Endocrine Abstracts (2008) 16 P800

Insulin resistance and oxidative stress induce advanced glycation end products formation in patients with clinical and subclinical hypothyroidism

Melpomeni Peppa1, Dimitrios Hadjidakis1, Maria Alevizaki2, George Dimitriadis1, Georgia Isari1, Theofanis Economopoulos1, Jaime Uribarri3, Helen Vlassara3 & Sotirios A Raptis1,4


1Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Athens University Medical School, Research Institute and Diabetes Center, ‘Attikon’ University Hospital, Athens, Greece; 2Endocrine Unit, Department of Clinical Therapeutics, Athens University Medical School, ‘Alexandra’ Hospital, Athens, Greece; 3Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, New York, USA; 4Hellenic National Diabetes Center, ‘Attikon’ University Hospital, Athens, Greece.


Introduction: Advanced glycation end products (AGEs) formation is accelerated in various pathological conditions characterized by insulin resistance (IR) and/or increased oxidative stress (OS). Hypothyroidism – overt (OH) or subclinical (SUH) – is associated with a variety of metabolic disorders leading to IR and increased OS.

Aim: To estimate the εN-carboxymethyl-lysine (CML) levels, in subjects with OH and SUH and seek for possible correlations with various metabolic parameters including IR and OS.

Subjects and methods: We studied patients with OH (n=15), with surgically induced OH (SOH) (n=15) and SUH (n=15), mean age 43±10 years (TSH: 40±10, 79±21, 7.7±3.4 μIU/ml, respectively). Fifty healthy subjects (C) matched for age and BMI, were also studied. Thyroid hormone levels, biochemical parameters, creatinine clearance and microalbuminuria were measured by standard laboratory techniques. CML and 8-isoprostanes levels were determined by ELISA. Dietary AGE intake (dAGE) was estimated by 3-day dietary records and specific questionnaires. The IR was estimated by HOMA index (GfastingχI fasting)/22.5).

Results: HOMA was higher in OH, SOH and SUH groups compared to C (2.4±1, 2±1, 2.2±0.7, 1.4±0.6, respectively, P<0.05). Levels of 8-isoprostanes were higher only in OH and SUH compared to C (230±44, 214±86, 133±69 pg/ml, respectively, P<0.05). Higher CML levels were observed in OH, SOH and SUH groups compared to C (15±5, 13±4, 11±4 U/ml, respectively, P<0.005) with positive correlation to HOMA index and 8-isoprostanes levels in all groups except the SOH (r=0.6, P<0.03, respectively). All the subjects had normal renal function and did not exhibit statistically different dAGE values.

Conclusion: Increased OS and IR possibly induce increased AGE formation in OH and SUH, which might contribute to the enhanced risk of cardiovascular disease. However, other mechanisms such as disrupted function of the AGE receptors cannot be excluded and warrant further investigation.