title: Systemic metabolic markers and myocardial glucose uptake in type 2 diabetic and coronary artery disease patients treated for 16 weeks with rosiglitazone, a PPARγ agonist.
abstract: BACKGROUND
  Treatment with rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, in type 2 diabetic mellitus (T2DM) patients is under scrutiny because it affects adversely cardiovascular outcomes. In T2DM patients, with existing coronary heart disease, short-term treatment with rosiglitazone increases myocardial glucose uptake (MGU). Serum metabolic and lipoprotein subclass changes, which may be associated with this rosiglitazone-induced improvement, are unknown.
  
  
  METHODS
  Patients with both T2DM and coronary heart disease were separated into placebo (n = 26) and treatment (rosiglitazone 4-8 mg; n = 25) groups. After 16 weeks of treatment, serum NMR metabolomics was used to measure circulating low-molecular-weight metabolites and lipoprotein subclasses and lipids that are associated with T2DM before and after the treatment. Significant metabolic measure changes after rosiglitazone treatment were correlated to MGU values assessed with [(18)F]fluorodeoxyglucose positron emission tomography.
  
  
  RESULTS
  Compared to placebo, the treatment significantly increased circulating glutamine and decreased lactate concentrations. Circulating lactate concentrations showed a significant inverse association with MGU after rosiglitazone treatment.
  
  
  CONCLUSIONS
  In T2DM patients with existing coronary heart disease, short-term rosiglitazone treatment caused minor improvements in metabolism: serum lactate and glutamine concentrations changed, reflecting improvements in insulin sensitivity, and circulating lactate concentrations inversely correlated to increases in myocardial glucose uptake.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital , Turku , Finland.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Badeau
authors.forename: Miikka-Juhani
authors.initials: MJ
authors.lastname: Honka
authors.forename: Riikka
authors.initials: R
authors.lastname: Lautamäki
authors.forename: Murray
authors.initials: M
authors.lastname: Stewart
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005973:Glutamine / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019344:Lactic Acid / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008074:Lipoproteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005973:Glutamine; D019344:Lactic Acid