Source: COLORADO STATE UNIVERSITY submitted to
OMEGA-3 FATTY ACIDS, ADIPONECTIN, AND INSULIN ACTION IN HISPANIC WOMEN
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0218740
Grant No.
(N/A)
Project No.
COL00603
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Jul 1, 2009
Project End Date
Jun 30, 2011
Grant Year
(N/A)
Project Director
Melby, C. L.
Recipient Organization
COLORADO STATE UNIVERSITY
(N/A)
FORT COLLINS,CO 80523
Performing Department
Food Science & Human Nutrition
Non Technical Summary
Our laboratory has found that Mexican-Americans exhibit greater markers of subclinical inflammation and insulin resistance when matched to non-Hispanic Whites for body fat and cardiorespiratory fitness. We have also found that pre-menopausal Hispanic women, even in the absence of obesity, have lower adiponectin concentrations than pre-menopausal nonHispanic white women (unpublished data), potentially predisposing them to insulin resistance, the metabolic syndrome, and T2D. Additionally, there are now data that have linked low intakes of fish to greater prevalence of diabetes and poorer diabetes control in Hispanic adults. Also, the nutrition transition in Mexico has led to a decrease in the availability of fish and seafood, a phenomenon that has likely resulted in low fish consumption in Mexican immigrants to the United States. Given the aforementioned information, there is a great potential to improve insulin sensitivity and lower risk for diabetes and the metabolic syndrome among Hispanic Americans by increasing their intake of long chain omega-3 PUFA. To our knowledge, the supplementation of omega-3 PUFA in Hispanic adults and the subsequent effect on adiponectin and insulin sensitivity has not been examined. Therefore, the purpose of our study is to determine if consumption of fish oil (2 capsules totaling 1.3 g EPA and 0.5 g DHA per day) versus placebo over a 3-month period improves both total and high molecular weight serum adiponectin concentrations, glucose tolerance and insulin action via an oral glucose tolerance test, and features of the metabolic syndrome in Hispanic pre-diabetic women.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70260101010100%
Goals / Objectives
We have shown that non-diabetic Mexican-Americans exhibit greater markers of subclinical inflammation and insulin resistance when matched to non-Hispanic Whites for body fat and cardiorespiratory fitness. We have also found that pre-menopausal Hispanic women, even in the absence of obesity, have lower adiponectin concentrations than pre-menopausal nonHispanic white women (unpublished data), potentially predisposing them to insulin resistance, the metabolic syndrome, and T2D. Additionally, there are now data that have linked low intakes of fish to greater prevalence of diabetes and poorer diabetes control in Hispanic adults. Also, the nutrition transition in Mexico has led to a decrease in the availability of fish and seafood, a phenomenon that has likely resulted in low fish consumption in Mexican immigrants to the United States. Given the aforementioned information, there is a great potential to improve insulin sensitivity and lower risk for diabetes and the metabolic syndrome among Hispanic Americans by increasing their intake of long chain omega-3 PUFA. To our knowledge, the supplementation of omega-3 PUFA in Hispanic adults and the subsequent effect on adiponectin and insulin sensitivity has not been examined. Therefore, this grant application has the following specific aim and hypothesis: Specific Aim: To determine if consumption of fish oil (2 capsules totaling 1.3 g EPA and 0.5 g DHA per day) versus placebo over a 3-month period improves both total and high molecular weight serum adiponectin concentrations, glucose tolerance and insulin action via an oral glucose tolerance test, and features of the metabolic syndrome in Hispanic pre-diabetic women. Hypothesis: Increasing dietary EPA and DHA will increase circulating adiponectin and improve insulin action and plasma lipids in Hispanic pre-diabetic females.
Project Methods
For this project we will use a double-blind, randomized, placebo-controlled trial to examine the efficacy of increasing long chain omega-3 PUFAs using a fish oil capsule on insulin sensitivity, plasma adiponectin and the features of the metabolic syndrome within a group of Hispanic women. After obtaining IRB approval, 50 pre-diabetic (fasting glucose > 100 mg/dL and < 126 mg/dL) Hispanic adult women between the ages of 35 and 60 years will be recruited for this study. Participants will be randomized into either the control group (N = 25) or the omega-3 PUFA group (N = 25), stratified for menopausal status and blood glucose. Exclusionary criteria for this study will be any known metabolic disorder, diagnosed cardiovascular disease, diagnosed diabetes mellitus, and/or regular physical activity (defined as >2 days/week of moderate activity). Further, those individuals who are taking medications or hormone therapy known to influence any of the dependent variables will be excluded, as well as those who have habitual diets high in PUFAs (PUFA:saturated fat ratio > 0.7, n-6:n-3 ratio < 7:1). Briefly, on day 1, participants will be asked to arrive at the Nutrition and Metabolic Fitness Laboratory in the Gifford Building or the Human Performance Clinical Laboratory (HPCRL) in Moby for review of the informed consent and measurement of baseline anthropometric, body composition, and blood pressure. Additionally, participants will be asked to complete a brief health history questionnaire that will include current health information, smoking, drinking, and physical activity habits. This information will be used when analyzing our data as potential confounders. On visit 2, a fasting blood sample will be drawn for measurement of adiponectin, HbA1c, insulin, glucose, and red blood cell omega-3 PUFAs. Following completion of the OGTT, participants will be given a two week supply of either placebo (olive oil) or omega-3 capsules (GNC Triple Strength Fish Oil Soft Gels = 900 mg omega-3 PUFA per capsule). Participants will be asked to consume 2 capsules per day. Every two weeks thereafter, participants will be instructed to return to the HPCRL for the next two-week supply of capsules and measurement of body weight. At the end of month 1 and 2, a fasting blood sample will be taken from each participant for determination of adiponectin, insulin, glucose, and omega-3 PUFA concentration. Insulin resistance will be estimated at these time points using the homeostatic model for the assessment of insulin resistance (HOMA-IR), which is mathematically derived from fasting insulin and glucose data. Following the 3-month supplementation period, participants will be asked to return to the HPCRL to repeat measurements from visit 2 in addition to post-supplementation anthropometric and body composition measurements. The dependent variables (adiponectin, glucose and insulin areas under the curve, plasma lipids, etc. will be analyzed for interactions and main effects using a two-way ANOVA (group [experimental vs control]) by time (pre-post for some variables, four time points for others). Post hoc tests will be run where appropriate.

