Classification of diabetic retinopathy and diabetic macular edema

The global incidence and prevalence of diabetes mellitus (DM) have reached epidemic proportions. Estimates indicate that more than 360 million people will be affected by DM by 2030. All of these individuals will be at risk of developing diabetic retinopathy (DR). It is extremely important to categorize, classify and stage the severity of DR in order to establish adequate therapy. With proper management more than 90% of cases of visual loss can be prevented. The purpose of the current paper is to review the classification of DR with a special emphasis on the International Clinical Disease Severity Scale for DR. This new classification is simple to use, easy to remember and based on scientific evidence. It does not require specialized examinations such as optical coherence tomography or fluorescein angiography. It is based on clinical examination and applying the Early Treatment of Diabetic Retinopathy Study 4:2:1 rule.     

Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema

The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme (APE) in the management of diabetic retinopathy and diabetic macular edema (DME). Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included. All cases were treated with an initial intravitreal injection of APE and reevaluated one month later, measuring changes in best-corrected visual acuity (BCVA), macular thickness and the status of the posterior hyaloid. A second APE injection was performed in cases with no evident posterior vitreous detachment (PVD) after the initial treatment. Sixty-three eyes were included in the present review. A complete PVD appeared in 38% of cases (24 eyes) after one injection of plasmin and the total increased to 51% (32 eyes) after the second injection, separated at least by one month. The central macular thickness improved in all cases (100%) and BCVA in 89%. Finally, in 50% of eyes with proliferative diabetic retinopathy, a high reduction of new vessels regression was observed. Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema.     

糖尿病周围神经病变在糖尿病骨病中的发病机制研究进展

糖尿病骨病是指糖尿病患者出现骨质减少、关节病变、骨皮质变薄、骨骼脆性增加甚至骨折的一种全身性、代谢性骨病,是糖尿病的重要并发症之一。随着糖尿病患者生活质量的提高以及病程的延长,患者的肌肉骨骼病变发生率在逐年提高,严重者可导致残疾或死亡。其发病机制目前尚未完全阐明,近年来,随着对糖尿病骨病的深入研究,发现糖尿病周围神经病变在骨骼疾病的发病和进展中起着重要作用。本文就糖尿病骨病、神经病变之间的关系加以综述,旨在探索神经病变导致骨代谢失调、骨密度下降、骨折风险的可能机制,为糖尿病骨病的诊断、预防、治疗提供新思路。     

Development of late-stage diabetic nephropathy in OVE26 diabetic mice

OVE26 mice are a transgenic model of severe early-onset type 1 diabetes. These mice develop diabetes within the first weeks of life and can survive well over a year with no insulin treatment, and they maintain near normal body weight. To determine whether OVE26 mice provide a valuable model of chronic diabetic nephropathy (DN), OVE26 diabetic mice were compared with their nondiabetic littermates for functional and structural characteristics of DN. OVE26 mice exhibited pronounced polyuria and significant albuminuria by 2 months of age (305 microg/24 h in OVE26 vs. 20 microg/24 h in controls). Albumin excretion rate increased progressively with age and exceeded 15,000 microg/24 h at 9 months of age. The profound loss of albumin led to hypoalbuminemia in some diabetic animals. Albuminuria coincided with an elevation in blood pressure as measured by tail cuff. The glomerular filtration rate (GFR) in OVE26 mice measured using fluorescein isothiocynate inulin clearance demonstrated that GFR increased significantly from 2 to 3 months of age and then decreased significantly from 5 to 9 months. GFR in 9-month-old diabetic mice was significantly lower than that of 9-month-old control mice. The decline in GFR coincided with a significant increase in renal vascular resistance. Structural studies showed an almost twofold increase in kidney weight between 2 and 5 months. Diabetic mice also showed progressively enlarged glomeruli and expanded mesangium with diffuse and nodular expansion of mesangial matrix. Tubulointerstitial fibrosis was also observed in these mice. Glomerular basement membrane was thickened in OVE26 mice. In summary, OVE26 mice demonstrate that most of the characteristics of human DN can be produced by chronic hyperglycemia in a murine model. This model will be useful for improved understanding and treatment of DN.     

Painful diabetic neuropathy

The podiatric physician often encounters complex painful neuropathies in daily practice. Diabetic neuropathy is one form of chronic neuropathic pain dealt with on a regular basis. The goal of this article is to review the pathophysiology, diagnosis, and treatment options of this complaint. Medical and surgical interventions are discussed, with a clinical emphasis on patient selection and prevention.     

The diabetic foot

Amputation of the lower extremity is more frequent in diabetic patients than in the general population. Causative factors include foot deformities, neuropathy, dysvascularity, infection, and gangrene. A grading and treatment program is outlined for aid in treating the lesions that develop in these feet.     

