title: Increased glycemic variability and decrease of the postprandial glucose contribution to HbA1c in obese subjects across the glycemic continuum from normal glycemia to first time diagnosed diabetes.
abstract: OBJECTIVE
  The contribution of postprandial glycemia (PPG) to hyperglycemia has been shown to decrease as HbA1c increased in type 2 diabetic patients. This study aimed at examining, in a series of overweight/obese patients without known glycemic disorder, the contribution of PPG to a "relative" hyperglycemia (glucose values≥5.5 mmol/L) and the presence of glycemic variability according to HbA1c levels.
  
  
  METHODS
  Seventy overweight/obese inpatients (body mass index 35.2±6.8 kg/m2) without known glycemic disorder were included. Participants were classified according to an oral glucose tolerance test (according to the American Diabetes Association criteria) as patients with normoglycemia (n=33), with intermediate hyperglycemia (n=24) or diabetes (n=13). They were separated into HbA1c quartiles (Q1 to Q4). A 24 hour continuous glucose monitoring was used under a 1800 kcal diet and minimal physical activity. We assessed PPG contribution (3 hour period after each meal) to the "relative" 24 hour hyperglycemia (glucose values ≥5.5 mmol/L); the remaining time was considered as the fasting/post-absorptive period.
  
  
  RESULTS
  HbA1c range was from 5.1% to 7.4% (32 to 57 mmol/mmol). From the lowest to the highest HbA1c quartile, the area under the curve (AUC) for the "relative" hyperglycemia presented a 17-fold increase for the fasting/post-absorptive (p<0.001) period and a 7-fold increase postprandially (p<0.001). The percent of PPG contribution to the "relative" hyperglycemia was calculated with the following formula [100×(postprandial 3 hour AUC-3 h AUC for a constant 5.5 mmol/L glycemia)/(total 24 h AUC-24 h AUC for constant 5. 5 mmol/L glycemia)] and decreased from Q1 to Q4 of HbA1c (81.2%, 66%, 65.8%, 57%; p<0.001). Increasing HbA1c quartiles were associated with higher daily mean blood glucose level (p<0.001) and higher levels of daily glucose variability indices, including mean amplitude of glycemic excursions (p<0.01).
  
  
  CONCLUSIONS
  In overweight/obese patients, HbA1c was associated with lower PPG contribution to "relative" hyperglycemia and greater glycemic variability. The present findings support the importance of postprandial period in glycemic exposure even before the appearance of diabetes.
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France.
authors.forename: Marinos
authors.initials: M
authors.lastname: Fysekidis
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France; Sorbonne Paris Cité, UMR U1153 Inserm/U1125 Inra/Cnam/Université Paris 13, Bobigny, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cosson
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France.
authors.forename: Isabela
authors.initials: I
authors.lastname: Banu
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France.
authors.forename: Régine
authors.initials: R
authors.lastname: Duteil
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Cyrille
authors.affiliation: AP-HP, Jean Verdier Hospital, Paris 13 University, Sorbonne Paris Cité, Department of Endocrinology-Diabetology-Nutrition, CRNH-IdF, CINFO, Bondy, France. Electronic address: paul.valensi@jvr.aphp.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Valensi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050177:Overweight / Q000097:blood; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin
keywords: Contribution to Hb1Ac; Obesity; Prediabetes