Insulin Resistance, Lipids, and the Metabolic Syndrome Trait Cluster: Impact of Race and Very Low Calorie Diet

Insulin resistance (IR) is central to the pathogenesis of cardiometabolic disorders. Early detection, along with appropriate interventions, is paramount to reduce the morbidity and mortality of IR-related diseases. The gold standard measurement for IR is the hyperinsulinemic-euglycemic clamp, which is markedly sophisticated for clinical evaluation but costly and invasive for clinical practice. Several alternative surrogate indicators of IR have been identified and used by clinicians, including insulin sensitivity indices derived from plasma glucose and insulin values, as well as other indicators that are independent of direct insulin measurements. In addition, lipid panel and lipoprotein subclass profile have emerged as markers of IR, and the cluster of abnormalities that define Metabolic Syndrome also have been used to predict IR and related outcomes in clinical settings. Race can confound the utility of IR indicators; however, there is no data to demonstrate which indicators may more accurately represent insulin dynamics and homeostasis in different populations. Although it is known that intervention strategies can improve IR, it is not clear whether the effect of interventions in insulin-related outcomes can be accurately captured by traditionally used methods. Thus, three specific aims were investigated in this project. First, we determined the predictability of commonly used insulin sensitivity indices compared to the hyperinsulinemic-euglycemic clamp in European Americans (EA) and African Americans (AA), demonstrating differences between groups and that the most reliable indices were the Matsuda index and the simple index assessing insulin sensitivity using oral glucose tolerance test. Second, we evaluated the relationship between IR and lipoprotein subclass profile between EAs and AAs, showing an association between IR and lipid subclass profile beyond the conventional lipid panel. Third, we determined changes in lipoprotein subclass profile and insulin sensitivity after a short-term very low calorie diet, verifying concomitant favorable changes in the Matsuda index and lipoprotein subclass profile after the intervention. Taken together, our findings demonstrated that the Matsuda index and lipoprotein subclass profile are appropriate markers for identifying and monitoring IR in a mixed-race population during regular screening and during diet-related interventions. Our work supports the need for race-specific tools in the evaluation of insulin-related outcomes

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition diagnosis of malnutrition

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure

Background and aims: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). Methods: Period of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. Results: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. Conclusions: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death

Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines.

PURPOSE: The benefits of aerobic exercise training on insulin sensitivity in subjects with the metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g. fractalkine, omentin and osteopontin) that are strongly involved in glucose homeostasis and therefore potentially contribute in the exercise-induced changes in insulin sensitivity. Therefore, we aim to examine changes in skeletal muscle RNA expression and plasma levels of novel cytokines after exercise training, and correlate these changes to the exercise-induced changes in insulin sensitivity. METHODS: Women with the metabolic syndrome (MetS, n=11) and healthy women (n=10) participated in a 6-month aerobic exercise training intervention (3/week, 45min per session at 65%-85% of individual heart rate reserve). Before and after training, we examined insulin sensitivity (M-value during hyperinsulinemic euglycaemic clamp), circulating blood levels of cytokines (venous blood sample; leptin, adiponectin, omentin, fraktalkin, osteopontin). Skeletal muscle RNA-expression of these cytokines (muscle biopsy) was examined in two subgroups (MetS n=6; healthy women n=6). RESULTS: At baseline, plasma levels of omentin (85.8±26.2ng/ml) and adiponectin (5.0±1.7μg/ml) levels were significantly higher in controls compared to MetS (51.1±27.1; 3.6±1.1 respectively), and leptin levels were lower in controls (18.7±11.5ng/ml vs 53.0±23.5). M-value was significantly higher in controls (8.1±1.9mg/kg/min) than in MetS (4.0±1.7). Exercise training significantly improved M-values in both groups (P0.05). CONCLUSION: Whilst exercise training successfully improves insulin sensitivity in MetS and healthy women, we found no change in plasma and mRNA expression levels of novel cytokines

Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans

BACKGROUND: Mitochondrial alterations have been observed in subjects with metabolic disorders such as obesity and diabetes. Studies on animal models and cell cultures suggest aberrant glucose and lipid levels, and impaired insulin signaling might lead to mitochondrial changes. However, the molecular mechanism underlying mitochondrial aberrance remains largely unexplored in human subjects. RESULTS: Here we show that the mitochondrial DNA copy number (mtDNAn) was significantly reduced (6.9-fold lower, p < 0.001) in the leukocytes from obese humans (BMI >30). The reduction of mtDNAn was strongly associated with insulin resistance (HOMA-IR: −0.703, p < 0.05; fasting insulin level: −0.015, p < 0.05); by contrast, the correlation between fasting glucose or lipid levels and mtDNAn was not significant. Epigenetic study of the displacement loop (D-loop) region of mitochondrial genome, which controls the replication and transcription of the mitochondrial DNA as well as organization of the mitochondrial nucleoid, revealed a dramatic increase of DNA methylation in obese (5.2-fold higher vs. lean subjects, p < 0.05) and insulin-resistant (4.6-fold higher vs. insulin-sensitive subjects, p < 0.05) individuals. CONCLUSIONS: The reduction of mtDNAn in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation, suggesting an insulin signaling-epigenetic-genetic axis in mitochondrial regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0093-1) contains supplementary material, which is available to authorized users

Comparing Performance of NAF and NT-2013 to SGA as Nutritional Assessment Tools in Systemic Sclerosis Patients

Malnutrition is one of the common complications of patients with systemic sclerosis (SSc). However, several nutritional assessment tools are implemented in Thailand. The study aimed to compare the performance of nutritional assessment tools including Nutritional Assessment Form (NAF) and Nutritional Triage 2013 (NT-2013) to Subjective Global Assessment (SGA) in SSc patients. A cross-sectional diagnostic study was conducted in adult SSc patients at Srinagarind Hospital, Thailand. To elucidate the efficacy and correlations of these tools, descriptive statistics, Pearson correlation analyses, and kappa coefficient of agreement were employed. A total of 208 SSc patients were included, of which 70.7% were females. The respective mean age and body mass index was 59.3 years and 21.1 kg/m2. Nearly half (45.7%) were malnourished based on SGA. Malnutrition diagnosis using the NAF and NT-2013 criteria were found in 80.3% and 34.6%, respectively. The respective sensitivity and specificity of NAF for diagnosis of malnutrition was 93.7% and 31.9%, while NT-2013 was 60.0% and 90.3%. Both NAF and NT-2013 had slight agreement with SGA with a kappa of 0.149 for NAF and 0.131 for NT-2013. Adjusting the cut-off points of NAF and NT-2013 could enhance sensitivity, specificity, and improve agreement for diagnosis with SGA

Moderately high-protein enteral formula improved retinol-binding protein in tube-fed patients: A multicentre open study

Background: Long-term inadequate dietary consumption may increase the possibility of malnutrition, morbidity and mortality. Enteral nutrition (EN) is a beneficial support that could help to maintain nutritional status and gut function. Aim: Our aim was to evaluate the effect of moderately high-protein enteral formula containing fibre on nutritional status, and its safety. Method: A total of 23 tube-feeding-dependent adult patients were included in this multicentre, open-label study. The patients were fed with the study formula for 7–12 days or equal to the required nutritional support period, during which we performed physical examinations and assessed nutritional status. The primary endpoint was the statistical difference in nutritional status after the treatment, and the secondary outcome was the desirable safety profile. Results: A significant improvement in cumulative energy balance after intervention was observed ( p = 0.008). However, the differences in nutritional status, weight and BMI before and after the intervention do not reach statistical significance. Retinol-binding protein (RBP), a marker for nutritional status, increased from baseline levels. Few cases of diarrhoea and constipation had been reported during the study as a safety concern. Conclusions: This study investigated the efficacy and safety of an enteral feed formulation containing fibre. The patients were nourished with the studied formulation via tube feeding for a short period without serious adverse events. After the intervention, the significant increase in cumulative energy balance was observed. However, an extended period of the intervention may be required to attain the significance in other indicators for nutritional status. </jats:sec