Progress 07/01/09 to 06/30/11

Outputs
OUTPUTS: After obtaining IRB approval for this study in the fall of 2009, it became apparent as we began to recruit study participants that we would be unable to enroll adequate numbers of pre-diabetic Mexican-American women from the Fort Collins Community into this study, which was designed to determine the effect of increased omega-3 fatty acids on insulin sensitivity. Thus we changed the scope of the project in the following ways: 1.) We obtained IRB approval to use the state-of-the-art approach to measuring insulin action, the hyperinsulinemic-euglycemic clamp procedure. Two faculty investigators and one graduate student were trained in this technique. Because this is a more accurate and sensitive method than what we previously proposed, it allowed us to enroll a smaller sample size. 2.) We relocated the study to El Paso, Texas, where we had greater success in recruiting Mexican-American women. We successfully completed 23 study participants in this 12-week intervention and are now analyzing the data. Partnerships were developed with with the University of Texas-El Paso, El Centro, Vida Sana, Northside Atzlan Center, Family Medicine Center, Associates in Family Medicine, La Salud, the Colorado Clinical and Translational Sciences Institute, and the University of Colorado-Denver. The nature of this study and the data from previous research using AES funds were presented by the PI of this project to family practice physicians: Ethnicity, the Cardiometabolic Syndrome, and Diabetes Risk. Poudre Valley Medical Center, Lifestyle Medicine Grand Rounds, Fort Collins, CO., January 2011. 3.)We conducted a separate study in which we examined the potential for exercise and compensatory calorie replacement to favorably modify the postprandial lipemic response to a high fat, sugar-rich meal. We presented the findings of this latter study at the American College of Sports Medicine meeting in 2011 and two graduate students completed their theses as part of the study. PARTICIPANTS: We successfully completed 23 study participants in this 12-week intervention. Partnerships were developed with with the University of Texas-El Paso, El Centro, Vida Sana, Northside Atzlan Center, Family Medicine Center, Associates in Family Medicine, La Salud, the Colorado Clinical and Translational Sciences Institute, and the University of Colorado-Denver. Two faculty members and one graduate student were trained in using the hyperinsulinemic-euglycemic clamp approach to measuring insulin sensitivity. A faculty member at the University of Texas-El Paso, Dr. George King, became a collaborator on this project. TARGET AUDIENCES: The target audience for this project is the Hispanic community. Several presentations regarding the importance of a healthy diet and regular physical activity were given by the investigators to a local coalition of Hispanic leaders in the community. Also, the PI of the project was a presenter at a community diabetes prevention forum sponsored by 3 state legislators. PROJECT MODIFICATIONS: Despite a concerted 1-year long effort by the investigative team to recruit study participants, it became clear that we would be unable to enroll an adequate number of study subjects. So, we changed the scope of the project in the following ways: 1.) We obtained IRB approval to use the state-of-the-art approach to measuring insulin action, the hyperinsulinemic-euglycemic clamp procedure. Because this is a more accurate and sensitive method than what we previously proposed, it allowed us to enroll a smaller sample size. 2.) We relocated the study to El Paso, Texas, where we had greater success in recruiting Mexican-American women. 3.) We completed a separate study in which we examined the potential for exercise and compensatory calorie replacement to favorably modify the postprandial lipemic response to a high fat, sugar-rich meal.

