Bone is now regarded as an endocrine organ modulating energy metabolism. Osteocalcin, which was a traditional bone remodeling marker, especially in its undercarboxylated form, was believed to be a metabolic active molecule involving in glucose homeostasis. Bone can uptake glucose through glucose transporter 1 expressed on osteoblasts, and this process is crucial for osteoblasts differentiation and bone formation. In addition, the osteoblasts specific insulin resistance may also lead to the dysregulation of whole body glucose metabolism. Clinical investigations generally echo the findings from mice studies. More work, especially prospective clinical studies are needed to prove the clinical utility of osteocalcin and/or other bone turnover parameters as solid predictors of pancreaticβcell function and incident diabetes, as well as the potential use of osteocalcin and/or its undercarboxylated form as an anti-diabetic agent. In the 11th issue of Diabetes in 2016, a review paper entitled as"Regulation of glucose handling by the skeleton:Insights from mouse and human studies" was published [Diabetes, 2016,65(11):3225-3232]. With the permission of Diabetes and American Diabetes Association, we translated the most important part of this review into Chinese with a new title:The regulatory role of skeleton in maintaining glucose homeostasis.

一、医学营养治疗(Medical Nutrition Therapy,MNT)MNT是临床上对特定疾病的营养障碍采取的特定营养干预措施。包括对患者进行个体化营养评估、制定相应的营养干预计划并在一定时期内实施并监测。20世纪70年代美国糖尿病学会(ADA)首次颁布"糖尿病患者营养与饮食推荐原则。20年后ADA提出MNT的概念,并与药物治疗相提并论。2006年ADA强调,糖尿病患者应接受个体化MNT以达到

多囊卵巢综合征(PCOS)是育龄妇女常见疾病,患病率为育龄妇女的5％ ～ 10％,闭经女性的20％,多毛、高雄激素血症女性的80％,且常伴肥胖、胰岛素抵抗、高血压、脂质代谢紊乱,已成为多学科关注的常见病.PCOS的病因并不明确,降低雄激素水平促进排卵是治疗中一个重要的目标,其方法为:卵巢楔型切除、腹腔镜卵巢钻孔术、LHRH类似物、芳香化酶抑制剂、抗雄激素药物及口服避孕药等[1].国人研究也证实高雄激素PCOS患者代谢综合征(MS)风险显著增加,胰岛素抵抗、雄激素水平与MS之间存在内在联系[2]。

肥胖症的危害已众所周知,节食与体育活动是减重的基础措施,但多数患者往往难以持之以恒.而减重可用的药物,如:芬氟拉明、西布曲明、奥利司他、各种中草药等,有的可能会有一定作用,但最终多因心血管或胃肠道等的不良反应,几乎均已相继退出正规减重的行列.二甲双胍对肥胖型2型糖尿病的治疗已被列为首选药物,但减重效果也比较有限.因此,胃肠减重手术(bariatric surgery,也称代谢手术)便得到青睐[1].国际糖尿病联盟(IDF)推荐,对体重指数≥35kg/m2、药物治疗效果不佳的2型糖尿病患者可用代谢手术2;美国糖尿病学会(ADA)指南中也有相似观点,同时强调术后对患者需进行终生随访,明确其长期临床益处、费用-效果比(cost-effectiveness)及相关风险评估,这需要长期的观察方能得出最终的评价.然而,现已有将此类手术扩展到非肥胖糖尿病患者中的动向[3],似应引起我们内分泌学界的关注。

阿尔茨海默病(Alzheimer Disease,AD)是当前最常见、最重要的大脑退行性疾病之一,其临床特征为进行性痴呆,并与患者原先的智力高低并无关系.该病于1907年首先由Alzheimer所描述,1911年Kraepelin把这组病态归为老年性痴呆Alzheimer型,以区别于老年期发病的血管性痴呆.对AD的发病机制有许多研究并有多种假设,如轴突营养不良,神经递质变化,免疫,代谢障碍,病毒感染等,并有家族性遗传发病的倾向.对AD的治疗目前主要是两类药:乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂.但这两类药仅只能轻度、暂时性地改善症状.虽抗抑郁药有时会有所帮助,但常会发现这些药的说明书上有黑框警示:不能用于阿尔茨海默病[1]。

鉴于颈部超声波检测在健康体检和临床诊断中已被广泛应用,加之日益普遍开展的细针穿刺或超声引导下的细针穿刺、细胞学检查,甲状腺癌的检出率已大大提高,其中大部分为分化型甲状腺癌(differentiated thyroid cancer,DTC),包括乳头状癌和滤泡状癌,尤以前者为多见,约占总检出数的80％以上,一经检出后,几乎所有DTC患者均经手术或手术加[3]Ⅰ治疗.

