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Diabetic foot ulcers (DFUs) pose a therapeutic challenge to surgeons, especially in developing countries where health care resources are limited and the vast majority of patients present to health facilities late with advanced foot ulcers. Of the total 4238 diabetic patients seen at BMC during the period under study, 136 (3.2%) patients had DFUs. Diabetic foot ulceration constitutes a major source of morbidity and mortality among patients with diabetes mellitus at Bugando Medical Centre and is the leading cause of non-traumatic lower limb amputation. Joseph B Mabula, Ramesh M Dass, Rodrick Kabangila, Hyasinta Jaka, Mabula D Mchembe, Johannes B Kataraihya, Nkinda Mbelenge and Japhet M Gilyoma contributed equally to this work. BackgroundDiabetic foot ulcers (DFUs) pose a major public health problem worldwide and contribute significantly to morbidity and mortality of patients with diabetes [1]. MethodsStudy design and settingThis was a hospital based prospective study of all patients with diabetic foot ulcers seen in the surgical wards and at the surgical outpatient clinics of Bugando Medical Centre (BMC) over a two-year period from February 2008 to January 2010 inclusive.
The diagnosis of surgical site infection was based on careful clinical examination (purulent discharge from the wound + signs of inflammation) and identification of micro-organisms from the area of the operative wound suspected of being infected.The DFUs were graded according to Wagner's classification [12].
ResultsOf the total 4238 diabetic patients seen at Bugando Medical Centre during the study period, 136 patients (3.2%) had foot ulcers. DiscussionIn this review, the prevalence of diabetic foot ulcers amongst diabetic patients at Bugando Medical Centre was 3.2% which is comparable to studies in Kenya and South Africa [5, 13]. ConclusionDiabetic foot ulceration constitutes a major source of morbidity and mortality among patients with diabetes mellitus at Bugando Medical Centre and is the leading cause of non-traumatic lower limb amputation. Science, Technology and Medicine open access publisher.Publish, read and share novel research.
Similar to the nontransplant settings, the use of fasting plasma glucose (FPG) versus oral glucose tolerance test (OGTT) to define diabetes mellitus also changes the prevalence of NODAT.
CASE MANAGEMENT DISCUSSION- PRESENTATION AND SHARING OF INFORMATION ON COMPLICATED SKIN AND SOFT TISSUE INFECTION Rommel Q.
Presentation on theme: "CASE MANAGEMENT DISCUSSION- PRESENTATION AND SHARING OF INFORMATION ON COMPLICATED SKIN AND SOFT TISSUE INFECTION Rommel Q.
The Department of General Internal Medicine is responsible for providing primary care for patients with all kinds of  diseases. Board certii¬?ed members of the Japanese Society of Internal Medicine in our stai¬€ provide high quality primary care to patients with undii¬€erentiated problems. We provide comprehensive evaluation and treatment for patients with disorders associated with metabolic syndrome. We are devoted to supporting patients with depression or psychological distress caused by malignant diseases, diabetes mellitus and other medical conditions. We make ei¬€orts to provide nutrition support as a part of treatment for metabolic syndrome, as well as digestive, respiratory, or renal diseases. Stroke is the third leading cause of death and a major cause of long-term morbidity in the United States. Fortunately, our understanding of the etiology of stroke has increased dramatically in recent years.
In general, as the atherosclerotic burden increases - leading to carotid artery diameter reduction - the risk of active carotid disease, or stroke, increases as well. The commonly identified risk factors that predispose patients to an ischemic stroke, in general, correlate with the well-established risk factors for the development of atherosclerosis.
Patients with one or more risk factors for atherosclerosis probably have it in some form or another as the disease is not usually isolated to one vascular bed, but more commonly occurs as a 'pan-atherosclerotic' process. The accurate determination of the degree of carotid artery stenosis is important in the routine clinical assessment of patients with suspected or confirmed carotid artery disease.
In asymptomatic patients with documented high-grade carotid stenosis by duplex scan, most often a confirmatory test such as carotid MRA or cerebral angiography should be obtained.
The severity of carotid artery stenosis strongly correlates with the relative risk of stroke. Asymptomatic carotid artery disease is highly prevalent in the general population, particularly the patient with evidence of other atherosclerotic disease and in the elderly.
The vast majority of patients with carotid artery occlusive disease are asymptomatic and can be managed medically.
Surgery for symptomatic carotid artery stenosis has the greatest impact with regard to stroke reduction.
Neither the service provider nor the domain owner maintain any relationship with the advertisers. A prospective descriptive study was done at Bugando Medical Centre from February 2008 to January 2010 to describe our experience in the surgical management of DFUs in our local environment and compare with what is known in the literature. A multidisciplinary team approach targeting at good glycaemic control, education on foot care and appropriate footware, control of infection and early surgical intervention is required in order to reduce the morbidity and mortality associated with DFUs. BMC is a tertiary care, consultant and teaching hospital for the Weill-Bugando University College of Health Sciences (WBUCHS). In order to describe the type of foot ulcers, both feet were examined for the presence or absence of peripheral sensation or pulses (dorsalis pedis and posterior tibial arterial pulses). Most patients who were treated surgically underwent lower limb amputations in 56.7% of cases (Table 4). Patients who developed postoperative complications stayed long in the hospital (P = 0.012). Detection and management of diabetes mellitus in recipients of solid organ transplants 12.1.
Sugested guidelines for pre-transplant baseline evaluation and post-transplant screening for NODAT12.3.
In a prospective study designed to evaluate the use of OGTT for risk-stratifying patients for NODAT, Sharif et al.
ObesitySimilar to the general population, obesity has been shown to be associated with the development of NODAT in most studies (Setoguchi et al., 2005). This finding has not yet been validated in either transplant recipients or prospective trials in the general population (Bosch et al., 2006). We also oi¬€er highly diverse and special-ized medical services while placing emphasis on building trust with our patients.
ESWL was carried out for a gallstone (upper panel, arrowhead), which was successfully fragmented (lower panel). This newly gained information has essentially paralleled a more complete definition of the complex pathophysiology and epidemiology of atherosclerosis. The explanation as to why higher degrees of stenoses equate with a higher risk of stroke is basically two-fold. Of these risk factors, the most readily modifiable are hypertension, smoking, and hyperlipidemia.
The onset of the disease is often insidious, but the presenting symptoms are most frequently dramatic, e.g.
This information determines whether surgical referral and subsequent intervention are warranted, or if the patient is best served by the administration of an antiplatelet agent with serial follow-up.
This allows both a confirmation of the duplex findings as well as a precise degree or stenosis and a definition of any anatomical abnormalities.
If a high-grade lesion is detected on duplex scan, and the patient has symptoms of active embolic carotid disease, there is evidence to suggest that additional imaging in no way effects the treatment of these patients, i.e. Through the removal of atherosclerotic plaques, carotid endarterectomy (CEA) restores cerebral blood flow and reduces the risk of cerebral ischemia.
Compared with symptomatic stenosis, however, most available data suggest that asymptomatic carotid artery stenosis is associated with a relatively low risk of ipsilateral cerebral infarction.
Medical strategies may include the use of platelet agents, risk factor modification, and evaluation for other forms of atherosclerosis.
However, patients with high grade asymptomatic carotid occlusive disease (>80%) also enjoy a long-term reduction in stroke risk after CEA.
In case of trademark issues please contact the domain owner directly (contact information can be found in whois). Due to polymicrobial infection and antibiotic resistance, surgical intervention must be concerned. Foot ulcers were categorized as ischemic when peripheral pulses were absent but the sensation was intact, neuropathic when sensation was absent but the peripheral pulses were intact and neuro-ischemic when both sensation and peripheral pulses were absent.Data collection and Statistical analysisData were collected using a designed questionnaire. The median duration of diabetes was 8 years while the median duration of foot ulcers was 18 weeks. These differences in prevalence may be a reflection of regional variations in prevalence of diabetes mellitus and the local operating risk factors of diabetic foot ulcer disease. There has been scant literature on the incidence of diabetes mellitus after a successful pancreas transplant. Of interest, ADPKD patients with normal native kidney function have been shown to have insulin resistance and compensatory hyperinsulinemia (Vareesangthip et al., 1997). Once thought to be a static or slowly progressive obstructive process, it is now clear that atherosclerosis is a dynamic, inflammatory disease that more commonly leads to symptoms secondary to plaque rupture with associated thrombosis, atheroembolism, or thromboembolism, rather than ischemia from a low-flow state. First, larger plaques are generally unstable and more prone to higher rates of intraplaque hemorrhage and distal embolization. If a patient presents with hard signs or symptoms of embolic cerebrovascular disease - amaurosis fugax, focal paresis or plegia, or dysphasia - or an asymptomatic cervical bruit, then a carotid duplex ultrasound is warranted. While medical therapy clearly plays a role in the management of atherosclerosis in general and carotid artery disease in particular, the results from three major prospective contemporary studies provide compelling evidence for the benefit of CEA versus medical therapy alone. Patients with asymptomatic disease should be considered for surgery when the lesion has reached 70-80%. In general, serial follow-up for carotid artery stenosis should be performed on an every sixth month basis.
The outcomes from surgical intervention have clearly been linked to the experience of the surgeon performing the procedure.
The prevalence of DFUs among hospitalized patients with diabetes in Iran was 20% [9].The burden of diabetic foot ulceration is heaviest in the resource-poor parts of the world where the incidence is high but sophisticated and efficient diagnostic, therapeutic and rehabilitative facilities are sparse.
