Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

The Vicious Cycle of Type 2 Diabetes Mellitus and Skeletal Muscle Atrophy: Clinical, Biochemical, and Nutritional Bases.

Today, type 2 diabetes mellitus (T2DM) and skeletal muscle atrophy (SMA) have become increasingly common occurrences. Whether the onset of T2DM increases the risk of SMA or vice versa has long been under investigation. Both conditions are associated with negative changes in skeletal muscle health, which can, in turn, lead to impaired physical function, a lowered quality of life, and an increased risk of mortality. Poor nutrition can exacerbate both T2DM and SMA. T2DM and SMA are linked by a vicious cycle of events that reinforce and worsen each other. Muscle insulin resistance appears to be the pathophysiological link between T2DM and SMA. To explore this association, our review (i) compiles evidence on the clinical association between T2DM and SMA, (ii) reviews mechanisms underlying biochemical changes in the muscles of people with or at risk of T2DM and SMA, and (iii) examines how nutritional therapy and increased physical activity as muscle-targeted treatments benefit this population. Based on the evidence, we conclude that effective treatment of patients with T2DM-SMA depends on the restoration and maintenance of muscle mass. We thus propose that regular intake of key functional nutrients, along with guidance for physical activity, can help maintain euglycemia and improve muscle status in all patients with T2DM and SMA.

Arginine and Lysine Supplementation Potentiates the Beneficial ß-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes.

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, ß-hydroxy ß-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes.

Bringing the Pediatric Endocrine Spanish Speaking Community Together: First Virtual Pediatric Endocrine Meeting in Low- and Middle-Income Countries in Central and South America.

BACKGROUND: Pediatric endocrinology is a specialty that is struggling worldwide to maintain adequately trained professionals. Pediatric endocrine care in Central America and Caribbean countries is often performed by pediatricians or adult endocrinologists due to the limited number of pediatric endocrinologists. These health care providers are seldom members of endocrine societies and frequently lack formal training in the field. OBJECTIVE: In this study, we describe the scope of a virtual conference in pediatric endocrinology and diabetes targeted to low- and middle-income countries to provide equal opportunities for access to medical education for health care professionals. METHODS: The virtual conference was sponsored by the Pediatric Endocrine Society (North America), Asociación Costarricense de Endocrinología (previously, Asociación Nacional Pro Estudio de la Diabetes, Endocrinología y Metabolismo), and Asociacion Centroamericana y del Caribe de Endocrinologia Pediátrica. The conference was free to participants and comprised 23 sessions that were either synchronous with ability for real-time interactive sessions or asynchronous sessions, where content was available online to access at their convenience. Topics included idiopathic short stature, polycystic ovarian syndrome, diabetes mellitus, telemedicine, Turner syndrome, congenital adrenal hyperplasia, obesity, central precocious puberty, and subclinical hypothyroidism. The participants were asked to evaluate the conference after its completion with a questionnaire. RESULTS: A total of 8 speakers from Spain, Canada, Costa Rica, and the United States delivered the virtual event to 668 health care professionals from Guatemala, Venezuela, Dominican Republic, Costa Rica, Ecuador, Peru, Uruguay, Mexico, Honduras, Argentina, the United States, Bolivia, Chile, Panama, El Salvador, Nicaragua, Paraguay, Belize, Spain, and Colombia. Name, profession, and country were fully disclosed by 410 (61.4%) of the 668 health care professionals. The profession or level of training of participants were as follows: pediatric endocrinologists (n=129, 19.3%), pediatricians (n=116, 17.4%), general practitioners (n=77, 11.5%), adult endocrinologists (n=34, 5.1%), medical students (n=23, 3.4%), residents in various specialties (n=14, 2.1%), and others (n=17, 2.6%). A total of 23 sessions were offered, most of which were bilingual (Spanish and English). Feedback from the evaluation questionnaire indicated that the content of the conference was very relevant to the participants' professional practice. Additionally, the participants reported that they were very satisfied with the organization, the web-based platform, and the sessions of the conference. CONCLUSIONS: Lack of accessibility to the latest and cutting-edge medical education in pediatric endocrinology and diabetes for medical professionals from low- and middle-income countries can be overcome with a virtual conference. Online availability, low cost, and easy-to-use technology were well received from the participants, who were overall very satisfied by the quality and the relevance of the sessions to their professional practice.

