Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: Their role in the prediction of vascular complications

Background and objectiveEndothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications.MethodsFifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay.ResultssEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p = 0.02, and p = 0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p = 0.04.ConclusionPatients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM.     

A quick,simple method for detecting circulating fluorescent advanced glycation end-products: Correlation with in vitro and in vivo non-enzymatic glycation

ObjectiveAdvanced glycation end-products (AGEs) constitute a highly heterogeneous family of compounds, relevant in the pathogenesis of diabetic complications, which could represent efficient biomarkers of disease progression and drug response. Unfortunately, due to their chemical heterogeneity, no method has been validated to faithfully monitor their levels in the course of the disease. In this study, we refine a procedure to quantitatively analyze fluorescent AGEs (fAGEs), a subset considered remarkably representative of the entire AGE family, and measure them in in vitro glycated BSA (gBSA) and in plasma and vitreous of diabetic rats, for testing its use to possibly quantify circulating AGEs in patients, as markers of metabolic control.MethodsfAGE levels were evaluated by spectrofluorimetric analysis in in vitro and in vivo experimental models. BSA was glycated in vitro with increasing D-glucose concentrations for a fixed time or with a fixed D-glucose concentration for increasing time. In in vivo experiments, streptozotocin-induced diabetic rats were studied at 1, 3, 6 and 12 weeks to analyze plasma and vitreous. To confirm the presence of AGEs in our models, non-diabetic rat retinal explants were exposed to high glucose (HG), to reproduce short-term effects, or in vitro gBSA, to reproduce long-term effects of elevated glucose concentrations. Rat retinal explants and diabetic retinal tissues were evaluated for the receptor for advanced glycation end-product (RAGE) by Western blot analysis.ResultsIn in vitro experiments, fluorescence emission showed glucose concentration- and time-dependent increase of fAGEs in gBSA (p ≤ 0.05). In streptozotocin-induced diabetic rats, fAGE in plasma and vitrei showed an increase at 6 (p ≤ 0.005) and 12 (p ≤ 0.05) weeks of diabetes, with respect to control. RAGE was time-dependently upregulated in retinas incubated with gBSA, but not with HG, and in diabetic retinal tissue, substantiating exposure to AGEs.ConclusionsApplying the proposed technique, we could show that fAGEs levels increase with glucose concentration and time of exposure in vitro. Furthermore, in diabetic rats, it showed that circulating fAGEs are similarly upregulated as those in vitreous, suggesting a correlation between circulating and tissue AGEs. These results support the use of this method as a simple and reliable test to measure circulating fAGEs and monitor diabetes progression.     

Paraoxonase 2 (PON2) decreases high glucose-induced macrophage triglycerides (TG) accumulation,via inhibition of NADPH-oxidase and DGAT1 activity: Studies in PON2-deficient mice

ObjectiveThe present study investigates the role of paraoxonase 2 (PON2) in the attenuation of macrophage triglycerides (TG) biosynthesis, and oxidative stress, under diabetic conditions.MethodsPeritoneal macrophages (MPM) from PON2-deficient and from C57BL/6 control mice were harvested and cultured under normal (5 mM) or high glucose concentration (30 mM), and evaluated for cellular TG metabolism as well as for their oxidative stress.ResultsIn PON2-deficient MPM vs. control MPM, under diabetic conditions (high glucose concentration), we observed substantial increment in TG accumulation (3 fold), TG biosynthesis (2.6 fold) and microsomal diacylglycerol acyltransferase1 (DGAT1) activity (+60%). Furthermore, in these cells we have demonstrated increased oxidative stress, as expressed by significant increment in cellular oxidative stress (+25%), macrophage-mediated LDL oxidation (+41%) and expression of the receptor for advanced glycation end products – RAGE (+18%). Apocynin, an NADPH-oxidase inhibitor, abolished the increment in MPM TG accumulation, MPM TG biosynthesis, and microsomal DGAT1 activity, as a result of PON2-deficiency, under diabetic conditions.ConclusionWe conclude that PON2 has a significant protective role against macrophage triglyceride accumulation, macrophage TG biosynthesis, microsomal DGAT1 activity and macrophage oxidative stress, under high glucose concentrations. We suggest that this protective effect may be mediated by PON2 through the attenuation of NADPH-oxidase activity. The use of appropriate means to increase macrophage PON2 expression can lead to attenuation in macrophage TG accumulation and in cellular oxidative stress, under diabetic conditions, and thus may contribute to the decrement in macrophage atherogenicity and foam cell formation, attenuating the development of vascular complications in diabetes mellitus.     

Modulation of CD36 protein expression by AGEs and insulin in aortic VSMCs from diabetic and non-diabetic rats

Background and aimIn type 2 diabetes, the interplay between cells and inflammatory mediators up-regulates CD36 expression in macrophages. The aim of this work was to investigate advanced glycation end products (AGE)-induced CD36 expression and its regulation by insulin in aortic vascular smooth muscle cells (VSMCs) from Goto–Kakisaki (GK) rats, a non-obese insulin model of both insulin resistance and type 2 diabetes. The context of overexpression of CD36 in aortas was also evaluated.Methods and resultsVSMCs were isolated and cultured from the aortas of GK rats and non-diabetic rats. The expression of proteins was evaluated by Western blot. The aortic production of superoxide anion (O₂^·−) was measured by luminescence on isolated tissue. AGEs and advanced oxidation protein products (AOPPs) were determined in plasma by fluorescence spectroscopy and spectrophotometry, respectively.AGE receptor (RAGE), NF-κB, and CD36 protein expression as well as O₂^·− production were higher in GK aortas than in control aortas, and AGEs and AOPPs were higher in GK plasma. In VSMCs from non-diabetic rats, insulin was able to reduce (10 nM) or suppress (100 nM) the protein overexpression of CD36 induced by AGEs–BSA. In contrast, in VSMCs from GK rats, insulin was unable to reduce AGEs–BSA-induced CD36 overexpression.ConclusionsThe results suggest an overexpression of CD36 in VSMCs from GK rats and impaired control by insulin. In the context of increased plasma AGEs, aortic RAGE overexpression and increased oxidative stress markers, the data are compatible with an AGEs induced CD36 overexpression in diabetes.     

Endothelial nitric oxide synthase (eNOS) is not upregulated in gastric mucosa of Helicobacter pylori (H. pylori)-positive patients with type 2 diabetes mellitus

AimTo evaluate the expression of eNOS and CD34 in gastric mucosa of Helicobacter pylori (H. pylori) positive diabetic patients, in correlation with glycaemic control and diabetic autonomic neuropathy (DAN).MethodsWe prospectively studied 49 diabetic type 2 patients (29 women, mean age 65.32 ± 8.56 years) and 30 control subjects (15 women, mean age 58.47 ± 12.40) that underwent endoscopy. Biopsies from the body and antrum were evaluated for H. pylori-gastritis, eNOS and angiogenic marker CD34 expression. Statistical analysis in correlation with mean glycosylated haemoglobin (HbA1c) of the last 3 years, and DAN was performed.ResultsThe two groups were matched for age (p = 0.144), sex (p = 0.335), H. pylori-infection (p = 0.617) and degree of gastritis (p = 0.78). eNOS and CD34 attenuated expression correlated with diabetes mellitus (DM) in the corpus (p = 0.009 and 0.02, respectively). eNOS and CD34 expression was upregulated in H. pylori-positive controls but not in H. pylori-positive diabetic patients (p = 0.010 and 0.007 for the corpus and p = 0.036 and 0.047 for the antrum, respectively). eNOS expression correlated with good glycaemic control (GGC) in the gastric corpus (p < 0.001) and antrum (p = 0.0037) and with absence of DAN (p = 0.009 and 0.036, respectively for the corpus and antrum).ConclusionChronic glycaemic control affects eNOS expression and angiogenesis in the gastric mucosa of patients with type 2 DM. eNOS expression is not upregulated in H. pylori-positive diabetic patients.     

The association between intensive glycemic control and vascular complications in type 2 diabetes mellitus: A meta-analysis

Background and AimIn patients with type 2 diabetes mellitus, the relationship between lowering glycated hemoglobin (HbA_1c) and macrovascular complications is not clear and therefore lowering the level of HbA_1c is controversial.Methods and ResultsWe searched for all randomized controlled trials comparing the effects of intensive and standard glycemic control on vascular events in patients with type 2 diabetes mellitus. The primary endpoint was combined macrovascular complications, including cardiac events, stroke and peripheral vascular disease. Fixed and random effect models were used to analyze the results.Eight studies were included according to selection criteria. The results showed no benefits of intensive glycemic control on macrovascular and microvascular complications (P > 0.1), but a higher rate of severe hypoglycemia (P < 0.00001) in the intensive control group when the target HbA_1c level was <7.0%. When the target HbA_1c level was lowered to 7.0–7.9%, intensive glycemic control showed benefits on the reduction of microvascular events (P < 0.05) without increasing the risk of severe hypoglycemia (P = 0.74), but no influence on macrovascular complications (P > 0.1).ConclusionThe results of this analysis suggest that a target HbA_1c level of 7.0–7.9% may be a better glycemic control target than that of <7.0% in patients with established type 2 diabetes mellitus.     

Plasma glycation adducts and various RAGE isoforms are intricately associated with oxidative stress and inflammatory markers in type 2 diabetes patients with vascular complications

BackgroundThe secondary vascular complications in diabetes mellitus (DM) are contributed by acute as well as inflammatory responses which get activated due to interaction between glycation adducts and respective receptors.AimThe present work was performed to understand the relationship between Advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE) interaction with oxidative stress and inflammation in vascular complications.MethodsFor the present work we recruited 103 controls, 200 patients with type 2 DM, and 200 patients with Diabetic complications. Different Plasma glycation adducts (fructosamine, carbonyls, AGEs, β-amyloid content, free amino groups, and free thiol groups); RAGE isoforms, level of antioxidant such as glutathione, catalase activity, nitric oxide level, total antioxidant capacity, and superoxide dismutase activity, as well as oxidative markers, and expression of Nε-carboxymethyl-lysine (CML), different isoforms of RAGE, NF-κB, and inflammatory markers were analyzed.ResultsGlycation adducts were higher in DM patients and more elevated in nephropathy patients where free amino groups and thiol groups lowered as compared to controls. sRAGE levels and expression were increased mainly in nephropathy. CML expression was higher in nephropathy patients. The antioxidant profile indicates a reduced level of different antioxidants while increased lipid peroxidation and intracellular ROS generation in DM and much higher in nephropathy patients. Expression of membrane RAGE, NF-κB, and inflammatory markers showed a remarkably increased level in DM patients with nephropathy.ConclusionThis work provides the first evidence of four different RAGE isoforms in diabetes and in complications. The glycation via the activation of RAGE, oxidative stress, and resultant inflammation plays a crucial role in the development of diabetic complications.     

PONI and its association with oxidative stress in type I and type II diabetes mellitus

ObjectiveParaoxonase (PON) is an antioxidant enzyme linked with cardiovascular disease (CVD), diabetes as it prevents LDL oxidation. The relation of PON with the other established risk factor of diabetic complications has not been looked into.Research design and methods370 subjects were included in the study. Dividing into four group, i.e. group I included type II DM (n = 220), group II was age matched control (n = 100), group III were type I DM (n = 25) and group IV (n = 25) were age matched control group. The protocol of the study was approved by the ethical committee of the institute. SOD, GSH, PON (paraoxonase and arylesterase activity), GHb, and MDA were estimated.ResultsA highly significant decrease in paraoxonase and arylesterase activity was seen in the type II DM (p < 0.0001) while in type I DM both the activity was not significant (p > 0.05). Paraoxonase and arylesterase activity of PONI showed a negative significant correlated with MDA (r = ?0.51, p < 0.0001 and r = ?0.23, p < 0.001) in type II DM but was not correlated in type I DM. The GHb and MDA levels were significantly increased (p < 0.0001) while the levels of SOD and GSH have been decreased in type I and type II DM.ConclusionPONI is definitely associated with development of the complications of diabetes. This may be due to the role of it as an antioxidant. As it also show a negative correlation with MDA like the other antioxidants studied.     

Association of glutathione-S-transferase with patients of type 2 diabetes mellitus with and without nephropathy

Statements of the problemHyperglycemia induced oxidative stress is implicated as a contributor to the onset and progression of type 2 diabetes mellitus (T2DM) and its complications like diabetic nephropathy (DN). Glutathione-S-transferase (GST) is primarily involved in the neutralization of reactive oxygen species (ROS) by enzymatic conjugation with the scavenger peptide glutathione (GSH). Therefore, present study was aimed to evaluate the role of GST along with oxidative stress markers and their correlation in patients with Type 2 diabetes mellitus with and without nephropathy.MethodsThis study comprised of 300 participants divided into three groups of 100 each: healthy controls (HC), T2DM without complications and DN. Plasma GST, malondialdehyde (MDA), reduced GSH levels and ferric reducing ability of plasma (FRAP) were estimated spectrophotometrically.ResultsHighest GST levels was observed in T2DM which was significantly higher (p < 0.05) as compared to DN and HC. However, GSH and FRAP levels were found to be significantly lowest whereas MDA levels were significantly highest in DN as compared to T2DM and HC. GST showed a significant negative correlation with GSH, FRAP and positive correlation with MDA in both patients groups.ConclusionsHighest activity of GST in T2DM might be as a compensatory mechanism in response to oxidative stress. GST is found to have significant negative association with decreased GSH. Altered redox milieu in DN collectively conspire to increase the risk of renal damage in T2DM.     

Beneficial effects of phlorizin on diabetic nephropathy in diabetic db/db mice

AimsThis study observes the effects of phlorizin on diabetic nephrology in db/db diabetic mice and explores possible underlying mechanisms.MethodsSixteen diabetic db/db mice and eight age-matched db/m mice were divided into three groups: vehicle-treated diabetic group (DM group), diabetic group treated with phlorizin (DMT group) and normal control group (CC group). Phlorizin was given in normal saline solution by intragastric administration for 10 weeks. Differentially expressed proteins in three groups were identified using iTRAQ quantitative proteomics and the data were further analyzed with ingenuity pathway analysis.ResultsThe body weight and serum concentrations of fasting blood glucose (FBG), advanced glycation end products (AGEs), total cholesterol, triglycerides, blood urea nitrogen, creatinine and 24-h urine albumin were increased in the DM group compared to those of the CC group (P < 0.05), and they were decreased by treatment with phlorizin (P < 0.05). Morphologic observations showed phlorizin markedly attenuated renal injury. Phlorizin prevented diabetic nephropathy by regulating the expression of a series of proteins involved in renal and urological disease, molecular transport, free radical scavenging, and lipid metabolism.ConclusionsPhlorizin protects mice from diabetic nephrology and thus may be a novel therapeutic approach for the treatment of diabetic nephrology.     

ABC goal achievement predicts microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study

HypothesisVascular complications of type 1 diabetes are thought to cluster. We examined the prevalence and incidence of vascular complications and American Diabetes Association's ABC goal achievements in a prospective cohort of adults with type 1 diabetes. We hypothesized that ABC achievement at baseline would predict both micro- and macrovascular complications over 6-years.MethodsParticipants (N = 652) were 19–56 year old at baseline and re-examined 6-years later. Microvascular complications included diabetic nephropathy (DN), defined as incident albuminuria (AER ≥ 20 μg/min) or rapid GFR decline (> 3.3%/year) by CKD-EPI cystatin C and proliferative diabetic retinopathy (PDR), defined as laser eye-therapy. Macrovascular complications were defined as coronary artery calcium progression (CACp), measured by electron-beam computed-tomography. ABC goals were defined as HbA1c < 7.0%, BP < 130/80 mmHg and LDL-C < 100 mg/dL.ResultsABC control was suboptimal with only 6% meeting all goals. Meeting no ABC goals at baseline compared to meeting all goals was associated with increased odds of developing microvascular complications (OR: 8.5, 2.3–31.5, p = 0.001), but did not reach significance for CACp (OR: 1.7, 0.8–3.9, p = 0.19).ConclusionABC achievement at baseline strongly predicted microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes, suggesting a need for novel therapeutic targets to complement conventional risk factors in treating macrovascular complications.     

Relationship between tissue glycation measured by autofluorescence and pulse wave velocity in young and elderly non-diabetic populations

ObjectiveAdvanced glycation end-products (AGEs) and pulse wave velocity (PWV) are pivotal indices of the processes of arterial ageing and damage accumulation. The aim of the present study was to investigate the impact of AGEs, as measured by a non-invasive skin autofluorescence method, on arterial stiffness, estimated by PWV, in two different age groups of non-diabetic subjects.Methods and patientsA total of 116 non-diabetic subjects were classified into two groups, with 55 subjects in the group aged < 65 years and 61 in the group aged ≥ 65 years. AGEs were measured by skin autofluorescence while carotid–femoral PWV was assessed by tonometry.ResultsA significant (positive) association was observed between PWV and AGE skin autofluorescence in the younger age group (r = 0.51; P < 0.0001). However, this association was no longer significant after further adjustments for age and other factors on multiple regression analyses. In contrast, this correlation was not found in the elderly group (r = 0.098; P = 0.454).ConclusionYounger non-diabetic subjects exhibit a different correlation profile between AGEs accumulated in skin and cfPWV as an index of arterial stiffness compared with elderly subjects. AGEs were significantly associated with cfPWV in younger individuals, but not in the elderly. A further study with a larger number of subjects is proposed to confirm the contribution of AGEs, the formation of which is manageable, as a determinant of arterial stiffness in younger subjects.     

Association of macrovascular complications of type 2 diabetes mellitus with serum magnesium levels

BackgroundDiabetes mellitus and its complications are a significant cause of morbidity and mortality worldwide. Micronutrients have been evaluated as potential preventive and therapeutic measures in diabetes. The present study evaluated serum magnesium levels in diabetic patients—uncomplicated and those with macrovascular complications.MethodThis study was done on 150 subjects (60 normal, healthy controls and 90 diabetics). The 90 diabetic patients were selected in the following categories—30 patients without complications (Study Group I), 30 diabetic patients with coronary artery disease (Study Group II) and 30 diabetic patients with peripheral vascular disease (Study Group III). Plasma glucose, glycated hemoglobin and serum magnesium levels were estimated in all the patients.ResultsFasting plasma glucose and glycated hemoglobin levels were significantly higher in all the 3 study groups as compared to the controls, however, serum magnesium levels were significantly lower (p < 0.05). In diabetic patients with coronary atherosclerosis or peripheral vascular disease, a significant negative correlation was observed between serum magnesium and fasting plasma glucose and glycated hemoglobin indicating the role of hypomagnesemia in diabetic complications.ConclusionDietary supplementation with magnesium in addition to classical therapies for diabetes may help in prevention of diabetic complications.     

Evaluation of trace elements and Malondialdehyde levels in type II diabetes mellitus

BackgroundThere are so many factors contributing to the pathophysiology of type II DM, some of these factors are trace elements and Malondialdehyde (MDA). Their increase or decrease may affect control of diabetes and delay the complications.AimZinc (Zn), copper (Cu), magnesium (Mg), chromium (Cr), selenium (Se) and MDA were studied in this work to clarify their role in the pathogenesis and complications of type II DM aiming at preventing or delaying its complications.Materials and methodsThe present study was conducted on 50 patients with type II DM divided into 2 groups: group I (controlled diabetic patients), n = 20 and group II which comprised 30 uncontrolled diabetic patients complicated with diabetic nephropathy, neuropathy and retinopathy. Their results were compared to 15 age and sex matched healthy group. Patients and controls were subjected to full history taking, complete clinical examination and laboratory investigations which included measuring fasting serum glucose, cholesterol, triglycerides, HDL-c and LDL-c. HbA1c was measured by column chromatography. MDA was assayed using colorimetric technique. The trace elements were measured in blood by means of atomic absorption spectrometer.ResultsThe mean levels of Zn, Mg, Se were significantly lower in the diabetic groups than the control group (P < 0.001), while MDA was significantly higher in the diabetic groups (P < 0.001). MDA showed significant positive correlation with HbA1c (r = 0.301), cholesterol (r = 0.394), triglycerides (0.315) and LDL-c (r = 0.354) and negative correlation with HDL-c (r = ?0.315). Significant negative correlation was found between each of Zn, Mg and Se and each of HbA1c and cholesterol. Copper positively correlated with HbA1c, cholesterol and LDL-c. MDA positively correlated with copper (r = 0.307) and negatively correlated with Zn, Mg and Se (r = ?0.356, ?0.282, ?0.513, respectively).ConclusionTrace elements and MDA could have a role as cofactors in the pathogenesis of type II DM. They could be used as markers to evaluate the glycemic control as well as showing the lipid status of diabetic patients. Trace elements supplementations as zinc, magnesium and selenium might have utility in the treatment of the complex disorder in type II DM and may help in control of blood glucose and lipid levels, thus preventing or delaying serious clinical events in these patients.     

Medication non-adherence and poor glycaemic control in patients with type 2 diabetes mellitus

AimsHyperglycemia causes generation of free radicals which leads to oxidative stress and apoptosis in various cells. The present study was undertaken to investigate the correlation between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wounds.MethodsThirty healthy, thirty uncontrolled type 2 diabetes mellitus (T2DM) and thirty uncontrolled T2DM with chronic, non healing, neuropathic diabetic foot patients were included in this study. Indices of oxidative stress inside the lymphocyte lysate were estimated by measuring content of superoxide dismutase (SOD), Catalase, Glutathione and malonaldialdehyde (MDA). Protein expression studies of pro and anti apoptotic markers were carried out to elucidate their possible involvement in diabetic context.ResultsSOD and MDA activity was significantly higher in the lymphocytes of diabetic patients having chronic, non healing diabetic wound as compared with healthy (p < 0.001); whereas catalase and GSH activity was significantly reduced (p < 0.001) in the same group. Expressions of pro apoptotic markers (Caspase-3, Fas and Bax) were significantly higher whereas reduced expression of anti-apoptotic marker (Bcl-2) were obtained in lymphocytes of diabetic and non diabetic individuals.ConclusionsHyperglycemia confers pro apoptotic manifestations which are mostly through altered indices of oxidative stress within lymphocytic milieu.     

