Prospective associations between a priori dietary patterns adherence and kidney function in an elderly Mediterranean population at high cardiovascular risk.

PURPOSE: To assess the association between three different a priori dietary patterns adherence (17-item energy reduced-Mediterranean Diet (MedDiet), Trichopoulou-MedDiet and Dietary Approach to Stop Hypertension (DASH)), as well as the Protein Diet Score and kidney function decline after one year of follow-up in elderly individuals with overweight/obesity and metabolic syndrome (MetS). METHODS: We prospectively analyzed 5675 participants (55-75 years) from the PREDIMED-Plus study. At baseline and at one year, we evaluated the creatinine-based estimated glomerular filtration rate (eGFR) and food-frequency questionnaires-derived dietary scores. Associations between four categories (decrease/maintenance and tertiles of increase) of each dietary pattern and changes in eGFR (ml/min/1.73m2) or ≥ 10% eGFR decline were assessed by fitting multivariable linear or logistic regression models, as appropriate. RESULTS: Participants in the highest tertile of increase in 17-item erMedDiet Score showed higher upward changes in eGFR (ß: 1.87 ml/min/1.73m2; 95% CI: 1.00-2.73) and had lower odds of ≥ 10% eGFR decline (OR: 0.62; 95% CI: 0.47-0.82) compared to individuals in the decrease/maintenance category, while Trichopoulou-MedDiet and DASH Scores were not associated with any renal outcomes. Those in the highest tertile of increase in Protein Diet Score had greater downward changes in eGFR (ß: - 0.87 ml/min/1.73m2; 95% CI: - 1.73 to - 0.01) and 32% higher odds of eGFR decline (OR: 1.32; 95% CI: 1.00-1.75). CONCLUSIONS: Among elderly individuals with overweight/obesity and MetS, only higher upward change in the 17-item erMedDiet score adherence was associated with better kidney function after one year. However, increasing Protein Diet Score appeared to have an adverse impact on kidney health. TRIAL REGISTRATION NUMBER: ISRCTN89898870 (Data of registration: 2014).

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study).

BACKGROUND: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. METHODS: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5µm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). RESULTS: In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 µg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. CONCLUSIONS: Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial.

INTRODUCTION: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. METHODS: Randomized controlled "PREvención con DIeta MEDiterránea-Plus" (PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (eGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired eGFR (<60 mL/min/1.73 m2) and micro- to macroalbuminuria (UACR ≥30 mg/g), and reversion of moderately (45 to <60 mL/min/1.73 m2) to mildly impaired GFR (60 to <90 mL/min/1.73 m2) or micro- to macroalbuminuria. RESULTS: After 1 year, eGFR declined by 0.66 and 1.25 mL/min/1.73 m2 in the intervention and control groups, respectively (mean difference, 0.58 mL/min/1.73 m2; 95% CI: 0.15-1.02). There were no between-group differences in mean UACR or micro- to macroalbuminuria changes. Moderately/severely impaired eGFR incidence and reversion of moderately to mildly impaired GFR were 40% lower (HR 0.60; 0.44-0.82) and 92% higher (HR 1.92; 1.35-2.73), respectively, in the intervention group. CONCLUSIONS: The PREDIMED-Plus lifestyle intervention approach may preserve renal function and delay CKD progression in overweight/obese adults.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Dietary folate intake and metabolic syndrome in participants of PREDIMED-Plus study: a cross-sectional study.

PURPOSE: We examined the association between dietary folate intake and a score of MetS (metabolic syndrome) and its components among older adults at higher cardiometabolic risk participating in the PREDIMED-Plus trial. METHODS: A cross-sectional analysis with 6633 with overweight/obesity participants with MetS was conducted. Folate intake (per 100 mcg/day and in quintiles) was estimated using a validated food frequency questionnaire. We calculated a MetS score using the standardized values as shown in the formula: [(body mass index + waist-to-height ratio)/2] + [(systolic blood pressure + diastolic blood pressure)/2] + plasma fasting glucose-HDL cholesterol + plasma triglycerides. The MetS score as continuous variable and its seven components were the outcome variables. Multiple robust linear regression using MM-type estimator was performed to evaluate the association adjusting for potential confounders. RESULTS: We observed that an increase in energy-adjusted folate intake was associated with a reduction of MetS score (ß for 100 mcg/day = - 0.12; 95% CI: - 0.19 to - 0.05), and plasma fasting glucose (ß = - 0.03; 95% CI: - 0.05 to - 0.02) independently of the adherence to Mediterranean diet and other potential confounders. We also found a positive association with HDL-cholesterol (ß = 0.07; 95% CI: 0.04-0.10). These associations were also observed when quintiles of energy-adjusted folate intake were used instead. CONCLUSION: This study suggests that a higher folate intake may be associated with a lower MetS score in older adults, a lower plasma fasting glucose, and a greater HDL cholesterol in high-risk cardio-metabolic subjects.

