The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth.
The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes.



A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity.



Despite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired β-cell function relative to insulin sensitivity.



In obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer β-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth.
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
Joon Young
JY
Kim
Human Performance and Exercise Science, Youngstown State University, Youngstown, OH.
Sara F
SF
Michaliszyn
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
Alexis
A
Nasr
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
SoJung
S
Lee
Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Hala
H
Tfayli
Sections of Pediatric Endocrinology and Diabetology, and Pediatric Comparative Effectiveness Research, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN.
Tamara
T
Hannon
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, Pittsburgh, PA.
Kara S
KS
Hughan
Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX.
Fida
F
Bacha
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, Pittsburgh, PA silva.arslanian@chp.edu.
Silva
S
Arslanian
D050154:Adiposity; D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D063766:Pediatric Obesity / Q000097:blood*; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D054795:Incretins; D007328:Insulin