Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes

Free Radic Biol Med. 2016 Jun;95:268-77. doi: 10.1016/j.freeradbiomed.2016.03.020. Epub 2016 Mar 29.


Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients.

Keywords: Diabetic ketoacidosis (DKA); Hyperketonemia; Ketogenic diet (KD); Ketones; Oxidative stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetoacetates / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / pathology
  • Energy Metabolism / genetics
  • Glucose / metabolism
  • Humans
  • Ketone Bodies / metabolism*
  • Ketones / metabolism
  • Ketosis / blood*
  • Ketosis / pathology
  • Oxidative Stress / genetics*
  • Risk Factors


  • Acetoacetates
  • Ketone Bodies
  • Ketones
  • acetoacetic acid
  • Glucose