Free fatty acids,glucose, and insulin in type 2 diabetes mellitus

Xu et al used the HOMA2 model to estimate the β-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels. This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities, which led to type 2 diabetes. However, significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids (FFAs) into the blood circulation, which leads to a marked reduction in membrane flexibility. These data favor a FFA-glucose-insulin axis. The authors are invited to extend their study with the introduction of the saturation index (number of carbon-carbon double bonds per 100 fatty-acyl chains), as observed in erythrocytes.     

Management of type 2 diabetes mellitus in youth

The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus(T2DM) in this age group.However,there are limited data on the efficacy of different antidiabetic agents in youth.In this context,the Treatment Options for Type 2 Diabetes in Adolescents and Youth trial recently reported that the majority of obese children and adolescents 10-17-years old with newly diagnosed T2DM(T2DM duration less than 2 years) could not achieve HbA1c levels < 8% for more than 1 year with metformin monotherapy,metformin plus rosiglitazone combination,or metformin and lifestyle changes.These findings suggest that,in the majority of youth with T2DM,tight long-term glycemic control with oral agents is an elusive goal and that most patients will require treatment with insulin within a few years of diagnosis to achieve HbA1c targets and reduce the risk of macroand microvascular complications.Therefore,reducing the incidence of T2DM by preventing pediatric obesity through the implementation of lifestyle changes in the community should be the primary objective of healthcare systems.     

罗格列酮联合二甲双胍治疗2型糖尿病临床疗效分析

目的观察罗格列酮联合二甲双胍治疗2型糖尿病的临床效果。方法将65例符合2型糖尿病诊断标准的门诊患者随机分组,试验组35例,予以口服罗格列酮及二甲双胍联合治疗;对照组30例,仅予以口服罗格列酮治疗。观察两组患者治疗前及治疗12周后FBG、FINS、DBP、SBP和IRI变化情况,并监测患者肝肾功能和血常规。结果治疗后两组患者血糖、血压及胰岛素均较治疗前有显著下降（P〈0.05）;试验组FBG、FINS、DBP、SBP及IRI等指标下降幅度均大于对照组,差异有统计学意义（P〈0.05）;两组患者均无肝、肾功能损害。结论罗格列酮联合二甲双胍治疗2型糖尿病,具有改善患者胰岛素抵抗和降低血压的作用,且临床疗效确切,优于单独使用罗格列酮。     

2型糖尿病合并胆囊结石的相关危险因素

目的 探讨2型糖尿病患者发生胆囊结石的相关危险因素.方法 回顾性分析2007年1月至2010年5月北京协和医院体检中心2574例2型糖尿病患者的临床资料,对其中429例2型糖尿病合并胆囊结石患者(研究组)和2145例2型糖尿病不合并胆囊结石患者(对照组),按照年龄、性别进行1∶5配比以进行病例对照研究.计数资料采用x2检验,对收缩压(SBP)、舒张压(DBP)、空腹血糖(FBG)、TC、TG、高密度脂蛋白胆固醇(HDL-CH)、低密度脂蛋白胆固醇(LDL-CH)和体质指数(BMI)等相关危险因素进行单因素分析,采用四格表x2检验筛选出有统计学意义的可疑危险因素,再对这些可疑因素进行多因素Logistic回归分析.结果 单因素分析结果显示在SBP、FBG、TC、HDL-CH及BMI 5个方面,研究组与对照组比较,差异有统计学意义(x2=20.323,4.365,4.028,7.049,7.319,P＜0.05).去除年龄、性别的影响后,多因素分析结果证实SBP、TC、HDL-CH及BMI是2型糖尿病合并胆囊结石患者的危险因素(x2=18.047,6.905,12.884,7.557,P＜0.05).结论 BMI、SBP和TC水平增高及HDL-CH浓度降低可能是2型糖尿病合并胆囊结石的危险因素.

