Altered lipid metabolism associated with insulin resistance and obesity is a major contributor to the onset and progression of type 2 diabetes

  title={Altered lipid metabolism associated with insulin resistance and obesity is a major contributor to the onset and progression of type 2 diabetes},
  author={Michael J. Christopher},
The Australian population and indeed most of the developed world are facing an obesity epidemic, which is associated with a dramatic increase in the incidence of type 2 diabetes (T2D). Obesity and insulin resistance (IR) are strong predictors of the development of T2D. Dyslipidaemia as assessed by “traditional” measures (raised plasma triglycerides and/or decreased high-density lipoprotein cholesterol) is also a major risk factor for the onset and progression of T2D. However, the measurement of… 
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Mapping the Associations of the Plasma Lipidome with Insulin Resistance and Response to an Oral Glucose Tolerance Test.

The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of insulin resistance, which underlie the involvement of molecular lipid species in the pathogenesis of insulin Resistance and possibly crosstalk between insulin resistance and sex-specific regulation of lipid metabolism.



Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes

Lipid classes and species associated with type 2 diabetes provide support for a number of existing paradigms of dyslipidemia and suggest new avenues of investigation.

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Irrespective of species, lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity, indicating that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.

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Results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.

Top-Down Lipidomics Reveals Ether Lipid Deficiency in Blood Plasma of Hypertensive Patients

Top-down shotgun lipidomics demonstrated that hypertension is accompanied by specific reduction of the content of ether lipids and free cholesterol that occurred independently of lipidomic alterations induced by obesity and insulin resistance.

Lipidomics is providing new insight into the metabolic syndrome and its sequelae

The ongoing identification and validation of lipid biomarkers will likely see their introduction into clinical practice for improved quantification of disease risk, earlier identification of disease and improved patient management in the near future.

Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β‐cell dysfunction

Evidence is discussed that FFA represent a crucial link between insulin resistance and β‐cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes.

Targeting Ceramide Synthesis to Reverse Insulin Resistance

This study supported the conclusion, drawn from in vitro work, that saturated fatty acids contribute to ceramide accumulation, whereas unsaturated fatty acids induce diabetes, and longer-term administration of the inhibitor was also able to improve glucose tolerance in genetically obese Zucker diabetic fatty rats and fat-fed mice.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study.

Lp-PLA(2) activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis.

Influence of gender, obesity, and muscle lipase activity on intramyocellular lipids in sedentary individuals.

The data suggest that intramyocellular DAG is an independent predictor of insulin resistance in humans and that its levels correlate with lipolytic enzymes activity in skeletal muscle but not with markers of adiposity.

Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism.

The role of ceramide and other sphingolipid metabolites in insulin resistance, beta-cell failure, cardiomyopathy, and vascular dysfunction is reviewed, focusing on in vivo studies that identify enzymes controlling sphingoipid metabolism as therapeutic targets for combating metabolic disease.