The severity of non-alcoholic fatty liver disease correlates with high sensitivity C-reactive protein value and is independently associated with increased cardiovascular risk in healthy population

ObjectivesWe aimed to investigate the correlation between non-alcoholic fatty liver disease (NAFLD) and risk of cardiovascular disease (CVD).Design and methodsWe analyzed 724 subjects without CVD according to presence or absence of NAFLD. Logistic regression model was used to determine if NAFLD was an independent risk factor of CVD.ResultsSubjects with NAFLD had increased percentage of 10-year cardiovascular risk ≧ 10% compared to those without NAFLD (p < 0.001). The severity of NAFLD significantly correlated with increasing Framingham risk score and C-relative protein (CRP) value. After adjusting for conventional CVD risk factors, the presence of NAFLD was an independent predictor for future CVD risk ≧ 10% [odds ratio: 1.89, p = 0.004]. Subgroup analysis showed the predictive value of NAFLD was significant among aged subjects and those with increased baseline hsCRP level.ConclusionsNAFLD is independently associated with increased CVD risk, especially among elderly subjects and those with increased CRP level.     

A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications.Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n = 57, DM micro-vascular complications n = 53, DM macro-vascular complications n = 47) and 40 healthy controls.ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control < DM without complications < DM-macro < DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA_1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH.ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.     

Correlations of creatine and six related pyrimidine metabolites and diabetic nephropathy in Chinese type 2 diabetic patients

ObjectivesThe assessment of the clinical significance of creatine, cytosine, cytidine, uridine, thymine, thymidine, and 2′-deoxyuridine concentrations in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between pyrimidine metabolites and disease.Design and methodsThe study group consisted of 119 subjects, which were divided to three groups: control (n = 31), type 2 diabetes without nephropathy (DM, n = 23), and with nephropathy (DN, n = 65). Levels of related metabolites were measured in plasma of all participants.ResultsThere is a significant increase in levels of cytosine (P < 0.001), cytidine (P < 0.001), and thymidine (P = 0.016) with DN compared to DM. The levels of uridine, thymine, 2′-deoxyuridine, and creatine did not change.ConclusionsThe levels of cytosine, cytidine, and thymidine may be useful for monitoring the progression of DM and evaluating the treatment.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer

ObjectivesThe receptor for advanced glycation end-products (RAGE) takes part in the pathogenesis of many diseases, including diabetes mellitus and cancer. AGE-precursors are detoxified by glyoxalase (GLO). sRAGE, soluble RAGE, is an inhibitor of pathological effects mediated via RAGE. The aim was to study sRAGE and polymorphisms of RAGE (AGER) and GLO genes in patients with pancreas cancer (PC).Design and MethodsThe studied group consisted of 51 patients with PC (34 with impaired glucose tolerance—IGT, 17 without IGT), 34 type 2 DM and 154 controls. For genetic analysis, the number of patients was increased to 170. Serum sRAGE was measured by ELISA and all polymorphisms (RAGE ?429T/C, ?374T/A, 2184A/G, Gly82Ser and GLO A419C) were determined by PCR-RFLP and confirmed by sequencing.ResultsSoluble RAGE is decreased in patients with PC compared to patients with DM and controls (975 ± 532 vs. 1416 ± 868 vs. 1723 ± 643 pg/mL, p < 0.001). Patients with PC and IGT have lower sRAGE levels compared to patients with PC without IGT (886 ± 470 vs. 1153 ± 616 pg/mL, p < 0.05). No relationship of sRAGE to the stage was found. We did not show any difference in allelic and genotype frequencies in all RAGE and GLO polymorphisms among the studied groups.ConclusionThis is the first study demonstrating decreased sRAGE in patients with pancreas cancer. Its levels are even lower than in diabetics and are lowest in patients with PC and IGT. Our study supports the role of glucose metabolism disorder in cancerogenesis. Further studies are clearly warranted, especially with respect to potential preventive and therapeutic implications.     

Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus

ObjectiveExposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology.MethodsOptimized voxel-based morphometry was performed on 21 unmedicated, right-handed subjects (18–25 years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV) – covaried by age, gender, parental education, financial stress, and total GMV – were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner).ResultsGMV was increased by 14.1% in the left superior temporal gyrus (STG, BA 22) (P = 0.004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal (ß = 0.544, P < 0.0001) and paternal (ß = 0.300, P < 0.02) verbal aggression and inversely associated with parental education (ß = ? 0.577, P < 0.0001).ConclusionPrevious studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke's and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally abusive language.     

Butyrylcholinesterase activity is reduced in haemodialysis patients: Is there association with hyperhomocysteinemia and/or oxidative stress?

Objectives:To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase.Materials and methods:Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood δ aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years.Results:The homocysteine was increased and butyrylcholinesterase decreased compared to control (p < 0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p < 0.05). The following correlations were found: homocysteine with butyrylcholinesterase (? 0.44); methahaemoglobin (0.41); ALA-D (? 0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was ? 0.30; all p < 0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems.Conclusion:Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress.     

Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil,doxorubicin and cyclophosphamide

ObjectivesBreast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.Design and methodsAO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.ResultsIncreased oxidative stress (LP: p < 0.05) and decreased AO enzyme activities (CuZnSOD: p < 0.01, GPx: p < 0.05, GR: p < 0.01) and GSH level (p < 0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p < 0.05), while it increased after the radiotherapy of breast cancer (p < 0.05).ConclusionFAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H₂O₂ detoxification (CAT, GPX and GSH) seems to have major contribution.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus

BackgroundThe pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated.Patients and methodsPatients with T2DM and poor glycemic control without known cardiovascular diseases (n = 119) at baseline were enrolled and followed for about 9 years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed.ResultsHigher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p < 0.05 for all). In univariate Cox regression analysis, PWV > 10 m/s, YKL-40 > 78 ng/ml and NGAL > 42 ng/ml were associated with cardiovascular events (p < 0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤ 2.2%) (p < 0.05 for all) were independently associated with cardiovascular events.ConclusionIn T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis.     

Serum glycated albumin levels,but not glycated hemoglobin,is low in relation to glycemia in non-diabetic men with nonalcoholic fatty liver disease with high alanine aminotransferase levels

ObjectivesWe have reported that serum glycated albumin (GA) levels are low in obese subjects, smokers and hyperuricemic subjects in whom high sensitive CRP (hs-CRP) is elevated. Because patients with nonalcoholic fatty liver disease with high alanine aminotransferase (ALT) levels are reported to show high levels of hs-CRP, the relationship between serum ALT and serum GA levels was investigated.Design and methodsThis study comprised 196 non-diabetic men without drinking habit.ResultsCompared with the normal ALT group (serum ALT ≤ 30 U/L; n = 158), the high ALT group (serum ALT > 30 U/L; n = 38) had significantly higher fasting plasma glucose (PG), OGTT 2-h PG and HbA_1C levels. Meanwhile, serum GA was significantly lower, and hs-CRP was significantly higher in the high ALT group.ConclusionsThe results obtained indicate that serum GA is under a negative control of hs-CRP in subjects with high ALT without drinking habit.     

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

Intrinsic foot muscle deterioration is associated with metatarsophalangeal joint angle in people with diabetes and neuropathy

BackgroundMetatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer.Methods23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age-matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance.FindingsThe diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), P < 0.001], and lower Foot and Ankle Ability Measure scores [65.1 (SD 24.4) vs. 98.3 (SD 3.3) %, P < 0.01]. The correlation between muscle deterioration ratio and metatarsophalangeal joint angle was r = ? 0.51 (P = 0.01) for all diabetic, neuropathic subjects, but increased to r = ? 0.81 (P < 0.01) when only subjects with muscle deterioration ratios > 1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers.InterpretationIndividuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown.     

Significantly elevated C-reactive protein serum levels are associated with very high 30-day mortality rates in hospitalized medical patients

Background:There is insufficient data regarding the differential diagnosis and the prognostic value of significantly elevated serum levels of C-reactive protein (CRP) in hospitalized medical patients.Design and methods:A retrospective review of medical charts of patients admitted to a tertiary hospital's Internal Medicine ward during a period of 1 year who had at least one CRP serum level measurement of 200 mg/L or more.Results:Overall, 341 patients with a mean age of 69.8 ± 1.0 years were included in the study. Acute infection was the most prevalent diagnosis (n = 293; 85.9%) with community-acquired pneumonia being the most common acute infection (n = 115; 33.7%). Non-infectious conditions accounted for 9.1% (n = 31) of the diagnoses and included mainly malignant metastatic diseases (n = 19; 5.6%). Overall, 70 (20.5%) patients died within 30 days of admission. Age and active malignancy, with metastasis or without metastasis, were independently associated with 30-day mortality.Conclusion:Significantly elevated CRP serum levels are associated with bacterial infections, malignant diseases, and very high rates of 30-day mortality in hospitalized medical patients.