Preventing Diabetic Osteoporosis With Exercise (DIABETICBONE)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Combination product: Behavior intervention of uphill exercise; Combination product: Dietary intervention of exercise before the meal; 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: Dietary intervention of exercise after the meal; Combination product: Behavior intervention of downhill exercise; Combination product: Behavioral intervention of downhill exercise; Combination product: Behavioral intervention of sedentary no-exercise trial; Combination product: Dietary intervention of eating two meals

Detailed Description

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
• Enrollment (Actual): 15
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Wisconsin, La Crosse
• Investigators: Principal Investigator: Katarina T Borer, Professor Emerita

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2009
• Primary Completion (Actual): December 5, 2012
• Study Completion (Actual): December 20, 2012

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Diabetes Mellitus, Type 2; Osteoporosis
• Other Study ID Numbers: HUM32227/ HUM32700; R15DK082800 (U.S. NIH Grant/Contract); M01RR024986 (Other Grant/Funding Number: Michigan Institute of Clinical and Health Research)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No