Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials.

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: 'adiponectin', 'dietary lipid', 'randomized controlled trials (RCT)'). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) µg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) µg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) µg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Evaluation of Bedtime vs. Morning Levothyroxine Intake to Control Hypothyroidism in Older Patients: A Pragmatic Crossover Randomized Clinical Trial.

Introduction: Drug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating L-thyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients. Materials and Methods: A randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60 min before breakfast) or bedtime LT4 intake (60 min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen. Results: A total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107. Discussion: Thyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime).

Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE).

BACKGROUND: The aging population is associated with increased multimorbidity and polypharmacy. Older adults are at a higher risk of adverse events and reduced therapeutic response. This phenomenon is partially explained by drug interactions and treatment adherence. Most randomized clinical trials have found no significant differences between morning and evening levothyroxine (LT4) administration in young adults, but there is little evidence regarding alternative LT4 regimens in older populations. Thus, the MONIALE trial aims to test an alternative schedule for LT4 administration in older adults. METHODS/DESIGN: This randomized crossover clinical trial will include participants aged 60 years or older with primary hypothyroidism. The trial groups will consist of morning LT4 intake (60 min before breakfast) or evening LT4 intake (60 min after supper). The primary outcome will be variation in serum thyrotropin (TSH) levels after 24 weeks of the LT4 protocol. The secondary outcomes will be the prevalence of drugs that potentially interact with LT4 and hypothyroidism control according to interaction status. The sample size was calculated to detect a minimum mean difference of 1 mUI/L in serum TSH level between the groups with 80% power and a 5% probability of type I error, resulting in 91 patients per group. The project was approved by the Hospital de Clínicas de Porto Alegre Ethics Committee. DISCUSSION: Considering the aging population, the increased prevalence of multimorbidity and polypharmacy, as well as potential drug interactions and treatment adherence difficulties, an alternative LT4 protocol could be useful for hypothyroidism treatment in the elderly. Prior studies comparing alternative LT4 administration protocols have mainly included young adult populations and have not addressed potential drug interactions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03614988. Registered 30 July 2018.

Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type 2 diabetes mellitus: a systematic review.

The HSD11B1 gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of HSD11B1 have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of HSD11B1 gene expression in abdominal adipose tissue and HSD11B1 polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case-control), conducted in adults, which analyzed the relationship of HSD11B1 polymorphisms and/or HSD11B1 expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral HSD11B1 expression with central and/or generalized obesity. Most studies reported that abdominal adipose HSD11B1 expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different HSD11B1 polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the HSD11B1 gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that HSD11B1 is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for HSD11B1 gene expression and MetS. Although an association of polymorphic variants of HSD11B1 with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of HSD11B1 and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.

Hypertension is the main determinant behind the association between metabolic syndrome and chronic kidney disease in subjects with different degrees of glucose tolerance / A hipertensão é o principal determinante da associação entre síndrome metabólica e doença renal crônica em indivíduos com diferentes graus de tolerância à glicose

Background: Chronic kidney disease (CKD) is a significant public health problem. It is still controversial if the metabolicsyndrome (MS) is associated with CKD.Methods: Cross-sectional study of individuals at high risk of developing diabetes at the endocrine outpatient clinic of Hospitalde Clínicas de Porto Alegre. Fasting and 2h-plasma glucose levels, A1c, insulin, cholesterol, triglycerides, creatinine, andurinary albumin excretion were measured. MS was defined as the presence of three out of five of the following factors: hypertension,low HDL-cholesterol, high triglyceride levels, elevated plasma glucose, and high waist circumference. Glomerularfiltration rate (GFR) was estimated by the Modified Diet in Renal Disease (MDRD) equation and insulin resistance wasmeasure using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Correlation analyses were performedbetween each MS components and the GFR.Results: CKD was present in 20.9% of the subjects. GFR was lower in subjects with MS compared with those without MS(P =0.019). Estimated GFR decreased with the increasing number of MS criteria (mean ± SD; zero or one criterion103.09±9.5 vs. two criteria 99.14±21.2 vs. three criteria 90.9±21.1 vs. four criteria 91.0±19.4 vs. five criteria 80.9±23.5mL/min per 1.73m2; P =0.053). Only systolic arterial blood pressure was related to eGFR (r = 0.280; P =0.003).Discussion: According to our data, the previously described association between MS and decreased renal function wasconfirmed, mostly determined by the hypertension criterion.Conclusion: These data suggest that the relationship between MS and CKD is driven mostly by abnormalities in blood pressurehomeostasis.

Introdução: A Doença Renal Crônica (DRC) é um problema de saúde pública. Ainda é controversa a existência de associa-ção entre a presença de Síndrome Metabólica (SM) e DRC.Métodos: Indivíduos com risco aumentado para o desenvolvimento de diabete melito acompanhados no ambulatório deEndocrinologia do Hospital de Clínicas de Porto Alegre foram analisados em um estudo transversal. Pacientes foram submetidosao Teste de Tolerância Oral à Glicose, e hemoglobina glicada (A1c), insulina, colesterol, triglicerídeos, creatinina eexcreção urinária de albumina foram medidos. A presença de SM era baseada na presença de três entre os cinco critérios aseguir: hipertensão, níveis séricos de colesterol HDL diminuídos, níveis aumentados de triglicerídeos, hiperglicemia e circunferênciaabdominal aumentada. A taxa de filtração glomerular (TFG) foi calculada pela equação do Modified Diet in RenalDisease (MDRD) e a resistência insulínica, pelo Homeostasis Model of Assessment – Insulin Resistance (HOMA-IR).Análises de correlação foram feitas entre cada componente da SM e a TFG.Resultados: DRC esteve presente em 20,9% dos indivíduos. Níveis diminuídos de TFG foram observados em pacientescom SM comparados com aqueles sem SM (P=0,019). TFG diminuiu com o aumento no número de critérios para SM (mé-dia±DP; 0 e 1 critério 103,09±9,5; vs. 2 critérios 99,14±21,2; vs. 3 critérios 90,9±21,1; vs. 4 critérios 91,0±19,4; vs. 5 crité-rios 80,9±23,3 ml/min; P=0,053). Apenas pressão arterial sistólica mostrou-se relacionada com a TFG (r=0,280; P=0,003).Discussão: Nosso trabalho confirmou a associação entre a presença de Síndrome Metabólica e TFG diminuída descritapreviamente por outros estudos, tendo, neste presente estudo, a hipertensão como o principal determinante desta relação.Conclusão: Nossos achados sugerem que a relação existente entre a presença de SM e o desenvolvimento de DRC é determinadaprincipalmente por anormalidades na homeostase pressórica.