A comparison of the levels of hepatocyte growth factor in serum in patients with type 1 diabetes mellitus with different stages of diabetic retinopathy

INTRODUCTION: The aim of this study was to evaluate the blood concentration of hepatocyte growth factor (HGF) in patients at various stages of retinopathy. We hypothesised that the high level of HGF found in diabetic patients may be an important marker of retinopathy progression and that HGF level may be an index of the risk of proliferative retinopathy. MATERIAL AND METHODS: The participants in the study were 76 patients with type 1 diabetes mellitus. Of these, 35 patients were without retinopathy and formed Group 1. Of the remaining 41 patients with retinopathy, 20 patients had non-proliferative diabetic retinopathy (NPDR) and formed Group 2, while 21 patients had proliferative diabetic retinopathy (PDR) and formed Group 3. We evaluated the concentration of HGF In the peripheral blood by an enzyme-linked immunosorbent assay. RESULTS: Mean serum concentrations of HGF in the control group were significantly lower than in the type 1 diabetic patients. We found a significant increase in HGF serum concentrations in diabetic patients with PDR compared with the control group. Mean serum HGF concentrations were significantly higher in diabetic subjects with PDR than in diabetic patients without retinopathy. CONCLUSION: HGF concentration is increased in patients with type 1 diabetes mellitus with proliferative retinopathy, and concentrations increase with the progression of retinopathy, suggesting that HGF plays a role in the pathogenesis of proliferative diabetic retinopathy.     

Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?

Background

To investigate the clinical differences between pulse wave velocity and augmentation index in diabetic retinopathy.

Methods

The subjects were 201 patients with type 2 diabetes. These subjects were measured for both augmentation index (AI) and brachial-ankle pulse wave velocity (baPWV) by a pulse wave analyzer. The relationships between AI, baPWV, and diabetic retinopathy were examined.

Results

BaPWV was significantly higher in patients with diabetic retinopathy than in individuals without the disease. (20.13 ± 3.66 vs.17.14 ± 3.60 m/s p < 0.001) AI was higher in patients with diabetic retinopathy, but not significantly. (19.5 ± 15.2 vs. 14.8 ± 20.5% p = 0.14) The association between baPWV and diabetic retinopathy remained statistically significant after adjustment. (Odds ratio: 1.21 Per m/s, 95% confidence interval: 1.07–1.37) On the other hand, the association between AI and diabetic retinopathy was not statistically significant. (Odds ratio: 1.01 Per %, 95% confidence interval: 0.98–1.03)

Conclusion

BaPWV is associated with diabetic retinopathy, but AI is not. The clinical significance appears to be different between PWV and AI in patients with diabetes.     

Quality of screening for diabetic retinopathy in the Rijeka region of Croatia

The aim of this study was to compare the quality of screening for diabetic retinopathy in cities of Rijeka and Zagreb, Croatia. Review of a random sample of 500 diabetic patient records and prospective ophthalmologic survey of 466 randomly selected diabetic patients in a secondary level diabetologic service in Rijeka (coastal region of Croatia). The main outcome measures were proportion of diabetic patient records with notes on ophthalmologic examination; rate of diabetic patients involved with screening for diabetic retinopathy; comparison with rates in Zagreb (Croatian capital). A total of 67% patients visited the ophthalmologist at least once after diagnosed with diabetes, and notes on ophthalmologic examination were found in only 28% patient records. Fifty percent of patients underwent an ophthalmologic examination within two years. Only one third of patients diagnosed with DM in last two years visited the ophthalmologist within this time, and 14% of patients older than 50 years never visited the ophthalmologist. Model of screening for diabetic retinopathy in Croatia works better in Zagreb than in Rijeka region, and needs certain improvements. The authors suggested modern methods of screening, the incorporation of the mechanisms of quality control, the obligatory reporting of newly diagnosed diabetic patients to the national registry, and the direct referral from diabetologist to ophthalmologist.     

