Showing papers in "Journal of Diabetes in 2013"

Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%-33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%-30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type 2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases.

Diabetes nurse case management and motivational interviewing for change (DYNAMIC): results of a 2-year randomized controlled pragmatic trial.

Abstract: Objective—To determine if the addition of nurse case managers (NCMs) trained in motivational interviewing (MI) to usual care would result in improved outcomes in high risk type 2 diabetes patients. Methods—A 2-year randomized controlled pragmatic trial randomized 545 patients to usual care control (n=313) or those who received the intervention (n= 232) with additional practice embedded NCM care, including MI-guided behavior change counseling. NCMs received intensive MI training with ongoing fidelity assessment. Results—Systolic BP was better in the intervention group (131±15.9 vs. 135±18.2, p < 0.05). HbA1c, LDL, and diastolic BP improved in both groups: HbA1c (control group 9.1% to 8.0%, intervention group 8.8% to 7.8%), LDL (control group 127 to 100 mg/dL, intervention group 128 to 102 mg/dL), diastolic BP (control group 78 to 74 mm Hg, intervention group 80 to 74 mm Hg). Depression symptom scores were better in the intervention group. The reduction in diabetesrelated distress approached statistical significance. Conclusions—NCMs and MI improved systolic BP and complications screening. The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect. Although nurses prompted providers for medication titration, strategies to reduce provider clinical inertia might also be needed. Significant findings of the study—In patients with type 2 diabetes, an intervention with nurse case management and motivational interviewing improves systolic blood pressure, depression, and screening for complications.

Association of statin use with peripheral neuropathy in the U.S. population 40 years of age or older.

Abstract: Background Peripheral neuropathy is a serious complication of diabetes and several conditions that may lead to the loss of lower extremity function and even amputations. Since the introduction of statins, their use has increased markedly. Recent reports suggest a role for statins in the development of peripheral neuropathy. The aims of the present study were to assess the association between statin use and peripheral neuropathy, and to determine whether this association varied by diabetes status. Methods Data from the lower extremity examination supplement of the 1999–2004 National Health and Nutrition Examination Survey were used. Results The overall prevalence of statin use was 15% and the prevalence of peripheral neuropathy was 14.9%. The prevalence of peripheral neuropathy was significantly higher among those who used statins compared with those who did not (23.5% vs 13.5%, respectively; P < 0.01). Multivariate logistic regression revealed that statin use (adjusted odds ratio 1.3; 95% confidence interval 1.1–1.6; Wald P = 0.04) was significantly associated with peripheral neuropathy, controlling for diabetes status, age, gender, race, height, weight, blood lead levels, poverty, glycohemoglobin, use of vitamin B12, alcohol abuse, hypertension, and non-high-density lipoprotein–cholesterol. Diabetes status, age, gender, height, weight, blood lead levels, poverty, and glycohemoglobin were also significantly associated with peripheral neuropathy. We found no effect modification between statin use and diabetes status, race, gender, age, vitamin B12, blood lead levels, or alcohol abuse. Conclusions In the present cross-sectional study, we found a modest association between peripheral neuropathy and statin use. Prospective studies are required to determine the causal direction.

Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.

Abstract: Background Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes-related genes/loci, T2DM and diabetic complications in Chinese She subjects. Methods A comprehensive gene-based association study was conducted using 17 single nucleotide polymorphisms in Chinese She subjects with normal glucose tolerance (n = 1119), impaired glucose regulation (n = 1767), and T2DM (n = 443). We applied major abnormal Minnesota Code findings to predict cardiovascular risk and estimated glomerular filtration rate to assess kidney function. Results Nine variants in FTO rs8050136, WFS1 rs10010131, CDKN2A/B rs10811661, KCNJ11 rs5219, CDC123/CAMK1D rs12779790, JAZF1 rs864745, SLC30A8 rs13266634, CDKAL1 rs10946398, and HHEX/IDE rs5015480 were significantly associated with T2DM (P < 0.05). Single nucleotide polymorphisms in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMK1D rs12779790, JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were associated with T2DM and impaired glucose regulation. Risk alleles in WFS1 rs10010131, IGF2BP2 rs4402960, CDKAL1 rs10946398, FTO rs8050136, KCNQ1 rs2237897, and ADAMTS9 rs4607103 were significantly associated with decreased homeostatic model assessment (HOMA)-β (P < 0.05). After adjusting for age, gender and body mass index, genetic variants JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were significantly related to reduced estimated glomerular filtration rate (P < 0.05). Genetic variants in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMID rs12779790, JAZF1 rs864745, FTO rs80501360, CDKAL1 rs10946398, and HHEX/IDE rs5015480 correlated with abnormal major Minnesota Code findings (P < 0.05). Conclusion Variants in WFS1, CDKN2A/B, KCNJ11, CDC123/CAMK1D, JAZF1, SLC30A8, FTO, CDKAL1, and HHEX/IDE genes are significantly associated with T2DM in She Chinese subjects. JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with diabetic nephropathy. WFS1, CDKN2A/B, CDC123/CAMK1D, JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with cardiovascular risk.

Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes.

Abstract: Background: New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes (T2D), a progressive disorder that often requires combination therapy. The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D. Methods: The present study was a randomized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America, Europe, and Asia in 278 patients with HbA1c ranging from ≥7.5% to ≤11.0% despite ongoing combination therapy with metformin (≥1500 mg/day) and rosiglitazone (≥4 mg/day). Patients were randomized (2:1) to receive sitagliptin 100 mg or placebo once daily. The main outcome measure was change from baseline in HbA1c at Week 18. Results: Mean baseline HbA1c was 8.8%. The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was −0.7% (P < 0.001) at Week 18 and −0.8% (P < 0.001) at Week 54. There were also significant (P < 0.001) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54. Significantly higher proportions of sitagliptin- than placebo-treated patients had HbA1c<7.0% at Weeks 18 (22% vs 9%; P = 0.003) and 54 (26% vs 14%; P = 0.015). Changes in body weight and the rates of adverse events overall, hypoglycemia, and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study. Conclusions: In patients with T2D, the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo. 摘要 背景：2型糖尿病（T2D）是一种进展性的疾病，它通常需要进行联合治疗，为了改善患者的血糖控制，需要新型的治疗方法。本研究评估了持续使用二甲双胍与罗格列酮联合治疗的T2D患者加用西格列汀治疗的有效性与安全性。 方法：本研究是一项随机、双盲、安慰剂对照、平行组、为期54周的研究，有41个研究地点，横跨北美、南美、欧洲以及亚洲，共278名持续使用二甲双胍(≥1500 mg/d)与罗格列酮(≥4 mg/d)联合治疗且HbA1c范围为≥7.5%至≤11.0%的患者入组。患者随机（2:1）分组后分别接受西格列汀100 mg或者安慰剂每日1次进行治疗。主要研究结果是测定HbA1c从基线至第18周时的变化。 结果：基线时的平均HbA1c为8.8%。使用西格列汀治疗后从基线至第18周时安慰剂校正后的平均HbA1c变化为-0.7%(P<0.001)，而从基线至第54周时的变化为-0.8% (P<0.001)。在第18周与第54周时，与安慰剂相比，使用西格列汀治疗后餐后2h血糖与空腹血糖也都有显著的下降(P<0.001)。与安慰剂治疗组患者相比较，西格列汀治疗组明显有更多比例的患者达到了HbA1c<7.0%，在第18周时有22%（安慰剂组为9%，P=0.003），在第54周时有26%（安慰剂组为14%，P=0.015）。在54周的研究期间，西格列汀组与安慰剂组患者的体重变化以及所有的不良事件、低血糖与胃肠道不良事件发生率都相似。

Novel therapies for the management of type 2 diabetes mellitus: part 1. pramlintide and bromocriptine-QR.

Abstract: Several classes of antidiabetic agents have been introduced into the market place over the past dozen years. As our understanding of the underlying pathophysiology of type 2 diabetes has advanced, attempts have been made to address these defects specifically. This brief review focuses on our experience with two such pharmacological approaches: (i) a synthetic amylin analog addressing amylin deficiency; and (ii) a dopaminergic agonist, focused on enhancing the lowered dopaminergic tone in patients with type 2 diabetes. Importantly, the use of these agents is not associated with hypoglycemia or weight gain. 摘要 在过去的十几年里有几类降糖药物已经被推向了市场。随着我们对2型糖尿病潜在病理生理学的理解日益深入，我们已经在尝试研制特别针对这些缺陷的药物。这篇简要的综述关注于我们对以下两个药物的使用经验：（i）一种合成的胰淀素类似物，用来解决胰淀素缺乏的问题；以及（ii）一种多巴胺受体激动剂，用来增强2型糖尿病患者降低的多巴胺效应。重要的是，使用这些药物与低血糖或者体重增加都没有关系。

Diabetes mellitus and decompensated cirrhosis: risk of hepatic encephalopathy in different age groups.

Abstract: Background The aim of the present study was to examine the association of diabetes mellitus (DM) with the prevalence and severity of hepatic encephalopathy (HE) in patients with decompensated cirrhosis (DC) and determine the impact of age and gender on this relationship. Methods West Haven criteria was used to prospectively evaluate 352 consecutive patients with DC for the presence of HE. Detailed clinicobiochemical profiling of patients was performed. Categorical data and ordered categorical variables were evaluated using the Chi-squared test for independence and trend, respectively. Continuous normal and non-parametric data were evaluated using the t-test and Mann–Whitney U-test, respectively. Results At the time of admission, HE was present in 50.3% of patients. In all, 118 patients had DM (33.5%). Patients with DM had a significantly higher prevalence (58.5% vs 42.6%; P = 0.03) and severity of HE (Ptrend = 0.01) than patients without DM. However, there were no significant differences between the two groups in terms of Child-Pugh class, MELD scores, the presence of ascites and esophageal varices. Patients with DM had higher platelet counts than those without DM (Ptrend = 0.003). In age and gender subgroup analyses, older patients and men with DM had significantly greater evidence of HE (P = 0.02 and 0.03, respectively). Multivariate analysis showed that DM (P = 0.03) and older age (P = 0.006) were independently related to HE, whereas the association of gender was non-significant. Conclusion Both DM and older age are independently associated with HE in patients with cirrhosis. 摘要 背景 本研究的目的是在失代偿性肝硬化患者中调查糖尿病与肝性脑病患病率以及严重性之间的关系，并且调查了年龄与性别对这种关系的影响。 方法 对连续的352名失代偿性肝硬化患者使用西黑文标准（West Haven criteria）前瞻性地评估了肝性脑病的发病情况。对患者进行了详细的临床生化分析。使用卡方检验分别评估了分类数据以及有序分类变量的独立性与趋势。使用T检验与Mann–Whitney U检验分别评估了连续性的正常数据以及非参数数据。 结果 在入院时，有50.3%的患者出现了肝性脑病。总共有118名患者有糖尿病（33.5%）。糖尿病患者的肝性脑病的患病率（58.5% vs 2.6%；P = 0.03）以及严重程度（Ptrend = 0.01）都比非糖尿病患者显著增高。然而，两组之间的Child-Pugh分级、MELD评分、腹水与食管静脉曲张的出现都没有显著性的差异。与那些非糖尿病患者相比较，糖尿病患者的血小板计数更高（Ptrend = 0.003）。在年龄与性别的亚组分析中，老年患者以及男性糖尿病患者出现肝性脑病的证据更显著（分别P = 0.02与0.03）。多元分析结果显示，糖尿病（P = 0.03）以及老龄（P = 0.006）均与HE呈独立相关，然而与性别的关系却没有显著性的意义。 结论 糖尿病和老龄均与肝硬化性肝性脑病独立相关。

FoxO6 in glucose metabolism (FoxO6).

Abstract: The forkhead box O (FoxO) subfamily has four members, namely FoxO1, FoxO3, FoxO4, and FoxO6. Unlike the other three members of the FoxO family, FoxO6 has garnered considerably less attention because of earlier reports that FoxO6 expression was limited to the brain. Recent data indicate that FoxO6 is produced in the liver of both rodents and humans. Hepatic FoxO6 activity, which remains at low basal levels in fed states, is markedly induced in fasted mice. FoxO6 activity becomes abnormally higher in the liver of mice with dietary obesity or type 2 diabetes (T2D). Genetically engineered mice with elevated FoxO6 activity in the liver exhibit prediabetes, culminating in the development of glucose intolerance, fasting hyperglycemia, and hyperinsulinemia. Conversely, inhibition of FoxO6 activity in the insulin-resistant liver results in a reduction in fasting hyperglycemia, contributing to the amelioration of hyperinsulinemia in T2D mice. These new data suggest that FoxO6 is an important regulator of hepatic glucose metabolism in response to insulin or physiological cues. Insulin inhibits FoxO6 activity by promoting its phosphorylation and disabling its activity in the nucleus without altering its subcellular distribution via a mechanism that is distinct from other members of the FoxO subfamily. In this article, we comprehensively review the role of FoxO6 in glucose metabolism in health and disease. We also address whether FoxO6 dysregulation is a contributing factor for the pathogenesis of fasting hyperglycemia and discuss whether FoxO6 is a potential therapeutic target for improving fasting hyperglycemia in T2D. 摘要 叉头框O（FoxO）亚科有4个成员，亦即FoxO1、FoxO3、FoxO4与FoxO6。与其他3个FoxO家族成员不一样的是，因为先前有研究报告了FoxO6仅在大脑中表达，所以很少有人关注FoxO6。最近的数据表明，在啮齿类以及人类的肝脏中都能够产生FoxO6。小鼠在进食状态下肝脏中的FoxO6活性维持在一个较低的基础水平，而禁食可以显著诱导产生FoxO6。喂养的肥胖或者2型糖尿病（T2D）小鼠肝脏中的FoxO6活性异常升高。肝脏FoxO6活性升高的遗传工程小鼠出现了糖尿病前期状态，最后发展成葡萄糖耐量异常、空腹高血糖以及高胰岛素血症。相反，在有胰岛素抵抗的肝脏中抑制FoxO6的活性可导致T2D小鼠的空腹高血糖下降，并且有利于高胰岛素血症的改善。这些新的数据表明，在肝脏对胰岛素或者生理学信号起反应的葡萄糖代谢过程中，FoxO6是一个重要的调节因素。胰岛素通过促进FoxO6的磷酸化来抑制它的活性，并且在细胞核中使它失活，但是并没有改变它的亚细胞分布，这与FoxO亚科中其他成员的作用机制有所不同。在这篇文章中，我们全面地回顾了FoxO6在健康人以及患者的葡萄糖代谢中的作用。我们讨论了FoxO6失调在空腹高血糖的发病机制中是否是一个促进因素，并且讨论了为了改善T2D患者的空腹高血糖，是否要将FoxO6作为一个潜在的治疗目标。

Vitamin D and type 2 diabetes mellitus (D2).

Abstract: Based on increasing evidence from animal and human studies, vitamin D deficiency is now regarded as a potential risk factor for Type 2 diabetes mellitus (T2DM). Vitamin D is involved in the pathogenesis of pancreatic β-cell dysfunction, insulin resistance, and systemic inflammation, conditions that contribute to the development of T2DM. Vitamin D can affect the progress of this disease directly through the activation of its own receptor, and indirectly via the regulation of calcium homeostasis. Observational studies have revealed the association between vitamin D deficiency and incident T2DM. More double-blind randomized control studies that investigate the effects of vitamin D supplementation on insulin sensitivity, insulin secretion, and the occurrence of T2DM are needed.

Diabetic retinopathy in patients with newly diagnosed type 2 diabetes mellitus in Jordan: prevalence and associated factors.

Abstract: Background To determine the prevalence of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in Jordan, as well as the factors associated with DR. Methods A cross-sectional study was conducted among 127 consecutive newly diagnosed (within the past 6 months) patients with T2DM attending one of two diabetic care centers. Complete ocular examinations were performed by an ophthalmologist and relevant data were collected. A fundus examination was performed using slit lamp indirect ophthalmoscopy after pupillary dilation with 1% tropicamide drops, with DR defined and classified according to the scale developed by the Global Diabetic Retinopathy Project Group. Results Of all the patients examined, 7.9% had DR. Of those with DR, 40% already had clinically significant macular edema necessitating laser photocoagulation or intravitreal injections. Multivariate analysis revealed that age and HbA1c were significantly associated with DR. The odds of DR increased by 11% for each 1 year increase in age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.02–1.20). For each 1% increase in HbA1c, the odds of DR increased by 43% (OR 1.43; 95% CI 1.09–1.88). Conclusions Fewer than one-tenth of newly diagnosed Jordanian patients with T2DM had DR, but more than one-third of these patients had significant maculopathy. Therefore, early screening is strongly recommended for all newly diagnosed T2DM patients. Increased age and HbA1c values are associated with increased odds of DR. A study with a larger sample size is needed to elucidate the risk factors for DR in newly diagnosed T2DM. 摘要 背景 测定约旦新诊断的2型糖尿病患者出现糖尿病视网膜病变的患病率，以及与糖尿病视网膜病变相关的因素。 方法 在就诊于两个糖尿病保健中心之一的连续的127名新诊断（在过去的6个月以内）的2型糖尿病患者中进行的横向研究。由一名眼科医师进行完整的眼部检查，并收集相关的数据。利用1%的托品酰胺滴剂散瞳后使用裂隙灯间接眼底镜检查法进行一次眼底检查，糖尿病视网膜病变的定义与分类依照全球糖尿病视网膜病变项目组制定的量表。 结果 在所有被检查的患者中，7.9%有糖尿病视网膜病变。在那些有糖尿病视网膜病变的患者中，40%在临床上已经出现显著的黄斑水肿，他们急需进行激光凝固治疗或者玻璃体内注射治疗。多元分析结果表明，年龄以及HbA1c均与糖尿病视网膜病变显著相关。年龄每增加1岁，出现糖尿病视网膜病变的几率增加11%（OR：1.11；95%Cl：1.02-1.20）。HbA1c每增加1%，出现糖尿病视网膜病变的几率增加43%（OR：1.43；95% CI：1.09-1.88）。 结论 约旦新诊断的2型糖尿病患者出现糖尿病视网膜病变的几率小于十分之一，但是出现糖尿病视网膜病变的患者中有显著黄斑病变的比例大于三分之一。因此，强烈推荐对所有新诊断的2型糖尿病患者进行早期筛查。年龄以及HbA1c值的增加均与糖尿病视网膜病变几率增加有关。需要进行一项更大样本量的研究来阐明新诊断的2型糖尿病患者出现糖尿病视网膜病变的危险因素。

Diabetes in China: Prevalence, diagnosis, and control

Abstract: Nearly 40% of those with diabetes in urban areas, but less than one-quarter of those with diabetes in rural areas, were aware of their diagnosis. Pharmacologic treatment was also more commonly used in urban than rural areas (for 33% and 22% of those with diabetes, respectively), although approximately 40% of both groups had HbA1c <7%. Both greater body mass index and a larger waist circumference were associated with diabetes, with other significant associations being male gender, a family history of diabetes, and increased systolic blood pressure, low-density lipoprotein– cholesterol, and triglyceride levels. Both cigarette and alcohol use were associated with a lower risk of diabetes. 1

Proprotein convertases subtilisin/kexin type 9, an enzyme turned escort protein: hepatic and extra hepatic functions.

Abstract: Proprotein Convertases Subtilisin/Kexin Type 9 (PCSK9) is a serine endoproteinase. Biosynthesized as a zymogen, it cleaves itself once, and then turns into an escort protein for transmembrane proteins, leading them into lysosomes for degradation. It is primarily produced and secreted by the liver. It attaches to the low-density lipoprotein receptor (LDLR) at the surface of hepatocytes and, after co-endocytosis, directs it into lysosomes where it is degraded. By downregulating LDLR, PCSK9 reduces hepatic clearance of LDL-cholesterol. Inborn or induced increase of this function causes hypercholesterolemia; its decrease causes hypocholesterolemia. This has been experimentally demonstrated ex vivo and in vivo, and corroborated by epidemiological studies associating PCSK9 genetic variations with plasma cholesterol levels. PCSK9 is now a proven target for inactivation in the treatment of hypercholesterolemia and associated atherosclerosis. However, it is still uncertain whether its severe or complete inactivation, combined with other predispositions, will be without undesirable side-effects. Some experimental data suggest that PCSK9 could contribute positively to the physiology of non-hepatic cells such as pancreatic islets β cells, adipocytes and macrophages, protecting them from excessive lipid uptake, in an endocrine, autocrine, or paracrine manner. Genetic variations that attenuate PCSK9 anti-LDLR activity are common in human populations. Their evolutionary significance still needs to be evaluated on the background of environmental pressures, such as infectious diseases, cold weather and famine, which have threatened survival and reproduction in the course of human prehistory and history.

HbA1c and the diagnosis of diabetes and prediabetes in a middle-aged and elderly Han population from northwest China (HbA1c).

Abstract: Objective To identify the optimal threshold of HbA1c and to evaluate the predictive performance of HbA1c levels in diagnosing diabetes and prediabetes in a middle-aged and elderly Han Chinese population from northwest China. Methods In all, 3354 participants aged ≥40 years with no history of diabetes from northwest China were enrolled in the present cross-sectional study. All subjects underwent a 75-g oral glucose tolerance test (OGTT), as well as HbA1c testing. HbA1c thresholds for diagnosing diabetes and prediabetes were identified by the highest sum of sensitivity and specificity of each cut-off point, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the HbA1c threshold. Results The mean (± SD) age of the participants was 57 ± 8 years, and 70.75% were women. Based on results of the OGTT, 1347 (40.16%) subjects had impaired fasting glucose and/or impaired glucose tolerance, and 725 (21.62%) had diabetes. The area under the ROC curve for detecting undiagnosed diabetes and prediabetes by HbA1c levels was 0.810 (95% confidence interval [CI] 0.796–0.823) and 0.732 (95% CI 0.717–0.747), respectively. HbA1c threshold of 6.4% and 6.1% produced the highest sum of sensitivity (60.00% and 61.49%) and specificity (87.33% and 73.24%) for diagnosing diabetes and prediabetes, respectively. Conclusion HbA1c is an effective and convenient method for diagnosing diabetes and prediabetes. HbA1c thresholds of 6.4% and 6.1% may be used as diagnostic criteria for diabetes and prediabetes, respectively, in the Han Chinese population living in northwest China. 摘要 目的 在中国西北地区中老年汉族人群中，探讨HbA1c用于诊断糖尿病和糖尿病前期的切点以及评价HbA1c其预测能力。 方法 本项横断面研究纳入了3354名年龄≥40岁、无糖尿病史的中国西北部地区的汉族人群，所有研究对象均接受了75 g口服葡萄糖耐量试验以及HbA1c的检测。HbA1c用于诊断糖尿病和糖尿病前期的切点通过敏感性和特异性之和的最大值来确定，并采用受试者工作特征曲线评价HbA1c用于诊断的准确性。 结果 研究人群的平均年龄（±SD）为57±8岁，女性占70.75%。根据OGTT试验结果，1347人（40.16%）有空腹血糖受损和/或糖耐量受损，725人（21.62%）患糖尿病。根据HbA1c水平检测无糖尿病和糖尿病前期时，ROC曲线下面积分别为0.810（95%CI 0.796–0.823）和0.732（(95% CI 0.717–0.747）。根据HbA1c水平诊断糖尿病和糖尿病前期时，当HbA1c值分别为6.4%和6.1%时，其敏感性 （60.00% 和61.49%）和特异性 （87.33% and 73.24%）之和最大。 结论 HbA1c是一个方便、有效的诊断糖尿病和糖尿病前期的检测方法。HbA1c值为6.4% 和 6.1%可作为中国西北部地区汉族糖尿病和糖尿病前期的诊断切点。

Latent autoimmune diabetes in adults in Asians: similarities and differences between East and West.

Abstract: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with features of both type 1 and type 2 diabetes and in the middle of the diabetes spectrum. Scientists clash on the question of whether this type of diabetes is a unique diabetes subtype. Multicenter studies have been performed in different countries, including the Korea National Diabetes Program (KNDP) collaboratory group, the Ehime study in Japan, the Not Insulin-Requiring Autoimmune Diabetes (NIRAD) study in Italy, the Nord-Trondelag Health (HUNT) study in Norway, the UK Prospective Diabetes Study (UKPDS) in the UK, the Action LADA study in Europe and the LADA China study in China. These studies found universal immunogenetic effects associated with LADA, but with some ethnic differences. Herein we summarize those multicenter studies and compare the ethnic similarities and differences between East and West from epidemiological, clinical, immune, and genetic viewpoints.

Diabetes and cancer relationships.

Abstract: Diabetes and cancer are both heterogeneous and multifactorial diseases with tremendous impact on health worldwide. Epidemiologic evidence suggests that certain malignancies may be associated with diabetes, as well as with diabetes risk factors and, perhaps, with certain diabetes treatments. Numerous biological mechanisms could account for these relationships. Insulin-like growth factor (IGF)-1, IGF-2, IGF-1 receptors, insulin, and the insulin receptor play roles in the development and progression of cancers. Although evidence from randomized controlled trials does not support or refute associations of diabetes and its treatments with either increased or reduced risk of cancer incidence or prognosis, consideration of malignancy incidence rates and the magnitude of the trials that would be required to address these issues explains why such studies may not be readily undertaken.

Kakkalide ameliorates endothelial insulin resistance by suppressing reactive oxygen species-associated inflammation.

Abstract: Background Kakkalide is the predominant isoflavone derived from the flowers of Pueraria lobata (Willd.) Ohwi. The aim of the present study was to investigate the effects of kakkalide on insulin resistance in the endothelium. Methods Human umbilical vein endothelial cells (HUVEC) were stimulated with 100 μmol/L palmitate (PA) for 30 min and the effects of 30 min pretreatment with 0.1–10 μmol/L kakkalide on reactive oxygen species (ROS)-associated inflammation in cells were evaluated by western blot analysis and reverse transcription–polymerase chain reaction. Furthermore, we investigated the biomodulation of insulin signaling by kakkalide along the insulin receptor substrate (IRS)-1/Akt/endothelial nitric oxide synthase (eNOS) pathway. We also determined the effects of 30 min pretreatment with 0.1–10 μmol/L kakkalide on insulin-mediated endothelium-dependent vasodilation of rat aorta in vitro following stimulation with 100 μmol/L PA. Results Kakkalide inhibited ROS overproduction and effectively restored mitochondrial membrane potential, demonstrating its chemoprotection of mitochondrial function. In addition, kakkalide inhibited ROS-associated inflammation in the endothelium by inhibiting tumor necrosis factor-α and interleukin-6 production and gene expression, as well as suppressing the phosphorylation of c-Jun N-terminal kinase and IκB kinase β/nuclear factor-κB. Inflammation impaired insulin phosphatidylinositol 3-kinase (PI3K) signaling and reduced insulin-mediated NO production in endothelial cells. Kakkalide facilitated PI3K signaling by positively regulating serine/tyrosine phosphorylation of IRS-1. Conclusions Kakkalide inhibited ROS-associated inflammation and ameliorated insulin-resistant endothelial dysfunction by beneficial effects on IRS-1 function. 摘要 背景 葛花苷是从野葛(P. lobata[Wild.] Ohwi)花中提取的一个具代表性的异黄酮成分。本课题旨在探讨葛花苷对血管内皮细胞胰岛素抵抗的作用。 方法 用100 µmol/L棕榈酸(PA)刺激人脐带内皮细胞（HUVEC）30分钟建立HUVEC胰岛素抵抗模型，通过Western Blot和RT-PCR法检测采用0.1–10 µmol/L的葛花苷进行30分钟的预处理对细胞活性氧相关（ROS）的炎症的抑制效果。检测了葛花苷通过胰岛素受体底物（IRS）-1/Akt/内皮细胞一氧化氮合成酶（eNOS）途径对胰岛素信号的生物调节作用。此外还检测了在体外以100 µmol/L的 PA刺激大鼠主动脉，再以0.1–10 µmol/L的葛花苷进行30分钟的预处理对胰岛素介导的内皮依赖性血管舒张功能的影响。 结果 葛花苷能够抑制活性氧的过度产生以及有效恢复降低的线粒体膜电位，显示了其对线粒体功能的化学保护作用。此外，葛花苷还能通过抑制TNF-α和IL-6的产生和基因表达来抑制内皮细胞ROS相关的炎症，同时抑制c-Jun氨基末端激酶和IKKβ/NF-κB的磷酸化。炎症损害胰岛素磷脂酰肌醇3激酶(PI3K)信号通路，减少胰岛素介导的内皮细胞的NO的产生。葛花苷通过对IRS-1的丝氨酸/酪氨酸磷酸化的正向调节帮助恢复胰岛素PI3K信号通路。 结论 葛花苷能够通过对IRS-1功能的正向调节抑制ROS相关的炎症并改善胰岛素抵抗的内皮功能紊乱。

Pharmacokinetics, safety, and tolerability of single- and multiple-dose exenatide once weekly in Chinese patients with type 2 diabetes mellitus.

Abstract: Background This open-label, single-period study assessed the pharmacokinetics, safety, tolerability, and pharmacodynamics of exenatide once weekly (q.w.), following single and multiple weekly subcutaneous (s.c.) injections in native Chinese patients with type 2 diabetes (T2D). Methods Patients (n = 25; mean [±SD] age 51.3 ± 8.2 years; body mass index 25.6 ± 2.4 kg/m2; HbA1c 7.4 ± 1.2%; duration of diabetes 3.1 ± 3.1 years) previously treated with diet modification and exercise alone or incombination with stable metformin doses were enrolled in the study. Twenty-five patients received weekly doses of 2 mg, s.c., exenatide q.w. for 10 weeks, followed by 10 weeks observation. Pharmacokinetic parameters of exenatide, fasting plasma glucose (FPG), HbA1c, and body weight were summarized using descriptive statistics. Results Steady state plasma exenatide concentrations (299 pg/mL) were attained within 8 weeks. Exenatide q.w. was generally well tolerated, and the majority of adverse events reported were mild in severity. The most frequent study drug-related adverse events were diarrhea and vomiting. Decreases were observed from baseline to 10 weeks in FPG (~3.0 mmol/L), HbA1c (~1.0%), and body weight (~3.8 kg). Conclusions This is the first clinical trial of exenatide q.w. in native Chinese patients with T2D. The results suggest that exenatide q.w. has a pharmacokinetic profile in this patient population similar to that observed in other ethnic and racial populations, and appears to be safe and generally well tolerated, with the potential to improve glycemic control and decrease body weight without increasing the risk of hypoglycemia. 摘要 背景 考察了对中国本土2型糖尿病患者给予单次和多次皮下注射艾塞那肽周制剂的药代动力学、药效动力学、安全性和耐受性。研究设计为开放性、单周期。 方法 入选对象为仅靠饮食控制和锻炼或联合使用稳定剂量的二甲双胍控制血糖的患者（n=25人，平均年龄51.3±8.2岁，BMI 25.6±2.4 kg/m2，HbA1c 7.4%±1.2%，糖尿病病程3.1±3.1年）。25名患者接受每周皮下注射艾塞那肽周制剂，剂量为2mg，共10周，并在停药后随访10周。对艾塞那肽的药代动力学参数、空腹血糖FBG、HbA1c和体重进行描述性统计。 结果 给药8周时艾塞那肽达到稳态血药浓度（299 pg/mL）。艾塞那肽周制剂耐受性良好，绝大多数报告的不良事件均为轻度。与研究药物相关的最常见的不良事件是腹泻和呕吐。与基线相比给药10周后FBG降低最多达3.0 mmol/L，HbA1c降低最多达1.0%，体重降低最多达3.8 kg。 结论 这是艾塞那肽周制剂首次用于中国本土2型糖尿病患者的临床试验。研究结果显示，艾塞那肽周制剂在中国糖尿病患者中的药代动力学特性和在其他种族中相似。该药物是安全的，耐受性良好，可以改善血糖控制和降低体重，同时不会增加低血糖风险。

Anti-atherogenic effect of chromium picolinate in streptozotocin-induced experimental diabetes.

Abstract: Background: Several studies have implicated changes in the levels of trace elements in diabetes. Chromium is one such element that seems to potentiate insulin action, thereby regulating carbohydrate and lipid metabolism. The aim of the present study was to evaluate the effect of chromium supplementation as chromium picolinate on the lipid profile of streptozotocin (STZ)-induced diabetic rats. Methods: Rats were rendered diabetic by a single injection of STZ (50 mg/kg, i.p.). Chromium picolinate (1 mg/kg per day, p.o.) was administered to rats for a period of 4 weeks. At the end of the treatment period, plasma total lipids, triglycerides, total cholesterol and lipoprotein levels were determined, as was hepatic glucose-6-phosphate dehydrogenase activity. Results: Total plasma lipids increased significantly in diabetic rats and this increase was ameliorated by chromium treatment for 4 weeks. Elevated total lipids in diabetic rats were due to increased plasma triglyceride and cholesterol levels. Chromium supplementation lowered plasma triglyceride and cholesterol levels to near normal. Chromium treatment also normalized low-density lipoprotein–cholesterol (LDL-C) and very low-density lipoprotein–cholesterol levels and improved the total cholesterol:high-density lipoprotein–cholesterol (HDL-C) and HDL-C:LDL-C ratios, suggesting an anti-atherogenic effect. In addition to improving the plasma lipid profile, chromium supplementation normalized liver glucose-6-phosphate dehydrogenase activity in diabetic rats. Conclusions: These results provide evidence that chromium picolinate effectively attenuates the dyslipidemia associated with diabetes and thus can be used as an adjuvant therapy in the treatment of diabetes and its associated complications. 摘要 背景：有几项研究表明糖尿病患者的微量元素水平有变化。在这些元素中铬似乎可以增强胰岛素的作用，从而调节碳水化合物与脂质的代谢。本研究的目的是评估吡啶甲酸铬作为铬元素添加剂对链脲霉素（STZ）诱导的糖尿病大鼠血脂谱的影响。 方法：大鼠通过单次注射STZ（50 mg⁄kg，腹腔内注射）诱导出糖尿病。大鼠使用吡啶甲酸铬（每日1 mg⁄kg口服）治疗4周时间。在治疗期结束时，测定血浆中的总脂质、甘油三酯、总胆固醇、脂蛋白水平以及肝脏中的葡萄糖-6-磷酸脱氢酶活性。 结果：在糖尿病大鼠中，血浆中的总脂质显著增加，而通过铬元素治疗4周后可以缓解这种情况。在糖尿病大鼠中，总脂质水平的升高与血浆中的甘油三酯以及胆固醇水平升高有关。铬元素添加剂可以将血浆中的甘油三酯与胆固醇水平降低到接近正常。使用铬元素治疗后还可以使低密度脂蛋白胆固醇（LDL-C）与极低密度脂蛋白胆固醇水平正常化，并且可以改善总胆固醇与高密度脂蛋白胆固醇（HDL-C）以及HDL-C与LDL-C的比值，表明它具有抗动脉粥样硬化作用。除了改善血脂谱，铬元素添加剂还可使糖尿病大鼠肝脏中的葡萄糖-6-磷酸脱氢酶活性正常化。 结论：这些结果证实吡啶甲酸铬可以有效地缓解糖尿病相关的血脂紊乱，因此它可以作为糖尿病及其相关并发症的辅助治疗。

Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 in db/db mice (奥美拉唑改善唾液素-4 对db/db小鼠的减肥与降糖作用)*

Abstract: Background: In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes. Methods: The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity. Results: Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content. Conclusions: Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.

Population-based survey of the prevalence of type 1 and type 2 diabetes in school children in Philadelphia.

Abstract: Background Population-based (PB) registries of type 1 diabetes mellitus (T1DM) in children have been essential in determining the geographic, racial, and temporal patterns of the disease. There is a paucity of PB data on the prevalence of type 1 and type 2 diabetes (T2DM) in youth. Methods The prevalence of diabetes in children was determined using a PB survey of the 628 schools in Philadelphia. Data obtained included type of diabetes, date of birth, race, gender, date of diagnosis, diabetes treatment, and most recent height and weight. Results The survey was completed by nurses at 510 schools (81% of schools) representing 252,896 children (70% of children in Philadelphia). Prevalence (per 1000) was computed. The survey identified 492 cases (355 T1DM, 88 T2DM, 49 type unknown). The overall prevalence of T1DM was 1.58 (0.73 White, 0.56 African American, 0.50 Hispanic); of T2DM was 0.35 (0.03 White, 0.28 African American, 0.05 Hispanic). Mean age at diagnosis was 8.6 and 11.9 years for T1DM and T2DM, respectively. The prevalence of T1DM was higher in boys- T2DM was higher in girls. Of children with T2DM, 25% were treated with insulin. BMI was ≥95th percentile in 20% of children weighed (10% of T1DM, 57% of T2DM). Conclusions Although the Philadelphia Pediatric Diabetes Registry is the longest ongoing US registry of its kind, these are the first PB diabetes prevalence data of children in Philadelphia. PB studies in schools are able to capture children with diabetes who are diagnosed and treated in a variety of settings. 摘要 背景 基于人口的1型糖尿病儿童登记表对于确定疾病的地理、种族以及时间规律来说很有必要。目前还缺乏有关青年人中1型与2型糖尿病患病率的基于人口的数据。 方法 在费城628所学校里采用基于人口的调查获取儿童中的糖尿病患病率。获取的数据包括糖尿病类型、出生日期、种族、性别、诊断日期、糖尿病治疗方案以及最近的身高与体重。 结果 由护士在510所学校（81%的学校）中对252896名儿童（70%的费城儿童）进行了调查。计算出（每1000名）患病率。这个调查鉴定出了492名病例（355名1型糖尿病，88名2型糖尿病，49名类型不明确）。1型糖尿病的总患病率为1.58（白人为0.73，非裔美国人为0.56，西班牙人裔为0.50）；2型糖尿病为0.35（白人为0.03，非裔美国人为0.28，西班牙人裔为0.05）。诊断1型糖尿病与2型糖尿病时的平均年龄分别为8.6岁与11.9岁。男孩中的1型糖尿病患病率更高，而女孩中的2型糖尿病患病率更高。在2型糖尿病儿童中，有25%的人使用胰岛素治疗。有20%的儿童BMI超过了第95百分位（1型糖尿病有10%，2型糖尿病有57%）。 结论 虽然费城儿科糖尿病登记表在美国同类登记表中持续时间最长，但这些是费城儿童第一份基于人口的糖尿病患病率的数据。在学校中进行的基于人口的研究能够获得在不同的机构进行诊断与治疗的儿童糖尿病数据。

Meta-analysis of insulin aspart versus regular human insulin used in a basal-bolus regimen for the treatment of diabetes mellitus.

Abstract: Background: The objective of the current study was to compare the efficacy of two different insulin formulations, insulin aspart (IAsp) and regular human insulin (RHI), for prandial insulin coverage with neutral protamine Hagedorn (NPH) insulin as basal insulin using a meta-analysis approach. The primary endpoint was change in A1c over time. Secondary endpoints included incidence of hypoglycemia and postprandial glycemic control. Methods Clinical trials (Type 1 and Type 2 diabetes) complying with Good Clinical Practice, and with individual patient data, were included in the meta-analysis. Trials were randomized, consisting of (at least) two treatment arms and had a minimum duration of 12 weeks. Estimates were calculated using fixed-effects and random-effects models. Heterogeneity was assessed for each analysis. The effect of baseline parameters on A1c was analyzed in extended simultaneous models. Results The mean difference in A1c was 0.1% (95% confidence interval [CI] [−0.15; −0.04], P < 0.001) in favor of IAsp. Higher accumulated dose of IAsp, higher age and increased rates of hypoglycemia were associated with improved A1c outcome. Fasting plasma glucose was not significantly different between regimens. Postprandial glucose was significantly lower after treatment with IAsp compared with RHI, but the analysis did present a significant level of heterogeneity (P < 0.001). The overall rate of hypoglycemia was the same with both regimens, but nocturnal hypoglycemia was significantly lower with IAsp. Conclusions: A basal–bolus regimen with IAsp as bolus insulin provided minimal, but statistically significant, improvement in overall glycemic control with a lower rate of nocturnal hypoglycemic episodes, compared with a corresponding regimen with bolus RHI. 摘要 背景 本研究的目的是使用Meta分析的方法比较两种不同胰岛素制剂的疗效，亦即在联合中性精蛋白锌胰岛素（NPH）作为基础胰岛素的基础上，比较门冬胰岛素（IAsp）与常规人胰岛素（RHI）作为餐时胰岛素的疗效。主要终点是随着时间变化的A1c。次要终点包括低血糖的发生率以及餐后血糖控制情况。 方法 入选Meta分析的临床试验（1型与2型糖尿病）都要遵守临床试验管理规范并且具备每个患者的数据。这些试验都是随机试验，（至少）包含2个治疗组并且持续时间最短为12周。使用固定效应与随机效应模型来计算评估结果。评估每个分析的异质性。在同步扩展模型中分析基线指标对A1c的影响。 结果 A1c的平均差异为0.1%（95% 置信区间[−0.15；−0.04]，P < 0.001），有利于IAsp组。随着A1c 结果的改善，IAsp的总剂量更高、年龄更大并且低血糖发生率更高。两种治疗方案之间的空腹血糖没有显著性差异。与RHI相比较，使用IAsp治疗后餐后血糖发生率显著更低，但是分析显示存在显著的异质性（P < 0.001）。两种治疗方案总的低血糖发生率是一样的，但是IAsp组的夜间低血糖发生率显著更低。 结论 与对应的将RHI作为餐时胰岛素的治疗方案相比较，在基础—餐时治疗方案中将IAsp作为餐时胰岛素后患者的总体血糖控制情况有微小的、但却有显著统计学意义的改善，并且夜间低血糖的发生率也更低。

Antidepressant Use, Depression, and New Onset Diabetes among Elderly Medicare Beneficiaries

Abstract: Background The aim of the present study was to examine the association between antidepressant use, diagnosed depression, and new-onset diabetes among elderly Medicare beneficiaries. Methods Longitudinal data from merged survey and claims from the nationally representative Medicare Current Beneficiary Survey(MCBS) from 1999 to 2005 were used. Diabetes incidence was extracted from claims and survey data over a 3-year period. Data regarding depression and antidepressant use over time were obtained. Multivariate logistic regression analysis was used to examine associations between antidepressant use, depression, and new-onset diabetes, adjusted for demographic, socioeconomic, and lifestyle risk factors. Analyses accounted for the complex design of the MCBS. Results The incident diabetes rate was 4.8% for those “without depression and without antidepressants” and 9.5% for those with any antidepressant use in all 3 years and diagnosed depression”. Compared with Medicare beneficiaries who did not report any antidepressant use, beneficiaries reporting antidepressant use in all 3 years were 50% more likely to have new-onset diabetes. However, when diagnosed depression was entered in the model, there was no significant association between long-term antidepressant use and new-onset diabetes. Medicare beneficiaries with any depression were twice as likely as those without depression to develop diabetes (adjusted odds ratio 2.04; 95% confidence interval 1.51, 2.75). Conclusions Depression independently increased the risk of developing diabetes in the MCBS population, although there is no evidence of an association between antidepressant use and new-onset diabetes. If replicated, these results have significant clinical implications. 摘要 背景 本研究的目的是在老年医疗保险受益者中调查抗抑郁药的使用、抑郁症的诊断与新发糖尿病之间的关系。 方法 纵向数据来自于合并的调查与索赔数据，即1999至2005年间全国典型的医疗保险当前受益人调查（Medicare Current Beneficiary Survey MCBS）数据。糖尿病发生率来自于超过3年的索赔与调查数据。并获取有关抑郁症以及随着时间的推移抗抑郁药使用情况的数据。使用多因素Logistic回归分析来检验抗抑郁药的使用情况以及抑郁症与新发糖尿病之间的关系，并且经过了人口统计学、社会经济学以及生活方式等危险因素的校正。分析解释了MCBS的复杂设计。 结果 那些“没有抑郁症也没有使用抗抑郁药物”的老年人糖尿病发生率为4.8%，那些“使用任何抗抑郁药物总共达到3年以及已经诊断抑郁症”的老年人糖尿病发生率为9.5%。与那些没有报告使用任何抗抑郁药的医疗保险受益者相比较，报告使用任何抗抑郁药物总共达到3年的受益者出现新发糖尿病的可能性高50%。然而，若将已经诊断的抑郁症也并入模型中，则长期使用抗抑郁药与新发糖尿病之间就没有显著的相关性了。合并任何程度抑郁症的医疗保险受益者发生糖尿病的可能性是那些未合并抑郁症受益者的2倍（校正后优势比为2.04；95%CI为1.51，2.75）。 结论 在MCBS人群中，抑郁症可独立增加患糖尿病的风险，虽然目前还没有证据表明抗抑郁药的使用与新发糖尿病之间具有相关性。如果能够得到重复研究的证实，那么这些结果将具有重要的临床意义。

Two-point discrimination in diabetic patients (糖尿病患者的两点辨别力)

Abstract: Background Diabetes mellitus (DM) is a common cause of polyneuropathy. The aim of the present study was to evaluate two-point discrimination (TPD) compared with nerve conduction studies in the early stages of DM. Methods Forty-eight patients with early diagnosed (<5 years) type 2 DM and 17 healthy controls were evaluated. Of the patients with DM, 26 had neuropathic pain and 22 were asymptomatic. TPD and electrophysiological evaluations was obtained for all subjects. Results Nerve conduction studies in patients showed findings related to both demyelination and axonal damage. Patients with neuropathic pain had higher TPD values on the plantar surface of the foot and both groups of DM patients had higher TPD values on the outer lateral malleolus compared with the control group (P < 0.05). There was a correlation between TPD and axonal damage in patients with neuropathic pain (P < 0.05). In patients without neuropathic pain, there was a correlation between TPD values and distal latencies of motor or sensory nerves (P < 0.05). In the control group, only third digit TPD values were related to the distal motor latency of the median nerve (P < 0.05). Conclusion In conclusion, the TPD method is a less painful, practical, costeffective, and more easily applicable method that was completed in less timethan nerve conduction studies. Higher TPD values in the lower extremities indicate nerve damage in patients. These findings suggest that increased TPD values can easily determine neuropathy starting in the early stages of diabetes in patients with DM. 摘要 背景 糖尿病是多发性神经病变最常见的病因之一。本研究的目的是在处于早期阶段的糖尿病患者中比较测定两点辨别力（two-point discrimination, TPD）与神经传导研究。 方法 评估了48名早期（< 5年）诊断的2型糖尿病患者以及17名健康对照者。在糖尿病患者中，26名患者有神经性疼痛，22名患者无症状。所有的受试者都要进行TPD与电生理学评估。 结果 患者的神经传导研究结果显示与脱髓鞘以及轴突损害都有关系。与对照组相比较，有神经性疼痛的患者足底面的TPD值更高，并且两组糖尿病患者外踝面的TPD值都更高（P < 0.05）。在有神经性疼痛的患者中，TPD与轴突损害具有相关性（P < 0.05）。在没有神经性疼痛的患者中，TPD值与运动或者感觉神经的远端潜伏期具有相关性（P < 0.05）。在对照组中，只有第三指的TPD值与正中神经的远端运动潜伏期具有相关性（P < 0.05）。 结论 总之，与神经传导研究相比较，测定TPD的方法是一种痛苦少、成本效益高、更容易施行的方法，并且可以在更短的时间内完成。患者下肢TPD值更高意味着神经损害。这些研究结果提示，在处于早期阶段的糖尿病患者中，从升高的TPD值可以很容易地判定是否有神经病变。

Glucagon: the renewal of an old hormone in the pathophysiology of diabetes.

Abstract: Type 2 diabetes (T2D) is one of the most common diseases, affecting 5-10% of the population in most countries; the progression of its prevalence has been constant over the past 50 years in all countries worldwide, creating a major public health problem in terms of disease management and financial burden. Although the pathophysiology of T2D has been attributed for decades to insulin resistance and decreased insulin secretion, particularly in response to glucose, the contributing role of glucagon in hyperglycemia has been highlighted since the early 1970s by demonstrating its glycogenolytic, gluconeogenic and ketogenic properties. More recently, the importance of glucagon in diabetes has been highlighted in a model of streptozotocin-induced diabetic mice becoming euglycemic in the absence of glucagon receptors and without insulin treatment. Understanding the dysregulation of α-cells in diabetes will be critical to better define the pathophysiology of diabetes and develop new antidiabetic treatment.

Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol.

Abstract: Background Based on recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of type 1 diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive for T1D autoantibodies, with oral calcitriol. Methods The present prospective trial was performed on 12 children (1.5–13 years old) who were investigated for the potential risk of T1D because of an already diagnosed association of celiac disease and autoimmune thyroiditis (four girls), autoimmune thyroiditis at a very young age (two girls, two boys), a diagnosis of T1D in siblings (two boys), and impaired glucose tolerance (IGT; one boy, one girl). Serum autoantibody levels, including islet cell autoantibodies, anti-glutamic acid decarboxylase (GAD) 65, insulin autoantibodies (IAA), and anti-tyrosine phosphatase, and markers of calcium metabolism were evaluated prior to and at 6-monthly intervals after the initiation of 0.25 μg/day calcitriol for 1–3 years. Results In all children, persistent negativation of the anti-GAD65 antibodies and IAA was observed within 0.4–2.1 years. Of the two children with IGT, the boy proved to have maturity onset diabetes of the young (MODY) 2, whereas the glycemic profile was normalized in the girl. Conclusions Despite the small number of subjects and the absence of a control group in the present study, 0.25 μg/day calcitriol effectively negativates anti-GAD65 antibodies and IAA after a median time of 6 months. This simple, safe, and low-cost strategy may prove effective in the prevention of T1D in the future. 摘要 背景 基于最近对1,25-二羟维生素D在1型糖尿病（T1D）发病机制中地位的认识以及动物模型给予1,25-二羟维生素D治疗的结果，我们进行了一项临床试验，对T1D自身抗体阳性的高风险儿童给予口服骨化三醇进行预防治疗。 方法 这项前瞩性的试验是在12名儿童（1.5–13岁）中进行的，经过调查发现他们有发生T1D的潜在风险，因为有4名女孩已经被诊断为乳糜泻以及自身免疫性甲状腺炎，有2名女孩与2名男孩在非常小的时候被诊断为自身免疫性甲状腺炎，有2名男孩的同胞被诊断为T1D，有1名女孩与1名男孩被诊断为葡萄糖耐量受损（IGT）。在使用0.25 µg/日的骨化三醇治疗之前以及治疗1-3年期间每隔6个月评估血清中的自身抗体水平，包括胰岛细胞自身抗体、抗谷氨酸脱羧酶（GAD）65抗体、胰岛素自身抗体（IAA）与抗酪氨酸磷酸酶抗体，以及钙代谢标志物水平。 结果 所有的儿童中，在0.4–2.1年之内，可观察到抗GAD65抗体与IAA持续阴性。在2名IGT儿童中，男孩被证实为青少年发病的成年型糖尿病（MODY 2型），而女孩的血糖谱正常了。 结论 尽管本研究的受试者数量较少并且缺乏对照组，但是经过中位数时间为6个月的骨化三醇0.25 µg/日的治疗后可以有效地维持抗GAD65抗体与IAA阴性。这种简单、安全并且花费较低的治疗策略在将来有可能会被证实能够有效地预防T1D。

Current role of short-term intensive insulin strategies in newly diagnosed type 2 diabetes.

Abstract: Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by worsening insulin resistance and a decline in β-cell function. Achieving good glycemic control becomes more challenging as β-cell function continues to deteriorate throughout the disease process. The traditional management paradigm emphasizes a stepwise approach, and insulin has generally been reserved as a final armament. However, mounting evidence indicates that short-term intensive insulin therapy used in the early stages of type 2 diabetes could improve β-cell function, resulting in better glucose control and more extended glycemic remission than oral antidiabetic agents. Improvements in insulin sensitivity and lipid profile were also seen after the early initiation of short-term intensive insulin therapy. Thus, administering short-term intensive insulin therapy to patients with newly diagnosed T2DM has the potential to delay the natural process of this disease, and should be considered when clinicians initiate treatment. Although the early use of insulin is advocated by some guidelines, the optimal time to initiate insulin therapy is not clearly defined or easily recognized, and a pragmatic approach is lacking. Herein we summarize the current understanding of early intensive insulin therapy in patients with newly diagnosed T2DM, focusing on its clinical benefit and problems, as well as possible biological mechanisms of action, and discuss our perspective.

Heart failure in hospitalized patients with diabetic foot ulcers: clinical characteristics and their relationship with prognosis.

Abstract: Background In the present study we: (i) evaluated the incidence of heart failure (HF) in patients with diabetic foot ulcer (DFU); and (ii) investigated the relationship between the clinical characteristics in these patients and prognosis. Methods The clinical characteristics of 330 consecutive Chinese patients (137 men, 193 women) hospitalized for DFU were collected and assessed to determine the effects of HF on DFU. All patients were followed for 3 months and rates of healing, the development of new ulcers, amputations, and mortality were calculated at the end of the follow-up period. Results Heart failure was present in 64.3% of patients with DFU, with the prevalence of HF increasing with Wagner grade from Wagner 1 through to Wagner 5 (42.4%, 59.1%, 64.7%, 73.3%, and 87.0%, respectively), higher than the 33.6% prevalence in diabetic patients without DFU (Wagner 0). The presence of HF conferred a greater increased relative risk of a worse prognosis. The 3-month healing rates of DFU in patients with and without HF were 60.3% and 75.7%, respectively. Recurrence (13.2% vs 7.5%) and amputations (28.6% vs 20.0%) were more frequent in patients with than without HF (P < 0.05). All-cause mortality was recorded for 14 of 126 patients with HF compared with three of 70 patients without HF (11.1% vs 4.3%, respectively; P < 0.05). Conclusions The prevalence of HF is high in Chinese inpatients with DFU, with the presence of HF indicating a worse prognosis for these patients. 摘要 背景 分析糖尿病足溃疡患者的心衰发病率，探讨此类患者的临床特点与其预后的关系。 方法 收集330例（男137例，女193例）糖尿病足溃疡住院患者的资料，分析心衰对糖尿病足溃疡的影响。随访3个月，随访期结束时计算患者的溃疡治愈率、复发率、截肢率及死亡率。 结果 糖尿病足溃疡住院患者的总体心衰发病率为64.3%，且随溃疡严重程度增加（Wagner分级从Wagner 1 至Wagner 5级）而逐渐升高（分别为42.4%，59.1%，64.7%，73.3%，87.0%），显著高于无糖尿病足溃疡患者（Wagner 0级）的心衰发病率（33.6%）。合并心衰的足溃疡患者预后差的相对危险性增加。有无心衰的两组患者3个月的溃疡愈合率分别为60.3%和75.7%。合并心衰患者的足溃疡复发率、截肢率及死亡率均较对照组高（13.2% vs 7.5%，28.6% vs 20.0%，11.1% vs 4.3%，P均 < 0.05）。 结论 中国糖尿病足溃疡住院患者的心衰发病率较高，合并心衰的足溃疡患者预后较差。

Sodium glucose transporter 2 inhibition: a new approach to diabetes treatment.

Abstract: A vexing aspect of the treatment of type 2 diabetes is the potential of both insulin and the sulfonylureas to cause hypoglycemia, with increasing recognition of the association of hypoglycemia with adverse outcome. It is hypoglycemia rather than normalization of glycemic control that appears (for certain individuals) to be undesirable. Although in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study intensive glycemic treatment was associated with an increase in mortality, there was actual reduction in mortality with excellent control, with the dilemma that those diabetic patients in worse control initially appeared to have greater risk of both hypoglycemia and mortality. Thus, the appearance of a new therapeutic class not intrinsically associated with hypoglycemia should be greeted with cautious optimism. Glucose is present in the glomerular filtrate and is, under usual circumstances, completely reabsorbed by a group of transport proteins in the renal tubular epithelium, with sodium glucose transporter (SGLT)-2 quantitatively the most important. Recent observations have shown that diabetic patients upregulate the expression of this and other renal glucose transporters, presumably to compensate for and reduce glycosuria. A number of orally absorbed small molecules can inhibit this transporter, leading to glycosuria at even modestly elevated glucose concentrations, a phenomenon that was used experimentally nearly three decades ago in studies demonstrating that glucose toxicity is a reversible contributor to both insulin resistance and impaired insulin secretion. Glucose excretion with administration of these SGLT2 inhibitors increases in degree as glucose levels rise, whereas the agents do not increase glycosuria to a major degree at euor hypoglycemic levels. In addition, by causing osmotic diuresis, these agents may have benefits in lowering blood pressure, and the glucose lost in the urine can lead to weight reduction. What are the clinical data? A number of SGLT2 inhibitors are being studied, including dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin. A series of Phase 3 clinical trials of dapagliflozin presented to the US Food and Drug Administration showed dose-related glucoselowering of similar efficacy to that of sulfonylureas and metformin, with a study of dapagliflozin added to metformin showing a glucose-lowering effect equal to that of glipizide, but with less than one-tenth as much hypoglycemia. In a meta-analysis of clinical studies, dapagliflozin was associated with significant weight loss and with a reduction in systolic blood pressure without increasing hypoglycemia. Dapagliflozin is approved for the treatment of type 2 diabetes in the European Union. Canagliflozin, which has recently been approved in the US, similarly lowers glucose, blood pressure, and body weight in a dose-related manner. In a study of type 2 diabetic patients treated with metformin plus sulfonylurea, canagliflozin at the highest dose lowered HbA1c to a greater extent than did sitagliptin. Empagliflozin and ipragliflozin have been less well studied, but appear to similarly lower glucose levels in monotherapy and in combination with metformin. It was thought that inhibition of the major intestinal glucose transporter SGLT1 would lead to undesirable gastrointestinal side effects, but interesting preliminary evaluation of LX4211, which inhibits SGLT1 as well as SGLT2, showed that in addition to similar glucoselowering efficacy to that of the SGLT2 inhibitors, LX4211increased levels of both glucagon-like peptide-1 (GLP-1) and peptide YY, suggesting that by increasing the delivery of glucose to the distal small intestine there may be L-cell stimulation. In fact, because of the higher drug concentrations in the gastrointestinal tract, the SGLT2 inhibitors may also act on gastrointestinal SGLT1, with studies of canagliflozin showing that it lowers postprandial glucose in association with a reduction in gastrointestinal glucose absorption, and reduces renal glucose reabsorption. However, there are a number of potential adverse effects to be considered in the use of SGLT2 inhibitors. By increasing glycosuria, they can predispose to both urinary infection and fungal genital tract infection, and concerns have been raised as to potential for the development of bladder and breast cancers with dapagliflozin; such effects did not appear to occur with canagliflozin. Although diuresis is beneficial in the treatment of hypertension, some treated patients may become dehydrated with the agent, which could lead to initial adverse cardiovascular effects, although there is no overall evidence of cardiac safety effects. Given the dependence of the glycosuria on glucose in the glomerular filtrate, there is bs_bs_banner

Effects of Syzygium aromaticum‐derived oleanolic acid on glucose transport and glycogen synthesis in the rat small intestine (丁香衍生物齐墩果酸对大鼠小肠中的葡萄糖转运以及糖原合成的影响)

Abstract: Background: In the present study, we investigated the effects of oleanolic acid (OA), which has hypoglycemic properties, on glucose transport and glycogen synthesis in the small intestine, an organ that secretes enzymes involved in carbohydrate metabolism. Methods: The OA was isolated from Syzygium aromaticum ethyl acetate-soluble fractions followed by recrystallization with ethanol. It was diluted to required concentrations in freshly prepared dimethyl sulfoxide (2 mL) and normal saline (19 mL) before being administered to rats (p.o.). Glycogen concentrations were determined in isolated small intestines from fasted and non-fasted non-diabetic and streptozotocin-diabetic rats after 18 h treatment with 80 mg/kg, p.o., OA or standard hypoglycemic drugs (i.e. 100 μg/kg, s.c., insulin; 500 mg/kg, p.o., metformin). In a separate series of experiments, the effects of 30-min incubation with graded concentrations of OA (0.82–6.56 mmol/L) on d-glucose were evaluated by monitoring changes in glucose concentrations inside and outside of intestinal sacs isolated from fasted, non-diabetic rats and mounted in an organ bath containing Krebs–Henseleit bicarbonate buffer. Results: All in vivo treatments increased the glycogen concentration in rat small intestine, although the effects of metformin treatment in non-fasted diabetic rats failed to reach statistical significance. In vitro, both OA (1.64–6.56 mmol/L) and phlorizin (10−5–10−3 mol/L) decreased glucose transport from the mucosa to the serosa. Conclusion: The data suggest that OA may be a potential alternative drug treatment for postprandial hyperglycemia because of its inhibition of glucose uptake across the small intestine and its concomitant conversion of glucose to glycogen in the intestinal wall. 摘要 背景：在本研究中，我们调查了齐墩果酸（OA，具有降血糖的特性）对小肠（可以分泌多种糖类代谢相关酶的器官）中的葡萄糖转运以及糖原合成的影响。 方法：丁香乙酸乙酯可溶部分使用乙醇重结晶后可分离出OA。用新鲜配制的二甲基亚砜（2 mL）与生理盐水（19 mL）将其稀释到要求的浓度后再给大鼠用药（口服）。使用80 mg⁄kg的OA口服或者标准降糖药物（如皮下注射100 μg/kg的胰岛素；口服500 mg/kg的二甲双胍）治疗18小时后，从禁食与非禁食的非糖尿病大鼠以及链脲霉素诱导的糖尿病大鼠中分离出小肠，测定其中的糖原浓度。在一个独立的系列实验中，从禁食的非糖尿病大鼠中分离出小肠，包埋在含有Krebs–Henseleit碳酸氢盐缓冲液的器官浴槽中，通过监测肠道内与肠道外的葡萄糖浓度变化来评估分级浓度的OA(0.82–6.56 mmol⁄L)培养30分钟后对右旋葡萄糖的影响。 结果：所有的体内治疗都可以增加大鼠小肠中的糖原浓度，不过使用二甲双胍治疗的非禁食糖尿病大鼠的增幅没有达到统计学上的差异。在体外，OA(1.64–6.56 mmol⁄L)与根皮苷(10-5–10-3 mol⁄L)都可以减少葡萄糖从粘膜向浆膜的转运。 结论：研究数据表明，对于餐后高血糖来说OA是一种潜在有效的治疗药物，因为它可以抑制小肠中的葡萄糖摄取，同时将肠壁内的葡萄糖转变成糖原。