Prevalence of low testosterone levels in men with type 2 diabetes mellitus: a cross‐sectional study
Background: A high prevalence of low serum testosterone (LST) in men with type 2 diabetes have been reported worldwide. The aim of this study was to determine the prevalence and associated factors of LST in men with type 2 diabetes. Latar Belakang: Prevalensi tinggi rendah serum testosteron (LST) pada pria dengan diabetes tipe 2 telah dilaporkan di seluruh dunia. Tujuan dari penelitian ini adalah untuk menentukan prevalensi dan faktor terkait dari LST pada pria dengan diabetes tipe 2. Materials and Methods: This was a cross‐sectional study, conducted among 1,089 men (aged 30‐ 70 years) with type 2 diabetes who consecutively attended a major diabetes center in Amman, Jordan, between August 2008 and February 2009. The patients’ demographic characteristics were collected using a prestructured questionnaire. Duration of diabetes, smoking habits, presence of retinopathy, neuropathy, and nephropathy were collected from the medical records. All participants were asked to complete the Androgen Deficiency in Ageing Male (ADAM) questionnaire. Venous blood sample was collected to test for total testosterone (TT), free testosterone (FT), sex hormone binding globulin (SHBG), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), serum lipids, and glycosylated hemoglobin (HbA1c). LST was defined as TT <3 ng/ml.
Bahan dan Metode: Penelitian ini merupakan studi cross-sectional, dilakukan di antara 1.089 laki-laki (usia 30 - 70 tahun) dengan diabetes tipe 2 yang berturut-turut menghadiri pusat diabetes besar di Amman, Yordania, antara Agustus 2008 dan Februari 2009. Karakteristik demografis pasien dikumpulkan menggunakan kuesioner terstruktur pra. Durasi diabetes, kebiasaan merokok, adanya retinopati, neuropati, nefropati dan dikumpulkan dari catatan medis. Semua peserta diminta untuk menyelesaikan kuesioner androgen Kekurangan Ageing Male (ADAM) . Sampel darah vena dikumpulkan untuk menguji testosteron total (TT), testosteron bebas (FT), hormon seks pengikat globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolaktin (PRL), lipid serum, dan hemoglobin glikosilasi (HbA1c). LST didefinisikan sebagai TT <3 ng / ml. Results: Overall, 36.5% of patients with diabetes had TT level <3 ng/ml and 29% had symptoms of androgen deficiency. Of those with serum testosterone level <3 ng/ml, 80.2% had symptoms of androgen deficiency, 16.9% had primary hypogonadism (HG),
and 83.1% had secondary HG. Univariate analysis showed a significant relationship between age, income, education, body mass index (BMI), smoking, duration of diabetes, diabetic nephropathy, diabetic neuropathy, and HbA1c. Multivariate logistic regression analysis indicated age, income, BMI, and diabetic neuropathy as the independent risk factors of LST. Conclusions: The prevalence of LST among men with type 2 diabetes is high. Age, income, BMI, and diabetic neuropathy were found to be the independent risk factors for LST Hasil: Secara keseluruhan, 36,5% dari pasien dengan diabetes memiliki tingkat TT <3 ng / ml dan 29% memiliki gejala defisiensi androgen. Dari mereka dengan kadar testosteron serum <3 ng / ml, 80,2% memiliki gejala defisiensi androgen, 16,9% memiliki hipogonadisme primer (HG), dan 83,1% memiliki sekunder HG. Analisis univariat menunjukkan hubungan yang signifikan antara umur, pendapatan, pendidikan, indeks massa tubuh (BMI), merokok, durasi diabetes, nefropati diabetik, neuropati diabetes, dan HbA1c. Analisis regresi logistik multivariat menunjukkan umur, pendapatan, BMI, dan neuropati diabetes sebagai faktor risiko independen dari LST. Kesimpulan: Prevalensi LST antara laki-laki dengan diabetes tipe 2 yang tinggi. Umur, pendapatan, BMI, dan neuropati diabetes ditemukan menjadi faktor risiko independen untuk LST. Introduction.
