Interplay between non-alcoholic fatty liver disease and cardiovascular risk in an asymptomatic general population.

BACKGROUND AND AIMS: Non-alcoholic fatty liver (NAFLD) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk in a general population. METHODS: Five hundred and forty-two subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (controlled attenuation parameter > 288 dB/m) and severe fibrosis (low risk, liver stiffness measurement [LSM] < 7.9 KPa with M probe and < 5.7 KPa with XL probe; intermediate risk, LSM 7.9-9.5 KPa with M probe and 5.7-9.2 KPa with XL probe; high risk, LSM ≥ 9.6 KPa with M probe and ≥ 9.3 KPa with XL probe) were assessed with FibroScan. Cardiovascular risk was evaluated by the atherosclerotic cardiovascular disease (ASCVD) risk estimator and defined low if < 5%, borderline if 5-7.4%, intermediate if 7.5-19.9% and high if ≥ 20%. Intima-media thickness (IMT) was measured with ultrasound. RESULTS: Prevalence of steatosis and of severe fibrosis in this cohort was 31.7% and 4.8%, respectively. ASCVD score was evaluated in patients with and without steatosis and according to the risk of severe fibrosis. By ordinal regression analysis, both steatosis (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.13-2.33, P = 0.009) and severity of fibrosis (OR 1.67, 95% CI 1.18-2.36, P = 0.003) were independent risk factors for a higher ASCVD risk after adjusting for obesity. Subjects with NAFLD, when compared with those without, did not differ for IMT (0.75 vs 0.72 mm; P = 0.11) and IMT ≥ 1 mm (15.6% vs 12.1%; P = 0.24). Higher prevalence of IMT ≥ 1 mm was found in patients at high or intermediate risk of severe fibrosis (24% and 28.6%, respectively) compared with those at low risk (12.1%) (P = 0.03); this association was maintained after adjusting for confounders (OR 2.70, 95% CI 1.01-2.86, P = 0.04). CONCLUSION: In the setting of a general adult population, the presence of NAFLD and severe fibrosis are associated with to a higher cardiovascular risk profile, pointing towards the need for specific preventive measures.

Serum Irisin Concentrations in Severely Inflamed Patients.

Irisin is a recently discovered exercise-induced myokine that has been attributed the role of favoring white-to-brown adipose tissue trans-differentiation. We confirmed in a population-based cohort that irisin serum concentrations are independently correlated with the habitual level of physical activity, but we also observed an independent correlation with serum concentrations of high-sensitivity C-reactive protein (hs-CRP), thus suggesting that inflammation may influence irisin production. In order to investigate the association between irisin and inflammation, we measured serum irisin concentrations in a group of inflamed inpatients. We hypothesized that if an association between irisin and inflammation exists, severely inflamed patients, even though physically inactive, might also exhibit high serum irisin levels. We recruited 40 consecutive markedly inflamed inpatients on the basis of serum CRP levels. Their irisin serum concentrations (Phoenix Europe, Germany) were compared with those obtained in the population-based cohort of the ABCD_2 study (Alimentazione, Benessere Cardiovascolare e Diabete) (ISRCTN15840340). The inflamed patients exhibited higher serum irisin concentrations (median: 6.77 ng/ml; 95% CI for the median: 5.97-7.23) than those observed in the ABCD cohort (median: 5.21 ng/ml; 95% CI for the median: 5.08-5.30; p <0.001). Irisin concentrations were significantly correlated with age (r=-0.44; p <0.001), creatinine (r=-0.35; p <0.05), and fibrinogen (r=0.40; p <0.05) concentrations. No association was observed between irisin, interleukine-6 and tumor necrosis factor alpha. This study confirms the association between inflammation and irisin concentrations. Further studies are needed to understand the mechanisms underlying this association and its possible clinical implications.

Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: Genetic and metabolic risk factors in a general population.