Impacts
Because of difficulties in recruiting Mexican American women into this study and the need to shift the location to El Paso, TX, we have been delayed in finishing this project. Our initial and cursory analysis of a subset of data shows that supplementation of Mexican-American women with 1.3 g eicosapentaenoic acid (EPA) and 0.5 g docosahexaenoic acid (DHA) per day may improve insulin sensitivity. However, the data analyses are incomplete, and this finding should be viewed as preliminary and not final. We are in the process of examining the possible association of changes in plasma adiponectin concentrations with improvements in insulin sensitivity. Our other study completed under this larger project showed that a low intensity exercise bout accompanied by additional calories ingested to compensate for those expended in exercise, failed to improve the postprandial lipid response to a high fat, high sugar meal challenge compared to the same meal challenge without exercise. Exercise may not be beneficial in attenuating postprandial lipemia unless it is accompanied by a resulting acute caloric deficit.

Publications

  • Schmidt, S.L., Hickey, M.S., Koblenz, K.M., Klamer, H., Botero, M.F., Pfaffenbach, K., Pagliassotti, M.J., Melby, C.L. 2011. Cardiometabolic plasticity in response to a short-term diet and exercise intervention in young Hispanic and nonHispanic white adults. PLoS One (Public Library of Science One, 6(2): e16987. doi:10.1371/journal.pone.0016987.
  • Smith, W., *Warro, D., *Krause, M., Hickey, M.S., Melby, C.L. 2011. Effect of Low Intensity Exercise with Energy Replacement on the Plasma Triglyceride Response to a High Fat Meal. Abstract. Medicine and Science in Sports and Exercise 43:S562, June 2011.
  • Warro, D. 2011. The effects of a single bout of exercise, with energy replacement, on plasma concentrations of tnf-α following consumption of a high-fat, high-carbohydrate mixed meal. Master's Thesis. Colorado State University.
  • Smith, W. 2011. The effects of a single bout of exercise on plasma triglycerides, glucose, and insulin following consumption of a high-fat mixed macronutrient meal. Master's Thesis. Colorado State University.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: This past year was spent in a variety of activities focused on recruitment of Hispanic women as study participants to examine the impact of increased omega-3 fatty acids on insulin action. Much of our investigative team time was spent visiting local physician's offices, clinics, churches, community service organizations, and Latino festivals and events. In the midst of our difficulties in recruiting study volunteers, we focused additional time on the following activities: 1.) learning and training the research team in the state-of-the-art approach to measuring insulin action, the hyperinsulinemic-euglycemic clamp procedure; 2.) completing a separate study to examine the impact of an acute prior exercise bout on the lipemic response to a high fat, high sugar meal; 3.) collaborating with a scientist at another university to explore the possibility of relocating our study in Hispanic women to El Paso, Texas, where we anticipate better success in recruitment. PARTICIPANTS: Chris Melby, PI. Responsible for oversight of the entire project, including supervision of graduate students, subject recruitment, data collection, and statistical analyses, as well as mentoring the Ph.D. student coordinating this project. Matthew Hickey, Co-PI. Responsible for academic oversight of the Ph.D. student who is conducting this sudy for her dissertation. Tracy Nelson, Co-I. Responsible for data analyses and mentoring of the Ph.D. student. Sarah Deemer, Ph.D. student Maria Botero, M.S. student Molly Krause, M.S. student All three of these students have been trained in bioethics, policies of the institutional review board (IRB), recruitment of study participants, data collection including personal and family medical history, anthropometric measures, dietary analyses, blood assays, the hyperinsulinemic-euglycemic approach to measuring insulin sensitivity, and methods of data analyses. Two of the three students have finished their theses. Partnerships have been developed with the University of Texas-El Paso, El Centro, Vida Sana, Northside Atzlan Center, Family Medicine Center, Associates in Family Medicine, La Salud, the Colorado Clinical and Translational Sciences Institute, and the University of Colorado-Denver. TARGET AUDIENCES: Young Mexican American Adults and nonHispanic White adults. PROJECT MODIFICATIONS: Because of a great deal of difficulty in recruiting Hispanic women in Northern Colorado, despite substantial efforts, we are shifting the location of this study to El Paso, TX, where we anticipate recruitment activities will be more successful. In the midst of recruitment difficulties we completed a study examining the effect of acute exercise on the lipemic response to a high fat, high sugar meal. We are now analyzing these data.