Diabetes mellitus (DM) affects an estimated 285 million people worldwide. This number is expected to reach 438 million by the year 2030, with two‐thirds of all cases occurring in low‐ to middle‐income countries.[1] Asians develop diabetes at a younger age, at lower degrees of obesity, and at much higher rates given the same amount of weight gain compared with Western populations.[2] The prevalence of type 2 diabetes is high in Jordan and more than half of the patients with diabetes have unsatisfactory metabolic control.[3] Diabetes mellitus (DM) mempengaruhi sekitar 285 juta orang di seluruh dunia. Jumlah ini diperkirakan akan mencapai 438 juta pada tahun 2030, dengan dua-pertiga dari semua kasus yang terjadi di negara-negara berpendapatan menengah. [1] Asia mengembangkan diabetes pada usia lebih muda, pada derajat yang lebih rendah dari obesitas, dan pada tingkat yang jauh lebih tinggi mengingat jumlah
yang sama berat badan dibandingkan dengan populasi Barat. [2] Prevalensi diabetes tipe 2 yang tinggi di Yordania dan lebih dari setengah dari pasien dengan diabetes memiliki kontrol metabolik memuaskan. [3]
The association between low serum testosterone (LST) and DM has recently received substantial attention.[4,5] Studies have reported that men with type 2 DM (T2DM) have a high prevalence of LST.[6‐8] Further, reduced total testosterone (TT) levels have been associated with insulin resistance and subsequent risk for developing T2DM.[9,10] The main symptoms of LST are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood, fatigue, low energy, and impaired quality of life. Hubungan antara serum testosteron rendah (LST) dan DM baru-baru ini mendapat perhatian yang cukup besar. [4,5] Studi telah melaporkan bahwa pria dengan DM tipe 2 (DMT2) memiliki prevalensi tinggi LST. [6-8] Selanjutnya, mengurangi total testosteron (TT) tingkat telah dikaitkan dengan resistensi insulin dan risiko selanjutnya untuk mengembangkan DMT2. [9,10] gejala utama LST berkurang libido / disfungsi ereksi, penurunan massa otot dan kekuatan, meningkatkan adipositas, osteoporosis / rendah massa tulang, mood depresi, kelelahan, energi rendah, dan gangguan kualitas hidup.
Researchers have highlighted the potential metabolic consequences of testosterone decline on age‐associated metabolic changes such as abdominal obesity, diabetes, and markers of prediabetes.[13‐15] hypogonadism (HG) is a clinical condition consisting of both symptoms and biochemical signs of testosterone deficiency. However, many studies in men with diabetes have defined LST solely on the basis of testosterone levels. Symptoms of HG have rarely been considered in combination with biochemical testosterone deficiency.[16] There is a growing interest in understanding the concurrence of symptoms of low testosterone and a low testosterone level since the clinical significance of a low testosterone
level alone is unclear.[17] TT concentrations are determined, to a large extent, by the circulating sex hormone binding globulin (SHBG) concentrations. In the blood of normal men, 44% of TT is bound to SHBG, 2% is unbound (free testosterone (FT)), and 54% circulates bound to albumin and other proteins.[18] It is not known whether the lower testosterone levels in diabetics are associated with changes in luteinizing hormone (LH) and follicular stimulating hormone (FSH). Previously published data show that the commonest form of gonadal dysfunction was hypogonadotropic HG. [19] Ando et al.,[20] reported low TT and normal LH levels in diabetics; whereas, Ali et al.,[21] found that subjects with diabetic neuropathy had low testosterone, high LH and FSH levels. The prevalence of LST is largely unknown both in the diabetic population and in the general population in Arab countries, including Jordan. This study was conducted to determine the prevalence of LST in men with T2DM and its associated factors. Para peneliti telah menyoroti konsekuensi metabolik potensi penurunan testosteron pada perubahan metabolik terkait usia seperti obesitas perut , diabetes , dan tanda pradiabetes . [ 13-15 ] hipogonadisme ( HG ) adalah kondisi klinis yang terdiri dari kedua gejala dan tanda-tanda biokimia testosteron kekurangan . Namun, banyak penelitian pada pria dengan diabetes telah menetapkan LST semata-mata