Evaluation of genetic predisposition to insulin resistance by nutrient-induced insulin output ratio (NIOR).
BACKGROUND
New tools to identify genotype-phenotype interactions need to be described and implemented. The aim of this study was to identify correlation between the risk originating from gene variation and diet-dependent development of insulin resistance.


METHODS
Insulin output in terms of area under the curve after an oral glucose tolerance test (AUC Ins OGTT) and lipid tolerance tests (AUC Ins OLTT) were measured in 167 overweight/obese patients. Estimation of the 18 common gene polymorphisms for obesity risk and standard phenotyping were performed.


RESULTS
Insulin output (AUC Ins OGTT) correlated strongly between both insulin treatments across the whole group. However, within the genotype sub-groups, correlation was lower or did not exist. Using a nutrient-induced insulin output ratio (NIOR), calculated as AUC Ins OLTT/AUC Ins OGTT, values ranged from 0.42 to 5.83 and correlated significantly with body mass index (BMI) and leptin, but not with age, gender, waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for poorer tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism. Thus, the new insulin index NIOR may distinguish gene variant carriers into groups of glucose- or lipid-sensitive phenotypes.


CONCLUSIONS
We suggest that the OLTT/OGTT insulin output ratio (NIOR) may be predictive for identifying individuals who are phenotypically susceptible to insulin resistance in response to high fat or carbohydrate in their habitual diet.
Wybranska
Iwona
I
Department of Clinical Biochemistry, The Jagiellonian University, Medical College, Krakow, Poland. mbwybran@cyf-kr.edu.pl
Malczewska-Malec
Malgorzata
M
Partyka
Lukasz
L
Kiec-Wilk
Beata
B
Kosno
Katarzyna
K
Leszczynska-Golabek
Iwona
I
Zdzienicka
Anna
A
Gruca
Anna
A
Kwasniak
Malgorzata
M
Dembinska-Kiec
Aldona
A
D000328:Adult; D019540:Area Under Curve; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D054439:Ghrelin / Q000235:genetics* / Q000502:physiology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity; D011110:Polymorphism, Genetic
D054439:Ghrelin; D007328:Insulin; D008055:Lipids