Assessing and targeting insulin resistance

The global obesity pandemic has led to a concomitant surge in obesity related diseases, collectively known as the metabolic syndrome. Many of these conditions add to an increased risk of cardiovascular disease. Impaired insulin action, or insulin resistance, is regarded as a key element of the metabolic syndrome. The aim of this thesis was to improve our understanding of insulin resistance and its relation to other aspects of the metabolic syndrome.
In Part I, we demonstrate that fasting plasma insulin is a reliable indicator of peripheral insulin resistance, and contrarily, impaired fasting glucose is associated with hepatic insulin resistance.
In Part II, we provide insight into the complex relationship between (postprandial) GLP-1 and fructose-induced FGF-21 release with insulin sensitivity in people with obesity, before and 1 year following weight loss due to gastric bypass surgery. We demonstrate an association between postprandial GLP-1 and insulin sensitivity before and after weight loss, and indicate that the novel phenomenon FGF-21 resistance does not improve following weight loss.
In Part III, we demonstrate that omega-3 fatty acid supplementation does not meaningfully reduce intrahepatic lipid or insulin resistance in liver or skeletal muscle. We do observe improved insulin-mediated suppression of adipose tissue lipolysis. We also demonstrate that oral administration of Anaerobutyricum soehngenii is a safe and well-tolerated potential treatment of insulin resistance in people with obesity.