Intake of slow-digesting carbohydrates is related to changes in the microbiome and its functional pathways in growing rats with obesity induced by diet.

Introduction: The main cause of insulin resistance in childhood is obesity, which contributes to future comorbidities as in adults. Although high-calorie diets and lack of exercise contribute to metabolic disease development, food quality rather than the quantity of macronutrients is more important than food density. The purpose of the present study was to examine the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on the composition of the gut microbiota and the profiles of the functional pathways in growing rats with obesity due to a high-fat diet (HFD). Methods: During the course of 4 weeks, rats growing on an HFD-containing carbohydrates with different digestive rates were fed either HFD-containing carbohydrates with a rapid digestion rate (OBE group) or HFD-containing carbohydrates with a slow digestion rate (OBE-ISR group). A non-obese group (NOB) was included as a reference, and rats were fed on a rodent standard diet (AIN93G). An analysis of gut microbiota was conducted using 16S rRNA-based metagenomics; a linear mixed-effects model (LMM) was used to determine changes in abundance between baseline and 4 weeks of treatment, and functional pathways were identified. Gut microbiota composition at bacterial diversity and relative abundance, at phylum and genus levels, and functional profiles were analyzed by integrating the Integrated Microbial Genomes (IMG) database. Results: The groups showed comparable gut microbiota at baseline. At the end of the treatment, animals from the ISR group exhibited differences at the phylum levels by decreasing the diversity of Fisher's index and Firmicutes (newly named as Bacillota), and increasing the Pielou's evenness and Bacteroidetes (newly named as Bacteroidota); at the genus level by increasing Alistipes, Bifidobacterium, Bacteroides, Butyricimonas, Lachnoclostridium, Flavonifractor, Ruminiclostridium 5, and Faecalibaculum and decreasing Muribaculum, Blautia, and Ruminiclostridium 9. Remarkably, relative abundances of genera Tyzzerella and Angelakisella were higher in the OBE group compared to NOB and OBE-ISR groups. In addition, some microbiota carbohydrate metabolism pathways such as glycolysis, glucuronic acid degradation, pentose phosphate pathway, methanogenesis, and fatty acid biosynthesis exhibited increased activity in the OBE-ISR group after the treatment. Higher levels of acetate and propionate were found in the feces of the ISR group compared with the NOB and OBE groups. Conclusion: The results of this study demonstrate that replacing rapidly digestible carbohydrates with slowly digestible carbohydrates within an HFD improve the composition of the gut microbiota. Consequently, metabolic disturbances associated with obesity may be prevented.

Quality More Than Quantity: The Use of Carbohydrates in High-Fat Diets to Tackle Obesity in Growing Rats.

Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARγ were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a high-fat diet promoted a protective effect against the development of obesity and its associated comorbidities.

Beneficial Effects of Bovine Milk Exosomes in Metabolic Interorgan Cross-Talk.

Extracellular vesicles are membrane-enclosed secreted vesicles involved in cell-to-cell communication processes, identified in virtually all body fluids. Among extracellular vesicles, exosomes have gained increasing attention in recent years as they have unique biological origins and deliver different cargos, such as nucleic acids, proteins, and lipids, which might mediate various health processes. In particular, milk-derived exosomes are proposed as bioactive compounds of breast milk, which have been reported to resist gastric digestion and reach systemic circulation, thus being bioavailable after oral intake. In the present manuscript, we critically discuss the available evidence on the health benefits attributed to milk exosomes, and we provide an outlook for the potential future uses of these compounds. The use of milk exosomes as bioactive ingredients represents a novel avenue to explore in the context of human nutrition, and they might exert important beneficial effects at multiple levels, including but not limited to intestinal health, bone and muscle metabolism, immunity, modulation of the microbiota, growth, and development.

Dietary Complex and Slow Digestive Carbohydrates Promote Bone Mass and Improve Bone Microarchitecture during Catch-Up Growth in Rats.

Catch-up growth is a process that promotes weight and height gains to recover normal growth patterns after a transient period of growth inhibition. Accelerated infant growth is associated with reduced bone mass and quality characterized by poor bone mineral density (BMD), content (BMC), and impaired microarchitecture. The present study evaluated the effects of a diet containing slow (SDC) or rapid (RDC) digestible carbohydrates on bone quality parameters during the catch-up growth period in a model of diet-induced stunted rats. The food restriction period negatively impacted BMD, BMC, and microarchitecture of appendicular and axial bones. The SDC diet was shown to improve BMD and BMC of appendicular and axial bones after a four-week refeeding period in comparison with the RDC diet. In the same line, the micro-CT analysis revealed that the trabecular microarchitecture of tibiae and vertebrae was positively impacted by the dietary intervention with SDC compared to RDC. Furthermore, features of the cortical microstructure of vertebra bones were also improved in the SDC group animals. Similarly, animals allocated to the SDC diet displayed modest improvements in growth plate thickness, surface, and volume compared to the RDC group. Diets containing the described SDC blend might contribute to an adequate bone formation during catch-up growth thus increasing peak bone mass, which could be linked to reduced fracture risk later in life in individuals undergoing transient undernutrition during early life.

Differences in muscle energy metabolism and metabolic flexibility between sarcopenic and nonsarcopenic older adults.

BACKGROUND: Metabolic flexibility is the ability of skeletal muscle to adapt fuel utilization to the demand for fuel sources [carbohydrates (CHO) and fats (FAT)]. The purpose of this study was to explore muscle energy metabolism and metabolic flexibility under various conditions in sarcopenic (S) versus nonsarcopenic (NS) older adults. METHODS: Twenty-two older adults aged 65 years or older were categorized as NS [n = 11; mean ± standard deviation (SD); age = 73.5 ± 6.0 years (males, n = 5; females, n = 6)] or S [n = 11; 81.2 ± 10.5 years (males, n = 6; females, n = 5) based on handgrip strength, body composition and physical performance. Indirect calorimetry was recorded before and after consumption of a high-CHO meal and during aerobic and anaerobic exercise. Respiratory quotient (RQ), CHO and FAT oxidation were assessed. Venous blood samples were collected for glucose and insulin concentrations. RESULTS: At rest, compared with NS, S exhibited a 5-8% higher RQ at 0 (0.72 vs. 0.76) and 120 (0.77 vs. 0.82), 150 (0.76 vs. 0.80), and 180 min (0.74 vs. 0.80) (P = 0.002-0.025); 59-195% higher CHO oxidation at 0, 120, and 180 min (0.0004-0.002 vs. 0.001-0.002 g·min-1 ·kg-1) (P = 0.010-0.047); and 20-31% lower FAT oxidation at 0, 15, and 90-180 min (0.0009-0.0022 vs. 0.0011-0.002 g·min-1 ·kg-1 ) (P = 0.004-0.038). Glucose levels were significantly elevated in S versus NS at 0, 60 and 75 min (144.64-202.78 vs. 107.70-134.20 mg·dL-1 ) but not insulin. During aerobic exercise, RQ was 5% greater (0.90 vs. 0.86) (P = 0.039), and FAT oxidation was 35% lower at 6-8 min (0.003 vs. 0.005 g·min-1 ·kg-1 ) (P = 0.033) in S versus NS. During anaerobic exercise, CHO oxidation was 31% greater in NS versus S at 60-80% time to exhaustion (0.011 vs. 0.007 g·min-1 ·kg-1 ) (P = 0.015). Per cent contribution to energy expenditure was greater in S for CHO but lower for FAT at 0 (CHO: 22% vs. 10%; FAT: 78% vs. 91%) and 120-180 min (CHO: 35-42% vs. 17-25%; FAT: 58-65% vs. 75%-84%) (P = 0.003-0.046) at rest and 6-8 min during aerobic exercise (CHO: 70% vs. 57%; FAT: 30% vs. 45%) (P = 0.046). CONCLUSIONS: The data show differences in skeletal muscle energy metabolism and substrate utilization between S and NS at rest, transitioning from fasted to fed state, and during exercise. Compared with NS, S displayed a diminished ability to adapt fuel utilization in response to feeding and exercise, reflecting metabolic inflexibility. Impaired metabolic flexibility could be a mechanism underlying the losses of strength and physical function accompanying sarcopenia.

Impact of slow versus rapid digesting carbohydrates on substrate oxidation in pre-pubertal children: A randomized crossover trial.

BACKGROUND & AIMS: Consumption of rapid digesting sugars by children are under increased scrutiny because of their contribution to unhealthy weight gain. Previous studies in adults and children have suggested that altering the blend of carbohydrates (CHOs) consumed may cause shifts in substrate utilization. The purpose of this study was to examine the effects of consuming a slow digesting carbohydrate (SDC) and rapid digesting carbohydrate (RDC) on CHO and fat oxidation, glucose, and insulin responses at rest, during exercise, and post-exercise rest in pre-pubescent children. METHODS: A randomized, double-blind, crossover design was used. Nineteen pre-pubescent children (n = 10 boys, n = 9 girls, mean ± standard error, age = 9.84 ± 0.37-yrs) participated. Visits to the laboratory began with a 30-min measurement of resting metabolism followed by consumption of either an RDC or SDC drink. Postprandial resting metabolism was recorded for 60-min, immediately followed by 60-min of submaximal cycling exercise while metabolism was recorded, which was immediately followed by another 60-min recording of post-exercise metabolism. Total CHO and fat oxidation, endogenous and exogenous CHO oxidation, blood glucose, and insulin were assessed. RESULTS: Total CHO oxidation rate (g∙min-1) was greater after the RDC drink at 60 min (p = 0.032). Endogenous CHO oxidation rate (g∙min-1) was greater after the SDC drink at 15 min (p ≤ 0.010). Cumulative endogenous CHO oxidation (g) was greater after the SDC drink at 45 min (p = 0.009). Endogenous CHO oxidation accounted for a greater proportion of substrate oxidation after the first 60-min rest period (p = 0.028), while exogenous CHO oxidation accounted for a greater proportion of substrate oxidation for the RDC at all time points (p ≤ 0.019). CONCLUSIONS: The present study provides novel data suggesting that an SDC promotes greater endogenous substrate utilization in pre-pubertal children, which may have beneficial health impacts on energy intake and carbohydrate regulation/metabolism during growth and development. CLINICAL TRIALS REGISTRY NUMBER: NCT03185884, clinicaltrials.gov.

Dietary Complex and Slow Digestive Carbohydrates Prevent Fat Deposits During Catch-Up Growth in Rats.

A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early caloric restriction: an increase in adiposity combined with poorer muscle performance, insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in myocyte enhancer factor 2D (MEF2D) and creatine kinase as markers of muscle differentiation as well as better insulin sensitivity, enhanced glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted glycogen storage and decreased fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as obesity, insulin resistance, dyslipidemia, and liver fat deposits later in life.

The Role of Dietary Carbohydrates in Gestational Diabetes.

Gestational diabetes (GDM) is hyperglycemia that is recognized for the first time during pregnancy. GDM is associated with a wide range of short- and long-term adverse health consequences for both mother and offspring. It is a complex disease with a multifactorial etiology, with disturbances in glucose, lipid, inflammation and gut microbiota. Consequently, its management is complex, requiring patients to self-manage their diet, lifestyle and self-care behaviors in combination with use of insulin. In addition to nutritional recommendations for all pregnant women, special attention to dietary carbohydrate (CHO) amount and type on glucose levels is especially important in GDM. Dietary CHO are diverse, ranging from simple sugars to longer-chain oligo- and poly- saccharides which have diverse effects on blood glucose, microbial fermentation and bowel function. Studies have established that dietary CHO amount and type can impact maternal glucose and nutritional recommendations advise women with GDM to limit total intake or choose complex and low glycemic CHO. However, robust maternal and infant benefits are not consistently shown. Novel approaches which help women with GDM adhere to dietary recommendations such as diabetes-specific meal replacements (which provide a defined and complete nutritional composition with slowly-digested CHO) and continuous glucose monitors (which provide unlimited monitoring of maternal glycemic fluctuations) have shown benefits on both maternal and neonatal outcomes. Continued research is needed to understand and develop tools to facilitate patient adherence to treatment goals, individualize interventions and improve outcomes.

Programming Skeletal Muscle Metabolic Flexibility in Offspring of Male Rats in Response to Maternal Consumption of Slow Digesting Carbohydrates during Pregnancy.

Skeletal muscle plays a relevant role in metabolic flexibility and fuel usage and the associated muscle metabolic inflexibility due to high-fat diets contributing to obesity and type 2 diabetes. Previous research from our group indicates that a high-fat and rapid-digesting carbohydrate diet during pregnancy promotes an excessive adipogenesis and also increases the risk of non-alcoholic fatty liver disease in the offspring. This effect can be counteracted by diets containing carbohydrates with similar glycemic load but lower digestion rates. To address the role of the skeletal muscle in these experimental settings, pregnant rats were fed high-fat diets containing carbohydrates with similar glycemic load but different digestion rates, a high fat containing rapid-digesting carbohydrates diet (HF/RD diet) or a high fat containing slow-digesting carbohydrates diet (HF/SD diet). After weaning, male offspring were fed a standard diet for 3 weeks (weaning) or 10 weeks (adolescence) and the impact of the maternal HF/RD and HF/SD diets on the metabolism, signaling pathways and muscle transcriptome was analyzed. The HF/SD offspring displayed better muscle features compared with the HF/RD group, showing a higher muscle mass, myosin content and differentiation markers that translated into a greater grip strength. In the HF/SD group, metabolic changes such as a higher expression of fatty acids (FAT/CD36) and glucose (GLUT4) transporters, an enhanced glycogen content, as well as changes in regulatory enzymes such as muscle pyruvate kinase and pyruvate dehydrogenase kinase 4 were found, supporting an increased muscle metabolic flexibility and improved muscle performance. The analysis of signaling pathways was consistent with a better insulin sensitivity in the muscle of the HF/SD group. Furthermore, increased expression of genes involved in pathways leading to muscle differentiation, muscle mass regulation, extracellular matrix content and insulin sensitivity were detected in the HF/SD group when compared with HF/RD animals. In the HF/SD group, the upregulation of the ElaV1/HuR gene could be one of the main regulators in the positive effects of the diet in early programming on the offspring. The long-lasting programming effects of the HF/SD diet during pregnancy may depend on a coordinated gene regulation, modulation of signaling pathways and metabolic flexibility that lead to an improved muscle functionality. The dietary early programming associated to HF/SD diet has synergic and positive crosstalk effects in several tissues, mainly muscle, liver and adipose tissue, contributing to maintain the whole body homeostasis in the offspring.

A Slow-Digesting, Low-Glycemic Load Nutritional Beverage Improves Glucose Tolerance in Obese Pregnant Women Without Gestational Diabetes.

BACKGROUND: Obesity is a risk factor for gestational diabetes (gestational diabetes). Low-glycemic index diets attenuate hyperglycemia. We designed a study to determine whether a slow-digesting, low-glycemic load (SD-LGL) beverage improves glucose tolerance in obese pregnant women without GDM. METHODS: This was a 3-arm comparison study comparing the effects of an SD-LGL nutritional beverage (glycemic load [GL] 730), an isocaloric control beverage (GL 1124), and habitual diet on glycemia in obese pregnant women. Sixteen women (mean body mass index 37 kg/m2) were recruited at 24-28 weeks to receive either the SD-LGL or eucaloric control beverage. This was consumed with breakfast and as a midafternoon snack over 2 days with a controlled diet. Following a 2-day washout period of habitual diet, women completed 2 days on the alternative beverage with controlled diet. A 10-h fast preceded each intervention phase. Twenty-four hour glucose was measured using continuous glucose monitoring. RESULTS: Consumption of the lower GL beverage was associated with improved measures of glycemia, compared with the control beverage and habitual diet at different time periods. Glucose estimates for control versus SD-LDL at 24 h (0.23 mmol/L [0.16 to 0.31], P < 0.001), daytime (0.26 mmol/L [0.18 to 0.34], P < 0.001), and nighttime (0.05 mmol/L [-0.01 to 0.11], P = 0.09). Postprandial glucose was lower after breakfast but not after dinner, compared with the control beverage (0.09 mmol/L [0.01 to 0.18], P = 0.03). CONCLUSION: A slow-digesting, low-glycemic nutritional beverage may facilitate improved glucose control in obese pregnant women. To address potential benefit for clinical outcomes, a randomized controlled trial is warranted.

Feeding a slowly digestible carbohydrate diet during pregnancy of insulin-resistant rats prevents the excess of adipogenesis in their offspring.

