-
1.
Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.
Rastrelli, G, Cipriani, S, Lotti, F, Cellai, I, Comeglio, P, Filippi, S, Boddi, V, Della Camera, PA, Santi, R, Boni, L, et al
Journal of endocrinological investigation. 2022;45(7):1413-1425
-
-
-
Free full text
-
Plain language summary
Benign prostatic hyperplasia (BPH) — also called benign prostate enlargement — is frequent in aging populations, with a 40 – 50% prevalence in men aged 50–60 years and up to 90% in men older than 80 years. The aim of this study was to verify whether testosterone therapy (TTh) in men with BPH, metabolic syndrome (MetS) and low testosterone is able to improve lower urinary tract symptoms (LUTS) and intraprostatic inflammation. This study is a double blind, randomised 24-week clinical trial in men with low testosterone and MetS and a candidate for prostate surgery for BPH. Patients (n=144) were centrally randomised 1:1 to one of the two groups; TTh or placebo. Results show that TTh administered for 24 weeks is a safe option and it improves prostatic inflammatory features thus ameliorating one of the pathogenic components of BPH. However, there were no differences in improvements of the urinary symptoms between both groups (TTh and placebo). Authors conclude that decreased inflammation is not accompanied by a consistent improvement in urinary symptoms, and that their findings show the safety of TTh in subjects with BPH of surgical significance.
Abstract
PURPOSE Benign Prostatic Hyperplasia (BPH) is a result of prostate inflammation, frequently occurring in metabolic syndrome (MetS). Low testosterone is common in MetS. A randomized clinical trial was designed to evaluate if 24 weeks of testosterone therapy (TTh) in BPH men with MetS and low testosterone improve urinary symptoms and prostate inflammation. METHODS One-hundred-twenty men with MetS waitlisted for BPH surgery were enrolled. They were categorized into normal testosterone (TT ≥ 12 nmol/L and cFT ≥ 225 pmol/L; n = 48) and testosterone deficient (TD) (TT < 12 nmol/L and/or cFT < 225 pmol/L; n = 72) then randomized to testosterone gel 2% (5 g/daily) or placebo for 24 weeks. At baseline and follow-up, questionnaires for urinary symptoms and trans-rectal ultrasound were performed. Prostate tissue was collected for molecular and histopathological analyses. RESULTS No differences in the improvement of urinary symptoms were found between TTh and placebo (OR [95% CI] 0.96 [0.39; 2.37]). In TD + TTh, increase in prostate but not adenoma volume was observed (2.64 mL [0.07; 5.20] and 1.82 mL [- 0.46; 0.41], respectively). Ultrasound markers of inflammation were improved. In a subset of 61 men, a hyper-expression of several pro-inflammatory genes was found in TD + placebo when compared with normal testosterone. TTh was able to counteract this effect. For 80 men, the inflammatory infiltrate was higher in TD + placebo than in normal testosterone (0.8 points [0.2; 1.4]) and TD + TTh men (0.9 points [0.2; 1.5]). CONCLUSIONS Twenty-four weeks of TTh in TD men with BPH and MetS improves ultrasound, molecular and histological proxies of prostate inflammation. This does not result in symptom improvement.
-
2.
Lifestyle factors and visceral adipose tissue: Results from the PREDIMED-PLUS study.
Galmes-Panades, AM, Konieczna, J, Abete, I, Colom, A, Rosique-Esteban, N, Zulet, MA, Vázquez, Z, Estruch, R, Vidal, J, Toledo, E, et al
PloS one. 2019;14(1):e0210726
-
-
-
Free full text
Plain language summary
Excess visceral adipose tissue (VAT, abdominal fat) is a risk factor for developing cardiovascular disease, type 2 diabetes mellitus and all cause mortality. Lifestyle factors, including diet and physical activity, are associated with VAT. This cross-sectional study evaluated the association between different levels of physical activity (PA), adherence to an energy-restricted Mediterranean diet and sedentary lifestyle with VAT in older people with overweight/obesity and metabolic syndrome. Data were taken from an ongoing randomised study evaluating the effect of a weight loss programme based on an energy-restricted Mediterranean diet, promotion of physical activity and behavioural support compared to usual care consisting of advice on an energy-unrestricted Mediterranean diet only. Total and moderate-to-vigorous physical activity and muscle strength were inversely, and sedentary behaviour was positively associated with VAT. There was no statistically significant association between VAT and light exercise, adherence to the energy-reduced Mediterranean diet and watching TV.
