酮症倾向的2型糖尿病研究进展

以自发性酮症起病的2型糖尿病具有1型和2型糖尿病的某些临床特征,其发生与重度胰岛素抵抗及胰岛β细胞功能不足有关。在中止胰岛素治疗后,部分患者可获得正常血糖缓解。测定胰岛自身免疫抗体和胰岛β细胞功能对自发性酮症起病的2型糖尿病的临床管理具有指导意义。     

Adipose tissue inflammation: Feeding the development of type 2 diabetes mellitus

The global increase in obesity-induced type 2 diabetes (T2DM) represents a burden for healthcare systems worldwide. Of particular concern is the increased morbidity associated with T2DM, in particular cardiovascular disease (CVD), leading to premature death. Obesity initially leads to the development of insulin resistance in adipose and other tissues. Insulin resistance is initially compensated by increased insulin secretion but ultimately insufficient insulin is produced and this leads to the development of T2DM. Understanding the causal mechanisms underpinning the development of obesity-induced insulin resistance may be beneficial in improving quality of life and life expectancy, with the potential for a major global impact on healthcare systems. There is abundant evidence from animal, human studies and in vitro studies to support functional roles for a number of inflammatory factors in obesity-induced insulin resistance. In this review we provide an overview of the evidence supporting a fundamental role for the fluid phase (in particular the complement system) and the cellular components of the innate immune system in the pathogenesis of obesity-induced insulin resistance and ultimately development of T2DM.     

Mitochondrial DNA variations in patients with Type 2 (non‐insulin dependent) diabetes mellitus and a Welsh control population

Type 2 (non‐insulin dependent) diabetes mellitus may be inherited along the maternal line and a variety of mitochondrial DNA (mtDNA) variants have been implicated in the pathogenesis. We have previously reported mutations in five regions of the mitochondrial genome which encompass 11 of the 22 tRNA genes. Now we employ the technique of single stranded conformational polymorphism (SSCP) analysis to investigate a further 6 regions of the mitochondrial genome, covering the remaining 11 tRNA genes in 40 patients with Type 2 diabetes and 30 racially‐matched normal controls. A variety of homoplasmic mutations were detected in patients with diabetes and these will be of value in further population association studies. Hum Mutat 13:412–413, 1999. © 1999 Wiley‐Liss, Inc.     

microRNA-146a与2型糖尿病的相关性研究进展

2型糖尿病是由遗传因素和环境因素共同导致的复杂疾病,胰岛素抵抗和胰岛β细胞功能障碍是其主要的发病机制.miRNAs是一类内源性非编码小RNA,通过调控各种基因的表达广泛参与细胞增殖、分化、凋亡、代谢等生物过程.近年研究发现,miRNA-146a与糖尿病、心血管疾病、自身免疫性疾病以及肿瘤等疾病密切相关,但miRNA-146a在2型糖尿病中的作用机制尚不清楚,还需进一步明确miRNA-146a对其的作用机制.该文就miRNA-146a与2型糖尿病及其并发症之间的相关性作一综述.     

Management of type 2 diabetes mellitus in the elderly

Aim

To provide evidence based recommendations for optimal care diabetes care in the elderly.

Background

Diabetes affects approximately 25% of the population ≥65 years, and that percentage is increasing rapidly, particularly in minorities who represent an important fraction of the uninsured/underinsured. Diabetes is an important cause of hospital admissions and a co-morbidity in as high as 50% of hospital inpatients. It impacts mortality and quality of life. While tools have become available to improve glycemic control, enthusiasm for their application must be tempered with the sober realization of the risks involved in intensification of glycemic control, chiefly hypoglycemia.

Methods

Weighted review from PubMed and other literature search tools in descending order of randomized control trials, observational studies, pilot studies, published guidelines, the authors’ clinical experience, and expert opinion.

Results/conclusions

• • 

  HbA1c targets should be stratified according to the frailty of the elderly diabetic patient: <7.0% in the generally well elderly and < 8.0% in the frail elderly.

• • 

  Therapies are available that achieve glycemic goals, while minimizing the risk of hypoglycemia, taking into consideration such factors as cognitive function, renal and hepatic function, bone density, fall risk, and hypoglycemia unawareness.

