Epidemiology of Micro- and Macrovascular Complications of Type 2 Diabetes in Korea

The prevalence of diabetes in Korea has increased six- to sevenfold over the past 40 years with its complications becoming major causes of morbidity and mortality. The rate of death among patients with diabetes is about twice as high as that among persons without diabetes and the most common cause of death is cardiovascular disease (30.6%). Despite the seriousness of diabetic complications, 30 to 70% of patients receive inadequate care, and only 40% of treated diabetic patients achieve the optimal control with HbA1c level <7% in Korea. In 2006, over 30 to 40% of patients with diabetes have microvascular complications and around 10% of them have macrovascular complications from our national data. Despite there are some debates about intensive glycemic control resulting in the deterioration of macrovascular complication, multifactorial treatment approaches including proper glycemic control are important to prevent diabetic complications. There have been needs for finding proper biomarkers for predicting diabetic complications properly but we still need more longitudinal studies to find this correlation with causal relationship. In this article, we wanted to review the recent status of micro- and macrovascular complications of type 2 diabetes in Korea from integration of many epidemiologic studies

Reconstructive strategies for lower one third leg soft tissue defect

INTRODUCTION; Increasingly, urban trauma is becoming a major health care issue. Large emergency departments are inundated with patients with multiple injuries, requiring state-of-the-art care. Most of these complex injuries involve trauma to the extremities, often due to motor vehicle accidents. In a study by MacKenzie et al. It was shown that lower extremity injuries accounted for about 40% of the charges for motor vehicle trauma treatment in a given year. Hospital-based studies reveal that disabilities persist for a long time with mean time taken to return to work ranges from 42 months to120 months. Coverage of soft tissue defect of the leg presents unique defects requiring the ingenuity of the surgeon in planning flaps for stable coverage. Though well established norms are in place regarding the time and nature of cover, it requires a team effort, practicing it with involvement of the orthopaedic surgeon and allied specialities like vascular surgeons, general surgeons. The relatively unprotected antero-medial portion of tibia results in exposed bone after trauma, which requires specialized soft tissue cover. Most muscles become tendons at this level hence flap cover becomes mandatory in case of soft tissue loss. We must periodically reassess our own work, chart our future developments, and summarize them for the benefit of all involved in patient care. It was with these concepts in mind that this study was conceived and planned. AIM: 1. To evaluate various reconstructive options for management of lower 1/3rd leg soft tissue defect and to highlight their merits and demerits. 2. To establish a definitive time based protocol in managing these patients. 3. To formulate an algorithm for treating patients requiring flap coverage for lower 1/3rd leg soft tissue defect at Government Rajaji Hospital, Madurai. MATERIALS AND METHODS: This study was conducted in the Department of Plastic Surgery, Government Rajaji Hospital, Madurai over a period of 30 months from Aug 2010 to Jan 2013. Only cases with soft tissue defect of lower 1/3rd leg requiring flap cover i.e defects with tendon, bone or implant exposed or in patients undergoing staged procedures were included in this study. A total of 73 patients were included in the study. Timing of coverage was classified into Acute - within 72 hours, Subacute - 3 days to 6 weeks, Chronic - Greater than 6 weeks. Defects were classified according to their site as per the usual norms of upper third, mid third and lower third. Inclusion criteria: All patients with post traumatic soft tissue defects of the lower 1/3rd leg who required a soft tissue cover were included in the study Exclusion criteria: Patients with degloving injuries, arterial injury, head injury, abdominal injury, thoracic injury, bony injuries elsewhere, brachial plexus injuries and patients who were not willing to participate in the study and for whom skin graft was planned were excluded from the study. Methodology: All the patients included in the study were admitted to the trauma ward under the care of the attending orthopedician and received first aid. They were then resuscitated to minimize bleeding, restore airway and correct shock. OBSERVATIONS AND RESULTS: The age of patients ranged from 10 to 70 years in this study. Common age group affected is between 21 to 30 years and 41 to 50 years, 19% each, n=14. Male to female ratio is 7: 1 (M = 64, F = 9). The most common indication for flap cover was exposed tibia (71%), followed by exposed tendon 21% and exposed Implant 8%. The most common size of defect was small i.e, less than 30 cms2 (51%), followed by medium sized defects 30 to 90 cms2 (40%) & Large defects greater than 90 cms2 (9%). The most commonly performed procedure is the inferiorly based fasciocutaneous flaps (45%), followed by reverse fasciocutaneous flaps (32%). Inferiorly based fasciocutaneous flap from lateral side(79%) was the most commonly performed fasciocutaneous flap because of the presence of reliable and constant perforator. Inferiorly based Fasciocutaneous flaps is the most common procedure performed for small to medium sized defect. Neurofasciocutaneous flaps are excellent choice for medium to large size defect. We have done a muscle flap for smaller defect Propeller flap was done in one patient with small defect. Free flaps were done in three patients with large sized defects. The average duration of hospitalization was least for fasciocutaneous flaps – (57% of patients were discharged within 10 days) and longest for pedicled Neurofaciocutaneous flaps and free flaps (2 to 5 weeks). Of the 46 patients who rated the reconstruction as Good, 26 (57%) had underwent distally based fasciocutaneous flap from lateral side, 12 (26%) had underwent distally based reverse neurofasciocutaneous flap of them rated the reconstruction as good, 2 islanded RSA, 1 muscle flap, 1 propellar flap, 1 ALT and 1 LD. Of the 5 patients who had rated the reconstruction as poor 3(60%) had underwent distally based reverse neurofasciocutaneous flap and 2 (40%) distally based fasciocutaneous flap. 70% of patients graded the reconstruction as Good, 23% as Fair and 7% as poor. CONCLUSION: Though Free flaps are the gold standard for coverage of lower 1/3 leg soft tissue defects, distally based fasciocutaneous flaps and distally based reverse neurofaciocutaneous flaps are still very useful in a set up like ours where sophisticated instruments, prolonged theatre time, back-up anesthesia team for re-exploration is not available all the time , and also because of the long wait list of trauma patients for surgery as ours is a tertiary care centre. Fasciocutaneous flaps are reliable, safe, and fast to learn

Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH2O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the “safety factor” opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D &amp;gt; 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening

Inflammation In The Pathogenesis Of Diabetic Retinopathy

The general purpose of these studies is to investigate inflammation in diabetic retinopathy in an effort to identify key intervention points to develop as treatments. Firstly, we showed that the neuropeptide VIP displayed protective immunoregulatory effects on retinal endothelial cells cultured under high glucose conditions. This effect was carried out, in part through the VPAC2 receptor. Next, we studied the β-adrenergic receptor agonist, Compound 49b, and its effect on the pro-resolving RvD1 pathway. Compound 49b was previously shown to suppress both inflammatory and apoptotic responses in DR. We demonstrated that Compound 49b rescued the high glucose-induced decrese in RvD1 and its receptors in diabetic animals and retinal endothelial cell culture, by upregulating 15-LOX enzyme expression. We also studied the phosphorylation of NF-κB p65 in two retinal cell types exposed to high glucose. High glucose conditions stimulated phosphorylation of NF-κB p65 at Thr-254, Ser-276, Ser-468, Ser-529, Thr-435 in retinal endothelial cells and Thr-254, Ser-281, Ser-311, Ser-468, Thr-435 in Müller cells. IL-4, an anti-inflammatory cytokine, suppressed phosphorylation at Thr-254, Ser-311, Thr-435 in retinal endothelial cells and Thr-254, Ser-276, Ser-281, Thr-435 in Müller cells. Futhermore, IL-4 also reduced related downstream NF-κB regulated molecules IL-8, TNF-α, and upregulated IL-10. The influence of type 1 vs type 2 immune backgrounds on DR-related damage using a model of retinal ischemia-reperfusion was studied in C57BL/6 and BALB/c mice. Notably, both neuronal and vascular degeneration were significantly less in BALB/c compared to B6 mice. Furthermore, key inflammatory molecules IL-1β, TNF-α, NF-κB, ICAM-1 and VEGF were downregulated in BLAB/c mice, as well. Collectively, we have shown the extensive role that inflammation plays in diabetic retinopathy pathogenesis. More importantly, the innate type 1/type 2 paradigm suggests that the potential of anti-inflammatory treamtents and pro-resolving lipid mediators in suppressing pathogenesis of DR. We expect our findings in pathogenesis of inflammation to contibute to development of anti-inflammatory and pro-resolving treatments for diabetic retinopathy

Retinal microvascular abnormalities and cognitive function in older people with type 2 diabetes

The deleterious effects of Type 2 diabetes on the brain have been shown to result in a greater prevalence of age-associated cognitive impairment and an enhanced risk of age-related cognitive decline in older diabetic populations. Type 2 diabetes is a complex metabolic disorder. Apart from the negative impact of abnormalities intrinsic to diabetes, diabetes-associated cerebral microvascular disease may contribute to this accelerated cognitive ageing. Direct in vivo evaluation of the cerebral microcirculation is difficult in humans and the vessels themselves are too small to permit detailed visualisation with current neuroimaging methods. The microvasculature of the retina may offer a window into such vascular status of the brain as there is considerable homology between the retina and cerebral microcirculations. Moreover, the retinal vasculature is known to be affected by a wide range of systemic pathologies and is unique in that it is the only vasculature that can be directly visualised and photographed. Retinal microvascular abnormalities (RMAs) have been understudied risk factors in cognitive ageing epidemiological research. Few reports have comprehensively examined cognitive function in relation to diabetic retinopathy. Also the relationship between cognitive function and quantitative aspects of retinal vascular network geometry has not been investigated in people with Type 2 diabetes. The results of a systematic review reported in this thesis showed inconsistent findings on the importance of the association between retinal microvascular abnormalities and cognitive dysfunction in predominantly non-diabetic populations. This may have reflected substantial differences between studies regarding the choice of population under study, the methods applied for measuring and defining RMAs, the types of neuropsychological tests administered for assessing cognitive function, and the approach taken in data analysis. The principal aim of the original research described in this thesis was to examine the associations of cognitive test performance with severity of diabetic retinopathy and quantitative parameters of retinal vascular network in a population-based sample of older people with Type 2 diabetes. Objective, reproducible and computerized retinal image analysis was used to quantify retinal vessel calibres and arteriolar bifurcation geometry in order to detect subtle changes in retinal vascular network. A valid estimation of peak prior cognitive ability allowed the further exploration of the impact of retinal microvascular abnormalities on imputed cognitive decline from best-ever levels of cognitive function to that measured in old age. The analysis was based on a cohort of 547 men and 519 women aged 60-75 years with Type 2 diabetes, randomly sampled from the Lothian Diabetes Register, Scotland, in 2006/2007 (the Edinburgh Type 2 Diabetes Study). A battery of seven cognitive tests was administered and standard 7-field binocular digital retinal photography undertaken. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Diabetic retinopathy was evaluated independently by two optometrists using a standardised grading protocol (a modification of the Early Treatment of Diabetic Retinopathy Scale). Quantitative retinal vascular parameters were measured by myself from a digital image of field 1 using semi-automated, computer-based methods. Retinal vessel calibres were summarised as the central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively) and arterio-venous ratio (AVR). Retinal arteriolar bifurcation geometry was expressed as arteriolar bifurcation angles (BA), arterial branching coefficient (BC), and sub-optimality (degree of deviation from optimality) of the retinal arteriolar angles. The statistical analyses were based on the 1,044 study participants who had both gradable retinal images and cognitive testing. Both general cognition, as indexed by a general cognitive factor reflecting the variance common to all the cognitive tests used, and most of the individual cognitive tests were negatively affected in participants with diabetic retinopathy relative to those without. These cognitive measures also showed a significant relationship with increasing severity of diabetic retinopathy (none, mild, and moderate-severe). Those with moderate-severe diabetic retinopathy had worst performances on general cognitive function, executive function, information processing speed, non-verbal memory and mental flexibility. When lifetime decline was estimated from peak, prior cognitive level, severity of diabetic retinopathy was significantly associated with a greater decline in information processing speed, non-verbal memory and mental flexibility and, in men for general cognition and executive function. The associations of severity of diabetic retinopathy with general cognition, executive function and information processing speed were independent of socio-demographic characteristics, cardiovascular risk factors, macrovascular disease, mood and hyperglycaemia. The associations with estimated decline in specific cognitive measures resulted principally from the impact of diabetic retinopathy on general cognitive ability. The study also showed that larger retinal arteriolar and venular calibres were both significantly associated with lower test scores on verbal memory in men. Multiple linear regression analyses demonstrated larger retinal arteriolar calibre was associated with a significantly greater decline in verbal memory after possible confounding by retinal venular calibre and vascular risk factors and disease was taken into account. In contrast, the study did not support an independent association between retinal venular calibre and cognitive decline in men or in women with Type 2 diabetes. Parameters of retinal arteriolar bifurcation geometry were not associated with cognitive outcome. Overall, these findings support the hypothesis that cerebral microvascular disease associated with Type 2 diabetes, reflected by the presence and severity of diabetic retinopathy, may exacerbate the effects of ageing on cognitive function. In particular, alterations in the blood-brain barrier may be an important pathophysiological mechanism in the occurrence of cognitive dysfunction in diabetic patients. They further may be added to the knowledge that gained from previous pathologic and brain imaging investigations demonstrating a relationship between markers of cerebral microvascular disease and cognitive dysfunction in diabetes. The role of quantitative parameters of retinal vascular network geometry in diabetes-related cognitive impairment is less clear. Prospective studies are required to clarify the temporal sequence of these associations and the eventual clinical significance of these small, early cognitive function changes. Such a follow-up project involving the present study population is underway. From a clinical perspective, if the above findings are substantiated, diabetes-associated cognitive dysfunction may be amenable to treatment and preventive strategies specifically targeted at protecting the cerebral microvasculature and reducing the risk of developing even mild microvascular disease in an ageing diabetic population