替米沙坦对2 型糖尿病合并高血压患者胰岛β 细胞功能影响的临床观察

目的:观察替米沙坦对糖尿病合并高血压患者胰岛β细胞功能的影响,探索血管紧张素Ⅱ阻断剂降压以外的胰岛功能修复作用.方法:70例糖尿病合并轻、中度高血压的患者随机分为替米沙坦治疗组和氨氯地平治疗组,每组35例患者;替米沙坦治疗组在控制血糖的治疗上给予替米沙坦进行降压治疗;氨氯地平治疗组在控制血糖的治疗上给予氨氯地平进行降压治疗;两组的观察周期均12周,每2周观察1次血压、空腹血糖、并记录低血糖及其它不良反应.治疗前后测糖化血红蛋白(HbAlc)、餐后2小时血糖,并按照HOMA稳态模型公式计算胰岛β细胞功能指数(HOMA-β)和胰岛素抵抗指数(HOMA-IR).结果:两组患者在降压效果方面无显著性差异,收缩压、舒张压对比,P＞0.05;与氨氯地平组比较,替米沙坦组胰岛素峰值和HOMA-3显著升高,HOMA-IR则显著降低.结论:替米沙坦可更显著改善糖尿病合并高血压的患者的胰岛β细胞功能,具有降压以外的改善胰岛细胞功能的作用.     

硝苯地平控释片联合替米沙坦对老年高血压患者动态血压及左室舒张功能的影响

目的:研究硝苯地平控释片联合替米沙坦对老年高血压患者动态血压以及左室舒张功能的影响。方法:选择我院2012年12月至2013年11月收治的轻、中度老年高血压合并左室舒张功能不全的患者84例为研究对象,并将其随机分为两组。对照组给予硝苯地平控释片30~60 mg/d,观察组在对照组的基础上,加用替米沙坦40 mg/d,降压未达疗效者,改为80 mg/d,疗程12周。期间观察和比较两组患者的动脉血压波动情况、左心室舒张功能及疗效。结果:对高血压的控制,观察组总有效率显著高于对照组(P0.05),显效率高于对照组,但无统计学意义(P0.05)。动态血压监测及血压负荷结果提示两组治疗后的24 h收缩压平均值(24hm SBP)、24 h舒张压平均值(24hm DBP)、日间收缩压平均值(dm SBP)、日间舒张压平均值(dm DBP)、夜间收缩压平均值(nm SBP)、夜间舒张压平均值(nm DBP)均显著低于治疗前,且观察组显著优于对照组(P0.05)。两组的左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、舒张期左室后壁厚度(LVPWD)、舒张期室间隔厚度(IVST)水平均较治疗前有所改善,但差异无统计学意义(P0.05);观察组各指标水平优于对照组,但差异亦无统计学意义(P0.05)。结论:硝苯地平控释片联合替米沙坦治疗老年高血压有助于更加有效地控制其动态血压波动,且在一定程度上可改善左心室舒张功能。     

替米沙坦及吡哆胺对自发性高血压大鼠脑组织氧化应激的影响

目的:探讨替米沙坦及吡哆胺对自发性高血压大鼠脑组织氧化应激的影响。方法:自发性高血压大鼠24只随机分为4组(n=6):高血压对照组(HC组);替米沙坦组(T组);吡哆胺组(P组);联合治疗组(TP组)。同龄WKY大鼠作为正常对照组(NC组)。药物干预16周,测定各组脑组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性及烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶p47phox mRNA表达。结果:与NC组比较,HC组脑组织中MDA含量明显升高、SOD活性明显减低(P<0.05);与HC组比较T组、P组、TP组MDA含量明显减低,SOD活性明显升高(P<0.05);与NC组比较HC组(NADPH)氧化酶p47phox mRNA表达显著上调(P<0.01);与HC组比较T组、TP组NADPH氧化酶p47phox mRNA表达明显下调(P<0.01);HC组与P组比较NADPH氧化酶p47phox mRNA表达无统计学差异(P>0.05)。结论:自发性高血压大鼠脑组织处于氧化应激状态,替米沙坦及吡哆胺可抑制自发性高血压大鼠脑组织的氧化应激水平,联合治疗并不优于替米沙坦单药治疗。     