• • 

  When insulin is used determir or glargine are safer choices than NPH.

• • 

  Ultra-short acting prandial insulins are safer than regular insulin.

• • 

  Pen devices for insulin delivery significantly reduce dosing errors and the risk of hypoglycemia.

• • 

  Sudden managed care formulary changes that disrupt patients’ diabetes treatment should be prevented through national policy initiatives.

• • 

  Up to date home medication lists help prevent dangerous medication errors.

• • 

  Widespread adoption of telehealth approaches can significantly improve glycemic control and render it safer.

     

抵抗素与2型糖尿病患者胰岛素抵抗的关系

研究血清抵抗素与2型糖尿病(DM)患者胰岛素抵抗(IR)的关系。应用EIA测定72例2型DM患者(非肥胖2型DM组33例,肥胖2型DM组39例)及34名健康者(对照组)的空腹血清抵抗素水平。对照组、肥胖2型DM组及非肥胖2型DM组血清抵抗素水平分别为11.0±6.5μg/L、30.2±9.5μg/L及19.1±8.3μg/L,肥胖2型DM组和非肥胖2型DM组血清抵抗素水平均显著高于对照组(P均<0.001),肥胖2型DM组血清抵抗素水平显著高于非肥胖2型DM组(P<0.001),血清抵抗素水平与2型DM患者HOMAIR指数和程度呈显著正相关(P<0.001)。     

2型糖尿病与血小板P2Y12受体

ADP-P2Y12受体途径在血小板激活、血栓形成中发挥重要作用。2型糖尿病血小板P2Y12受体途径异常可能是血小板功能亢进的重要原因之一。在正常人，胰岛素对P2Y12途径有抑制作用，而2型糖尿病由于血小板存在胰岛素抵抗，导致P2Y12途径的高敏感性。许多2型糖尿病对普通剂量的抗血小板药物反应性降低，但是加大P2Y12阻断剂的剂量后可能会克服这种耐药现象。     

Enlarged PLIN5-uncoated lipid droplets in inner regions of skeletal muscle type II fibers associate with type 2 diabetes

Skeletal muscle physiology remains of paramount importance in understanding insulin resistance. Due to its high lipid turnover rates, regulation of intramyocellular lipid droplets (LDs) is a key factor. Perilipin 5 (PLIN5) is one of the most critical agents in such regulation, being often referred as a protector against lipotoxicity and consequent skeletal muscle insulin resistance. We examined area fraction, size, subcellular localization and PLIN5 association of LDs in two fiber types of type 2 diabetic (T2D), obese (OB) and healthy (HC) individuals by means of fluorescence microscopy and image analysis. We found that T2D type II fibers have a significant sub-population of large and internalized LDs, uncoated by PLIN5. Based on this novel result, additional hypotheses for the pathophysiology of skeletal muscle insulin resistance are formulated, together with future research directions.     

Genetic determinants of type 2 diabetes mellitus

Type 2 diabetes refers to a group of disparate metabolic diseases, which are typically characterized by insulin resistance in peripheral tissues, together with impaired insulin secretion from pancreatic beta-cells. The complexity of type 2 diabetes is related to factors such as genetic heterogeneity, interactions between genes, and the modulating role played by the environment. Recent progress has included defining the molecular basis of monogenic forms of type 2 diabetes, such as familial partial lipodystrophy and the subtypes of maturity-onset diabetes of the young (MODY), and also the identification of chromosomal regions that may harbor type 2 diabetes susceptibility genes. Many common variants in functional and positional candidate genes, including ADRB3, PPARG, ENPP1, and CAPN10, have also been studied for their possible role as determinants of type 2 diabetes, with varying levels of agreement between studies. The availability of a relatively complete sequence of the human genome will increase the amount of genetic information that can be used to evaluate hypotheses for the genetic basis of type 2 diabetes. To make sense of human type 2 diabetes in the post-genomic era, it is essential to have well-defined phenotypes in addition to sufficient numbers of individuals with the appropriate pedigree structure from families and/or communities.     

