Subset Of Diabetic Patients Research Articles

Comparison of Nonalbuminuric and Albuminuric Diabetic Kidney Disease Among Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BackgroundDiabetic kidney disease (DKD) is one of most common complications of diabetes. Recently, the classical phenotype of DKD, which is characterized by albuminuria preceding renal insufficiency, has been challenged since a subset of diabetic patients with renal insufficiency but without albuminuria has been increasingly reported. However, the available evidence is inconsistent. Thus, the present systematic review will assess and summarize the available data regarding nonalbuminuric diabetic kidney disease (NADKD).MethodsPubMed, Embase, and Cochrane were searched for clinical trials related to NADKD. The results were limited to full-text articles published in English, without restrictions on the publication time. The quality of clinical trials was appraised, and the data were extracted. Meta-analysis was conducted using a random-effects model. Descriptive analysis was performed if the data were insufficient.ResultsA final total of 31 articles were included in this review. The meta-analysis of 18 studies showed that compared with albuminuric DKD, patients with NADKD were older (MD = 1.04 years old, 95% CI [0.52, 1.57], p < 0.05); were more often women (Male RR = 0.74, 95% CI [0.68, 0.81], p < 0.05); had shorter diabetes duration (MD = −2.9 years, 95% CI [−3.63, −2.18], p < 0.05), lower HbA1c levels (MD = −0.34%, 95% CI [−0.42, −0.25], p < 0.05), and lower blood pressure (systolic blood pressure MD = −6.21 mmHg, 95% CI [−9.41, −3.0], p < 0.05; diastolic blood pressure MD = −1.27 mmHg, 95% CI [−2.15, 4.0], p < 0.05); less frequently experienced diabetic retinopathy (RR = 0.58, 95% CI [0.51, 0.67], p < 0.05); and less frequently used renin–angiotensin–aldosterone system (RAAS) inhibitors. The underlying pathology of NADKD might be different from that of the classic phenotype of DKD, which is associated with more advanced tubulointerstitial and vascular lesions but mild typical glomerular lesions. The annual estimated glomerular filtration rate decline tended to be lower in patients with NADKD than in those with albuminuric DKD. The risk for cardiovascular disease, end-stage renal disease, and all-cause death was lower for patients with NADKD than patients with albuminuric DKD.ConclusionsThe prevalence of NADKD has increased in recent decades, and its characteristics, pathology, and prognosis are different from those of albuminuric DKD; thus, diagnosis and treatment strategies should be different. More attention should be given to this phenotype.

Euglycemic diabetic ketoacidosis: Etiologies, evaluation, and management.

Diabetic ketoacidosis is an endocrine emergency. A subset of diabetic patients may present with relative euglycemia with acidosis, known as euglycemic diabetic ketoacidosis (EDKA), which is often misdiagnosed due to a serum glucose <250mg/dL. This narrative review evaluates the pathogenesis, diagnosis, and management of EDKA for emergency clinicians. EDKA is comprised of serum glucose <250mg/dL with an anion gap metabolic acidosis and ketosis. It most commonly occurs in patients with a history of low glucose states such as starvation, chronic liver disease, pregnancy, infection, and alcohol use. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which result in increased urinary glucose excretion, are also associated with EDKA. The underlying pathophysiology involves insulin deficiency or resistance with glucagon release, poor glucose availability, ketone body production, and urinary glucose excretion. Patients typically present with nausea, vomiting, malaise, or fatigue. The physician must determine and treat the underlying etiology of EDKA. Laboratory assessment includes venous blood gas for serum pH, bicarbonate, and ketones. Management includes resuscitation with intravenous fluids, insulin, and glucose, with treatment of the underlying etiology. Clinician knowledge of this condition can improve the evaluation and management of patients with EDKA.

Diabetic retinopathy, diabetic macular edema, and cardiovascular risk: the importance of a long-term perspective and a multidisciplinary approach to optimal intravitreal therapy.

Diabetic retinopathy (DR), diabetic macular edema (DME), and cardiovascular disease (CVD) resulting from vascular damage from persistently elevated blood glucose levels are among the serious secondary pathologies associated with long-standing diabetes mellitus. The established link between DR and CVD suggests the need for appropriate and early management of patients with diabetes to minimize CV risk. This is of particular importance in patients with recent, or a history of, major CV events. Early management of DR is a complex task that requires comprehensive evaluation and a multidisciplinary approach to manage complications, risk factors, and interactions between different aspects of the disease. Anti-vascular endothelial growth factor (VEGF) agents have become an important therapeutic modality in ophthalmology. However, their use is contraindicated in patients with DR and/or DME with a CV event in the previous 3months. In patients with DME, corticosteroids target the multifaceted inflammatory pathways involved in the pathogenesis of DR, with a broader spectrum of action than anti-VEGF agents. In this context, recent guidelines suggest the use of corticosteroids, and in particular dexamethasone intravitreal implant, as a well-tolerated and efficacious first-line treatment in patients with high CV risk, such as a history of or recent major CV events. This review focuses on the subset of diabetic patients with a prior CV event, DR, and DME and discusses the need for a holistic approach in evaluating the optimal therapeutic choice for the care of the individual patient, supported by real-world clinical experience on long-term dexamethasone intravitreal implant therapy.

Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKε and Reveal Mechanisms for Selective Inhibition.

Chronic low-grade inflammation is a hallmark of obesity, which is a risk factor for the development of type 2 diabetes. The drug amlexanox inhibits IκB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) to promote energy expenditure and improve insulin sensitivity. Clinical studies have demonstrated efficacy in a subset of diabetic patients with underlying adipose tissue inflammation, albeit with moderate potency, necessitating the need for improved analogs. Herein we report crystal structures of TBK1 in complex with amlexanox and a series of analogs that modify its carboxylic acid moiety. Removal of the carboxylic acid or mutation of the adjacent Thr156 residue significantly reduces potency toward TBK1, whereas conversion to a short amide or ester nearly abolishes the inhibitory effects. IKKε is less affected by these modifications, possibly due to variation in its hinge that allows for increased conformational plasticity. Installation of a tetrazole carboxylic acid bioisostere improved potency to 200 and 400 nM toward IKKε and TBK1, respectively. Despite improvements in the in vitro potency, no analog produced a greater response in adipocytes than amlexanox, perhaps because of altered absorption and distribution. The structure-activity relationships and cocrystal structures described herein will aid in future structure-guided inhibitor development using the amlexanox pharmacophore for the treatment of obesity and type 2 diabetes.

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Rosuvastatin for Reduction of Myocardial Damage during Coronary Angioplasty - the Remedy Trial.

Periprocedural myocardial infarction (MI) is a frequent complication of percutaneous coronary intervention (PCI). Statins might reduce its incidence. The aims of the present studyare to assess whether such benefit is a class-effect or whether differences exist between various lipid-lowering strategies and whether cardioprotectionis exerted by increasing circulating endothelial progenitor cells (EPCs). The REMEDY study will enroll a total of 1080 patients submitted to elective PCI. Eligible patients will be randomized into 4 groups: 1) placebo; 2) atorvastatin (80mg+40mg before PCI); 3) rosuvastatin (40mg twice before PCI); and 4) rosuvastatin (5mg) and ezetimibe (10mg) twice before PCI. Peri-procedural MI is defined as an elevation of markers of cardiac injury (either CK-MB or troponin I or T) values >5x the upper reference limit estimated at the 99th percentile of the normal distribution, or a rise >20% in case of baseline values already elevated. EPCs will be assessed before, at 24h and - in a subset of diabetic patients - at 3months after PCI (EPC-substudies). The primary endpoint of the main REMEDY study is the rate of peri-procedural MI in each of the 4 treatment arms. Secondary endpoints are the combined occurrence of 1-month major adverse events (MACE, including death, MI, or the need for unplanned revascularization); and any post-procedural increase in serum creatinine. Endpoints of the EPC-substudies are the impact of tested regimens on 1) early (24-h) and 3-month EPC levels and functional activity; 2) stent strut re-endothelialization and neointimal hyperplasia; 3) 1-year MACE. REMEDY will add important information on the cardioprotective effects of statins after PCI.

Change in microRNA profile predicts diabetes associated renal pathology non‐invasively

Over a third of diabetes patients develop diabetic nephropathy. To categorize such subset of diabetic patients there is a need for non‐invasive biomarker that regulate very early in the pathogenesis. We tested miRNAs in urinary exosomes (UE) as candidate molecule using serial urine sample from diabetic rats before and during the course of diabetes. Wistar rats were injected with streptozotocin (50 mg/kg. body weight). For exosome isolation, serial urine samples were collected before (ND) and after diabetes induction. Differentially expressed miRNAs were identified using small RNA sequencing, followed by Taqman based qRT‐PCR validation on UE RNA. Histomorphometric analysis of kidneys was performed at the end of the study. Heat maps revealed 114 miRNAs, common at all 4 stages, including miR 215 and 494, miRs reported to have predominant expression in the kidney relative to other tissues. Moreover, certain miRNAs, such as miR 451 and 10, although absent in the common heat maps, had significantly altered expression at 9th week of diabetes relative to ND or initial diabetic period i.e., 3rd week. qRT‐PCR validated significantly decreased levels of all 4 miRNAs in UE after diabetes induction. At 9th week, however, miR 494 restored to similar level as ND stage while miR 451 showed robust rise. Moreover, levels of 215 and 494 were significantly different between the diabetic rats with severe renal pathology, higher glomerulosclerosis index, relative to diabetic rats with moderate pathology. Overall, the findings suggest that change in miRNA expression in urinary exosomes during the course of diabetes can non‐invasively predict extent of renal pathology. DBT funding to ST

Effect of eprosartan-based antihypertensive therapy on coronary heart disease risk assessed by Framingham methodology in Canadian patients with diabetes: results of the POWER survey.

ObjectiveAs part of the Physicians’ Observational Work on Patient Education According to their Vascular Risk (POWER) survey, we used Framingham methodology to examine the effect of an eprosartan-based regimen on total coronary heart disease (CHD) risk in diabetic patients recruited in Canada.MethodsPatients with new or uncontrolled hypertension (sitting systolic blood pressure [SBP] >140 mmHg with diastolic blood pressure <110 mmHg) were identified at 335 Canadian primary care practices. Initial treatment consisted of eprosartan 600 mg/day, which was later supplemented with other antihypertensives as required. Outcomes included change in SBP at 6 months (primary objective) and absolute change in the Framingham 10-year CHD risk score (secondary objective).ResultsWe identified an intention-to-treat diabetes population of 195 patients. Most diabetic patients were prescribed two or more antihypertensive drugs throughout the survey. Mean reductions in SBP and diastolic blood pressure were 20.8±14.8 mmHg and 9.5±10.7 mmHg, respectively. The overall absolute mean 10-year CHD risk, calculated using Framingham formulae, declined by 2.9±3.5 points (n=49). Average baseline risk was higher in men than women (14.8±8.6 versus 5.6±1.8 points); men also had a larger average risk reduction (4.2±4.3 versus 1.5±1.3 points). The extent of absolute risk reduction also increased with increasing age (trend not statistically significant).ConclusionEprosartan-based therapy substantially reduced arterial blood pressure in our subset of diabetic patients; while there was a slight reduction in Framingham risk, there are indications from our data that both blood pressure control and the wider management of CHD risk in diabetic patients remains suboptimal in Canadian primary care.

Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome

Background: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. Methods: A total of 46 patients (27 female, mean age of 48.9 ± 11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. Results: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. Conclusion: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.

Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes.

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage.

163 Hyperglycemia-Induced Hyperplasia of Interstitial Cells of Cajal (ICC) and ICC Stem Cells (ICC-SC) Is Associated With Accelerated Gastric Emptying in Obese Diabetic LeprDb/Db Mice