替米沙坦对肥胖高血压大鼠认知功能和肠道菌群的影响

目的探讨替米沙坦对于肥胖型高血压大鼠认知功能的影响和肠道菌群变化,探讨其潜在的作用机制。方法高脂饮食诱导肥胖型高血压大鼠（OHR）,并将其分为模型组（MG）、替米沙坦组（TG）;并选择正常大鼠作为对照组（NG）。使用替米沙坦干预TG的同时,MG与NG均给予等量生理盐水。每周检测大鼠的收缩压、舒张压变化;每两周水迷宫实验检测认知功能,持续干预8周。HE染色观察海马体中神经细胞形态变化;ELISA检测其相关血清学指标差异;采用16S rRNA测序检测各组肠道菌群。结果与NG相比较,MG组收缩压、平均压、舒张压、寻找平台时间（逃逸潜伏期）均升高（P＜0.05）;HE染色显示海马体中可见到大量空泡;血清中神经肽（NP-Y）、去甲肾上腺素（NE）、血管紧张素Ⅱ（Ang-Ⅱ）、C反应蛋白（CRP）和基质金属蛋白酶9（MMP-9）水平均升高（P＜0.05）,6−酮−前列环素F1α（6-keto-PGF1α）水平降低（P＜0.001）;肠道菌群中蓝藻门、梭菌纲和Melainabacteria相对丰度升高（P＜0.05）,芽孢杆菌纲相对丰度降低（P＜0.05）。与MG组相比较,TG组收缩压、平均压和舒张压均降低（P＜0.05）逃逸潜伏期缩短（P=0.001）;HE染色显示海马体空泡数量减少（P＜0.001）;血清NP-Y、Ang-Ⅱ、NE、MMP-9和CRP水平均降低（P＜0.001）,6-keto-PGF1α水平升高（P＜0.001）;肠道菌群中放线菌门和放线菌纲相对丰度升高（P＜0.001）,梭菌纲相对丰度降低（P＜0.001）。LEfSe分析发现,MG组优势菌为梭菌纲、梭菌目和瘤胃球菌科,TG组为布劳特菌属。结论替米沙坦可以改善OHR血压水平及认知功能,其机制可能与改善肠道菌群组成相关。     

纳络酮对脑梗塞患者血清降钙素原及叶酸水平及临床疗效的影响

目的:探讨纳络酮对脑梗塞患者血清降钙素原、叶酸水平及临床疗效的影响。方法:收集我院收治的110例急性脑梗死患者,随机分为实验组和对照组,每组55例。两组患者入院后根据实际情况给予抗血小板聚集,保护脑细胞,调控血压,脱水降低颅内压降颅压等对症治疗。对照组患者给予疏血通注射液6 m L+0.9%氯化钠注射液250 m L静脉滴注,1次/d;实验组患者在对照组基础上给予盐酸纳洛酮注射液3.2 g/d,+0.9%氯化钠注射液250 m L静脉滴注,治疗疗程为14 d。观察并比较两组患者治疗前后血清降钙素原(PCT)、同型半胱氨酸(Hcy)、叶酸水平以及临床治疗有效率。结果:与治疗前相比,两组患者治疗后的血清PCT、Hcy水平均显著下降,叶酸水平均明显升高,差异均具有统计学意义(P0.05);与对照组相比,实验组患者的PCT、Hcy水平较低,差异具有统计学意义(P0.05);与对照组相比,实验组患者治疗后的血清叶酸水平、临床治疗有效率均较高,差异具有统计学意义(P0.05)。结论:纳络酮能够显著提高脑梗塞患者的临床疗效,可能与其减轻炎症反应,降血清Hcy水平,升高血清叶酸水平有关。     

老年高血压合并2型糖尿病患者血清同型半胱氨酸、血尿酸水平变化及临床意义

目的：探讨老年高血压合并2型糖尿病患者血清同型半胱氨酸（Homocysteine,Hcy）、血尿酸（Serum uric acid,SUA）水平变化及其临床意义。方法：2012年9月至2013年9月期间,我院诊治的40例单纯高血压和40例高血压合并2型糖尿病患者,分别作为对照组和研究组,检测两组血清Hcy、SUA水平。结果：两组患者收缩压、舒张压比较无统计学差异（P〉0.05）。研究组空腹血糖、餐后2h血糖、血清Hcy、SUA均显著高于对照组（P〈0.05）。研究组中血管并发症患者血清Hcy、SUA为（25.0±5.0）μmol/L和（390.0±65.0）mmol/L显著高于无血管并发症患者（17.0±4.0）μmol/L和（330.0±55.0）mmol/L,血管并发症患者FBG、餐后2h血糖与无血管并发症患者比较无统计学差异（P〉0.05）。结论：高血压合并2型糖尿病患者血清Hcy、SUA异常升高,且存在慢性血管并发症患者两者水平更高,血清Hcy、SUA是老年高血压合并2型糖尿病的危险因素。     

