Estimated insulin sensitivity, cardiovascular risk, and hepatic steatosis after 12 years from the onset of T1D.

AIM: To test the hypothesis that intensive insulin treatment and optimal glycaemic control are not fully protective against reduction of insulin sensitivity in children with type 1 diabetes. MATERIAL AND METHODS: Cohort study of 78 normal-weight patients with prepubertal onset (T0 ) and follow-up waves at 1 (T1 ), 5 (T5 ), 10 (T10 ), and 12 (T12 ) years; matched for age and sex to 30 controls at T12 . Estimated insulin sensitivity (eIS) by three formulae; ultrasound evaluation of para and perirenal fat thickness; hepatic steatosis (HS); carotid intima media thickness (cIMT) at T12 . RESULTS: At T12, the 36 patients (46%) who had constantly or prevalently haemoglobin A1c (HbA1c) < 58 mmol/l during follow-up showed better eIS indexes (p = 0.049 to <0.0001); lipid profile (p = 0.042 to <0.0001), reduced fat mass (p = 0.012) and required lower insulin dose (p = 0.032) than the 42 patients (54%) with HbA1c ≥ 58 at T12. Patients (N = 25) with eISEDC  < 8.77 mg kg-1  min-1 showed higher cIMT (p < 0.0001). HS was found in 6 patients (∼8%). In patients and normal-weight controls, fat mass (p = 0.03), age (p = 0.03), cIMT (p = 0.05) predicted HS; eIS indexes (p from 0.04 to <0.0001) predicted cIMT. Body mass index, perirenal fat, fat mass, and triglycerides to high density lipoprotein cholesterol ratio were associated with eIS indexes (p from 0.03 to <0.0001). CONCLUSIONS: Young T1D patients have reduced insulin sensitivity and higher cIMT. Adiposity, glucose, and lipid control over follow-up are likely to influence both. Enhanced adiposity seems of paramount relevance for the onset of HS in T1D patients alike in healthy youths.

Lower Heart Rate Variability Is Associated with Lower Pulse Pressure Amplification: Role of Obesity.

BACKGROUND: Heart rate variability (HRV), pulse pressure amplification, and obesity represent risk factors for cardiovascular events. The aims of the present study are (1) to explore the impact of HRV on pulse pressure amplification and (2) to investigate whether the association between HRV and pulse pressure amplification differs in obese and lean subjects. METHODS: A total of 342 patients (age 61 ± 11 years) were enrolled. HRV was analyzed concerning both the frequency and time domain as well as concerning the HRV triangular index. Pulse pressure amplification was estimated as the ratio between brachial and carotid pulse pressure, the latter measured with SphygmoCor. RESULTS: Time domain HRV indices were directly correlated with pulse pressure amplification (the lower the HRV indices, the lower the pulse pressure amplification). This association was stronger in obese than in lean subjects after controlling for age and sex. CONCLUSION: Larger controlled studies are needed to provide a more detailed insight into the relation between HRV and pulse pressure amplification and to determine which pathways are differentially activated in lean and obese subjects.

Arachidonate cascade, apoptosis, and vitamin E in peripheral blood mononuclear cells from hemodialysis patients.

BACKGROUND: Lipid peroxidation and oxidative stress are enhanced in peripheral blood mononuclear cells (PBMCs) from hemodialysis (HD) patients because of upregulation of the 5-lipoxygenase pathway of the arachidonate cascade. 5-Lipoxygenase activity is specifically inhibited by vitamin E both in vitro and in vivo regardless of its administration route. METHODS: The effect of arachidonate cascade enzymes and vitamin E on oxidative stress and apoptosis was investigated in PBMCs from 16 maintenance HD patients treated for at least 6 months with cuprammonium rayon membranes in a two-step crossover study: after a 4-week treatment with vitamin E-coated cuprammonium rayon membranes and again after a 4-week treatment with oral vitamin E. Control PBMCs were obtained from 16 healthy volunteers. RESULTS: Membrane lipoperoxidation, cellular luminescence, membrane fluidity, and leukotriene B(4) content were significantly greater in PBMCs from HD patients; lipoxygenase was upregulated, but prostaglandin H synthase (PHS) was not affected. Regardless of administration route, vitamin E partially controlled lipid peroxidation and oxidative stress through direct inhibition of 5-lipoxygenase. Cultured PBMCs from HD patients showed a significant increase in apoptotic cells compared with controls. Vitamin E markedly reduced cell luminescence, membrane fluidity, and apoptosis, whereas the PHS inhibitor indomethacin was ineffective. Similar results were obtained with control PBMCs induced to apoptosis by hydrogen peroxide. CONCLUSION: Reported data suggest that the 5-lipoxygenase branch of the arachidonate cascade is only responsible for membrane peroxidation, oxidative stress, and apoptosis of PBMCs of HD patients, and administration of vitamin E may be helpful in the control of oxidative stress-related disease in these subjects.