细菌脂多糖(LPS)在糖尿病视网膜微血管病变中的作用

本研究旨在通过Akita小鼠糖尿病模型及糖尿病人群血浆样本,探讨病原体相关性分子细菌脂多糖(lipopolysaccharide,LPS)在糖尿病视网膜病变中的重要作用。本研究选择6个月糖尿病病程的Akita小鼠(Ins2+/Akita)及其同年龄组野生型(wild type,WT)小鼠(C57BL/6J)尾静脉内注射脂多糖(LPS)或生理盐水对照共7 d,从影像学、电生理及病理学水平评估糖尿病视网膜眼病进展。最后收集糖尿病视网膜眼病患者及对照人群血标本,通过ELISA测定血浆LPS表达水平。通过光学相干断层扫描技术分析,发现Akita小鼠的视网膜层间厚度较WT小鼠组相比明显变薄(p=0.000 2),LPS处理进一步加重糖尿病小鼠视网膜结构损害(p=0.000 7)。视网膜电图检测发现LPS处理Akita小鼠组的视网膜细胞幅值较生理盐水处理Akita小鼠显著减慢,有统计学意义(p<0.05)。胰酶消化法分离及PAS染色小鼠眼球视网膜微血管网后,计数测得LPS处理显著增加了Akita小鼠视网膜中无细胞毛细血管数量(p=0.002 6),提示LPS在糖尿病微血管损伤中的重要作用。为保证该研究的临床转化性,我们进一步检测了糖尿病视网膜病变患者(n=19)、糖尿病患者(无微血管并发症)(n=23)及健康对照组(n=20)的血浆LPS水平,发现糖尿病患者血浆LPS水平较健康对照组显著升高(p=0.002 3),其中糖尿病视网膜病变患者LPS升高最为显著(p<0.000 1)。本研究表明,循环中细菌脂多糖增加在糖尿病视网膜病变进展中起到重要作用。     

Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy

Diabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by approximately 3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.     

Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy

The changes in retinal thickness and visual function in type 2 diabetic patients without clinical evidence of diabetic retinopathy were evaluated. A total of 141 diabetic subjects without retinopathy and 158 healthy subjects were enrolled in this study. Superior macular ganglion cell complex thicknesses were significantly decreased in diabetic cases, and no significant peripapillary retinal nerve fiber layer thickness changes were observed. The contrast sensitivities at all space frequencies were significantly different between diabetic patients and controls. The mean P50 amplitude from pattern electroretinogram results was reduced significantly in the diabetic group. In the diabetic group, average superior ganglion cell complex thicknesses positively correlated with both contrast sensitivities at high spatial frequencies and P50 amplitudes. The results indicated that ganglion cell complex thickness and visual function changes could be observed in diabetic subjects before the onset of any significant diabetic retinopathy. Macular ganglion cell complex reduction occurred much earlier than peripapillary retinal nerve fiber layer thinning in diabetic patients without retinopathy.     

Retinal blood flow in diabetic retinopathy.

OBJECTIVES--(a) To report on the basic parameters of retinal blood flow in a population of diabetic patients with and without retinopathy and non-diabetic controls; (b) to formulate a haemodynamic model for the pathogenesis of diabetic retinopathy from this and other studies. DESIGN--Laser-Doppler velocimetry and computerised image analysis to determine retinal blood flow in a large cross sectional study. SETTING--Diabetic retinopathy outpatient clinic. SUBJECTS--24 non-diabetic controls and 76 diabetic subjects were studied (63 patients with insulin dependent diabetes, 13 with non-insulin dependent diabetes). Of the diabetic subjects, 12 had no diabetic retinopathy, 27 had background retinopathy, 13 had pre-proliferative retinopathy, 12 had proliferative retinopathy, and 12 had had pan-retinal photocoagulation for proliferative retinopathy. MAIN OUTCOME MEASURES--Retinal blood flow (microliters/min) and conductance (rate of flow per unit of perfusion pressure). RESULTS--In comparison with non-diabetic controls (9.52 microliters/min) and diabetic patients with no diabetic retinopathy (9.12 microliters/min) retinal blood flow was significantly increased in all grades of untreated diabetic retinopathy (background 12.13 microliters/min, pre-proliferative 15.27 microliters/min, proliferative 13.88 microliters/min). There was a significant decrease in flow after pan-retinal photocoagulation in comparison with all the other groups studied (4.48 microliters/min). Conductance of the retinal circulation was higher in the untreated diabetic retinopathy groups. These results were independent of age, sex, type of diabetes, duration of diabetes, glycated haemoglobin concentration, blood glucose concentration, blood pressure, and intraocular pressure. CONCLUSIONS--Retinal blood flow is significantly increased in diabetic retinopathy in comparison with non-diabetic controls and diabetic subjects with no retinopathy. This has implications for controlling hypertension and hyperglycaemia as a strategy in reducing morbidity from diabetic retinopathy.     

