA). Results: In agreement with other studies, the mean response to the 12 weeks intervention was positive for the majority of parameters. Overall, 89% improved BMI, 80% waist circumference, and 81% body fat while only 64% improved fasting plasma glucose and 60% 2 h glucose. The impact of the intervention by glycaemic group did not show any phenotypic differences in response between NGT, IFG, and IGT. A hierarchical cluster analysis of change in glucose tolerance identified four sub-groups of “responders” (high and moderate) and “non-responders” (no response or deteriorated) but there were few differences in baseline clincal and physiological parameters or in response to the intervention to explain the overall variance. A further PCA analysis of 19 clinical and physiological univariables could explain less than half (48%) of total variability. Conclusion: We found that phenotypic characteristics from standard clinical and physiological parameters were not sufficient to account for the inter-individual variability in glucose tolerance following a 12 weeks lifestyle intervention in inidivuals at high risk for type 2 diabetes. Further work is required to identify biomarkers that complement phenotypic traits and better predict the response to glucose tolerance.

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

“…Another challenge for countermeasure design and implementation is the individual variation in response to lifestyle interventions (Bouchard and Rankinen, 2001;Solomon, 2018;O'Donoghue et al, 2019). While a specific exercise program may, on average, be effective there can be a broad range in the individual response.…”

“…Interestingly, the improvement in insulin sensitivity was greater in the CTRL group than in the JUMP group. It has previously been highlighted that there is substantial inter-individual variability in physiological responses following lifestyle interventions (Bouchard and Rankinen, 2001;Solomon, 2018;O'Donoghue et al, 2019). In addition, the genes and pathways underlying the response to exercise training and physical inactivity differ (Booth et al, 2012;Pillon et al, 2020).…”

Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia

“…[18][19][20][21][22] We cannot assume outcomes of earlier trials (in different high risk glycemic populations with IGT), are simply translatable to populations with current high risk intermediate glycemic categories , who differ in pathophysiology, progression rates, and vascular risk. [24][25][26][27] The diabetes prevention benefit found in the earlier high intensity landmark trials [19][20][21][22] has been much less marked in 'real world' pragmatic interventions. 28,29 This means that although there is a need for lower cost, more pragmatic intervention models, the current evidence to support their effectiveness is limited.…”

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

“…However, not all findings are consistent with the aforementioned results. Recent findings wherein 285 participants aged 18-75 years participated in a 12-week lifestyle intervention including both dietary and exercise guidance suggested that those who experienced greater improvement in glucose tolerance presented with higher baseline weight, visceral fat, fasting glucose, and triglyceride concentration compared to those who did not respond (9). Thus, it is unclear whether and how baseline phenotypes influence insulin sensitivity responses to diet and exercise-induced weight loss, and response likely depends on multiple factors.…”