Abstract
The frequent ACE insertion/deletion polymorphism (I/D) is, albeit inconsistently, associated with impaired glucose tolerance and insulin resistance. We recently observed an enhanced upregulation of ACE by elevated fat intake in GG-carriers of the I/D-surrogate rs4343 variant and therefore investigated its potential nutrigenetic role in glucose metabolism. In this nutritional intervention study 46 healthy and non-obese twin pairs consumed recommended low fat diets for 6 weeks before they received a 6-week high fat (HF) diet under isocaloric conditions. Intravenous glucose tolerance tests were performed before and after 1 and 6 weeks of HF diet. While glucose tolerance did not differ between genotypes at baseline it significantly declined in GG-carriers after 6 weeks HF diet (p = 0.001) with higher 2 h glucose and insulin concentrations compared to AA/AG-carriers (p = 0.003 and p = 0.042). Furthermore, the gene-diet interaction was confirmed in the cross-sectional Metabolic Syndrome Berlin Potsdam study (p = 0.012), with the GG-genotypes being significantly associated with prevalent type 2 diabetes for participants with high dietary fat intake ≥37% (GG vs. AA/AG, OR 2.36 [1.02–5.49], p = 0.045). In conclusion, the association between the rs4343 variant and glucose tolerance is modulated by dietary fat intake. The ACE rs4343 variant is a novel nutrient-sensitive type 2 diabetes risk marker potentially applicable for nutrigenetic dietary counseling.
Highlights
The D allele of the frequent ACE insertion/deletion (I/D) polymorphism, which is characterized by the presence (I) or absence (D) of a 287-bp Alu repeat sequence in the 16th intron of the ACE gene, was associated with decreased insulin sensitivity and impaired glucose tolerance in a healthy cohort[8]
LF6: Clinical investigation days (CIDs) after 6 weeks of LF diet; HF1/HF6: CID after 1/6 weeks of high fat (HF) diet. (Fig. 2b and c; repeated measures ANOVA, piAUCglucose = 0.001), whereas no change was observed for AA/ AG-carriers. incremental area under the curve (iAUC) for insulin was significantly higher in GG-carriers after 6 weeks of HF diet compared to AA/AG-carriers (Fig. 2d, piAUCinsulin = 0.027)
The results of the NUtriGenomic Analysis in Twins (NUGAT) study showed that dietary fat intake decisively modulated the association of the ACE rs4343 variant with impaired glucose metabolism and insulin resistance in healthy and non-obese subjects
Summary
The D allele of the frequent ACE insertion/deletion (I/D) polymorphism, which is characterized by the presence (I) or absence (D) of a 287-bp Alu repeat sequence in the 16th intron of the ACE gene, was associated with decreased insulin sensitivity and impaired glucose tolerance in a healthy cohort[8]. We identified ACE as nutrition-responsive gene in the NUtriGenomic Analysis in Twins (NUGAT) study, with increased ACE concentrations in response to an isocaloric high fat diet in healthy and non-obese subjects independent of weight gain[13]. We intended to investigate potential effects of a high fat diet on glucose tolerance as well as insulin sensitivity in our NUGAT study dependent on the frequent ACE rs4343 variant, a surrogate. The cross-sectional Metabolic Syndrome Berlin Potsdam (MeSyBePo) study, which includes nutritional assessments, was analyzed to evaluate the influence of dietary fat intake on the association between ACE genotype and type 2 diabetes prevalence in order to complement and validate the analysis in the NUGAT study
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