original article
Wien Klin Wochenschr (2009) 121: 262–269 DOI 10.1007/s00508-009-1162-2 Printed in Austria © Springer-Verlag 2009
Wiener klinische Wochenschrift The Middle European Journal of Medicine
Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome Elisabeth Wehr1, Reinhard Möller2, Renate Horejsi2, Albrecht Giuliani3 , Daisy Kopera4 , Natascha Schweighofer1, Andrea Groselj-Strele 5 , Thomas R. Pieber1, Barbara Obermayer-Pietsch1 1 Department
of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University Graz, Austria of Physiological Chemistry, Center for Physiological Medicine, Medical University Graz, Austria 3 Department of Obstetrics and Gynecology, Medical University Graz, Austria 4 Department of Dermatology, Medical University Graz, Austria 2 Institute
5 Center
for Medical Research, Medical University Graz, Austria
Received December 5, 2008, accepted after revision March 5, 2009
Subkutane Fett Topographie und metabolische Störungen beim Polyzystischen Ovar Syndrom Zusammenfassung. Hintergrund: Das Polyzystische Ovar Syndrom (PCOS) ist die häufigste Endokrinopathie bei fertilen Frauen, wobei die zentrale Form der Adipositas ein bedeutender Faktor in der zugrundeliegenden Pathophysiologie ist. Wenig ist bekannt über die Rolle des subkutanen Fettgewebes („subcutaneous adipose tissue“, SAT). Ziel dieser Studie war es zu untersuchen, ob es einen Zusammenhang zwischen SAT Topographie und Insulinresistenz, Glucosetoleranz und metabolischen Parametern beim PCOS gibt. Methoden: 36 Frauen mit PCOS (16–41 Jahre) und 87 gesunde Frauen (20–34 Jahre) wurden untersucht. Messungen des SAT mittels Lipometer, metabolische und hormonelle Parameter, orale Glucosetoleranztests und Hirsutismus-Scores wurden analysiert. Die Insulinresistenz wurde mittels HOMA-Index („homeostasis model assessment“) errechnet. Ergebnisse: Zentral gelegene SAT Messpunkte korrelierten signifikant positiv mit dem HOMA-Index, periphere Messpunkte waren negativ korreliert. Eine multiple Regressionsanalyse zeigte eine positive Assoziation zwischen HOMA-Index und den Messpunkten „unterer Bauch“ und „oberer Rücken“. Der Messpunkt „Hüfte“ war negativ mit dem HOMA-Index assoziiert. Bei übergewichtig/adipösen PCOS-Patientinnen waren die Messpunkte „unterer Bauch“ und „oberer Rücken“ signifikant positiv mit der Insulinresistenz korreliert, während bei normalgewichtigen Frauen mit PCOS keine signifikante Korrelation mit der SAT-Topographie gefunden wurde. Weiters hatten PCOS-Frauen mit gestörter Glucosetoleranz signifikant mehr zentrales und weniger peripheres Fettgewebe verglichen mit PCOS-Frauen Correspondence: Elisabeth Wehr, MD, Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University Graz, Auenbruggerplatz 15, 8036 Graz, Austria, E-mail:
[email protected]
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mit normaler Glukosetoleranz. Dickere zentrale SATSchichten waren überdies mit einem ungünstigen Serumlipidprofil assoziiert, während umgekehrt vermehrtes Fettgewebe an den Beinen positiv mit HDL-Cholesterin korrelierte. Schlussfolgerung: Bei Frauen mit PCOS scheinen dickere zentral gelegene subkutane Fettgewebs-Schichten mit Insulinresistenz, gestörter Glukosetoleranz und einem ungünstigen Serumlipidprofil assoziiert zu sein. Vermehrtes Fettgewebe an den Beinen scheint bei Frauen mit PCOS nicht mit metabolischen Veränderungen einherzugehen. Summary. Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Central obesity plays a major role in the pathophysiology of PCOS. However, there is little information on the impact of subcutaneous adipose tissue (SAT) on metabolic disturbances in PCOS. The aim of this study was to investigate whether SAT topography influences insulin resistance, impaired glucose tolerance and metabolic parameters in women with PCOS. Methods: 36 women aged 16–41 years with PCOS and 87 healthy women aged 20–34 years were examined using lipometry, metabolic and hormonal measurements, oral glucose tolerance tests, hirsutism scores, and questionnaires. The homeostasis model assessment (HOMA) index was used for determination of insulin resistance. Results: SAT measurement points on the trunk showed significant positive correlation with the HOMA index. A negative correlation between calf SAT and the HOMA index was seen. Multiple regression analysis detected a positive association between the HOMA index and lower-abdomen SAT and upper-back SAT, whereas hip SAT showed a negative association with the HOMA index. In overweight/obese patients with PCOS, lowerabdomen and upper-back SAT showed significant posi-