天然维生素(Vit)D有两种形式:Vit D2为麦骨化醇(ergocalciferol),多存在于植物性食品(如蘑菇)中;Vit D3称胆骨化醇(cholecalciferol),多存在于动物性食品,如鱼油中.人体内源性的Vit D3主要来自皮肤中7-脱氢固醇,经290 ～ 330 nm波长的紫外线(UVB)照射转化为活性羟化的Vit D而起作用.Vit D2、Vit D3及其羟化形式25-羟Vit D2[25(OH)D2]及25(OH) D3在人血液中均可检测到,但其生物活性很低;虽然经肾脏1α羟化酶进一步羟化后的1,25二羟Vit D最具活性,因其半寿期短,难以精确测定,故多项研究均以测25(OH)D替代之。

Objective To explore the possible correlation of adiponectin with ISI and acute insulin response(AIR) in subjects with impaired IGT and the newly diagnosed T2DM patients.Methods The 28 normal subjects,31 subjects with IGT,and 31 patients with newly diagnosed T2DM were included in the study.The ISI and AIR were assessed by the reduced sample number Bergmans minimal model method.And the level of serum adiponectin was measured at the same time.Results The level of serum adiponectin was negatively correlated with BMI,WHR,SBP,FPG,2 hPG,FIns,postprandial insulin(PI),HbA1c and TG(all P0.01),and positively correlated with ISI(r=0.565,P0.01),however,no correlation with AIR.Conclusion The decrease of serum adiponectin may play a role in the development of insulin resistance and metabolic syndrome.

传统的地中海饮食包括:大量的橄榄油、水果、蔬菜、坚果及谷类食物,适量的鱼与禽类,较少食用乳制品、红肉、腌制肉及糖果,在进食时一般会同时饮适量葡萄酒. 已有研究证实惯用地中海饮食的人群因心血管疾病的死亡率较人种相近而生活在北欧国家和美国地区的要低[1].

目前在全世界范围内,生育率均在持续下降,尤见于许多欧洲及亚洲国家.其原因各不相同:如国家的计划生育政策,家庭及个人的选择,以及经济、房屋条件限制等原因.不管出于上述何种动机,其结果均导致全球范围内第一胎产儿童占所有儿童的比例增加.已有报道称,第一胎产儿童其后发生1型糖尿病的危险增加[1],血压也会增高[2],从而可能影响到当今已实施节育人群后一代人口群体的总体健康质量。

代谢综合征(MS)是一组危险因子的聚集,这些因子包括:中心性肥胖、高血压、高甘油三酯血症、低高密度脂蛋白(HDL)胆固醇血症、空腹血糖升高及胰岛素抵抗等.MS患者患2型糖尿病及心血管疾病的风险增加[1].由于MS高发,如能作一以人群为基础的前瞻性队列研究,以某些生化指标来预测以后发生MS的可能性是很有临床和流行病学意义的探索.

More and more extrapancreatic actions of incretin-based therapies have been demonstrated and recently case reports have linked glucagon-like peptide-1 (GLP-1) receptor agouist therapy with the improvements in psoriasis.Psoriasis is a common skin disorder characterized by chronic inflammation.Epideminological studies have showed that patients with psoriasis exhibit increased rates of cardiovascular disease,obesity,and type 2 diabetes,owing probably to the enhanced local and (or) systemic inflammation.The observations of anti-inflammatory actions of GLP-1,which exerts direct and indirect actions on immune function,together with the improved psoriasis,offer new insights into the investigation of non-classical anti-inflammatory actions of incretin-based therapeutics and provide a new direction for the research of the novel clinical application of GLP-1.

2012年诺贝尔化学奖已授于两名美国医学专家,其中一位是Robert J.Lefkowitz医学博士,他自1999年起为美国内分泌学会会员,在美国北卡州Duke大学医学中心工作.他的突破性的发现是观察到G蛋白耦联受体细胞内的作用机制.对G蛋白耦联受体的这一机制的阐明对机体与环境的相互作用,蛋白激素的作用机制,以及许多药物的起效途径均十分重要.

血促甲状腺素(TSH)浓度增高而T3、T4正常的状态被称为亚临床甲状腺功能减退症(亚甲减).亚甲减与心血管功能,尤其是冠心病(CHD)、心力衰竭(HF),还有老年人的死亡率的关系令人关注.美国70岁以上老年人15％ TSH高于正常值[1].有一对11项队列研究结果的meta分析提示:仅只有在严重的亚甲减状态(TSH≥10 mU/L)时,其CHD死亡率方增加,且与年龄无明显关系.老年人每个个体TSH水平不同,平均每13年TSH增加0.32 mU/L[2].

