Diabetes Disease State Research Articles

Evaluation of hemoglobin A1c control among Medicare advantage patients not meeting non‐insulin diabetes medication adherence metric

AbstractBackgroundClinical pharmacists are often tasked with improving medication‐related performance metrics such as medication adherence to diabetes medications (MAD). Although the primary goal in patient care is excellent clinical outcomes, it is unknown if poor diabetes disease state control correlates with nonadherence to diabetes medications per the Centers for Medicare and Medicaid Services (CMS) MAD metric specifications. This retrospective study aimed to identify the degree of disease state control in patients identified as nonadherent to their diabetes medications among patients in value‐based Medicare Advantage payer‐provider reimbursement models and its impact on the clinical pharmacist.MethodsPatients attributed to a health system‐employed primary care provider group from January 1, 2022 to December 31, 2022 and identified as non‐adherent (percentage of days covered [PDC] <80%) for non‐insulin diabetic medications were included in the study.ResultsOf the 370 patients who met criteria for study inclusion, 256 (69%) had a controlled hemoglobin A1C of <7.5%; 305 patients also had a previous A1c available in the electronic medical record. Of those, 260 (85%) had an A1C that had improved or was unchanged between the two most recent readings. One hundred sixty (43%) patients had a reason listed for gaps within refill history including verbal dose change, adverse reaction, manufacturer‐supplied medications, fills from Veteran's Affairs pharmacy, provider samples, or nondiabetes diagnosis.ConclusionA large percentage of patients identified as non‐adherent had a high degree of disease state control suggesting an issue with the measurement of adherence rather than a true reflection of patients' adherence with prescribed drug regimens. Strategies to improve diabetes medication adherence based on PDC will likely need to look beyond disease state control.

Sustained metabolic dysregulation and the emergence of diabetes: associations between HbA1c and metabolic syndrome components in Tunisian diabetic and nondiabetic groups

IntroductionMetabolic Syndrome (MetS), diabetes, and other noncommunicable diseases (NCDs) have been a major focus of research in recent decades as the prevalence of these conditions continues to rapidly increase globally. However, the timing and patterns of development from metabolic risk factors to disease states are less well understood and are especially critical to understand in low- and middle-income countries (LMICs) and populations undergoing epidemiological transitions.MethodsNationally representative sociodemographic, anthropometric, and point-of-care biomarker data from the 2016 Tunisian Health Examination Survey (n = 8170) were used to determine the prevalence of diabetes and MetS components in Tunisia and to investigate associations between glycated hemoglobin (HbA1c) and MetS components (blood pressure [BP], HDL cholesterol [HDL], triglycerides [TG], and waist circumference [WC]) in participants aged 15-97 years old. To better understand how sustained metabolic dysregulation and disease states impact these associations, diabetic and nondiabetic groups were analyzed separately.ResultsThe overall prevalence of diabetes based on measured HbA1c was 18.2%. The diabetic groups had a higher prevalence of each individual MetS component, and significantly higher (BP, TG, WC, and HbA1c) and lower (HDL) values than the nondiabetic groups. Yet, there were a higher number of significant associations between HbA1c and MetS components found in nondiabetic women and men when compared to diabetic women and men. HbA1c was positively associated with the cumulative number of MetS components, irrespective of diabetes status in men and women.ConclusionsThe prevalence of both diabetes and MetS components (particularly low HDL cholesterol and elevated TG) is high among the Tunisian population. More MetS components were associated with HbA1c in nondiabetic individuals, showing a strong connection between the development of MetS components and diabetes. However, once the diabetes disease state manifests, there is more variability in the relationships. These results show the potential for HbA1c to be an indicator of metabolic health below clinical disease cutoffs, which may allow insights into the physiological changes that precipitate the emergence of diabetes.

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use.

Botanicals have a long history of medicinal use for a multitude of ailments, and many modern pharmaceuticals were originally isolated from plants or derived from phytochemicals. Among these, artemisinin, first isolated from Artemisia annua, is the foundation for standard anti-malarial therapies. Plants of the genus Artemisia are among the most common herbal remedies across Asia and Central Europe. The species Artemisia scoparia (SCOPA) is widely used in traditional folk medicine for various liver diseases and inflammatory conditions, as well as for infections, fever, pain, cancer, and diabetes. Modern in vivo and in vitro studies have now investigated SCOPA’s effects on these pathologies and its ability to mitigate hepatotoxicity, oxidative stress, obesity, diabetes, and other disease states. This review focuses on the effects of SCOPA that are particularly relevant to metabolic health. Indeed, in recent years, an ethanolic extract of SCOPA has been shown to enhance differentiation of cultured adipocytes and to share some properties of thiazolidinediones (TZDs), a class of insulin-sensitizing agonists of the adipogenic transcription factor PPARγ. In a mouse model of diet-induced obesity, SCOPA diet supplementation lowered fasting insulin and glucose levels, while inducing metabolically favorable changes in adipose tissue and liver. These observations are consistent with many lines of evidence from various tissues and cell types known to contribute to metabolic homeostasis, including immune cells, hepatocytes, and pancreatic beta-cells. Compounds belonging to several classes of phytochemicals have been implicated in these effects, and we provide an overview of these bioactives. The ongoing global epidemics of obesity and metabolic disease clearly require novel therapeutic approaches. While the mechanisms involved in SCOPA’s effects on metabolic, anti-inflammatory, and oxidative stress pathways are not fully characterized, current data support further investigation of this plant and its bioactives as potential therapeutic agents in obesity-related metabolic dysfunction and many other conditions.

Impact of pharmacist-led interventions on diabetes management at a community pharmacy in Pakistan: A quasi-experimental study.

To determine the impact of pharmacist-led interventions on satisfaction, disease state knowledge and perception of self-management of diabetes patients. The interventional, quasi-experimental study was conducted in Bahawalpur, Pakistan, from December 1, 2018, to June 30, 2019, and comprised data data from a community pharmacy of patients who had diagnosed type 2 diabetes for at least one year. Both non-pharmacological and pharmacological interventional tools were used as part of a care package administered by pharmacists. The modified version of the Diabetes Disease State Management Questionnaire was used to assess patient satisfaction, disease state knowledge and perception of self-management. Data was analysed using SPSS 20. Of the 100 patients initially enrolled, 80(80%) completed the follow-up. The mean age of the sample was 49.33±8.31 years. Of the total, 63(78.8%) patients had diabetes for <10 years. A significant improvement was seen in patient satisfaction (p=0.04), disease state knowledge (p=0.009) and self-management of diabetes (p=0.02) scores after the intervention. Interventions by pharmacists in a community pharmacy resulted in significant improvement in patient satisfaction, disease state knowledge and perception of self-management among type 2 diabetes patients.

Computer-aided Approaches to Support the Ethnopharmacological Importance of Dillenia pentagyna Roxb.: An In silico Study

Dillenia pentagyna Roxb., a deciduous and medium sized tree, is an ethnobotanically important species of several Asian countries including Bangladesh, Srilanka, and India. Various parts of this endangered tree including leaf, bark, root etc. are used in folkloric medicine systems for a very long time. It is locally used in the treatment of pain, wound healing, diabetes, diarrhea and other disease states. Molecular docking is an important technique to validate the exerted pharmacological actions of a plant or specific phytoconstituents by assessing the binding affinity and interaction pattern between small molecules and particular target receptors. Thus, to justify the notable ethnobotanical importances of D. pentagyna, an in silico study was designed employing selected phytochemicals i.e. isorhamnetin, lupeol, quercetin, kaempferol, and betulin isolated from this plant based on previous literature searches. The molecular docking revealed strong binding affinities (-4.8 to -12.9 kcal/mol) with the respective target proteins: 2OYE, 6COX, 4YK5, 5ZHP, and 1A5H. Besides, in accordance with the Lipinski’s rules, all five selected compounds of D. pentagyna showed promising orally active drug-like characteristics. To recapitulate, the present study has been found parallel with the existing ethnobotanical significance of D. pentagyna as the source of pain, fever, thrombosis, and diarrhea management agent. Bangladesh Pharmaceutical Journal 24(2): 125-132, 2021

Phenotyping the Association between Nocturia and Hypertension: A Systematic Review and Meta-Analysis.

The association between nocturia and hypertension has been widely reported yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the clinical urology setting. We synthesized current evidence on the relationship between nocturia and hypertension as a function of nocturia severity, age, gender, race, body mass index and diuretic use. We searched PubMed®, EMBASE® and Cochrane databases for studies published up to May 2020. Random effects meta-analyses were performed to identify pooled odds ratios for nocturia given the presence of hypertension. Meta-regression and subgroup analyses were performed to identify differences across study samples. Of 1,193 identified studies, 25 met the criteria for inclusion. The overall pooled OR for the association of nocturia with hypertension was 1.25 (95% CI 1.21-1.28, p <0.001). Pooled estimates were 1.20 (1.16-1.25, p <0.001) and 1.30 (1.25-1.36, p <0.001) using a 1-void and 2-void cutoff for nocturia, respectively (p <0.001 between cutoffs). The association was more robust in patient-based (1.74 [1.54-1.98], p <0.001) vs community-based (1.24 [1.24-1.29], p <0.001) study samples (p <0.001). The association was stronger in females compared to males (1.45 [1.32-1.58] vs 1.28 [1.22-1.35], p <0.001), and Black (1.56 [1.25-1.94]) and Asian (1.28 [1.23-1.33]) vs White subgroups (1.16 [1.08-1.24]; p <0.05 for both). No effect was observed for age or body mass index. Evidence on diuretics was limited. Hypertension is associated with a 1.2-fold to 1.3-fold higher risk of nocturia. This association is more robust at a higher nocturia cutoff, in patient-based study samples, among females and in Black and Asian patients, but unrelated to age or body mass index.

Chip-based sensing for release of unprocessed cell surface proteins in vitro and in serum and its (patho)physiological relevance.

To study the possibility that certain components of eukaryotic plasma membranes are released under certain (patho)physiological conditions, a chip-based sensor was developed for the detection of cell surface proteins, which are anchored at the outer leaflet of eukaryotic plasma membranes by a covalently attached glycolipid, exclusively, and might be prone to spontaneous or regulated release on the basis of their amphiphilic character. For this, unprocessed, full-length glycosylphosphatidylinositol-anchored proteins (GPI-AP), together with associated phospholipids, were specifically captured and detected by a chip- and microfluidic channel-based sensor, leading to changes in phase and amplitude of surface acoustic waves (SAW) propagating over the chip surface. Unprocessed GPI-AP in complex with lipids were found to be released from rat adipocyte plasma membranes immobilized on the chip, which was dependent on the flow rate and composition of the buffer stream. The complexes were identified in the incubation medium of primary rat adipocytes, in correlation to the cell size, and in rat as well as human serum. With rats, the measured changes in SAW phase shift, reflecting specific mass/size or amount of the unprocessed GPI-AP in complex with lipids, and SAW amplitude, reflecting their viscoelasticity, enabled the differentiation between the lean and obese (high-fat diet) state, and the normal (Wistar) and hyperinsulinemic (Zucker fatty) as well as hyperinsulinemic hyperglycemic (Zucker diabetic fatty) state. Thus chip-based sensing for complexes of unprocessed GPI-AP and lipids reveals the inherently labile anchorage of GPI-AP at plasma membranes and their susceptibility for release in response to (intrinsic/extrinsic) cues of metabolic relevance and may, therefore, be useful for monitoring of (pre-)diabetic disease states.

Benefits of a Clinical Pharmacist in Outpatient Diabetes Disease State Management

Diabetes is a chronic disease state affecting millions of patients, many of which have uncontrolled diabetes and not under a physician's care. The economic and health impacts that a pharmacist can have on patients overall health is well known. As an increasing number of patients suffer from uncontrolled diabetes and its complications which makes the role of pharmacists more important than ever to provide patients with knowledge of the many therapeutic options available, appropriate self-testing techniques, and other important lifestyle modifications. The role of pharmacists has expanded to include ambulatory care in an outpatient setting. The purpose of this study is to evaluate the impact of pharmacist involvement in diabetes management in an ambulatory clinic, where there previously has been no pharmacist participation. Comparing data from a pilot study performed without pharmacist involvement, pharmacists have been able to achieve better Hgb A1C reductions than the pilot study performed in fiscal year 16 (FY16) at an average of 3.36 ± 1.76. Although the sample size of patients was small at only 5, these are promising results of the impact that in depth patient education can have on improving outcomes.

Natural rubber latex biodevice as controlled release system for chronic wounds healing

The chronic wounds problem affect millions of people worldwide, becoming a great challenge to the healthcare systems. The normal healing consists of three phases: inflammation, proliferation and remodelation. Problems in any of these can lead to chronic wounds. The disease diabetes, for example, induces systemic production of free radicals, and also the antioxidant capacity decreases, which induces severe tissue damage decreasing the healing process. The diabetic disease state can also disrupt the balance between promoting vessel growth and proliferation and promoting vessel maturation and quiescence. The idea was to develop an antioxidant extract loaded matrix and evaluate the in vitro released antioxidant activity by the comparison between two spectrometric techniques to obtain a model dressing that could provide the biological advantages of both starting materials, increased vascularization for the natural latex matrix, and antioxidant activity for the S. marginata extract. According to FTIR analysis, matrix and extract did not interact chemically. Furthermore, at 67 h, up to 27% of all incorporated extract was released. The SEM images showed a portion of extract on the matrix surface, being responsible for the burst release. On the other hand, another portion remains within the matrix, being responsible for the slower release. The extract antioxidant activity was maintained even after its incorporation into the matrix. The comparison between the results obtained showed that the fact that the DPPH EPR spectrum has a relatively simple signal due only to the free radical is an advantage in relation to the optical spectroscopy. Based on the obtained results, it was possible to conclude that matrix is able to load the extract and maintain its antioxidant activity. However, in vivo and clinical assays are needed in the future to prove the clinical efficiency of the developed dressing.

Diabetic macular oedema: under-represented in the genetic analysis of diabetic retinopathy.

Diabetic retinopathy, a complication of both type 1 and type 2 diabetes, is a complex disease and is one of the leading causes of blindness in adults worldwide. It can be divided into distinct subclasses, one of which is diabetic macular oedema. Diabetic macular oedema can occur at any time in diabetic retinopathy and is the most common cause of vision loss in patients with type 2 diabetes. The purpose of this review is to summarize the large number of genetic association studies that have been performed in cohorts of patients with type 2 diabetes and published in English-language journals up to February 2017. Many of these studies have produced positive associations with gene polymorphisms and diabetic retinopathy. However, this review highlights that within this large body of work, studies specifically addressing a genetic association with diabetic macular oedema, although present, are vastly under-represented. We also highlight that many of the studies have small patient numbers and that meta-analyses often inappropriately combine patient data sets. We conclude that there will continue to be conflicting results and no meaningful findings will be achieved if the historical approach of combining all diabetic retinopathy disease states within patient cohorts continues in future studies. This review also identifies several genes that would be interesting to analyse in large, well-defined cohorts of patients with diabetic macular oedema in future candidate gene association studies.

Remote control of glucose homeostasis in vivo using photopharmacology

Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas. These studies provide the first demonstration that photopharmacology may one day be applicable to the light-guided treatment of type 2 diabetes and other metabolic disease states in vivo in humans.

Mouse Specific Cleavage-Resistant RAGE Splice Variant.

Receptor for Advanced Glycation Endproducts (RAGE), a transmembrane, multi-ligand, pattern recognition receptor, has been implicated in a range of inflammatory disease including diabetes, cancers, and cardiovascular disease (CVD) [1]. In addition to the full length receptor, soluble form of RAGE (sRAGE) has been shown to prevent the development of numerous pathologic states, and therefore highlights RAGE as an attractive therapeutic target [2–7]. sRAGE lacks the trans-membrane domain and is secreted to the extracellular milieu [6]. RAGE and sRAGE share the entire extracellular portion encompassing the V, C1 and C2 immunoglobulin-like domains (Fig 1). This feature renders sRAGE to function as a decoy that binds ligands and reduces the inflammatory signaling capacity of its membrane-bound counterpart [5, 7]. The importance of sRAGE is underscored by clinical cohort studies showing that serum sRAGE levels are correlated with clinical disease states including CVD, diabetes, cancer and various inflammatory disease states [6, 8].

Patient Satisfaction With Pharmacist-Led Chronic Disease State Management Programs

Purpose: To assess patient satisfaction, perception of self-management, and perception of disease state knowledge with pharmacist-led diabetes and cardiovascular disease state management (DSM) programs. Methods: A self-insured chain of grocery store pharmacies in the Kansas City metropolitan area administers pharmacist-led diabetes and cardiovascular DSM programs for eligible employees and dependents. A modified version of the Diabetes Disease State Management Questionnaire was used to assess patient satisfaction with the DSM programs. Demographic information was also collected. Survey items were based on a 5-point Likert scale (1 = strongly disagree and 5 = strongly agree). Patients were eligible to complete the survey if he or she had been in at least 1 DSM program for 6 months. Data were assessed using descriptive statistics and analysis of variance. Results: Across 20 pharmacies, 281 eligible participants were identified, and 46% (n = 128) completed a survey. Means for summed items relating to overall satisfaction (8 items), self-management (5 items), and knowledge (4 items) were 36.6/40 (standard deviation [SD] = 3.9), 20.9/25 (SD = 3.4), and 17.6/20 (SD = 2.1), respectively. Participant comments further indicated that the program and pharmacists are helpful and increase motivation and accountability. Conclusions: Positive patient responses to the program support use of pharmacist-led DSM programs.

Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes.

Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.

A microfluidic interface for the culture and sampling of adiponectin from primary adipocytes.

Secreted from adipose tissue, adiponectin is a vital endocrine hormone that acts in glucose metabolism, thereby establishing its crucial role in diabetes, obesity, and other metabolic disease states. Insulin exposure to primary adipocytes cultured in static conditions has been shown to stimulate adiponectin secretion. However, conventional, static methodology for culturing and stimulating adipocytes falls short of truly mimicking physiological environments. Along with decreases in experimental costs and sample volume, and increased temporal resolution, microfluidic platforms permit small-volume flowing cell culture systems, which more accurately represent the constant flow conditions through vasculature in vivo. Here, we have integrated a customized primary tissue culture reservoir into a passively operated microfluidic device made of polydimethylsiloxane (PDMS). Fabrication of the reservoir was accomplished through unique PDMS "landscaping" above sampling channels, with a design strategy targeted to primary adipocytes to overcome issues of positive cell buoyancy. This reservoir allowed three-dimensional culture of primary murine adipocytes, accurate control over stimulants via constant perfusion, and sampling of adipokine secretion during various treatments. As the first report of primary adipocyte culture and sampling within microfluidic systems, this work sets the stage for future studies in adipokine secretion dynamics.

Evaluation of Patient Satisfaction with Diabetes Management Provided by Clinical Pharmacists in the Patient-Centered Medical Home

The patient-centered medical home (PCMH) model is a multidisciplinary, team-based approach to healthcare that focuses on actively involving the patient in clinical decision making. Multiple studies have demonstrated improved clinical outcomes from utilizing clinical pharmacists in the primary care setting, particularly in management of diabetes. No study has evaluated patient satisfaction with pharmacist in the PCMH model. Our objective was to evaluate patient satisfaction of care received in pharmacist-managed primary care clinics among patients with diabetes mellitus within the PCMH. This study was a single-center, cross-sectional analysis of patients who were seen by a clinical pharmacy specialist (CPS). The setting for this study was eight outpatient primary care clinics within a Veterans Affairs healthcare system where diabetes management services were provided by eight CPSs. A total of 1,468 patients with a hemoglobin A1c >7.0 % who were seen in clinic by a CPS at the primary care clinics between 1 October 2008 and 1 April 2012 were mailed the Modified Diabetes Disease State Management Questionnaire (DDSM-QM). The DDSM-QM was a 15-item questionnaire that assessed overall patient satisfaction with pharmacist care, as well as patient satisfaction within three major domains: 'service,' 'self-management,' and 'knowledge'. A response rate of 42.7 % was attained, with 627 patients consenting to participate by completing and returning the self-administered questionnaire. The mean overall satisfaction score was 90.6 ± 10.6 % (mean ± standard deviation). Mean percentage scores within the 'service,' 'knowledge,' and 'self-management' domains were 92.0 ± 10.8, 89.7 ± 11.3, and 89.2 ± 12.0 %, respectively. Patients with diabetes seen by a CPS within the PCMH model were very satisfied with the care they received overall.

Sex, sex steroids, and diabetic cardiomyopathy: making the case for experimental focus

More than three decades ago, the Framingham study revealed that cardiovascular risk is elevated for all diabetics and that this jeopardy is substantially accentuated for women in particular. Numerous studies have subsequently documented worsened cardiac outcomes for women. Given that estrogen and insulin exert major regulatory effects through common intracellular signaling pathways prominent in maintenance of cardiomyocyte function, a sex-hormone:diabetic-disease interaction is plausible. Underlying aspects of female cardiovascular pathophysiology that exaggerate cardiovascular diabetic risk may be identified, including increased vulnerability to coronary microvascular disease, age-dependent impairment of insulin-sensitivity, and differential susceptibility to hyperglycemia. Since Framingham, considerable progress has been made in the development of experimental models of diabetic disease states, including a diversity of genetic rodent models. Ample evidence indicates that animal models of both type 1 and 2 diabetes variably recapitulate aspects of diabetic cardiomyopathy including diastolic and systolic dysfunction, and cardiac structural pathology including fibrosis, loss of compliance, and in some instances ventricular hypertrophy. Perplexingly, little of this work has explored the relevance and mechanisms of sexual dimorphism in diabetic cardiomyopathy. Only a small number of experimental studies have addressed this question, yet the prospects for gaining important mechanistic insights from further experimental enquiry are considerable. The case for experimental interrogation of sex differences, and of sex steroid influences in the aetiology of diabetic cardiomyopathy, is particularly compelling-providing incentive for future investigation with ultimate therapeutic potential.

