Although a close relationship exists among raised liver fat levels, insulin resistance, and raised liver enzyme levels (52), high levels of liver fat are not inevitably associated with hepatic insulin resistance. This is analogous to the discordance observed in the muscle of trained athletes in whom raised intramyocellular triacylglycerol is associated with high insulin sensitivity (53). This relationship is also seen in muscle of mice overexpressing the enzyme DGAT-1, which rapidly esterifies diacylglycerol to metabolically inert triacylglycerol (54). In both circumstances, raised intracellular triacylglycerol stores coexist with normal insulin sensitivity. When a variant of PNPLA3 was described as determining increased hepatic fat levels, it appeared that a major factor underlying nonalcoholic fatty liver disease and insulin resistance was identified (55). However, this relatively rare genetic variant is not associated with hepatic insulin resistance (56). Because the responsible G allele of PNPLA3 is believed to code for a lipase that is ineffective in triacylglycerol hydrolysis, it appears that diacylglycerol and fatty acids are sequestered as inert triacylglycerol, preventing any inhibitory effect on insulin signaling.
Watch for thirst or a very dry mouth, frequent urination, vomiting, shortness of breath, fatigue and fruity-smelling breath. You can check your urine for excess ketones with an over-the-counter ketones test kit. If you have excess ketones in your urine, consult your doctor right away or seek emergency care. This condition is more common in people with type 1 diabetes but can sometimes occur in people with type 2 diabetes.
Note that these medications used to treat type 2 diabetes are typically not used in pregnant or breastfeeding women. At present the only recommended way of controlling diabetes in women who are pregnant or breastfeeding is by diet, exercise, and insulin therapy. You should speak with your health-care professional if you are taking these medications, are considering becoming pregnant, or if you have become pregnant while taking these medications.