Daytime variability of postprandial glucose tolerance and pancreatic B-cell function using 12-h profiles in persons with Type 2 diabetes.
OBJECTIVE
To study the variation in daytime glucose tolerance and pancreatic B-cell function at different levels of glycated haemoglobin (HbA(1c)) in subjects with Type 2 diabetes (T2DM).


METHODS
T2DM subjects (n = 49; 34 men) had 12-h daytime plasma glucose (PG), insulin (PI), total (PTp) and intact proinsulin (PIp) profiles determined in response to three identical test meals at 4-h intervals. Subjects were divided into three groups according to HbA(1c)--group 1: < 7.3% (n = 18); group 2: 7.3-8.0% (n = 17); group 3: > 8.0% (n = 14). Fasting and preprandial (prior to meals 2 and 3) concentrations, total area under the curve (AUC), AUC above fasting (dAUC) and maximum postprandial metabolic concentrations (C(max)) were compared between the three meals and across the groups.


RESULTS
Subjects in group 1 had significantly higher fasting plasma glucose (FPG) compared with preprandial PG concentrations (7.1 +/- 0.2 vs. 5.9 +/- 0.3 vs. 5.4 +/- 0.2; P < 0.01). Subjects in groups 2 and 3 had significantly higher FPG compared with preprandial PG levels prior to meal 3. PG.dAUC was highest in response to meal 1 and lowest following meal 2 (P < 0.05). FPI concentrations were significantly lower compared with preprandial PI concentrations. Subjects in group 1 had significantly higher PI prior to meal 2 compared with meal 3. PI.dAUC was highest in response to meal 1. Subjects in group 1 had lowest PI.dAUC following meal 2. FTp and FIp concentrations were also significantly lower compared with preprandial concentrations. PTp.dAUC and PIp.dAUC was highest in response to meal 1.


CONCLUSIONS
There appears to be a shift in diurnal variation in glucose homeostasis and pancreatic B-cell function. Subjects had decreased glucose tolerance in response to the first and third meal of the day irrespective of glycaemic control. The variability in glucose tolerance was reflected by both quantitative and qualitative dysfunction of the pancreatic B-cell.
Peter
R
R
Diabetes Research Unit, University Hospital Llandough, Penarth, UK. rajpeter@aol.com
Dunseath
G
G
Luzio
S D
SD
Chudleigh
R
R
Roy Choudhury
S
S
Owens
D R
DR
D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D011384:Proinsulin / Q000378:metabolism
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D011384:Proinsulin; C517652:hemoglobin A1c protein, human