High levels of stearic acid, palmitoleic acid, and dihomo-γ-linolenic acid and low levels of linoleic acid in serum cholesterol ester are associated with high insulin resistance

Abstract

The association of fatty acid composition with insulin resistance and type 2 diabetes has been reported in Western populations, but there is limited evidence of this association among the Japanese, whose populace consume large amounts of fish. To test the hypothesis that high palmitic, palmitoleic, and dihomo-γ-linolenic acids and low levels of linoleic and n-3 fatty acids are associated with higher insulin resistance among the Japanese, the authors investigated the relationship between serum fatty acid composition and serum C-peptide concentrations in 437 Japanese employees aged 21 to 67 years who participated in a workplace health examination. Serum cholesterol ester and phospholipid fatty acid compositions were measured by gas-liquid chromatography. Desaturase activity was estimated by fatty acid product-to-precursor ratios. A multiple regression was used to assess the association between fatty acid and C-peptide concentrations. C-peptide concentrations were associated inversely with linoleic acid levels in cholesterol ester and phospholipid (P for trend = .01 and .02, respectively) and positively with stearic and palmitoleic acids in cholesterol ester (P for trend =.02 and .006, respectively) and dihomo-γ-linolenic acid in cholesterol ester and phospholipid (P for trend < .0001 for both). C-peptide concentrations were not associated with n-3 polyunsaturated fatty acids. C-peptide concentrations significantly increased as δ-9-desaturase (16:1 n-7/16:0) and δ-6-desaturase (18:3 n-6/18:2 n-6) increased (P for trend = .01 and .03, respectively) and δ-5-desaturase (20:4 n-6/20:3 n-6) decreased (P for trend = .004). In conclusion, a fatty acid pattern with high levels of serum stearic, palmitoleic, or dihomo-γ-linolenic acids; δ-9-desaturase (16:1 n-7/16:0) or δ-6-desaturase (18:3 n-6/18:2 n-6) activities; and low levels of serum linoleic acid or δ-5-desaturase (20:4 n-6/20:3 n-6) activity might be associated with higher insulin resistance in Japanese adults.

Introduction

Type 2 diabetes is among the most common chronic diseases in the world, and the prevalence of diabetes in Japan has increased markedly in the past several decades [1]. A high intake of saturated fat is a known dietary risk factor for type 2 diabetes [2]. However, evidence is conflicted regarding the effect of monounsaturated fatty acids (MUFAs), n-3 polyunsaturated fatty acids (PUFAs), and n-6 PUFAs on diabetes risk and glucose metabolism [2]. The lack of consistent association shown for these fatty acids in previous studies may be ascribed, at least in part, to the difficulty in assessing dietary fat intake through dietary surveys, which tend to underestimate true intake [3]. Cholesterol esters and phospholipids in the serum or plasma fatty acid are good biomarkers of dietary fatty acid intake [4].

Several studies have shown that fatty acid patterns with large proportions of palmitic (16:0) [5], [6], [7], [8], palmitoleic (16:1 n-7) [5], [6], [7], [8], [9], [10], [11], [12], [13], and dihomo-γ-linolenic acids (20:3 n-6) [5], [7], [8], [9], [10], [11], [12], [13], [14] and low levels of linoleic acid (LA) (18:2 n-6) [5], [6], [7], [8], [9], [12] are associated with markers of insulin resistance or type 2 diabetes. The fatty acid profile reflects both dietary intake and endogenous conversion of ingested fatty acids by desaturation or elongation. Insulin resistance and its associated disorders including type 2 diabetes are associated with an increase in estimated activity of the δ-9-desaturase (D9D) [5], [11], [12], [14], [15] and δ-6-desaturase (D6D) [5], [11], [15] as well as a decrease in activity of the δ-5-desaturase (D5D) [5], [11], [12], [14], [15].

To date, epidemiologic evidence on the association between serum fatty acid composition in cholesterol esters or phospholipids and markers of insulin resistance were derived only from Western populations [6], [8], [10], [11], [13]. To our knowledge, no prior study has investigated this relationship among the Japanese who have leaner body mass [16] and consume larger amounts of fish [17] (a rich source of long-chain n-3 fatty acids) compared with Western populations. A recent meta-analysis of prospective studies revealed that the association between dietary intake of long-chain n-3 fatty acids (eicosapentaenoic acid [EPA] 20:5 n-3) and docosahexaenoic acid [DHA] 22:6 n-3) and type 2 diabetes differed by study area; a positive association was found in the United States, no association was found in Europe, and an inverse association was found in both Asia and Australia [18]. C-peptide is cleaved from proinsulin in equivalent amounts with insulin [19], is not extracted by the liver, and has a longer half-life than insulin [20]. C-peptide is highly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) [21] and may serve as a better marker than insulin for estimating insulin resistance in epidemiologic studies [20]. We hypothesized that high levels of palmitic (16:0), palmitoleic (16:1 n-7), and dihomo-γ-linolenic acids (20:3 n-6) and low levels of LA (18:2 n-6), EPA (20:5 n-3), and DHA (22:6 n-3) are associated with higher C-peptide concentrations and that increased D9D and D6D and decreased D5D activities are related to higher levels of insulin resistance markers and tested this hypothesis by examining the relationship between serum fatty acid composition and serum C-peptide concentrations in Japanese employees.