High-Dose Vitamin D Supplementation Improves Microcirculation and Reduces Inflammation in Diabetic Neuropathy Patients.

We assessed the effect of different doses of vitamin D supplementation on microcirculation, signs and symptoms of peripheral neuropathy and inflammatory markers in patients with type 2 diabetes (T2DM). Sixty-seven patients with T2DM and peripheral neuropathy (34 females) were randomized into two treatment groups: Cholecalciferol 5000 IU and 40,000 IU once/week orally for 24 weeks. Severity of neuropathy (NSS, NDS scores, visual analogue scale), cutaneous microcirculation (MC) parameters and inflammatory markers (ILs, CRP, TNFα) were assessed before and after treatment. Vitamin D deficiency/insufficiency was detected in 78% of the 62 completed subjects. Following treatment with cholecalciferol 40,000 IU/week, a significant decrease in neuropathy severity (NSS, p = 0.001; NDS, p = 0.001; VAS, p = 0.001) and improvement of cutaneous MC were observed (p < 0.05). Also, we found a decrease in IL-6 level (2.5 pg/mL vs. 0.6 pg/mL, p < 0.001) and an increase in IL-10 level (2.5 pg/mL vs. 4.5 pg/mL, p < 0.001) after 24 weeks of vitamin D supplementation in this group. No changes were detected in the cholecalciferol 5000 IU/week group. High-dose cholecalciferol supplementation of 40,000 IU/week for 24 weeks was associated with improvement in clinical manifestation, cutaneous microcirculation and inflammatory markers in patients with T2DM and peripheral neuropathy.

Will the plant-based movement redefine physicians' understanding of chronic disease?

The world is experiencing a cataclysmically increasing burden from chronic illnesses. Chronic diseases are on the advance worldwide and treatment strategies to counter this development are dominated by symptom control and polypharmacy. Thus, chronic conditions are often considered irreversible, implying a slow progression of disease that can only be hampered but not stopped. The current plant-based movement is attempting to alter this way of thinking. Applying a nutrition-first approach, the ultimate goal is either disease remission or reversal. Hereby, ethical questions arise as to whether physicians' current understanding of chronic illness is outdated and morally reprehensible. In this case, physicians may need to recommend plant-based diets to every patient suffering from chronic conditions, while determining what other socioecological factors and environmental aspects play a role in the chronic disease process. This article provides insights to aspects of diet and chronic illness and discusses how the plant-based movement could redefine current understanding of chronic disease. The ethical justifications for recommending of a plant-based diet are analyzed. The article concludes that not advocating for plant-based nutrition is unethical and harms the planet and patients alike.

The role of dietary non-heme iron load and peripheral nerve inflammation in the development of peripheral neuropathy (PN) in obese non-diabetic leptin-deficient ob/ob mice.

INTRODUCTION: Here, we investigated inflammatory signs of peripheral nerves in leptin-deficient obese ob/ob mice and the modulating effects of the exogenous iron load. METHODS: Ob/ob and ob/+ control mice were fed with high, standard, or low iron diet for four months. RESULTS: We found intraepidermal nerve fiber degeneration in foot skin and low-grade neuropathic abnormalities including mildly slowed motor and compound sensory nerve conduction velocities and low-grade macrophage and T-cell infiltration without overt neuropathology in sciatic nerves of all ob/ob mice. Low dietary iron load caused more pronounced abnormalities than high iron load in ob/ob mice. DISCUSSION: Our data suggest that dietary non-heme iron deficiency may be a modulating factor in the pathogenesis of peripheral neuropathy in obese ob/ob mice with metabolic syndrome. Once the mechanisms can be further elucidated, how low dietary iron augments peripheral nerve degeneration and dysfunction via pro-inflammatory pathways and new therapeutic strategies could be developed. ABBREVIATIONS: CMAP: compound muscle action potential; cSNCV: compound sensory nerve conduction velocity; IENFD: intraepidermal nerve fiber density; LDL: low-density lipoprotein; MetS: metabolic syndrome; MNCV: motor conduction velocity; NCV: nerve conduction velocity; PN: peripheral neuropathy; PNS: peripheral nervous system; STZ: streptozotocin; T2D: type 2 diabetes mellitus; TNF alpha: tumor necrosis factor alpha; WHO: World Health Organization.