老年高血压合并2 型糖尿病患者血清同型半胱氨酸、血尿酸水平变化及临床意义

目的：探讨老年高血压合并2 型糖尿病患者血清同型半胱氨酸（Homocysteine, Hcy）、血尿酸（Serum uric acid, SUA）水平变化及其临床意义。方法：2012 年9 月至2013 年9 月期间,我院诊治的40 例单纯高血压和40 例高血压合并2 型糖尿病患者,分别作为对照组和研究组,检测两组血清Hcy、SUA水平。结果：两组患者收缩压、舒张压比较无统计学差异（P>0.05）。研究组空腹血糖、餐后2h 血糖、血清Hcy、SUA 均显著高于对照组（P<0.05）。研究组中血管并发症患者血清Hcy、SUA为（25.0± 5.0）umol/L 和（390.0± 65.0）mmol/L显著高于无血管并发症患者（17.0± 4.0）umol/L 和（330.0± 55.0）mmol/L,血管并发症患者FBG、餐后2h 血糖与无血管并发症患者比较无统计学差异（P>0.05）。结论：高血压合并2 型糖尿病患者血清Hcy、SUA异常升高,且存在慢性血管并发症患者两者水平更高,血清Hcy、SUA是老年高血压合并2 型糖尿病的危险因素。     

叶酸联合维生素B12对儿童癫痫患者同型半胱氨酸水平的影响

目的：观察叶酸联合维生素B12对儿童癫痫患者同型半胱氨酸（Hcy）水平的影响。方法：选取我院2017年1月—2020年12月就诊,接受治疗的98例儿童癫痫患者为研究对象。按照随机数字表,将98例患者随机分为干预组和对照组各49例,两组患者性别、年龄、病程、发病频率间均无差异（P>0.05）,具有可比性。对照组患者选择临床一线治疗药物进行抗癫痫治疗,干预组患者在对照组用药基础上,添加0.4 mg叶酸+100 μg维生素B12进行辅助治疗,对患者进行为期3个月的跟踪随访。测定两组患者干预前、干预1个月、干预3个月后血清Hcy、叶酸和维生素B12水平,比较两者患者干预前后血清Hcy、叶酸和维生素B12水平变化,同时记录患者癫痫发作次数和每次发作持续时间,比较两者患者发作次数和持续时间的差异。结果：治疗前,两组患者血清Hcy、叶酸和维生素B12水平比较均无统计学差异。经叶酸联合维生素B12干预1个月、3个月后,干预组患者血清Hcy水平均显著降低（P<0.05）,叶酸及维生素B12水平均显著增高（P<0.05）,而对照组患者血清Hcy水平出现增高现象（P<0.05）,叶酸及维生素B12水平未观察到差异（P>0.05）,干预组与对照组相比,血清Hcy、叶酸和维生素B12水平均有差异（P<0.05）;干预组患者癫痫发作频率显著低于对照组患者,发作持续时间显著短于对照组患者（P<0.001）。结论：叶酸联合维生素B12对儿童癫痫患者进行辅助治疗,可显著降低血清Hcy水平,降低癫痫发作频率,缩短癫痫发作时间,值得在临床推广应用。     

2 型糖尿病患者尿微量白蛋白排泄率与eGFR 的关系及相关危险因素

目的:分析2型糖尿病(T2DM)患者尿微量白蛋白排泄率(UAER)与肾小球滤过率(eGFR)的关系,并探讨相关的危险因素。方法:选取我院收治的2型糖尿病患者470例,根据UAER及eGFR的检查结果进行分组,收集患者的一般资料,研究UAER与e GFR的关系,并分析其相关危险因素。结果:不同UAER体质量、体表面积、BMI,DBP,SBP,高血压病程、TG,TC,血肌酐以及尿酸水平比较,差异有统计学意义(P0.05)。不同e GFR年龄、体质量、糖尿病病程、体表面积、BMI、高血压的病程、HbA1c,HDL-C,血肌酐以及尿酸水平比较,差异有统计学意义(P0.05)。大量清蛋白尿患者肾功能异常发生率最高,正常清蛋白尿患者肾功能异常发生率最低,差异有统计学意义(P0.05)。eGFR≥90 mL·min~(-1)·1.73 m~(-2)患者正常、微量、大量清蛋白尿分别占82.08%、13.68%、4.25%,根据交叉检验分析,UAER与e GFR间有相关性(P0.05)。Logistic回归分析结果显示,与UAER相关危险因素包括血肌酐、收缩压及体质指数,与e GFR相关危险因素包括年龄、体质量、血肌酐(P0.05)。结论:UAER与e GFR间存在相关性,一并进行检测对早期诊断2型糖尿病肾损伤有利。而两者相关危险因素包括血肌酐、收缩压及体质指数。     

