Relationship between gestational diabetes mellitus and type 2 diabetes: evidence of mitochondrial dysfunction.
BACKGROUND
We examined the pathogenesis of gestational diabetes mellitus (GDM) in a large Dutch multiethnic cohort.


METHODS
We used a 2-step testing procedure to stratify 2031 consecutive pregnant women into 4 groups according to American Diabetes Association criteria: (a) normal glucose tolerance (NGT), (b) mild gestational hyperglycemia (MGH), (c) GDM without early postpartum diabetes within 6 months of delivery (GDM1), and (d) GDM with early postpartum diabetes (GDM2). Antepartum and postpartum clinical characteristics and measures of glucose tolerance were documented.


RESULTS
Overall, 1627 women had NGT, 237 had MGH, 156 had GDM1, and 11 had GDM2. Prepregnancy body mass index values progressively increased from NGT to MGH to GDM1. The fasting plasma glucose concentration, the 100-g oral glucose tolerance test (OGTT) area under the curve, and the mean glucose concentration during the OGTT all increased progressively among the 4 groups. The fasting C-peptide concentration displayed an inverted-U pattern, with a maximum at a mean plasma glucose concentration during the OGTT of 9.6 mmol/L in the transition from GDM1 to GDM2. The fasting C-peptide/glucose concentration ratio decreased by 42% in GDM patients compared with NGT patients, whereas the ratios in MGH and NGT women were similar.


CONCLUSIONS
Progressive metabolic derangement of glucose tolerance 1st detected during pregnancy mimics the pathogenesis of type 2 diabetes. In addition, our results imply an impaired basal glucose effectiveness in the early prediabetic state. To explain the parallel in both metabolic derangements, we postulate that GDM, like type 2 diabetes, is attributable to the same inherited mitochondrial dysfunction.
Weijers
Rob N M
RN
Department of Clinical Chemistry and Haematology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. robw01@xs4all.nl
Bekedam
Dick J
DJ
D000328:Adult; D002096:C-Peptide / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000503:physiopathology*; D016640:Diabetes, Gestational / Q000208:ethnology / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009426:Netherlands; D011247:Pregnancy
D002096:C-Peptide