Epidemiological evidence regarding the association between vitamins and diabetic complications remains inconsistent. This study aims to explore the potential causal relationships between diabetic complications and circulating vitamins in diabetics. We selected vitamin A (VitA) genetic variants (n = 5,006), vitamin B6 (VitB6) genetic variants (n = 64,974), vitamin C (VitC) genetic variants (n = 52,018) and vitamin D (VitD) genetic variants (n = 441,291) as exposures of interest from large-scale Genome-Wide Association Studies (GWAS) databases. Then we performed two-sample Mendelian randomization (MR) analyses to evaluate the causal association of plasma vitamin levels with diabetic complications, which included maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy and retinopathy. Multiple methods were performed and used including the inverse-variance weighted (IVW), the weighted median, MR-Egger and MR-PRESSO regression. Heterogeneity and sensitivity analyses were conducted. The results of the IVW method revealed that the level of VitB6 were associated with diabetic hypoglycemia with (OR: 8.54; 95% CI: 1.77 to 41.2; p: 0.01). No association was detected between other vitamins (VitA, VitC or VitD) and diabetic complications (maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy or retinopathy). After MR-PRESSO analysis, there was no causal relationship detected between VitD and diabetic hypoglycemia (OR: 0.867, CI: 0.64 to 1.18, p: 0.37), diabetic ketosis (OR: 0.763515, CI: 0.58 to 1.00, p: 0.055), diabetic maculopathy (OR: 0.72, CI: 0.48 to 1.07, p: 0.105). This analysis provided genetic evidence that the level of VitB6 may be the risk factor for diabetic hypoglycemia. VitA, VitC, or VitD were not associated with various diabetic complications. Monitoring for excess VitB6 and suitable supplements might be important, and other vitamins may have limited effects in complications prevention, and further investigations were needed to unveil the mechanisms.

Rationale: Prader-Willi syndrome (PWS) is a genetic disorder affecting multiple systems. Approximately one-quarter of PWS patients will develop diabetes. Given the uncontrolled hyperphagia and resultant severe obesity in these patients, their glycemic management poses a significant challenge. Case report: We present the clinical profile of a male patient diagnosed with both PWS and diabetes. Previous administration of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Canagliflozin resulted in improved glycemic control and weight management. But at the age of 25, the patient was hospitalized due to worsened glycemic control and the detection of ketonuria. After thorough examination and clinical observation, we discovered that the patient ketonuria was associated with enhanced lipid metabolism related to Canagliflozin. After excluding the risk of SGLT-2 inhibitor-induced euglycemic diabetic ketoacidosis, adjustments of the hypoglycemic regimen, building upon prior treatment, were recommended for the patient. Conclusion: It is important to note that among patients with both PWS and diabetes, the utilization of SGLT-2 inhibitors can lead to the emergence of ketonuria due to increased lipolysis. Therefore, any decision to discontinue SGLT-2 inhibitors should undergo thorough evaluation.

Background The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing. Methods After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels. Results The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database. Conclusion These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.

目的 观察腹部八法治疗餐后不适综合征(postprandial distress syndrome,PDS)伴焦虑状态的临床疗效.方法 将88例PDS伴焦虑状态的患者随机分为对照组和治疗组,各44例.治疗组采用腹部八法治疗,对照组采用口服枸橼酸莫沙比利治疗,共治疗4周.治疗前后以及4周、8周随访时分别对2组进行餐后不适综合征症状积分、HAMA焦虑量表评分,记录2组治疗过程中的不良反应.结果 治疗后,治疗组总有效率97.7％,高于对照组的86.4％,差异有统计学意义(P＜0.05).与治疗前比较,治疗4周后及4、8周随访时,2组餐后腹胀不适、早饱、胃纳减少、嗳气、上腹灼热症状积分及总分均降低(P＜0.05);2组8周随访时上腹灼热评分比较,差异无统计学意义(P＞0.05),其他各项评分治疗组均低于对照组(P＜0.05).治疗4周及4、8周随访,2组HAMA评分均较治疗前降低(P＜0.05),且治疗组HAMA评分均低于对照组(P＜0.05).治疗过程中及8周随访时,2组均未出现不良反应.治疗组无明显复发,对照组有4例患者在治疗结束后4～8周出现复发.结论 腹部八法能够明显缓解PDS患者的临床症状和焦虑状态,安全且无复发.

目的:应用Meta分析针刺联合中药内服治疗糖尿病视网膜病变(diabetic retinopathy,DR)的临床疗效.方法:检索PubMed、Embase、Web of Science、Cochrane Library、中国知网(CNKI)期刊数据库、万方数据库及中国生物医学文献数据库(SinoMed)中针刺联合疗法治疗DR的文献,运用Stata进行Meta分析.结果:共纳入10篇文献,Meta分析结果显示,与其他治疗疗法相比,针刺联合中药内服显著提高了总有效率(RR=1.21,95％CI为1.13～1.30)、视力水平(WMD=0.18,95％CI为0.11～0.25)、黄斑厚度(WMD=-32.25,95％CI为-48.94～-15.56)和视敏度(WMD=2.92,95％CI为2.57～3.27),与对照组相比差异均有统计学意义(P<0.01).结论:针刺联合中药内服用于治疗DR可以显著提高患者视力水平和视敏度,降低黄斑厚度,减缓疾病发展,改善患者症状.

中和医派治疗糖尿病及其并发症,中和思想贯穿始终,理论上提出"脾藏精",治疗上重视益气养阴,活血化瘀,中药常联合中成药 、针灸 、降糖药,以提高疗效,高效控糖,减缓或避免并发症.强调日常养护,从根本上控糖.

目的 观察孙氏降糖饮治疗气阴两虚型2型糖尿病的临床疗效.方法 将入选的90例气阴两虚型2型糖尿病患者随机分为2组,各45例,均给予基础治疗,对照组予二甲双胍治疗,治疗组加用孙氏降糖饮中药治疗.比较治疗12周后患者空腹(FPG)及餐后2h血糖(2 hPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素敏感指数(ISI)、体质指数(BMI)、中医证候积分及血常规、肝肾功的变化情况.结果 治疗12周后,治疗组与对照组FPG、2hPG、HbA1c、FINS均有明显下降,治疗组较对照组下降显著,差异有统计学意义(均P＜0.05);ISI均较治疗前明显升高,治疗组较对照组升高显著,差异有统计学意义(P＜0.05);BMI均较治疗前降低,但2组差异无统计学意义(P＞0.05).治疗组中医证候疗效显著优于对照组,差异有统计学意义(P＜0.05);2组血常规、肝肾功均无明显变化.结论 孙氏降糖饮配合二甲双胍治疗2型糖尿病,能够显著降低患者的血糖指标,减轻胰岛素抵抗,缓解临床不适症状,安全有效.

Objective To evaluate the clinical effect of Xueluokang decoction lavipeditum on diabetic peripheral neuropathy(DPN) of cold-stagnation and blood-stasis type.Methods From January 2017 to January 2018,70 DPN patients in Beijing Hepingli Hospital were randomly divided into observation group and control group,with 35 cases in each group.Both groups were treated by rational diet,exercise guidance,hypoglycemic drugs and mecobalamin tablets.The control group was given lavipeditum with warm water and the observation group had lavipeditum with Xueluokang decoction once daily for 4 weeks.Total curative effect,score of Toronto Clinical Scoring System(TCSS),vibration perception threshold(VPT) were assessed and adverse reactions were observed.Results Total effective rate in observation group was significantly higher than that in control group[85.7％ (30/35) vs 60.0％ (21/35)] (P ＜ 0.05).After treatment,TCSS score and VPT of bilateral lower limbs were lower than those before treatment and they were lower in observation group than those in control group [(3.2 ± 0.8) vs (6.2 ± 0.6),left VPT:(14.1 ±1.9)V vs (18.2±2.1)V,right VPT:(13.5 ±1.5)V vs (18.0 ± 1.6)V] (all P＜ 0.05).There was no significant difference of the incidence of adverse reactions between groups (P ＞ 0.05).Conclusion Xueluokang decoction lavipeditum can alleviate clinical symptoms,improve TCSS score and VPT in DPN oatients.

笔者结合《黄帝内经》与临床实践,提出"脾藏精"的假说,从以下几个方面探讨糖尿病糖代谢:血糖源于饮食由脾所主;血糖属土为脾所主;血糖为脾所藏之精气,正常范围内的血糖称为"脾藏精气而不泻也,满而不实";尿糖是脾藏精功能失常的体现;多余的血糖在脾主藏精的作用下转为肌、肝糖原,"脾不藏精",脾失主糖,则糖原分解增多,糖异生作用增强,血糖升高;治疗要重视益气固摄与健脾收涩以恢复脾藏精的功能.本假说对从脾论治糖尿病提供一个角度的理论支持,尤其是健脾益气固摄与健脾收涩的药物应用.

现代医学中的“血糖”,在中医学中应当属于“水谷精微”的范畴.贺仲晨主任认为初发糖尿病血糖异常及胰岛素抵抗与“脾主运化”、“脾藏精”、“脾主内”等功能失调有关,并提出脾主糖的理论.在调理脾胃的治疗方法上,可从养脾阴、益脾气、化脾湿等方面入手.根据辨证,或与清胃同施,或与益肾相兼,终这脾运得健,水谷精微的转输与利用恢复正常,血糖降低、糖尿病并发症等得以好转为目的.

To evaluate the effect of serum containing Jinmaitong Capsule (c < e"parts per thousand eEuroee integral a > S, JMT) on apoptosis of Schwann cells (SCs) that are cultured in high glucose at the cellular and molecular levels.SCs were cultured in Dulbecco's modified Eagle's medium (control group), high glucose (50 mmol/L) medium supplemented with 20% rat serum (HG group), and 50 mmol/L glucose medium supplemented with serum containing JMT (JMT group). SC apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling kit. The expression of Bcl-2 and the caspase-3 p20 subunit in SCs were detected by realtime fluorogenic quantitative polymerase chain reaction and confocal laser scanning microscopy, respectively.No apoptosis was detected in SCs that were cultured in the control group. The percentage of apoptosis of SCs cultured in the HG group was much higher than that in the control group. The apoptosis of SCs in the JMT group was lower than that in the HG group. Fluorescence intensity of Bcl-2 and the expression of Bcl-2 mRNA in SCs that were cultured in the HG group were much lower than those in the control group and much higher than those in the JMT group (P < 0.01). The fluorescence intensity of caspase-3 p20 and the expression of caspase-3 p20 mRNA in SCs that were cultured in the HG group were much higher than those in the control group (P < 0.01), and they were remarkably lower in the JMT group (P < 0.01).JMT effectively prevents SC apoptosis that is induced by high glucose. This effect may be because of increased expression of Bcl-2 mRNA and protein and decreased expression of caspase-3 p20 mRNA and protein.

Objective To explore the clinical effect and safety of routine therapy combined with self made thirsty removing and glucose decreasing formula for type 2 diabetes mellitus(T2DM).Methods Eighty six patients with T2DM were randomly divided into two groups,43 cases in each group.The patients in both groups were given dietary control and kinesitherapy,and their complicationswere also positively treated.They received diformin tablets during the same period.Based on this treatment,the combined group was given self made thirsty removing and glucose decreasing formula.The changes of fasting plasma glucose(FPG),2 h postprandial glucose(2 hPG),glycosylated hemoglobin(HbAlc),hemorheological indexes and each composite score by filling in diabetes specific quality of life scale in two groups were compared,and the incidence of adverse reactions was observed.Changes of all dimensions were compared through particular life quality scale.The incidence of negative effectswasobserved.Results After treatment,FPG and 2 hPG levels in both groups significantly decreased,and the decreased degrees of FPG and 2 hPG levels in combined group were bigger than those in western group markedly.After treatment,the whole blood viscosity(high cut,middle cut and low cut),plasma viscosity and fibrinogen level in combined group as well as the whole blood viscosity(high cut and middle cut)and plasma viscosity in western group all improved notably,and the decreased degree of each hemorheological index in combined group were significantly bigger than those in western group.After treatment, the improved degrees of physical,psychological,mental and treatment composite in combined group were all larger than in western group.The adverse reactions in two groups were mild.Conclusion Routine therapy combined with self made thirsty removing and glucose decreasing formula can effectively ameliorate the level of blood glucose and hemorheological indexes in patients with T2DM,improve quality of life,achieve the expected physical and psychological aims,and has good safety.

OBJECTIVE:To study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy.METHODS:Sixty male SD rats were randomly divided into normal group and model groups. The diabetic rat models were established using Streptozotocin (STZ) method (60 mg/kg of intraperitoneal injection), and then randomly divided Jinmaitong low, middle, and high-dose groups and vitamin C group. All the experimental rats were sacrificed at 16-week and then the DRG was isolated. The morphological changes of DRG were observed using the Nissl's staining, and the NADPH oxidase subunit p22-phox, Cyt C, Bcl-2, and Caspase-3 of DRG in rats were detected by immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR). Cell apoptosis was detected by TUNEL.RESULTS:Compared with the model group, the expressions of NADPH oxidase subunit p22-phox protein, Cyt expression of C protein, Caspase-3 protein, and mRNA cell apoptosis rate in each treatment group significantly decreased whereas the expressions of Bcl-2 mRNA and protein significantly increased (P<0.05 or P<0.01). The Jinmaitong high-dose group had the best effect and was significantly different from that of the vitamin C group (P<0.01).CONCLUSIONS:Jinmaitong capsule can prevent the nerve injury in rats with diabetic peripheral neuropathy by inhibiting oxidative stress and decreasing the apoptosis. The high-dose Jinmaitong capsule has the best effect and is superior to vitamin C.

OBJECTIVE:To observe the effect of Jinmaitong capsule (JMT), a compound traditional Chinese medicine, on expressions of inducible nitric oxide synthase (iNOS) and nitro tyrosine (NT) protein in streptozocin-induced diabetic (STZ-DM) rats.METHOD:Intraperitoneal injection of streptozocin in rats to establish a model. STZ-DM rats were randomly divided into the model control group (distilled water), the small-dose JMT group (JMT at dose of 0.45 g x kg(-1) x d(-1)), the medium-dose JMT group (JMT at dose of 0.88 g x kg(-1) x d(-1)), the large-dose JMT group (JMT at dose of 1.75 g x kg(-1) x d(-1)) and Vitamin C group (VC at dose of 0.05 g x kg(-1) x d(-1)). Ten normal rats with matching weight and age were selected as the normal control group (distilled water). After intragastric administration for 16 weeks, the expressions of iNOS and NT in sciatic nerve were detected by the immunohistochemistry method.RESULT:The expression levels of iNOS and NT protein in diabetic rats were higher than those in normal rats (P<0.05, P<0.01). Compared with the model group, the levels of iNOS and NT protein in JMT and VC groups were significantly decreased (P<0.05, P<0.01). Particularly, the medium-dose JMT group showed a better effect than the VC group (P<0.05, P<0.01).CONCLUSION:JMT could down-regulate the expressions of iNOS and NT protein of sciatic nerve in diabetic rats.

Objective To investigate the influence of Chinese compound formula Jinmaitong on the Nissl's staining of dorsal root ganglion (DRG) of diabetic rats and on the expressions of NADPH oxidase and inducible nitric oxide synthase (iNOS).Methods Dabetic rat models were induced after the intraperitoneal injection of streptozotocin (STZ) to 70 male Sprague Dawley rats.These rats were then divided into five groups (n=14):model group (placebo),Jinmaitong high-dose group (20-fold dose recommended for human),Jinmaitong middle-dose group (10-fold dose recommended for human),Jinmaitong low-dose group (5-fold dose recommened for human),and vitamin C group (10-fold dose recommened for human).Meanwhile,10 rats without STZ intervention were set as normal group.Drugs (or placebo) were intragastically administered once per day.Sixteen weeks later,DRG tissues were isolated for Nissl's staining as well as immunohistochemistry staining to detect the expressions of NADPH oxidase p22phox and iNOS.Results Nissl's bodies depleted obviously in model group.In Jinmaitong high-dose and middle-dose groups,the morphologic abnormality of Nissl's bodies was slight.Compared to model group,the expression of NADPH p22phox and iNOS in all Jinmaitong groups reduced significantly (P<0.05).Conclusions The study gives evidence that oxidative stress exists in peripheral sensory nerve ganglion of diabetic rats.Jinmaitong can counteract oxidative stress and protect neurons.

目的 探讨筋脉通含药血清对高糖培养施万细胞8-羟基脱氧鸟苷(8-hydoxydeoxyguanosine,8-OHdG)水平及活化的半胱氨酸天冬氨酸酶3(cysteine aspartase-3,caspase-3,)(17kDa)蛋白及mRNA表达的影响.方法 将体外培养的施万细胞分为高糖组、筋脉通组(加入筋脉通含药血清)、维生素C组(加入维生素C含药血清)及正常对照组,采用酶联免疫吸附法检测施万细胞上清液中8-OHdG的分泌量,免疫荧光法检测活化的caspase-3(17kDa)蛋白表达,实时荧光定量PCR法检测活化的caspase-3(17kDa)mRNA的表达.结果 与正常对照组比较,高糖培养施万细胞上清液中8-OHdG的分泌量及细胞内活化的caspase-3(17kDa)蛋白和mRNA表达均明显升高(P＜0.01)；与高糖组比较,筋脉通组细胞上清液中8-OHdG的分泌量及细胞内活化的caspase-3(17kDa)蛋白和mRNA表达明显降低(P＜0.01).结论 筋脉通含药血清可改善高糖导致的施万细胞DNA氧化损伤和细胞凋亡,提示筋脉通可能改善糖尿病神经病变之氧化损伤及细胞凋亡.

