ISSN 1849-9031 (Online)

ISSN 1849-8922    (Print)

Ketosis in type 2 diabetes mellitus: complication or compensatory mechanism?
Ivan Kruljac, Miroslav Ćaćić, Petra Ćaćić, Milan Vrkljan.

Abstract


The exact clinical role of diabetic ketosis in patients presenting to emergency departments with hyperglycemic crises is largely unknown. The aim of this brief review is to provide insights into possible mechanisms and clinical impact of diabetic ketosis in patients with hyperglycemic crises and clinical features of type 2 diabetes mellitus (T2DM). Patients with T2DM have impaired ketogenesis and lower blood ketone levels. High insulin, low glucagon, IGF-I, ghrelin and adiponectin levels are associated with suppressed ketogenesis. Adenosine 5’-monophosphate-activated protein kinase is an enzyme expressed in skeletal muscle and seems to have pivotal role in impaired ketogenesis. An increase in ketogenesis is associated with weight loss, increase in insulin sensitivity and serum IGF-I levels, which have beneficial effects on glycemia but also on cardiovascular morbidity and mortality. Ketone bodies are far more efficient fuel sources than glucose, especially in diabetics with heart failure and kidney disease. In theory, ketogenesis in patients with T2DM can be improved by low- carbohydrate and low-calorie diet, physical activity, moderate alcohol use, metformin, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 agonists and sodium/glucose cotransporter 2 (SGLT-2) inhibitors. SGLT-2 inhibitors are the most potent inducers of ketogenesis. They induce profound glycosuria with a consequent shift to fatty acid metabolism and increased ketogenesis. This could potentially explain how SGLT-2 inhibitor empagliflozin lowers cardiovascular mortality and slowers progression of kidney disease. Therefore, we believe that diabetic ketosis in patients with hyperglycemic crisis may be a compensatory mechanism, rather than a complication itself. Further prospective studies are needed to test this hypothesis.