BMC is one of the four largest referral hospitals in the country and serves as a referral centre for tertiary specialist care for a catchment population of approximately 13 million people from Mwanza, Mara, Kagera, Shinyanga, Tabora and Kigoma.
The questionnaire was pre-tested before use to a small sample of 10 diabetic patients to determine whether the respondents have any difficulty in understanding the questionnaire and whether there are ambiguous or biased questions. Although not a risk factor per se, increased insulin clearance after a successful kidney transplant can unmask pre-transplant impaired glucose tolerance or pre-existing diabetes mellitus that manifests clinically as NODAT. Although some studies failed to demonstrate an association between obesity and the development of NODAT, obesity and its associated peripheral insulin resistance state is a known risk factor for type 2 diabetes. Carotid atherosclerosis develops almost exclusively in the region of the carotid bulb and proximal internal carotid artery. And second, higher rates of thrombus formation occur in areas of high shear stress - such as that which develops in a high-grade stenosis - leading to subsequent distal embolization. Other predictors of stroke include TIA's (as mentioned above), previous stroke, carotid bruit or defined stenosis, and others. Given the magnitude of the problem, the evaluation and management algorithm for patients with significant risk factors for, clinical symptoms of, or physical findings suggestive of carotid artery disease bears mentioning. Duplex ultrasonography has revolutionized the approach to peripheral vascular in general and carotid artery disease in particular.
Others recommend a confirmatory study for the same reasons cited in the asymptomatic lesion discussion.
When performed by experienced surgeons, CEA, most prominently, improves the chance of stroke-free survival in high-risk symptomatic patients. All surgeons undertaking CEA should be able to honestly discuss their operative results with their patients to allow the patient to make an informed choice.
The challenge of management of DFUs in developing countries is that most patients with DFUs present to healthcare facilities late with advanced foot ulcers. Diabetic patients are first seen in the internal medicine department where screening for the foot at risk for ulceration is done, and only patients who are found to have active foot ulceration are presented to surgeons.Study subjectsAll patients who presented to the surgical wards or surgical outpatient clinic with diabetic foot ulcers were consented for the study and those who met the inclusion criteria were consecutively enrolled into the study.
Male predominance may be attributed to their smoking habits which were recorded in 35.3% of cases (all of them were males). The variation in the reported incidence may be due in part to the lack of a standard definition of the condition, the duration of follow-up, the presence of both modifiable and non-modifiable risks factors, and the type of organ transplants among others.


Risk factors for NODATRisk factors for the development of NODAT are categorized as non-modifiable and modifiable or potentially modifiable, the former category to facilitate the identification of high risk individuals, and the latter two categories to optimize the management of NODAT. Pharmacological managementWhen lifestyle modification fails to achieve adequate glycemic control, medical intervention is recommended. Unfortunately, most strokes occur without warning, and stroke survivors are frequently left markedly disabled, leading to a staggering financial and emotional burden to both patient and family - and to the health care system in general.
There are many theories as to why this region is prone to atherosclerosis, but the most commonly accepted one suggests that the lateral arterial wall is exposed to an area of low shear stress, a common finding in areas of atherosclerosis. A concomitant carotid duplex scan should be obtained to detect progression of carotid stenosis in an effort to identify those patients who may benefit from surgical intervention. The reasons for the late presentation include poor economic capabilities in cost shared healthcare systems, inadequate knowledge of self-care, socio-cultural reasons and poor and inadequate diabetes healthcare [5]. Smoking is a contributory factor as a result of vascular wall thickening, reduction in blood circulation and ischemic changes in the affected neurons [15]. Nonetheless, the pattern of body fat distribution has been suggested to play a contributory role.
Orally administered agents can be used either alone or in combination with other oral agents or insulin.
All patients should be counseled as to the warning signs of TIA and stroke, and told to go to the closest Emergency Department immediately should they occur. Studies in Tanzania have shown that surgical intervention of DFUs after the onset of gangrene may be too late to prevent death [10, 11], therefore early presentation by patients and prompt surgical intervention during less severe rather than during later stages of an ulcer may improve patients outcome and reduce mortality rates [11].There is paucity of published data on surgical management of DFUs in our environment as there is no local study which has been done in any hospital in Tanzania and Bugando Medical Centre in particular. Identification of patients with the foot at risk for ulceration was done in the medical wards or diabetic clinics and diabetic patients who were found to have active foot ulceration were referred to the surgical wards or surgical outpatient clinics for proper surgical management.
Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas spp and Proteus spp) had multiple resistant to almost all tested antibiotics (such as ampicillin, augumentin, cotrimoxazole, tetracycline, penicillin, gentamicin, erythromycin, oxacillin etc). Pham5[1] Department of Medicine, Nephrology Division, Kidney Transplant Program, David Geffen School of Medicine at UCLA, United States of America[2] Department of Medicine, Greater Los Angeles VA Medical Center and David Geffen School of Medicine at UCLA, United States of America[3] Department of Medicine, Cardiology Division, Bay Pines VA Medical Center, Bay Pines, Florida, United States of America[4] Department of Medicine, Division of Cardiovascular Diseases, VA Medical Center, University of Tennessee Health Science Center, Memphis, TN, United States of America[5] Department of Medicine, Nephrology Division, UCLA-Olive View Medical Center and David Geffen School of Medicine, United States of America1.
Corticosteroid-associated NODATThe now well-established contributory role of corticosteroid on NODAT was first described by Starlz in 1964 in renal transplant recipients. Studies in healthy women showed that upper body or male-type obesity has a much greater association with insulin resistance and impaired glucose tolerance than lower body or female-type obesity (Kissebah et al., 1982).
The choice of pharmacologic therapy is based on the potential advantages and disadvantages associated with the different classes of oral agents. This study was intended to describe our own experience in the surgical management of DFUs in our local setting, outlining the prevalence, pattern and treatment outcome of DFUs and compare our results with that reported in literature.
Diabetic foot ulcer was operationally defined as a breach on the normal skin occurring as induration, ulceration or change of color on the foot for duration equal to or more than two weeks.
Introduction New onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. In one single-center study consisting of 126 lung and heart-lung transplant recipients, diabetes has a reported prevalence of 6% at 1 year and 7% at 5 years. Table 3 summarizes the mechanisms of action and potential advantages and disadvantages of different classes of oral agents. The student's t test was used to test for differences between quantitative variables and Chi squared test was used to test for associations and comparisons of proportions. These studies were conducted in different centers that offer diabetes care of different qualities. The lower prevalence of diabetes in this study was thought to be due in part to a lower frequency of cystic fibrosis patients (8.7% vs.
It is speculated that intra-abdominal fat or waist-to-hip ratio may be more important risk factors for NODAT than total body weight or BMI (Davidson et al., 2003). This comparable mean age may suggest certain time-dependent risk factors in the evolution and course of diabetic foot ulcer disease which are common to diabetes in whatever environment. Kidney transplant recipients who develop NODAT have variably been reported to be at increased risk of fatal and nonfatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes.
In contrast to the DOPPS study results, in an analysis of the national cohort study consisting of more than 5,000 dialysis patients with type 2 diabetes Brunelli et al. Age of onset of diabetes is also different in continents.In this study, the median duration of diabetes is in keeping with other studies [5, 10, 17]. Limited clinical studies in liver, heart and lung transplants similarly suggested that NODAT has an adverse impact on patient and graft outcomes. Ischemic heart disease was also found to be associated with an increased incidence of NODAT (Ye et al., 2010b). The following chapter presents an overview of the literature on the current diagnostic criteria for NODAT, its incidence after solid organ transplantation, suggested risk factors and potential pathogenic mechanisms.
In a single-center study consisting of 97 consecutive adult heart transplant recipients, a family history of diabetes and the need for insulin beyond the first 24 hours after transplantation were shown to be risk factors for the development NODAT (Depczynski et al., 2000).
Whether complete withdrawal of chronic low dose corticosteroid therapy (prednisolone 5 mg daily) improves glucose metabolism remains to be studied. In a recent retrospective analysis consisting of 640 nondiabetic renal transplant recipients Bayer et al.
This finding may imply the differences in the quality of diabetes care where German and Indian patients, on average have longer duration of diabetes exposure before they develop foot ulcers.
The impact of NODAT on patient and allograft outcomes and suggested guidelines for early identification and management of NODAT will also be discussed. Nonetheless, in recent years several studies have suggested a potential beneficial effect of steroid-free immunosuppression on NODAT risk reduction (Luan et al., 2011). Bacterial profile revealed polymicrobial pattern and Staphylococcus aureus was the most frequent microorganism isolated. It is possible that better diabetes care that they receive delays the onset of foot ulcer disease.The majority of patients in the present study presented to the surgical department between four weeks and 52 weeks (median of 18 weeks) of onset of an ulcer. Multivariate analysis incorporating the individual metabolic syndrome components as covariates demonstrated that of all the pre-transplant metabolic syndrome components, only low-density lipoprotein was independently associated with the development of NODAT.The precise role of the metabolic syndrome or metabolic syndrome component(s) in the development of NODAT remains to be defined. Nonetheless, great caution should be exercised when rosiglitazone is used in the setting of kidney transplantation because all kidney transplant recipients should be regarded as having at least stage II-IV chronic kidney disease. All the microorganisms isolated showed high resistance to commonly used antibiotics except for Meropenem and imipenem, which were 100% sensitive each respectively.
