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Microvascular Complications (microvascular + complications)
Selected AbstractsType 2 diabetes mellitus and obesity in sub-Saharan AfricaDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2010Vivian C. Tuei Abstract While communicable diseases such as human immunodeficiency virus/acquired immune deficiency syndrome, malaria, and tuberculosis have continued to pose greater threats to the public health system in sub-Saharan Africa (SSA), it is now apparent that non-communicable diseases such as diabetes mellitus are undoubtedly adding to the multiple burdens the peoples in this region suffer. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes (90,95%), exhibiting an alarming prevalence among peoples of this region. Its main risk factors include obesity, rapid urbanization, physical inactivity, ageing, nutrition transitions, and socioeconomic changes. Patients in sub-Saharan Africa also show manifestations of ,-cell dysfunction and insulin resistance. However, because of strained economic resources and a poor health care system, most of the patients are diagnosed only after they have overt symptoms and complications. Microvascular complications are the most prevalent, but metabolic disorders and acute infections cause significant mortality. The high cost of treatment of T2DM and its comorbidities, the increasing prevalence of its risk factors, and the gaps in health care system necessitate that solutions be planned and implemented urgently. Aggressive actions and positive responses from well-informed governments appear to be needed for the conducive interplay of all forces required to curb the threat of T2DM in sub-Saharan Africa. Despite the varied ethnic and transitional factors and the limited population data on T2DM in sub-Saharan Africa, this review provides an extensive discussion of the literature on the epidemiology, risk factors, pathogenesis, complications, treatment, and care challenges of T2DM in this region. Copyright © 2010 John Wiley & Sons, Ltd. [source] Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USAPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2000Michael Tuck First page of article [source] Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literatureDIABETES OBESITY & METABOLISM, Issue 4 2010L. Nalysnyk Aim: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). Methods: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. Results: A total of 18 studies ,8 on type 1 DM and 10 on type 2 DM patients,meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Conclusions: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base. [source] Novel pathways for glycaemic control in type 2 diabetes: focus on bile acid modulationDIABETES OBESITY & METABOLISM, Issue 11 2008Eliot A. Brinton Type 2 diabetes is a common disorder with high risk of macrovascular and microvascular complications. These complications are largely driven by hyperglycaemia, dyslipidaemia and hypertension, for which aggressive treatment is thus warranted. Achieving and maintaining control of all three risk factors is especially difficult, however, and new therapeutic approaches could be useful. Bile acids have a well-established and important role in cholesterol homeostasis. Normally, their levels are maintained primarily by ileal reabsorption and enterohepatic recycling. Bile acid sequestrants bind bile acids in the intestine, reduce this recycling and deplete the bile acid pool, thereby stimulating use of hepatic cholesterol for bile acid synthesis, which leads to accelerated removal of LDL from the plasma and a decrease in LDL-cholesterol levels. Interestingly, recent evidence suggests that bile acid sequestrants can lower glucose levels to a clinically meaningful degree. This review presents this evidence and the possible mechanisms by which these glucose-lowering effects occur and discusses the apparently unique ability of bile acid sequestrants among lipid-lowering agents to significantly improve two cardiovascular risk factors, hyperglycaemia and dyslipidaemia. There is renewed interest in the use of bile acid sequestrants in individuals with type 2 diabetes, most of whom would benefit from additional reductions in both LDL-cholesterol and glycaemia. [source] Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implicationsDIABETES OBESITY & METABOLISM, Issue 6 2007Andrew J. Krentz Convention partitions the complications of diabetes into two main subtypes. First are the diabetes-specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy. [source] Does ethnic origin have an independent impact on hypertension and diabetic complications?DIABETES