The two specific aims of the study were to determine whether: 1. Greater mechanical loading of downhill exercise will increase the osteogenic index (ratio between CICP, the marker of bone formation (c-terminal propeptide of type I collagen, and CTX, the marker of bone resorption (c terminal telopeptide of type I collagen)) to a greater extent than uphill exercise that provides lower ground-reaction force; 2. Exercise after the meals will induce greater osteogenic response than exercise pefore the meals as it is known that meal eating during daytime inhibits bvone resorption markers.
The study addresses the problem that postmenopausal women with type 2 diabetes have a higher incidence of bone breaks despite their often normal bone mineral density (BMD). The investigators pursued two hypotheses, that: 1. 40-minute bout of downhill exercise will increase the CICP/CTX osteogenic index to a greater extent than the same amount of uphill exercise; and 2. Performing exercise one hour after the meals will be more osteogenic than exercise before the meals. Subjects were 15 postmenopausal women with type 2 diabetes, age 57.7 years, BMI 27.2 kg/m2 who were randomly assigned to two out of 5 trials: Uphill exercise before the meals (UBM), Uphill exercise after the meals (UAM), Downhill exercise before the meals (DBM), Downhill exercise after the meals (DAM), and Sedentary, no-exercise, trial (SED). All subjects signed an informed consent approved by the University of Michigan Medical School Institutional Review Board. Subjects had their BMD measured with DXA at the outset. Weight-maintenance meals contained 50% carbohydrate, 15% protein, and 25% fat and were provided at 10 h and 17 h. Exercise (40 minutes at 50% of maximal effort) on either uphill (+6o slope) or downhill treadmill (-6o slope) was performed either before the two meals, at 9 h and 16 h, respectively, or after the meals. at 11 h and 18 h, respectively. Blood was drawn through an intravenous catheter from ante-cubital vein at hourly intervals between 8 and 20 h with two additional blood draws at 0 h and 6 h the next morning. Blood was treated with protease inhibitors, and plasma, frozen at -80o C, was used to measure bone markers, CICP, CTX, osteocalcin , and bone-specific alkaline phosphatase using Millipore chemoluminescen reagents, glucose by glucose oxidase, and hormones insulin, cortisol, parathyroid hormone (PTH) , and growth hormone (GH) by radio-immunoassays.. Mixed-model ANOVA was used for analysis of outcome measures where the trial procedures served as fixed variable and individual subjects as intercept variables.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
40 minutes of uphill exercise
40 minutes of uphill exercise completed 1 h before the meal
40 minutes of uphill exercise
C-terminal propeptide of type I collagen
Change over time in plasma concentration of c-terminal propeptde of type 1 collagen (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
C-terminal telopeptide of type 1 collagen
Change over time in plasma concentration of c-terminal telopeptide of type 1 collagen (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Osteocalcin
Change over time in plasma concentration of osteocalcin (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Bone-specific alkaline phosphatase
Change over time in plasma concentration of bone-specific alkaline phosphatase (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Insulin
Change over time in plasma concentration of insulin (µU/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Parathyroid hormone
Change over time in plasma concentration of parathyroid hormone (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Cortisol
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40 minutes of uphill exercise started 1 hour after gthe meal
40 minutes of downhill exercise
40 minutes of downhill exercise completed 1 hour before the meal
40 minutes of downhill exercise
40 minutes of downhill exercise started 1 hour after the meal
Sedentary no-exercise trial
Meals eaten at 10 and 17 h during a sedentary trial
Change over time in plasma concentration of cortisol (m/L)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Growth hormone
Change over time in plasma concentration of growth hormone (ng/ml)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Glucose
Change over time in plasma concentration of glucose (mg/dl)
Time frame: Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial
Dual-energy X-ray radiography
Whole-body dual-energy X-ray radiography scan
Time frame: A week prior to the study baseline
Novel Pedar
Mechanosensitive shoe inserts for measurement of ground reaction force
Time frame: During two one-hour bouts of the exercise intervention