On Glucose Metabolism in Patients with the m.3243A>G Mutation
Lindroos, Markus (2013-06-01)
On Glucose Metabolism in Patients with the m.3243A>G Mutation
Lindroos, Markus
(01.06.2013)
Annales Universitatis Turkuensis D 1071 Turun yliopisto
Julkaisun pysyvä osoite on:
https://urn.fi/URN:ISBN:978-951-29-5396-7
Siirretty Doriasta
https://urn.fi/URN:ISBN:978-951-29-5396-7
Kuvaus
Siirretty Doriasta
Tiivistelmä
Background: The m.3243A>G mutation in mitochondrial DNA is the most common
cause for mitochondrial diabetes. In addition, unexpected deaths related to the
m.3243A>G associate with encephalopathy and cardiomyopathy. Failing
mitochondrial respiratory chain in neurons, myocytes and beta cells is considered to
underlie the multiorgan manifestations of the m.3243A>G.
Aims: The primary aim of the study was to characterize the organ-specific glucose
metabolism in patients with m.3243A>G and secondly, to study patients with or
without signs of diabetes, cardiomyopathy or encephalopathy. The insulin-stimulated
glucose metabolism in brain, heart, skeletal muscle, adipose tissue and liver were
measured with 2-deoxy-2-[18F]fluoro-α-D-glucose in 15 patients and 14 controls. Brain
oxygen metabolism was assessed with [15O]oxygen and insulin secretion was modelled
based on oral glucose tolerance test.
Results: The glucose oxidation in brain was globally decreased in patients with or
without clinical encephalopathy. The insulin-stimulated glucose influx to skeletal
muscle and adipose tissue was decreased in patients with or without diabetes as the
hepatic glucose metabolism was normal. Impaired beta cell function and myocardial
glucose uptake were associated with the high m.3243A>G heteroplasmy.
Conclusions: This cross-sectional study suggests that: 1) The ability of insulin to
stimulate glucose metabolism in skeletal muscle and adipose tissue is weakened before the beta cell failure results in mitochondrial diabetes. 2) Glucose oxidation defect is
detected in otherwise unaffected cerebral regions in patients with the m.3243A>G, thus
it likely precedes the clinical encephalopathy. 3) Uneconomical glucose
hypometabolism during hyperinsulinemia contributes to the cardiac vulnerability in
patients with high m.3243A>G heteroplasmy
cause for mitochondrial diabetes. In addition, unexpected deaths related to the
m.3243A>G associate with encephalopathy and cardiomyopathy. Failing
mitochondrial respiratory chain in neurons, myocytes and beta cells is considered to
underlie the multiorgan manifestations of the m.3243A>G.
Aims: The primary aim of the study was to characterize the organ-specific glucose
metabolism in patients with m.3243A>G and secondly, to study patients with or
without signs of diabetes, cardiomyopathy or encephalopathy. The insulin-stimulated
glucose metabolism in brain, heart, skeletal muscle, adipose tissue and liver were
measured with 2-deoxy-2-[18F]fluoro-α-D-glucose in 15 patients and 14 controls. Brain
oxygen metabolism was assessed with [15O]oxygen and insulin secretion was modelled
based on oral glucose tolerance test.
Results: The glucose oxidation in brain was globally decreased in patients with or
without clinical encephalopathy. The insulin-stimulated glucose influx to skeletal
muscle and adipose tissue was decreased in patients with or without diabetes as the
hepatic glucose metabolism was normal. Impaired beta cell function and myocardial
glucose uptake were associated with the high m.3243A>G heteroplasmy.
Conclusions: This cross-sectional study suggests that: 1) The ability of insulin to
stimulate glucose metabolism in skeletal muscle and adipose tissue is weakened before the beta cell failure results in mitochondrial diabetes. 2) Glucose oxidation defect is
detected in otherwise unaffected cerebral regions in patients with the m.3243A>G, thus
it likely precedes the clinical encephalopathy. 3) Uneconomical glucose
hypometabolism during hyperinsulinemia contributes to the cardiac vulnerability in
patients with high m.3243A>G heteroplasmy
Kokoelmat
- Väitöskirjat [2763]