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      男性早發(fā)型2型糖尿病的臨床特點(diǎn)及與睪酮的關(guān)系

      2019-12-30 01:42:23袁虎許燕茅丹
      中國實(shí)用醫(yī)藥 2019年34期
      關(guān)鍵詞:睪酮胰島素

      袁虎 許燕 茅丹

      【摘要】 目的 了解男性早發(fā)型2型糖尿病(EDM)的臨床特點(diǎn)并探討其與睪酮之間的關(guān)系。

      方法 選取54例男性EDM患者作為研究組, 另選取37例年齡≤40歲的糖代謝正常男性作為對照組。檢測兩組研究對象的一般指標(biāo)、生化指標(biāo)、內(nèi)分泌激素, 并進(jìn)行組間比較。結(jié)果 54例男性EDM患者中, 有17例(31.5%)肥胖患者, 18例(33.3%)超重患者;其中19例(35.2%)患者尿酮體陽性;高血壓占24.1%(13/54), 高脂血癥占66.7%(36/54), 脂肪肝占63.0%(34/54), 高尿酸血癥占27.8%(15/54)。兩組的年齡、舒張壓、低密度脂蛋白膽固醇(LDL-C)、前列腺特異抗原(PSA)、游離前列腺特異抗原(fPSA)、空腹C肽、空腹胰島素水平比較差異無統(tǒng)計學(xué)意義(P>0.05)。研究組的體質(zhì)量指數(shù)(BMI)、收縮壓、空腹血糖、糖化血紅蛋白(HbA1c)、總膽固醇(TC)、甘油三酯(TG)水平均明顯高于對照組, 差異具有統(tǒng)計學(xué)意義(P<0.05);而研究組的血紅蛋白、白蛋白、高密度脂蛋白膽固醇(HDL-C)、尿酸、睪酮水平均顯著低于對照組, 差異均具有統(tǒng)計學(xué)意義(P<0.05)。EDM患者的空腹胰島素與睪酮水平呈正相關(guān)(r=0.524, P=0.012<0.05)。

      結(jié)論 男性EDM患者存在嚴(yán)重的代謝紊亂, 睪酮可能通過影響胰島素分泌參與了男性EDM的發(fā)生。

      【關(guān)鍵詞】 早發(fā)型2型糖尿病;男性;胰島素;睪酮;代謝異常

      DOI:10.14163/j.cnki.11-5547/r.2019.34.005

      Clinical characteristics of male early-onset type 2 diabetes mellitus and its correlation with testosterone ?YUAN Hu, XU Yan, MAO Dan, et al. Department of Endocrinology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China

      【Abstract】 Objective ? To understand the clinical characteristics of male early-onset type 2 diabetes mellitus (EDM) and its correlation with testosterone. Methods ? 54 male patients with EDM were selected as the research group, and 37 male patients with normal glucose metabolism ≤40 years old were selected as the control group. The general index, biochemical index and endocrine hormone of the two groups were detected and compared. Results ? Among 54 male EDM patients, 17 cases (31.5%) were obese, 18 cases (33.3%) were overweight, 19 cases (35.2%) were positive for urinary ketone body, 24.1%(13/54) were hypertension, 66.7%(36/54) were hyperlipidemia, 63.0%(34/54) were fatty liver, 27.8%(15/54) were hyperuricemia. There was no statistically significant difference in age, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), prostate specific antigen (PSA), free prostate specific antigen (fPSA), fasting C peptide and fasting insulin levels between the two groups (P>0.05). The levels of body mass index (BMI), systolic blood pressure, fasting blood glucose, glycosylated hemoglobin (HbA1c), triglycerides (TC) and total cholesterol (TG) in the research group was obviously higher than those in the control group, and their difference was statistically significant (P<0.05). The levels of hemoglobin, albumin, high-density lipoprotein cholesterol (HDL-C), uric acid, testosterone in the research group was significantly lower than those in the control group, and their difference was statistically significant (P<0.05). There was a positive correlation between fasting insulin and testosterone in EDM patients (r=0.524, P=0.012<0.05). Conclusion ? There is a serious metabolic disorder in male patients with EDM. Testosterone may be involved in the development of EDM by influencing insulin secretion.

      素[8]。因此, 早期干預(yù)高血壓和高脂血癥對預(yù)防EDM也非常重要。

      此外, 作者還發(fā)現(xiàn)男性EDM患者的血漿睪酮水平顯著低于對照組, 差異具有統(tǒng)計學(xué)意義(P<0.05)。睪酮水平在青春期達(dá)到峰值, 之后隨著年齡增長而降低, 40歲之后下降更為明顯。已有大量臨床研究顯示睪酮水平降低是T2DM的獨(dú)立影響因素, 甚至低睪酮可以用來預(yù)測T2DM的發(fā)生[17]。Oh等[18]及丹麥哥本哈根的20年隨訪觀察[3]提示低睪酮是男性T2DM的危險因素, 睪酮水平與T2DM之間存在顯著的負(fù)相關(guān)。前列腺癌患者在接受雄激素剝奪治療后, T2DM發(fā)生率顯著上升, 這也印證了睪酮對血糖的調(diào)節(jié)作用[19]。目前有關(guān)睪酮與糖尿病等代謝疾病的研究都集中在中老年人群, 本研究首次報道了中國男性EDM患者睪酮降低, 說明睪酮水平對男性EDM的發(fā)生、發(fā)展起著重要作用。目前主要的觀點(diǎn)均認(rèn)為睪酮水平對維持胰島素敏感性至關(guān)重要。目前的研究大多認(rèn)為雄激素水平降低, 首先是影響脂質(zhì)代謝紊亂, 導(dǎo)致向心性肥胖, 繼而誘導(dǎo)了胰島素抵抗的發(fā)生[20]。Jones 等[21]的研究顯示T2DM及肥胖患者在睪酮治療后胰島素抵抗指數(shù)(HOMA-IR)可以下降15%。本研究發(fā)現(xiàn)睪酮水平與空腹胰島素水平呈正相關(guān)。隨著睪酮水平的下降, 空腹胰島素水平降低。之前的國內(nèi)研究也提示EDM較遲發(fā)型有更嚴(yán)重的胰島β細(xì)胞功能衰退, 本研究提示在初次診斷的男性EDM患者, 尿酮體陽性率達(dá)35.2%。提示在中國EDM, 特別是男性EDM胰島β細(xì)胞功能衰退出現(xiàn)較早。