The diabetic foot

Lower extremity complications are common in patients with diabetes and include neuropathy, ulceration, infection, and peripheral arterial disease. Foot infections represent the single most common cause of hospitalization and lower extremity amputation in persons with diabetes. Foot ulceration as a result of diabetic peripheral sensory neuropathy, rigid osseous deformities and soft-tissue contractures, repetitive trauma from unprotected ambulation, and peripheral vascular disease can all lead to a limb- or life-threatening infection. Antibiotic therapy for diabetic soft-tissue and osseous infections is usually inadequate as an isolated form of therapy. The mainstay of treatment involves well-planned surgical procedures, including extensive and properly placed incisions to perform adequate drainage of abscesses and débridement of necrotic soft-tissue and osseous structures from which deep cultures are obtained for specific antibiotic coverage. Initial antibiotic therapy should provide broad-spectrum coverage, and when final culture results are available the regimen should be revised to organism-specific coverage. Detailed and timely evaluation of the vascularity of the limb is paramount, followed by timely vascular reconstruction involving various endovascular and open surgical procedures to restore pulsatile flow to the full extent of the limb.     

Familial clustering of diabetic nephropathy in Brazilian type 2 diabetic patients

There is evidence for genetic predisposition to diabetic nephropathy in type 1 diabetic patients. However, there are few studies on type 2 diabetic patients, and most of those have been conducted on ethnic minorities or Caucasian individuals. The aim of this study was to ascertain the presence of an inherited predisposition to diabetic nephropathy in a sample of Brazilian type 2 diabetic patients. Families with two or more type 2 diabetic siblings were identified. Subjects with the longest duration of known diabetes were considered probands. Some 90 probands and their 107 diabetic siblings were studied. Urinary albumin excretion rate was measured in a sterile 24-h urine sample on at least three different occasions. Probands and siblings were classified according to urinary albumin excretion rate as normo- (<20 microg/min), micro- (20-200 microg/min), or macroalbuminuric (>200 microg/min). Patients with end-stage renal disease were included in the macroalbuminuric group. Macroalbuminuria was identified in 5.2% of the siblings of normoalbuminuric probands and in 24.1% of the siblings of macroalbuminuric probands (P = 0.024). In multiple logistic regression, the presence of diabetic nephropathy in probands (micro- or macroalbuminuria and end-stage renal disease) was significantly associated with the presence of sibling diabetic nephropathy (odds ratio = 3.75, 95% CI = 1.36-10.40, P = 0.011) adjusted for proband fasting plasma glucose and diabetes duration. Interpretation of these results should take into account the possibility that the families including siblings with diabetic nephropathy may have been overcounted and, on the other hand, that the siblings without diabetic nephropathy may have been undercounted. In conclusion, there is a familial aggregation of diabetic nephropathy in this sample of type 2 diabetic patients.     

Hand infections in the diabetic and the diabetic renal transplant recipient

We present a series of 41 diabetic patients with severe tissue destruction and deformity secondary to hand infections. Thirty (73%) of the patients showed propagation of the infection to bone, tendons, or deep palmar spaces, and 26 of 41 (63%) required amputations. Sixty-three percent of the cultures were mixed; pure Staphylococcus aureus accounted for only 12%. Diabetics who were renal transplant recipients were at increased risk, with a 100% amputation rate and an average hospitalization of 41 days. Recommendations for management of diabetic hand infections are given to reduce the mortality and morbidity in these patients.     

氯沙坦对糖尿病大鼠肾脏保护作用的探讨

目的 探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对糖尿病大鼠肾小球病变的保护作用及其机制。方法 观察氯沙坦对糖尿病鼠肾血流量、肾脏体积及尿蛋白排泄的影响,以及对血、肾组织局部一氧化氮（ＮＯ）,内皮素（ＥＴ）、转化生长因子－β（ＴＧＦ－β１）含量的影响。结果 氯沙垣可降低尿白蛋白、β２微球蛋白（β２－ｍ）排泄率,肌酐清除率（Ｃｃｒ）及阻遏早期肾小球肥大,且不同程度降低肾组织局部ＮＯ、ＥＴ含量,大剂量氯沙垣还能     

The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.     

Sertoli cell function in diabetic, insulin-treated diabetic, and semi-starved rats

It is well documented that long-term diabetes mellitus results in numerous deleterious consequences. However, considerable controversy exists concerning male reproductive function in diabetes. The purpose of this investigation was to study several endocrine parameters in diabetic male rats with emphasis on Sertoli cell function. Male Wistar rats were injected with streptozotocin and then either left untreated for 30 days or injected with insulin so as to prevent spillover of glucose into the urine. These two groups were compared with control animals that had only been injected with the vehicle for streptozotocin. Semi-starved control animals were included to determine if any of the potential endocrine alterations were related to body weight changes which occur in streptozotocin-injected rats. It was found that FSH, LH, PRL, and GH serum levels were reduced in diabetic animals. Only FSH was restored to normal by insulin injections. The testis, seminal vesicle, and epididymis weights were all reduced in diabetic animals. Insulin injections raised all organ weights; however, only testis weights were fully restored. Levels of epididymal ABP activity were found to be higher in diabetic animals when expressed per mg protein. Similar patterns of organ weight loss and hormonal alterations were observed in semi-starved rats. However, epididymal levels of ABP activity were unaffected by the semi-starved condition. While weight loss should be taken into consideration when interpreting cause and effect relationships in streptozotocin-treated animals, epididymal ABP levels appear to be well correlated with the altered metabolic state characteristic of diabetes.