The acute effect of Orlistat on dietary glycotoxins in diabetics and healthy women.
OBJECTIVE
Advanced glycation end products (AGEs) formation is implicated in diabetic complications. Exogenous AGEs, namely glycotoxins, are present in certain foods and are absorbed from the gastrointestinal tract. Experimental data suggest that lifestyle interventions reducing their content in diet have beneficial effect.


METHODS
Fourteen healthy (age: 42.14 +/- 12.38 years; body mass index [BMI]: 27.85 +/- 7.06 kg/m2) and ten women with type 2 diabetes (T2DM) (age: 48.70 +/- 9.31 years; BMI: 32.55 +/- 7.14 kg/m2) were enrolled in the study. A meal rich in AGEs was provided in a two-day protocol and on day 2, 240 mg of Orlistat were administered post-meal.


RESULTS
On day 1, serum AGEs levels showed a rise at 3 hours post-meal compared to baseline values in both groups (controls: 12.2%; P<0.001), T2DM: 2.6%; P=0.013), but at 5 hours post-meal only in the controls (control: 12.2%; P<0.001); T2DM: 1.9%; P=0.075). On day 2 at 3 hours post-meal control values showed a rise of 3.1% (P=0.003); T2DM of 1.9% (P=0.013); at 5 hours post-meal rise for controls was 4.6% (P=0.012); and for T2DM was 1.8% (P=0.009). The corresponding rise was significantly lower on day 2 only in controls at 3 and 5 hours post-meal (P=0.003; P=0.05, respectively).


CONCLUSIONS
Orlistat reduced the absorption of glycotoxins acutely and improved the metabolic profile in the control group, without an apparent beneficial effect in the diabetic group. The clinical significance of this observation should be further investigated in normal population, while in diabetics long-term studies may be required to demonstrate possible clinically significant effects.
Diamanti-Kandarakis
E
E
Endocrine Section, First Department of Medicine, Laiko Hospital, Medical School, University of Athens, Athens, Greece. akandara@otenet.gr
Piperi
C
C
Alexandraki
K I
KI
Papailiou
J
J
Ekonomou
F
F
Koulouri
E
E
Kandarakis
H
H
Creatsas
G
G
D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000178:diet therapy; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000077403:Orlistat; D019518:Postprandial Period / Q000187:drug effects
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D007783:Lactones; D000077403:Orlistat