Corneal Confocal Microscopy Detects Neuropathy in Patients with Type 1 Diabetes without Retinopathy or Microalbuminuria

Objective

Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.

Materials and Methods

All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)].

Results

53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.

Conclusions

IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.     

Microvascular reactivity in patients with hypercholesterolemia: effect of lipid lowering treatment

Impaired NO-dependent vasodilation of resistance vessels is an early marker of an increased risk of atherosclerosis; utility of the examination of microcirculation, however, is far less established. We have therefore tested the hypothesis that hypercholesterolemia is associated with an impaired microvascular reactivity and that this defect is at least partially reversible by lipid-lowering treatment. Twenty-seven otherwise healthy patients with severe hypercholesterolemia (HLP) were examined at rest and then after 10 weeks of atorvastatin treatment (20 mg/day). Skin microvascular reactivity (MVR) was examined by laser-Doppler flowmetry. Baseline MVR values of the studied group were compared to healthy control subjects, HLP patients with coronary artery disease (CAD) and diabetic patients with and without diabetic retinopathy. MVR was normal in HLP subjects without CAD. On the contrary, MVR was impaired in HLP patients with CAD. There was no effect of atorvastatin on MVR, despite the profound reduction of serum lipids. MVR values did not correlate with cholesterol levels. In diabetic subjects, the MVR was substantially impaired only in patients with retinopathy. In the subjects without retinopathy, MVR was either normal (type I diabetes) or moderately impaired (type II diabetes). MVR was thus normal in HLP patients without manifest vascular disease and was not influenced by lipid lowering therapy. Impairment in the MVR was only evident in subjects with HLP and severe CAD. These results suggest that microcirculation is not involved in the early vascular dysfunction induced by HLP and that MVR rather reflects changes which appear later in the course of the atherosclerotic disease.     

A Marker of Early Stages of Diabetic Retinopathy

A comparative estimate of the hormonal status and coagulatory activity was carried out in patients with diabetes mellitus at the functional and subclinical stages of diabetic retinopathy and in those without signs of diabetic retinopathy. In all patients, the blood level of hormones was elevated, while in patients with functional and subclinical stages of diabetic retinopathy, the changes in hormonal status were accompanied by increased local and systemic potentials, disturbed microcirculation, and decreased functional activity of the retina outer layers. The increased hormone level affected the hemostatic potentials and induced their elevation at a certain stage. The reliably increased local hemostatic potential was one of the first signs of pathological action of the increased hormone level, while the increase of systemic hemostatic potential was unreliable. The combination of elevated blood level of hormones and coagulatory activity of the tear fluid is a marker fore revealing the group of risk for development of diabetic retinopathy in patients with diabetes mellitus.     

Erythrocyte Phospholipid and Polyunsaturated Fatty Acid Composition in Diabetic Retinopathy

Background

Long chain polyunsaturated fatty acids (LCPUFAs) including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans.

Methodology and Principal Findings

We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was determined by gas chromatography and the phospholipid structure was determined by liquid chromatography equipped with an electrospray ionisation source and coupled with a tandem mass spectrometer (LC-ESI-MS/MS). A significant decrease in levels of docosahexaenoic acid and arachidonic acid in erythrocytes of diabetic patients with or without retinopathy was observed. The origin of this decrease was a loss of phosphatidyl-ethanolamine phospholipids esterified with these LCPUFAs. In diabetic patients without retinopathy, this change was balanced by an increase in the levels of several phosphatidyl-choline species. No influence of diabetes nor of diabetic retinopathy was observed on the concentrations of plasmalogen-type phospholipids.

Conclusions and Significance

Diabetes and diabetic retinopathy were associated with a reduction of erythrocyte LCPUFAs in phosphatidyl-ethanolamines. The increase of the amounts of phosphatidyl-choline species in erythrocytes of diabetic patients without diabetic retinopathy might be a compensatory mechanism for the loss of LC-PUFA-rich phosphatidyl-ethanolamines.     

Impairment of Colour Vision in Diabetes with No Retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SNDREAMS- II,Report 3)

Purpose

To assess impairment of colour vision in type 2 diabetics with no diabetic retinopathy and elucidate associated risk factors in a population-based cross-sectional study.