Background & Aims: ICC depletion is the most common cellular change in diabetic gastroparesis. However, in up to 22% of diabetic patients with gastric symptoms, gastric emptying (GE) is accelerated, rather than delayed. The fate of ICC in these patients is unclear. Previously we reported ICC and ICC-SC hyperplasia in hyperinsulinemic, diabetic Lepr mice. Here, we studied the relationship between GE of solids and ICC/ICC-SC numbers, and investigated the contribution of insulin/IGF1-dependent Kit ligand (Kitl) expression and hyperglycemia-induced ERK MAPK activation to ICC/ICC-SC hyperplasia. Methods: Lepr (n=32) and agesexand strain-matched controls (n=30) were studied 13-65 weeks after the onset of diabetes. ICC and ICC-SC were quantified by flow cytometry. Serum insulin was measured by enzyme immunoassay. Oxidative stress was determined by measuring serum malondialdehyde (MDA) and gastric 8OHdG. GE of solids was analyzed by 13C breath test. Gene expression was studied by qRT-PCR and WB. Effects of high glucose were investigated in murine gastric ICC primary cultures, a conditionally immortalized cell line derived from murine gastric ICC (ICL2A), and in an ICC-SC line isolated from the mouse stomach (2XSCS2F10). ERKMAPK signaling was evaluated byWB and pharmacological inhibition of MAPKK with PD98059. Cell proliferation and apoptosis were determined byMTS assay andCaspase Glo-3/7 assay, respectively. Results: Leprmice had significantly higher blood glucose (median[IQR]: 515[462;577] vs. 124[115;134] mg/dL; P,0.001) and serum insulin levels. Serum MDA and gastric 8OHdG were moderately increased (2.4and 2.2-fold, respectively, P,0.001). In Lepr mice, ICC and ICC-SC increased 2.0±0.1-fold (P,0.001) and 1.5±0.3-fold (P,0.05), respectively, and GE was accelerated (T1/2: 67±10 vs. 100±11 min; P,0.05). GE was similarly accelerated in Kit mice with generalized ICC hyperplasia due to an activating Kit mutation. In Lepr mice, total/soluble Kitl mRNA and Kitl protein were reduced. High glucose (500 mg/dL) significantly increased the numbers of primary ICC and stimulated proliferation and ERK MAPK phosphorylation in ICL2A and 2XSCS2F10 cells. PD98059 (20 μM) inhibited cell proliferation induced by high glucose without affecting basal proliferation. In contrast, osmotic stress induced by mannitol had no effect on ICC numbers, cell proliferation and ERK MAPK phosphorylation. ICC and ICC-SC were resistant to apoptosis induced by hyperglycemia at levels seen in Lepr mice. Conclusions: In the absence of major oxidative stress, hyperglycemia induces ICCSC and ICC hyperplasia via the ERK MAPK pathway even in the presence of reduced Kitl signaling. ICC hyperplasia, in turn, leads to accelerated GE and may contribute to gastric symptoms in a subset of diabetic patients. Grant support: NIH DK58185, DK68055.

Common Variants in the Type 2 Diabetes KCNQ1 Gene Are Associated with Impairments in Insulin Secretion During Hyperglycaemic Glucose Clamp

BackgroundGenome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients.MethodologyThe KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp.Principal FindingsWe found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07–1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications.ConclusionsCommon variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism.

Diabetic nephropathy: Progression and pathophysiology

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ~30% of type 1 and type 2 diabetic patients. This review focuses on the progression and pathophysiological aspects of the condition. The natural history of diabetic nephropathy is characterized by specific renal morphological and functional alterations. Features of early diabetic renal changes are microalbuminuria (30-300mg/day), glomerular hyperfiltration, glomerular and renal hypertrophy, increased basement membrane thickness, and mesangial expansion with the accumulation of extracellular matrix proteins such as collagen, fibronectin, and laminin. Advanced diabetic nephropathy is characterized by macroalbuminuria ( >300mg/day), a progressive decline in glomerular filtration rate, decreasing creatinine clearance, glomerulosclerosis, and interstitial fibrosis. Although poor glycemic control is an important risk factor, glycemia does not fully explain why only a subset of diabetic patients progress to end stage renal disease. Several decades of extensive research has elucidated various pathways to be implicated in the development of diabetic kidney disease such as systemic and glomerular hypertension, advanced glycation endproducts and the aldose reductase system. Furthermore, hemodynamic factors, the reninangiotensin system, the endothelin system, the intracellular signaling molecule protein kinase C, transforming growth factor-s, growth hormone, insulin like growth factors, vascular endothelial growth factor, and platelet-derived growth factor are believed to be involved in the pathogenesis. Thus, there are clearly many points at which therapeutic approaches could be tried to provide renoprotection in diabetes. It is likely that due to its complexity, targeting multiple points in altered metabolism in the diabetic kidney will be more successful in attenuating the development of diabetic nephropathy, rather than a single approach.

The Relationship Between Diabetes Mellitus and Exfoliation Syndrome in a United States Veterans Affairs Population

Earlier studies suggest that an inverse relationship exists between diabetes mellitus and exfoliation syndrome (ES). We evaluated the relationship between diabetes mellitus and ES while controlling for important covariates. In addition, we investigated whether glucose control, as measured by glycosylated hemoglobin (HbA1c) levels, differed between the subset of diabetic patients with and without ES. This retrospective case-control study included outpatients seen in Veterans Affairs Boston Healthcare System eye clinics. Exfoliation cases (n=328) and controls (n=328) were drawn from the same clinic and matched for age. For all participants, we ascertained diabetes status, sex, race, body mass index, and glaucoma status. Among patients with diabetes mellitus, we collected the 5 most recent HbA1c levels and type of diabetes control. Diabetes mellitus was present in 96 (29.2%) cases and in 114 (34.8%) controls. In multivariate analysis, no statistically significant relationship between diabetes mellitus and ES (OR=0.77; 95% CI, 0.55-1.07) was identified. When glaucoma status was added as a covariate, the results were essentially unchanged (OR=0.81, 95% CI, 0.57-1.14). Adjusted mean HbA1c levels were similar in diabetic patients with (6.85%; 95% CI, 6.66-7.04) and without (7.05%; 95% CI, 6.87-7.22) ES (P=0.14). In this predominately white male population, we did not observe a statistically significant relationship between diabetes mellitus and ES. In addition, HbA1c levels did not vary among diabetic patient based on exfoliation status.

Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications

AimsTo test autoantibodies from subsets of diabetes with painful neuropathy, maculopathy and nephropathy for effects in neurons. MethodsProtein-A eluates from plasma of 27 diabetic and 19 age-matched controls were tested for effects on endothelial cell survival, and neurite outgrowth in rat pheochromocytoma PC12 cells. Painful diabetic neuropathy or control autoantibodies were compared for binding to PC12-derived heparan sulfate proteoglycans. The mechanism of the effects from pathologic autoantibodies was investigated by changes in intracellular calcium in endothelial cells, whole cell current in neurons, or using the Rho kinase inhibitor Y27632. ResultsAutoantibodies from diabetic patients with maculopathy, nephropathy, and painful neuropathy (n=5) caused significantly greater mean inhibition of neurite outgrowth (p<0.005) than diabetic or control patients with fewer or no complications (n=30). Painful diabetic autoantibodies (3μg/mL) bound neuronal heparan sulfate proteoglycan (HSPG) more than autoantibodies from diabetic or control subjects without painful neuropathy (p<.0001). Inhibition of PC12 neurite outgrowth by the painful neuropathy antibodies was completely prevented by 1μM concentrations of Y27632. ConclusionThese results suggest anti-endothelial and anti-neuronal effects from auto-antibodies in a subset of diabetic patients with a cluster of microvascular complications.

Hard to heal pressure ulcers (stage III–IV): Efficacy of injected activated macrophage suspension (AMS) as compared with standard of care (SOC) treatment controlled trial

The objective of this study was to compare local injections of AMS with SOC treatments for stage III and IV pressure ulcers in elderly patients. It was designed as historically prospective 2-arms non-parallel open controlled trial, and conducted in a department of geriatric medicine and rehabilitation of a university affiliated tertiary hospital. We studied 100 consecutive elderly patients with a total of 216 stage III or IV pressure ulcers, 66 patients were assigned to the AMS group and had their wounds injected, while 38 patients were assigned to the SOC group. Primary outcome was rate of complete wound closure. Time to complete wound closure and 1-year mortality served as secondary outcomes. Statistical analyses were performed at both patient and wound levels. Percentage of completely closed wounds (wound level and patient level) were significantly better ( p < 0.001/ p < 0.001, respectively) in all patients in favor of AMS, as well as in the subset of diabetic patients ( p < 0.001/ p < 0.001). Similarly, AMS proved significantly better for the subset of those with leg ulcers and with baseline wounds ≤15 cm 2, compared with SOC. There were no statistically significant differences with regard to time to complete closure or 1-year mortality rates in the two groups. It is concluded that there is a significant difference in favor of stage III and IV wound closure rates by AMS, as compared with SOC treatments.

Type 2 Diabetes: Local Inflammation and Direct Effect of Bacterial Toxic Components

Objectives: It has been known for almost a century that amyloidosis is frequently associated with chronic bacte- rial infection. Islet amyloid deposit is characteristic of type 2 diabetes. Periodontal disease, which is predominantly caused by several Gram negative bacteria, is a risk factor for type 2 diabetes. The goal of the study was to explore whether bacte- ria or their toxic components may play a role in type 2 diabetes. Material & Methods: The pancreas in 22 autopsy cases was analyzed for the presence of lipopolysaccharide (LPS), bacte- rial peptidoglycan (BPG) and local inflammatory processes. Ten of the cases had clinically diagnosed type 2 diabetes, and 12 were age matched controls. Results: The results of an immunohistochemical analysis showed the presence of LPS and BPG in association with islet amyloid deposits in all the 10 diabetic cases as well as in 3 controls with clinically silent amyloid deposits. Chlamydia pneumoniae and Helicobacter pylori specific antigens were detected in the affected islets in a subset of diabetic patients. Clumps of HLA-DR positive activated macrophages, abundant immunoreactivity to the activated complement compo- nents C3d, C4d and C5b-9, the terminal attack complex, and a moderate numbers of T4 and particularly of T8 lympho- cytes were present in the pancreas of all diabetic cases. Conclusions: These results suggest that bacteria or their slowly degradable remnants may initiate and sustain chronic in- flammation in the pancreas and therefore play a role in the pathogenesis of type 2 diabetes. They also indicate that local immune responses, including activation of the classical complement pathway are important in the pathogenesis of type 2 diabetes. There may also be some involvement of the adaptive immune system. Further investigations are essential since a parallel use of antibacterial and anti-inflammatory drugs may prevent or slow down the disease progression.

Nephrotoxicity of iodixanol versus ioversol in patients with chronic kidney disease: The Visipaque Angiography/Interventions with Laboratory Outcomes in Renal Insufficiency (VALOR) Trial

Iso-osmolar contrast medium iodixanol has been reported to be less nephrotoxic than selected low-osmolar contrast media (LOCM) in chronic kidney disease (CKD) patients with diabetes mellitus. This study compared the nephrotoxicity of iodixanol and the LOCM ioversol in CKD patients undergoing coronary angiography. This is a prospective double-blind trial in 337 patients with stable CKD who were randomly assigned to receive the iso-osmolar contrast medium iodixanol or the LOCM ioversol. The co-primary end points were the mean peak percentage change (MPPC) in baseline serum creatinine and the incidence of contrast-induced nephropathy (rise of > 0.5 mg/dL in baseline serum creatinine within 72 hours postcontrast) for the 2 contrast media in the 72-hour period after contrast administration. Prespecified analyses included stratification on diabetic state and the use of N-acetylcysteine. In the 299 patients with complete post-contrast media creatinine data, the incidence of contrast-induced nephropathy was 21.8% in the iodixanol subjects and 23.8% in the ioversol subjects (P = .78). For all patients, the MPPC was 14.7% with iodixanol and 20.0% with ioversol (P = .06), whereas in the subset of diabetic patients, this value was significantly lower in the iodixanol (12.9%) compared with the ioversol subjects (22.4%, P = .01). Overall, the nephrotoxicity associated with iodixanol was not significantly different from that observed with ioversol in CKD patients undergoing coronary angiography, although in diabetic patients, MPPC was significantly lower in the iodixanol group.

The use of a compliant EHR when providing clinical pathway driven care to a subset of diabetic patients: recommendation from a Working Group.

The Belgian National Health Insurance Institute (NHII) and other Healthcare Authorities intend to improve the quality of care through promoting clinical pathway driven care and by optimising cooperation between the responsible primary care physician and the diabetologist. Patients and healthcare professionals are granted some (financial) benefits when meeting the conditions defined in a mutual agreement.This article describes the conditions and the functional requirements to be met by an EHR to enable and to maximise the benefits of a clinical pathway driven patient care to a specific group of diabetic type 2 patients, based on a mandate issued by the NHII.The generic and specific functional requirements are then translated in test criteria for certification and prioritised in an implementation plan.

Antiplatelet therapy for primary and secondary prevention in Jordanian patients with diabetes mellitus

Introduction Guidelines for diabetes treatment recommend the routine use of aspirin in patients with diabetes mellitus (DM) who have cardiovascular disease (CVD), those with at least one CVD risk factor, and for anyone with DM who is>30 years of age or, if contraindicated, an alternative antiplatelet agent. We evaluated the adherence to these recommendations in a subset of diabetic patients in Jordan, and identified physician and patient characteristics associated with the use of antiplatelet therapy. Materials and methods A cross–sectional observational study conducted in randomly selected outpatient clinics. The study included 199 adult patients with DM who were eligible for antiplatelet prophylaxis. Review of medical charts and direct interviews with patients were performed to obtain information on demographic characteristics of the patients, clinical factors and medication prescription. Bivariate analysis and multivariate logistic regression methods were used to determine what factors were related to antiplatelet drug use. Results Among diabetic patients eligible for antiplatelet prophylaxis, the prevalence of antiplatelet drug use for primary or secondary prevention was 84%. Factors associated with antiplatelet prophylaxis were male gender (odds ratio, OR 2.97), presence of angina (OR 3.00), history of myocardial infarction (OR 3.75), history of coronary revascularization (OR 3.12), five or more prescription medications (OR 4.61), and physician’s specialty other than endocrinology ( OR 4.35). Conclusions Adherence rates to the international guidelines regarding routine antiplatelet prophylaxis in adults with DM who are eligible for such prophylaxis are suboptimal. Efforts towards increasing these rates of antiplatelet prophylaxis are necessary.