Abstract：

Objective To explore risk factors for type 2 diabetes mellitus complicated with gallstone disease. Methods The clinical data of 429 type 2 diabetes mellitus patients complicated with gallstone disease (case group) and 2145 type 2 diabetes mellitus patients without gallstone disease (control group) were collected from the Health Center of Peking Union Medical College Hospital from January 2007 to May 2010. According to sure (SBP), diastolic blood pressnre (DBP), fasting blood glucose (FBG), total cholesterol (TC), Triglyceride (TG), high-density lipoprotein cholesterol (HDL-CH), low-density lipoprotein cholesterol (LDL-CH) and body mass index (BMI) were statistically analyzed by fourfold table chi-square test or conditional Logistic regression.Results Univariate analysis showed that there was a significant difference in the levels of SBP, FBG, TC, HDL-CH and BMI between the case group and the control group (x2 =20.323, 4.365, 4.028, 7.049, 7.319, P＜0.05). Multivariate analysis confirmed that SBP, TC, HDL-CH and BMI were risk factors for gallstone disease in patients with type 2 diabetes mellitus (x2 = 18. 047, 6. 905, 12. 884, 7. 557, P ＜ 0. 05). Conclusion Increased SBP, TC and BMI and decreased HDL-CH may be the risk factors for type 2 diabetes mellitus complicated with gallstone disease.     

Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.     

2型糖尿病患者血清胆红素和尿酸水平变化及意义

目的探讨2型糖尿病（T2DM）患者血清胆红素、尿酸（UA）和血脂水平变化及意义。方法采用全自动生化分析仪，检测46例T2DM血管病变患者血清胆红素、UA及血脂水平，并与50例对照组比较分析。结果T2DM伴血管病变患者血清总胆红素（TBIL）和间接胆红素（NDBIL）含量明显低于无并发症组（P〈0．01），血清UA含量显著高于对照组（P〈0．01），大、微血管组TBIL、UA比较均无统计学意义；血管病变组总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）含量与无并发症组和对照组比较显著升高，而高密度脂蛋白胆固醇（HDL—C）则降低（P〈0．01）。结论低胆红素血症、UA升高及血脂异常与T2DM血管病变密切相关，检测三者含量对判断T2DM伴发血管病变具有重要意义。     

胃肠外科手术治疗肥胖症及2型糖尿病

肥胖症是现今社会所面临的最严重的公共健康问题之一,手术治疗是使肥胖症患者获得长期而稳定的减重效果的唯一方法。自从1954年报道第1例减肥手术以来,外科手术治疗肥胖症在全球范围内获得了很大的发展,逐渐成为治疗病态性肥胖的＂金标准＂。随着研究的不断深入,越来越多的证据表明,胃肠外科手术不仅能减重,同时可以改善甚至治愈肥胖症相关的多种代谢性疾病,尤其是2型糖尿病。目前国内外的胃肠外科医师们正致力于将手术推广到2型糖尿病的治疗中去。外科手术治疗肥胖症及2型糖尿病将有巨大的发展空间。     

血清脂联素及尿酸水平与2型糖尿病视网膜病变的相关性研究

目的观察2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂联素及尿酸水平变化,初步探讨其与糖尿病视网膜病变(diabetic retinopathy,DR)的相关性。方法回顾性分析2017年6月至2019年6月在青岛市中心医院内分泌科住院治疗的120例T2DM患者的临床资料,根据眼底结果分为无DR组(40例)、增生型DR组(45例)、非增生型DR组(35例),同期选取健康体检者30例作为对照组。比较4组受试者实验室生化指标、血清脂联素及尿酸水平。多因素Logistic回归分析影响DR的危险因素。结果4组受试者总胆固醇(cholesterol total,TC)比较差异无统计学意义(P>0.05),空腹血糖(fasting blood-glucose,FPG)、甘油三酯(glycerin trilaurate,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)比较差异有统计学意义(F=1.638、0.582、2.715、5.382、5.174,P=0.007、0.016、0.028、0.003、0.001);无DR组、非增生型DR组及增生型DR组TG、HbA1c、FPG均显著高于对照组(无DR组vs对照组:t=2.246、12.440、14.539,P=0.028、0.000、0.000;非增生型DR组vs对照组:t=3.127、14.775、14.767,P均=0.000;增生型DR组vs对照组:t=3.349、16.197、12.755,P=0.001、0.000、0.000),且随病情加重而上升。非增生型DR组及增生型DR组HDL-C显著低于对照组(非增生型DR组vs对照组:t=2.113,P=0.040;增生型DR组vs对照组:t=2.778,P=0.007),且随病情加重而下降。4组血清脂联素及尿酸水平比较差异具有统计学意义(F=4.728、26.491,P=0.004、0.001),无DR组、非增生型DR组及增生型DR组血清脂联素水平均显著低于对照组(无DR组vs对照组:t=2.227,P=0.031;非增生型DR组vs对照组:t=5.198,P=0.000;增生型DR组vs对照组:t=6.827,P=0.000),且随病情加重而下降。无DR组、非增生型DR组及增生型DR组血清尿酸水平均显著高于对照组(无DR组vs对照组:t=5.681,P=0.000;非增生型DR组vs对照组:t=13.688,P=0.000;增生型DR组vs对照组:t=23.620,P=0.000),且随病情加重而上升。多因素Logistic回归分析结果显示,糖尿病病程、HbA1c、脂联素及尿酸是影响DR的独立危险因素。结论DR患者血清脂联素水平降低,尿酸水平升高,且与DR进展相关,脂联素和尿酸是影响DR的危险因素。     

胃旁路术治疗2型糖尿病的研究进展

随着国内外相关减重手术治疗2型糖尿病（T2DM）病例报道的增多,并显现出了良好的短期及长期的临床效果,该方法更加引人关注。然而手术治疗2型糖尿病的机制如何尚无明确结论,认为可能的治疗机制是十二指肠和近端空肠被旷置,从而引发胃肠道激素分泌的变化,使T2DM得到控制。本文分别对手术的类别、治疗效果及治疗机制进行综述。     

减重手术治疗2型糖尿病机制研究进展

2型糖尿病患者接受减重手术后糖尿病症状显著缓解并能长期维持,主要是因为术后胃肠道激素的改变,此外体质量下降、饮食减少以及其他的因素也起着一定作用。随着其治疗机制研究的不断深入,减重手术有望成为治疗2型糖尿病的一种主要手段。     

SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis. The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2) inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched Pub Med/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included. Data from eight studies(four randomised controlled trials and four observational studies) were extracted and a narrative synthesis was done. A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level. Out of eight studies, seven studies showed a significant decrease in serum alanine aminotransferase level. Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase. Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors. Likewise, among the three studies that evaluated a change in indices of hepatic fibrosis, two studies revealed a significant improvement in liver fibrosis. Moreover, there was an improvement in obesity, insulin resistance,glycaemia, and lipid parameters in those subjects taking SGLT-2 inhibitors. The studies disclosed that about 17%(30/176) of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23) of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence, SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.     

Bone fragility in type 2 diabetes mellitus

The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is increasing in aging and westernized societies. Both disorders predispose elderly people to disabling conditions by causing fractures and vascular complications, respectively. Recent animal studies have shown that administration of osteocalcin, which is specifically secreted from osteoblasts, can increase insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride levels in mice fed a high-fat diet. Moreover, several studies have shown that antagonism of Wnt signaling by oxidative stress contributes to the development of osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone metabolism and glucose/fat metabolism seem to be etiologically related to each other. Meta-analyses of multiple clinical studies in humans have shown that hip fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not sensitive enough to assess the risk. These findings suggest that bone fragility in T2DM, which is not reflected by BMD, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor for advanced glycation endproducts, and insulin-like growth factor-I seem to be such candidates, although further studies are required to clarify whether or not these markers could predict the occurrence of new fractures of T2DM patients in a prospective fashion.     