Update on the Evaluation of Repeated Stone Formers

Office management of stone disease is an important component of a urologist's practice. Evaluation should include analysis of stone composition, 24-hour urine studies, identification of modifiable risk factors, and targeted dietary, lifestyle, and/or medical therapy. A sizeable portion of investigated etiologies and risk factors for stone disease have centered on the complex interplay between obesity, diabetes, and other disease states that comprise the metabolic syndrome. Alternatives to traditional preventive therapy, such as probiotics and various fruit juices, are still being studied but may prove useful adjuncts to traditional preventive therapy, where the mainstays remain increased fluid intake, dietary modification, and pharmacologic therapy. Future studies on preventive therapy of urolithiasis are likely to focus on strategies to increase compliance, cost-effectiveness, and systems-based implementation.

High-fat diet and age-dependent effects on enteric glial cell populations of mouse small intestine

Diabetes and obesity are increasing in prevalence at an alarming rate throughout the world. Autonomic diabetic neuropathy is evident in individuals that experience a long-standing diabetic disease state, and gastrointestinal (GI) dysmotility is thought to be the outcome of neuropathies within the enteric nervous system (ENS) of these patients. To date, an analysis of enteric glial cell population changes during diabetic symptoms has not been performed, and may bring insight into disease pathology and neuropathy, given glial cell implications in gastrointestinal and neuronal homeostasis. Diabetes and obesity were monitored in C57Bl/6J mice fed a 72% high-fat diet, and duodenal glial expression patterns were evaluated by immunohistochemistry and RT-PCR for S100β, Sox10 and GFAP proteins and transcripts, as well as transmission electron microscopy (TEM). The high-fat diet caused obesity, hyperglycemia and insulin resistance after 4 weeks. These changes were associated with a significant decline in the area density indices of mucosa-associated glial cell networks, evidenced by S100β staining at 8 and 20 weeks. All three markers and TEM showed that myenteric glial cells were unaffected by early and late disease periods. However, analysis of Sox10 transcript expression and immunoreactivity showed a diet independent, age-associated decline in glial cell populations. This is the first study showing that mucosal glia cell damage occurs during diabetic symptoms, suggesting that mucosal enteric glia injury may have a pathophysiological significance during this disease. Our results also provide support for age-associated changes in longitudinal studies of enteric glial cells.

益气养阴化瘀法治疗糖尿病肾病的用药策略

目的：在KDOQI糖尿病指南和慢性肾脏病指导下，结合中医对糖尿病和糖尿病肾病的病因病机的认识，旨在揭示益气养阴化瘀法治疗DN的用药规律与机理。方法：基于KDOQI的糖尿病和慢性肾脏病指南，选取益气养阴化瘀法治疗DN的文献，寻找有关药物对糖尿病和慢性肾脏病的用药规律与机理。结果与结论：气阴两虚，瘀血阻肾是DN基本病机，益气养阴化瘀法是治疗DN的基本治法。益气养阴化瘀法治疗DN的用药规律为：在益气、养阴、活血化瘀类中草药中注重选取降糖、降压、调脂、抗凝类的中药；同时注重选取护肾、抗肾脏纤维化类中药保护肾功能。益气养阴化瘀法治疗DN的中药药理机制为：降糖、降压、调脂、抗凝、阻止肾脏纤维化。 Objective: KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease state that: controlling blood sugar, lowering blood pressure, regulating blood lipids, anticoagulation, preventing renal fibrosis, controlling proteinuria, controlling protein intake, reducing weight and so on are effective ways for prevention and treatment of diabetes and DN. This study aims to reveal herbal administration regularity and mechanism of tonifying qi, nourishing yin and dissolving stasis method (TQNYDSM) for treating DN. Method: Based on KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease, we select literatures of DN treated by TQNYDSM, looking for herbal administration regularity and mechanism of TQNYDSM for Treating DN. Results and Conclusion: Deficiency of both qi and yin, renal blood stasis is the key pathogenesis of DN, TQNYDSM is the DN basic treatment method. Herbal Administration Regularity of TQNYDSM for Treating DN: try to add traditional Chinese medicine with effects on lowering blood sugar, blood pressure, regulating lipid, anticoagulation, against renal fibrosis into the prescription to protect renal function. Herbal mechanism of TQNYDSM for treating DN: hypoglycemic, antihypertensive, lipid-lowering, anticoagulation, preventing renal fibrosis.