[Diabetic Dyslipidemia]. / Dyslipidämie bei Diabetes.

Diabetic dyslipidemia is a major cause of the increased cardiovascular risk in diabetes. This lipid disorder is characterized by increased plasma triglycerides, increased remnant particles of triglyceride-rich lipoproteins, small dense LDL particles and reduced HDL cholesterol. The main pathogenetic triggers are obesity and insulin resistance. In addition to lifestyle measures, statins, ezetimibe and eventually PCSK9 inhibitors are available to treat diabetic dyslipidemia and to reduce the cardiovascular risk. Fibrates and omega-3 fatty acids currently do not play a significant therapeutic role. A consistent and target-oriented therapy of diabetic dyslipidemia is a prerequisite for a cardiovascular risk reduction in patients with diabetes, which has been well proven in clinical studies.

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules.

ETHNOPHARMACOLOGICAL RELEVANCE: Leeches (pinyin name Shui Zhi; Latin scientific name Hirudo; Hirudinea; Hirudinidae) and centipedes (pinyin name Wu Gong; Latin scientific name Scolopendridae; Chilopoda; Scolopendridae) are traditional Chinese medicines, and they belong to the family entomology. A combination of leech and centipede is used as an effective medicine to promote blood circulation and remove blood stasis in traditional Chinese medicine, and "leech-centipede" medicine has been used in many prescriptions to treat diabetic vascular disease, including diabetic erectile dysfunction (DIED). However, its specific mechanism remains unclear and requires in-depth study. AIM OF THE STUDY: This study aimed to investigate the mechanism of "leech-centipede" medicine to improve erectile dysfunction-associated diabetes by detecting PKC pathway-related molecules. MATERIALS AND METHODS: The active ingredients of "leech-centipede" medicine were identified using high performance liquid chromatography (HPLC). Fifty male SPF rats were injected with streptozotocin to induce the DM model. Eight weeks later, the DMED model was validated with apomorphine. The DIED rats were divided into five groups-T,P,DD,DZ, and DG-and were separately treated with tadalafil, pathway inhibitor LY333531 and low-, medium-, and high-dose "leech-centipede" medicine for 8 weeks. After treatment, the blood glucose level was measured, erectile function with apomorphine was assessed, the LOX-1, sE-selectin, sICAM-1, SOD, and MDA in serum was evaluated by enzyme-linked immunosorbent assay, and flow cytometry was performed. After the collection of penile tissue, the related protein and mRNA expression was assessed by Western blotting and PCR, and the tissue and ultrastructure were analysed by HE staining, immunohistochemistry and scanning electron microscopy. RESULTS: After treatment, the erectile function of rats was significantly improved in the T,P,DD,DZ, and DG groups compared with that in the model group. Thus, "leech-centipede" medicine can significantly reduce the levels of LOX-1, sE-selectin, sICAM-1, EMPs and CD62P to protect vascular endothelial function and anti-platelet activation, improving DIED rat erectile function. Additionally, "leech-centipede" medicine can increase SOD expression and decrease MDA expression, reducing the possibility of oxidative stress injury in DIED rats and improving the antioxidant capacity. Moreover, "leech-centipede" therapy can dramatically reduce the protein and mRNA expression of DAG, PKCß, NF-κB, and ICAM-1, improve vascular endothelial injury in DIED rats and inhibit abnormal platelet activation. CONCLUSION: "leech-centipede" medicine can improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protects endothelial function and anti-platelet activation.

Efficacy of gastric electrical stimulation in intractable nausea and vomiting at 10 years: A retrospective analysis of prospectively collected data.

BACKGROUND: Gastric electrical simulation has been shown to relieve nausea and vomiting in medically refractory patients. Efficacy of gastric electrical stimulation has been reported mostly in short-term studies, but none has evaluated its efficacy beyond 10 years after implantation. METHODS: Patients implanted at our center for medically refractory severe and chronic nausea and/or vomiting were evaluated before and over 10 years after implantation using symptomatic scale and quality of life (GIQLI) score. Improvement was defined as a reduction of more than 50% in vomiting frequency. KEY RESULTS: A total of 50 patients were implanted from January 1998 to December 2009. Among them, 7 were explanted due to a lack of efficacy and/or side effects, 2 died, and 4 were lost to follow-up. Mean follow-up was 10.5 ± 3.7 years. In intention-to-treat analysis, 27/50 (54%) patients reported an improvement. Beyond 10 years, an improvement in early satiety (3.05 vs 1.76, <0.001), bloating (2.51 vs 1.70, P = .012), nausea (2.46 vs 1.35, P = .001), and vomiting (3.35 vs 1.49 P < .001) scores were observed. Quality of life improved over 10 years (GIQLI score: 69.7 vs. 86.4, P = .005) and body mass index (BMI: 23.4 vs. 26.2 kg/m2 ; P = .048). CONCLUSIONS AND INFERENCES: Gastric electrical simulation is effective in the long-term in patients with medically refractory nausea and vomiting, with an efficacy of 54% at 10 years on an intention-to-treat analysis. Other long-term observational studies are warranted to confirm these results.

Estrogen-dependent hypersensitivity to diabetes-evoked cardiac autonomic dysregulation: Role of hypothalamic neuroinflammation.

AIMS: To investigate if autonomic dysregulation is exacerbated in female rats, subjected to diabetes mellitus (DM), via a paradoxical estrogen (E2)-evoked provocation of neuroinflammation/injury of the hypothalamic paraventricular nucleus (PVN). MAIN METHODS: We measured cardiac autonomic function and conducted subsequent PVN neurochemical studies, in DM rats, and their respective controls, divided as follows: male, sham operated (SO), ovariectomized (OVX), and OVX with E2 supplementation (OVX/E2). KEY FINDINGS: Autonomic dysregulation, expressed as sympathetic dominance (higher low frequency, LF, band), only occurred in DM E2-replete (SO and OVX/E2) rats, and was associated with higher neuronal activity (c-Fos) and higher levels of TNFα and phosphorylated death associated protein kinase-3 (p-DAPK3) in the PVN. These proinflammatory molecules likely contributed to the heightened PVN oxidative stress, injury and apoptosis. The PVN of these E2-replete DM rats also exhibited upregulations of estrogen receptors, ERα and ERß, and proinflammatory adenosine A1 and A2a receptors. SIGNIFICANCE: The E2-dependent autonomic dysregulation likely predisposes DM female rats and women to hypersensitivity to cardiac dysfunction. Further, upregulations of proinflammatory mediators including adenosine A1 and A2 receptors, TNFα and DAPK3, conceivably explain the paradoxical hypersensitivity of DM females to PVN inflammation/injury and the subsequent autonomic dysregulation in the presence of E2.

Anthocyanin-rich extract from black rice (Oryza sativa L. Japonica) ameliorates diabetic osteoporosis in rats.

Diabetic osteoporosis (DOP) is a systemic endocrine-metabolic osteopathy which has the characteristics of bone mineral density (BMD) reduction and bone microstructural destruction. Although anthocyanin-rich extract from black rice (AEBR) was reported to have a beneficial effect on diabetic rats, no studies have been performed on whether black rice anthocyanins are beneficial for diabetic osteoporosis. Therefore, in this study, a streptozotocin-induced diabetic rat model was established to investigate the protective effect of AEBR on diabetes-induced osteoporosis and its possible mechanism. AEBR at three doses (0.5, 1.0, and 2.0 g kg-1 d-1) were administered by oral gavage to diabetic rats for 8 weeks. The blood glucose, BMD, bone histomorphometry parameters, serum bone turnover biomarkers, bone marrow adipocyte numbers, as well as osteoprotegerin (OPG), runt-related transcription factor 2 (RUNX 2), and receptor activator of nuclear factor-κ B ligand (RANKL) protein expression in bone and serum were detected. The results indicated that AEBR dose-dependently decreased the blood glucose, increased the BMD, and decreased the serum bone turnover markers. The bone microstructure and osteoclast numbers in bone tissues returned to normal in the high AEBR dosage group; at the same time, the AEBR dose-dependently suppressed bone marrow adipogenesis. The RUNX 2 as well as the OPG/RANKL ratio in diabetic rats' bone tissues increased significantly in the AEBR treatment group. Our results indicate that AEBR administration can ameliorate bone loss caused by diabetes; this is mainly attributed to its inhibition of bone turnover, suppression of bone marrow adipogenesis, and up-regulation of RUNX 2 and the OPG/RANKL expression ratio.

Effect of Horse-chestnut seed extract on matrix metalloproteinase-1 and -9 during diabetic wound healing.

The effects of aqueous-ethanol extract of Horse chestnut (HCE) on MMP-1 and MMP-9 expressions during cutaneous wound healing in diabetic rats were investigated in this study. The expressions of MMP-1 and MMP-9, wound closure, myeloperoxidase (MPO) activity, hydroxyproline, and malondialdehyde (MDA) levels in wound tissue were measured. Quercetin glucuronide in HCE was identified as main compound using a LC-MS/MS. The hydroxyproline level was significantly increased in the treated group versus control after the 3rd and 7th days (p < 0.05). The MDA level and MPO activity were significantly lower in the treatment group (p < 0.05). MMP-1 gene expression level in treated rats was increased in the 7th day while it was reduced in 14th day. MMP-9 gene expression level in treated rats was decreased in 7th, and 14th days compared to control (p < 0.05). These results show that HCE accelerated the cutaneous wound-healing process in diabetic rats via MMP-1 and MMP-9 regulation. PRACTICAL APPLICATIONS: The main function of MMPs is to degrade and deposite the various components of the extracellular matrix. Also, they participate physiological processes such as inflammation, angiogenesis, and tissue remodeling. Horse chestnut seeds (HC) are known to be rich in saponins and flavonoids. HC are used for the treatment of abdominal pain, stomach ache, cold, hemorrhoids, arterial stiffness, rheumatism, oedema, diarrhea, chronic venous insufficiency and also as an antihemorrhagic and antipyretic in traditional medicine. It has been shown that HC has anti-inflammatory, antioedema, vessel protective, and free radical scavenging properties. This study indicates that HCE could be an effective agent for wound healing in diabetic wound model via its ability to suppress the MMP-9 gene expression and regulates MMP-1 gene expression besides its antioxidative, anti-inflammatory effects.

Review of the Effect of Natural Compounds and Extracts on Neurodegeneration in Animal Models of Diabetes Mellitus.

Diabetes mellitus is a chronic metabolic disease with a high prevalence in the Western population. It is characterized by pancreas failure to produce insulin, which involves high blood glucose levels. The two main forms of diabetes are type 1 and type 2 diabetes, which correspond with >85% of the cases. Diabetes shows several associated alterations including vascular dysfunction, neuropathies as well as central complications. Brain alterations in diabetes are widely studied; however, the mechanisms implicated have not been completely elucidated. Diabetic brain shows a wide profile of micro and macrostructural changes, such as neurovascular deterioration or neuroinflammation leading to neurodegeneration and progressive cognition dysfunction. Natural compounds (single isolated compounds and/or natural extracts) have been widely assessed in metabolic disorders and many of them have also shown antioxidant, antiinflamatory and neuroprotective properties at central level. This work reviews natural compounds with brain neuroprotective activities, taking into account several therapeutic targets: Inflammation and oxidative stress, vascular damage, neuronal loss or cognitive impairment. Altogether, a wide range of natural extracts and compounds contribute to limit neurodegeneration and cognitive dysfunction under diabetic state. Therefore, they could broaden therapeutic alternatives to reduce or slow down complications associated with diabetes at central level.

Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model.

BACKGROUND: Erectile dysfunction (ED) is a common complication of diabetes. This study aimed to explore the beneficial effect of Danshen injection on ED in a streptozotocin (STZ)-induced diabetic rat model and the underlying mechanism. METHODS: The diabetic rat model was established by an intraperitoneal injection of 60 mg/kg STZ in male Sprague-Dawley rats. The diabetic rats were intraperitoneally injected with Danshen solution (0.5 or 1 mL/kg/day) or the same volume of saline for 6 weeks. Age-matched rats served as controls. After 6 weeks, erectile function and histological morphology of the corpora cavernosum were assessed. Oxidative stress indicators, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels, were measured in penile tissues. The expression levels of glucose-regulated protein 78 (Grp78), growth arrest and DNA damage-inducible gene 153 (GADD153/CHOP) were determined by immunohistochemistry, immunoblotting, and RT-PCR. Apoptosis was detected by a TUNEL assay. RESULTS: The erection times of diabetic rats were significantly less than those of control rats. Danshen injection could improve erectile function via increased erection times. Danshen injection was also found to ameliorate the morphological abnormalities of the corpora cavernosum, to reduce the number of apoptotic cells, and to suppress caspase-3 activation in penile tissue, accompanied by downregulation of the endoplasmic reticulum stress biomarkers Grp78 and CHOP. Danshen injection could increase SOD activity as well as reduce ROS and MDA levels in diabetic rats, indicating suppression of oxidative stress. CONCLUSION: Danshen injection could rescue diabetes-associated ED, possibly via suppressing the oxidative stress and endoplasmic reticulum (ER) stress-induced apoptosis pathways.

Acupoint Therapy on Diabetes Mellitus and Its Common Chronic Complications: A Review of Its Mechanisms.

Acupoint therapy is one of the therapeutic means in Traditional Chinese Medicine (TCM) concerning acupoints and meridians, including manual acupuncture, electroacupuncture, moxibustion, external application, acupoint injection, and catgut embedding. In the treatment of diabetes and its common chronic complications, acupoint therapy has proved to have specific curative effect and notable advantages. Single or combined with western medicine, it has superior efficacy and less side effects than western medicine alone. Studying its mechanism can provide experimental basis for clinical treatment. Relevant researches in the recent 5 years mainly focused on the mechanism of electroacupuncture, point injection, catgut embedding, etc. in the treatment of diabetes and common diabetic complications such as neuropathy, nephropathy, and hepatopathy. The possible theories involve the regulation of nerve conduction, signal pathways, hormone level, protein expression, oxidative stress level, structure restoration, etc. The most studied acupoints are Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Yishu (EX-B3), and Zhongwan (CV12). However, most of the studies have been based on diabetes model rats rather than clinical trials. Moreover, the mechanism of acupoint therapy treating other chronic complications like diabetic retinopathy and that of other effective methods like pressing ear with beans, auricular points plaster therapy, and external application remain unclear. Therefore, this aspect still awaits further research.

Physicochemical properties and in vivo evaluation of Pt/TiO2-SiO2 nanopowders.

AIM: Sol-gel is a suitable and advantageous method to synthesize mixed oxide nanomaterials with unique physicochemical and biological properties. MATERIALS & METHODS: In this work, TiO2-SiO2 nanopowders cogeled with platinum acetylacetonate were developed and studied in the perspective of nanomedicine. The physicochemical properties of the Pt/TiO2-SiO2 nanopowders, named NanoRa2-Pt, were evaluated in detail by means of complementary spectroscopic and microscopic tools. The nanopowder's biocatalytic efficiency in wound healing was evaluated in a Type I diabetes animal model. RESULTS: These are TiO2-SiO2 submicron mesoporous particles with variable size and shape containing ultra-small platinum nanoparticles with catalytic properties. CONCLUSION: The use of NanoRa2-Pt catalyzes the natural healing processes with a faster remodeling stage. These sols, which we call nanobiocatalysts, belong to an emerging and very promising research field known as catalytic nanomedicine.

Effect of glycemic control on the Diabetes Complications Severity Index score and development of complications in people with newly diagnosed type 2 diabetes.

BACKGROUND: The aim of the present study was to assess the longitudinal accumulation of diabetes-related complications and the effect of glycemic control on the Diabetes Complications Severity Index (DCSI) score in people with newly diagnosed type 2 diabetes (T2D). METHODS: A retrospective cohort study was conducted using electronic health records from a large integrated healthcare system. People with newly diagnosed T2D were identified between 2005 and 2016 and stratified by initial HbA1c category (<7%, <8%, ≥8%). The DCSI scores were determined for each study year, and the cumulative incidence of diabetes-related complications was assessed. A Cox proportional hazard model was used to evaluate the effect of baseline HbA1c and worsening glycemic (HbA1c) control on longitudinal changes in DCSI scores. RESULTS: Of 32 174 people identified as having newly diagnosed T2D, 14 016 (44%), 21 657 (67%), and 9983 (31%) had an initial or baseline HbA1c <7%, <8%, and ≥8%, respectively. Ten years after diabetes diagnosis, retinopathy, chronic kidney disease, coronary heart disease, and neuropathy were diagnosed in 22%, 29%, 24%, and 36% of people. Baseline HbA1c did not affect the observed trend in longitudinal changes in DCSI scores throughout the 11-year period. For people in each of the initial HbA1c groups (<7%, <8%, ≥8%), worsening or persistently poor glycemic control was significantly associated with a 10%, 19%, or 16% increase in the risk of experiencing an increased DCSI score, respectively (all P < 0.01). CONCLUSIONS: Baseline glycemic control had no apparent effect on longitudinal changes in DCSI score. Worsening or persistently poor glycemic control was associated with an increased risk of an increase in the DCSI score.

Does Oxidative Stress Play a Role in Altered Characteristics of Diabetic Bone? A Systematic Review.

Diabetes mellitus (DM) has been associated with increased bone fracture rates, impaired bone regeneration, delayed bone healing, and depressed osteogenesis. However, the plausible pathogenic mechanisms remain incompletely understood. The aim of the present systematic review was to investigate whether oxidative stress (OS) plays a role in altered characteristics of diabetic bone under in vivo conditions. An electronic search of the MEDLINE (via PubMed) and Embase databases was performed. In vivo animal studies involving DM and providing information regarding assessment of OS markers combined with analyses of bone histology/histomorphometry parameters were selected. A descriptive analysis of selected articles was performed. Ten studies were included in the present review. Both bone formation and bone resorption parameters were significantly decreased in the diabetic groups of animals compared to the healthy groups. This finding was consistent regardless of different animal/bone models employed or different evaluation periods. A statistically significant increase in systemic and/or local OS status was also emphasised in the diabetic groups in comparison to the healthy ones. Markers of OS were associated with histological and/or histomorphometric parameters, including decreased trabecular bone and osteoid volumes, suppressed bone formation, defective bone mineralisation, and reduced osteoclastic activity, in diabetic animals. Additionally, insulin and antioxidative treatment proved to be efficient in reversing the deleterious effects of high glucose and associated OS. The present findings support the hypotheses that OS in the diabetic condition contributes at least partially to defective bone features, and that antioxidative supplementation can be a valuable adjunctive strategy in treating diabetic bone disease, accelerating bone healing, and improving osteointegration.

Diabetes associated with male reproductive system damages: Onset of presentation, pathophysiological mechanisms and drug intervention.

Diabetes mellitus (DM) is a major health problem that affects patients' quality of life quality throughout the world due to its many complications. Reproductive dysfunction is one of the major secondary complications in both diabetic animals and human beings. Furthermore, DM has recently broken the age barrier and has been heavily diagnosed in children and young persons of reproductive age. In the past few years, many studies on DM in male reproductive functions in both diabetic men and experimental diabetic animals have been published. It is recognized that sustained hyperglycemia, which impairs reproductive function in diabetic men, is at risk of developing. DM harmfully affects male reproductive functions in multiple areas; these may include spermatogenesis, sperm maturation, fertility capability, penile erection, and ejaculation. Traditional medicine and folklore worldwide have used numerous medicinal plants to manage the diabetic reproductive dysfunction because bioactive phyto-constituents are affluent in many places. Unfortunately, the exact reasons for diabetic male reproductive dysfunction are not completely understood and currently there are no treatments in reproductive medicine specifically for such lesions. The aim of this review is to summarize current research findings of DM on reproductive functions, to elaborate the underlying mechanisms related to these diseases via in vivo and in vitro studies, and to describe the ameliorative effects of medicinal plants or their products. The review findings provide a systematic understanding of DM on the reproductive functions and lay the theoretical foundation for developing the direction of reproductive medicine.

Beneficial effects of Lycium barbarum polysaccharide on spermatogenesis by improving antioxidant activity and inhibiting apoptosis in streptozotocin-induced diabetic male mice.

Spermatogenic dysfunction is one of the major secondary complications of diabetes. L. barbarum polysaccharide (LBP) has long been considered to possess anti-apoptotic activities and antioxidant, anti-inflammatory and fertility-enhancing properties in traditional medical practices in China. The aim of the current study was to seek out scientific evidence to determine if LBP also contributes to the recovery from spermatogenic dysfunction in diabetic individuals. We investigated whether the oral administration of LBP in streptozotocin (STZ)-induced type-1 diabetic male mice would reverse spermatogenic dysfunction and improve histological damage in testes. After the oral administration of LBP (10, 20 or 40 mg kg-1, respectively), sildenafil citrate (5 mg kg-1) or saline for 62 consecutive days, the sperm parameters were analyzed. Macroscopic and microscopic changes in the reproductive organs, including their weight, and photomicroscope and electronmicroscope images were also assessed. In addition, the antioxidant capacity and levels of malondialdehyde in the testes were determined according to the instructions provided with the assay kits and the expression of the apoptosis-related proteins, Caspase-3, Bax and Bcl-2, in the testes was analyzed using western-blot analysis. LBP treatment of diabetic mice considerably recovered the sperm parameters, increased the weight of the reproductive organs, ameliorated their histological appearance and increased antioxidant enzyme activity to different degrees. Moreover, our data also showed a marked decrease in Caspase-3 expression and an increase in the ratio of Bcl-2/Bax 43 after LBP administration (40 mg kg-1) when compared to the diabetic group. These results demonstrate that LBP exerts protective effects on diabetes induced male spermatogenic dysfunction, which is likely to be mediated through increasing antioxidant enzyme activities and inhibiting cell death.

Geraniol alleviates diabetic cardiac complications: Effect on cardiac ischemia and oxidative stress.

The present study was planned to assess the possible protective effect of geraniol on cardiovascular complications in an animal model with diabetes. Diabetes was induced in rats by a single streptozotocin injection. In the treated group, geraniol (150mgkg-1day-1) was administered orally starting from the 15th day after induction of diabetes, and ending after 7 weeks; diabetic control rats were given vehicle for the same period. At the end of the study, cardiac contractility was assessed by using a Millar microtip catheter in anesthetised rats, and cardiac conductivity determined by a surface ECG. Serum levels of glucose, cholesterol, triglyceride and adiponectin as well as urine 8-isoprostane were determined. In addition, cardiac superoxide dismutase (SOD) and catalase activity were measured. Geraniol administration significantly alleviated the attenuated cardiac systolic function associated with diabetes as indicated by inhibiting the decrease in the rate of rise (dP/dtmax) in ventricular pressure and the increase in systolic duration observed in diabetic rats. In addition, geraniol alleviated impaired diastolic function as shown by inhibiting the decrease in the rate of fall (dP/dtmin) in ventricular pressure and increased isovolumic relaxation constant (Tau) observed in diabetic rats. ECG recordings showed that geraniol prevented any increase in QTc and T-peak-T-end intervals, and markers of LV ischemia and arrhythmogenesis, seen in diabetic animals. Geraniol suppressed the exaggerated oxidative stress as evidenced by preventing the increase in 8-isoprotane. In diabetic heart tissue, geraniol prevented the inhibition in catalase activity but did not affect the heart SOD. Geraniol partially reduced hyperglycemia, prevented the hypercholesterolemia, but did not affect the serum level of adiponectin in diabetic animals. Results obtained in this study suggest that geraniol provides a potent protective effect against cardiac dysfunction induced by diabetes. This ameliorative effect could be attributed to its suppression of oxidative stress.

Effectiveness of Mindfulness-based interventions on physiological and psychological complications in adults with diabetes: A systematic review.