Nonetheless, the overlapping metabolic risk factors for type 2 diabetes and cardiovascular disease (e.g.
Late presentation in our patients may be attributed to low socioeconomic status, poverty, lack of diabetes education (regarding the importance of general foot care, the significance of diabetes and its complications), unrecognized foot trauma from walking barefoot and lack of access to medical care.
Figure 1.Risk Factors for NODATSimilar to type 2 diabetes in the general population, both genetic and environmental factors have been suggested to play a role in the development of NODAT.
The cumulative incidence of NODAT within three years post-transplant were 12.3% in steroid-free vs.
Other contributing factors for late presentation include attempts at home surgery, trust in faith healers and undetected diabetes.Wagner's classification which is based on severity of diabetic foot is widely used by surgeons [18]. There is strong evidence suggesting that individuals with a family history of diabetes among first-degree relatives have an increased risk of developing NODAT with one study reporting a seven fold increase in the condition (Davidson et al., 2003).
ProteinuriaEarly report from single-center study suggested an association between proteinuria on day 5 after transplantation and the development of NODAT (Kuypers et al., 2008). A randomized, placebo-controlled, double-blind, prospective trial to evaluate the safety and efficacy of vildagliptin in patients with NODAT is currently underway (Haidinger et al., 2010). According to Wagner's classification our patients were in the severe forms as grades IV and V constituted 52.9% collectively, and this is similar to what has been reported in other studies with an incidence range from 42% to 68% [2, 18, 19], but still less than the 74% reported in a western Sudan study [14]. The current WHO and American Diabetes Association (ADA) guidelines for the diagnosis of prediabetic states (IFG and IGT) and diabetes mellitus are provided in Table 1 (modified from Davidson et al., 2003).
The increased prevalence of NODAT associated with a family history of diabetes has been documented across all types of solid organ transplantation. Overall, steroid-containing regimens at the time of hospital discharge were associated with a 42% increased risk for NODAT. However, these findings have been challenged because proteinuria on day 5 may just reflect the highly concentrated urine associated with hyperglycemia-induced osmotic diuresis from the early posttransplant use of high dose corticosteroid or residual native kidney proteinuria. Caution should be exercised when these agents are used in the transplant setting, particularly with regards to drug to drug interactions.
High percentages of advanced foot ulcer disease in our study may be related to duration of diabetes, late presentation to healthcare professionals and presence of co-morbidities.Wagner's classification score may be different for a surgeon as compared to physicians in the internal medicine. Notably, patients from programs that frequently adopted steroid-free regimens had reduced odds of NODAT compared with those from programs that commonly used steroid-contatining regimens.
Furthermore, it has been shown that immediate posttransplant proteinuria generally resolves several weeks after transplantation (Myslak et al., 2006). Vildagliptin should be avoided in patients with hepatic impairment and stage IV-V chronic kidney disease and the dose of sitagliptin should be adjusted for renal insufficiency.
Physicians in the internal medicine receive diabetic foot problem at an earlier stage as compared to surgeons in the surgical department, where patients are admitted at advanced stages.
Other non-modifiable risk factors include recipient male gender, the presence of certain HLA antigens such as HLA A 30, B27, B42, increasing HLA mismatches, DR mismatch, deceased donor kidneys, male donor, and acute rejection history (Depczynski et al., 2000). The dose dependent diabetogenic effect of corticosteroid was also observed in recipients of nonrenal organ transplants. Nonetheless, in a subsequent single-center retrospective study designed to evaluate the impact of early proteinuria (3 and 6 months after transplantation) and urinary albumin excretion (UAE) on NODAT, Roland et al. Some patients may report to surgeons directly but the vast majority of them are referred to surgeons by physicians from internal medicine or endocrinologists, as part of the combined management. Adult polycystic kidney disease (ADPKD) has been suggested to confer an increased risk of developing NODAT in some studies but not in others (P.T. This is evident from our study where most of patients presented to the surgical department with advanced disease (Wagner's grade IV-V).
SummaryNODAT is a common complication after solid organ transplantation and has variably been reported to have an adverse impact on patient and allograft outcomes. NODAT-free survival was greater in patients with normoalbuminuria than in those with microalbuminuria, and greater in those with microalbuminuria than in those with macroalbuminuria (p=0.0326). Risk stratification and intervention to minimize risk should be an integral part in the management of the transplant recipients. Diabetic foot ulcer is one of the preventable and curable complications of diabetes [18, 19]. The authors also demonstrated that pulse pressure was an independent risk factor for NODAT, suggesting that early low-grade proteinuria and pulse pressure may be markers of the metabolic syndrome or vascular damage or both.
