**4. ABCA1, Glucose Metabolism and Type 2 Diabetes**

β-cell failure and insulin resistance in muscle and liver represent the core pathophysiologic defects in type 2 diabetes [99]. Although ABCA1 and cholesterol homeostasis are critical in β-cell function and play a role in insulin resistance, global loss of ABCA1 function is not enough to cause type 2 diabetes (T2D). Diabetes is not a characteristic feature of Tangier disease and was not a feature reported in global *Abca1*−/<sup>−</sup> mice [100], although some consider diabetes as a complication of Tangier [101]. Moreover, while several patients suffering simultaneously from both diseases have been reported in the medical literature, particularly in the Japanese population [60,102–104], there are no reports on whether the prevalence of T2D is higher in Tangier patients. Still, several lines of evidence including tissue-specific *Abca1* KO models, human gene variation and ABCA1 expression studies point to a strong role of cholesterol homeostasis and ABCA1 in β-cell organization, function, and survival. Additionally, studies in muscle cell, hepatocyte and adipocyte-specific KO models, and some studies in humans, have shown ABCA1 also plays a role in peripheral insulin resistance. Altogether, this suggests that ABCA1 function is one of many factors which, acting in concert, contribute to the etiology of T2D.