This systematic review aimed to examine the effectiveness of Mindfulness-based interventions in reducing diabetes-related physiological and psychological symptoms in adults with types 1 and 2 diabetes. Five databases were systematically searched. A total of 11 studies satisfied the inclusion criteria. Mindfulness-based intervention effectiveness for physiological outcomes (glycaemic control and blood pressure) was mixed. Mindfulness-based interventions appear to have psychological benefits reducing depression, anxiety and distress symptoms across several studies. Studies' short-term follow-up periods may not allow sufficient time to observe physiological changes or illustrate Mindfulness-based interventions' potential long-term efficacy. More long-term studies that include a consistent, standardised set of outcome measures are required.

Delayed auditory conduction in diabetes: is metformin-induced vitamin B12 deficiency responsible?

The present study aims to evaluate the functional integrity of the auditory pathway in patients with diabetes taking metformin. A further aim is to assess its association with vitamin B12 deficiency induced by metformin. Thirty diabetics taking metformin and 30 age-matched non-diabetic controls were enrolled. Stimulus-related potentials and vitamin B12 levels were evaluated in all the subjects. The diabetics showed deficient vitamin B12 levels and delayed wave III latency and III-V interpeak latency in the right ear and delayed Na and Pa wave latencies in the left ear compared with the controls. The dose and duration of metformin showed no association with the stimulusrelated potentials. Therefore, although vitamin B12 levels were deficient and auditory conduction impairment was present in the diabetics on metformin, this impairment cannot be attributed to the vitamin B12 deficiency.

Reversibility of endothelial dysfunction in diabetes: role of polyphenols.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

[Diabetic constipation treated with acupoint embedding therapy and forlax: a randomized controlled trial].

OBJECTIVE: To compare the difference among the combined method of oral administration of forlaxand acupoint embedding therapy, the simple acupoint embedding therapy and the simple oral administration of for-lax in the clinical efficacy on diabetic constipation. METHODS: One hundred and fifty patients were randomized intoa comprehensive group, an acupoint embedding group and a forlax group, 50 cases in each one. In the acupointembedding group, the embedding therapy was applied to bilateral Tianshu (ST 25), Daheng (SP 15), Shangjuxu(ST 37) and Dachangshu (BL 25), once a week. In the forlax group, forlax (polyethylene glycol) was prescribedfor oral administration, once a day, 10 g each time. In the comprehensive group, the acupoint embedding therapyand forlax were combined and the methods were the same as the first two groups. The treatment for 4 weeks wasas one session, and 2 sessions were required in the three groups. Separately, in 4 weeks, 8 weeks of treatment and2 months after treatment, the constipation symptom scores were compared among the three groups. At the end of2 sessions of treatment, the clinical efficacy and adverse reactions were compared among the three groups. In2 months after treatment, the recurrence rate was compared among the three groups. RESULTS: The total effectiverate was 98. 0% (49/50) in the comprehensive group, better than 86. 0% (43/50) in the acupoint embeddinggroup and 78. 0% (11/50) in the forlax group (both P<0. 01). In the 4 weeks and 8 weeks of treatment, the con-stipation symptom scores were reduced significantly as compared with those before treatment in the three groups(all P<0. 05). The results in the comprehensive group were lower than those in the other two groups (all P<0. 05). In the 4 weeks of treatment, the scores were not different significantly between the acupoint embedding group and the forlax group (P>0.05). In 8 weeks of treatment and 2 months after treatment, the scores in the acupoint embedding group were better tan those in the forlax group (all p<0.05). There were 2 cases of drug adverse reaction in the comprehensive group, 6 cases in the forlax group and 0 case in the acupoint embedding group. The recurrence rate was 8.1% (4/49) in the comprehensive group, lower than 32.6% (14/43) in the acupoint embedding group and 59.0% (23/39) in the forlax group (both P<0.01). CONCLUSION: the combined therapy of acupoint embedding and forlax achieves the better clinical efficacy on diabetic constipation and constipation symptom scores as compared with the simple acupoint embedding therapy and the oral administration of forlax the short-term efficacy of the simple acupoint embedding therapy is not different significantly from the simple forlax medication, but the long-term efficacy and safety are better than those of simple forlax medicaiton.

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.