Impaired eady phase insulin secretion is an important reason for leading to postprandial hyperglycemia.Nateglinide is a rapid-acting insulin secretagogue,which reduces postprandial blood glucose of type 2diabetic patient by restoring early phase insulin secretion.The efficacy and safety have been fully verified by clinical administration and it is more widely used to treat type 2 diabetic patients.Both sulfonylureas and glinides were named insulin secretagogue agents and regarded as alternative first-line drugs in the 2010 Chinese Guideline for treatment of type 2 diabetes.AACE/ACE Consensus statement claimed that glinides would be one of the important choices after metformin.In order to further guide the clinical application of nateglinide,16 national specialists in the field of endocrinology and metabolism of China discussed,drafted,and edited this consensus.The current consensus combined clinical evidences at home and abroad.systematically reviewed and summarized tlle results of these studies about nateglinide.It will provide guiding recommendations and reference concerning how to reasonably and effectively use nateglinide in the clinical practice.

Objective To analyze CYP17A1 gene mutation in a patient with 46,XY disordered sex development and to explore the possible influence on the phenotype of the patient.Methods Eight exons of CYP17AI gene in the patient and her parents were amplified and directly sequenced.In order to construct Mini-gene system,PCR fragments containing wildtype and mutant splicing sites were inserted in expression vector,and then transfected into cells.RT-PCR was used to observe the influence of splicing site mutation.Wildtype and aberrant splicing CYP17A1 cDNA expression plasmids were constructed and transfected into cells respectively,and CYP17A1 enzyme activity was tested in vitro.Results Mutation analysis revealed compound heterozygous CYP17A1 mutations,with Y329fs in one allele and a synonymous substitution( c.1263G＞A:GCG＞GCA) in another allele.In vitro analysis showed that the synonymous substitution induced a novel splicing site,which resulted in aberrant splicing of CYP17A1 mRNA and lacked six or seven amino acids after 415 in splicing product.In vitro transfection and enzyme activity experiment showed that the aberrant splicing product abolished the enzyme activity completely.However,this mutation did not completely influence splicing.The patient also had a part of normal splicing product,which was a coincidence to the phenotype of the patient.Conclusion This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17ot-hydroxylase deficiency phenotype.The functional study of the aberrant splicing variant has been initiated.

美国内分泌学会的临床指南小组遵循国际GRADE组织(Grading of Recommendations,Assessment,Development,and Evaluation goup)的分级推荐标准,结合近期相关领域的研究成果,编写了该指南(以符号(+)○○○、(+)(+)○ ○、(+)(+)(+)○和(+)(+)(+)(+)分别表示从低到高的证据质量).指南建议的内容又分为“推荐”和“建议”,分别用“1”和“2”表示,根据推荐施行,通常对患者利多于弊,而如按建议执行时则需要更多考虑患者的个体化情况.

In 2011 ADA/Lancet Forum, a randomized control trial in England was reported. Participants were with intensive diet intervention, or plus a physical activity program. The primary endpoints were improved in both groups, compared to control group, without any difference between two intervention groups. In another multinational trial, although significant improvement of cardiovascular risk factors in the intensive treatment group compared to routine group treated by general practitioners (GP), no significant differences on first cardiovascular event and all-cause mortality were found. This result is attributed to the good practice following guidelines by GP. While in China, a survey on current status of patients with type 2 diabetes who failed to reach the glycemic control target, and an another survey by a questionnaire about Chinese guidelines of diabetes treatment, answered by medical staff at different levels in Shanghai,gave us worrisome concerns. The training of medical staff from community hospitals seems to be particular emergent.

Objective To investigate the current status of type 2 diabetic patients who failed to achieve the glycemic control target, and provide theoretic evidences for making corresponding strategies. Methods The 2 diabetic patients who failed to reach the glycemic target were recruited from 181 hospitals in 26 cities and received a standard questionnaire, the conditions of their blood glucose level, lifestyle intervention, blood sugar monitoring, and drug therapy were recorded. Totally 3 861 questionnaires with complete information were collected. And the causes which account for glycemic control status were analyzed. Results Among these patients, the mean HbA1c was 7.9%, the mean fasting plasma glucose was 8.2 mmol/L, and the mean postprandial plasma glucose was 11.5 mmol/L. Only 25.6% of patients take their diet control strictly as prescribed and 44. 5% of patients have little exercise. 35. 8% and 47.8% of patients did not monitor their fasting and postprandial plasma glucose,respectively. Glycemic control in the patients aged ＞ 60 years was similar to the younger patients, but the hypoglycemia incidence in the elder group reached 35.5%, which was higher than those in the other 2 groups (20.8% and 21.4%, both P＜0. 05 ). The proportion of patients with mono-therapy and combination therapy was 46. 1% and 51.7%, while the proportion with combination therapy rose in the patients aged ＞60 years (58.7%;Compared with the other age-groups, all P＜0.05 ). 75 % of patients have adjusted their drug administration regimen since initial treatment. Conclusions Inadequate or inappropriate drug therapy regimen is a major cause responsible for this poor glycemic control status. In addition, the unhealthy life styles, insufficient blood sugar monitoring, and poor compliance were also important causes. Thus, for these patients, it is necessary to further enhance patients' education, to improve life style intervention, as well as to select more effective, safer, and compliant drug therapy regimens. Finally, the glycemic control target for the elder patients should be more flexible.