Background
Discussion
Epidemiological associations
Genes strengthen causal links between obesity and diabetes
Evidence for the ectopic fat hypothesis in T2DM
Ethnicity, sex, and the ectopic fat hypothesis
The crucial role of ectopic liver fat and related molecular explanations
Is type diabetes reversible via loss of fat or ectopic fat?
Summary
Type of evidence | Findings |
---|---|
Epidemiological | BMI is the dominant risk factor for type 2 diabetes. Whereas RRs for CVD with rising BMI tend to be around twofold to threefold once BMI levels reach around 30-35 kg/m2, RRs for diabetes are often around a log scale higher, approaching 50 to 80 times at BMI 35 kg/m2 versus BMI of 21 kg/m2. |
Genetic | Genes linked to higher BMI, in particular the FTO gene, have been clearly shown to predict T2DM. |
Mechanistic | Ectopic fat in key organs that are relevant to glucose metabolism appears to be crucial for tissue insulin resistance. In the liver, ectopic fat via metabolic intermediates interferes with insulin signalling and thereby contributes to higher fasting glucose levels and hypertriglyceridaemia. Characteristics linked to earlier ectopic fat gain include male sex, family history of diabetes and certain ethnic origins. |
Clinical | BMI or waist size make up around half of the weighting in diabetes risk scores, regardless of ethnicity. Moreover, around half of all patients with diabetes are obese. |
Reversibility | Weight loss via dietary or surgical methods can reverse T2DM and even some patients previously on insulin can show remission, suggesting improvements in β-cell function. Rapid reductions in glucose levels appear to relate to changes in liver fat content in the short term whereas diabetes remission appears to relate to the amount of fat loss in the longer term. |