Emerging parameters of the insulin and glucose response on the oral glucose tolerance test: reproducibility and implications for glucose homeostasis in individuals with and without diabetes.
OBJECTIVE
Recent studies have suggested that novel parameters of the insulin and glucose response on the oral glucose tolerance test (OGTT) can provide metabolic insight beyond glucose tolerance, but have not evaluated their reproducibility. Thus, our aim was to evaluate the reproducibility of these parameters and, if confirmed, characterize their clinical/pathophysiologic relevance in healthy and diabetic individuals.


METHODS
Thirty healthy adults each underwent 3 replicate OGTTs, enabling assessment of the reproducibility of the following 5 parameters: time to insulin peak, shape of the glucose curve, glucose nadir below baseline, 1-h post-challenge glucose, and time to glucose peak. The only reproducible parameter was then further evaluated in 63 patients with early type 2 diabetes (T2DM) before and after 4-weeks of intensive insulin therapy (IIT) designed to improve beta-cell function (measured by Insulin Secretion-Sensitivity-Index-2 (ISSI-2)).


RESULTS
Of the five parameters, only time to glucose peak displayed reliable reproducibility on replicate testing (κ=0.76). Over 80% of controls had their glucose peak at 30-min post-load, whereas all but one of the diabetic patients had their peak at 60-min or later. ISSI-2 was lower in T2DM patients with peak at ≥90-min than in those with peak at ≤60-min (P=0.012). In patients in whom IIT improved beta-cell function by ≥20% from baseline, 39.1% had glucose peak on the post-therapy OGTT shift to an earlier timepoint, as compared to 15.4% with similar shift in those without such improvement(P=0.03).


CONCLUSIONS
Time to glucose peak is a reproducible characteristic on the OGTT and associated with beta-cell function in early T2DM.
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada; Division of Endocrinology, University of Toronto, Toronto, Canada.
Caroline Kaercher
CK
Kramer
Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Division of Endocrinology, Li Ka Shing Knowledge Institute and Keenan Research Centre, St. Michael's Hospital, Toronto, Canada.
Vladimir
V
Vuksan
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.
Haysook
H
Choi
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada; Division of Endocrinology, University of Toronto, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
Bernard
B
Zinman
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada; Division of Endocrinology, University of Toronto, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada. Electronic address: rretnakaran@mtsinai.on.ca.
Ravi
R
Retnakaran
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
D001786:Blood Glucose; D007328:Insulin
Beta-cell function; Oral glucose tolerance test; Patterns; Reproducibility; Time to glucose peak