Abstract
BACKGROUND Visceral adipose tissue (VAT) is a strong predictor of cardiometabolic health, and lifestyle factors may have a positive influence on VAT depot. This study aimed to assess the cross-sectional associations between baseline levels of physical activity (PA), sedentary behaviours (SB) and adherence to the Mediterranean diet (MedDiet) with VAT depot in older individuals with overweight/obesity and metabolic syndrome. METHODS Baseline data of the PREDIMED-Plus study including a sample of 1,231 Caucasian men and women aged 55-75 years were used. Levels of leisure-time PA (total, light, and moderate-to-vigorous, in METs·min/day) and SB (total and TV-viewing, in h/day) were evaluated using validated questionnaires. Adherence to the MedDiet was evaluated using a 17-item energy-restricted MedDiet (erMedDiet) screener. The chair-stand test was used to estimate the muscle strength. VAT depot was assessed with DXA-CoreScan. Multivariable adjusted linear regression models were used to evaluate the association between lifestyle factors and VAT. For the statistics we had used multiadjusted linear regression models. RESULTS Total leisure-time PA (100 METs·min/day: β -24.3g, -36.7;-11.9g), moderate-to-vigorous PA (β -27.8g, 95% CI -40.8;-14.8g), chair-stand test (repeat: β -11.5g, 95% CI -20.1;-2.93g) were inversely associated, and total SB (h/day: β 38.2g, 95% CI 14.7;61.7) positively associated with VAT. Light PA, TV-viewing time and adherence to an erMedDiet were not significantly associated with VAT. CONCLUSIONS In older adults with overweigh/obesity and metabolic syndrome, greater PA, muscle strength, and lower total SB were associated with less VAT depot. In this study, adherence to an erMedDiet was not associated with lower VAT.
-
3.
A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
-
-
-
Free full text
-
Plain language summary
Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
-
4.
Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial.
Cefalo, CMA, Conte, C, Sorice, GP, Moffa, S, Sun, VA, Cinti, F, Salomone, E, Muscogiuri, G, Brocchi, AAG, Pontecorvi, A, et al
Obesity (Silver Spring, Md.). 2018;26(4):651-657
-
-
-
Free full text
-
Plain language summary
Vitamin D concentration has been inversely associated with impaired glucose regulation, insulin resistance and risk of metabolic dysfunction. The aim of the study was to evaluate whether Vitamin D supplementation could improve insulin sensitivity in patients with a high risk of diabetes. The study is a randomised, double-blind, placebo-controlled trial. The participants with obesity were supplemented with Vitamin D or placebo on top of a hypocaloric diet. Results indicate that Vitamin D supplementation combined with weight loss is linked with a significant improvement in insulin sensitivity in vitamin D deficient participants with obesity.
Abstract
OBJECTIVE The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes. METHODS Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention. RESULTS Body weight in both groups decreased significantly (-7.5% in the vitamin D group and -10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg-1 ·min-1 ; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg-1 ·min-1 ; P = 0.84). CONCLUSIONS Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity.
-
5.
Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW).
Christensen, P, Meinert Larsen, T, Westerterp-Plantenga, M, Macdonald, I, Martinez, JA, Handjiev, S, Poppitt, S, Hansen, S, Ritz, C, Astrup, A, et al
Diabetes, obesity & metabolism. 2018;20(12):2840-2851
-
-
-
Free full text
-
Plain language summary
Overweight and obesity are major risk factors for developing type 2 diabetes mellitus. Men and women respond differently to weight loss programmes, with men typically losing more weight and more abdominal fat, whilst women lose more subcutaneous fat. The aim of this large multinational study was to compare the effects of weight loss induced by an 8‐week low energy diet on metabolic outcomes in overweight men and women with prediabetes. Study participants followed the Cambridge Weight Plan which is based on four formula meals, with a total of approximately 810kcal, per day, for eight weeks. Small amounts of non-starchy vegetables were allowed, as were psyllium husks in case of digestive problems. Men lost significantly more weight than women, 11.8% versus 10.3%. Insulin resistance improved similarly in men and women, but metabolic syndrome score improved more in men than in women. Men lost more fat than women and generally had more beneficial metabolic changes. Women had higher reductions in fat-free mass, bone mineral content and HDL cholesterol than men, raising the question whether rapid weight loss may have negative longer term effects for women.
Abstract
AIMS: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. MATERIALS AND METHODS All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. RESULTS In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. CONCLUSIONS An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.
-
6.
Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial.
Bae, JC, Lee, WY, Yoon, KH, Park, JY, Son, HS, Han, KA, Lee, KW, Woo, JT, Ju, YC, Lee, WJ, et al
Diabetes care. 2015;38(7):1245-52
-
-
-
Plain language summary
Non-alcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of metabolic syndrome, and it is associated with insulin resistance independent of obesity and other metabolic components. Carnitine is a modulator of mitochondrial free fatty acid transport and oxidation, and several studies have demonstrated the antioxidant activity of carnitine in hepatocytes. The aim of this study was to evaluate the effects of carnitine-orotate complex in patients with NAFLD and diabetes. This study is a multicentre, randomised, double-blind, placebo-controlled trial. Patients were randomly assigned to receive carnitine-orotate complex or placebo during the 12-week treatment period. Results show that treatment with carnitine-orotate complex improves hepatic steatosis in patients with diabetes and NAFLD, and has a beneficial effect on glucose metabolism, particularly in relation to improvement of hepatic steatosis. Authors conclude that further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.
Abstract
OBJECTIVE We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODS Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTS After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (-0.33 ± 0.82% [-3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONS Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.
-
7.
Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study.
Runchey, SS, Pollak, MN, Valsta, LM, Coronado, GD, Schwarz, Y, Breymeyer, KL, Wang, C, Wang, CY, Lampe, JW, Neuhouser, ML
European journal of clinical nutrition. 2012;66(10):1146-52
-
-
-
Free full text
-
Plain language summary
Dietary intervention studies have shown detrimental metabolic effects of high-glycaemic load diets. The glycaemic index (GI) is the numerical classification of a particular food’s blood glucose-raising effect. The aim of this study was to evaluate the effect of a high-glycaemic load diet on circulating levels of insulin-like growth factor-1 (IGF-1) [hormone] and insulin-like growth factor-binding protein 3 (IGFBP-3) [protein] compared to a low-glycaemic load diet. The study is a randomised controlled crossover study which enrolled 84 normal weight and overweight-obese healthy individuals. The study included two 28-day weight-maintaining high- and low-glycaemic load diets. Results indicate that consumption of a low-glycaemic load diet resulted in lower post-prandial [after a meal] insulin and glucose responses and modestly lower fasting IGF-1 and IGF-1/IGFBP-3 concentrations. However, there were no observable effects of glycaemic load on insulin resistance or glucose-adjusted post-prandial insulin responses in these healthy participants. Authors conclude that further intervention studies are required in order to weigh the impact of dietary glycaemic load on risk for chronic disease.
Abstract
BACKGROUND/OBJECTIVES The effect of a low glycemic load (GL) diet on insulin-like growth factor-1 (IGF-1) concentration is still unknown but may contribute to lower chronic disease risk. We aimed to assess the impact of GL on concentrations of IGF-1 and IGF-binding protein-3 (IGFBP-3). SUBJECTS/METHODS We conducted a randomized, controlled crossover feeding trial in 84 overweight obese and normal weight healthy individuals using two 28-day weight-maintaining high- and low-GL diets. Measures were fasting and post-prandial concentrations of insulin, glucose, IGF-1 and IGFBP-3. In all 80 participants completed the study and 20 participants completed post-prandial testing by consuming a test breakfast at the end of each feeding period. We used paired t-tests for diet component and linear mixed models for biomarker analyses. RESULTS The 28-day low-GL diet led to 4% lower fasting concentrations of IGF-1 (10.6 ng/ml, P=0.04) and a 4% lower ratio of IGF-1/IGFBP-3 (0.24, P=0.01) compared with the high-GL diet. The low-GL test breakfast led to 43% and 27% lower mean post-prandial glucose and insulin responses, respectively; mean incremental areas under the curve for glucose and insulin, respectively, were 64.3±21.8 (mmol/l/240 min; P<0.01) and 2253±539 (μU/ml/240 min; P<0.01) lower following the low- compared with the high-GL test meal. There was no effect of GL on mean homeostasis model assessment for insulin resistance or on mean integrated post-prandial concentrations of glucose-adjusted insulin, IGF-1 or IGFBP-3. We did not observe modification of the dietary effect by adiposity. CONCLUSIONS Low-GL diets resulted in 43% and 27% lower post-prandial responses of glucose and insulin, respectively, and modestly lower fasting IGF-1 concentrations. Further intervention studies are needed to weigh the impact of dietary GL on risk for chronic disease.