Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with a strong family history of type 2 diabetes.
OBJECTIVE
Gut-derived hormone peptide YY (PYY) is low in subjects with obesity and type 2 diabetes (T2D). However, it is unknown whether this is a primary defect or a consequence of metabolic disturbances. In this study, we aimed to assess whether low fasting and postprandial PYY secretion is an early defect, potentially promoting the development of obesity and T2D, and whether it is modified by macronutrient content.


METHODS
Prospective cross-sectional cohort study.


METHODS
Nine individuals with a strong family history of T2D (REL) and seven age and adiposity matched individuals with no family history of T2D (CON).


METHODS
Metabolic studies including hyperinsulinemic-euglycemic clamp, dual X-ray absorptiometry and two meal tests containing 1000 kcal with an either high fat (76%) or high carbohydrate (76%) content.


METHODS
Fasting and postprandial PYY levels were measured and analyzed for potential correlations with markers for adiposity and insulin resistance.


RESULTS
Insulin sensitivity was not different between REL and CON. Fasting glucose, insulin, triglycerides and PYY were also not different between groups. However, the postprandial incremental area under curve (AUC) of PYY was significantly lower in REL after the high carbohydrate (HCHO) meal (+27.3 vs +60.6% increase from baseline, P=0.038). The AUC of insulin during HCHO meal correlated negatively with both AUC and fasting level of PYY (r=-0.58 and -0.60, respectively, P<0.05).


CONCLUSIONS
A blunted postprandial PYY secretion is observed in a very early stage in the development of T2D in genetically susceptible individuals. This defect precedes the presence of insulin resistance and adiposity, and could therefore predispose to the development of T2D.
Viardot
A
A
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. a.viardot@garvan.org.au
Heilbronn
L K
LK
Herzog
H
H
Gregersen
S
S
Campbell
L V
LV
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D018450:Disease Progression; D019858:Enteroendocrine Cells / Q000378:metabolism; D016021:Epidemiologic Studies; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D019894:Peptide YY / Q000097:blood* / Q000235:genetics; D019518:Postprandial Period / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D019894:Peptide YY