Clinicians must be familiar with the patients’ immune history prior to manipulating their immunosuppressive therapy.in an attempt to ameliorate NODAT risk. Physicians in internal medicine have an important role in the prevention, early diagnosis and management of diabetic foot complications. When lifestyle modification fails to achieve adequate glycemic control, medical intervention is often necessary. HypomagnesemiaIn the general population, not only has hypomagnesemia been shown to be associated with type 2 diabetes, but numerous studies have also reported an inverse relationship between glycemic control and serum Mg levels (P.C. The routine care of patients with NODAT should include an evaluation of hemoglobin A1C level every three months and regular screening for diabetic complications. This high amputation rate in our study could be attributed to the late presentation and severity of the disease on presentation.
It should be noted that hemoglobin A1C cannot be accurately interpreted within the first three months post transplantation due to various factors including possible blood transfusions in the early posttransplant period and the presence of anemia or impaired allograft function.
It is clearly evident from our study that more than half of our patients presented with high Wagner's grade (a‰? 4) which resulted in the high rate of amputation. Similar to the nontransplant settings, hypomagenesemia has also been shown to be an independent predictor of NODAT in recipients of renal and liver transplants. Blood transfusions may render the test invalid until new hemoglobin is formed and the presence of anemia and kidney impairment can directly interfere with the A1C assay. In this study, patients who had major lower limb amputation had significantly high complication rate than patients who underwent minor lower limb amputation.Measures such as strict glycaemic control as well as participation in multi-disciplinary diabetic clinics consisting of vascular, orthopedic surgeons, internist, podiatrist, rehabilitation physician, orthopaedic shoemaker, and diabetic specialist nurse have been shown to significantly reduce complications and amputation rates [4, 11].
In a single-center retrospective analysis consisting of 254 renal transplant recipients Van Laecke et al.


An artifactual reduction in A1C level has been reported in islet cell transplant recipients taking dapsone for pneumocystis carinii (P.
While the association between the use of CNIs was strongly related to hypomagnesemia, NODAT disappeared after adjustment for Mg levels suggesting that the diabetogenic effect of CNIs is at least in part related to hypomagnesemia. In this study, surgical site infection was the most common postoperative complication accounting for 18.8% of cases. Furthermore, a lower proportion of CsA-ME patients with NODAT required hypoglycemic medication or dual therapy with insulin and oral hypoglycemic agents compared with their tacrolimus-treated counterparts. Conversely, the use of mTOR inhibitors appeared to be a risk factor for NODAT after adjustment for Mg levels.
In transplant recipients with multiple CVD risk factors, more frequent monitoring of lipid profile should be performed at the discretion of the clinicians.
The bacteriological patterns revealed polymicrobial bacterial growths with Staphylococcus aureus and Escherichia coli predominating.
The greater diabetogenic effect of tacrolimus compared to CSA has been reported to occur across renal and nonrenal transplant groups. The same group of authors subsequently demonstrated that both pretransplant hypomagenesemia and hypomagnesemia in the first-month posttransplantation were independent predictors of NODAT in recipients of liver transplants (Van Laecke et al., 2010).
Statins or the HMG-CoA reductase inhibitors are the most widely used lipid lowering agents in both the nontransplant and transplant settings.
In a meta-analysis to evaluate the reported incidence of NODAT after solid organ transplantation, Heisel and colleagues found a higher incidence of insulin-dependent diabetes mellitus (IDDM) in Tac- vs.
Ati et al[28] reported a high frequency of monomicrobial bacterial infections.All the microorganisms isolated in this study showed high resistance to commonly used antibiotics except for Meropenem and imipenem which were all 100% sensitive respectively. Unfortunately, these antibiotics are expensive for the level of economical development which subsists in this part of the developing world.
Whether Mg supplementation and correction of Mg deficiency reduce the incidence of insulin resistance or NODAT remains to be studied. The finding of polymicrobial infection and multiple resistant to commonly used antibiotics calls for immediately surgical intervention.
Impaired glucose tolerance before transplantationAbnormal glucose metabolism has been reported to be a risk factor for the development of NODAT in some but not all studies. The reason for high mortality rate in our study can be explained by the fact that, some of the patients were admitted in our hospital with advanced DFUs and sepsis, leading to multiple organ failure and death. Nonetheless, not all studies showed that Tac is more diabetogenic than cyclosporine (Meiser et al., 1998). A study in Tanzania revealed that the overall mortality rates for amputees and non-amputees were similar (29%); the highest in-patient mortality rate (54%) was observed among patients with severe (Wagner grade a‰? 4) ulcers who did not undergo surgery. Thus mortality rates among patients with severe ulcers remain high despite surgery and surgery undertaken during the less severe stages of ulcers may improve patient outcome. Early recognition of lesions and prompt initiation of the appropriate antibiotic therapy, as well as aggressive surgical debridement of necrotic tissue and bones, and modification of host factors i.e. In a single-center study consisting of 45 OLT recipients treated with either CSA (n=9) or high- (n=15) vs.
