Prevalence, Diagnosis, and Treatment with 3 Different Statins of Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis in Military Personnel. Do Genetics Play a Role?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. AIMS: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. METHODS: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomized into 4 groups (n=151 each): diet-exercise, atorvastatin, rosuvastatin, or pitavastatin for 1 year (i.e., until the next routine evaluation). RESULTS: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001), and a total of 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs. 5.62, p=0.07; FIB-4 3.42 vs. 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). CONCLUSION: Atorvastatin, rosuvastatin, and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/- NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

Differentiation in the short- and long-term effects of smoking on plasma total ghrelin concentrations between male nonsmokers and habitual smokers.

To explore the association between the anorexigenic effects of nicotine and the orexigenic properties of ghrelin, plasma total ghrelin levels were measured in nonsmokers and habitual smokers before and after short-term exposure to cigarette smoke. Thirty-one male smokers and 23 nonsmoking volunteers were matched for age and body mass index. After an overnight fast and abstinence from smoking, they all smoked 2 cigarettes consecutively (same brand, rate of inhalation, and duration of smoking). Total ghrelin concentrations were measured by radioimmunoassay before smoking (baseline), immediately afterward, and 30, 60, and 90 minutes after the second cigarette. Baseline ghrelin levels were not different between smokers and nonsmokers. Smoking did not have an immediate influence on ghrelin concentrations in smokers (analysis of variance for repeated measurements, P=0.74), whereas there was a progressive decline in nonsmokers, reaching statistical significance at 30 minutes (P=.04) and a nadir at 60 minutes (P=.04) after smoking. Moreover, the area under the curve for the changes of ghrelin over time after smoking was lower in nonsmokers than in smokers (-287.2+/-167.1 vs 29.2+/-125.3 ng.min/L, P=.03). In conclusion, fasting plasma total ghrelin concentrations are not different between male smokers and nonsmokers. Smoking does not provoke any short-term change in ghrelin levels in smokers, but induces a decline in nonsmokers. If the anorectic effect of smoking is ghrelin induced, this effect may be present only in people not habituated to smoke exposure. In habitual smokers, ghrelin suppression by short-term smoking could be blunted as a result of desensitization due to prolonged nicotine exposure.

QT dispersion: comparison between participants with Type 1 and 2 diabetes and association with microalbuminuria in diabetes.

BACKGROUND AND AIMS: The interlead variation of QT duration in surface electrocardiogram [ECG; QT dispersion (QTd)] has been shown to predict mortality in both diabetic and general population. Diabetic cardiac autonomic neuropathy (CAN) is a common complication of diabetes, and it is also associated with worse prognosis among the diabetic population. In this study, we investigated the association between QTd duration and CAN, as well as other complications of diabetes in participants with Types 1 and 2 diabetes. METHODS: A total of 184 patients with either Type 1 (n=63) or 2 (n=121) diabetes, as well as 100 control participants, matched for age and sex with the diabetic individuals, were studied. QT and RR intervals were measured on 12 leads of resting ECG tracing. QTd was calculated semiautomatically using a computer program as the difference between the maximum and the minimum QT in any of the 12 leads. CAN was diagnosed when two out of the four classical tests were abnormal. RESULTS: QTd was not significantly different between controls and patients with either Type 1 or 2 diabetes. Age-adjusted QTd intervals were not significantly different between patients with Types 1 and 2 diabetes (P=.86). For both types of diabetes, no significant differences were found in QTd between patients with and without CAN. Multivariable linear regression analysis, after adjustment for a number of confounding factors, demonstrated a positive association between QTd and duration of diabetes (P=.02) in the group of the patients with Type 1 diabetes. In those with Type 2 diabetes, QTd was associated with age (P=.006) and presence of microalbuminuria (P=.001). In addition, no significant association was found with retinopathy or blood pressure levels. CONCLUSIONS: Age-adjusted QTd interval was not different between patients with Types 1 and 2 diabetes. CAN is not associated with QTd interval in both types of diabetes. Furthermore, microalbuminuria was found to be the strongest predictor of QTd in patients with Type 2 diabetes. Because long QTd interval predicts cardiac mortality in participants with diabetes, it is suggested that it may be a useful adjuvant index in the evaluation of cardiovascular risk in participants with Type 2 diabetes and microalbuminuria.

The association between cardiac autonomic neuropathy with metabolic and other factors in subjects with type 1 and type 2 diabetes.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a common diabetes complication associated with poor prognosis. This cross-sectional study aimed to examine for associations between CAN and metabolic and other parameters in patients with either type 1 (T1DM) or type 2 (T2DM) diabetes. PATIENTS AND METHODS: A total of 600 patients (T1DM, n=200; T2DM, n=400) were recruited. Participants with overt nephropathy, macrovascular complications, and treated hypertension were excluded. CAN was diagnosed when two of the four classical autonomic function tests were abnormal. RESULTS: CAN was diagnosed in 42.0% and in 44.3% of the participants with T1DM and T2DM, respectively. Multivariate logistic regression analysis demonstrated that, in T1DM, the odds [OR (95% confidence intervals)] of CAN increased with higher waist circumference [1.36 (1.01-2.02)], systolic blood pressure [1.16 (1.03-1.31)], hypertension [1.19 (1.03-2.67)], smoking [1.10 (1.12-1.40], fasting glucose [1.01 (1.00-1.01)], HbA(1c) [1.69 (1.07-2.76)], pubertal diabetes onset [1.08 (1.03-1.24)], LDL cholesterol [1.01(1.00-1.02)], triglycerides [1.58 (1.24-1.48)], retinopathy [1.13 (1.04-1.41)], peripheral neuropathy [2.53 (1.07-2.99)], glomerular filtration rate [0.93 (0.87-0.99)], and microalbuminuria [1.24 (1.12-1.36)]. The same analysis in T2DM demonstrated that the odds of CAN increased with higher waist circumference [1.08 (1.00-1.39)], systolic blood pressure [1.06 (1.02-1.12)], hypertension [1.50 (1.24-2.03)], smoking [1.22 (1.14-1.49)], diabetes duration [1.20 (1.09-1.34)], fasting glucose [1.21 (1.12-1.31)], HbA(1c) [1.25 (1.08-1.45)], LDL cholesterol [1.35 (1.04-1.75)], triglycerides [1.30 (1.00-1.68)], retinopathy [1.24 (1.16-1.35)], peripheral neuropathy [1.79 (1.07-2.01)], glomerular filtration rate [0.96 (0.95-0.97)], and microalbuminuria [1.20 (1.14-1.36)]. CONCLUSIONS: CAN is common in diabetes and is associated with modifiable factors including central fat distribution, hypertension, dyslipidemia, worse diabetes control, and smoking, and with the other microvascular complications of diabetes. Our findings emphasize the need for a multifactorial intervention for the prevention of CAN.

QT dispersion: comparison between diabetic and non-diabetic individuals and correlation with cardiac autonomic neuropathy.

INTRODUCTION: The QT interval on the resting electrocardiogram (ECG) expresses the myocardial depolarisation and repolarisation time. Elevated values of QT dispersion (QTd) are associated with cardiovascular mortality in diabetics. Cardiac autonomic neuropathy (CAN) is a common complication of diabetes that is also associated with increased morbidity and mortality. However, there are no data in the literature concerning the relation between CAN and QTd in diabetics. The aim of this study was to investigate: 1) the differences in QTd between diabetics and non-diabetics; 2) the differences in QTd between those with type 1 and type 2 diabetes; 3) the relation between QTd and CAN. METHODS: The study population included 184 diabetics (63 type 1, group D1; 121 type 2, group D2) and 100 healthy controls who had similar age and sex distribution to D1 (n=44) and D2 (n=56) subjects. CAN assessment was made using the standard Ewing and Clarke tests. The QT interval was measured on the 12-lead resting ECG. QTd was calculated automatically using special software. RESULTS: QTd values did not differ significantly between controls and D1 (p=0.15) or D2 (p=0.27). QTd was significantly greater in D2 than in D1 (p=0.02). There was no significant difference in QTd between those with and without CAN in either group of diabetics. CONCLUSIONS: QTd values do not differ between individuals with and without diabetes. Type 2 diabetes is associated with higher QTd values than is type 1 diabetes. CAN does not affect QTd in diabetics.