强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效观察

目的观察强化控糖后加用盐酸吡格列酮治疗2型糖尿病的临床疗效。方法 60例使用口服降糖药物治疗的血糖控制不佳的2型糖尿病患者,入院后先进行胰岛素泵强化控糖治疗,患者血糖达到目标值后（FPG〈7.0 mmol/L,2 h PG〈10.0 mmol/L）,改为三餐前门冬胰岛素联合睡前甘精胰岛素继续强化治疗,1周后按1：1的比例随机分为两组,一组继续使用三餐前门冬胰岛素联合睡前甘精胰岛素治疗（对照组）,一组在三餐前门冬胰岛素联合睡前甘精胰岛素的基础上加用盐酸吡格列酮30 mg/日（治疗组）。1～4周我院住院治疗,5～12周门诊随访,若出现FPG及2 h PG明显下降或低血糖反应,则减少胰岛素用量。观察加用盐酸吡格列酮治疗前以及治疗12周时FPG、2 h PG、HbAlc、胰岛素用量、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、体重指数的变化情况。结果 （1）治疗组胰岛素用量明显下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）;对照组的胰岛素用量治疗前后无明显差异（P〉0.05）;（2）治疗组与对照组加用盐酸吡格列酮治疗前后FPG、2hPG均无明显差异（P〉0.05）。（3）治疗组HbAlc有所下降,与加用盐酸吡格列酮治疗前有明显差异（P〈0.05）,对照组HbAlc也有所下降,差异明显（P〈0.05）,但治疗后两组比较无明显差异（P〉0.05）。（4）加用盐酸吡格列酮后,治疗组TG下降,HDL-C升高,与同组治疗前相比,差异明显（P〈0.05）,对照组与治疗前相比差异不明显,组间比较差异有显著性（P〈0.05）。结论在强化控糖血糖达标后,加用盐酸吡格列酮继续治疗,可以明显降低患者胰岛素的使用剂量,提高患者的依从性,并且能改善血脂代谢紊乱,对于减少心血管并发症的发生有一定益处。     

Sleep quality and sleep duration,but not circadian parameters are associated with decreased insulin sensitivity in Type 1 diabetes

ABSTRACT

The objective of this cross-sectional analysis was to investigate in 109 adults with type 1 diabetes the relationship between sleep, circadian parameters and insulin sensitivity, as assessed by estimated glucose disposal rate (eGDR). In multiple regression analysis only poor sleep quality and sleep duration were negatively associated with eGDR (β = ?0.219 [95%CI:-1.977; ?0.445], p = .002 for poor sleep quality; β = ?0.183 [95%CI: ?0.645; ?0.111], p = .006 for sleep duration) independent of age, gender, smoking status and body mass index. In conclusion, poor sleep quality and longer sleep duration were significant predictors of decreased insulin sensitivity. Social jetlag, chronotype, and sleep debt had no effect on insulin sensitivity.     

The Relationship Between Breakfast Skipping,Chronotype, and Glycemic Control in Type 2 Diabetes

Breakfast skipping is associated with obesity and an increased risk of type 2 diabetes. Later chronotypes, individuals who have a preference for later bed and wake times, often skip breakfast. The aim of the study was to explore the relationships among breakfast skipping, chronotype, and glycemic control in type 2 diabetes patients. We collected sleep timing and 24-h dietary recall from 194 non-shift-working type 2 diabetes patients who were being followed in outpatient clinics. Mid-sleep time on free days (MSF) was used as an indicator of chronotype. Hemoglobin A1C (HbA_1C) values were obtained from medical records. Hierarchical linear regression analyses controlling for demographic, sleep, and dietary variables were computed to determine whether breakfast skipping was associated with HbA_1C. Additional regression analyses were performed to test if this association was mediated by chronotype. There were 22 participants (11.3%) who self-reported missing breakfast. Breakfast skippers had significantly higher HbA_1C levels, higher body mass indices (BMI), and later MSF than breakfast eaters. Breakfast skipping was significantly associated with higher HbA_1C values (B?=?0.108, p?=?0.01), even after adjusting for age, sex, race, BMI, number of diabetes complications, insulin use, depressive symptoms, perceived sleep debt, and percentage of daily caloric intake at dinner. The relationship between breakfast skipping and HbA_1C was partially mediated by chronotype. In summary, breakfast skipping is associated with a later chronotype. Later chronotype and breakfast skipping both contribute to poorer glycemic control, as indicated by higher HbA_1C levels. Future studies are needed to confirm these findings and determine whether behavioral interventions targeting breakfast eating or sleep timing may improve glycemic control in patients with type 2 diabetes.     

Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus

Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n = 48) with Type 2 DM we investigated the effects of supplementation with zinc (40 mg/d) and flaxseed oil (FSO; 2 g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P = 0.001) and HOMA-IR (P = 0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P = 0.003) and HOMA-IR (P = 0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P = 0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.     

Increased serum HSP70 levels are associated with the duration of diabetes

The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n = 36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n = 36) and patients with diabetes duration of more than 5 years (n = 37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p < 0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p < 0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r = −0.500, p = 0.002), positively correlated with the history of hypertension in newly diagnosed patients (p < 0.001), and positively correlated with age in patients with diabetes (r = 0.531, p = 0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.     

Outdoor artificial light at night,obesity, and sleep health: Cross-sectional analysis in the KoGES study

Obesity is a common disorder with many complications. Although chronodisruption plays a role in obesity, few epidemiological studies have investigated the association between artificial light at night (ALAN) and obesity. Since sleep health is related to both obesity and ALAN, we investigated the association between outdoor ALAN and obesity after adjusting for sleep health. We also investigated the association between outdoor ALAN and sleep health. This cross-sectional survey included 8526 adults, 39–70 years of age, who participated in the Korean Genome and Epidemiology Study. Outdoor ALAN data were obtained from satellite images provided by the US Defense Meteorological Satellite Program. We obtained individual data regarding outdoor ALAN; body mass index; depression; and sleep health including sleep duration, mid-sleep time, and insomnia; and other demographic data including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking status and consumption of caffeine or alcohol before sleep. A logistic regression model was used to investigate the association between outdoor ALAN and obesity. The prevalence of obesity differed significantly according to sex (women 47% versus men 39%, p < 0.001) and outdoor ALAN (high 55% versus low 40%, p < 0.001). Univariate logistic regression analysis revealed a significant association between high outdoor ALAN and obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.14–1.35, p < 0.001). Furthermore, multivariate logistic regression analyses showed that high outdoor ALAN was significantly associated with obesity after adjusting for age and sex (OR 1.25, 95% CI 1.14–1.37, p < 0.001) and even after controlling for various other confounding factors including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking, consumption of caffeine or alcohol before sleep, delayed sleep pattern, short sleep duration and habitual snoring (OR 1.20, 95% CI 1.06–1.36, p = 0.003). The findings of our study provide epidemiological evidence that outdoor ALAN is significantly related to obesity.     

Relationships between chronotype,social jetlag,sleep, obesity and blood pressure in healthy young adults

Sleep disturbances, chronotype and social jetlag (SJL) have been associated with increased risks for major chronic diseases that take decades to develop, such as obesity, metabolic syndrome and cardiovascular disease. Potential relationships between poor sleep, chronotype and SJL as they relate to metabolic risk factors for chronic disease have not been extensively investigated. This prospective study examined chronotype, SJL and poor sleep in relation to both obesity and elevated blood pressure among healthy young adults.

SJL and objective sleep measures (total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency) were derived from personal rest/activity monitoring (armband actigraphy) among 390 healthy adults 21–35 years old. Participants wore the device for 6–10 days at 6-month intervals over a 2-year period (n = 1431 repeated observations). Chronotypes were categorized into morning, intermediate and evening groups using repeated measures latent class analysis. Means of SJL and sleep measures among latent chronotype groups were compared using partial F-tests in generalized linear mixed models. Generalized linear mixed models also were used to generate odds ratios (ORs) with 95% confidence intervals (CIs) examining the relationship between repeated measures of chronotype, SJL, sleep and concurrent anthropometric outcome measures (body mass index, percentage of body fat, waist-to-hip ratio, waist-to-height ratio), systolic blood pressure and diastolic blood pressure.

Sleep latency ≥12 min was associated with increased odds of a high waist-to-height ratio (OR = 1.37; CI: 1.03–1.84). Neither chronotype nor SJL was independently associated with anthropometric outcomes or with blood pressure. Relationships between poor sleep and anthropometric outcomes or blood pressure varied by chronotype. Morning types with total sleep time <6 h, sleep efficiency <85% or wake after sleep onset ≥60 min were more likely to have an increased percentage of body fat, waist-to-hip ratio and waist-to-height ratio relative to those with an intermediate chronotype. Similarly, sleep latency ≥12 min was associated with increased odds of elevated systolic blood pressure (OR = 1.90; CI: 1.15–3.16, p_interaction = 0.02) among morning versus intermediate chronotypes. No relationships between poor sleep and obesity or elevated blood pressure were observed among evening chronotypes.

The results from this study among healthy young adults suggest that poor sleep among morning types may be more strongly associated with obesity and elevated blood pressure relative to those with an intermediate (neutral) chronotype. Sleep-related metabolic alterations among different chronotypes warrant further investigation.     

MicroRNAs and type 2 diabetes/obesity

MicroRNAs belong to a newly identified class of small non-coding RNAs that have been widely implicated in the fine-tuning of many physiological processes such as the pathogenesis of type 2 diabetes(T2D) and obesity.Microarray studies have highlighted an altered profile of miRNA expression in insulin target tissues in diabetic and obese models.Emerging evidences suggest that miRNAs play significant roles in insulin production,secretion and actions,as well as in diverse aspects of glucose homeostasis and adipocyte differentiation. The identification of tissue-specific miRNAs implicated in T2D and obesity might be useful for the future development of effective strategies for early diagnosis and therapeutic intervention of obesity-related medical complications.     

微量白蛋白尿与2型糖尿病合并代谢综合征的相关性

目的:探讨2型糖尿病(T2DM)患者微量白蛋白尿与代谢综合征(MS)的相关性。方法:282例T2DM患者根据是否合并MS分为MS组(163例)和非MS组(119例),测定24h尿白蛋白(UAlb)及相关生化指标,比较两组UAlb水平及糖尿病肾病(DN)患病率,采用多元Logistic回归方法分析T2DM患者微量白蛋白尿的危险因素。结果:MS组的UAlb及DN患病率明显高于非MS组,且随着MS组分增加,UAlb水平显著升高。多元Logistic回归分析表明甘油三酯、糖化血红蛋白、收缩压为影响UAlb的独立危险因素。结论:T2DM患者微量白蛋白尿与MS密切相关,需采取综合干预措施避免或延缓DN的发生发展。     

Novel protein tyrosine phosphatase 1B inhibitors: interaction requirements for improved intracellular efficacy in type 2 diabetes mellitus and obesity control

Resistance to the hormones insulin and leptin are hallmarks in common for type 2 diabetes mellitus and obesity. Both conditions are associated with increased activity and expression of protein tyrosine phosphatase (PTP)1B. Therefore, inhibition of PTP1B activity or down-regulation of its expression should ameliorate insulin and leptin resistance, and may hold therapeutic utility in type 2 diabetes mellitus and obesity control. This background has motivated the fervent search for PTP1B inhibitors, carried out in the recent years. The purpose of this review is to provide the most recent advances in understanding the structural details of PTP1B molecule relevant to the interactions with inhibitors, and the progress towards compounds with enhanced membrane permeability, affinity, specificity, and potency on intracellular PTP1B; several inhibitors of benefit in type 2 diabetes mellitus and obesity control are presented and discussed.     

