Preventing Diabetic Osteoporosis With Exercise

Study Overview
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Brief Summary
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The two specific aims of the study were to determine whether: 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; 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.

Detailed Description
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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: 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 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.

Official Title
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Parameters of Exercise to Prevent Type 2 Diabetic Osteoporosis in Postmenopausal Women

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Combination Product: Behavior intervention of uphill exercise
* Combination Product: Dietary intervention of exercise before the meal
* Combination Product: Dietary intervention of uphill exercise
* Combination Product: Dietary intervention of exercise after the meal
* Combination Product: Behavior intervention of downhill exercise
* Combination Product: Dietary intervention of exercise before the meal
* Combination Product: Behavioral intervention of downhill exercise
* Combination Product: Dietary intervention of exercise after the meal
* Combination Product: Behavioral intervention of sedentary no-exercise trial
* Combination Product: Dietary intervention of eating two meals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal type-2 diabetes melllitus age between 50 and 65 exercise less than 20 minutes three times a week Exclusion Criteria: metabolic disease other than type-2 diabetes and hormonally-corrected hypothyroidism musculo-skeletal disability that would preclude exercise smoker do not meet inclusion criteria

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Study consisted of 5 experimental trials (or arms), of which 4 were compared to a sedentary (or control) arm. The five trials were: Uphill exercise before the meals (UBM), Uphill exercise after the meals (UAM), Downhill exercise before the meals (DBM), and Downhill exercise after the meals (DAM), and the Sedentary (Sed) or control trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Uphill exercise before the meals<br>40 minutes of uphill treadmill exercise at +6o slope completed 1 hour before eating the meal | Combination Product: Behavior intervention of uphill exercise<br>* 40 minutes of uphill exercise<br>Combination Product: Dietary intervention of exercise before the meal<br>* 40 minutes of uphill exercise completed 1 h before the meal<br>|
| Experimental: Uphill exercise after the meals<br>40 minutes of uphill treadmill exercise at +6o slope started 1 hour after eating the meal | Combination Product: Dietary intervention of uphill exercise<br>* 40 minutes of uphill exercise<br>Combination Product: Dietary intervention of exercise after the meal<br>* 40 minutes of uphill exercise started 1 hour after gthe meal<br>|
| Experimental: Downhill exercise before the meals<br>40 minutes of downhill treadmill exercise at -6o slope completed 1 hour before eating the meal | Combination Product: Behavior intervention of downhill exercise<br>* 40 minutes of downhill exercise<br>Combination Product: Dietary intervention of exercise before the meal<br>* 40 minutes of downhill exercise completed 1 hour before the meal<br>|
| Experimental: Downhill exercise after the meals<br>40 minutes of downhill treadmill exercise at -6o slope started 1 hour after eating the meal | Combination Product: Behavioral intervention of downhill exercise<br>* 40 minutes of downhill exercise<br>Combination Product: Dietary intervention of exercise after the meal<br>* 40 minutes of downhill exercise started 1 hour after the meal<br>|
| Sham Comparator: Sedentary trial<br>A trial with no exercise | Combination Product: Behavioral intervention of sedentary no-exercise trial<br>* Sedentary no-exercise trial<br>Combination Product: Dietary intervention of eating two meals<br>* Meals eaten at 10 and 17 h during a sedentary trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-terminal propeptide of type I collagen | Change over time in plasma concentration of c-terminal propeptde of type 1 collagen (ng/ml) | 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) | 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) | 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) | Hourly over 12 hours from the start of the trial, then at 16 hours, and at 22 hours, after the start of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin | Change over time in plasma concentration of insulin (µU/ml) | 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) | 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 | Change over time in plasma concentration of cortisol (m/L) | 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) | 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) | 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 | A week prior to the study baseline | 
| Novel Pedar | Mechanosensitive shoe inserts for measurement of ground reaction force | During two one-hour bouts of the exercise intervention |