      本研究通過對初次診斷的男性EDM患者進(jìn)行臨床觀察, 發(fā)現(xiàn)男性EDM患者有嚴(yán)重的代謝紊亂、胰島素抵抗, 而這些都是心腦血管疾病的高危因素, 對于肥胖的青年男性, 特別是伴有高血壓、高血脂等代謝異常的人群應(yīng)該進(jìn)行早期的積極干預(yù)。男性EDM患者睪酮降低明顯, 且可能通過調(diào)節(jié)胰島素的分泌促進(jìn)糖尿病的發(fā)生發(fā)展。但睪酮替代治療的有效性及安全性仍存在較多的爭議, 有待進(jìn)一步的研究, 特別是大規(guī)模的臨床研究來證實(shí)。

      參考文獻(xiàn)

      [1] Cowie CC, Rust KF, Ford ES, et al. Full accounting of diabetes and pre-diabetes in the U. S. population in 1988-1994 and 2005-2006. Diabetes Care, 2009, 32(2):287-294.

      [2] Sharma M, Nazareth I, Petersen I. Trends in incidence, prevalence and prescribing in type 2 diabetes mellitus between 2000 and 2013 in primary care: a retrospective cohort study. Bmj Open, 6(1):e010210.

      [3] Holmboe SA, Jensen TK, Linneberg A, et al. LowTestosterone: ARiskMarkerRather Than aRisk FactorforType 2 Diabetes. J Clin Endocrinol Metab, 2016, 101(8):3180-3190.

      [4] Cai X, Tian Y, Wu T, et al. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian J Androl, 2014(1):146-152.

      [5] Ma RCW, Chan JCN. Type 2 diabetes in East Asians: Similarities and differences with populations in Europe and the United States. Annals of the New York Academy of Sciences, 2013, 1281(1):64-91.

      [6] Zou X, Zhou X, Ji L, et al. The characteristics of newly diagnosed adult early-onset diabetes: a population-based cross-sectional study. Scientific Reports, 2017(7):46534.

      [7] Hatunic M, Burns N, Finucane F, et al. Contrasting clinical and cardiovascular risk status between early and later onset type

      2 diabetes. Diabetes & vascular disease research: official journal of the International Society of Diabetes and Vascular Disease, 2005, 2(2):73-75.

      [8] Yu H, Xie LF, Chen K, et al. Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients. Chin Med J (Engl), 2016, 129(7):778-784.

      [9] Burns N, Finucane FM, Hatunic M, et al. Early-onset type

      2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training. Diabetologia, 2007, 50(7):1500-1508.

      [10] Golubic R, Wijndaele K, Sharp SJ, et al. Physical activity, sedentary time and gain in overall and central body fat: 7-year follow-up of the ProActive trial cohort. Int J Obes (Lond), 2015, 39(1):142-148.

      [11] Irving R, Tusie-Luna MT, Mills J, et al. Early onset type 2 diabetes in Jamaica and in Mexico. Opportunities derived from an interethnic study. Rev Invest Clin, 2011, 63(2):198-209.

      [12] Jimenez-Corona A, Rojas R, Gomez-Perez FJ, et al. Early-onset type 2 diabetes in a Mexican survey: results from the National Health and Nutrition Survey 2006. Salud Publica Mex, 2010(52Suppl 1):S27-S35.

      [13] 唐秀玲. 早發(fā)2型糖尿病臨床特點(diǎn)及相關(guān)危險因素分析. 中國全科醫(yī)學(xué), 2012, 15(14):1562-1565.

      [14] Zhang M, Mao J, Tuerdi A, et al. The Constellation of Macrovascular Risk Factors in Early Onset T2DM: A Cross-Sectional Study in Xinjiang Province, China. J Diabetes Res, 2018(2018):3089317.

      [15] Rhodes ET, Prosser LA, Hoerger TJ, et al. Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus. Diabet Med, 2012, 29(4):453-463.

      [16] Wong J, Molyneaux L, Constantino M, et al. Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors. Diabetes Care, 2008, 31(10):1985-1990.

      [17] Allan CA. Sex steroids and glucose metabolism. Asian J Androl, 2014, 16(2):232-238.

      [18] Oh JY, Barrett-Connor E, Wedick NM, et al. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care, 2002, 25(1):55-60.

      [19] Haidar A, Yassin A, Saad F, et al. Effects of androgen deprivation on glycaemic control and on cardiovascular biochemical risk factors in men with advanced prostate cancer with diabetes. Aging Male, 2007, 10(4):189-196.

      [20] Vandenput L, Mellstrom D, Lorentzon M, et al. Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men. J Clin Endocrinol Metab, 2007, 92(11):4130-4137.

      [21] Jones TH, Arver S, Behre HM, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 Study). Diabetes Care, 2011, 34(4):828-837.

      [收稿日期:2019-08-28]

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