Time matters: an insight into the relationship between chrononutrition and diabetes.

Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention.

Associated factors to the consumption of non-nutritive sweeteners in the Mexican adult population.

OBJECTIVE: To identify the associated factors to the consumption of non-nutritive sweeteners (NNS) in the Mexican adult population since its consumption has increased exponentially worldwide. MATERIALS AND METHODS: An online survey was applied to 5 038 Mexican adults to evaluate the frequency of NNS consumption and classify the population in tertiles. The sociodemographic, lifestyle and health status characteristics of the participants were compared by gradient of NNS consumption, and a multiple linear regression analysis was performed to determine the associated factors to the NNS consumption. RESULTS: The variables that showed a positive association (p≤0.01) with the consumption of NNS were economic income, BMI, smoking, physical activity, diet quality, the presence of chronic diseases (diabetes, hypertension, or dyslipidemias), and the consumption of fruit. The age and the consumption of confectionery and sugar-sweetened beverages were negatively associated (p<0.01) with the consumption of NNS. CONCLUSION: The results of this study help to characterize the target population that is a consumer of NNS since it is recommended not encourage the preference for sweet taste and to promote a decrease in the consumption of both caloric and NNS, preferring the natural flavor of food.

Validity and reliability of simple surrogate indexes to evaluate beta-cell function and insulin sensitivity.

BACKGROUND: Simple surrogate indexes (SSI) to assess beta-cell function, insulin sensitivity (IS) and insulin resistance (IR) are an easy and economic tool used in clinical practice to identify glucose metabolism disturbances. AIM: To evaluate the validity and reliability of SSI that estimate beta-cell function, IS and IR using as a reference the parameters obtained from the frequently sampled intravenous glucose tolerance test (FSIVGTT). MATERIAL AND METHODS: We included 62 subjects aged 20-45 years, with a normal body mass index and without diabetes or prediabetes. SSI were compared with the acute insulin response to glucose (AIRg), insulin sensitivity index (Si) and disposition index (DI) obtained from the FSIVGTT using the minimal model approach. Half of the participants (n = 31) were randomly selected for a second visit two weeks later to evaluate the reliability of all the variables. RESULTS: HOMA1-%B and HOMA2-%B had a significant correlation with AIRg (Spearman Rho (rs) = 0.33 and 0.37 respectively, p < 0.01). The SSI evaluating IS/IR that showed stronger correlation (rs > 0.50) with Si were fasting insulin, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI, and the McAuley index. The parameters that showed good reliability with an intraclass correlation coefficient (ICC) > 0.75 were AIRg, HOMA1-%S, HOMA2-%S, and QUICKI. CONCLUSIONS: Our results suggest that most of the SSI are useful and reliable.

Non-Nutritive Sweeteners: Evidence on their Association with Metabolic Diseases and Potential Effects on Glucose Metabolism and Appetite.

There is ongoing debate concerning non-nutritive sweeteners, their usage, and their effects on metabolism. The association between non-nutritive sweeteners consumption, development of metabolic diseases, and changes in appetite-regulating hormones is not clear. The aim of this article is to present an overview of non-nutritive sweeteners and to examine the scientific evidence of their effects on glucose metabolism and appetite-regulating hormones. Some observational studies suggest an association between non-nutritive sweeteners consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in these studies. Results of the available clinical trials are heterogeneous and not comparable because of major differences between them. Future controlled studies evaluating specific non-nutritive sweeteners, with an appropriate sample size, including a uniform study group, with sufficient exposure time, and considering adjustment for confounder variables, such as anthropometric characteristics, previous consumption of non-nutritive sweeteners, and coexistence of significant metabolic comorbidities, are needed.

[Prevalence of non-nutritive sweeteners consumption in a population of patients with diabetes in Mexico]. / Prevalencia del consumo de edulcorantes no nutritivos (ENN) en una población de pacientes con diabetes en México.

OBJECTIVE: To estimate the prevalence of non-nutritive sweeteners (NNS) consumption in a sample of patients with diabetes. MATERIAL AND METHODS: We applied two questionnaires, one of food frequency adapted to products containing NNS and the other of beliefs related to NNS. The prevalence of NNS consumption was determined and correlated with the body mass index, energy and sugar consumption, waist circumference, glycated hemoglobin, triglycerides, diabetes type, education and socioeconomic status. RESULTS: The prevalence of NNS consumption was 96%; the consumption was greater in men and in patients with type 1 diabetes. A negative correlation was found between the consumption and age and a positive correlation with glycated hemoglobin and education. CONCLUSIONS: The prevalence of NNS consumption is high due to the great availability of products in the market.

Beliefs concerning non-nutritive sweeteners consumption in consumers, non-consumers, and health professionals: a comparative cross-sectional study.