BACKGROUND & AIMS: The worldwide spread of obesity is leading to a dramatic increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its complications. We aimed to evaluate both prevalence and factors associated with NAFLD in a general population in a Mediterranean area. METHODS: We considered 890 consecutive individuals included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340). Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured with FibroScan. Participants were genotyped for PNPLA3 rs738409 and TM6SF2 rs58542926 variants. RESULTS: The prevalence of NAFLD in the cohort was 48%. NAFLD participants exhibited elevated LSM values, suggesting advanced fibrosis (6.5% of cases). Both NAFLD and advanced fibrosis were independently associated with traditional risk factors (NAFLD: age >50 years, obesity, hypertension, elevated ALT and low HDL-cholesterol serum concentrations. Advanced fibrosis: IFG/diabetes, elevated ALT serum concentrations). A high prevalence (>60%) of NAFLD was found in obese people, while it varied widely in non-obese people according to the presence of metabolic risk factors. PNPLA3 G variant (OR = 1.33, 95% C.I. = 1.01-1.8; P < .05) was independently associated with NAFLD. Prevalence of advanced fibrosis (high LSM values) ranged from 3.4% (no risk factors) to 60% (presence of all risk factors). TM6SF2 T variant (OR = 3.06, 95% C.I. = 1.08-8.65, P < .05) was independently associated with advanced fibrosis (high LSM values). CONCLUSIONS: In a cohort of a general population, the prevalence of NAFLD was very high, and among NAFLD patients a significant proportion had advanced fibrosis (high LSM values). Apart from traditional risk factors, genetic factors may have a significant role that needs to be further investigated.

Does iris(in) bring bad news or good news?

Irisin, a novel myokine produced in response to physical activity, promotes white-to-brown fat transdifferentiation. The name irisin referred to the ancient Greek goddess Iris, the messenger who delivered (bad) news from the gods. In mice, it has been demonstrated that irisin plays a key role in metabolic regulation, energy expenditure and glucose homeostasis. New findings from various studies carried out in both animals and humans suggest that irisin might also have other favorable effects, such as increasing bone cortical mass, preventing hepatic lipid accumulation, and improving cognitive functions, thus mediating many exercise-induced health benefits. However, data on the role and function of irisin in humans have prompted controversy, due mostly to the only recent confirmation of the presence of irisin in humans. Another strong limitation to the understanding of irisin mechanisms of action is the lack of knowledge about its receptor, which until now remains unidentified in humans and in animals. This review presents an overall analysis of the history of irisin, its expression, and its involvement in health, especially in humans. Level of Evidence Level V, review.

Endothelial function in healthy centenarians living in the Madonie's district (Italy).

BACKGROUND: Endothelial function declines with age and plays a critical role in cardiovascular health. Therefore, investigating endothelial function in successful aging models, such as centenarians, is of interest. Flow-mediated dilation (FMD) of the brachial artery is the gold standard for measuring endothelial function in vivo in humans. Therefore, we investigated, for the first time, the FMD of the brachial artery in a group of healthy centenarians. METHODS: Selected as part of the ABCD project (nutrition, cardiovascular wellness, and diabetes) centenarians (aged ≥100 years) living in the municipalities of Madonie (Palermo, Italy) were compared with a younger (aged <65 years) sex-matched control group from the ABCD general cohort. FMD of the brachial artery was measured in all participants using a real-time computed video analysis system for B-mode ultrasound images. Body composition (bioimpedance), carotid intima-media thickness (IMT), and ankle-brachial index (ABI) were also measured. RESULTS: Eleven participants (males 36.4 %; age: 101 ± 1 years) out of 28 healthy centenarians successfully cooperated with the FMD test procedures, which require remaining with the upper limb immobile for approximately 10 min. This subgroup was compared with a control group of 76 healthy and younger individuals (males 36.8 %; aged: 41 ± 14 years; P < 0.001). Centenarians exhibited better endothelial function than the control group (FMD: 12.1 ± 4.3 vs 8.6 ± 5.3 %; P < 0.05). The carotid IMT was higher in the centenarian group than in the control group (0.89 ± 0.09 vs 0.56 ± 0.18 mm; P < 0.001), whereas the ABI was comparable between the two groups. CONCLUSIONS: This small group of centenarians demonstrated an unusually favorable endothelial function, which may contribute to their unique aging profile. Further research is needed to determine whether FMD is a valid prognostic marker for successful aging.

Factors associated with body weight gain and insulin-resistance: a longitudinal study.

BACKGROUND: Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight. SUBJECTS: A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of ß-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, PNPLA3 was genotyped. RESULTS: Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, P < 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m2, P = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg, P = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg, P < 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (P < 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (P < 0.001). CONCLUSIONS: EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow. CLINICAL TRIAL REGISTRATION: ISRCTN15840340.

Very Prolonged Treatment with Albendazole of a Case of Disseminated Abdominal Cystic Echinococcosis.

Cystic echinococcosis is a zoonosis caused by the ingestion of food or water contaminated by Echinococcus eggs. E. granulosus is the most common causative agent of cystic echinococcosis that still has a relevant incidence in Italy, especially on the islands of Sicily and Sardinia. We report the case of a 64-year-old man with disseminated abdominal cystic echinococcosis (liver, spleen, peritoneum). The patient was asymptomatic and non-eligible for surgical treatment. Treatment with albendazole 400 mg/twice daily was started in 2012 for 15 cycles (each cycle consisted of three 28-day treatments at 14-day intervals) over 10 years for a total of 1260 days of treatment. Serum anti-Echinococcus antibody titers and imaging (echography, TC) were evaluated to monitor the evolution of the disease. Imaging techniques documented the regression of all cyst lesions, but it was less evident for the peritoneal localizations that still are in follow-up. In this case, the prolonged treatment with albendazole was effective, safe and free of side effects. Until today, the patient displays a good clinical condition.

BNT162b2 Booster Dose Elicits a Robust Antibody Response in Subjects with Abdominal Obesity and Previous SARS-CoV-2 Infection.

Little is known about the long-term durability of the induced immune response in subjects with obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody responses after BNT162b2 vaccine booster dose, comparing individuals with and without abdominal obesity (AO), discerning between individuals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, on the 21st day after vaccine dose 1, and at 1, 3, 6, and 9 months from dose 2, and at 1 and 3 months following the booster dose. To detect SARS-CoV-2 infection, nucleocapsid antibodies were measured at baseline and at the end of the study. Multivariable linear regression evaluated the three-month difference in the absolute variation in IgG-TrimericS levels from booster dose, showing AO and SARS-CoV-2 infection status interactions (p = 0.016). Regardless of possible confounding factors and IgG-TrimericS levels at the booster dose, AO is associated with a higher absolute change in IgG-TrimericS in prior infected individuals (p = 0.0125). In the same regression model, no interaction is highlighted using BMI (p = 0.418). The robust response in the development of antibodies after booster dose, observed in people with AO and previous infection, may support the recommendations to administer a booster dose in this population group.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

Role of Dietary Carotenoids in Frailty Syndrome: A Systematic Review.

Unbalanced diets and altered micronutrient intake are prevalent in the aging adult population. We conducted a systematic review to appraise the evidence regarding the association between single (α-carotene, ß-carotene, lutein, lycopene, ß-cryptoxanthin) or total carotenoids and frailty syndrome in the adult population. The literature was screened from study inception to December 2021, using six different electronic databases. After establishing inclusion criteria, two independent researchers assessed the eligibility of 180 retrieved articles. Only 11 fit the eligibility requirements, reporting five carotenoid entries. No exclusion criteria were applied to outcomes, assessment tools, i.e., frailty constructs or surrogates, recruitment setting, general health status, country, and study type (cohort or cross-sectional). Carotenoid exposure was taken as either dietary intake or serum concentrations. Cross-sectional design was more common than longitudinal design (n = 8). Higher dietary and plasma levels of carotenoids, taken individually or cumulatively, were found to reduce the odds of physical frailty markedly, and the evidence showed consistency in the direction of association across all selected studies. Overall, the methodological quality was rated from moderate (27%) to high (73%). Prevention of micronutrient deficiencies has some potential to counteract physical decline. Considering carotenoids as biological markers, when monitoring micronutrient status, stressing increased fruit and vegetable intake may be part of potential multilevel interventions to prevent or better manage disability.

Effects of Mediterranean Diet Combined with CrossFit Training on Trained Adults' Performance and Body Composition.

CrossFit is a high-intensity training discipline increasingly practiced in recent years. Specific nutritional approaches are usually recommended to maximize performance and improve body composition in high-intensity training regimens; notwithstanding, to date there are no targeted nutritional recommendations for CrossFit athletes. The Mediterranean Diet (MD) is a diet approach with a well-designed proportion of macronutrients, using only available/seasonal food of the Mediterranean area, whose health benefits are well demonstrated. No studies have evaluated this dietary strategy among CrossFit athletes and practitioners; for this reason, we tested the effects of 8 weeks of MD on CrossFit athletes' performance and body composition. Participants were assigned to two groups: a diet group (DG) in which participants performed CrossFit training plus MD, and a control group (CG) in which participants partook in the CrossFit training, continuing their habitual diet. Participants were tested before and after the 8 weeks of intervention. At the end of the study, no significant difference was noted in participants' body composition, whereas improvements in anaerobic power, explosive strength of the lower limbs, and CrossFit-specific performance were observed only in the DG. Our results suggest that adopting a MD in CrossFit athletes/practitioners could be a useful strategy to improve specific strength, endurance, and anaerobic capacity while maintaining overall body composition.

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women.

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the "Mater Domini" University Hospital in Catanzaro, Calabria region, and the "P. Giaccone "University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.

Obesity and Circulating Levels of Vitamin D before and after Weight Loss Induced by a Very Low-Calorie Ketogenic Diet.

Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10-12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass-kg (r = -0.40; p < 0.05) and body mass index (r = -0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass-kg (r = -0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss.

Influence of Habitual Dairy Food Intake on LDL Cholesterol in a Population-Based Cohort.

BACKGROUND: Cholesterol has a pivotal role in human physiology, exerting both structural and functional activity. However, higher blood cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are a major cardiovascular risk factor. Therefore, special attention has been given to the effect of dietary factors in influencing LDL-C blood levels. In particular, much research has focused on dairy products, since they are a main component of different dietary patterns worldwide. A large body of evidence did not support the hypothesis that dairy products significantly increase circulating LDL-C, but no definitive data are available. Hence, we aimed to assess the relationships among LDL-C, habitual dairy food intake and anthropometric variables in a cohort representative of the general population in a Mediterranean area. METHODS: We evaluated 802 healthy adults included in the ABCD_2 (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. The habitual intake of dairy products was assessed with a validated food frequency questionnaire, and LDL-C serum levels and several anthropometric parameters were measured. RESULTS: The group with high LDL-C serum concentrations (≥130 vs. <130 mg/dL) exhibited higher age, body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage, systolic and diastolic blood pressure, carotid intima-media thickness and glycated hemoglobin. The habitual diet was not different between the groups in terms of macronutrient, cholesterol, egg and dairy food intake, with the exception of the weekly number of portions of milk (higher in the low LDL-C group vs. the high LDL-C group) and ricotta cheese (higher in the high LDL-C group vs. the LDL-C group). No significant correlation was found between LDL-C blood levels and the habitual intake of dairy products or the dietary intake of cholesterol and fats. The multivariate regression analyses (R2 = 0.94) showed that LDL-C blood levels were significantly associated with the habitual intake of milk (p < 0.005) and ricotta cheese (p < 0.001) and with BMI (p < 0.001). CONCLUSION: Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations. More studies are needed to better characterize the relationship between dairy products and circulating LDL-C.

Endothelial Function in Obese Patients Treated with Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) is becoming an increasingly frequent treatment option especially in people with morbid obesity, demonstrating that it is able to reduce total mortality and cardiovascular (CV) risk. Despite endothelial dysfunction is an essential requisite contributing to atherosclerosis and predicting CV events, only some studies have investigated the effects of BS on endothelial function with controversial results. In this study, the effects of weight loss on endothelial function were investigated in obese patients after BS and compared with patients after medical nutrition treatment (MNT). PATIENTS AND METHODS: Seventeen obese patients who underwent BS procedures (9 adjustable gastric bands, 3 gastric by-passes and 5 biliopancreatic diversions) were included in the study and compared with 18 obese individuals who underwent MNT. Endothelial function was investigated by flow-mediated dilation (FMD) of the brachial artery. Also, carotid intima-media thickness (c-IMT) was measured as a marker of subclinical atherosclerosis. RESULTS: At the end of follow-up, the mean weight loss was 18.8% in the BS group and 7.0% in the MNT group. After treatment, FMD significantly decreased in the BS group (mean ± SD before: 9.0 ± 4.7; after: 6.1 ± 2.9%; P= 0.04); however, no significant change was observed in the MNT group (before: 9.4 ± 5.8; after: 8.3 ± 5.3; P= 0.41). The modification of endothelial function was negatively correlated with c-IMT change in the BS group (r= -0.63; P <0.007). CONCLUSION: A significant endothelial dysfunction occurred following BS but not after MNT. Furthermore, the decline of endothelial function observed in the BS group might have contributed to atherosclerosis.

Metabolic and Cardiovascular Effects of Switching Thiazides to Amlodipine in Hypertensive Patients With and Without Type 2 Diabetes (the Diuretics and Diabetes Control Study).

Background: Different studies have indicated that thiazide diuretics can increase the risk of developing type 2 diabetes (T2D). Therefore, in this study, we investigated whether switching from hydrochlorothiazide (HCTZ) to amlodipine resulted in ameliorating different cardiovascular and metabolic measures in hypertensive patients with or without T2D. Methods: This study [Diuretics and Diabetes Control (DiaDiC)] was a 6-week, single-blind, single-center randomized controlled trial. The first 20 normal glucose-tolerant, 20 prediabetic, and 20 T2D consecutive patients were randomized to continue the previous antihypertensive treatment with HCTZ (12.5-25 mg/day) or to switch from HCTZ to amlodipine (2.5-10 mg/day). The primary endpoints were the absolute change in 7-day continuous subcutaneous glucose monitoring (CSGM) glycemia, serum uric acid concentrations, and endothelial function [measured as flow-mediated dilation (FMD)]. Other secondary endpoints were investigated, including changes in glycated hemoglobin (HbA1c), glycemic variability from 7-day CSGM, and the estimated glomerular filtration rate (eGFR). Results: Amlodipine treatment was associated with a significant reduction in HbA1c (P = 0.03) for both 7-day CSGM glycemia (P = 0.01) and glycemic variability (coefficient of variability %: HCTZ +3%, amlodipine -2.8%), and a reduction in uric acid concentrations (P < 0.001), especially in participants with T2D or prediabetes. Following amlodipine treatment, a significant increase in both eGFR (P = 0.01) and FMD (P = 0.02) was also observed. Conclusions: This study demonstrates that the replacement of HCTZ with amlodipine has several metabolic and cardiovascular beneficial effects. However, further intervention studies are necessary to confirm the clinical effects of thiazides, especially in diabetic people and in those at risk of diabetes.

Effects of vildagliptin, a DPP-4 inhibitor, in elderly diabetic patients with mild cognitive impairment.

INTRODUCTION: There is an unclear association between type 2 diabetes and mild cognitive impairment in the elderly. Both diseases are more prevalent in the older adults compared to the younger counterpart. Some anti-diabetic drugs seem to influence positively the evolution of mild cognitive impairment. This retrospective study investigated the effect of vildagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), on the cognitive functioning of elderly diabetic patients with mild cognitive impairment (MCI) documented at mini mental state examination (MMSE). METHODS: We included 60 diabetic elderly people which were divided in 2 groups: Group A, 30 patients with HbA1c (glycated hemoglobin) ≤7.5% and treated with metformin, and Group B, 30 patients with HbA1c >7.5%, and treated with metformin plus vildagliptin. We collected data on MMSE, fasting plasma glucose (FPG) and HbA1c at baseline and after 180 ±â€¯10 days from the beginning of treatment. RESULTS: The two groups exhibited significantly different values in FPG (P < 0.05) and HbA1c (P < 0.01) at baseline, and in MMSE score (P < 0.001) after treatment. The intragroup comparison showed a significant (P < 0.05) reduction in MMSE score in group A, and in HbA1c (P = 0.01) in group B. CONCLUSION: Vildagliptin in addition to metformin resulted in the maintenance of MMSE score, showing a protecting role on cognitive functioning compared to the metformin only group.

Resting Energy Expenditure and Substrate Oxidation in Malnourished Patients With Type 1 Glycogenosis.

CONTEXT: Type 1a and 1b glycogenosis [glycogen storage disorder (GSD)1a, GSD1b] are rare diseases generally associated with malnutrition. Although abnormal substrate oxidation rates and elevated energy expenditures might contribute to malnutrition, this issue has not been investigated. OBJECTIVE: To investigate whether abnormal resting energy expenditure (REE) and substrate oxidation rate characterize patients with GSD1. DESIGN: Cross-sectional study. SETTING: Outpatient referral center for rare diseases and laboratory of clinical nutrition at the University Hospital of Palermo. PATIENTS: Five consecutive patients with GSD1 (4 type a, 1 type b; 3 men, 2 women; age range, 19 to 49 years). MAIN OUTCOME MEASURES: The usual clinical procedures for patients with malnutrition, including REE and basal substrate oxidation rate (both indirect calorimetry), body composition (bioimpedance method), muscle strength (hand-grip test), and the usual laboratory tests, were performed. RESULTS: Malnutrition was clearly diagnosed in 2 patients (1 GSD1a and 1 GSD1b), with REE elevated in all five patients, and especially, in the two malnourished patients (+124% and +32.1% vs predictive values using Harris-Benedict equations). The two malnourished patients also exhibited lower basal protein oxidation rates (7.7% and 6.6%) than the nourished patients (range, 12.1% to 24.7%), with higher carbohydrate or lipid oxidation rates. Additionally, the two malnourished patients exhibited higher blood concentrations of lactic acid than the nourished patients. CONCLUSIONS: According to data obtained from our small sample of patients with GSD1, elevated REEs seem to be a common characteristic that might contribute to malnutrition. Low basal protein oxidation rates and elevated blood lactic acid concentrations appear to be associated with malnutrition.

Hypothyroidism as a Predictor of Surgical Outcomes in the Elderly.

There is a high prevalence of hypothyroidism in the elderly population, mainly among women. The most important cause is autoimmune thyroiditis, but also iodine deficiency, radioiodine ablation, and surgery may be responsible for hypothyroidism in elderly hospitalized patients. Thyroid-related symptoms are sometimes comparable to physiological manifestations of the aging process, and hypothyroidism may be related with many symptoms which can be present in critical patients, such as cognitive impairment, cardiovascular, gastrointestinal, and hematological alterations, and eventually myxedema coma which is a severe and life-threatening condition in older adults. Adequate thyroid hormone levels are required to achieve optimal outcomes from any kind of surgical intervention. However, only few randomized clinical trials investigated the association between non-thyroidal illness (or low-T3 syndrome), and adverse surgical outcomes, so far. The goal of this review is to discuss the role of thyroid function as a predictor of surgical outcomes in the elderly.

Association of obesity and diabetes with thyroid nodules.

AIM: There are conflicting data concerning the possibility that obesity and diabetes raise the risk of thyroid nodules. The incidence of thyroid nodules is increasing, as is that of obesity and diabetes; therefore, understanding whether these metabolic and nutritional disorders influence nodular thyroid disease is important for organizing prevention strategies. This study investigated the association between thyroid nodules, obesity, diabetes, and dietary habits. MATERIALS AND METHODS: A cohort of randomly selected adults (455 males, 746 females; age: 18-90 years) living in Palermo (Italy), a mild iodine deficiency area, was cross-sectionally investigated. Participants underwent high-resolution ultrasonographic evaluation of the thyroid, and answered a food frequency questionnaire. Laboratory blood measurements were obtained in 587 participants. RESULTS AND DISCUSSION: Thyroid nodules were detected in 475 (39.5%) participants. The number of thyroid nodules was correlated with age (r = 0.19; P < 0.001), gender (r = 0.08; P = 0.005), and body mass index (r = 0.07; P = 0.02). No significant correlation was observed between the number of nodules and glycated hemoglobin, serum insulin concentrations, and homeostasis model assessment of insulin resistance. Age-adjusted and gender-adjusted prevalence of both overweight/obesity and type 2 diabetes of each group of participants divided according to the number of nodules significantly increased with the number of nodules (P < 0.05 in both cases). The group of participants with nodules exhibited a significantly lower age-adjusted and gender-adjusted habitual intake of milk (P = 0.02). Multivariate regression analysis showed that age, gender, body mass index, diabetes, and habitual consumption of milk were independently correlated with presence of thyroid nodules. CONCLUSION: This study seems to indicate that an association exists between obesity, diabetes, and thyroid nodules.