2型糖尿病患者血浆抵抗素和游离脂肪酸与胰岛素抵抗关系研究

目的比较2-型糖尿病患者血浆抵抗素（resistin,R）和游离脂肪酸（FFA）与胰岛素抵抗（Insulin restance,IR）的关系.方法按体质量指数（BMI）将64例初诊糖尿病人分为糖尿病非肥胖组（A组28例,BMI〈25）和糖尿病肥胖组（B组36例,BMI≥25）与正常对照组（C组30例）进行比较.测量身高、体质量、计算BMI、胰岛素抵抗指数（HOMA-IR）.已糖激酶法测定空腹葡萄糖（FPG）;化学发光法测定空腹胰岛素（FINS）;酶联免疫吸附法测定血浆R;酶法测定FFA.结果血浆抵抗素A、B二组显著高于C组且差异有显著性（P〈0.01）;B组高于A组且差异有显著性（P〈0.01）;FFA,A、B二组均高于C组且差异有显著性（P〈0.01）;B组高于A组,且差异有显著性（P〈0.01）;R和FFA与IR均有较好的相关性,相关系数分别为（r=0.47,P〈0.01;r=0.36,P〈0.01）.结论R与FFA与胰岛素抵抗关系密切,是重要的致IR物质,也是IR存在时重要的标志.     

NAT2基因多态性与2型糖尿病的关系

目的探讨NAT2基因多态性与2型糖尿病易感性的关系,为糖尿病的有效防治提供科学依据。方法采用PCR及测序技术对174例2型糖尿病患者和174例健康者的NAT2基因4个常见突变位点进行检测。结果糖尿病组中NAT2等位基因频率分别为：Wt（69.54%）,M2（16.37%）,M3（10.63%）,M1（3.44%）。与正常对照组比较差异无显著性。NAT2基因型（WT/WT,WT/Mx,Mx/Mx）在糖尿病组中分布频率分别为44.82%,49.42%,5.74%,两组间比较差异显著。糖尿病组中快乙酰化者164例（占94.25%）,慢乙酰化者10例（占5.75%）,两组间比较有差异。携带NAT2快乙酰化基因型者患2型糖尿病的风险是携带NAT2慢乙酰化基因型者的3.98倍。结论本研究提示快乙酰化代谢表型可能是糖尿病的一个遗传易感因素,而慢乙酰化代谢表型可能对糖尿病的发生具有一定保护作用。     

Metabolic bariatric surgery and type 2 diabetes mellitus: an endocrinologist's perspective

Traditional treatment of T2DM consisting of modification of diet, an exercise regimen, and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time, now bariatric surgery is recommended for treatment of obese patients with T2DM because its great improvements on weight loss and metabolic. In this article, effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.     

Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice

The objective of this study was to characterise the fulminant type 1 diabetes mellitus (DM) accompanying abrupt hyperglycaemia and ketonuria observed in insulin receptor substrate 2 (IRS2)-deficient mice. IRS2-deficient mice backcrossed onto the original C57BL/6J:Jc1 background (B6J-IRS2(-/-) mice) for more than 10 generations were used. Eight male IRS2-deficient mice with ketonuria and abrupt increase in plasma glucose concentrations over 25 mmol/l were used as the fulminant type 1 diabetic mice (diabetic mice) and 8 male IRS2-deficient mice (8 weeks old) without glycosuria were used as the control mice. Plasma metabolite, immunoreactive insulin (IRI) and C-peptide concentrations, hepatic energy metabolism related enzyme activities and histopathological change in pancreatic islets were investigated. The diabetic mice showed significantly higher plasma glucose and cholesterol concentrations and lower plasma IRI and C-peptide concentrations than the control mice. In livers of the diabetic mice, glycolytic and malate-aspartate shuttle enzyme activities decreased significantly and gluconeogenic, lipogenic and ketone body synthesis enzyme activities increased significantly compared to those in the control mice. The pancreatic islets of the diabetic mice decreased significantly in size and number of beta cells. The diabetic IRS2-deficient mice did not show the islet-related antibodies observed in the diabetic NOD mice in their sera. The characteristics of the diabetic IRS2-deficient mice resembled those of the human nonautoimmune fulminant type 1 DM. IRS2-deficient mice may be a useful animal model for studying the degradation mechanism of pancreatic beta cells in the process of development of fulminant type 1 DM.     

Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus

Recent animal studies have indicated that overexpression of the elongation of long-chain fatty acids family member 6 (Elovl6) gene can cause insulin resistance and β-cell dysfunction. These are the major factors involved in the development of type 2 diabetes mellitus (T2DM). To identify the relationship between single nucleotide polymorphisms (SNP) of ELOVL6 and T2DM pathogenesis, we conducted a case-control study of 610 Han Chinese individuals (328 newly diagnosed T2DM and 282 healthy subjects). Insulin resistance and islet first-phase secretion function were evaluated by assessment of insulin resistance in a homeostasis model (HOMA-IR) and an arginine stimulation test. Three SNPs of the ELOVL6 gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism, with DNA sequencing used to confirm the results. Only genotypes TT and CT of the ELOVL6 SNP rs12504538 were detected in the samples. Genotype CC was not observed. The T2DM group had a higher frequency of the C allele and the CT genotype than the control group. Subjects with the CT genotype had higher HOMA-IR values than those with the TT genotype. In addition, no statistical significance was observed between the genotype and allele frequencies of the control and T2DM groups for SNPs rs17041272 and rs6824447. The study indicated that the ELOVL6 gene polymorphism rs12504538 is associated with an increased risk of T2DM, because it causes an increase in insulin resistance.     

2型糖尿病患者血清脂联素、胰岛素、高敏C-反应蛋白和瘦素水平变化分析

通过对2型糖尿病(T2DM)患者血清中脂联素、胰岛素、C-反应蛋白和瘦素等检测分析,探讨胰岛β细胞功能胰岛素抵抗机理,为其早期诊断治疗提供依据.用化学发光、酶联免疫分析、放射免疫分析方法对184例T2DM患者(病例组)和30名正常对照者及75例T2DM患者(治疗前后观察组)经一年治疗前后的上述指标检测比较分析.结果显示,正常对照组与病例组比较,胰岛素、瘦素、C-反应蛋白、胰岛素抗体有显著性差异(P＜0.01),且呈正相关;脂联素有显著性差异(P＜0.001),但呈负相关.临床治疗后除脂联素、胰岛素抗体外,其它几项指标较治疗前明显下降,有统计学意义,而脂联素较治疗前明显升高(P＜0.001),有显著性差异.结论:2型糖尿病标志物的检测,对其早期诊断、治疗预后及生理机制的研究具有重要意义.     

谷氨酸脱羧酶抗体在2型糖尿病患者中的检出率及分布特征

目的:观察谷氨酸脱羧酶抗体(GAD-Ab)在2型糖尿病(T2DM)患者中的检出率和分布特征。方法:采用ELISA检测1970例T2DM患者的GAD-Ab总检出率及GAD-Ab在不同性别、年龄、病程和体重指数(BMI)中的分布情况;用电化学发光法检测GAD-Ab阳性和阴性T2DM患者的空腹、餐后2h胰岛素(FINS、2hINS)和空腹、餐后2hC肽(FCP、2hCP)水平,并与健康人群比较。结果:1970例T2DM患者GAD-Ab阳性126例,总检出率为6.39%,GAD-Ab阳性主要分布在30～39岁年龄组(P<0.05),低BMI组检出率较高(P<0.05),不同病程组检出率无明显差异(P>0.05)。GAD-Ab阳性组T2DM FINS、2hINS、FCP和2hCP均低于GAD-Ab阴性组和健康对照组(P<0.05)。结论:GAD-Ab检测有助于临床对T2DM患者胰岛素功能变化进行评价。     

不同治疗方式对新发2型糖尿病患者胰岛β细胞功能及胰岛素抵抗的影响

目的 比较采用胰岛素治疗(INS)与口服降糖药物治疗(OHA)等不同治疗方式对新发2型糖尿病(T2DM)患者胰岛β细胞功能及胰岛素抵抗的影响,推断新发T2DM的最佳治疗方案.方法 将62例新发T2DM患者随机分为胰岛素治疗组(INS组)和口服降糖药物组(OHA组).OHA组首选磺脲类或二甲双胍,或二者合用,疗效欠佳时增加噻唑烷二酮类,一般为2药或3药合用.两组治疗期均为3个月.每组根据血糖调整剂量,目标为空腹血糖(FBG)＜6.0 mmol/L,餐后2h血糖(2hPG)＜8.0mmol/L.观察两组治疗前后FBG、2h PG、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、空腹及餐后2hC肽(FCP、2hCP)水平的变化;用稳态模型(Homa)计算胰岛β细胞功能指数(Homaβ=20×FINS/(FBG-3.5)和胰岛素抵抗指数[HomaIR=(FBG×FINS)/22.5].用治疗后CP、Homaβ、HomaIR等相关指标进行组间比较,以评价胰岛β细胞功能及外周胰岛素抵抗的变化.结果 :(1)治疗后,两组患者FBG、2hPG、HbA1C水平较治疗前均有明显下降(P＜0.01),而在两组间比较差异无统计学意义;(2)治疗后,INS组患者FINS、FCP、2hCP、Homaβ较治疗前升高(P＜0.05),OHA组则无明显变化(P＞0.05),两组间比较差异有统计学意义(P＜0.05);(3)治疗后,INS组患者HomaIR较治疗前有明显下降(P＜0.05),OHA组仅略有下降,两组间比较差异有统计学意义(P＜0.05).结论 早期应用胰岛素治疗可以改善新发T2DM患者胰岛β细胞分泌功能及外周胰岛素抵抗.与OHA相比,INS能更好地保护患者的胰岛B细胞功能.     

A nomothetic-idiographic study of daily psychological stress and blood glucose in women with Type I diabetes mellitus

Although there has been some study of the extralaboratory generality of stress effects on diabetic metabolism, analysis of the diabetic response to everyday life stress is needed. The secondary objective of this study was to investigate whether personal characteristics moderate the daily stress-glucose relationship. Twenty-five women with Type I diabetes completed measures of internality and self-esteem and subsequently monitored daily stress and blood glucose for 30 consecutive days. Data were analyzed by both time-series and conventional correlational analyses. Glucose was higher on high-stress days than on low-stress days, with one-third of the sample showing significant positive associations between stress and same-day glucose. However, stress showed little relation to next-day glucose. Personal characteristics failed to explain differences in stress-glucose associations. Implications for practice and future research are presented.This work was funded by a grant and fellowship from the Medical Psychology Program at the University of Alabama at Birmingham and NIH/NICH Grants HD24322, HD25310, and HD00867. LifeScan Incorporated (a Johnson & Johnson Company, Mountainview, CA) and Missy Atkins, Professional Representative, donated the necessary instruments and related supplies.     

慢性阻塞性肺疾病合并2型糖尿病的老年患者肺功能、免疫失衡研究

目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)老年患者的肺功能、免疫水平变化及其临床意义.方法 选取北京市垂杨柳医院2015年1月至2016年1月收治的120例COPD患者进行研究,其中合并T2DM患者48例(T2DM组)、单纯COPD患者62例(单纯COPD组),比较两组患者肺功能、免疫指标的差异.结果 T2DM组的CD3+、CD4+、CD4+/CD8+测定值均低于单纯COPD组患者(t=4.209、t=4.598、t=5.617,P<0.05),T2DM组CD8+测定值高于单纯COPD组(t=4.157,P<0.05);T2DM组的血清IFN-γ、IL-10的水平均显著的低于单纯COPD组患者(t=4.839、t=8.529,P<0.05),T2DM组的血清IL-4、IL-8的水平高于单纯COPD组(t=4.209、t=4.517,P<0.05);T2DM组的用力肺活量(forced vital capatiry,FVC)、用力呼气容积(forced expiratory volume in 1 second,FEV lung for carbon monoxide,DLCO)水平均显著的低于单纯COPD组患者(t=3.006、t=5.966,t=6.210,P<0.05).结论 老年COPD合并T2DM患者的肺功能损害更加严重,可能与炎症反应水平增强及免疫失衡有关.     

Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection

The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9%) outpatients and in 34 of 186 (18.7%) dialysis patients. Among HCV+ patients, 32 were men (43.8%). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 μKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 μKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 μKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 μM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7%; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.