Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Plasma lipidomics are associated with insulin sensitivity and secretion in overweight and obese, non-diabetic adults (#132)

Aya Mousa 1 , Negar Naderpoor 1 , Estifanos Baye 1 , Josphin Johnson 1 , Natalie Mellett 2 , Peter Meikle 2 , Barbora de Courten 1
  1. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
  2. Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia

Background: Dyslipidaemia is a key risk factor for type 2 diabetes and cardiovascular disease. Novel lipidomics methods are providing new insights into the pathophysiology of these diseases; however, data from human studies are limited. We examined whether certain lipid species and/or classes were associated with insulin sensitivity and secretion measured by gold-standard methods, in overweight or obese, non-diabetic adults.

Method: In 65 overweight or obese (mean BMI=31.5±5.2 kg/m2) non-diabetic adults (35M/19F; mean age=31.3±8.5 years), we performed lipid profiling of 459 lipid species across 26 lipid classes (liquid chromatography mass spectrometry). Gold-standard methods were used to assess body composition (%body fat, dual X-ray absorptiometry), insulin sensitivity (hyperinsulinaemic-euglycaemic clamps) and total, first-phase, and second-phase insulin secretory response (area under the curve (AUC) by intravenous glucose tolerance tests). Additional measures included anthropometry (BMI, waist-to-hip ratio) and oral glucose tolerance tests (OGTT) for fasting and 2-hour post-OGTT blood glucose concentrations. Multivariable regression was performed with adjustment for age, sex and % body fat, and all analyses were adjusted for multiple testing using Benjamini-Hochberg correction.

Results: On univariable analyses, fasting glucose, 2-hour post-OGTT glucose, fasting insulin, and insulin sensitivity were not associated with lipid species or classes (all p>0.05). However, total and second-phase insulin AUC were positively associated with the lysophosphatidylinositol (LPI) lipid class (r=781.9 mU/L,p=0.02 and r=521.3 mU/L,p=0.02, respectively). After adjustment for age, sex, and % body fat, LPI remained associated with total (p=0.02) and second-phase insulin AUC (p=0.01), and insulin sensitivity was negatively associated with the dihydroceramide (dhCer) lipid class (p=0.01) and several diacylglycerol and triacylglycerol lipid species (all p<0.05). 

Conclusion: In overweight or obese non-diabetic adults, we found that increased dhCer and LPI were associated with reduced insulin sensitivity and impaired insulin secretory response, respectively. Our findings suggest that these lipid classes may be involved in the pathophysiology of type 2 diabetes.