OBESITY & METABOLISM, Issue 2 2006V. Baskar Aim:, The morbidity and mortality from cardiovascular complications in diabetes reputedly differ with ethnicity. We have evaluated the prevalence of hypertension and vascular complications amongst Afro-Caribbean (AC), Caucasian (C) and Indo-Asian (IA) ethnic subgroups of a district's diabetes population to estimate the impact of ethnic origin as an independent risk variable. Methods:, Of the 6485 registered adult individuals, 6047 had ethnic data available and belonged to one of the three ethnic groups described (AC 9%, C 70% and IA 21%). Statistical analyses were performed using spss version 11.5. Results:, Results are presented as mean ± s.d. or percentage. IAs were younger (AC 63 ± 13, C 61 ± 15 and IA 57 ± 13 years), were less obese (body mass index 30 ± 8, 29 ± 9, 28 ± 6 kg/cm2) and had lower systolic blood pressure (155 ± 25, 149 ± 24, 147 ± 24 mmHg) and lower prevalence of hypertension (82%, 74% and 68%) compared with C, who had lower values than AC (all p < 0.01). Relative to C group, the AC group had higher prevalence of hypertension and microvascular complications but lower macrovascular disease burden, while the IA group had lower hypertension and macrovascular complications but with comparable microvascular disease burden [microvascular (51%, 44% and 46%; p < 0.01) and macrovascular (33%, 40% and 32%; p < 0.001)]. On logistic regression, this effect of ethnic origin on diabetic complications was found to be significant and independent of other risk variables. Conclusion:, Hypertension and diabetic complication rates were different amongst ethnic subgroups. On logistic regression, it was found that the difference in distribution of age and diabetes duration largely accounted for this difference, although ethnic origin remained an independent risk factor. [source] Metabolic memory in diabetes,focus on insulinDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Derek LeRoith Abstract Large-scale clinical trials have demonstrated that metabolic control achieved early in the course of diabetes substantially reduces development and progression of diabetes and the associated microvascular complications. Additionally, prospective observational studies have demonstrated that atherogenic and inflammatory mediators are elevated even prior to the onset of diabetes and significantly contribute to subsequent development of macrovascular complications. Collectively, these data suggest that metabolic memories are stored early in the course of diabetes. We believe that insulin suppresses inflammation and also suppresses glucotoxicity and lipotoxicity (and the consequences thereof, such as the formation of advanced glycation end products and epigenetic phenomena), and thus has a pivotal and beneficial role. Comprehensive metabolic control, especially when instituted early, may alter the natural history of diabetic complications by affecting this metabolic memory. Thus, our overall goal is to understand in more detail the molecular mechanisms involved in these changes, thereby affording us opportunities to reduce the long-term effects of diabetes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Postprandial hyperglycaemia in type 2 diabetes: pathophysiological aspects, teleological notions and flags for clinical practiceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2004Eleni I. Boutati Abstract Type 2 diabetes subjects carry an excess risk for micro- and macrovascular disease and a higher cardiovascular morbidity and mortality rate. The beneficial impact of tight glycaemic control,evidenced by the integrated marker of fasting glucose and postprandial glucose values, the HbA1c,for the prevention of microvascular complications is definitely confirmed. Over the past few years, several studies have identified postprandial hyperglycaemia as a better predictor of cardiovascular or even of all-cause mortality, as well as an independent risk factor for atherosclerosis. The continuous glucose monitoring could offer a rationale means for the detection of postprandial hyperglycaemia and ultimately for its effective management. Advances in technology keep a promise for a reliable, convenient and closer to the idea of the artificial endocrine pancreas glucose sensor. Subcutaneous glucose levels charted by one of the new sensors were found to be well correlated with venous glucose measurements. Intervention for a healthy lifestyle is frequently hampered by patients' poor compliance. The availability of diverse antidiabetic agents provides options for targeting the glycaemic goal and a choice more fitted to the particularized pathophysiology of each individual subject. Drugs targeting postprandial glycaemia may prove to represent the ,sine qua non' for the ,return' of postprandial glucose values at a ,non-deleterious' threshold, either as monotherapy for the early stages of the disease or as combination therapy later in the progression of diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectivesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2003Ruth B. Caldwell Abstract Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered. Copyright © 2003 John Wiley & Sons, Ltd. [source] Addressing insulin resistance in Type 1 diabetesDIABETIC MEDICINE, Issue 9 2008T. T. L. Pang Abstract Type 1 diabetes is recognised to include an element of insulin resistance. Insulin resistance is an independent risk factor for the development of macro- and microvascular complications of Type 1 diabetes and may also contribute to the development of the disease. This understanding comes at a time when the incidence of Type 1 diabetes appears to be rising and the public health burden from its vascular complications is high. A variety of safe and efficacious manoeuvres are available to redress insulin resistance in Type 2 diabetes. So far however, clinical trials addressing insulin resistance in Type 1 diabetes have been small with only short periods of follow-up. Regardless, these trials have yielded promising results. This review examines the evidence for insulin resistance in the pathophysiology of Type 1 diabetes and its complications, the problems associated with its measurement, and summarizes the trials aimed at reducing insulin resistance in Type 1 diabetes. This includes a meta-analysis of controlled trials of adjuvant metformin in Type 1 diabetes. [source] Persistent poor glycaemic control in adult Type 1 diabetes.DIABETIC MEDICINE, Issue 12 2004A closer look at the problem Abstract Around 25% of the adult Type 1 diabetes population is in persistent poor glycaemic control and thus at increased risk of developing microvascular complications. We here discuss correlates of long-standing poor glycaemic control and review the efficacy of clinical strategies designed to overcome persistent poor control. Only a few studies have identified determinants and correlates of long-standing poor glycaemic control in Type 1 diabetes. There is some evidence implicating genetic factors, as well as lower economic status, and psychological factors, including lack of motivation, emotional distress, depression and eating disorders. Ways of improving glycaemic control include strategies to enable self-management, e.g. motivational strategies, coping-orientated education, psychosocial therapies, and/or intensifying insulin injection therapy plus continuous subcutaneous insulin infusion. Long-standing poor glycaemic control appears to be a heterogeneous and complex phenomenon, for which there is no simple, single solution. Comprehensive psycho-medical assessment in diabetes care may prove useful in tailoring interventions. Further research is warranted, to increase our understanding how psychosocial and biomedical factors, separately and in interaction, determine poor outcomes in Type 1 diabetes. [source] What does postprandial hyperglycaemia mean?DIABETIC MEDICINE, Issue 3 2004R. J. Heine Abstract Aims The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well-established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes. Results Post-prandial hyperglycaemia is a risk indicator for micro- and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes. Conclusions The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome. [source] N- acetylglucosamine-phosphate mutase genotype and diabetic microvascular complicationsDIABETIC MEDICINE, Issue 5 2003H. Pang No abstract is available for this article. [source] Decreased red blood cell aggregation subsequent to improved glycaemic control in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 4 2003B. Chong-Martinez Abstract Aims Reports of rheological changes following intensification of metabolic control are limited and not concordant. The present study was designed to test the hypothesis that intensification of management of Type 2 diabetes (T2DM) with diet, exercise and insulin improves haemorheological behaviour by reducing red blood cell (RBC) aggregation. Methods Blood was sampled from 55 subjects before and following 14 ± 3 weeks of intensified management. RBC aggregation was measured in vitro for cells in plasma or in an aggregating 70 kD dextran solution. Plasma viscosity and whole blood viscosity were also measured. Results During treatment, fasting glucose fell 27%, HbA1c fell 21%, and serum triglycerides and total cholesterol fell 28% and 12%, respectively (P < 0.0001 for each). The extent and strength of RBC aggregation in plasma fell by 10,13% (P < 0.002). Similar decreases of RBC aggregation were seen for cells suspended in dextran (P < 0.002). Plasma viscosity decreased by 3% (P < 0.02) and high shear blood viscosity by 6,7% (P < 0.0001). Changes of RBC aggregation in plasma and in dextran were significantly correlated, supporting a cellular rather than a plasmatic origin for these changes. However, there were no significant correlations between RBC aggregation changes and changes of fasting glucose, HbA1c, serum triglycerides, serum cholesterol, or plasma fibrinogen. Conclusions Intensified metabolic control results in a reduction of RBC aggregation that appears to be intrinsic to RBC. Since increased RBC aggregation can impair microcirculatory flow, it is possible that haemorheological factors may contribute to the reduction of microvascular complications resulting from improved metabolic control in T2DM. [source] Resource consumption and costs in Dutch patients with Type 2 diabetes mellitus.DIABETIC MEDICINE, Issue 3 2002Results from 29 general practices Abstract Aims The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non-medical costs of patients with Type 2 diabetes in The Netherlands. Methods Twenty-nine Dutch general practitioners provided information on all Type 2 diabetes patients in their practice (n = 1371), information on demography, clinical characteristics, treatment type, the presence of complications and the type and amount of medical consumption during the previous 6 months. Medical costs were analysed using multivariate linear regression. Estimates of costs seen in The Netherlands were based on these results plus information from other sources regarding costs of end-stage renal disease, appliances, travel and productivity loss. Results Although only 9% of patients were hospitalized within the previous 6 months, hospitalization costs represented one-third of the medical costs, drug costs 40% and ambulatory costs 26%. Patients using insulin, patients with macrovascular complications only or in combination with microvascular complications incurred higher medical costs than other patients. Age and hyperlipidaemia were also positively related to medical costs. When these results were combined with other data sources, we estimated that patients with Type 2 diabetes are responsible for £365 500 000 (1 271 000 000 guilders) or 3.4% of the relevant parts of health care costs in 1998. The non-medical costs (travel costs, productivity costs) are limited: 52 500 000 (183 000 000 guilders). Conclusions Independent determinants of the medical costs of Type 2 diabetes in The Netherlands include age, complications, insulin use and hyperlipidaemia. Diabet. Med. 19, 246,253 (2002) [source] Advanced glycation end-products and the kidneyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2010Martin Busch Eur J Clin Invest 2010; 40 (8): 742,755 Abstract Background, Advanced glycation end-products (AGEs) are increased in situations with hyperglycemia and oxidative stress such as diabetes mellitus. They are products of nonenzymatic glycation and oxidation of proteins and lipids. The kidney plays an important role in clearance and metabolism of AGEs. Methods, Medline© and other relevant databases were searched. In addition, key review articles were scanned for relevant original publication. Finally, original data from our research group were also included. Results, Kidney podocytes and endothelial cells express specific receptors for AGEs. Their activation leads to multiple pathophysiological effects including hypertrophy with cell cycle arrest and apoptosis, altered migration, and generation of proinflammatory cytokines. AGEs have been primarily implicated in the pathophysiology of diabetic nephropathy and diabetic microvascular complications. AGEs are also involved in other primary renal diseases as well as in the development and progression of atherosclerosis. However, serum or plasma concentrations of AGEs do not correlate well with cardiovascular events in patients with chronic kidney disease (CKD). This is likely due to the fact that serum concentrations failed to correlate with AGEs deposited in target tissues. Several inhibitors of the AGE-RAGE axis are currently tested for various indications. Conclusion, AGEs and their receptors are involved in the pathogenesis of vascular and kidney disease. The role of circulating AGEs as biomarkers for cardiovascular risk estimation is questionable. Whether putative inhibitors of AGEs will get the maturity for its therapeutic use in the future remains open. [source] Evaluation of glargine group-start sessions in patients with type 2 diabetes as a strategy to deliver the serviceINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2007A. A. Tahrani Summary Improving glycaemic control in patients with type 2 diabetes reduces microvascular complications. The national service framework for diabetes and the new general medical service contract have been aiming to direct more focus on improving HbA1c. These measures have resulted in increasing number of patients being initiated on insulin therapy, which increases the workload of diabetes specialist nurses (DSNs). Initiating insulin on a one-to-one basis is time consuming. As a result DSN-led insulin group-start sessions were introduced. To evaluate DSN-led glargine group-start and self-titration as a strategy of providing service. We assessed the impact of this method on the use of DSNs time, HbA1c and on patients' satisfaction. A prospective audit in a district general hospital. Groups of 5,7 patients received two 2-h sessions at weeks 0 and 2. During these sessions, patients were initiated on insulin glargine and received an educational package and a self-titration protocol. DSNs did not see patients after week 2. Patients were able to phone the DSNs for advice till the end of the titration period. Patients completed Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline, week 2 and 12 months. Weight and HbA1c were assessed at base line and 12 months later. Twenty-nine consecutive patients were included. Baseline HbA1c improved at 6 months and remained stable at 12 months (medians 10.0, 8.7 and 8.9 respectively, p < 0.001). DTSQ score improved between week 0 and 2 and this was maintained at 12 months (medians 26, 35 and 34 respectively, p < 0.001). After week 2, the DSNs spent a median of 21 min advising patients by phone during the titration period. Weight did not increase significantly. In our centre, DSN-led insulin group-start sessions and self-titration improved glycaemic control. Patients were satisfied with this method of starting insulin. This was achieved with minimal DSNs time and input and proved to be effective, yet less time consuming. [source] Searching for genes in diabetes and the metabolic syndromeINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2004G. A. Hitman Summary Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4, (HNF4,) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPAR,) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified , such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1, mutations being the most common causes of MODY. GCK variants result in ,mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1,- associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies. [source] Early changes in renal hemodynamics in children with diabetes: Doppler sonographic findingsJOURNAL OF CLINICAL ULTRASOUND, Issue 6 2008Piernicola Pelliccia MD Abstract Purpose Although clinically evident diabetes-related microvascular complications are extremely rare in childhood, early functional and structural abnormalities may be present a few years after the onset of the disease. Renal Doppler resistance index (RI) is widely used for the evaluation of blood flow in renal parenchymal diseases. This study was designed to investigate the possible alteration of intrarenal Doppler RI in children with diabetes compared with healthy children. Methods The study was performed in 42 children with diabetes (age range, 6,18 years) and in 41 age-matched healthy controls, all having normal renal function. RI was measured with Doppler sonography in interlobular renal arteries. Results RI values were significantly greater in children with diabetes than in age-matched healthy controls (0.64 ± 0.03 versus 0.60 ± 0.04, P < 0.035). RI correlated positively with HbA1c (P < 0.001, r = 0.42) and diabetes duration (P < 0.05, r = 0.39). Conclusion Early changes in renal hemodynamics are detectable on Doppler sonography in children with diabetes without any evidence of renal dysfunction and may suggest a preclinical stage of diabetic nephropathy. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008. [source] Multidisciplinary Teaming to Promote Effective Management of Type 1 Diabetes for AdolescentsJOURNAL OF SCHOOL HEALTH, Issue 6 2001MaryAnn Tapper Strawhacker BSN, RN Special Education Nursing Consultant ABSTRACT: Intensive diabetes therapy can reduce the long-term microvascular complications of Type 1 diabetes and improve glucose control. Managing the demands of intensive therapy however, often poses a burden on adolescents and their families. Through multidisciplinary teaming, the school health office can facilitate active participation in treatment, coordinate services, and maximize use of community resources. This paper presents a general overview of intensive diabetes therapy, psychosocial implications of chronic illness in adolescence, effects of chronic illness on the family, and behavior change strategies to improve adherence with disease management guidelines. [source] Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection CoefficientMICROCIRCULATION, Issue 7 2007RACHEL M. PERRIN ABSTRACT Objective: Increased microvascular permeability contributes to the development of diabetic microvascular complications and diabetic vasculopathy is correlated with blood glucose levels. The mechanisms underlying increased permeability, however, are poorly understood. Methods: The Landis-Michel technique was used to measure water permeability (hydraulic conductivity, Lp) and macromolecular permeability (reflection coefficient, ,) of exchange capillaries in frogs and rats. Results: Dialysed normoglycemic plasma from diabetic patients had no effect on Lp. The same plasma with 20 mM glucose increased hydraulic conductivity from (mean ± SEM × 10,7 cm · s,1· cm H2O,1) 5.73 ± 2.01 to 13.09 ± 2.67 (P < .01). Nondiabetic control plasma did not affect Lp, but addition of 20 mM glucose increased Lp to a similar degree. The effect of glucose alone was examined. Glucose at 20 mM increased Lp, from 2.82 ± 0.61 to 4.71 ± 1.35 × 10, 7 cm · s, 1· cm H2O,1 (P = .002, n = 13). A similar increase was seen in rat mesenteric microvessels, from 1.04 ± 0.40 in control perfusions to 2.18 ± 0.56, P < .05. The microvascular macromolecular reflection coefficient in all the above experiments was unaltered. The use of specific inhibitors indicated that the glucose-induced increased Lp did not appear to be mediated through protein kinase C (PKC), free radical generation, glucose metabolism, or albumin glycation. Conclusions: These data suggest that hyperglycemia induced increased apparent protein permeability may be secondary to a glucose-mediated change in macromolecular convective flux rather than any change in protein permeability per se. The authors speculate that the increased microvascular permeability to water in vivo is mediated by direct interaction of glucose with the endothelial cells (perhaps with the glycocalyx). [source] Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetesPEDIATRIC DIABETES, Issue 4pt2 2008Esko J Wiltshire Abstract:, Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C,T, 1298A,C in MTHFR, and 66A,G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06,1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG. [source] Self-monitoring of blood glucose in children and teens with diabetesPEDIATRIC DIABETES, Issue 1 2005Helen Bui Abstract:, Improved metabolic control has unequivocally been demonstrated to delay the onset and slow the progression of microvascular complications in adolescents and adults with diabetes mellitus. Growing evidence also supports the association of tighter glucose control and more frequent blood glucose monitoring. Therefore, self-monitoring of blood glucose (SMBG) has become a fundamental part of diabetes care in children. Here, we review recent advances and ongoing trends in glucose monitoring in children with diabetes. Technologies have been developed to improve patient compliance with recommended monitoring, requiring less blood, involving less pain, and providing results more quickly. Alternate-site testing (AST) is also a potential means of improving patient compliance with SMBG by avoiding the sensitive fingertip area. The Continuous Glucose Monitoring System (CGMS) and the GlucoWatch® Biographer are two recent tools that can track glucose levels continuously. However, inconsistency in their accuracy and precision remain challenges when using these technologies to guide management. [source] Protein kinase C inhibition in diabetic retinopathy and microvascular diseasePRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 5 2007Dr C Walton FRCP Abstract Protein kinase C (PKC) activation by hyperglycaemia may play an important role in the evolution of diabetic retinopathy and other microvascular complications. The PKC-, inhibitor ruboxistaurin belongs to a new class of drugs and has been studied in several clinical trials in microvascular disease, the outcomes of which are described in this review. Ruboxistaurin exhibits promise as the first oral treatment shown to reduce visual loss and the need for laser treatment for macular oedema in patients with moderate to severe non-proliferative diabetic retinopathy. Copyright © 2007 John Wiley & Sons. [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patientsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2007Taeoh Kim Abstract Diabetes can lead to serious microvascular complications like proliferative diabetic retinopathy (PDR), which is the leading cause of blindness in adults. The proteomic changes that occur during PDR cannot be measured in the human retina for ethical reasons, but could be reflected by proteomic changes in vitreous humor. Thus, we considered that comparisons between the proteome profiles of the vitreous humors of PDR and nondiabetic controls could lead to the discovery of novel pathogenic proteins and clinical biomarkers. In this study, the authors used several proteomic methods to comprehensively examine vitreous humor proteomes of PDR patients and nondiabetic controls. These methods included immunoaffinity subtraction (IS)/2-DE/MALDI-MS, nano-LC-MALDI-MS/MS, and nano-LC-ESI-MS/MS. The identified proteins were subjected to the Trans-Proteomic Pipeline validation process. Resultantly, 531 proteins were identified, i.e., 415 and 346 proteins were identified in PDR and nondiabetic control vitreous humor samples, respectively, and of these 531 proteins, 240 were identified for the first time in this study. The PDR vitreous proteome was also found to contain many proteins possibly involved in the pathogenesis of PDR. The proteins described provide the most comprehensive proteome listing in the vitreous humor samples of PDR and nondiabetic control patients. [source] Proteomic analysis of human proximal tubular cells exposed to high glucose concentrationsPROTEOMICS - CLINICAL APPLICATIONS, Issue 7-8 2008Eun-Jeong So Abstract Hyperglycemia is a major key factor in the pathogenesis of microvascular complications of diabetes, including diabetic nephropathy (DN). Most studies to date have focused on the glomerular abnormalities found in DN. However, nephromegaly in the early stages of diabetes and the correlation of tubulointerstitial pathology rather than glomerular pathology with declining renal function in DN suggests the involvement of the tubulointerstitium. The etiology of the tubulointerstitial pathology in DN, however, is not fully understood. In this study, to understand the DN pathways, we constructed an initial 2-DE reference map for primitively cultured human proximal tubule (HK-2) cell in the presence of 5,mM and 25,mM glucose, which correspond to blood glucose concentrations during the normal and hyperglycemia conditions, respectively. Differentially expressed HK-2 cell cellular proteins at the high glucose concentration were identified via ESI-Q-TOF MS/MS and confirmed by Western blotting; enolase 1 (up-regulated) and lactate dehydrogenase (down-regulated). The regulation of these proteins will help in understanding DN mechanism through the glycolysis metabolic pathways in high glucose stimulated HK-2 cells. [source] Influence of Diabetes and/or Myocardial Infarction on Prevalence of Abnormal T-Wave AlternansANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2009David T. Martin M.D., F.A.C.C., F.R.C.P. Background: Subjects with microvolt-level T-wave alternans (TWA) in association with structural heart disease have an increased risk for sudden cardiac death. The presence of diabetes (DM) is associated with an increased risk of sudden death but there is limited data on the impact of DM and previous myocardial infarction (MI) on TWA prevalence. Methods: We performed a case-control cross-sectional study in 140 patients referred for routine exercise testing within a large multispecialty clinic. All patients with a history of DM and MI status within the past year were eligible: group 1 (no DM or MI), group 2 (DM only), group 3 (MI only), group 4 (DM and MI). Patients performed a symptom-limited Bruce protocol exercise test with assessment of TWA by the spectral method using commercially available equipment. We used published criteria for the blinded interpretation of TWA; all tests not unequivocally negative were considered abnormal. Results: Age and gender were similar in all groups. The prevalence of abnormal TWA in groups 1,4 was 24%, 20%, 48%, and 62%, respectively (between group P = 0.002). Logistic regression analysis in all patients showed that abnormal TWA was related to prior MI [OR (95% CI): 4.0 (1.8,8.9), P < 0.001] but not to prevalent DM [0.9 (0.4,1.8), P = 0.72]. In patients with DM, the prevalence of abnormal TWA was related to reduced ejection fraction (P = 0.034) but not to BMI, DM duration, glycemic control, insulin use, or the presence of microvascular complications. Conclusion: The presence of DM alone does not increase risk of abnormal TWA. Prospective studies are required to establish the prognostic value of TWA in patients with DM. [source] Glucagon is absorbed from the rectum but does not hasten recovery from hypoglycaemia in patients with type 1 diabetesBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008David R. Parker WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Patients with type 1 diabetes experience recurrent hypoglycaemia and have abnormal glucose counter regulatory responses with a failure to secrete glucagon. It is unknown if rectal glucagon is absorbed and what effect this may have on counter regulation from hypoglycaemia. WHAT THIS STUDY ADDS , A rectal suppository of glucagon results in a rise in plasma glucagon with metabolic effects in normal subjects. Similarly rectal glucagon results in a rise in plasma glucagon in patients with type 1 diabetes, but 1 mg does not improve recovery rates from experimental hypoglycaemia when compared with placebo. , Larger doses of glucagon per rectum may provide pharmacological circulating concentrations with resulting therapeutic benefit during recovery from hypoglycaemia and deserves further study. AIMS A failure to secrete glucagon during hypoglycaemia is near universal in patients with type 1 diabetes 5 years after disease onset and may contribute to delayed counter-regulation during hypoglycaemia. Rectal glucagon delivery may assist glucose recovery following insulin-induced hypoglycaemia in such patients and has not been previously studied. METHODS Six male patients (age 21,38 years) with type 1 diabetes (median duration 10 years) without microvascular complications, were studied supine after an overnight fast on two separate occasions at least 14 days apart. After omission of their usual morning insulin and 45 min rest, hypoglycaemia was induced by an intravenous insulin infusion which was terminated when capillary glucose concentration reached 2.5 mmol l,1. Subjects were randomized to insert a rectal suppository containing 100 mg indomethacin alone (placebo) or 100 mg indomethacin plus 1 mg glucagon at the hypoglycaemic reaction. Serial measurements were made for 120 min. RESULTS In the two groups, mean (SD) plasma glucose concentrations fell to a similar nadir of 1.8 (0.7) mmol l,1 (placebo) and 2.1 (1.2) mmol l,1 (glucagon). Peak plasma glucagon following hypoglycaemia was higher in the glucagon group; 176 (32) ng l,1vs. 99 (22) ng l,1 after placebo (P = 0.006). However, the glucose recovery rate over 120 min after hypoglycaemia did not differ significantly. CONCLUSIONS Our results provide evidence for the absorption of glucagon from the rectum. They also indicate that 1 mg does not constitute a useful mode of therapy to hasten recovery from hypoglycaemia in patients with type 1 diabetes. [source] Abnormal myocardial perfusion and contractile recruitment during exercise in type 1 diabetic patientsCLINICAL CARDIOLOGY, Issue 2 2005Roldano Scognamiglio M.D. Abstract Background: No data are available on the relationship between myocardial perfusion and left ventricular (LV) function in type 1 diabetes mellitus (T1DM), which may constitute a factor explaining the progressive contractile dysfunction to the overt phase of diabetic cardiomyopathy. Hypothesis: This study was undertaken to test whether myocardial perfusion abnormalities are present at rest and during exercise and whether they are related to contractile dysfunction in T1DM. Methods: Twenty-two patients with T1DM, aged 32 ± 8.3 years, without macro-or microvascular complications, and 10 controls, aged 31 ± 3 years, were studied. Left ventricular function and myocardial perfusion were assessed by two-dimensional and myocardial contrast echocardiography at rest and during handgrip (HG). Results: Fourteen patients with T1DM showed a decline in LV ejectionfraction (LVEF) during HG (Group 1) while 8 had a normal response (Group 2). Both basal myocardial blood volume (MBV) and velocity ((3) were normal inT1DM. During exercise, MBV and (3 increased and were associated with an increase in myocardial blood flow (MBF) in controls. In T1DM, (3 did not change and MBV increased only in Group 2, while this increase was not observed in Group 1 (controls: 14.9 ±2.3 vs. Group 1:7.6± 1.6, p< 0.001; and vs. Group2:10.2± 2.8, p<0.001), (3(0.86±0.12vs.0.68±0.14, p<0.001;and vs. 0.67±0.15, p<0.001). A correlation between the ratio exercise MBF/resting MBF and LVEF at peak exercise in T1DM was observed (r=0.805, p< 0.001). Conclusions: A large proportion of patients with T1DM exhibit abnormalities in myocardial adaptable capacity to match an acute overload, which are related to a defective increase in myocardial perfusion. [source] | ||||||||||||||||||||||||||||