Introduction: Introduction: the consumption of non-nutritive sweeteners (NNS) has increased. Recent studies have reported possible metabolic effects of NNS, and this may influence the perception regarding their consumption in the general population and health professionals. Objective: to describe and compare the beliefs about NNS in consumers, non-consumers, and health professionals; and to explore the reasons and opinions of health professionals for recommending or not their consumption. Methods: surveys were applied to 100 consumers, 100 non-consumers and 100 health professionals (dietitians and physicians) to evaluate a positive, negative, or neutral attitude towards certain beliefs regarding NNS, including the information they have, safety, price, side effects and taste. In addition, the opinion of health professionals for recommending or not the consumption of NNS and the related reasons was evaluated. Results: statistically significant differences regarding the safety, side effects and taste of NNS were found between the three groups (p < 0.01). The most frequent opinion of health professionals (48 %) is that NNS should be limited, used as a transition and in certain patients. Consumers tend to have a more positive opinion about NNS except for the price, non-consumers have a more neutral position except for taste, and health professionals have a more negative perception of NNS in all aspects. Conclusions: the beliefs regarding NNS differed among the studied groups, which might influence their consumption or recommendation of its use.

Introducción: Introducción: el consumo de edulcorantes no nutritivos (ENN) se ha incrementado. Estudios recientes han reportado posibles efectos metabólicos de los ENN, por lo que la percepción de su consumo podría haber cambiado en población general y profesionales de la salud. Objetivo: describir y comparar las creencias sobre los ENN en consumidores, no consumidores y profesionales de la salud, así como conocer las principales opiniones de los profesionales de la salud para recomendar o no el consumo de ENN. Métodos: se aplicaron encuestas a 100 consumidores, 100 no consumidores y 100 profesionales de la salud (nutriólogos y médicos) para evaluar actitudes positivas, negativas o neutras en torno a ciertas creencias de los ENN, la información que creen tener, seguridad, precio, efectos secundarios y sabor. Además, se evaluó la opinión de los profesionales de la salud para recomendar o no su consumo y las razones asociadas. Resultados: se encontraron diferencias entre los tres grupos en torno a la seguridad, los efectos secundarios y el sabor de los ENN (p < 0.01). La postura más frecuente de los profesionales de la salud (48 %) es que los ENN deben limitarse, utilizarse transitoriamente y en ciertos pacientes. Se observó una postura más positiva con respecto a los ENN en los consumidores excepto por su precio, más neutral en los no consumidores excepto por su sabor y más negativa en los profesionales de la salud en todos los aspectos. Conclusiones: las creencias sobre los ENN difieren entre los grupos estudiados, lo cual puede influir en su consumo o en la recomendación de su uso.

Sucralose and Cardiometabolic Health: Current Understanding from Receptors to Clinical Investigations.

The excess consumption of added sugar is consistently found to be associated with weight gain, and a higher risk of type 2 diabetes mellitus, coronary heart disease, and stroke. In an effort to reduce the risk of cardiometabolic disease, sugar is frequently replaced by low- and null-calorie sweeteners (LCSs). Alarmingly, though, emerging evidence indicates that the consumption of LCSs is associated with an increase in cardiovascular mortality risk that is amplified in those who are overweight or obese. Sucralose, a null-caloric high-intensity sweetener, is the most commonly used LCS worldwide, which is regularly consumed by healthy individuals and patients with metabolic disease. To explore a potential causal role for sucralose in increased cardiovascular risk, this present review summarizes the preclinical and clinical data from current research detailing the effects of sucralose on systems controlling food intake, glucose homeostasis, and gut microbiota.

Sucralose Consumption over 2 Weeks in Healthy Subjects Does Not Modify Fasting Plasma Concentrations of Appetite-Regulating Hormones: A Randomized Clinical Trial.

BACKGROUND: The effect of nonnutritive sweeteners on appetite is controversial. Some studies have found changes in certain appetite control hormones with sucralose intake that may be through interaction with sweet taste receptors located in the intestine. OBJECTIVE: The aim of this study was to evaluate whether sucralose consumption could produce changes in fasting plasma concentrations of appetite-regulating hormones, including glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, and leptin, and secondarily in insulin resistance. DESIGN: A 2-week parallel randomized clinical trial with an additional visit conducted 1 week after dosing termination. PARTICIPANTS/SETTING: Sixty healthy, normal-weight individuals, without habitual consumption of nonnutritive sweeteners were recruited from July 2015 to March 2017 in Mexico City. INTERVENTION: Daily sucralose consumption at 15% of the acceptable daily intake by using commercial sachets added to food. The control group followed the same protocol without an intervention. MAIN OUTCOMES MEASURED: Fasting concentrations of appetite regulating hormones before and after the intervention. Fasting glucose and insulin concentrations were measured to assess insulin resistance as a secondary outcome. STATISTICAL ANALYSIS PERFORMED: Basal and final concentrations were compared using Wilcoxon matched-pairs test and Mann-Whitney U test for analysis between groups. Repeated measures analysis of variance was used to evaluate changes in the homeostasis model assessment of insulin resistance. RESULTS: Sucralose was not associated with changes in any of the hormones measured. One week postintervention, an incremental change (P=0.04) in the homeostasis model assessment of insulin resistance was found in the intervention group. CONCLUSIONS: Sucralose intake is not associated with changes in fasting concentrations of glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, or leptin. An increase in the homeostasis model assessment of insulin resistance observed only at 1 week postdosing is of unknown clinical significance, if any.