绝经后2型糖尿病患者慢性并发症与骨质疏松症关系临床研究

目的:探讨绝经后T2DM患者慢性并发症与骨密度(BMD)、骨质疏松症(OP)患病率情况的关系.方法:回顾性分析168例绝经后T2DM患者,收集年龄、体重、身高、腰围、臀围、病程及绝经年限等临床资料,应用双能X线骨密度仪测定间腰椎及髋部等各部位BMD值.将全体受试者按照糖尿慢性并发症分组,进一步按照各年龄组平均DM病程分组.结果:①除DN组Ward's区、DR组T-hip部位BMD值显著低于NC组(P＜0.05)外,各组间腰椎及髋部等各部位的BMD值、OP患病率均无显著性差异(P＞0.05).不同病程的患者进行比较,年龄、绝经年限、BMI、HbAlc、各部位BMD值和OP患病率均无统计学差异(P＞0.05).②多元逐步回归分析提示,绝经后T2DM患者BMD值的主要影响因素为年龄、BMI、HbAlc以及绝经年限(P＜0.05),而糖尿病病程、并发症类型均非BMD的独立影响因素.结论:未发现绝经后T2DM患者BMD及OP患病率与糖尿病慢性并发症(DN、DR、DPN)有相关关系.     

Chronotype,bed timing and total sleep time in seniors

Many older adults (seniors) experience problems with getting enough sleep. Because of the link between sleep and circadian rhythms, changes in bedtime lead to changes in the amount of sleep obtained. Although primarily determined genetically, chronotype changes with advancing age towards a more morning-type (M-type) orientation. In a 2006 study, we have found a linear relationship, by which the earlier a senior’s bedtime, the more sleep she/he will obtain. The aim of this study was to see whether this relationship differs for M-type seniors, as compared to seniors outside the M-type category. Retired seniors (n?=?954, 535?M, 410F, 65?years+, mean age 74.4?years) taking part in a telephone interview were divided into M-types and Other types (O-types) using the Composite Scale of Morningness (CSM). The relationship between bedtime and Total Sleep Time (TST), and between rise-time and TST, was tested using linear regression separately for M-types and O-types. For each participant, habitual bedtime, rise-time and total Sleep Time (TST) [after removing time spent in unwanted wakefulness] were obtained using a telephone version of the Sleep Timing Questionnaire (STQ). Both chronotype groups showed a significant linear relationship between bedtime and TST (p?<?0.001); with earlier bedtimes leading to more TST (M-type 5.6?min; O-type 4.4?min per 10?min change [slope difference p?=?0.05]); and an opposite relationship between rise-time and TST with earlier rise-times leading to less TST (M-type 6.7?min; O-type 4.2?min per 10?min change [slope difference p?=?0.001]). M-types retired to bed 56?min earlier (p?<?0.001), awoke 93?min earlier (p?<?0.001) and obtained 23?min less TST (p?<?0.001) than O-types. In conclusion, both chronotypes showed TST to be related in a linear way to bedtime and rise-time; the overall shorter TST in M-types was due to them rising 93?min earlier, but only retiring to bed 56?min earlier than O-types; as well as having a steeper rise-time versus TST relationship.     

Insulin Treatment Is Associated with Increased Mortality in Patients with COVID-19 and Type 2 Diabetes

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Serum sialic acid levels and selected mineral status in patients with type 2 diabetes mellitus