Attenuating type 2 diabetes with postpartum interventions following gestational diabetes mellitus

Women with a history of gestational diabetes should be screened during and after the postpartum period because of a high risk for developing type 2 diabetes mellitus. Although differences exist between guidelines practiced throughout various parts of the world, all recommend the use of cutoffs for fasting and/or post-load plasma glucose to diagnose diabetes or pre-diabetes. The use of these glycemic parameters could be optimized when a trend is observed, rather than considering them as isolated values at various time points. As the presence of insulin resistance and beta-cell dysfunction start before glycemic changes are evident, the estimation of insulin sensitivity and beta-cell function by Homeostatic Model Assessment is suggested for women who have additional risk factors for diabetes, such as obesity. Disease-modifying lifestyle intervention should be the first-line strategy to prevent or delay the onset of diabetes in women with a history of gestational diabetes mellitus. Intensive lifestyle interventions are designed to decrease caloric intake and increase physical activity in order to reduce body weight and fat, which will in turn reduce insulin resistance. This article also reviews unique problems of postpartum women, which should be considered when designing and implementing an intervention. Innovative “out of the box” thinking is appreciated, as continued adherence to a program is a challenge to both the women and the health care personnel who deal with them.     

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

BackgroundPancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged.MethodsIn total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups.ResultsMajority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.ConclusionsT2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.     

胃转流术治疗2型糖尿病的机制

胃转流术是目前2型糖尿病外科治疗的主流术式之一,但其治疗2型糖尿病的相关机制并不完全清楚.现有的相关研究表明,胃转流术对2型糖尿病的治疗作用可能通过如下机制：摄入受限和吸收不良、胰岛素抵抗的改善和胰岛β细胞功能的恢复、胃肠道激素水平的变化等.此外,脂肪因子以及血清胆汁酸水平的变化也可能发挥了一定作用.下一步的研究需要进一步明确胃转流术对于机体神经内分泌系统的影响机制,并探讨胃转流术消化道重建方式对于相关激素的影响情况.     

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

Hepatitis C virus(HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus(T1DM) and T2 DM. T2 DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1 DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2 DM and chronic hepatitis C(CHC) infection. The processes through which CHC is associated with T2 DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immunemediated mechanisms. Few data have been reported on the association of CHC and T1 DM and reports on the potential association between T1 DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoim-munity and in certain cases lead to the development of T1 DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with nondiabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effec-tive programmes for the surveillance and treatment of diabetic CHC patients.     

Pharmacogenetic studies update in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.     

腹腔镜Roux-en-Y胃旁路手术治疗肥胖症和2型糖尿病

目的 探讨腹腔镜Roux-en-Y胃旁路手术（LRYGB）治疗肥胖症和（或）2型糖尿病的可行性及疗效.方法 对21例单纯性肥胖症及9例2型糖尿病患者施行LRYGB,观察肥胖症患者体质量、BMI、超重体质量减少率（EWL%）改善情况;观察糖尿病患者术后的空腹血糖和口服葡萄糖耐量试验（OGTT）变化情况;观察全组患者手术时间、术中出血量、术后恢复、术后并发症情况.结果 本组30例皆成功完成手术,无中转开放手术者,手术时间110～270（平均168）min.术中出血量10～75（平均24.0）ml.本组21例单纯性肥胖症患者术前体质量及BMI分别为（97.2±15.0）kg和35.3±3.5;术后随访2个月至5年,术后1个月体质量及BMI即显著下降[（85.1±10.1）kg和31.2±2.2,均P〈0.01],至术后2～3年降至最低水平[（66.8±9.2）kg和24.3±1.1],之后维持在此水平;EWL%则相应增高（均P〈0.05）.9例2型糖尿病患者术前空腹血糖及OGTT 2 h血糖分别为（12.6±2.6）mmol/L和（17.8±4.1）mmol/L;术后随访3～8个月,空腹血糖及OGTT2 h血糖均显著下降[（5.9±1.4）mmol/L和（7.8±1.4）mmol/L,均P〈0.05];其中合并肥胖症的4例患者BMI明显降低（P〈0.05）,而5例未合并肥胖症者BMI无明显变化（P〉0.05）.本组30例患者中5例（16.7%）术后出现并发症,其中1例因急性暴发性胰腺炎死亡外,1例因肠系膜裂孔疝致肠梗阻行再次手术治愈,余3例均经保守治疗治愈.结论 LRYGB治疗肥胖症和（或）2型糖尿病手术安全可行,术后近期减重和（或）降糖效果显著.