Cross-sectional association between non-soy legume consumption, serum uric acid and hyperuricemia: the PREDIMED-Plus study.

PURPOSE: To assess the association between the consumption of non-soy legumes and different subtypes of non-soy legumes and serum uric acid (SUA) or hyperuricemia in elderly individuals with overweight or obesity and metabolic syndrome. METHODS: A cross-sectional analysis was conducted in the framework of the PREDIMED-Plus study. We included 6329 participants with information on non-soy legume consumption and SUA levels. Non-soy legume consumption was estimated using a semi-quantitative food frequency questionnaire. Linear regression models and Cox regression models were used to assess the associations between tertiles of non-soy legume consumption, different subtypes of non-soy legume consumption and SUA levels or hyperuricemia prevalence, respectively. RESULTS: Individuals in the highest tertile (T3) of total non-soy legume, lentil and pea consumption, had 0.14 mg/dL, 0.19 mg/dL and 0.12 mg/dL lower SUA levels, respectively, compared to those in the lowest tertile (T1), which was considered the reference one. Chickpea and dry bean consumption showed no association. In multivariable models, participants located in the top tertile of total non-soy legumes [prevalence ratio (PR): 0.89; 95% CI 0.82-0.97; p trend = 0.01, lentils (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01), dry beans (PR: 0.91; 95% C: 0.84-0.99; p trend = 0.03) and peas (PR: 0.89; 95% CI 0.82-0.97; p trend = 0.01)] presented a lower prevalence of hyperuricemia (vs. the bottom tertile). Chickpea consumption was not associated with hyperuricemia prevalence. CONCLUSIONS: In this study of elderly subjects with metabolic syndrome, we observed that despite being a purine-rich food, non-soy legumes were inversely associated with SUA levels and hyperuricemia prevalence. TRIAL REGISTRATION: ISRCTN89898870. Registration date: 24 July 2014.

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

BACKGROUND: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. METHODS: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. RESULTS: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). CONCLUSIONS: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Adipose Tissue LPL Methylation is Associated with Triglyceride Concentrations in the Metabolic Syndrome.

BACKGROUND: DNA methylation is one of the epigenetic mechanisms that regulate gene expression. DNA methylation may be modified by environmental and nutritional factors. Thus, epigenetics could potentially provide a mechanism to explain the etiology of metabolic disorders, such as metabolic syndrome (MetS). The aim of this study was to analyze the level of DNA methylation of several lipoprotein lipase (LPL)-promoter-CpG dinucleotides in a CpG island region and relate this to the gene and protein expression levels in human visceral adipose tissue (VAT) from individuals with and without MetS. METHODS: VAT samples were collected from laparoscopic surgical patients without and with MetS, and levels of LPL mRNA, LPL protein, and LPL DNA methylation were measured by qPCR, western blot, and pyrosequencing. Biochemical and anthropometric variables were analyzed. Individuals included in a subset underwent a dietary fat challenge test, and levels of postprandial triglycerides were determined. RESULTS: We found higher levels of DNA methylation in MetS patients but lower gene expression and protein levels. There was a negative association between LPL methylation and LPL gene expression. We found a positive association between LPL methylation status and abnormalities of the metabolic profile and basal and postprandial triglycerides, whereas LPL gene expression was negatively associated with these abnormalities. CONCLUSIONS: We demonstrate that LPL methylation may be influenced by the degree of metabolic disturbances and could be involved in triglyceride metabolism, promoting hypertriglyceridemia and subsequent associated disorders, such as MetS.

IGFBP-3 Interacts with the Vitamin D Receptor in Insulin Signaling Associated with Obesity in Visceral Adipose Tissue.

Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD) metabolism, and it has been proposed that it can act as a VD storage tissue. The active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is able to modify adipocyte and adipose tissue physiology via the VD receptor (VDR), decreasing the expression of pro-inflammatory cytokines in adipose tissue. Moreover, VD deficiency and VDR has been reported to be associated with obesity and diabetes. However, the results of the different studies are not conclusive. Insulin growth binding proteins (IGFBPs) have been identified in adipose tissue, but their roles are poorly understood. Therefore, the objective of this study was to analyze the plasma levels of VD and the gene expression of VDR in the adipose tissue of subjects with morbid obesity (MO) and with different degrees of insulin resistance (IR), as well as the functionality of direct interaction between IGFBP-3 and VDR, which could explain its inhibitory role in adipogenesis. Our results show a novel role of the VD system in the regulation and activation of IGFBP-3 in visceral adipose tissue (VAT) of patients with MO, as a new and alternative mechanism proposed in the insulin signaling associated with obesity.

Au@16-pH-16/miR-21 mimic nanosystem: An efficient treatment for obesity through browning and thermogenesis induction.

Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 µg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity.

Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study.

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.

Lipidomic Analysis Reveals Alterations in Hepatic FA Profile Associated With MASLD Stage in Patients With Obesity.

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the intracellular lipid accumulation in hepatocytes. Excess caloric intake and high-fat diets are considered to significantly contribute to MASLD development. OBJECTIVE: To evaluate the hepatic and serum fatty acid (FA) composition in patients with different stages of MASLD, and their relationship with FA dietary intake and MASLD-related risk factors. METHODS: This was a case-control study in patients with obesity undergoing bariatric surgery at a university hospital between January 2020 and December 2021. Participants were distributed in 3 groups: no MASLD (n = 26), steatotic liver disease (n = 33), and metabolic dysfunction-associated steatohepatitis (n = 32). Hepatic and serum FA levels were determined by gas chromatography-mass spectrometry. Nutritional status was evaluated using validated food frequency questionnaires. The hepatic expression of genes involved in FA metabolism was analyzed by reverse transcription quantitative polymerase chain reaction. RESULTS: The hepatic, but not serum, FA profiles were significantly altered in patients with MASLD compared with those without MASLD. No differences were observed in FA intake between the groups. Levels of C16:0, C18:1, and the C18:1/C18:0 ratio were higher, while C18:0 levels and C18:0/C16:0 ratio were lower in patients with MASLD, being significantly different between the 3 groups. Hepatic FA levels and ratios correlated with histopathological diagnosis and other MASLD-related parameters. The expression of genes involved in the FA metabolism was upregulated in patients with MASLD. CONCLUSION: Alterations in hepatic FA levels in MASLD patients were due to enhancement of de novo lipogenesis in the liver.

Potential neuroprotective effects of fermented foods and beverages in old age: a systematic review.

Purpose: Numerous articles have recently studied the involvement of the gut microbiota in neurological diseases. Aging is associated with changes in the microbiome, which implies a reduction in microbial biodiversity among other changes. Considering that the consumption of a fermented-food diet improves intestinal permeability and barrier function, it seems of interest to study its participation in the prevention of neurodegenerative diseases. This article reviews existing studies to establish whether the consumption of fermented foods and fermented beverages prevents or ameliorates neurodegenerative decline in old age. Methods: The protocol used was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Details of the protocol for this systematic review are registered on PROSPERO (CRD42021250921). Results: Out of 465 articles identified in the Pubmed, Scopus, and Cochrane Library databases, a total of 29 that examined the relationship of the consumption of fermented products with cognitive impairment in old people were selected (22 cohort, 4 case-control, and 3 cross-sectional studies). The results suggest that low-to-moderate alcohol consumption and daily intake of coffee, soy products, and fermented-food diets in general are associated with a lower risk of dementia and Alzheimer's disease. Conclusion: Daily consumption of fermented foods and beverages, either alone or as part of a diet, has neuroprotective effects and slows cognitive decline in old people. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=250921, identifier: CRD42021250921.

Management of thyroid dysfunction and thyroid nodules in the ageing patient.

Thyroid dysfunction is a common endocrine disorder in the general population, with a reported prevalence of 10-15%. However, this rate is even higher in older adults, with an estimated prevalence of ≈25% in some populations. Since elderly patients usually present more comorbidities than younger individuals, thyroid dysfunction may carry a synergistic negative health impact, mainly due to increased cardiovascular disease risk. Moreover, thyroid dysfunction in the elderly can be more difficult to diagnose due to its subtle or even asymptomatic clinical presentation, and the interpretation of thyroid function tests may be affected by drugs that interfere with thyroid function or by the coexistence of several diseases. On the other hand, thyroid nodules are also a prevalent condition in older adults, and its incidence increases with age. The assessment and management of thyroid nodules in the ageing patient should take into account several factors, as risk stratification, thyroid cancer biology, patient´s overall health, comorbidities, treatment preferences, and goals of care. In this review article, we summarize the current knowledge on the pathophysiology, diagnosis, and therapeutic management of thyroid dysfunction in elderly patients and we also review how to identify and manage thyroid nodules in this population.

Hepatic and serum branched-chain fatty acid profile in patients with nonalcoholic fatty liver disease: A case-control study.

OBJECTIVE: Alterations in the hepatic lipidome are a crucial factor involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the serum and hepatic profile of branched-chain fatty acids (BCFAs) in patients with different stages of NAFLD. METHODS: This was a case-control study performed in 27 patients without NAFLD, 49 patients with nonalcoholic fatty liver, and 17 patients with nonalcoholic steatohepatitis, defined by liver biopsies. Serum and hepatic levels of BCFAs were analyzed by gas chromatography-mass spectrometry. The hepatic expression of genes involved in the endogenous synthesis of BCFAs was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A significant increase in hepatic BCFAs was found in subjects with NAFLD compared with those without NAFLD; no differences were observed in serum BCFAs between study groups. Trimethyl BCFAs, iso-BCFAs, and anteiso-BCFAs were increased in subjects with NAFLD (either nonalcoholic fatty liver or nonalcoholic steatohepatitis) compared with those without NAFLD. Correlation analysis showed a relationship between hepatic BCFAs and the histopathological diagnosis of NAFLD, as well as other histological and biochemical parameters related to this disease. Gene expression analysis in liver showed that the mRNA levels of BCAT1, BCAT2, and BCKDHA were upregulated in patients with NAFLD. CONCLUSIONS: These results suggest that the increased production of liver BCFAs might be related to NAFLD development and progression.

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study.

Objectives: Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined. Method: This is an observational, ambispective, multicenter, nationwide, real-world study designed to compare safety/efficacy of OW s.c. 1 mg semaglutide in T2D patients with or without CKD. The influence of CKD severity was also addressed. Patients were followed up for 12 months. Primary end-points were glycosylated hemoglobin (HbA1c), weight, and renal outcomes. Secondary end-points included insulin resistance, atherogenic and hepatic steatosis indexes, and changes in antihyperglycemic medications. Results: A total of 296 and 190 T2D patients without or with CKD, respectively, were recruited. Baseline CKD risk was moderate, high, or very high in 82, 53, and 45 patients, respectively. Treatment reduced HbA1c by 0.90%-1.20%. Relevant differences were seen neither between non-CKD and CKD patients nor among CKD subgroups. Notable weight losses were achieved in both non-CKD and CKD patients. The median reduction was higher in the former at 6 months (5.90 kg vs. 4.50 kg, P = 0.008) and at end of study (6.90 kg vs. 5.00 kg, P = 0.087). A trend toward slightly lower weight losses as CKD severity increased was observed. CKD markers improved across all CKD subgroups. Relevant differences were not observed for other variables, either between non-CKD and CKD patients, or among CKD subgroups. Safety concerns were not reported. Conclusion: The safety/efficacy of OW s.c. semaglutide to improve glycemic control and weight in T2D patients with CKD is not notably lower than that in T2D patients without renal failure. CKD severity barely influences treatment response. OW s.c. semaglutide can be useful to manage T2D patients with CKD in daily clinical practice.

Comprehensive approach to people with type 2 diabetes. Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition.

OBJECTIVE: To provide practical recommendations for the comprehensive approach of people with type 2 diabetes according to evidence-based medicine. PARTICIPANTS: Members of the Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition. METHODS: The recommendations were formulated according to the degrees of evidence of the Standards of Medical Care in Diabetes-2022. After reviewing the available evidence and formulating recommendations by the authors of each section, several rounds of comments were developed incorporating the contributions and voting on controversial points. Finally, the final document was sent to the rest of the members of the area for review and incorporation of contributions, to finally carry out the same process with the members of the Spanish Society of Endocrinology and Nutrition Board of Directors. CONCLUSIONS: The document establishes practical recommendations based on the latest available evidence for the management of people with type 2 diabetes.