Objective:Observe the effects of Jinmaitong capsule on reducing the expression of AGEs and its receptor in the streptozotocin-induced diabetic rats' sciatic nerve.Methods:Production of STZ diabetic rats were randomly divided into model group,a small dose,middle dose,high dose of Jinmaitong group and normal control group.The small,medium and large dose of Jinmaitong groups were adult dose by 5 times,10 times and 20 times the dose;Model group and normal group was fed distilled water.Detected before treatment and after treatment 4w,8w,12w and 16w of body weight and blood glucose,using Immunohistochemical determination of AGEs and their receptors in sciatic nerve.Results:STZ-DM rats's blood glucose,weight and the MSPT were significantly different form the normal group(P0.01);but the model group showed no significant difference;Comparison with the normal group,DM group's AGEs and RAGE IOD accumulated significantly higher(P0.01),the treatment group was decreased than the DM group.Compared with DM group,the Jin Mai Tong group through the middle dose group was significantly lower,there were significant differences(P0.01).Conclusion:Jinmaitong capsule treatment can improve the pathological form of the sciatic nerve,lower the expression of AGEs and its receptor in DM rat sciatic nerve.

目的 观察中药筋脉通对糖尿病大鼠坐骨神经NADPH 氧化酶p22-phox亚基表达的影响.方法 将STZ诱导的糖尿病大鼠随机分为模型组,维生素C组,筋脉通小、中、大剂量组,并设立正常对照组,连续灌胃16周.检测各组治疗前及治疗后 4、8、12、16周的体重、血糖;测定第16周时大鼠机械痛阈值;采用免疫组化法测定大鼠坐骨神经NADPH 氧化酶p22-phox亚基的表达,并进行半定量分析.结果 与正常组相比,各组糖尿病大鼠体重均显著下降(P<0.01),血糖均明显升高(P<0.01);与模型组比较,各治疗组大鼠体重及血糖在各时间点均无显著差异(P>0.05).与正常组相比,模型组、VC组、筋脉通小、大剂量组机械痛阈值显著降低(P<0.01);各治疗组机械痛阈值较模型组均明显升高(P<0.01);与VC组比较,筋脉通中剂量组机械痛阈值显著升高(P<0.01).与正常组相比,模型组及各治疗组p22亚基的IOD值明显升高(P<0.05,P<0.01);各治疗组p22亚基的IOD值较模型组均显著降低(P<0.01);与VC组比较,筋脉通中、大剂量组p22亚基IOD值显著降低(P<0.01,P<0.05).结论 筋脉通能显著降低大鼠坐骨神经NADPH 氧化酶p22-phox亚基的表达.

OBJECTIVE:To investigate the effects of medicated serum prepared by administration of Jinmaitong (JMT), a compound Chinese herbal medicine, on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22-phox subunit and inducible nitric oxide synthase (iNOS) of rat Schwann cells cultured in high-glucose medium.METHODS:Wistar rats were divided into normal control group (distilled water), JMT (JMT at dose of 1.31 g/(kg·d)) group and vitamin C (vitamin C at dose of 0.08 g/(kg·d)) group to prepare medicated serum. Bilateral sciatic nerves of new born Wistar rats were used to separate Schwann cells. Schwann cells cultured in high-glucose medium were divided into high glucose group (cultured with 50 mmol/L glucose medium), JMT group (cultured with JMT-medicated serum) and vitamin C (VC) group (cultured with VC-medicated serum). Schwann cells cultured in DMEM were used as the normal control. After 48 h culturing, the expression of iNOS was detected by immunofluorescence method and p22-phox mRNA was tested by real-time fluorescent quantitative polymerase chain reaction.RESULTS:The expression levels of iNOS and p22-phox mRNA in the high glucose group were higher than those in the normal control group (P<0.01). Compared with the high glucose group, expressions of iNOS protein and p22-phox mRNA in JMT group were significantly decreased (P<0.01) and JMT-medicated serum had better effect than VC (P<0.01).CONCLUSION:JMT-medicated serum can down-regulate the expressions of iNOS protein and NADPH oxidase p22-phox subunit mRNA of Schwann cells cultured in high-glucose medium.

近年来全球糖尿病患病人数急剧上升,糖尿病及其并发症给人类健康带来巨大的危害.糖尿病慢性并发症的发病机制尚未完全阐明,存在多个假说,目前业内已公认氧化应激是糖尿病慢性并发症的主要发病机制之一[1].NADPH氧化酶作为一种过氧化物酶,催化产生活性氧(ROS),参与介导体内的氧化应急损伤,有足够的实验和观测数据表明其与糖尿病慢性并发症的氧化应激机制密切相关.现就NADPH氧化酶与糖尿病慢性并发症的关系及中西药干预现状进行综述.