Methods

This is part of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular-genetics Study (SN-DREAMS II) which was conducted between 2007–2010. FM 100 hue-test was performed in 253 subjects with no clinical evidence of diabetic retinopathy. All subjects underwent detailed ophthalmic evaluation including cataract grading using LOCS III and 45° 4-field stereoscopic fundus photography. Various ocular and systemic risk factors for impairment of colour vision (ICV) were assessed in subjects with diabetes but no retinopathy. P value of < 0.05 was considered statistically significant.

Results

The mean age of the study sample was 57.08 ± 9.21 (range: 44–86 years). Gender adjusted prevalence of ICV among subjects with diabetes with no retinopathy was 39.5% (CI: 33.5–45.5). The mean total error score in the study sample was 197.77 ± 100 (range: 19–583). The risk factors for ICV in the study were women OR: 1.79 (1.00–3.18), increased resting heart rate OR: 1.04 (1.01–1.07) and increased intraocular pressure OR: 1.12 (1.00–1.24). Significant protective factor was serum high-density lipoprotein OR: 0.96 (0.93–0.99).

Conclusions

Acquired ICV is an early indicator of neurodegenerative changes in the retina. ICV found in diabetic subjects without retinopathy may be of non-vascular etiology.     

Apoptotic factors (Bcl-2 and Bax) and diabetic retinopathy in type 2 diabetes

The expression of apoptotic factors Bcl-2 and Bax were studied in the conjunctiva of diabetic patients with and without retinopathy. All patients underwent a complete ophthalmic examination including ocular fundus and retinal fluorescein angiography. The indirect immunoperoxidase method was performed on 15 normal conjunctiva taken during cataract surgery (group 1), on 40 eyes of 40 patients with type 2 diabetes without diabetic retinopathy (group 2) and 13 eyes of 13 patients with diabetic retinopathy (group 3). In normal human conjunctiva, Bax showed positive expression in epithelial, vascular and stromal cells whereas Bcl-2 staining was negative. In the conjunctiva of diabetic patients without diabetic retinopathy, Bax was widely, and strongly, expressed in epithelial cells, vascular endothelial cells, fibroblasts and infiltrating cells such as macrophages. For patients with diabetic retinopathy, Bax was consistently strong to very strong. Bcl-2 protein expression became weak to negative for diabetic patients both with and without diabetic retinopathy. Immunoreactivity was not correlated between Bcl-2 and Bax in the conjunctiva of diabetic patients. Bax was always localized in tissues characterized by a high rate of apoptosis, whereas, Bcl-2 was absent. Our results suggest that diabetic human conjunctiva, with its inflammatory phenomena, is considered as a privileged target for programmed cell death.     

Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients

Purpose

To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR).

Methods

A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids.

Results

Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP < 14.5mmHg and mean HbA1c of 8.1±1.1, while 72 subjects had an IOP ≥ 14.5mmHg and a mean HbA1c of 9.0±2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (<1%) exhibited reduced IOP levels.

Conclusions

Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients.     

Vitamin D insufficiency in diabetic retinopathy

ObjectiveTo assess the relationship between vitamin D status and diabetic retinopathy.MethodsA clinic-based, cross-sectional study was conducted at Emory University, Atlanta, Georgia. Overall, 221 patients were classified into 5 groups based on diabetes status and retinopathy findings: no diabetes or ocular disease (n = 47), no diabetes with ocular disease (n = 51), diabetes with no background diabetic retinopathy (n = 41), nonproliferative diabetic retinopathy (n = 40), and proliferative diabetic retinopathy (PDR) (n = 42). Patients with type 1 diabetes and those taking > 1,000 IU of vitamin D daily were excluded from the analyses. Study subjects underwent dilated funduscopic examination and were tested for hemoglobin A_1c, serum creatinine, and 25-hydroxyvitamin D [25(OH)D] levels between December 2009 and March 2010.ResultsAmong the study groups, there was no statistically significant difference in age, race, sex, or multivitamin use. Patients with diabetes had lower 25(OH)D levels than did those without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; P < .001). The mean 25(OH)D levels, stratified by group, were as follows: no diabetes or ocular disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background diabetic retinopathy = 24.3 ng/ mL; nonproliferative diabetic retinopathy = 23.6 ng/mL; and PDR = 21.1 ng/mL. Univariate analysis of the 25(OH) D levels demonstrated statistically significant differences on the basis of study groups, race, body mass index, multivitamin use, hemoglobin A_1c, serum creatinine level, and estimated glomerular filtration rate. In a multivariate linear regression model with all potential confounders, only multivitamin use remained significant (P < .001).ConclusionThis study suggests that patients with diabetes, especially those with PDR, have lower 25(OH)D levels than those without diabetes. (Endocr Pract. 2012; 18:185-193)     

Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy.