An obesogenic environment during pregnancy has been shown to increase the risk of dysregulation on adipogenesis and insulin resistance in the offspring. Being essential for the growing fetus, glucose supply is guaranteed by a number of modifications in the mother's metabolism, and thus, glucose control during pregnancy especially among obese or diabetic women is paramount to prevent adverse consequences in their children. Besides the election of low-glycemic-index carbohydrates, the rate of carbohydrate digestion could be relevant to keep a good glucose control. In the present study, we compared the effects of two high-fat diets with similar glycemic load but different rates of carbohydrate digestion given to pregnant insulin-resistant rats. After birth, all animals were fed a standard diet until age 14 weeks. We analyzed offspring body composition, plasma and adipocyte lipidomics, lipid metabolism in adipose tissue and insulin sensitivity. Those animals whose mothers were fed the rapid-digesting carbohydrate diet exhibited an excessive adipogenesis. Thus, these animals showed a marked lipidemia, increased lipid synthesis in the adipose tissue and reduced glucose transporter amount in the adipose. On the contrary, those animals whose mothers were fed the slow-digesting carbohydrate diet showed a profile in the measured parameters closer to that of the offspring of healthy mothers. These results support the hypothesis that not only glycemic index but the rate of carbohydrate digestion during gestation may be critical to regulate the programming of adipogenesis in the offspring.

A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model for Bed Rest?

Bed rest has been an established treatment in the past prescribed for critically illness or convalescing patients, in order to preserve their body metabolic resource, to prevent serious complications and to support their rapid path to recovery. However, it has been reported that prolonged bed rest can have detrimental consequences that may delay or prevent the recovery from clinical illness. In order to study disuse-induced changes in muscle and bone, as observed during prolonged bed rest in humans, an innovative new model of muscle disuse for rodents is presented. Basically, the animals are confined to a reduced space designed to restrict their locomotion movements and allow them to drink and eat easily, without generating physical stress. The animals were immobilized for either 7, 14, or 28 days. The immobilization procedure induced a significant decrease of food intake, both at 14 and 28 days of immobilization. The reduced food intake was not a consequence of a stress condition induced by the model since plasma corticosterone levels -an indicator of a stress response- were not altered following the immobilization period. The animals showed a significant decrease in soleus muscle mass, grip force and cross-sectional area (a measure of fiber size), together with a decrease in bone mineral density. The present model may potentially serve to investigate the effects of bed-rest in pathological states characterized by a catabolic condition, such as diabetes or cancer.

Influencia del suplemento con inulina enriquecida con fructooligosacáridos sobre el contenido y la densidad mineral ósea tras el parto y la lactación en ratas.

Introducción: la gestación y lactancia están relacionadas con pérdidas temporales en la densidad mineral ósea (DMO) materna. Una suplementación con calcio podría resultar beneficiosa para evitar la pérdida de masa ósea del esqueleto materno. Otros nutrientes como los prebióticos han sido identificados como responsables de un incremento en la absorción de minerales, pudiendo condicionar la mineralización ósea.Objetivo: estudiar el efecto de la suplementación de la dieta materna con el prebiótico inulina enriquecida con oligofructosa, durante la gestación y la lactancia sobre el contenido mineral óseo (CMO) y la DMO al final del periodo de lactancia.Métodos: las ratas gestantes fueron alimentadas con dieta estándar (grupo CC), dieta fortificada en calcio (grupo Ca) o enriquecida con el prebiótico inulina enriquecida con oligofructosa (grupo Pre) hasta el final del periodo de lactancia. Posteriormente se evaluó el CMO y DMO por absorciometría de rayos X (DEXA) y el pH del contenido cecal.Resultados:en términos generales, el grupo Pre presenta los mayores valores absolutos de CMO y DMO de entre los tres grupos, siendo en la tibia significativamente diferentes en los grupos CC y Pre frente al grupo Ca. El pH del contenido cecal del grupo Pre es significativamente inferior al de los grupos CC y Ca.Conclusión:la suplementación con inulina enriquecida con oligofructosa, en condiciones nutricionales no deficientes en calcio, durante la gestación y la lactancia, ejerce una protección del esqueleto materno en las ratas y puede ser considerada como una estrategia nutricional para proteger la masa ósea materna en el periodo perinatal.

Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease.

