Markers Of Insulin Sensitivity Research Articles

Area Under the Curve of carotid artery Doppler as a sensitive marker of insulin sensitivity among Iraqi women with polycystic ovarian syndrome: a cross sectional study

Area Under the Curve of carotid artery Doppler as a sensitive marker of insulin sensitivity among Iraqi women with polycystic ovarian syndrome: a cross sectional study

Lipoatrophic diabetes in familial partial lipodystrophy type 2: From insulin resistance to diabetes

Subjects with Familial Partial Lipodystrophy type 2 (FPLD2) are at high risk to develop diabetes. To better understand the natural history and variability of this disease, we studied glucose tolerance, insulin response to an oral glucose load, and metabolic markers in the largest cohort to date of subjects with FPLD2 due to the same LMNA variant. A total of 102 patients aged > 18 years, with FPLD2 due to the LMNA 'Reunionese' variant p.(Thr655Asnfs*49) and 22 unaffected adult relatives with normal glucose tolerance (NGT) were enrolled. Oral Glucose Tolerance Tests (OGTT) with calculation of derived insulin sensitivity and secretion markers, and measurements of HbA1c, C-reactive protein, leptin, adiponectin and lipid profile were performed. In patients with FPLD2: 65% had either diabetes (41%) or prediabetes (24%) despite their young age (median: 39.5 years IQR 29.0-50.8) and close-to-normal BMI (median: 25.5 kg/m2 IQR 23.1-29.4). Post-load OGTT values revealed insulin resistance and increased insulin secretion in patients with FPLD2 and NGT, whereas patients with diabetes were characterized by decreased insulin secretion. Impaired glucose tolerance with normal fasting glucose was present in 86% of patients with prediabetes. Adiponectin levels were decreased in all subjects with FPLD2 and correlated with insulin sensitivity markers. OGTT reveals early alterations of glucose and insulin metabolism in patients with FPLD2, and should be systematically performed before excluding a diagnosis of prediabetes or diabetes to adapt medical care. Decreased adiponectin is an early marker of the disease. Adiponectin replacement therapy warrants further study in FPLD2.

Exploring interindividual differences in fasting and postprandial insulin sensitivity adaptations in response to sprint interval exercise training

ABSTRACT Previous studies have concluded that wide variance in changes in insulin sensitivity markers following exercise training demonstrates heterogeneity in individual trainability. However, these studies frequently don’t account for technical, biological, and random within-subject measurement error. We used the standard deviation of individual responses (SDIR) to determine whether interindividual variability in trainability exists for fasting and postprandial insulin sensitivity outcomes following low-volume sprint interval training (SIT). We pooled data from 63 untrained participants who completed 6 weeks of SIT (n = 49; VO2max: 35 (7) mL⋅kg−1⋅min−1) or acted as no-intervention controls (n = 14; VO2max: 34 (6) mL⋅kg−1⋅min−1). Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin sensitivity were measured pre- and post-intervention. SDIR values were positive and exceeded a small effect size threshold for changes in fasting glucose (SDIR = 0.27 [95%CI 0.07,0.38] mmol⋅L−1), 2-h OGTT glucose (SDIR = 0.89 [0.22,1.23] mmol⋅L−1), glucose area-under-the-curve (SDIR = 66.4 [−81.5,124.3] mmol⋅L−1⋅120min−1) and The Cederholm Index (SDIR = 7.2 [−16.0,19.0] mg⋅l2⋅mmol−1⋅mU−1⋅min−1), suggesting meaningful individual responses to SIT, whilst SDIR values were negative for fasting insulin, fasting insulin resistance and insulin AUC. For all variables, the 95% CIs were wide and/or crossed zero, highlighting uncertainty about the existence of true interindividual differences in exercise trainability. Only 2–22% of participants could be classified as responders or non-responders with more than 95% certainty. Our findings demonstrate it cannot be assumed that variation in changes in insulin sensitivity following SIT is attributable to inherent differences in trainability, and reiterate the importance of accounting for technical, biological, and random error when examining heterogeneity in health-related training adaptations. Highlights This study tested whether true interindividual variability exists for changes in insulin sensitivity and glyceamic control following 6-weeks of low volume sprint interval training (SIT). The high level of technical, biological, and random error associated with repeated measurements of insulin sensitivity and glycaemic control, means we can neither confidently conclude that there is evidence of true interindividual differences in the trainability of these outcomes following SIT, nor confidently identify responders or non-responders for such parameters. Researchers contrasting responders vs. non-responders for a given parameter, either to understand mechanisms of adaptation and/or develop physiological/genetic/epigenetic predictors of response, need to be aware that identification of responders and non-responders with sufficient certainty may not be achievable for parameters with a high level of technical, biological, and random error.

