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To the Editor: Increased daily physical activity is associated with improved health,¹ but it is uncertain whether it prevents initial metabolic events that produce chronic diseases. We are aware of no evidence in healthy, young adults that reduced daily stepping within a free-living environment is associated with negative metabolic consequences. The purpose of this study was to reduce daily steps and assess metabolic changes.

Methods
Participants were recruited for 2 substudies by advertisement and received compensation. Inclusion criteria were asymptomatic nonsmokers without family history of diabetes mellitus, medication use, or physical abnormalities; exclusion criteria were walking fewer than 3500 steps per day measured over 1 week (Yamax Digi-Walker SW-200 pedometer; Great Performance Ltd, London, United Kingdom) or performing more than 2 hours of regular exercise per week. The studies were approved by the local scientific-ethical committee, and participants provided written informed consent.

Participants were instructed to reduce daily steps by taking elevators instead of stairs and riding in cars instead of walking or bicycling. In substudy 1, 8 men (mean [SD] age, 27.1 [5.7] y; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 22.9 [4.0]) decreased their pedometer-recorded daily steps from a mean value of 6203 to 1394 with outcome measurements made preintervention and at 7, 14, and 22 days into intervention (Table; Figure). In substudy 2, 10 men (mean [SD] age, 23.8 [4.6] y; mean [SD] body mass index, 22.1 [2.1]) reduced daily steps from a mean value of 10 501 to 1344 with measurements made preintervention and at 2 weeks (Table; Figure). Dietary records were kept before and throughout the studies to ensure that habitual dietary intakes were maintained.

View this table: [in this window] [in a new window] [as a PowerPoint slide]   Table. Changes in Metabolic and Physical Characteristics With Reduced Daily Steps

View larger version (29K): [in this window] [in a new window] [as a PowerPoint slide]   Figure. Preintervention and Postintervention Step Count for Each Participant Squares indicate mean values.

We performed a 3-hour oral glucose (75 g) tolerance test (day 1 preintervention [substudy 1 and 2]; days 7, 14, and 22 postintervention [substudy 1]; day 14 postintervention [substudy 2]) and an 8-hour oral fat tolerance test (2 mL/kg Calogen; Nutricia, Allerød, Denmark) (day 3 preintervention and day 12 postintervention [substudy 2]). Blinded plasma analyses for triglycerides (substudy 2) were obtained with a Cobas-Fara automatic analyzer (Roche, Basel, Switzerland) and insulin (substudy 1 and 2) and C-peptide (substudy 2) by enzyme-linked immunosorbent assay (DAKO, Glostrup, Denmark); areas under the curve (AUC) were calculated. A 3-Tesla Siemens Magnetom Total imaging matrix magnetic resonance scanner (Siemens, Erlangen, Germany) determined intra-abdominal fat (days 1-8 preintervention and days 12-14 postintervention [substudy 2]) and a GE Lunar Prodigy Advance DXA scanner (GE Healthcare, Madison, Wisconsin) determined body composition (day 3 preintervention and day 12 postintervention [substudy 2]). The absence of previous studies on these outcomes precluded power analysis. A 2-sided P value of .05 or less was considered significant. Analyses indicated in the table were performed using SAS version 9.1 (SAS Institute Inc, Cary, North Carolina).

Results
For the oral glucose tolerance test in substudy 1, plasma insulin AUC increased from 757 pmol/L/3h (95% confidence interval [CI], 488-1026 pmol/L/3h) atbaseline to 1352 pmol/L/3h (95% CI, 1025-1678 pmol/L/3h) at 3 weeks (P = .004) (Table). In substudy 2, over 2 weeks there was an increase in both plasma insulin AUC (from 599 pmol/L/3h [95% CI, 489-709 pmol/L/3h] to 942 pmol/L/3h [95% CI, 443-1440 pmol/L/3h]; P = .04) and plasma C-peptide AUC (from 4310 pmol/L/3h [95% CI, 3676-4944 pmol/L/3h] to 5795 pmol/L/3h [95% CI, 3911-7678 pmol/L/3h]; P = .03) (Table). For the oral fat tolerance test, the AUC for plasma insulin, C-peptide, and triglycerides increased (Table).