Time Matters: An Insight into the Relationship Between Chrononutrition and Diabetes

ABSTRACT Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention. (Rev Invest Clin. 2024;76(2):80-90)

Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial.

Background: Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. Objective: The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. Design: We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). Methods: The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Results: Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of -17.7% (-29.3% to -1.0%) in comparison to -2.8% (-30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350-1040 mU · L-1· min) to 671 mU · L-1· min (376-1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. Conclusions: Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes.

OBJECTIVE: We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic-hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D). DESIGN AND METHODS: The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G0)+TG0)*BMI)/(Ln(HDL-c)) (G0: fasting glucose, TG0: fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects. RESULTS: METS-IR demonstrated the better correlation with the MFFM (ρ = -0.622, P < 0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78-0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53-0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels (P < 0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile (>50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25-6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P < 0.001). CONCLUSION: METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.

Validity and reliability of simple surrogate indexes to evaluate beta-cell function and insulin sensitivity

BACKGROUND: Simple surrogate indexes (SSI) to assess beta-cell function, insulin sensitivity (IS) and insulin resistance (IR) are an easy and economic tool used in clinical practice to identify glucose metabolism disturbances. AIM: To evaluate the validity and reliability of SSI that estimate beta-cell function, IS and IR using as a reference the parameters obtained from the frequently sampled intravenous glucose tolerance test (FSIVGTT). MATERIAL AND METHODS: We included 62 subjects aged 20-45 years, with a normal body mass index and without diabetes or prediabetes. SSI were compared with the acute insulin response to glucose (AIRg), insulin sensitivity index (Si) and disposition index (DI) obtained from the FSIVGTT using the minimal model approach. Half of the participants (n = 31) were randomly selected for a second visit two weeks later to evaluate the reliability of all the variables. RESULTS: HOMA1-%B and HOMA2-%B had a significant correlation with AIRg (Spearman Rho (rs) = 0.33 and 0.37 respectively, p 0.50) with Si were fasting insulin, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI, and the McAuley index. The parameters that showed good reliability with an intraclass correlation coefficient (ICC) > 0.75 were AIRg, HOMA1-%S, HOMA2-%S, and QUICKI. Conclusions: Our results suggest that most of the SSI are useful and reliable.

ANTECEDENTES: Los índices simples subrogados (ISS) que evalúan la función de célula beta, sensibilidad a la insulina (SI) y resistencia a la insulina (RI) son herramientas sencillas y económicas que se usan en la práctica clínica para identificar alteraciones del metabolismo de la glucosa. OBJETIVO: Evaluar la validez y confiabilidad de ISS para estimar la función de célula beta, SI y RI usando como referencia los parámetros de la prueba de tolerancia a la glucosa intravenosa con muestreo frecuente (FSIVGTT). MATERIAL Y MÉTODOS: Se incluyeron 62 sujetos de 20-45 años, con índice de masa corporal normal y sin diabetes mellitus o prediabetes. Los ISS se compararon con la respuesta aguda de la insulina a la glucosa (AIRg), índice de sensibilidad a la insulina (Si) e índice de disposición (DI) obtenidos de la FSIVGTT en base al modelo mínimo. La mitad de los participantes (n = 31) se seleccionaron aleatoriamente para acudir dos semanas después y evaluar la confiabilidad de todas las variables. RESULTADOS: HOMA1-%B y HOMA2-%B presentaron una correlación significativa con AIRg (Rho de Spearman (rs) = 0,33 and 0,37, respectivamente, p 0,50) con Si fueron insulina en ayuno, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI y el índice de McAuley. Los parámetros que tuvieron buena confiabilidad (coeficiente de correlación intraclase > 0,75) fueron AIRg, HOMA1-%S, HOMA2-%S y QUICKI. Conclusiones: La mayoría de los ISS son instrumentos útiles y confiables.

Effects of the Non-Nutritive Sweeteners on Glucose Metabolism and Appetite Regulating Hormones: Systematic Review of Observational Prospective Studies and Clinical Trials.

BACKGROUND: The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in metabolism. OBJECTIVES: The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones. RESULTS: Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified. CONCLUSIONS: Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed.