Background : The most important lifestyle factors associated with insulin resistance and the development of diabetes are certainly dietary habits and the level of physical activity (1). Changes in serum phospholipid fatty acid composition may play a role in modulating insulin action in peripheral tissues (2). Arachidonic acid (20:4, n-6 fatty acid) supplement may be beneficial to control blood glucose and to modulate appetite in men and women (3-5). Furthermore, dietary polyunsaturated fats are associated with a decreased risk to develop diabetes (6).
Objective : This thesis examined the impact of an oil supplement rich in arachidonic acid (AA) on blood glucose and on the expression of specific molecules involved in blood glucose control (PPAR-gamma, GLUT4, adiponectin). The second aim of the present thesis was to verify the impact of AA on appetite profile and plasma leptin levels. The third study of this work looked at the relationship between changes in dietary fat and changes in glucose tolerance markers in a large population of Canadian men and women who took part in the Quebec Family Study (QFS). Finally, the fourth study used the Quebec Family Study cohort to look for relationships between the changes in dietary fat and the changes in glucose tolerance markers. It also compared the diet composition of people who developed diabetes to the diet of people who did not develop diabetes over a period of 6 years.
Design : Study #1 : Fifteen healthy non-diabetic men and women were randomly assigned to the placebo group (corn-soy oil capsules) or the AA group (800mg AA rich oil/day). Anthropometric measurements. Oral Glucose Tolerance Test (OGTT) and fasting serum leptin were performed before and after the 3-week treatment. Study #2 : Ten Type 2 diabetic men and women were part of a randomized cross-over trial composed of 2 periods of 3-week treatment (0.8g/ day AA or Placebo) separated by a 2-week wash-out. Fasting plasma glucose, insulin, leptin, appetite profile (with visual analogue scales) and anthropometric measurements were performed before and after each period of treatment. Moreover, an abdominal subcutaneous fat biopsy was done before and after the AA. Finally, the mRNA expression of PPAR-gamma, GLUT4 and adiponectin from the adipose tissue biopsies was measured by RT-PCR. Study #3 : A cross-sectional study in which anthropometric measurements and Oral Glucose Tolerance Tests were performed on 472 Canadian men and women. These participants were asked to complete food diaries from which the dietary fatty acid composition was estimated. Study #4: In this longitudinal study, anthropometric measurements and OGTT were performed in 183 subjects before and after a period of 6 years. Secondly, the baseline diet of 32 patients who developed diabetes was compared to the diet of 32 patients matched for percentage body fat and age.
Results: No significant impact of treatments were observed on anthropometric measurements, fasting blood glucose, leptin and insulin levels in diabetic and non diabetic patients of study #1 and #2. The Area Under the Curve of glucose during the OGTT was similar before and after the treatments in non-diabetic patients. Moreover, the PPAR-gamma and GLUT4 mRNA expression measured in adipose tissue of diabetic patients did not change with the increased AA intake. In diabetic patients, the only significant variation was the adiponectin mRNA expression increase after the AA treatment. The appetite profile measured in Type 2 diabetic patients did not change significantly with the treatments. In study #3, high intake of monounsaturated fat and arachidonic acid seems to be related to higher glucose or higher insulin values. The stepwise regression analysis showed that 22-32% of the variance of blood glucose control markers was explained by age and anthropometric variables. Finally, the longitudinal study (study #4) revealed that participants who developed diabetes over a period of 6 years had a higher energy intake, a higher protein intake and a higher monounsaturated fatty acid intake compared to subjects who did not develop diabetes.
Conclusions : A short-term supplement of 0.8g AA/day has not been perceived as an effective complement to help controlling blood glucose and improve appetite when no other changes in the diet were prescribed. Among the types of dietary fat, monounsaturated fat seems to be the best predictor of glucose tolerance changes in our cohort of patients.