西格列汀对2 型糖尿病患者微量白蛋白尿影响的研究

目的:研究西格列汀对2型糖尿病患者微量白蛋白尿的影响,分析其可能机制和临床应用价值。方法:选取160例伴微量白蛋白尿的2型糖尿病患者,随机分为西格列汀组和其他药物组,各80例。比较两组患者治疗前和治疗3个月后血糖水平、尿微量白蛋白、超敏C反应蛋白及血浆还原型谷胱甘肽水平。结果:经3个月治疗,两组患者空腹血糖、餐后2 h血糖、Hb A1c均较治疗前下降,但差异无明显统计学意义(P0.05);西格列汀治疗组患者尿微量白蛋白和血浆Hs-CRP水平明显下降,血浆还原型谷胱甘肽水平明显升高,与其他口服药物治疗组相比差异具有统计学意义(P0.05)。结论:西格列汀可能通过改善机体炎症状态,降低氧化和应激水平等机制降低2型糖尿病患者的尿微量白蛋白水平。     

2型糖尿病患者肾小管功能测定及其相关因素分析

目的：探讨2型糖尿病（DM）患者的肾小管功能改变,分析其相关因素。方法：将64例2型DM患者根据尿微量白蛋白量分为3组：正常蛋白尿组（〈30mg/24h）21例、微量白蛋白尿组（30~300mg/24h）20例和临床蛋白尿组（〉300mg/24h）23例,测定各组尿β2微球蛋白（U-β2MG）和尿渗透压（U-OSM）。探讨年龄、DM病程、24h尿白蛋白量、糖化血红蛋白、血压、血脂水平与肾小管功能损害的关系。结果：2型DM患者均有不同程度的尿β2MG增高及尿渗透压减低,在正常蛋白尿组即有4例尿β2-MG和7例尿OSM存在异常;方差分析显示,随尿白蛋白量的增高,尿β2MG逐步增高,尿渗透压逐步减低,三组间差异有统计学意义（F=26.123和13.889,P均〈0.01）,任两组比较差异均有统计学意义（P均〈0.05）。线性回归显示,尿β2MG及尿OSM改变与DM病程、尿白蛋白（U-ALB）、收缩压（SBP）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、低密度脂蛋白（LDL-C）独立有关。结论：2型DM肾脏损害并非仅累及肾小球,在尿微量白蛋白出现之前即可出现肾小管功能异常。联合检测24h尿白蛋白量、尿β2-MG、尿OSM有助于全面评估2型糖尿病患者的肾脏损害情况。严格控制血糖,尽早纠正代谢紊乱对肾小管功能有保护作用。     

Renal Hyperfiltration and Systemic Blood Pressure in Patients with Uncomplicated Type 1 Diabetes Mellitus

Background

Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m²) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.

Methods

BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4–6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9–11 mmol/L).

Results

Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m², p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H.

Conclusions

DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.     

Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).MethodsElectronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients’ baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.ResultsWe identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P < .001), despite a 45% discontinuation of premeal insulin use (P < .001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P < .001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.ConclusionExenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects. (Endocr Pract. 2008;14:285-292)     

2型糖尿病大鼠模型的肾脏和动脉血管并发症

目的制备发病过程类似人类2型糖尿病的动物模型,并观察其肾脏和主动脉的病变特点。方法8周龄SD大鼠高脂、高糖饮食一个月后给予小剂量STZ腹腔注射建立2型糖尿病模型,于成模后4周及8周观察血管功能指标和肾脏功能指标,并对肾脏和血管的病理改变进行观察。结果模型组于成模后4周及8周出现高血糖、高血脂、胰岛素抵抗、肾功能改变和血管功能改变。肾脏光镜下见肾小球内皮及系膜细胞增生;肾小管水肿,管腔内有大量蛋白管型和细胞管型;肾盂区有大量淋巴细胞浸润。动脉血管电镜下见内皮细胞局部损伤严重;内皮细胞与内弹力板连接处空隙增加等。结论用高脂高糖饮食加小剂量STZ腹腔注射可成功制备2型糖尿病大鼠模型,成模后4周及8周后观察肾脏及大血管相继出现病变,是2型糖尿病血管病变研究的理想模型。     

