Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans

Norbert Stefan, Konstantinos Kantartzis, Nora Celebi, Harald Staiger, Jürgen Machann, Fritz Schick, Alexander Cegan, Michaela Elcnerova, Erwin Schleicher, Andreas Fritsche, Hans-Ulrich Häring, Norbert Stefan, Konstantinos Kantartzis, Nora Celebi, Harald Staiger, Jürgen Machann, Fritz Schick, Alexander Cegan, Michaela Elcnerova, Erwin Schleicher, Andreas Fritsche, Hans-Ulrich Häring

Abstract

Objective: We investigated whether palmitoleate, which prevents insulin resistance in mice, predicts insulin sensitivity in humans.

Research design and methods: The fasting fatty acid pattern in the plasma free fatty acid (FFA) fraction was determined in 100 subjects at increased risk for type 2 diabetes. Insulin sensitivity was estimated during an oral glucose tolerance test (OGTT) at baseline and after 9 months of lifestyle intervention and measured during the euglycemic-hyperinsulinemic clamp (n = 79).

Results: Circulating palmitoleate (OGTT:F ratio = 8.2, P = 0.005; clamp:F ratio = 7.8, P = 0.007) but not total FFAs (OGTT:F ratio = 0.6, P = 0.42; clamp:F ratio = 0.7, P = 0.40) correlated positively with insulin sensitivity, independently of age, sex, and adiposity. High baseline palmitoleate predicted a larger increase in insulin sensitivity. For 1-SD increase in palmitoleate, the odds ratio for being in the highest versus the lowest tertile of adjusted change in insulin sensitivity was 2.35 (95% CI 1.16-5.35).

Conclusions: Circulating palmitoleate strongly and independently predicts insulin sensitivity, suggesting that it plays an important role in the pathophysiology of insulin resistance in humans.

Figures

Figure 1
Figure 1
Cross-sectional relationships of circulating palmitoleate with insulin sensitivity estimated from the OGTT (A) and measured by the clamp (B) at baseline. Insulin sensitivity was adjusted for age, sex, and body fat in multivariate linear regression models (regression line and 95% CI). arb. units, arbitrary units.

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