TyGIS: improved triglyceride-glucose index for the assessment of insulin sensitivity during pregnancy

BackgroundThe triglyceride-glucose index (TyG) has been proposed as a surrogate marker of insulin resistance, which is a typical trait of pregnancy. However, very few studies analyzed TyG performance as marker of insulin resistance in pregnancy, and they were limited to insulin resistance assessment at fasting rather than in dynamic conditions, i.e., during an oral glucose tolerance test (OGTT), which allows more reliable assessment of the actual insulin sensitivity impairment. Thus, first aim of the study was exploring in pregnancy the relationships between TyG and OGTT-derived insulin sensitivity. In addition, we developed a new version of TyG, for improved performance as marker of insulin resistance in pregnancy.MethodsAt early pregnancy, a cohort of 109 women underwent assessment of maternal biometry and blood tests at fasting, for measurements of several variables (visit 1). Subsequently (26 weeks of gestation) all visit 1 analyses were repeated (visit 2), and a subgroup of women (84 selected) received a 2 h-75 g OGTT (30, 60, 90, and 120 min sampling) with measurement of blood glucose, insulin and C-peptide for reliable assessment of insulin sensitivity (PREDIM index) and insulin secretion/beta-cell function. The dataset was randomly split into 70% training set and 30% test set, and by machine learning approach we identified the optimal model, with TyG included, showing the best relationship with PREDIM. For inclusion in the model, we considered only fasting variables, in agreement with TyG definition.ResultsThe relationship of TyG with PREDIM was weak. Conversely, the improved TyG, called TyGIS, (linear function of TyG, body weight, lean body mass percentage and fasting insulin) resulted much strongly related to PREDIM, in both training and test sets (R2 > 0.64, p < 0.0001). Bland–Altman analysis and equivalence test confirmed the good performance of TyGIS in terms of association with PREDIM. Different further analyses confirmed TyGIS superiority over TyG.ConclusionsWe developed an improved version of TyG, as new surrogate marker of insulin sensitivity in pregnancy (TyGIS). Similarly to TyG, TyGIS relies only on fasting variables, but its performances are remarkably improved than those of TyG.

Antiplasmodial Activity of Phyllanthus amarus and Associated Impact on Surrogate Markers of Insulin Sensitivity and Resistance Indices

ABSTRACT The antimalarial activity of different parts (leaf, fruit, stem, and root) of Phyllanthus amarus and their associated impact on surrogate markers of insulin sensitivity in experimental mice, having ascertained their toxicity (LD50) index were documented. Results showed that the plant parts were nontoxic (LD50 > 5,000 mg kg−1) and were antimalarial in a dose-dependent manner, with the ethanol leaf extract having the highest parasite suppression followed by the fruit, root, and stem extracts. However, the root extract had the most profound impact on insulin sensitivity compared to other parts, although all showed improvement, with insulin sensitivity/resistance indices, with QUICKI vs. HOMA-IR showing a strong positive correlation (r = 0.993), but QUICKI vs. HOMA-IR and HOMA-IR vs. 1/HOMA = IR having strong negative correlation (r = −0.963 and −0.927, respectively). So, QUICKI and 1/HOMA-IR are surrogate indices of insulin sensitivity and HOMA-IR and TyG index, insulin resistance surrogate markers.

Metabolic syndrome in primary care: A latent variable analysis of electronic medical records

BackgroundThe best definition of the metabolic syndrome (MetSyn) remains controversial. The aim was to develop a latent variable measurement model for the MetSyn using primary care data. MethodsThis retrospective case-control study was based on the data from the IQVIA Disease Analyzer (DA) database including a representative panel of general and internal medicine practices in Germany. 23,020 adult patients, who were newly diagnosed with ≥1 component of the MetSyn (cases; median age [IQR]: 60 [50–72] years; 54 % males) between January 2016 to December 2019, and 2,144 patients without any MetSyn component (controls; 48 [38–61] years; 45 % males) were included. MetSyn was modeled by ICD-10 codes (E66: obesity, I10: hypertension, E11: type 2 diabetes, E78: lipid disorders) and physiological measures (BMI, HbA1c, blood pressure, HDL-cholesterol, LDL-cholesterol, triglycerides). ResultsThe covariance structure of the ICD codes and physiological measures could not be accounted for by a single MetSyn factor (root mean square error of approximation, RMSEA=0.085). Enrichment by another factor “Likelihood to Diagnose” significantly increased model fit with the observed data (RMSEA=0.054). “Likelihood to Diagnose” hardly correlated with MetSyn (r = 0.06), and was differentially associated with male sex, older age, and corresponding cardio- and cerebrovascular diseases. MetSyn showed the highest loading on four subordinate factors “hyperlipidemia” (0.70), “obesity” (0.66), “type 2 diabetes” (0.60), followed by “hypertension” (0.42). The ICD codes E66 and E78 were less indicative of these factors relative to BMI and triglycerides/HDL-cholesterol, respectively, whereas E11 and I10 were similarly indicative as their corresponding physiological measures. ConclusionsMetSyn was best indicated by BMI, triglycerides (an indirect marker of insulin sensitivity), HbA1c, and ICD-10 diagnosis E11 (type 2 diabetes). The factor “Likelihood to diagnose” probably constitutes a method factor of differential diagnosis systematically contributing to the common consistency of the MetSyn diagnosis in primary care.

From the Editor’s Desk…

From the Editor’s Desk…

Effects of Avocado Oil Supplementation on Insulin Sensitivity, Cognition, and Inflammatory and Oxidative Stress Markers in Different Tissues of Diet-Induced Obese Mice.

Obesity induces insulin resistance, chronic inflammation, oxidative stress, and neurocognitive impairment. Avocado oil (AO) has antioxidants and anti-inflammatory effects. This study evaluated the effect of AO supplementation on obese mice in the adipose tissue, muscle, liver, and hippocampus. Male C57BL/6J mice received a standard and high-fat diet (20 weeks) and then were supplemented with AO (4 mL/kg of body weight, 90 days) and divided into the following groups: control (control), control + avocado oil (control + AO), diet-induced obesity (DIO), and diet-induced obesity + avocado oil (DIO + AO) (n = 10/group). AO supplementation was found to improve insulin sensitivity and decrease hepatic fat accumulation and serum triglyceride levels in DIO mice. AO improved cognitive performance and did not affect mood parameters. Oxidative marker levels were decreased in DIO + AO mice in all the tissues and were concomitant with increased catalase and superoxide dismutase activities in the epididymal adipose tissue and quadriceps, as well as increased catalase activity in the liver. AO in obese animals further induced reductions in TNF-α and IL-1β expressions in the epididymal adipose tissue and quadriceps. These results suggest that AO supplementation has the potential to be an effective strategy for combating the effects of obesity in rats, and human studies are needed to confirm these findings.

Using Free-Breathing MRI to Quantify Pancreatic Fat and Investigate Spatial Heterogeneity in Children.

