Peripheral polyneuropathy in severely obese patients with metabolic syndrome but without diabetes: Association with low HDL-cholesterol.

INTRODUCTION:: The purpose of this study was to evaluate the prevalence of peripheral polyneuropathy (PPN) in subjects with grade II and III obesity (Ob-II,III) and metabolic syndrome (MetS) but without diabetes and to investigate possible associated factors. METHOD:: A cross-sectional study was performed in non-diabetic Ob-II,III,MetS patients using the Michigan Neuropathy Screening Instrument (MNSI) to assess the presence of PPN. RESULTS:: A total of 24 of 218 non-diabetic Ob-II,III,MetS patients had PPN. Based on univariate analysis, serum levels of LDL-cholesterol (p=0.046) were significantly associated with PPN, while serum triglycerides (p=0.118) and low HDL-cholesterol (p=0.057) showed a tendency toward this association. On a Poisson regression analysis, when the three possible associations were included, low HDL-cholesterol (p=0.047) remained independently associated. CONCLUSION:: In non-diabetic Ob-II,III,MetS patients, PPN defined by the MNSI showed a high prevalence and was associated with low levels of HDL-cholesterol. In order to diagnose that complication, neurological evaluation should be performed in these patients.

Peripheral polyneuropathy in severely obese patients with metabolic syndrome but without diabetes: Association with low HDL-cholesterol / Polineuropatia periférica em pacientes obesos graves com síndrome metabólica sem diabetes: associação com baixo HDL-colesterol

Summary Introduction: The purpose of this study was to evaluate the prevalence of peripheral polyneuropathy (PPN) in subjects with grade II and III obesity (Ob-II,III) and metabolic syndrome (MetS) but without diabetes and to investigate possible associated factors. Method: A cross-sectional study was performed in non-diabetic Ob-II,III,MetS patients using the Michigan Neuropathy Screening Instrument (MNSI) to assess the presence of PPN. Results: A total of 24 of 218 non-diabetic Ob-II,III,MetS patients had PPN. Based on univariate analysis, serum levels of LDL-cholesterol (p=0.046) were significantly associated with PPN, while serum triglycerides (p=0.118) and low HDL-cholesterol (p=0.057) showed a tendency toward this association. On a Poisson regression analysis, when the three possible associations were included, low HDL-cholesterol (p=0.047) remained independently associated. Conclusion: In non-diabetic Ob-II,III,MetS patients, PPN defined by the MNSI showed a high prevalence and was associated with low levels of HDL-cholesterol. In order to diagnose that complication, neurological evaluation should be performed in these patients.

Resumo Objetivo: Avaliar a prevalência da polineuropatia periférica (PNP) em indivíduos obesos graus II e III com síndrome metabólica (Ob-II,III,SM) sem diabetes e buscar possíveis fatores associados. Método: Em um estudo transversal, realizado em indivíduos Ob-II,III,SM e sem diagnóstico de diabetes, o Instrumento de Screening de Michigan (MNSI) foi utilizado para avaliar a presença de PNP. Resultados: Um total de 24 de 218 pacientes Ob-II,III,SM e sem diabetes tinham PNP. Quando observamos as associações com PNP em uma análise univariada, níveis séricos de LDL-colesterol (p=0.046) estiveram significativamente associados e houve também uma tendência à associação com níveis séricos de triglicerídeos (p=0.118) e baixo HDL-colesterol (p=0.057). Em uma análise de regressão de Poisson, quando as três possíveis associações foram incluídas, baixo HDL-colesterol (p=0.047) manteve-se independentemente associado. Conclusão: Em pacientes Ob-II,III,SM, mas sem diabetes, a PNP definida pelo MNSI tem uma prevalência elevada e está associada a baixos níveis de HDL-colesterol. Para diagnóstico dessa complicação, recomenda-se realizar o exame neurológico desses pacientes.

Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.

Why targeting HDL should work as a therapeutic tool, but has not.

Atherosclerosis is one of the most common causes of death and disability in the United States today despite the availability of statins, which reduce hyperlipidemia, a risk factor that predisposes individuals to this disease. Epidemiology of human populations has overwhelmingly demonstrated an inverse correlation between the concentration of plasma high-density lipoprotein (HDL) cholesterol (HDL-C) and the likelihood of developing cardiovascular disease (CVD). Decades of observations and mechanistic studies suggest that one protective function of HDL is its central role in reverse cholesterol transport. In this pathway, the ATP-binding cassette transporter A1 releases intracellular cholesterol, which is packaged with apolipoprotein A-I (apoA-I) into nascent HDL particles and released from the plasma membrane. Further lipidation and maturation of HDL occur in plasma with the eventual uptake by the liver where cholesterol is removed. It is generally accepted that CVD risk can be reduced if plasma HDL-C levels are elevated. Several different pharmacological approaches have been tried; the most popular approach targets the movement of cholesteryl ester from HDL to triglyceride-rich particles by cholesteryl ester transfer protein. Inhibition of cholesteryl ester transfer protein increases plasma HDL-C concentration; however, beneficial effects have yet to be demonstrated, likely the result of off-target effects. These revelations have led to a reevaluation of how elevating HDL concentration could decrease risk. A recent, landmark study showed that the inherent cholesterol efflux capacity of an individual's plasma was a better predictor of CVD status than overall HDL-C concentration. Even more provocative are recent studies showing that apoA-I, the principle protein component of HDL modulates cellular inflammation and oxidation. The following will review all these potential routes explaining how HDL apoA-I can reduce the risk of CVD.

Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance.

BACKGROUND: Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (SA index) for the identification of IR and related metabolic conditions. METHODS: A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the SA index were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated. RESULTS: The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 vs. 0.669, P = 0.74), obesity (0.592 vs. 0.610, P = 0.32), hypertriglyceridemia (0.661 vs. 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624 vs. 0.633, P = 0.58) were similar. A total adiponectin level of 8.03 mug/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 mug/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.The area under the ROC curve of the SA index for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677]. CONCLUSIONS: Total adiponectin, HMWA and the SA index had similar utility for the identification of IR and metabolic disturbances.