atas dasar kadar testosteron . Gejala HG jarang dipertimbangkan dalam kombinasi dengan defisiensi testosteron biokimia . [ 16 ] Ada minat yang tumbuh dalam memahami persetujuan dari gejala testosteron rendah dan tingkat testosteron rendah sejak signifikansi klinis dari tingkat testosteron rendah saja tidak jelas . [ 17 ] konsentrasi TT ditentukan , untuk sebagian besar , oleh hormon seks globulin mengikat beredar ( SHBG ) konsentrasi . Dalam darah orang normal, 44 % dari TT terikat SHBG , 2 % tidak terikat ( testosteron bebas ( FT ) ) , dan 54 % beredar terikat albumin dan protein lain [ 18 ] . Hal ini tidak diketahui apakah testosteron rendah tingkat pada penderita diabetes berhubungan dengan perubahan hormon luteinizing ( LH ) dan hormon perangsang folikel ( FSH ) . Data yang sebelumnya diterbitkan menunjukkan bahwa bentuk paling umum dari disfungsi gonad adalah HG hipogonadisme [ 19 ] Ando et al , [ 20 ] melaporkan TT rendah dan tingkat LH normal
pada penderita diabetes ; . . . Sedangkan , Ali et al , [ 21 ] menemukan bahwa subyek dengan neuropati diabetes memiliki testosteron rendah , LH yang tinggi dan tingkat FSH . Prevalensi LST sebagian besar tidak diketahui baik pada populasi diabetes dan pada populasi umum di negara-negara Arab , termasuk Yordania . Penelitian ini dilakukan untuk mengetahui prevalensi LST pada pria dengan diabetes mellitus tipe 2 dan faktor terkait .
MATERIALS AND METHODS A total of 1,089 men (aged 30‐70 years) with type 2 diabetes who consecutively attended at a major diabetes center in Amman, Jordan, between August 2008 and February 2009 were included in the study. Patients with any inflammatory disease or infection and already receiving hormone replacement therapy were excluded. Informed verbal consent was obtained from all the patients to participate in the study, and the local research ethics committee approved the protocol. The sample size of 1,089 yielded a power of more than 80% at the confidence level of 95%, and a 5% margin of error. BAHAN DAN METODE Sebanyak 1.089 laki-laki (usia 30-70 tahun) dengan diabetes tipe 2 yang berturut-turut menghadiri di sebuah pusat diabetes besar di Amman, Yordania, antara Agustus 2008 dan Februari 2009 dilibatkan dalam penelitian tersebut. Pasien dengan penyakit radang atau infeksi dan sudah menerima terapi penggantian hormon dikeluarkan. Persetujuan lisan didapatkan dari semua pasien untuk berpartisipasi dalam penelitian ini, dan komite etika penelitian lokal menyetujui protokol. Ukuran sampel dari 1.089 menghasilkan daya lebih dari 80% pada tingkat kepercayaan 95%, dan margin 5% dari kesalahan.
The respondents were purposely and conveniently selected according to their availability during their routine visit to the outpatient clinics. The patients’ demographic characteristics were collected using a prestructured questionnaire. Information on the duration of diabetes, presence of retinopathy, neuropathy, and nephropathy was collected from their
medical records. Smoking habits were assessed by dividing men into categories of current, former, and never smokers. Study participants were asked to complete the androgen deficiency in ageing male (ADAM) questionnaire. This questionnaire has 88% sensitivity and 60% specificity.[22] A positive response is based on a decrease in libido or the strength of erections, or any three nonspecific questions that may include a decrease in muscle strength, fatigability, mood changes, and loss of height. Para responden sengaja dan nyaman dipilih sesuai dengan ketersediaan mereka selama kunjungan rutin ke klinik rawat jalan. Karakteristik demografis pasien dikumpulkan dengan menggunakan kuesioner prestructured. Informasi tentang durasi diabetes, kehadiran retinopati, neuropati, nefropati dan dikumpulkan dari catatan medis mereka. kebiasaan merokok dinilai dengan membagi orang ke dalam kategori saat ini, mantan, dan tidak pernah perokok. Peserta penelitian diminta untuk melengkapi kekurangan androgen pada laki-laki penuaan (ADAM) kuesioner. Kuesioner ini memiliki sensitivitas 88% dan 60% spesifisitas. [22] Sebuah respon positif didasarkan pada penurunan libido atau kekuatan ereksi, atau tiga pertanyaan spesifik yang mungkin termasuk penurunan kekuatan otot, kelelahan, perubahan mood, dan kehilangan tinggi.
