title: Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes.
abstract: OBJECTIVE
  Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM.
  
  
  METHODS
  We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose.
  
  
  RESULTS
  Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity.
  
  
  CONCLUSIONS
  European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.
authors.affiliation: Section of Endocrinology and Metabolic Medicine, Imperial College Faculty of Medicine, St Mary's Hospital, London, UK. mark.mccarthy@drl.ox.ac.uk
authors.forename: Eleni
authors.initials: E
authors.lastname: Kousta
authors.forename: Natasha J
authors.initials: NJ
authors.lastname: Lawrence
authors.forename: Ian F
authors.initials: IF
authors.lastname: Godsland
authors.forename: Anna
authors.initials: A
authors.lastname: Penny
authors.forename: Victor
authors.initials: V
authors.lastname: Anyaoku
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Millauer
authors.forename: Ester
authors.initials: E
authors.lastname: Cela
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Johnston
authors.forename: Stephen
authors.initials: S
authors.lastname: Robinson
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D011247:Pregnancy; D012189:Retrospective Studies; D012306:Risk; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides