Lifestyle precision medicine: the next generation in type 2 diabetes prevention?

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Abstract

The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Traditionally, chronically elevated blood glucose concentrations have been the hallmark of diabetes; however, many individuals will either remain ‘prediabetic’ or regress to normoglycemia. Thus, there is a growing need for innovative strategies to tackle diabetes at scale. The emergence of biomarker technologies has allowed more targeted therapeutic strategies for diabetes prevention (precision medicine), though largely confined to pharmacotherapy. Unlike most drugs, lifestyle interventions often have systemic health-enhancing effects. Thus, the pursuance of lifestyle precision medicine in diabetes seems rational. Herein, we review the literature on lifestyle interventions and diabetes prevention, describing the biological systems that can be characterized at scale in human populations, linking them to lifestyle in diabetes, and consider some of the challenges impeding the clinical translation of lifestyle precision medicine.

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Most cited references 95

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Methods of integrating data to uncover genotype-phenotype interactions.

Marylyn D Ritchie, Emily R. Holzinger, Ruowang Li … (2015)

Recent technological advances have expanded the breadth of available omic data, from whole-genome sequencing data, to extensive transcriptomic, methylomic and metabolomic data. A key goal of analyses of these data is the identification of effective models that predict phenotypic traits and outcomes, elucidating important biomarkers and generating important insights into the genetic underpinnings of the heritability of complex traits. There is still a need for powerful and advanced analysis strategies to fully harness the utility of these comprehensive high-throughput data, identifying true associations and reducing the number of false associations. In this Review, we explore the emerging approaches for data integration - including meta-dimensional and multi-staged analyses - which aim to deepen our understanding of the role of genetics and genomics in complex outcomes. With the use and further development of these approaches, an improved understanding of the relationship between genomic variation and human phenotypes may be revealed.

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TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program.

Jose C Florez, Kathleen A Jablonski, Nick Bayley … (2006)

Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in which lifestyle intervention or treatment with metformin was compared with placebo. We genotyped these variants in 3548 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors. We assessed the effect of genotype on measures of insulin secretion and insulin sensitivity at baseline and at one year. Over an average period of three years, participants with the risk-conferring TT genotype at rs7903146 were more likely to have progression from impaired glucose tolerance to diabetes than were CC homozygotes (hazard ratio, 1.55; 95 percent confidence interval, 1.20 to 2.01; P<0.001). The effect of genotype was stronger in the placebo group (hazard ratio, 1.81; 95 percent confidence interval, 1.21 to 2.70; P=0.004) than in the metformin and lifestyle-intervention groups (hazard ratios, 1.62 and 1.15, respectively; P for the interaction between genotype and intervention not significant). The TT genotype was associated with decreased insulin secretion but not increased insulin resistance at baseline. Similar results were obtained for rs12255372. Common variants in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance. The risk-conferring genotypes in TCF7L2 are associated with impaired beta-cell function but not with insulin resistance. (ClinicalTrials.gov number, NCT00004992. [ClinicalTrials.gov]). Copyright 2006 Massachusetts Medical Society.

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An obesity-associated FTO gene variant and increased energy intake in children.

Joanne Cecil, Roger Tavendale, Peter Watt … (2008)

Variation in the fat mass and obesity-associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown. We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for FTO variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the FTO variant with adiposity, energy expenditure, and food intake. In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to obesity in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82). The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. 2008 Massachusetts Medical Society

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Author and article information

Contributors

Paul W. Franks: +4640391149 , paul.franks@med.lu.se

Journal

Journal ID (nlm-ta): BMC Med

Journal ID (iso-abbrev): BMC Med

Title: BMC Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1741-7015

Publication date (Electronic): 22 September 2017

Publication date PMC-release: 22 September 2017

Publication date Collection: 2017

Volume: 15

Electronic Location Identifier: 171

Affiliations

[1 ]ISNI 0000 0004 0623 9987, GRID grid.412650.4, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, , Lund University, Skåne University Hospital, ; SE-205 02 Malmö, Sweden

[2 ]ISNI 0000 0001 1034 3451, GRID grid.12650.30, Department of Public Health & Clinical Medicine, , Umeå University, ; Umeå, Sweden

[3 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Nutrition, , Harvard School of Public Health, ; Boston, MA USA

[4 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliff Department of Medicine, , University of Oxford, ; Oxford, UK

Article

Publisher ID: 938

DOI: 10.1186/s12916-017-0938-x

PMC ID: 5609030

PubMed ID: 28934987

SO-VID: 391fd76e-2990-463b-970c-666ebbd6eda9

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 10 May 2017

Date accepted : 30 August 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;

Award ID: CoG-2015_681742_NASCENT

Award Recipient : Paul W. Franks

Funded by: Innovative Medicines Initiative

Award ID: 115317; 115881

Award Recipient : Paul W. Franks

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: review,type 2 diabetes,lifestyle factors,overweight/obesity,precision medicine,biomarkers,intervention,prevention

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ScienceOpen disciplines: Medicine

Keywords: review, type 2 diabetes, lifestyle factors, overweight/obesity, precision medicine, biomarkers, intervention, prevention

Lifestyle precision medicine: the next generation in type 2 diabetes prevention?

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Tobacco Prevention & Cessation

Most cited references 95

Methods of integrating data to uncover genotype-phenotype interactions.

TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program.

An obesity-associated FTO gene variant and increased energy intake in children.

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