Ankle-brachial index and diabetic neuropathy: study of 225 patients / Index tornozelo-braquial e neuropatia diabética: estudo de 225 pacientes

ABSTRACT Objective To evaluate neuropathic pain and peripheral vascular disease in diabetics and compare this with the length of time since diagnosis in type 1, and type 2 diabetes. Methods A cross-sectional study with 225 diabetics chosen from their responses on the DN4 questionnaire, who were then evaluated with the ankle-brachial index (ABI), separating type 1 diabetes from type 2 diabetes. Results A higher incidence of neuropathic pain in those over 60 years of age showed an ABI > 1.3. Neuropathic pain was related to an abnormal ABI in 144 patients (64.2%). A statistically significant value was obtained in type 2 diabetes patients with more than 10 years from disease onset, 69 with altered ABI and 25 with normal ABI. There was an altered ABI (< 0.9) observed in 33% of type 1 diabetes patients and in 67% of type 2 diabetes patients. Conclusion The ABI test in type 1 diabetes and type 2 diabetes patients is important even in those who are asymptomatic. A diagnosis of more than 10 years prior, regardless of the presence of neuropathic pain or ischemic signs, altered the ABI.

RESUMO Objetivo Avaliar dor neuropática e doença vascular periférica em diabéticos e comparar com, tempo de diagnóstico de diabetes tipo 1(DM 1) e diabetes tipo 2(DM2). Métodos Estudo de corte transversal onde, 225 diabéticos responderam ao questionário (DN4) sendo submetidos ao índice tornozelo-braquial (ITB). Resultados predomínio de dor neuropática foi em pacientes acima de 60 anos com (DM2), com um ITB > 1,3 nesta população; assim a dor neuropática foi relacionada com o ITB anormal em 144 pacientes, total de 64,2%. Um valor estatisticamente significativo foi com (DM2).Um ITB alterado (< 0,9) em 33% no (DM 1) e em 67% (DM 2). Totalizando 132 indivíduos com alterações no ITB. Conclusão O teste ITB é útil em pacientes com DM 1 e DM 2 quando a dor neuropática é suspeita, mesmo em assintomáticos. E o tempo prolongado de diabetes (> 10 anos), independentemente da presença de dor ou sinais isquêmicos, alterou o ITB.

Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy.

Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells. Diabetic rats and high glucose-exposed N2A cells showed reduction in SIRT1 expression with consequent decline in mitochondrial biogenesis and autophagy. ILQ (10 & 20 mg/kg, po) administration to diabetic rats for 2 weeks and exposure to glucose-insulted N2A cells resulted in significant SIRT1 activation with concurrent increase in mitochondrial biogenesis and autophagy. ILQ administration also enhanced NAD+/NADH ratio in peripheral sciatic nerves which explains its possible SIRT1 modulatory effect. Functional and behavioural studies show beneficial effect of ILQ as it alleviated nerve conduction and nerve blood flow deficits in diabetic rats along with improvement in behavioural parameters (hyperalgesia and allodynia). ILQ treatment to N2A cells reduced high glucose-driven ROS production and mitochondrial membrane depolarization. Further, ILQ-mediated SIRT1 activation facilitated the Nrf2-directed antioxidant signalling. Overall, results from this study suggest that SIRT1 activation by ILQ mimic effects of calorie restriction, that is, PGC-1α-mediated mitochondrial biogenesis, FOXO3a mediated stress resistance and AMPK mediated autophagy effects to counteract the multiple manifestations in experimental DN.

Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes.

The purpose of this study was to determine the effect of supplementing the diet of a mouse model of type 2 diabetes with menhaden (fish) oil or daily treatment with resolvin D1 on diabetic neuropathy. The end points evaluated included motor and sensory nerve conduction velocity, thermal sensitivity, innervation of sensory nerves in the cornea and skin, and the retinal ganglion cell complex thickness. Menhaden oil is a natural source for n-3 polyunsaturated fatty acids, which have been shown to have beneficial effects in other diseases. Resolvin D1 is a metabolite of docosahexaenoic acid and is known to have anti-inflammatory and neuroprotective properties. To model type 2 diabetes, mice were fed a high-fat diet for 8 wk followed by a low dosage of streptozotocin. After 8 wk of hyperglycemia, mice in experimental groups were treated for 6 wk with menhaden oil in the diet or daily injections of 1 ng/g body wt resolvin D1. Our findings show that menhaden oil or resolvin D1 did not improve elevated blood glucose, HbA1C, or glucose utilization. Untreated diabetic mice were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities, had decreased innervation of the cornea and skin, and had thinner retinal ganglion cell complex. These end points were significantly improved with menhaden oil or resolvin D1 treatment. Exogenously, resolvin D1 stimulated neurite outgrowth from primary cultures of dorsal root ganglion neurons from normal mice. These studies suggest that n-3 polyunsaturated fatty acids derived from fish oil could be an effective treatment for diabetic neuropathy.