The intervention in substudy 2 was associated with a 7% increase in intra-abdominal fat mass (from 693 mL [95% CI, 485-902 mL] to 740 mL [95% CI, 552-929 mL]; P = .046) without a change in total fat mass while total fat-free mass and body mass index decreased (Table).

Comment
In this preliminary study, a group of young healthy men decreased their daily stepping for 2 to 3 weeks to 1500 steps from the range recommended for US adults of around 10 000² or from 6000 steps. In this time, they developed metabolic changes suggestive of decreased insulin sensitivity³ and attenuation of postprandial lipid metabolism⁴ and physical changes that suggest that calories used to maintain muscle mass with greater stepping may have been partitioned to visceral fat.⁵ If confirmed, these abnormalities could represent a link between reduced exercise and the risks that have been associated with the progression of chronic disorders and premature mortality.⁶

Author Contributions: Dr Krogh-Madsen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Olsen, Krogh-Madsen, Thomsen, Pedersen.

Acquisition of data: Olsen, Krogh-Madsen, Thomsen, Pedersen.

Analysis and interpretation of data: Olsen, Krogh-Madsen, Thomsen, Booth, Pedersen.

Drafting of the manuscript: Olsen, Krogh-Madsen, Thomsen, Booth, Pedersen.

Critical revision of the manuscript for important intellectual content: Olsen, Krogh-Madsen, Thomsen, Booth, Pedersen.

Statistical analysis: Krogh-Madsen, Booth.

Obtained funding: Pedersen.

Administrative, technical, or material support: Olsen, Krogh-Madsen, Thomsen, Pedersen.

Study supervision: Pedersen.

Financial Disclosures: None reported.

Funding/Support: The study was supported by the Commission of the European Communities (contract LSHM-CT-2004-005272 EXGENESIS) and by grants from the Augustinus Foundation and from Unilever. Dr Olsen received a scholarship from the Danish Research Council. The Centre of Inflammation and Metabolism is supported by grant DG 02-512-555 from the Danish National Research Foundation.

Role of the Sponsors: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Additional Contributions: We acknowledge the uncompensated contributions by Remi Mounier, PhD (Centre of Inflammation and Metabolism, Rigshospitalet, University of Copenhagen, Denmark), for assistance during the trials; Richard W. Madsen, PhD (University of Missouri, Columbia), for statistical advice; and John P. Thyfault, PhD (Research Service, Harry S Truman Memorial Veterans Affairs Hospital, University of Missouri), for advice on the manuscript.

Rasmus H. Olsen, MD; Rikke Krogh-Madsen, MD
krogh-madsen{at}inflammation-metabolism.dk
Centre of Inflammation and Metabolism

Carsten Thomsen, MD, DMSc
Department of Radiology
Rigshospitalet
University of Copenhagen
Copenhagen, Denmark

Frank W. Booth, PhD
Health Activity Center
Department of Biomedical Sciences
University of Missouri
Columbia

Bente K. Pedersen, MD, DMSc
Centre of Inflammation and Metabolism
Rigshospitalet
University of Copenhagen

1. Chakravarthy MV, Joyner MJ, Booth FW. An obligation for primary care physicians to prescribe physical activity to sedentary patients to reduce the risk of chronic health conditions. Mayo Clin Proc. 2002;77(2):165-173. FREE FULL TEXT 2. Bravata DM, Smith-Spangler C, Sundaram V; et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA. 2007;298(19):2296-2304. FREE FULL TEXT 3. Kahn CR, Vicent D, Doria A. Genetics of non–insulin-dependent (type-II) diabetes mellitus. Annu Rev Med. 1996;47:509-531. FULL TEXT | ISI | PUBMED 4. Ginsberg HN, Illingworth DR. Postprandial dyslipidemia: an atherogenic disorder common in patients with diabetes mellitus. Am J Cardiol. 2001;88(6A):9H-15H. ISI | PUBMED 5. McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest. 2002;109(5):595-601. FULL TEXT | ISI | PUBMED 6. Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol. 2002;93(1):3-30. FREE FULL TEXT

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2008;299(11):1261-1263.

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