Skeletal muscle is recognized as vital to physical movement, posture, and breathing. In a less known but critically important role, muscle influences energy and protein metabolism throughout the body. Muscle is a primary site for glucose uptake and storage, and it is also a reservoir of amino acids stored as protein. Amino acids are released when supplies are needed elsewhere in the body. These conditions occur with acute and chronic diseases, which decrease dietary intake while increasing metabolic needs. Such metabolic shifts lead to the muscle loss associated with sarcopenia and cachexia, resulting in a variety of adverse health and economic consequences. With loss of skeletal muscle, protein and energy availability is lowered throughout the body. Muscle loss is associated with delayed recovery from illness, slowed wound healing, reduced resting metabolic rate, physical disability, poorer quality of life, and higher health care costs. These adverse effects can be combatted with exercise and nutrition. Studies suggest dietary protein and leucine or its metabolite ß-hydroxy ß-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. Considerable evidence shows that use of high-protein oral nutritional supplements (ONS) can help maintain and rebuild muscle mass and strength. We review muscle structure, function, and role in energy and protein balance. We discuss how disease- and age-related malnutrition hamper muscle accretion, ultimately causing whole-body deterioration. Finally, we describe how specialized nutrition and exercise can restore muscle mass, strength, and function, and ultimately reverse the negative health and economic outcomes associated with muscle loss.

Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance.

BACKGROUND: Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells. METHODS: Acute effect of APE on the postprandial hyperglycemic response was assayed in 15 week old obese Zucker rats (OZR), by using a meal tolerance test (MTT). The ability of APE to improve whole peripheral insulin sensitivity was also assayed in a chronic study by using the euglycemic-hyperinsulinemic clamp technique. To elucidate the molecular mechanisms, rat L6 myotubes were used. Glucose uptake was measured by using 2-[3H]-Deoxy-Glucose (2-DG) and specific inhibitors, as well as phosphorylation status of key kinases, were used to determine the implicated signaling pathway. RESULTS: In vivo study showed that nutritional intervention with APE induced an increase of insulin sensitivity with an increase of glucose infusion rate (GIR) of 45 %. Additionally, in vitro results showed a synergistic effect between APE and insulin as well as increased glucose uptake through GLUT4 translocation in muscle cells. This translocation was mediated by phosphatydil inositol 3-kinase (PI3K) and peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathways. CONCLUSIONS: As a whole, this study describes the mechanisms involved in the insulin sensitizing effect of APE, which could be considered a promising ingredient for inclusion in nutritional products focused on the management of chronic diseases such as diabetes.

Conversion of leucine to ß-hydroxy-ß-methylbutyrate by α-keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes.

BACKGROUND: L-Leu and its metabolite ß-hydroxy-ß-methylbutyrate (HMB) stimulate muscle protein synthesis enhancing the phosphorylation of proteins that regulate anabolic signalling pathways. Alterations in these pathways are observed in many catabolic diseases, and HMB and L-Leu have proven their anabolic effects in in vivo and in vitro models. The aim of this study was to compare the anabolic effects of L-Leu and HMB in myotubes grown in the absence of any catabolic stimuli. METHODS: Studies were conducted in vitro using rat L6 myotubes under normal growth conditions (non-involving L-Leu-deprived conditions). Protein synthesis and mechanistic target of rapamycin signalling pathway were determined. RESULTS: Only HMB was able to increase protein synthesis through a mechanism that involves the phosphorylation of the mechanistic target of rapamycin as well as its downstream elements, pS6 kinase, 4E binding protein-1, and eIF4E. HMB was significantly more effective than L-Leu in promoting these effects through an activation of protein kinase B/Akt. Because the conversion of L-Leu to HMB is limited in muscle, L6 cells were transfected with a plasmid that codes for α-keto isocaproate dioxygenase, the key enzyme involved in the catabolic conversion of α-keto isocaproate into HMB. In these transfected cells, L-Leu was able to promote protein synthesis and mechanistic target of rapamycin regulated pathway activation equally to HMB. Additionally, these effects of leucine were reverted to a normal state by mesotrione, a specific inhibitor of α-keto isocaproate dioxygenase. CONCLUSION: Our results suggest that HMB is an active L-Leu metabolite able to maximize protein synthesis in skeletal muscle under conditions, in which no amino acid deprivation occurred. It may be proposed that supplementation with HMB may be very useful to stimulate protein synthesis in wasting conditions associated with chronic diseases, such as cancer or chronic heart failure.