Body mass index (BMI) was computed by dividing the weight in kilograms by the square of height in meters. Blood pressure was measured using a standardized sphygmomanometer. A trained nurse performed the procedure while the subject was in a sitting position, with the arm at the level of the heart and after 5 min rest. Hypertension was defined as elevated systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure. A venous blood sample (20 ml) was drawn between 8:00 and 10:00 am after an overnight fast. Blood was withdrawn from the cubital fossa and/or dorsum of the hand veins from each participant, using a disposable syringe. It was injected into the plain complete blood count tube; the specimen immediately centrifuged, and serum was aliquoted and stored at −20°C to determine
TT, FT, SHBG, FSH, LH, prolactin (PRL), glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride. Laboratory technicians were blinded to participants’ characteristics. TT was assessed using radioimmunoassay. FT was assessed using Axsym, which is based on a microparticle enzyme immunoassay. [16] SHBG was tested by means of an immunochemiluminometric assay. LH, FSH, and PRL were measured by chemiluminescent immunometric assays. HbA1c was analyzed using high performance liquid chromatography (HPLC) method (Bio‐Rad). Information concerning HbA1c was adopted from tests made in the National Center for Diabetes, Endocrinology, and Genetics lab. Total cholesterol, triglyceride, HDL, and LDL were assayed through the automated spectrophotometer, enzymatic colorimetric method, COBAS INTEGRA using commercial kits supplied by Roche Diagnostics. Indeks massa tubuh ( BMI ) yang dihitung dengan membagi berat dalam kilogram dengan kuadrat tinggi dalam meter . Tekanan darah diukur dengan menggunakan sphygmomanometer standar . Seorang perawat yang terlatih melakukan prosedur saat subjek berada dalam posisi duduk , dengan lengan di tingkat jantung dan setelah 5 menit istirahat. Hipertensi didefinisikan sebagai peningkatan sistolik ( ≥ 140 mmHg ) atau diastolik ( ≥ 90 mmHg ) tekanan darah . Sampel darah vena ( 20 ml ) ditarik 8:00-10:00 setelah puasa semalam . Darah ditarik dari fossa cubiti dan / atau dorsum dari vena tangan dari masing-masing peserta , menggunakan jarum suntik sekali pakai . Hal itu disuntikkan ke dalam lengkap jumlah darah tabung polos , spesimen segera disentrifugasi , dan serum aliquoted dan disimpan pada -20 ° C untuk menentukan TT , FT , SHBG , FSH , LH , prolaktin ( PRL ) , hemoglobin glikosilasi ( HbA1c ) , kolesterol total , kolesterol HDL , kolesterol LDL , trigliserida dan . Teknisi laboratorium telah menjadi buta dengan karakteristik peserta . TT dinilai menggunakan radioimmunoassay . FT dinilai menggunakan AxSYM , yang didasarkan pada immunoassay enzim mikropartikel . [ 16 ] SHBG diuji dengan menggunakan assay immunochemiluminometric . LH , FSH , dan PRL diukur dengan tes Immunometric chemiluminescent . HbA1c dianalisis menggunakan kromatografi cair kinerja tinggi ( HPLC ) metode ( Bio -
Rad ) . Informasi mengenai HbA1c diadopsi dari pengujian yang dilakukan di Pusat Nasional untuk Diabetes , Endokrinologi , dan Genetika lab . Kolesterol total , trigliserida , HDL , LDL dan diuji melalui spektrofotometer otomatis , metode kolorimetri enzimatik , COBAS INTEGRA menggunakan kit komersial yang disediakan oleh Roche Diagnostics .
In this study, LST was defined as TT <3.0 ng/ml and TT used as reference parameter to define LST.[8,23,24] Symptomatic androgen deficiency was defined as TT <3.0 ng/ml in addition to a positive response to ADAM questionnaire. Primary HG was defined as LH >10 MIU/ml with TT <3.0 ng/ml, while the secondary HG was defined as LH <2 MIU/ml with TT <3.0 ng/ml.[16]
