Date

April 2009

Document Type

Thesis

Degree Name

M.S.

Institution

Oregon Health & Science University

Abstract

Background: Osteocalcin, a protein secreted during bone formation has been shown to impact glucose homeostasis. It has been theorized that the undercarboxylated osteocalcin may act in an endocrine fashion to positively modulate adiponectin to decrease fat stores. Undercarboxylated osteocalcin may also increase the proliferation of β-cells in the pancreas and thus insulin ecretion. The carboxylated form of osteocalcin has been shown to increase bone strength and decrease the risk of osteoporosis. Previous studies have examined the effects of single nutrients on the circulating concentration of this protein, and found a correlation between dietary composition and carboxylation status and excursion of osteocalcin concentration. The purpose of this study is to characterize the effects of low carbohydrate (LC) versus high complex carbohydrate (HC) meals on total osteocalcin and undercarboxylated osteocalcin concentrations in the acute postprandial state. Significance: The results of this study may provide further insight into the impact of dietary composition on the protein osteocalcin. If diet is shown to modulate concentration and/or form of this protein, novel individualized medical nutrition therapy may prove instrumental in the treatment of obesity, osteoporosis and diabetes. Methodology: Ten healthy men and women from the Portland area completed a randomized crossover feeding trial consisting of two, three day run-periods, followed by a day of HC or LC dietary intervention. On intervention days participants consumed either HC or LC breakfast and lunch meals and provided blood samples while fasting and then every hour postprandially. Plasma was analyzed for total (intact) and undercarboxylated osteocalcin concentrations using ELISA. Incremental area under the curve (iAUC) using the trapezoidal method was calculated for intact osteocalcin, undercarboxylated osteocalcin and the undercarboxylated : intact osteocalcin ratio (UCR). Results: Following the HC breakfast meal, circulating intact osteocalcin concentration decreased for the first 2 hours, followed by a rise towards baseline before lunch. After the HC lunch meal, circulating intact osteocalcin concentration was more stable in pattern. Following the LC meals, intact osteocalcin was fairly stable throughout the day. Absolute undercarboxylated osteocalcin concentration was significantly higher after the HC breakfast than the LC breakfast for the first 5 hours of the day [iAUC 3.24 ± 2.25ng/mL* hr0800-1300 vs. -1.55 ± 2.15 ng/mL* hr0800-1300, (as mean ± standard deviation, ± SD), p=0.02] and for the duration of the sample collection (iAUC- 7.01 ± 4.51 ng/mL* hr0800-1730 vs. –1.77 ± 4.55 ng/mL* hr0800-1730, ± SD, p= 0.03). Significant differences in iAUC were not seen in total circulating intact osteocalcin concentrations, absolute undercarboxylated osteocalcin concentrations following the lunch meal, or the UCR at any time interval. Trends showed a higher intact osteocalcin excursion and UCR following the LC lunch versus the HC lunch. The trends in patterns of change exhibited for undercarboxylated and circulating intact osteocalcin concentration suggest that significant differences may exist and may be better captured if studied over a longer period of time.

Identifier

doi:10.6083/M4M906M2

Division

Graduate Programs in Human Nutrition

School

School of Medicine

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