Onychomycosis Incidence in Type 2 Diabetes Mellitus Patients

The onychomycosis incidence was determined in 250 type 2 diabetes mellitus (T2DM) patients who were registered at the Internal Medicine Service from a Mexico city General Hospital throughout a year (January-December 2006). Out of the total of studied T2DM patients, 93 (37.2%) showed ungual dystrophy and from these, in 75.3% a fungal etiology was corroborated. Out of 70 patients, 34 were men and 36 women, with an average of 63.5 years. Correlation between T2DM evolution time and onychomycosis was significant (P < 0.01). Distal-lateral subungual and total dystrophic onychomycosis were the most frequent clinical types (55.1% and 33.7%, respectively). Fifty-eight fungal isolates were obtained; 48.6% corresponded to dermatophytes, Trichophyton rubrum being the first species (37.1%). All these strains corresponded to two morphological varieties: "yellow" and typical downy. From the yeast-like isolates, 12 corresponded to Candida spp., firstly C. albicans and C. parapsilosis; three to Cryptococcus spp. (C. albidus, C. uniguttulatus and C. laurentii); two Trichosporon asahii; and only one to Pichia ohmeri. Six non-dermatophytic molds were isolated: two Chrysosporium keratinophylus, two Scopulariopsis brevicaulis, one Aspergillus fumigatus, and one Acremonium sp. The fungal mixture corresponded to T. mentagrophytes with C. guilliermondii; T. mentagrophytes with C. glabrata; T. rubrum with C. glabrata; T. rubrum with P. ohmeri.     

Effects of Choline and Magnesium Concurrent Supplementation on Coagulation and Lipid Profile in Patients with Type 2 Diabetes Mellitus: a Pilot Clinical Trial

Biological Trace Element Research - Metabolic failure is associated with dyslipidemia and coagulation which can result in a higher risk of cardiovascular disease (CVD) in type 2 diabetes mellitus...     

Circadian Pattern of Ambulatory Blood Pressure in Hypertensive Patients With and Without Type 2 Diabetes

There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. Accordingly, we evaluated the influence of diabetes on the circadian BP pattern by 48-h ABPM (rather than for 24?h to increase reproducibility of results) during which participants maintained a diary listing times of going to bed at night and awakening in the morning. This cross-sectional study involved 12 765 hypertensive patients (6797 men/5968 women), 58.1?±?14.1 (mean?±?SD) yrs of age, enrolled in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of northwest Spain. Among the participants, 2954 (1799 men/1155 women) had type 2 diabetes. At the time of study, 525/3314 patients with/without diabetes were untreated for hypertension, and the remaining 2429/6497 patients with/without diabetes were treated. Hypertension was defined as awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85?mm Hg, or asleep SBP/DBP mean ≥120/70?mm Hg, or BP-lowering treatment. Hypertensive patients with than without diabetes were more likely to be men and of older age, have diagnoses of microalbuminuria, proteinuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, and/or obesity, plus higher glucose, creatinine, uric acid, and triglycerides, but lower cholesterol and estimated glomerular filtration rate. In patients with diabetes, ambulatory SBP was significantly elevated (p?<?.001), mainly during the hours of nighttime sleep and initial hours after morning awakening, independent of presence/absence of BP-lowering treatment. Ambulatory DBP, however, was significantly higher (p?<?.001) in patients without diabetes, mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p?<?.001) throughout the entire 24?h in patients with diabetes, even after correcting for age. Prevalence of non-dipping was significantly higher in patients with than without diabetes (62.1% vs. 45.9%; p?<?.001). Largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 8.1% in patients with and without diabetes, respectively; p?<?.001). Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with diabetes; thus, among the uncontrolled hypertensive patients with diabetes, 89.2% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with diabetes. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment. (Author correspondence: rhermida@uvigo.es)     

Self-Care Associated with Home Exercises in Patients with Type 2 Diabetes Mellitus