7–8/2009 Subcutaneous adipose tissue topography and metabolic disturbances
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original article
tive correlations with insulin resistance. There was no correlation of SAT topography with insulin resistance in lean women with PCOS. Compared with PCOS women with normal glucose tolerance, patients with glucose intolerance had significantly increased trunk obesity and decreased leg fat. Increased SAT layers on the trunk were related to an unfavorable serum lipid profile, whereas increased leg fat correlated positively with HDL cholesterol. Conclusions: Increased SAT layers on the trunk are associated with insulin resistance, impaired glucose tolerance and an unfavorable lipid profile in women suffering from PCOS. Increased thickness of leg SAT emerges as being protective against metabolic disturbances in PCOS. Key words: Polycystic ovary syndrome, subcutaneous adipose tissue topography, insulin resistance, impaired glucose tolerance, central obesity.
Introduction Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting approximately 5–10% of women of reproductive age [1]. PCOS is characterized by increased ovarian and adrenal androgen secretion, hyperandrogenic symptoms such as hirsutism, acne and/ or alopecia, menstrual irregularity and polycystic ovaries. The disorder is frequently associated with insulin resistance accompanied by compensatory hyperinsulinemia, creating an increased risk for the development of type 2 diabetes mellitus [2]. Obesity, in particular central obesity, plays a key role in the development of PCOS [3]. Obese patients with a gynoid distribution of fat are at relatively low cardiovascular and metabolic risk, whereas patients suffering from central obesity have higher levels of insulin and lipid alterations and are at high risk for metabolic sequelae [4]. The increase of visceral fat is frequently blamed for these metabolic disturbances [5], but some data suggest that subcutaneous adipose tissue (SAT) may also play a major role in insulin resistance [6]. Previous studies in PCOS have used a variety of imaging techniques for assessment of body fat distribution, including ultrasound [7], dual-energy x-ray absorptiometry (DXA) [4, 8, 9], magnetic resonance imaging (MRI) [10, 11] and lipometry [12, 13]. DXA and MRI can accurately measure the thicknesses of SAT layers but include radiation exposure and are expensive and time-consuming [5]. The lipometer allows non-invasive, rapid and safe measurement of SAT [14] with precision comparable to that of DXA [15]. The device has been used to investigate patients with PCOS [12, 13], type 2 diabetes mellitus [16-18], obese juveniles [19] and women with a history of weight cycling [20]. To date, the lipometer has not been used to examine the association of SAT topography with insulin resistance and glucose tolerance in women with PCOS. The aim of this study was to investigate the relation between patterns of SAT and insulin resistance, imwkw
paired glucose tolerance and metabolic parameters in women with PCOS.
Methods Patients The study population comprised 36 women with verified PCOS aged 16–41 years. The diagnosis was based on the Rotterdam criteria [21], where two out of three of the following are required for the diagnosis: oligo- and/or anovulation, clinical and/or biochemical signs of hyperandrogenism, polycystic ovaries (by ultrasound). Disorders with a similar clinical presentation, such as congenital adrenal hyperplasia, Cushing’s syndrome, and androgen-secreting tumors, must be excluded. Oligo- and/or anovulation were defined by presence of oligomenorrhea or amenorrhea. Hyperandrogenism was defined by the clinical presence of hirsutism (Ferriman–Gallwey score ≥ 8), acne or alopecia and/or elevated androgen levels (normal ranges: testosterone