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.     

Thrombin-induced breakdown of phosphoinositides in platelets from patients with NIDDM.

We have examined thrombin-induced metabolism of phosphoinositides in the platelets from fifteen NIDDM (non-insulin-dependent diabetes mellitus) patients and fifteen healthy subjects (control). The diabetic patients were divided into two groups. One group (group I) had diabetic retinopathy (microangiopathy) and the other group (group II) had atherosclerosis of great vessels (macroangiopathy). In platelets incubated with [32P] orthophosphate for 80 min, the incorporation of 32P radioactivity into phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was significantly lower in the group II than in the control. The addition of thrombin induced a marked decrease in PIP2 radioactivity at 10 sec in platelets from group I compared with that from the control. These results suggest that the breakdown of polyphosphoinositides is increased in platelets from diabetic subjects with retinopathy, and also that the formation of polyphosphoinositides is decreased in the platelets from diabetic subjects with macroangiopathy.     

Relationship between C-Reactive Protein Level and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Objectives

To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR.

Methods

A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and /or matched healthy persons constituted the control group, and patients with DR were the case group.

Results

Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11–0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30–0.70].

Conclusions

The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR.     

WITHDRAWN: Expression of p53, p63, and p73 isoforms in squamous cell carcinoma and adenocarcinoma of esophagus☆,☆☆

Diabetic microangiopathy is often observed in diabetic patients, but there is little evidence regarding the relationship between post-prandial glycemia or insulinemia and the incidence of diabetic microangiopathy. In this study, to elucidate the relationship between post-prandial glycemia (or insulinemia) and diabetic microangiopathy, we performed a cross-sectional study of 232 subjects with type 2 diabetes mellitus who were not being treated with insulin injections. A multiple regression analysis showed that post-prandial hyperglycemia independently correlated with the incidence of diabetic retinopathy and neuropathy. Post-prandial hyperglycemia also correlated, although not independently, with the incidence of diabetic nephropathy. In addition, interestingly, post-prandial hypoinsulinemia independently correlated with the incidence of diabetic retinopathy, although not correlated with diabetic neuropathy or nephropathy. In conclusion, post-prandial hyperglycemia, rather than fasting glycemia or hemoglobin A1c levels, is an important predictor of the incidence of diabetic microangiopathy in Japanese type 2 diabetic patients.     

Chronobiological pattern of growth hormone secretion in normal subjects and in retinopathic diabetics. Lack of suppression by a plurichronocorticoid drug.

Nyctohemeral variations in plasma concentrations of HGH, glucose, and FFA were studied in 22 normal subjects and 48 diabetic patients affected with retinopathy. In the normal subjects, (fourteen males and eight females, mean age 40+/-3 years; body weight less than 110% of I.B.W.) the determinations were made on blood samples drawn every hour. Seven of these normal subjects were examined before and after 10 days of administration of a new plurichronocorticoid drug (administered at 08(00) and 15(00), with a total amount of 14 mg of prednisolone and 15 mg of cortisone). In patients with diabetic retinopathy (32 male and sixteen female patients, mean age 46+/-2 years, body weight less than 110% of I.B.W.) the determinations were made on blood samples drawn every 3 hrs. All the diabetic patients were insulin treated and were under good or discrete metabolic control, and presented advanced retinopathy. Both in the normal subjects and in retinopathic diabetics, the mean HGH curve showed a characteristic elevation during the early nighttime hours (between 21(00) and 02(00). Despite higher values in plasma glucose and FFA, in diabetics the nocturnal elevation of HGH was only slightly lower than in the normals. The comparison between daytime and nighttime determinations, both in the normal subjects and in the diabetics, reveals statistically significant differences. These results suggest that in subjects with diabetic retinopathy, in the phase of good or discrete metabolic control, spontaneous HGH secretion is not increased, and that nocturnal elevation of HGH is not substantially influenced by higher plasma levels of glucose and FFA. Ten days of plurichronocorticoid treatment with a new drug which exhausts its activity before the evening, did not modify the circadian rhythm of HGH.