Terapia nutricional na gastroparesia diabética: [revisão] / Terapia nutricional para la gastroparesia diabética: [revisión] / Nutrition therapy for diabetic gastroparesis: [review]

O diabetes mellitus (DM) é condição causal da neuropatia autonômica, complicação crônica decorrente da ausência de um controle glicêmico eficiente ao longo dos anos. A gastroparesia consequentemente à neuropatia é um dos distúrbios de motilidade mais comuns entre os diabéticos e afeta cerca de 58% dos indivíduos com DM. Apesar dos avanços no conhecimento relacionado à sua fisiopatologia, a gastroparesia diabética ainda constitui uma complicação de difícil abordagem clínica, com sucesso terapêutico limitado. Seu tratamento inclui medidas dietéticas e nutricionais e o uso de drogas pró-cinéticas. O rigoroso controle glicêmico, juntamente a medidas dietéticas, constitui o eixo central da prevenção e da terapêutica da gastroparesia. A dieta direcionada ao paciente com DM tem por objetivo contribuir para a normalização da glicemia, atingir e manter o peso corpóreo adequado para o indivíduo, diminuir os fatores de risco cardiovascular, prevenir as complicações agudas e crônicas do DM e promover a saúde por meio de nutrição adequada. O manejo nutricional na gastroparesia diabética implica em modificações na consistência da dieta, oferecimento de pequenos volumes durante as refeições, exclusão de alimentos não tolerados e de difícil digestão, utilização de suplementos líquidos se os alimentos sólidos não forem tolerados, e nutrição enteral e parenteral se necessário. Este teve como objetivo realizar uma revisão bibliográfica sobre a terapia nutricional na gastroparesia diabética, complicação pouco conhecida, entretanto, bastante prevalente entre os pacientes diabéticos. A pesquisa bibliográfica foi realizada em diferentes bases de dados, utilizando artigos nacionais e internacionais, datados a partir do ano de 1988.

La diabetes mellitus (DM) es una condición causal de la neuropatía autonómica, las complicaciones crónicas derivadas de la falta de un control de glucosa en sangre eficaz en los últimos años. La gastroparesia la neuropatía es una consecuencia de trastornos de la motilidad más común entre los diabéticos y afecta a alrededor del 58% de las personas con DM. A pesar de los avances en los conocimientos relacionados con la fisiopatología, la gastroparesia diabética sigue siendo una complicación de difícil abordaje clínico, con un éxito terapéutico limitado. Su tratamiento incluye medidas nutricionales y dietéticas y el uso de fármacos procinéticos. El control estricto de la glucemia, junto con las medidas dietéticas, es el eje de la prevención y el tratamiento de la gastroparesia. La dieta dirigida a los pacientes diabéticos tiene como objetivo contribuir a la normalización de la glucosa en la sangre para lograr y mantener un peso corporal adecuado para la persona, reducir los factores de riesgo cardiovascular, la prevención de complicaciones agudas y crónicas de la diabetes y promover la salud a través de una nutrición adecuada. Manejo nutricional en la gastroparesia diabética implica cambios en la consistencia de la dieta, ofrecer pequeñas cantidades con las comidas, excluidos los alimentos no se tolera y difícil de digerir, el uso de suplementos líquidos que los alimentos sólidos no se toleran, y es la nutrición enteral y parenteral es necesario. Este objetivo de llevar a cabo una revisión bibliográfica sobre la terapia nutricional en la gastroparesia diabética, una complicación poco conocida, sin embargo, bastante frecuente entre los pacientes diabéticos. La búsqueda bibliográfica se realizó en diferentes bases de datos, el uso de artículos nacionales e internacionales, que data del año 1988.

Diabetes mellitus (DM) is a causal condition of autonomic neuropathy, chronic complications arising from the absence of an effective blood glucose control over the years. The gastroparesis the neuropathy is a consequence of motility disorders more common among diabetics and affects about 58% of individuals with DM. Despite advances in knowledge related to its pathophysiology, diabetic gastroparesis is still a complication of difficult clinical approach, with limited therapeutic success. His treatment includes nutritional and dietary measures and use of prokinetic drugs. Strict glycemic control, along with dietary measures, is the lynchpin of prevention and treatment of gastroparesis. The diet aimed at the diabetic patients aims to contribute to the normalization of blood glucose to achieve and maintain appropriate body weight for the individual, reduce cardiovascular risk factors, prevention of acute and chronic complications of diabetes and promote health through adequate nutrition. Nutritional management in diabetic gastroparesis involves changes in diet consistency, offer small amounts with meals, excluding food is not tolerated and difficult to digest, use of liquid supplements that solid foods are not tolerated, and enteral and parenteral nutrition is necessary. This aimed to conduct a literature review on nutritional therapy in diabetic gastroparesis, a complication little known, however, quite prevalent among diabetic patients. The literature search was performed in different databases, using national and international articles, dating from the year 1988.

Prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids.

The influence of diets containing gamma-linolenic acid (GLA; 18:3n-6) on sciatic nerve conduction velocity (NCV) was determined in diabetic rats. NCV was lower in diabetic rats fed diets supplemented with olive oil or sunflower seed oil than in nondiabetic rats; rats supplemented with GLA during a 5-wk diabetic period, however, did not exhibit significantly lower NCV. The mean proportion of the phospholipid fatty acid linoleic acid (18:2n-6) was higher in the sciatic nerves of diabetic rats than in the nondiabetic groups irrespective of dietary lipid treatment. Additionally, the proportion of linoleic acid was higher in the diabetic rats fed sunflower oil than in all other groups. Dietary GLA supplementation did not significantly influence the fatty acid composition of nerve membrane phospholipids and there was no obvious correlation between the fatty acid composition of nerve membrane phospholipids and NCV. The content of fructose and glucose in sciatic nerves was higher, whereas that of myo-inositol was lower, in diabetic rats than in nondiabetic rats; however, this was not significantly influenced by dietary GLA. GLA administration did not significantly influence Na(+)-K(+)-exchanging ATPase or ouabain binding activity in sciatic nerve preparations, both of which remained nonsignificantly different in the diabetic and nondiabetic groups. The results suggest that dietary GLA can prevent the deficit in NCV induced by diabetes and that this effect is independent of the nerve phospholipid fatty acid profile, sugar and polyol content, Na(+)-K(+)-exchanging ATPase activity, and ouabain binding. GLA may prevent the deficit in NCV indirectly, possibly by its role as a precursor of vasodilatory prostaglandins. These results confirm that GLA is the active component of evening primrose oil.

Alterations of Na,K-ATPase isoenzymes in the rat diabetic neuropathy: protective effect of dietary supplementation with n-3 fatty acids.

Diabetic neuropathy is a degenerative complication of diabetes accompanied by an alteration of nerve conduction velocity (NCV) and Na,K-ATPase activity. The present study in rats was designed first to measure diabetes-induced abnormalities in Na,K-ATPase activity, isoenzyme expression, fatty acid content in sciatic nerve membranes, and NCV and second to assess the preventive ability of a fish oil-rich diet (rich in n-3 fatty acids) on these abnormalities. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (D) and nondiabetic control animals (C) were fed the standard rat chow either without supplementation or supplemented with either fish oil (DM, CM) or olive oil (DO, CO) at a daily dose of 0.5 g/kg by gavage during 8 weeks. Analysis of the fatty acid composition of purified sciatic nerve membranes from diabetic animals showed a decreased incorporation of C16:1(n-7) fatty acids and arachidonic acids. Fish oil supplementation changed the fatty acid content of sciatic nerve membranes, decreasing C18:2(n-6) fatty acids and preventing the decreases of arachidonic acids and C18:1(n-9) fatty acids. Protein expression of Na,K-ATPase alpha subunits, Na,K-ATPase activity, and ouabain affinity were assayed in purified sciatic nerve membranes from CO, DO, and DM. Na,K-ATPase activity was significantly lower in sciatic nerve membranes of diabetic rats and significantly restored in diabetic animals that received fish oil supplementation. Diabetes induced a specific decrease of alpha1- and alpha3-isoform activity and protein expression in sciatic nerve membranes. Fish oil supplementation restored partial activity and expression to varying degrees depending on the isoenzyme. These effects were associated with a significant beneficial effect on NCV. This study indicates that fish oil has beneficial effects on diabetes-induced alterations in sciatic nerve Na,K-ATPase activity and function.

Polineurite assintomática: ponto de partida para o diagnóstico de diabetes / Asymptomatic polyneuritis: starting point for the diagnosis of diabetes

Oitenta pacientes que se submeteram a consulta neurológica ambulatorial por motivos diversos (excluídas polifagia, polidipsia, poliúria e modificaçäo na massa corporal) e nos quais o exame neurológico revelou uma polineurite foram submetidos a testes de tolerância à glicose, que resultaram anormais em 41 (todos tinham glicemia de jejum normal). A principal conclusäo a que chega o autor é de que oa polineurite é parte integrante do quadro geral do diabete, podendo representar uma de suas manifestaçöes mais iniciais e eventualmente preceder a detecçäo da própria alteraçäo metabólica pelo menos no que concerne às técnicas atualmente empregadas. O tratamento - limitado à dieta adequada - pode propiciar notória mellhora subjetiva