Impacts
PURPOSE: This study examined whether or not a single, acute bout of low intensity exercise with a compensatory replacement of energy in comparison to a no-exercise condition would attenuate the postprandial increases in plasma triglycerides (TG), glucose, and insulin in response to a high-fat, mixed macronutrient meal (HFMM) in young, habitually sedentary women. METHODS: 8 nonobese, sedentary females aged 19.6 (1.3) years participated in two trials in random order: sedentary (SED) and exercise (EX). On day 1 of the SED trial subjects did not exercise and were fed to maintain energy balance. On the morning of day 2 subjects provided a fasting blood sample and tehn underwent the HFMM test (12.5 kcal/kg BW; 53% energy fat). Plasma samples were obtained 30, 60, 90, 120, 150, 180, 210, 240, 300, and 360 minutes after ingestion of the HFMM and later analyzed for TG, glucose, and insulin concentrations.For the EX trial, a similar protocol was followed with addition of an exercise bout the afternoon of day 1, in which subjects cycled at 45-50% of their VO2peak (x duration =70 min; net energy cost ~ 300 kcal). A snack was provided shortly after the exercise bout to prevent negative energy balance. The morning of day 2 subjects underwent the same HFMM challenge test. RESULTS: There were no significant treatment by time interactions and no main effects of treatment for glucose and insulin. Plasma TG were not different for Ex compared to SED during the first 4 hours, nor was the peak postprandial TG (SED X=136.6 mg/dl, EX =137.0 mg/dl). However, the average TG concentration was lower (p<0.05) for the last two hours of the postprandial period for EX compared to SED (80.9 vs 99.2 mg/dl). CONCLUSIONS: In young, habitually sedentary women, low intensity exercise without an energy deficit compared to no exercise does not attenuate the postprandial TG response during the first 4 hours of the postprandial period following a high fat mixed meal challenge. However, the low intensity exercise does result in significantly lower postprandial TG at 5 and 6 hours following meal ingestion.

Publications

  • Botero, M. 2010. Effects of a One Week Controlled Diet And Exercise Intervention on Plasma Adiponectin Levels in Young Non-Hispanic White and Mexican American Adults. Master's Thesis. Colorado State University
  • Krause, M. 2010. A Single Session of Moderate Exercise, Without Energy Deficit, May Reduce sVCAM-1 Concentrations in Young, Sedentary Females. Master's Thesis. Colorado State University
  • Melby, C. Schmidt, S. Hickey,M.H. 2010. Functional Foods, Insulin Resistance, and Diabetes, Chapter 24 in N.M.B. Costa and Rosa, C.O.B.(ed.) Functional foods: bioactive compounds and physiological effects.


Progress 07/01/09 to 12/31/09

Outputs
OUTPUTS: This project began in late summer of 2009 with the recruitment of a Hispanic graduate student. During this time the investigators have worked with a commercial laboratory to obtain the gel capsules of eicosapentaenoic acid and docosahexaenoic acid supplements, obtained IRB approval, developed the recruitment approach, and trained the graduate student in all aspects of the study including subject recruitment, intravenous catheter placement, blood sampling, laboratory assays, and data analysis. The first cohort of subjects will be enrolled in February, 2010. PARTICIPANTS: Sarah Deemer, Hispanic Ph.D. student is working on this project as part of her dissertation. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
None as yet. Project is just underway

Publications

  • No publications reported this period