Increased serum concentrations of persistent organic pollutants among prediabetic individuals: potential role of altered substrate oxidation patterns.
BACKGROUND
There is a need for a better understanding of the potential role of persistent organic pollutants (POPs) in the pathogenesis of type 2 diabetes.


OBJECTIVE
Our objective was to determine the association of serum concentrations of POPs with early signs of type 2 diabetes in regard to glucose and lipid metabolism.


METHODS
In this cross-sectional study, we used recent studies of 148 Danish middle-aged normoglycemic, prediabetic, and diabetic individuals examined by the euglycemic-hyperinsulinemic clamp technique with indirect calorimetry; 66 of these individuals also had an i.v. glucose tolerance test. Concentrations of POPs were analyzed in banked serum from the participants. Associations with basal and insulin-stimulated glucose and lipid metabolism were assessed after adjustment for age, sex, and body fat percentage.


RESULTS
Individuals with prediabetes and diabetes had higher serum concentrations of several POPs compared with normoglycemic individuals. In the nondiabetic population, higher POPs levels were associated with elevated fasting plasma glucose concentrations as well as reduced glucose oxidation, elevated lipid oxidation, and elevated serum concentrations of free fatty acids (P < 0.05). We found no associations of POPs with first-phase insulin secretion, hepatic or peripheral insulin sensitivity, or nonoxidative glucose metabolism.


CONCLUSIONS
Diabetic and prediabetic individuals have elevated serum concentrations of POPs. In nondiabetic individuals, POPs exposure is related to altered substrate oxidation patterns with lower glucose oxidation and higher lipid oxidation rates. These findings indicate that POPs may affect peripheral glucose metabolism by modifying pathways involved in substrate partitioning rather than decreasing insulin-dependent glucose uptake.
Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. krif@steno.dk
Kristine
K
Færch
Kurt
K
Højlund
Birgitte F
BF
Vind
Allan
A
Vaag
Christine
C
Dalgård
Flemming
F
Nielsen
Philippe
P
Grandjean
D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D010084:Oxidation-Reduction; D010186:Pancreatic Function Tests; D011236:Prediabetic State / Q000097:blood*
D004785:Environmental Pollutants; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin