Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes. METHODS: In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination. CONCLUSIONS: Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.

Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy.

Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.

Cause-specific mortality rates in patients with diabetes according to comorbid macro- and microvascular complications: BioBank Japan Cohort.

Objective: This study aimed to compare cause-specific mortality rates in patients with type 2 diabetes with and without various vascular complications. Methods: In Japanese hospitals, we followed up 30 834 patients with a mean age of 64.4 (standard deviation [SD]: 11.1) years. Patients were followed up from 2003 to 2007 for a median of 7.5 (interquartile range: 6.1-9.7) years. We calculated cause-specific mortality rates (number of deaths/1000 person-years) and confounder-adjusted hazard ratios in patients with macrovascular disease and in those with diabetic nephropathy, neuropathy and retinopathy, allowing for overlap of complications. Results: All-cause mortality rate was highest (51.4) in the nephropathy group, followed by the macrovascular disease group (45.2), the neuropathy group (39.5), the retinopathy group (38.7) and the nonvascular complication group (18.1). In the nephropathy group, morality rates of ischaemic heart, cerebrovascular, and infectious diseases and cancer were also highest among the groups. However, the cancer mortality rate was similar among the vascular complication groups. Relative to the nonvascular complication group, covariate-adjusted hazard ratios for ischaemic heart and cerebrovascular disease mortality were triple to quadruple in the macro- and microvascular complication groups. All-cause mortality rates rose exponentially according to age. Conclusion: Highest risks of all-cause, cancer, and ischaemic heart, infectious, and cerebrovascular disease mortality were determined in Japanese patients with diabetic nephropathy. Although cancer is the primary cause of death in Japanese patients with diabetes, cancer mortality rates are similar among those with and without vascular complications.

Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus.

The impairment of cardiovascular autonomic control among the underdiagnosed complication of diabetes mellitus (DM) with a high prevalence rate of up to 60% in type 2 DM (T2DM). Cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality, arrhythmia, silent ischemia, any major cardiovascular event, and heart failure. We aimed to evaluate cardiovascular autonomic activity by different physiological maneuvers, study risk factors for diabetic CAN including age, gender, duration of diabetes, body mass index (BMI), and glycemic control, and correlate CAN stage with risk factors. One hundred and forty-two T2DM patients consisted of 62 males and 80 females and 100 volunteers as a control sample. Cardiac autonomic functions were assessed by Ewing's tests. Glycated hemoglobin (HbA1c), body weight, height, body mass index (BMI), and waist-hip ratio (WHR) were also measured. Cardiovascular autonomic functions and Ewing scores were significantly different in people with diabetes when compared with control healthy subjects. Ewings test values and Ewing scores were significantly different between diabetics with and without CAN and within patients with different CAN staging. People with diabetes with CAN have a significantly longer duration of disease when compared to those without CAN. A strong association has been found between CAN severity and patient age, duration of disease, HbA1c severity, and the WHR (P < 0.001) but not with BMI. The duration of disease and HbA1c level appear to be associated with the development of CAN (P = 0.001 and P = 0.008, respectively). The poorer glycemic control and the longer the duration of the disease, the higher the prevalence of CAN in T2DM. Age, duration of disease, WHR, and HbA1c are well correlated with the severity of CAN. Parasympathetic impairment is more sensitive to the detection of autonomic dysfunctions than do sympathetic impairment.

Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality.

PURPOSE: Type 2 diabetes-related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). METHODS: A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. RESULTS: Of 43 945 patients with type 2 diabetes (age 64.6 ±â€…14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). CONCLUSIONS: Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study.

BACKGROUND: The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. METHODS: BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. RESULTS: Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). CONCLUSIONS: Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.

Relationship between diabetic neuropathic pain and comorbidity. Their impact on pain intensity, diabetes complications and quality of life in patients with type-2 diabetes mellitus.

OBJECTIVE: To compare cognitive function, mood and sleep status in patients with and without diabetic neuropathic pain (DNP) and their relationship with pain intensity, diabetes complications, and quality of life. To determine whether these relationships differ depending on the sensorial phenotype. METHODS: Cross-sectional study performed on patients with type-2 diabetes-mellitus and neuropathy. Presence of DNP, pain intensity and phenotype, mood status, sleep characteristics and quality of life were measured. RESULTS: A total of 130 patients (65 with DNP) were included. DNP was related to poor sleep quality (OR = 1.03;CI95%:1.02-1.05), pain treatment (OR = 3.00,CI95%:1.24-7.29) or previous anxiety (OR = 2.70,CI95%:1.05-6.99). Patients with specific phenotypes or depression (=0.82,CI95%:-0.02-1.67) referred more severe pain. More complications were related to older age (OR = 1.40,CI95%:1.12-1.66), higher pain intensity (OR = 1.51,CI95%:1.00-2.28), lower cognitive performance (OR = 1.25,CI95%:1.09-1.43), previous anxiety (OR = 10.48,CI95%:1.46-75.24) and insulin treatment (OR = 124.50,CI95%:6.64-2335.06). Decrease in mental quality of life was associated with sleep disorders (ß = -0.33,CI95%:-0.48,-0.23), physical comorbidities (ß = -9.73,CI95%:-18.15, -1.31) and previous anxiety (ß = -7.91,CI95%:-13.04, -2.77). Lower scores in physical quality of life were related to sleep disorders (ß = -0.12,CI95%:-0.21, -0.18), obesity (ß = -8.35,CI95%:-13.16, -3.55), longer time since diagnosis (ß = -0.72,CI95%:-1.44;0.01) and disability (ß = -14.58,CI95%:-24.69; -4.48). CONCLUSIONS: The results support the idea that mental comorbidity and sleep disorders are factors associated with DNP and greater pain intensity, more diabetes complications and lower quality of life. Moreover, they highlight the relationship between sensorial phenotypes and pain intensity, and lower cognitive performance and diabetes complications.

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study.

BACKGROUND: Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS: Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS: In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

Diabetic foot ulcer incidence and survival with improved diabetic foot services: an 18-year study.

AIMS: To ascertain the effects of improvements in diabetic foot services over 18 years on incidence of diabetic foot ulceration. We also compared survival time from first ulcer development with presence of neuropathy, peripheral vascular disease, age and healing. METHODS: Persons with new ulceration and those at high risk of ulcer development were referred to community podiatry from 1998. Their details were recorded, with verbal consent, on a central database. The effects of neuropathy, peripheral vascular disease, healing and age on survival were analysed by Cox proportional hazards ratios. RESULTS: The incidence of first ulcer presentation decreased from 11.1 to 6.1 per 1000 persons between 2003 to 2017 (P <0.0001). Recurrent ulceration incidence remained stable. Prevalence of chronic and new foot ulceration combined increased from 20.7 to 33.1 per 1000 persons (P <0.0001). Ten-year survival was 85% for persons presenting with first ulcer and aged < 65 years, 50% for those aged 65-74 years and 25% for those aged 75-81 years (P < 0.0001). In those with peripheral vascular disease 5-year survival was 35% (P <0.001). CONCLUSIONS: Integrated care for the diabetic foot in one National Health Service (NHS) health service area over 18 years was associated with a reduction in first presentations of diabetic foot ulceration, but failed to reduce recurrent ulceration. Cumulative prevalence of all ulcers continues to increase. Monitoring ulceration incidence can inform audit and planning of diabetic foot care services. Survival is better than reported previously in persons < 65 years and in the absence of peripheral vascular disease.

Cardiovascular autonomic neuropathy in type 2 diabetic patients.

Diabetes is one of the most common chronic pathologies around the world, involving treatment with general clinicians, endocrinologists, cardiologists, ophthalmologists, nephrologists and a multidisciplinary team. Patients with type 2 Diabetes Mellitus (T2DM) can be affected by cardiac autonomic neuropathy, leading to increased mortality and morbidity. In this review, we will present current concepts, clinical features, diagnosis, prognosis, and possible treatment. New drugs recently developed to reduce glycemic level presented a pleiotropic effect of reducing sudden death, suggesting a potential use in patients at risk.

Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study.

AIMS/HYPOTHESIS: The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications. METHODS: This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden. RESULTS: During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA1c, LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years. CONCLUSIONS/INTERPRETATION: Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.

Cardiovascular autonomic neuropathy in type 2 diabetic patients

SUMMARY Diabetes is one of the most common chronic pathologies around the world, involving treatment with general clinicians, endocrinologists, cardiologists, ophthalmologists, nephrologists and a multidisciplinary team. Patients with type 2 Diabetes Mellitus (T2DM) can be affected by cardiac autonomic neuropathy, leading to increased mortality and morbidity. In this review, we will present current concepts, clinical features, diagnosis, prognosis, and possible treatment. New drugs recently developed to reduce glycemic level presented a pleiotropic effect of reducing sudden death, suggesting a potential use in patients at risk.

RESUMO Diabetes é uma das mais frequentes patologias crônicas em todo o mundo, cujo tratamento envolve uma equipe multidisciplinar, médicos generalistas, endocrinologistas, cardiologistas, nefrologistas e oftalmologistas. Pacientes com diabetes mellitus tipo 2 (DMT2) podem apresentar neuropatia autonômica cardíaca (NAC), levando a aumento de mortalidade e morbidade. Nesta revisão, apresentaremos atuais conceitos, características clínicas, diagnóstico, prognóstico e possíveis tratamentos. Novas drogas recentemente desenvolvidas para redução de níveis glicêmicos apresentaram efeito pleiotrópico de redução de morte súbita, sugerindo um potencial uso neste perfil de pacientes.

Effects of nursing care on patients in an educational program for prevention of diabetic foot. / Riscos associados à mortalidade em pacientes atendidos em um programa de prevenção do pé diabético.

OBJECTIVES: Identify in patients with type 2 diabetes what changes in the feet would be associated with demographic, clinical, biochemical and treatment characteristics and which would increase the risk of mortality. METHODS: Retrospective longitudinal study evaluating the alterations in feet of outpatients attended at a nursing visit. Data from the clinical history and foot exam were collected from 918 medical records of a convenience sample. RESULTS: At 10 years, the cumulative mortality attributable to peripheral polyneuropathy was 44.7%, to peripheral artery disease was 71.7%, to both conditions were 62.4%, and to amputation was 67.6%. After multivariate analysis, duration of nursing follow-up remained as the only protective factor against death (p < 0.001). CONCLUSIONS: The risk of death in these patients decreased when they had consultations with a nurse educator. Ischemic feet, amputation, and coronary artery disease remained independent risk factors.

Mortality and complications after treatment of acute diabetic Charcot foot.

AIMS: Charcot foot is a rare but disabling complication to diabetic neuropathy, and can cause permanent, limb-threatening deformities. The aim of this study was to investigate a population of patients a Charcot foot on a case-by-case basis, in order to assess the consequences of an acute Charcot foot and its complications. METHODS: The study was conducted a retrospective study of patients admitted to the Copenhagen Wound Healing Center between 1996 and 2015 with the diagnosis of Charcot foot (DM14.6) and diabetes mellitus type 1 or 2 (DE10.X and DE11.X). Physical and electronic records were used, and compared to data from the Danish Diabetes Registry. RESULTS: In total 392 patients were identified of which 173 were included. There were 26% with type 1 diabetes (initial HbA1c 81.7 ±â€¯21.4 mmol/mol) and 74% with type 2 diabetes (initial HbA1c 66.5 ±â€¯20.3 mmol/mol). Primary off-loading was with a removable walker in 95% of the cases (average off-loading time 8.3 months). The 5-year mortality was 14% with a mean survival time of 12.7 years. There was an association between lack of compliance and occurrence of foot complications, as well as between having a Charcot foot and leaving the workforce. CONCLUSION: More patients had type 1 diabetes compared to the background population, and they had a higher HbA1c than the general population of diabetes patients. A total of 67% developed complications such as ulcers, while patients non-compliant to treatment did significantly worse than those being compliant. The 5-year mortality was low, 14%, and comparable to diabetes patients without Charcot foot.

Association of Ultrafiltration Rate with Mortality in Incident Hemodialysis Patients.

BACKGROUND/AIMS: Ultrafiltration rate (UFR) appears to be associated with mortality in prevalent hemodialysis (HD) patients. However, the association of UFR with mortality in incident HD patients remains unknown. METHODS: We examined a US cohort of 110,880 patients who initiated HD from 2007 to 2011. Baseline UFR was divided into 5 groups (<4, 4 to <6, 6 to <8, 8 to <10, and ≥10 mL/h/kg body weight [BW]). We examined predictors of higher baseline UFR using logistic regression and the association of baseline UFR and all-cause and cardiovascular (CV) mortality using Cox proportional hazard models with adjustments for demographics, comorbidities, and markers of malnutrition-inflammation-cachexia syndrome. RESULTS: Patients were 63 ± 15 years, with 43% women, 32% African Americans, and had a mean baseline UFR of 7.5 ± 3.1 mL/h/kg BW. In the fully adjusted logistic regression models, factors associated with higher UFR (≥7.5 mL/h/kg BW) included Hispanic ethnicity, diabetes, and higher dietary protein intake. There was a linear association between UFR and all-cause and CV mortality, where UFR ≥10 mL/h/kg BW (reference UFR 6-<8 mL/h/kg BW) conferred the highest risk in both unadjusted (HR 1.15 [95% CI 1.10-1.19]) and adjusted models (HR 1.23 [95% CI 1.16-1.31]). The linear association with all-cause mortality remained consistent across strata of age, urine volume, and treatment time. CONCLUSIONS: Higher UFR is independently associated with higher all-cause and CV mortality in incident HD patients. Clinical trials are warranted to examine the effects of lowering UFR on outcomes.

Riscos associados à mortalidade em pacientes atendidos em um programa de prevenção do pé diabético / Efecto del cuidado de enfermería en pacientes atendidos en un programa de prevención del pie diabético / Effects of nursing care on patients in an educational program for prevention of diabetic foot

Resumo OBJETIVO SIdentificar em pacientes com diabetes tipo 2 quais alterações nos pés estariam associadas às características demográficas, clínicas, bioquímicas e de tratamento e quais delas aumentariam o risco de mortalidade. MÉTODOS Estudo longitudinal retrospectivo que avaliou as alterações nos pés de pacientes externos atendidos em consulta de enfermagem. Os dados da história clínica e do exame dos pés foram coletados de 918 prontuários de uma amostra por conveniência. RESULTADOS Em 10 anos, a mortalidade cumulativa atribuída a polineuropatia sensitiva periférica foi 44,7%, pela doença vascular periférica 71,7%, pela associação das duas condições 62,4% e pela amputação 67,6%. Após análise multivariável, o tempo de acompanhamento com enfermeiros permaneceu como único fator de proteção para a mortalidade (p < 0,001). CONCLUSÃO O risco de morrer nesses pacientes diminuiu quando consultaram com enfermeiros educadores. Permaneceu como fator de risco independente pacientes com pé isquêmico, amputação e doença arterial coronariana.

Resumen OBJETIVOS Identificar en pacientes con diabetes tipo 2 que alteraciones en los pies estarían asociadas a las características demográficas, clínicas, bioquímicas y de tratamiento y cuáles de ellas aumentarían el riesgo de mortalidad. MÉTODOS Estudio longitudinal retrospectivo que evaluó los cambios en los pies de pacientes externos atendidos en consulta de enfermería. Los datos de la historia clínica y del examen de los pies fueron recolectados de 918 prontuarios, una muestra por conveniencia. RESULTADOS En 10 años, la mortalidad acumulativa atribuida a la polineuropatía sensitiva periférica fue 44.7%, por la enfermedad vascular periférica 71.7%, por la asociación de las dos condiciones 62.4% y por la amputación 67.6%. Después del análisis multivariable, el tiempo de acompañamiento con enfermeros permaneció como único factor de protección para la mortalidad (p < 0,001). CONCLUSIÓN El riesgo de morir en estos pacientes disminuyó cuando consultaron con enfermeros educadores. Se mantuvo como factor de riesgo independiente pacientes con pie isquémico, amputación y enfermedad arterial coronaria.

Abstract OBJECTIVES Identify in patients with type 2 diabetes what changes in the feet would be associated with demographic, clinical, biochemical and treatment characteristics and which would increase the risk of mortality. METHODS Retrospective longitudinal study evaluating the alterations in feet of outpatients attended at a nursing visit. Data from the clinical history and foot exam were collected from 918 medical records of a convenience sample. RESULTS At 10 years, the cumulative mortality attributable to peripheral polyneuropathy was 44.7%, to peripheral artery disease was 71.7%, to both conditions were 62.4%, and to amputation was 67.6%. After multivariate analysis, duration of nursing follow-up remained as the only protective factor against death (p < 0.001). CONCLUSIONS The risk of death in these patients decreased when they had consultations with a nurse educator. Ischemic feet, amputation, and coronary artery disease remained independent risk factors.

The Diabetic Foot as a Proxy for Cardiovascular Events and Mortality Review.

PURPOSE OF REVIEW: This article reviewed very recent papers (2016) discussing or bringing clinical evidences of the possible common pathways leading to diabetic foot syndrome (DFS) and increased mortality rates. RECENT FINDINGS: Diabetic patients with diabetic foot syndrome have a mortality rate greater than twofold when compared with non-ulcerated diabetics. In addition, the 5-year mortality rate following amputation is estimated at 39-68%, a life expectancy comparable to aggressive types of cancer or advanced congestive heart failure. The majority of patients with diabetic foot ulcer also present insulin resistance, central obesity, dyslipidemia, and hypertension that characterize the metabolic syndrome that, in turn, is associated with an elevated risk of major cardiovascular events. Sensory neuropathy is the primary cause of more the 60% of diabetic foot ulcer. Diabetic peripheral neuropathy is a microvascular complication of diabetes mellitus and in type 2 diabetes, not only hyperglycemia but also other metabolic alterations and persistent inflammatory status due to adiposity play a major role in axon injury. Elevated triglycerides have been showed to be an independent risk factor for lower extremity amputation in diabetic patients. Also, toxic adiposity, oxidative stress, mitochondrial dysfunction, activation of the polyol pathway, accumulation of advanced glycation end products (AGEs), and elevation of inflammatory markers are also implicated in diabetic vascular disease and neuropathy. The hypotheses that the association between DFS and increased rates of mortality reflects the progression of micro- and macrovascular complications are reinforced by the additional association of DFU to renal failure and retinopathy.

Neuropathy and presence of emotional distress and depression in longstanding diabetes: Results from the Canadian study of longevity in type 1 diabetes.

AIM: To determine the association of neuropathy and other complications with emotional distress and depression among patients with longstanding type 1 diabetes (T1DM). METHODS: Canadians with ≥50years of T1DM completed a questionnaire including assessment of distress and depression by the Problem Areas in Diabetes Scale (PAID) and Geriatric Depression Scale (GDS), respectively. Complications were determined using the Michigan Neuropathy Screening Instrument (Questionnaire Component), fundoscopy reports, renal function tests, and self-reported peripheral-(PVD) and cardiovascular (CVD) disease. Associations were analyzed by Poisson regression. RESULTS: Among 323 participants, 137 (42.4%) had neuropathy, 113 (36.5%) nephropathy, 207 (69.5%) retinopathy, 95 (29.4%) CVD, and 31 (9.8%) PVD. The neuropathy subgroup had higher prevalence of distress (13 (9.5%) vs. 6 (3.3%), p=0.029) and depression (34 (24.9%) vs. 12 (6.5%), p<0.001). Adjusting for diabetes complications, neuropathy was associated with higher PAID (adjusted RR 1.44 (95% CI 1.14-1.82), p=0.003) and GDS scores (adjusted RR1.57 (1.18-2.11), p=0.002). Independent of potential confounders, neuropathy remained associated with higher PAID (adjusted RR 1.39 (1.10-1.76), p=0.006) and GDS scores (adjusted RR 1.37 (1.03-1.83), p=0.032). Associations with neuropathy were not fully explained by neuropathic pain. CONCLUSION: Compared to other complications, neuropathy had the greatest association with distress and depression in longstanding T1DM, independent of pain. Strategies beyond pain management are needed to improve quality of life in diabetic neuropathy.

Stereological study on the number of synapses in the rat spinal dorsal horn with painful diabetic neuropathy induced by streptozotocin.

Our previous studies showed that direct injury to the sciatic nerve (chronic constriction injury or axotomy) is associated with a numerical increase in synaptic number in the rat spinal dorsal horn. The aim of this study was to determine whether painful diabetic neuropathy (PDN) was also associated with numerical changes in the synaptic or neuronal numbers in the spinal dorsal horn. Overall, 17 adult SD rats were allocated randomly into the control group (n=5) and the streptozotocin (STZ) group (n=12). STZ was injected intraperitoneally to induce diabetes. In the STZ group, seven rats (STZ-H) showed hyperglycemia (fasting blood glucose >11.1 mM) and the rest of the five rats (STZ-N) did not. Rats were fed and observed for 28 days after hyperglycemia. Two of the seven STZ-H rats died of infection during the observation period. Body weight and paw withdraw threshold (PWT) decreased in the rest of the five STZ-H rats. Twenty-eight days after hyperglycemia, the L5 segment of the spinal cord was removed; paraffin-embedded sections were prepared and stained with Nissl's method and synaptophysin immunohistochemistry, respectively. The optical dissector (a stereological technique) was used to estimate the numbers of neurons and synapses in the spinal dorsal horn. Compared with the control group, the synaptic number and ratio between the numbers of synapses and neurons in the L5 segment of the spinal dorsal horn were increased significantly in the STZ-H rats (P<0.05), whereas the neuronal number did not change significantly (P>0.05). Parameters of STZ-N rats showed no significant changes. In conclusion, PDN, a form of neuropathic pain, is also associated with a synaptic plasticity (numerical increase) in the spinal dorsal horn. This numerical change might be the reason for central sensitization resulting in reduced pain threshold, enhanced responsiveness, and expanded receptive fields associated with PDN. Therefore, our studies indicate that neuropathic pain conditions with different etiologies might show the same synaptic numerical plasticity changes.

Association between diabetes mellitus and incidence of intracerebral haemorrhage and case fatality rates: A retrospective population-based cohort study.

We investigated the associations between diabetes (type 1, type 2 or no diabetes) and intracerebral haemorrhage (ICH) incidence as well as case fatality after ICH, in a retrospective cohort study of people aged 40 to 89 years in Scotland during the period 2004 to 2013, using linkage of population-based records of diagnosed diabetes, hospital discharges and deaths. We calculated ICH incidence and 30-day case fatality after hospital admission for ICH, along with their relative risks (RR) and 95% confidence intervals (CIs), among people with type 1 or type 2 diabetes compared to people without diabetes, adjusting for age, sex and socio-economic status (SES). There were 77, 1275 and 9778 incident ICH events and the case-fatality rate was 44% (95% CI 33, 57), 38% (95% CI 35, 41) and 36% (95% CI 35, 37) in people with type 1, type 2 and without diabetes, respectively. In comparison with absence of diabetes, type 1 diabetes was associated with a higher incidence of ICH (1.74, 95% CI 1.38-2.21) and higher case fatality after ICH (1.35, 95% CI 1.01-1.70), after adjustment for age, sex and SES. The small increases in ICH incidence (1.06, 95% CI 0.99-1.12) and case-fatality (1.04, 95% CI 0.96-1.13) in people with type 2 diabetes compared with people without diabetes were not statistically significant.