Prevention of Post-Prandial Hypoglycemia Using n-3/n-6 PUFA in PCOS

Summary

Principal Investigator: SIDIKA KARAKAS
Abstract: This proposal is in response to the PAR-04-087 (The GCRC Complementary and Alternative Medicine Research Program) and utilizes the resources of the UC Davis GCRC. The aim is to determine whether the essential and/or the long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) can prevent postprandial hypoglycemia and its unfavorable endocrine consequences in polycystic ovary syndrome (PCOS). PCOS affects 1 in 16 women and manifests with insulin resistance, hyperinsulinemia, androgen excess, hirsutism, infertility, and commonly with obesity. Treatment of insulin resistance and obesity improves ovarian function and infertility. We demonstrated that PCOS patients frequently develop postprandial hypoglycemia, which in turn stimulates secretion of cortisol and adrenal androgens. Since these hormones promote central obesity, insulin resistance and possibly hirsutism, prevention of postprandial hypoglycemia can be very beneficial. Our previous research suggests that n-3 PUFA supplementation may be useful in preventing postprandial hypoglycemia in PCOS. The hypothesis is: In women with PCOS, both the essential and the long-chain n-3 PUFAs can prevent postprandial hypoglycemia, but possibly through different mechanisms: The long-chain n-3 PUFAs from fish oil decrease insulin secretion, whereas the essential n-3 PUFA from flax seed oil re-sets the pancreatic glucose sensor to a higher threshold. This hypothesis will be tested in 90 women with PCOS using a randomized, double- blinded, placebo-controlled, parallel-design intervention that has two phases: I. Lead-in (4 weeks) and II. Intervention (6 weeks). During the lead-in period all participants will receive a placebo. During the intervention, the participants will be randomized to 3 treatment arms: placebo, fish oil or flax seed oil. Changes in blood glucose, insulin sensitivity, insulin secretion, pancreatic reserve and hypoglycemic symptoms will be investigated. We anticipate that n-3 PUFAs will prevent hypoglycemia, and thus secretion of cortisol and adrenal androgens. This R21 proposal will determine the best n-3 PUFA supplement to be tested in future large clinical trials in order to decrease obesity, central obesity, insulin resistance, hirsutism, and the risks for diabetes and infertility in young women with PCOS --an understudied population. Polycystic ovary syndrome (PCOS) is a common disease that affects 1 out of 16 women. There are almost 7 million PCOS patients in the USA. This disease causes infertility, facial hair growth, and increases the risk for obesity, diabetes and heart disease. We discovered that PCOS patients experience low blood sugars (hypoglycemia) frequently. In turn, hypoglycemia causes sugar craving and overeating, and increases secretion of the hormones that lead to obesity and diabetes. Avoiding hypoglycemia may protect these patients from gaining additional weight and becoming diabetic. We think we can achieve this goal by using fish oil and/or flax seed oil supplements. We do not know yet however which one of these supplements would be the better choice. Our aim is to identify the best supplement that can prevent hypoglycemia and its unwanted consequences in these young women-an under-studied patient population.
Funding Period: 2007-05-01 - 2010-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Lean mass and insulin resistance in women with polycystic ovary syndrome
    Kevin B Comerford
    Nutritional Biology Graduate Group, Department of Nutrition, The University of California at Davis, Davis, California, USA
    Metabolism 61:1256-60. 2012
  2. ncbi Utility of hemoglobin-A1C in nondiabetic women with polycystic ovary syndrome
    Rami Mortada
    Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of California Davis, Davis, CA 95817, USA
    Endocr Pract 19:284-9. 2013
  3. pmc In polycystic ovary syndrome, adrenal steroids are regulated differently in the morning versus in response to nutrient intake
    Dumindra Gurusinghe
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, The University of California at Davis, Davis, California, USA
    Fertil Steril 93:1192-9. 2010
  4. pmc Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers
    SIDIKA E KARAKAS
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, The University of California at Davis, Davis, CA 95817, USA
    Metabolism 58:1002-7. 2009
  5. pmc Determinants of impaired fasting glucose versus glucose intolerance in polycystic ovary syndrome
    SIDIKA E KARAKAS
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, University of California, Davis, Davis, California, USA
    Diabetes Care 33:887-93. 2010
  6. pmc Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome
    M Luisa Vargas
    Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California at Davis, Davis, CA 95817, USA
    Metabolism 60:1711-8. 2011

Scientific Experts

  • SIDIKA E KARAKAS
  • Kyoungmi Kim
  • Rogelio U Almario
  • Rami Mortada
  • Kevin B Comerford
  • M Luisa Vargas
  • Dumindra Gurusinghe
  • Kevin Comerford
  • K James Kallail
  • Wendy Buchan
  • William F Horn
  • Nancy L Keim
  • Sharan Gill
  • Jennifer Lee

Detail Information

Publications6

  1. ncbi Lean mass and insulin resistance in women with polycystic ovary syndrome
    Kevin B Comerford
    Nutritional Biology Graduate Group, Department of Nutrition, The University of California at Davis, Davis, California, USA
    Metabolism 61:1256-60. 2012
    ..7±1.7 and 48.9±1.6 kg) but discordant for fat mass (43.3±2.6 vs 30.3±8.9 kg) showed no differences in insulin resistance parameters. These novel findings indicate that lean mass relates directly to insulin resistance in PCOS...
  2. ncbi Utility of hemoglobin-A1C in nondiabetic women with polycystic ovary syndrome
    Rami Mortada
    Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of California Davis, Davis, CA 95817, USA
    Endocr Pract 19:284-9. 2013
    ..Compared to the general population, women with polycystic ovary syndrome (PCOS) have a higher risk for diabetes. Our goal was to determine what glucose homeostasis abnormalities can be identified by A1C ≥5.7% in women with PCOS...
  3. pmc In polycystic ovary syndrome, adrenal steroids are regulated differently in the morning versus in response to nutrient intake
    Dumindra Gurusinghe
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, The University of California at Davis, Davis, California, USA
    Fertil Steril 93:1192-9. 2010
    ..To investigate adrenal steroid regulation in polycystic ovary syndrome...
  4. pmc Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers
    SIDIKA E KARAKAS
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, The University of California at Davis, Davis, CA 95817, USA
    Metabolism 58:1002-7. 2009
    ..In conclusion, fasting FABP4 related to metabolic risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured after glucose loading may provide better risk assessment than the fasting values...
  5. pmc Determinants of impaired fasting glucose versus glucose intolerance in polycystic ovary syndrome
    SIDIKA E KARAKAS
    Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, University of California, Davis, Davis, California, USA
    Diabetes Care 33:887-93. 2010
    ..To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI)...
  6. pmc Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome
    M Luisa Vargas
    Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California at Davis, Davis, CA 95817, USA
    Metabolism 60:1711-8. 2011
    ..Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably...