Oral AGE Restriction Ameliorates Insulin Resistance in Obese Individuals With the Metabolic Syndrome: A Randomised Controlled Trial

Diabetologia. 2016 Oct;59(10):2181-92. doi: 10.1007/s00125-016-4053-x. Epub 2016 Jul 29.

Abstract

Aims/hypothesis: We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome.

Methods: A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome.

Results: Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ± 1.8 to 1.9 ± 1.3 (p < 0.001) in the L-AGE group, while it increased from 2.9 ± 1.2 to 3.6 ± 1.7 (p < 0.002) in the Reg-AGE group.

Conclusions/interpretation: L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat 'at-risk' obesity.

Trial registration: ClinicalTrials.gov NCT01363141 FUNDING: The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231).

Keywords: AGER1; Cardiovascular disease; Diabetes; Glycotoxins; Inflammation; Innate defence; RAGE; SIRT1.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Aged
  • Aged, 80 and over
  • Animals
  • Blood Glucose / drug effects
  • Blotting, Western
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Glycation End Products, Advanced / therapeutic use*
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy
  • Insulin / blood
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / drug therapy
  • Mice
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Waist Circumference / drug effects
  • Waist Circumference / genetics

Substances

  • Blood Glucose
  • Glycation End Products, Advanced
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT01363141