The aim of the present study was to investigate whether altered serum total sialic acid (TSA), lipid-associated sialic acid (LSA), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), iron (Fe), and magnesium (Mg) levels had an interactive connection with diabetes and also whether they were correlated with each other in diabetic patients. Two study groups (control and type 2 diabetic subjects) were included. Two hundred patients (108 female and 92 male), diagnosed and treated for type 2 diabetes in the Yuzuncu Yil University Hospital (Van, Turkey), were selected consecutively to represent type 2 diabetic patients. Fifty healthy individuals (29 female and 21 male) served as the control group matched for age, sex, body mass index, and smoking status were selected from hospital staff and other outpatient clinics. All participants had not taken vitamin or mineral supplements for at least 2 wk before sampling. Blood samples were drawn after an overnight fasting in both groups for the determination of serum glucose, TSA, LSA, Cu, Zn, Mn, Cr, Fe, and Mg. It was found that diabetics had higher TSA, LSA, Fe, Mn, Fe/Zn, and Cu/Zn levels, and lower Zn and Mg levels than those of controls. Although, Cu levels were higher, and Cr levels were lower in total and male diabetic patients, they were not different in female diabetic patients than in controls. The Cu/Fe ratio was lower in total and female diabetic patients, but not different in male diabetic patients than controls. The Zn/Cr ratio, on the other hand, was not different in diabetics than in controls. There was only a positive correlation between Fe-Mn levels in male diabetic patients. There was a negative correlation in LSA-Mn, Fe-Cu, Cu-Fe/Zn, and Mn-Cu/Zn levels in total diabetic patients. There was a positive correlation in TSA-Cr, TSA-Mg, LSA-Cu/Fe, LSA-Zn/Cr levels, and a negative correlation in TSA-Cu/Zn, LSA-Mn, Fe-Cu, Mn-Cu, Cu-Fe/Zn, Fe-cholesterol, and Cr-cholesterol in female diabetic patients. Our results showed that TSA, LSA, and selected minerals have interactive connections with diabetes mellitus (DM). There are also many sex-related positive or negative correlations between the altered parameters in diabetic patients. These parameters might be used as diagnostic index in patients with DM.     

高脂高糖饮食结合链脲佐菌素建立2型糖尿病大鼠模型的改良

目的对目前常用的高脂高糖饮食结合链脲佐菌素建（STZ）建立2型糖尿病大鼠模型的方法进行改良。方法选择40只雄性SD幼鼠,对传统方法进行改良。改良的方法包括：1.采用幼鼠（4周龄）造模;2.用实验方法确定STZ致糖尿病的亚致病剂量;3.大鼠生化指标检测根据用血量不同采取尾静脉、尾动脉和摘除眼球取血等多种取血方式。结果实验组大鼠血糖明显升高（13.7±1.57 mmol/L）。大鼠肝脏、胰腺、脑组织和肾脏等多个器官出现了病变,实验大鼠生存时间较长（9个月以上）。结论本研究完善了2型糖尿病的建模方法。     

女性2型糖尿病患者尿路感染病原菌的分布及耐药性监测

目的探讨女性2型糖尿病患者尿路感染病原菌的种类及耐药性,为临床合理用药提供科学依据。方法对2009年1月至2011年1月在绍兴市人民医院住院的女性2型糖尿病患者尿路感染病原菌的分布及耐药性进行回顾性分析。结果分离的112株病原菌,以大肠埃希菌为主,占58.9%,其次为肺炎克雷伯菌和真菌,分别为10.7%和8.9%;其中产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌株检出率为40.9%,产ESBLs的肺炎克雷伯菌株检出率为8.3%;大肠埃希菌对碳青霉烯类、头霉素类、丁胺卡那和呋喃妥因的耐药率较低,而肺炎克雷伯菌对多种抗菌药物具有较好的敏感性。结论女性2型糖尿病患者易患尿路感染,病原菌以大肠埃希菌为主,且对多种抗菌药物的耐药率较高,临床应根据药敏结果合理选用抗菌药物。     

2型糖尿病鼠类模型的研究进展

小鼠、大鼠糖尿病模型对基础与临床防治研究十分重要,不同的研究目标对应不同的动物模型载体。本文就目前常用的2型糖尿病鼠类模型的构建、主要疾病特征及应用等进行评述,为研究者了解、选择适合的动物模型提供参考。