The objective of this study was to verify self-care guidelines together with lower limb home exercises alter ankle and foot plantar pressure and alignment in patient with Type 2 Diabetes Mellitus (DM) measuring health and sociodemographic factors. The health factors analyzed were sensitivity and circulation aspects, risk rating, and neuropathy symptom score, ankle and foot alignment (photogrammetry), plantar pressures, and postural stability (baropodometry) before and after administering these guidelines and home exercises in 97 patients type 2 DM during 10 months. The self-care guidelines and exercises changed the forefoot alignment (Right Foot – Initial vs Final, p = 0.04; Left Foot, P<0.01), the center of the force displacement in the mediolateral (Right Foot - Initial versus Final, p = 0.02; Left Foot, P<0.01), and the anterior-posterior (Right foot - Initial versus Final, p = 0.01) direction, and body balance (Initial versus Final, p = 0.02). There was no change in the remaining assessed parameters. Self-care associated with the guidelines for home exercises for the lower limbs in patients with type 2 DM are effective in maintaining and improving the alignment of the feet, mediolateral stability and prevention of complications.

Trial Registration

The Brazilian Clinical Trials Registry RBR-8854CD     

Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus

Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin has complex effects due to gut-based pharmacology which might provide insights into novel therapeutic approaches to treat T2DM and associated metabolic diseases.

Trial Registration:

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01357876","term_id":"NCT01357876"}}NCT01357876     

Nicotinamide Effects Oxidative Burst Activity of Neutrophils in Patients with Poorly Controlled Type 2 Diabetes Mellitus

Neutrophil functions are impaired in patients with diabetes mellitus. Bacterial phagocytosis and oxidative burst activity are reduced at high glucose concentrations in diabetic patients. Defects in neutrophil oxidative burst capacity are of multifactorial origin in diabetes mellitus and correlate with glucose levels. It has been reported that neutrophil NADPH oxidase activity is impaired and superoxide production is reduced in diabetic patients with or without any infections. Nicotinamide is a vitamin B3 derivative and a NAD precursor with immunomodulatory effects. In vitro studies demonstrated that nicotinamide increases NAD and NADH content of beta cells. The authors hypothesized that nicotinamide may restore the impaired oxidative burst capacity of neutrophils in diabetic patients by increasing the NADH content as an electron donor and possibly through NADPH oxidase activity of the cell. In order to test the hypothesis, this placebo-controlled and open study was designed to evaluate neutrophil functions in infection-free poorly controlled type 2 diabetic patients as compared to healthy subjects and assess the effects of nicotinamide on neutrophil phagocytosis as well as oxidative burst activity. Thirty patients with type 2 diabetes mellitus were enrolled in the study. Sixteen were females and 14 were males, with a mean age 58 ± 10. All patients were on sulphonylurea treatment and their hemoglobin A_1c (HbA_1c) levels were above 7.5%. The control group consisted of 10 voluntary healthy subjects. Diabetic and control subjects were not significantly different in terms of age, body mass index (BMI), leucocyte and neutrophil counts, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR), but HbA_1c and fasting glucose levels were significantly higher in patients with diabetes mellitus. Phagocytic activity and respiratory burst indexes were measured by flow cytometric analyses as previously described by Rothe and Valet (Methods Enzyml., 233, 539–548, 1994) and compared in diabetic subjects and healthy controls. Diabetic patients were grouped to receive either 50 mg/kg oral nicotinamide (n = 15) or placebo (n = 15) for a period of 1 month. The 2 groups did not differ in terms of treatment, frequency of hypertension, BMI, diabetes duration, age, fasting plasma glucose (FPG), HbA_1c, CRP, ESR, polymorphonuclear leukocyte (PNL) and neutrophil counts. Neutrophil functions were reassessed after the treatment period. Phagocytic activity represented as indexes were lower in diabetic patients when compared to healthy subjects, but the differences were not statistically significant (P > .05). Patients with diabetes mellitus had significantly lower oxidative burst indexes when compared to healthy controls (P values < .05). In diabetic patients, a negative correlation between neutrophil functions and HbA_1c was found which was not statistically significant (P values > .05). Phagocytic indexes were similar in nicotinamide and placebo groups after treatment period (P > .05). But oxidative burst activity in patients receiving nicotinamide was greater when compared with placebo and the difference was statistically significant at 30 and 45 minutes (P values .04 and .03). This effect of nicotinamide may be due to increased NADH content and NADPH oxidase activity of the cell, which needs to be further studied. Impaired neutrophil functions may aggravate various infections in patients with diabetes mellitus and blood glucose regulation is an important target of treatment to improve neutrophil functions. But nicotinamide treatment may help to improve prognosis in diabetic patients with severe infections.