A study of diabetes complications in an endogamous population: An emerging public health burden

AimThe aims of this study were to determine the prevalence of diabetic complications namely neuropathy, nephropathy, and retinopathy among Qatari's DM patients; and to find associations between these complications and socio-demographic and clinical characteristics in a highly consanguineous population.DesignIt is an observational cohort study.SettingThe survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar.SubjectsThe study was conducted from May 2011 to January 2013 among Qatari nationals above 20 years of age. Of the 2346 registered with diagnosed diabetes attending Hamad General Hospital and PHC centers, 1633 (69.3%) agreed and gave their consent to take part in this study.MethodsQuestionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed.ResultsOut of 1633 diabetic patients, 842 (51.6%) were males. The prevalence of diabetic nephropathy 12.4% and retinopathy was 12.5% followed by neuropathy 9.5% among diabetic population. The proportion of diabetic neuropathy and nephropathy were significantly higher among diabetic patients with age 60 years and above as compared to younger age groups (p = 0.010). Nephropathy was significantly higher among male diabetic (p = 0.014) and smokers (p < 0.001) while diabetic neuropathy was more common among diabetic hypertensive patients (p = 0.028). Multivariate logistic regression showed that Age (p = 0.025), being male (p = 0.045), and having high blood pressure (p = 0.006) were significant predictors of diabetic neuropathy. For diabetic retinopathy, family history of DM (p < 0.001), consanguinity (p = 0.010), having high blood pressure (p = 0.042) and physical activity (p < 0.001) were significant predictors of diabetic retinopathy. Meanwhile, for diabetic nephropathy, age (p < 0.001), smoking (p = 0.045), physical activity (p < 0.001) hypertension (p < 0.001) and gender (p = 0.012) were the significant predictors.ConclusionDiabetes exerts a significant burden in Qatar, and this is expected to increase. Many diabetic patients face significant challenges accessing diagnosis and treatment, which contributes to the high morbidity and mortality and prevalence of complications observed. The significant interactions between diabetes and associated complications highlight the need and opportunity for health planners to develop integrated responses to communicable and non-communicable diseases.     

Geographic variation in Medicare spending and mortality for diabetic patients with foot ulcers and amputations

AimsThe purpose of this study was to identify the presence or absence of geographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers (DFU) and lower extremity amputations (LEA).MethodsDiabetic beneficiaries with foot ulcers (n=682,887) and lower extremity amputations (n=151,752) were enrolled in Medicare Parts A and B during the calendar year 2007. We used ordinary least squares (OLS) regression to explain geographic variation in per capita Medicare spending and one-year mortality rates.ResultsHealth care spending and mortality rates varied considerably across the nation for our two patient cohorts. However, higher spending was not associated with a statistically significant reduction in one-year patient mortality (P= .12 for DFU, P= .20 for LEA). Macrovascular complications for amputees were more common in parts of the country with higher mortality rates (P< .001), but this association was not observed for our foot ulcer cohort (P= .12). In contrast, macrovascular complications were associated with increased per capita spending for beneficiaries with foot ulcers (P= .01). Rates of hospital admission were also associated with higher per capita spending and increased mortality rates for individuals with foot ulcers (P< .001 for health spending and mortality) and lower extremity amputations (P< .001 for health spending, P= .01 for mortality).ConclusionsGeographic variation in Medicare spending and mortality rates for diabetic patients with foot ulcers and amputations is associated with regional differences in the utilization of inpatient services and the prevalence of macrovascular complications.     

Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus

As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA_1c levels measured every 6 months as far back as the last 5 years were also collected. The association of AF with the patients’ past glucose control, based on their latest HbA_1c values, and the means of the last five and 10 HbA_1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th–75th percentiles: 1.7–2.4] arbitrary units (AU), and this was associated with age (β = 0.15 per 10 years, P < 0.001) and diabetes duration (β = 0.17 per 10 years, P < 0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA_1c values (β = 0.10 per 1% of HbA_1c, P = 0.005, and β = 0.13 per 1% of HbA_1c, P = 0.001, respectively). In addition, the skin AF was associated with retinopathy (P < 0.001), albuminuria (P < 0.001) and decreased eGFR (P < 0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.