Among patients with IFG pretransplant, 70% had hyperglycemia at one year (IFG 43% and NODAT 27%). However, despite this limitation, the study has highlighted our experiences in the surgical management of diabetic foot ulcers.
Interaction between tacrolimus and concomitant hepatitis C infection (HCV)In a retrospective study of more than 400 kidney transplant recipients with no known pre-transplant diabetes, Bloom and colleagues have shown that among the HCV(+) cohort, NODAT occurred more often in the Tac- compared with the CSA-treated groups (57.8% vs.
HCV-associated NODATThe association between HCV infection and impaired fasting glucose or the development of overt type 2 diabetes mellitus in the general population has long been suggested. In contrast, among the HCV (-) cohort, the rates of NODAT were similar between the two calcineurin inhibitor (CNI) groups (Tac vs.
Potential mechanisms of the diabetogenic effect of HCV infection include insulin resistance, decreased hepatic glucose uptake and glycogenesis, and direct cytopathic effect of the virus on pancreatic ? cells (Bloom & Lake, 2006). Similar to the non-transplant settings, the link between hepatitis C and the development of NODAT has also been recognized in solid organ transplant recipients. Whether concomitant exposure to tacrolimus and HCV plays a synergistic role in the development of NODAT remains speculative.
Clinical studies in recipients of orthotopic liver transplant (OLT) recipients have implicated insulin resistance associated with active HCV infection as a predominant pathogenic mechanism. Effects of sirolimus on glucose metabolismEarly large randomized clinical trials suggested that sirolimus is devoid of diabetogenic effects either used alone or in combination therapy with CNI.
It was suggested that the virus had a direct effect on insulin resistance as no difference in ? cell function or hepatic insulin extraction between the HCV (+) and (-) groups was observed.
In one single-center study, tacrolimus and sirolimus combination therapy was found to be associated with a higher incidence of NODAT than tacrolimus alone immunosuppression (Sulanc et al., 2005).
Subsequent large registry study also demonstrated an association between sirolimus and the development of NODAT. Cytomegalovirus-associated NODATThe link between cytomegalovirus (CMV) infection and the development of NODAT was first reported in 1985 in a renal transplant recipient (Lehr et al., 1985).
In an analysis of the USRDS database consisting of more than 20,000 primary kidney transplant recipients receiving sirolimus (Sir) or CNI (CsA or Tac) or both in various combination therapy with an antimetabolite (MMF or AZA), Johnston et al. Limited studies suggested that both asymptomatic CMV infection and CMV disease are independent risk factors for the development of NODAT.
Patients with active CMV infection had a significantly lower median insulin release compared to their CMV negative counterparts, suggesting that impaired pancreatic ? cell insulin release may be involved in the pathogenic mechanism of CMV-associated NODAT. It is speculated that CMV-induced release of proinflammatory cytokines may lead to apoptosis and functional disturbances of pancreatic ?-cells (Hjelmasaeth et al., 2005). Anti-CD25 monoclonal antibodies In a single-center study consisting of 74 stable kidney transplant recipients with 3 month-follow-up, Bayes et al. Kidney transplantsClinical studies evaluating the impact of NODAT on patient and allograft outcomes after solid organ transplantation have yielded variable results. The development of NODAT has also been shown to be associated with an adverse impact on patient survival and an increased risk of graft rejection and graft loss, as well as an increased incidence of infectious complications (Ojo, 2006). Calcineurin inhibitorsImpaired insulin secretion has been suggested to contribute to the development of CNI-associated NODAT (Crutchlow & Bloom, 2007). The study consisted of >37,000 renal transplant recipients with a functioning transplant for at least 1 year. Risk stratification according to diabetes status (pre-transplant diabetes, NODAT) and acute rejection (AR) at 1 year demonstrated that pre-transplant diabetes is the major predictor of all-cause and cardiovascular mortality whereas acute rejection during the first year is the major predictor of death-censored transplant failure.
In recipients of pancreas transplants, both calcineurin inhibitors CSA and Tac have been shown to cause reversible toxicity to islet cells. In contrast, NODAT alone was not associated significantly with any study outcomes (Kuo et al., 2010). In a study of 26 pancreas allograft biopsies from 20 simultaneous kidney-pancreas transplant recipients, a significant correlation was seen between the presence of islet cell damage and serum levels of Tac and CSA, as well as with the Tac peak level (Drachenberg et al., 1999). Nonetheless, the study results were regarded as inconclusive due to the wide confidence intervals and the relatively short duration of follow-up. Cytoplasmic swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in ?-cells were demonstrated on electron microscopy. It is noteworthy that in a large registry study consisting of more than 27,000 primary kidney transplant recipients with graft survival of at least 1 year and with longer-term follow-up, Cole et al. Serial biopsies from two patients with hyperglycemia and evidence of islet cell damage receiving Tac immunosuppression demonstrated reversibility of the damage upon discontinuation of tacrolimus. Sirolimus (mTOR inhibitors)Suggested pathogenic mechanisms of sirolimus-induced hyperglycemia include sirolimus-associated impaired insulin-mediated suppression of hepatic glucose production, ectopic triglyceride deposition leading to insulin resistance, and direct ? cell toxicity (Crutchlow & Bloom, 2007). However, studies on the effects of sirolimus on insulin action and secretion have yielded variable and conflicting results. Currently existing literature suggests that the effects of sirolimus on glucose metabolism appear to be cell-species- and dose-dependent (Subramanian & Trence, 2007).
Anti-CD25 monoclonal antibodiesThe pathogenic mechanisms of anti-CD25-induced NODAT have not been established.
However, suppression of regulatory T-cells has been suggested to play a contributory role (Aasebo et al., 2010). However, there was no difference in patient survival between the two groups at 1-, 2- and 5-years follow-up. Studies in diabetes-prone mice have shown that anti-IL2-antibody treatment trigger insulinitis and early onset diabetes through inhibition of Foxp3-expressing CD25+ CD4+ regulatory T-cells (Setoguchi et al., 2005). Suggested pathogenic mechanisms of immunosuppressive drug-induced NODAT are summarized in table 2. Pre-transplant baseline evaluationSuggested guidelines for pre-transplant baseline evaluation of potential transplant candidates is shown in Figure 2. Patients with evidence of IGT or abnormal OGTT before transplantation should be counseled on lifestyle modifications including weight control, diet, and exercise. The goals for the life-style modification involved achieving and maintaining a weight reduction of at least 7 percent of initial body weight through a healthy low-calorie, low-fat diet and at least 150 minutes of physical activity per week. Selection of an immunosuppressive regimen should be tailored to each individual patient, weighing the risk of developing diabetes after transplantation against the risk of acute rejection. Early detection of NODAT after transplantation Studies investigating the best predictive tool for identifying patients at risk for developing NODAT early after transplantation are currently lacking. While fasting plasma glucose (FPG) is readily available in clinical practice it may be normal in kidney transplant recipients with abnormal glucose homeostasis. It has been suggested that transplant patients have an atypical form of insulin resistance and their plasma glucose often peeks before lunch. However, it is noteworthy that while acute rejection has been suggested to increase the risk for NODAT, it usually does not occur before day 5. Obtaining OGTT and FPG at day 5, therefore, may preclude the subset of patients with higher risk of developing NODAT. Hence, it has been suggested that performing OGTT at 10-12 weeks post-transplantation might be useful as an alternative or supplementary test to day 5 OGTT (P.T. The routine recommendation of performing an OGTT early after transplantation awaits further studies. Suggested pre-transplant baseline evaluation and post-transplant screening for NODAT is shown in Figure 2. Management of established NODATThe management of NODAT should follow the conventional approach for patients with type 2 diabetes mellitus as recommended by many clinical guidelines established by well-recognized organizations including the American Diabetes Association (ADA). Nonetheless, it should be noted that the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was discontinued prematurely because of a satistically significant increase in all-cause mortality in the intensive- compared with the standard- glycemic treatment groups (Gerstein et al., 2008).
Study similar to that of the ACCORD study in recipients of solid organ transplantation is lacking.
Nonetheless, the determination of hemoglobin A1C target levels for solid organ transplant recipients should be individualized based on hypoglycemia risks.
Dietary modification and physical activityThe Diabetes Prevention Program has demonstrated that a structured diet and physical activity program that achieves and maintains modest weight loss for overweight adults with IGT can significantly reduce the development of diabetes.
Defining realistic goals such as a target weight loss of 5-10% of total body weight and patient- centered approach to education may be invaluable in achieving success. Modification of immunosuppressionModification of immunosuppression should be considered in high-risk patients.
Corticosteroid dose reduction has been shown to significantly improve glucose tolerance during the first year after transplantation (Kasiske et al., 2003).
Steroid-sparing regimen or steroid avoidance protocol should be tailored to each individual patient. Tac to CSA conversion therapy in patients who fail to achieve target glycemic control or in those with difficult to control diabetes has yielded variable results. Belatacept -- a selective T cell costimulation blocker, is a promising new immunosuppressant that has been suggested to have better cardiovascular and metabolic risk profiles compared with cyclosporine (lower blood pressure, better lipid profiles and lower NODAT incidence) (Vanrenterghem et al., 2011).



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