Type 2 diabetes (T2D) is a growing concern as more people are getting diagnosed each year. According to the CDC, 86 million American adults (~1 in 3) have prediabetes, and 9 out of 10 do not know it. 15-30% of those with prediabetes will develop T2D within 5 years. Patients with prediabetes can reduce their risk for developing T2D by modifying their diet and exercise habits. Cutting risk for T2D is important since once someone has T2D, their risk for heart disease, stroke, kidney failure, blindness and a variety of other conditions increases. Also, people with T2D are at a 50% higher risk of death than adults without the disease, and medical cost for someone with T2D are twice as high compared to people who do not have diabetes. Since T2D (like all diseases) is much easier to prevent than to reverse, it would be important for people at increased risk for T2D to know it. Some tests can help with this including triglyceride, HDL-cholesterol, glucose and hemoglobin A1c, but other markers are needed to better predict who is and who is not going to get T2D.
In the study summarized here, Dr. Harris (founder and president of OmegaQuant) and colleagues found that lower levels of palmitic acid were also associated with a lower risk of T2D. Their results were recently published in a paper entitled, “Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study” (Harris W et al. PLoS ONE 2016).
Description of Cohort
A baseline red blood cell (RBC) fatty acid composition was determined for 6,379 participants in the Women’s Health Initiative Memory Study (WHIMS), a large cohort of postmenopausal women in the United States. These women were followed for the development of T2D for about 11 years. Incident T2D was defined as a positive answer to the question regarding “newly prescribed treatment for diabetes with pills or insulin shots”, which was asked annually of participants.
There were 703 cases of T2D in this cohort. Those participants who developed T2D were more likely to be of African American, to be overweight, to have a larger waist circumference, to exercise less, to drink alcohol less frequently and to have a family history of the disease.
Fatty acids that were related to the development of T2D
Palmitic Acid (C16:0)
RBC palmitic acid gave the strongest signal with incident T2D of all the fatty acids examined. Palmitic acid fatty acid levels were directly associated with increased risk of T2D. Compared with a palmitic acid value of less than 19.0% (lowest risk; 1st quintile), patients with values greater than 22.4% were almost 2 times as likely to develop T2D over the 11 years of follow-up. Although palmitic acid is the third most prevalent fatty acid in the diet (about 20% of total), its levels in RBCs do not correlate very well with intake nor do they respond proportionally to changes in intake. This is largely because palmitic acid is also an “endogenous” fatty acid synthesized de novo (from scratch) from the products of carbohydrate metabolism. Thus it is practically impossible to predict palmitic fatty acid levels without measuring them.
Palmitoleic Acid (C16:1n7)
Palmitoleic was also directly associated with incident T2D. Since palmitoleic acid is increased with high-carbohydrate diets and is a marker of de novo lipogenesis (fatty acid synthesis) it too is very hard to predict levels without measuring. The author’s stated that palmitoleic was also directly related to risk in 8 of the 9 previous studies in which it was examined, so this study confirms these earlier findings strengthening the link between palmitoleic and future risk for T2D.
Delta-5 Desaturase (D5D) and Delta-6 Desaturase (D6D) Ratios
The delta-5 and delta-6 desaturases are hepatic enzymes that, in concert with other enzymes, add new double bonds and 2-carbon units to make longer fatty acid chains with more double bonds (i.e., more “unsaturated”). Specifically, these enzymes convert linoleic and alpha-linolenic acids (the short chain essential fatty acids) to their respective longer-chain metabolites: dihomo-gamma linolenic (DGLA) and arachidonic acid (AA) from the former, and EPA, DHA and n-3 docosapentaenoic acid (DPA n-3) from the latter. As the activities of these hepatic enzymes cannot be measured directly, they are conventionally estimated from product/precursor ratios measured in blood. D5D activity is estimated from the ratio of AA to DGLA, and D6D is estimated from the ratio DGLA to LA.
In this study higher levels of the D5D ratio were associated with decreased relative risk for T2D. The estimated incident rates for T2D at 10 years of follow-up based on the highest vs the lowest D5D ratio were 8.0% vs 14.4%. Higher levels of the D6D ratio were associated with increased relative risk for incident T2D. The estimated incident rates for T2D at 10 years of follow-up based on the highest vs the lowest D6D ratio were 15.6% vs 8.4%.
The authors stated that among the most consistent fatty acid metrics associated with risk for T2D are the desaturase ratios. Of the six past studies that examined them, five found significant inverse relations with disease for the D5D ratio and/or direct relations for the D6D ratio; and the study that did not find these associations included only 30 events.
Of the fatty acids examined in this study palmitic acid levels had the strongest association with the development of T2D. While palmitoleic, D5D, and D6D levels were also strong predicators as well. Whether there is a causal link between these fatty acid distributions and incident disease cannot be confirmed in this study, but RBC fatty acid data may have value in identifying patients at risk of developing T2D.
So can dietary changes actually alter levels of palmitic and palmitoleic acid? Yes! The best way to alter these is to eat less simple carbohydrates (sugar, high fructose corn syrup) because in excess, these are converted to these two fatty acids in the liver.
Why is this important?
Without knowing that they have pre-diabetes, most people will continue on with their current lifestyle. But if they know they are at risk, they at least have a chance of changing. The fatty acid levels discussed above may be another way to help people (and their doctors) identify their risk of developing T2D early. This would allow people to change the direction of their future health, and potentially live a longer and happier life.