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Rigshospitalet - a part of Copenhagen University Hospital
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Mitochondrial mutation m.3243A>G associates with insulin resistance in non-diabetic carriers

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  • Jakob Høgild Langdahl
  • Anja Lisbeth Frederiksen
  • John Vissing
  • Morten Frost Nielsen
  • Knud Bonnet Yderstræde
  • Per Heden Andersen
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AIM: This case-control study aimed to examine impairments in glucose metabolism in non-diabetic carriers of the mitochondrial mutation m.3243A>G by evaluating insulin secretion capacity and sensitivity.

METHODS: Glucose metabolism was investigated in 23 non-diabetic m.3243A>G carriers and matched healthy controls with an extended 4-hour oral glucose tolerance test (OGTT). Insulin sensitivity index and acute insulin response were estimated on basis of the OGTT. This was accompanied by examination of body composition by Dual-energy X-ray Absorptiometry (DXA), maximum aerobic capacity, and a Recent Physical Activity Questionnaire (RPAQ).

RESULTS: Fasting p-glucose, s-insulin and s-c-peptide levels did not differ between m.3243A>G carriers and controls. Insulin sensitivity index (BIGTT-S1) was significantly lower in the m.3243A>G carriers, but there was no difference in the acute insulin response between groups. P-lactate levels were higher in carriers throughout the OGTT. VO2max, but not BMI, waist and hip circumferences, lean and fat body mass %, MET or grip strength, was lower in mutation carriers. BIGTT-S1 remained lower in mutation carriers after adjustment for multiple confounding factors including VO2max in regression analyses.

CONCLUSIONS: Glucose metabolism in m.3243A>G carriers was characterized by reduced insulin sensitivity, which could represent the earliest phase in the pathogenesis of m.3243A>G-associated diabetes.

Original languageEnglish
JournalEndocrine Connections
Volume8
Issue number7
Pages (from-to)829-837
Number of pages9
ISSN2049-3614
DOIs
Publication statusPublished - 1 May 2019

    Research areas

  • Insulin resistance, Mitochondrial DNA point mutation m.3243A>G, Mitochondrial dysfunction, Monogenic diabetes

ID: 58155781