Increased leukotriene B4 plasma concentration in type 2 diabetes individuals with cardiovascular autonomic neuropathy.

BACKGROUND AND AIM: A low-grade inflammation is associated with cardiac autonomic neuropathy (CAN) and increased concentration of leukotriene B4 (LTB4) was found in individuals with type 1 diabetes and definitive CAN. This cross-sectional study evaluated plasma concentration of LTB4 and of other inflammatory mediators, namely, tumor necrosis factor (TNF), interleukin (IL)1B, and IL10 in individuals with type 2 diabetes (T2D) and different degrees of CAN, and correlated these inflammatory mediators with the degree of glycemic control and with a surrogate marker of insulin resistance. METHODS: TNF, IL1B, IL10 and LTB4 plasma concentrations were measured in 129 T2D subjects (62% women with [median] age of 63 years, disease duration of 8 years and HbA1c of 7.3%) with or without CAN. The Lipid accumulation product index was used as a surrogate marker of insulin resistance. RESULTS: LTB4 concentration was significantly higher in those presenting incipient CAN (69.7 ± 16.6 pg mL-1) and definitive CAN (71.5 ± 15.7 pg mL-1) versus those without CAN (57.0 ± 13.9 pg mL-1). The groups without CAN and with incipient CAN were pooled (group without definitive CAN) and compared to those with definitive CAN. LTB4 concentration was higher in the latter group, as well as TNF concentration, while IL10 concentration was lower in this group. After adjustment for confounding variables, only LTB4 concentration remained significantly different between the groups with and without definitive CAN. Plasma concentration of LTB4 did not correlate with the degree of glycemic control. After sorting the participants by sex, a borderline weak correlation was found between LTB4 and the Lipid accumulation product index in women. CONCLUSION: In the T2D setting, circulating LTB4 concentration seems to be associated with cardiovascular dysautonomia.

Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study.

The paucity of epidemiological data regarding diabetes complications in Brazil motivated us to evaluate the prevalence rates of distal symmetric polyneuropathy (DSP) and of cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes (T2D) followed in a primary care unit. A total of 551 individuals (59.3% women, 65 years old; diabetes duration of 10 years; HbA1c of 7.2%, medians) were included in this cross-sectional study. DSP was diagnosed by sum of the Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score (NDS) and by the Semmes-Weinstein monofilament. CAN was diagnosed by cardiovascular autonomic reflex tests combined with spectral analysis of heart rate variability. The prevalence rates of DSP were 6.3% and 14.3%, as evaluated by the sum of NSS and NDS and by the Semmes-Weinstein monofilament, respectively. Those with DSP diagnosed by monofilament presented longer diabetes duration, worse glycemic control and a higher stature. The prevalence rates of incipient and definitive CAN were 12.5% and 10%, respectively. Individuals with definitive CAN presented a higher frequency of hypercholesterolemia and of arterial hypertension. The higher prevalence rate of DSP with the use of the monofilament suggests that it may be a more appropriate tool to diagnose DSP in the primary care setting in Brazil.

Diabetes Mellitus: a raiz do problema / Diabetes mellitus: the root of the problem

A doença cardiovascular (DCV) de origem aterosclerótica é a principal causa da morbidade e mortalidade em pacientes com diabetes mellitus (DM). Tanto os fatores de risco cardiovascular associados à resistência à insulina (RI) no contexto da síndrome da adiposidade visceral (SAV) quanto a hiperglicemia crônica contribuem para o risco da DCV na DM. A hiperinsulinemia compensatória que se estabelece na RI estimula os fatores de transcrição SREBP1c e SREBP1 em que se ativam os genes lipogênicos, levando à grande produção hepática de triglicérides. A hipertrigliceridemia é o gatilho para as demais alterações lipídicas que contribuem para o perfil pró-aterogênico na RI, caracterizando-se pelo predomínio de LDL pequenas e densas e redução do colesterol HDL. A hiperinsulinemia, também, está intimamente ligada à hipertensão arterial, pois aumenta o tônus simpático e a reabsorção renal de sódio. A RI é considerada o melhor fator preditivo para a ocorrência de DM tipo 2 (DM2), sendo necessário um defeito concomitante na secreção de insulina para que a hiperglicemia se estabeleça. Os efeitos deletérios da hiperglicemia devem-se à ativação de vias bioquímicas que resultam em inflamação e estresse oxidativo celular. A dislipidemia e a hipertensão arterial secundárias à RI, assim como a hiperglicemia, são importantes moduladores do risco cardiovascular na SAV e na DM2 e devem ser intensiva e conjuntamente abordados no tratamento e prevenção da DCV.

Cardiovascular disease (CVD) of atherosclerotic origin is the main cause of morbidity and mortality in patients with diabetes mellitus (DM). Both the cardiovascular risk factors associated with insulin resistance (IR) in the context of visceral adiposity syndrome (VAS) and chronic hyperglycemia contribute to the risk of CVD in DM. Compensatory hyperinsulinemia established in IR stimulates the transcription factors SREBP1c and SREBP1a, which activate lipogenic genes, leading to high hepatic production of triglycerides. Hypertriglyceridemia triggers other lipid changes that contribute to the pro-atherogenic profile in IR, which is characterized by the predominance of small and dense LDL and reduction of HDL-cholesterol. Hyperinsulinemia is also closely linked to arterial hypertension, as it increases sympathetic tone and renal sodium reabsorption. IR is considered the best predictive factor for the occurrence of type 2 DM (DM2), and a concomitant defect in insulin secretion is required for hyperglycemia to be established. The harmful effects of hyperglycemia are due to activation of biochemical pathways that result in inflammation and cellular oxidative stress. Dyslipidemia and hypertension secondary to IR, as well as hyperglycemia, are important modulators of cardiovascular risk in VAS and DM2 and should be intensively and jointly addressed in the management and prevention of CVD.