MRI acquisition for pediatric pancreatic fat quantification is limited by breath-holds (BH). Full segmentation (FS) or small region of interest (ROI) analysis methods may not account for pancreatic fat spatial heterogeneity, which may limit accuracy. To improve MRI acquisition and analysis for quantifying pancreatic proton-density fat fraction (pPDFF) in children by investigating free-breathing (FB)-MRI, characterizing pPDFF spatial heterogeneity, and relating pPDFF to clinical markers. Prospective. A total of 34 children, including healthy (N=16, 8 female) and overweight (N=18, 5 female) subjects. 3 T; multiecho gradient-echo three-dimensional (3D) stack-of-stars FB-MRI, multiecho gradient-echo 3D Cartesian BH-MRI. A radiologist measured FS- and ROI-based pPDFF on FB-MRI and BH-MRI PDFF maps, with anatomical images as references. Regional pPDFF in the pancreatic head, body, and tail were measured on FB-MRI. FS-pPDFF, ROI-pPDFF, and regional pPDFF were compared, and related to clinical markers, including hemoglobin A1c. T-test, Bland-Altman analysis, Lin's concordance correlation coefficient (CCC), one-way analysis of variance, and Spearman's rank correlation coefficient were used. P < 0.05 was considered significant. FS-pPDFF and ROI-pPDFF from FB-MRI and BH-MRI had mean difference=0.4%; CCC was 0.95 for FS-pPDFF and 0.62 for ROI-pPDFF. FS-pPDFF was higher than ROI-pPDFF (10.4% ± 6.4% vs. 4.2% ± 2.8%). Tail-pPDFF (11.6% ± 8.1%) was higher than body-pPDFF (8.9% ± 6.3%) and head-pPDFF (8.7% ± 5.2%). Head-pPDFF and body-pPDFF positively correlated with hemoglobin A1c. FB-MRI pPDFF is comparable to BH-MRI. Spatial heterogeneity affects pPDFF quantification. Regional measurements of pPDFF in the head and body were correlated with hemoglobin A1c, a marker of insulin sensitivity. 2 TECHNICAL EFFICACY: Stage 2.

Changes in Insulin Sensitivity and Lipid Profile Markers Following Initial and Secondary Bouts of Multiple Eccentric Exercises.

An acute bout of eccentric exercise affects insulin sensitivity and lipid profile, but how the magnitude of muscle damage affects them is not clear. We compared changes in blood insulin sensitivity and lipid markers after the first (EC1) and second (EC2) eccentric exercise bouts. Fifteen sedentary young men performed arm, leg and trunk muscle eccentric exercises, and repeated them 2 weeks later. Fasting blood samples were taken before, 2 h and 1–5 days after each exercise bout to analyze plasma creatine kinase (CK) activity, serum glucose (GLU), insulin, homeostasis model assessment (HOMA), triacylglycerols (TG), total (TC) and low- (LDLC) and high-density lipoprotein cholesterol (HDLC) concentrations as well as TC/HDLC ratio. Changes in these measures were compared between bouts and relationships to peak plasma CK activity were analyzed. Plasma CK activity increased (p < 0.05) after EC1 (peak: 101,668 ± 58,955 IU/L) but not after EC2. The magnitude of changes in GLU (peak after EC1: 26 ± 10% vs. EC2: 7 ± 6%), insulin (46 ± 27% vs. 15 ± 8%), HOMA (86 ± 48% vs. 24 ± 15%), TC (−20 ± 5% vs. −6 ± 4%), TG (−32 ± 11% vs. −6 ± 3%), LDHC (−47 ± 15% vs. −12 ± 9%), HDLC (35 ± 26% vs. 7 ± 4%), and TC/HDLC ratio (−139 ± 13% vs. −11 ± 7%) were significantly greater after EC1 than EC2. Peak plasma CK activity was significantly (p < 0.05) correlated with the peak changes in blood insulin sensitivity and lipid markers for the combined data of EC1 and EC2. These results suggest that the greater the magnitude of muscle damage, the greater the magnitude of changes in the insulin sensitivity to a negative direction and lipid markers to a positive direction.

337-OR: Tirzepatide Improved Markers of Islet-Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared with Semaglutide in People with Type 2 Diabetes

Tirzepatide (TZP) achieved significantly greater HbA1c and weight reductions with all doses (5, and 15 mg) vs. semaglutide 1 mg (SEMA) in a Phase 3 trial of 1879 people with type 2 diabetes (T2D) on background metformin (mean age 56.6 years; T2D duration 8.6 years; baseline HbA1c 8.3% [67 mmol/mol]; BMI 34.2 kg/m2) (SURPASS-2) . Changes in fasting markers of islet cell function and insulin sensitivity were assessed by mixed model repeated measures in the modified intent-to-treat population. At 40 weeks, all TZP doses improved HOMA2-B, calculated with C-peptide, as indicated by a significant increase by 97-120% on average with TZP, compared to 84% with SEMA. Fasting glucagon levels, adjusted for fasting serum glucose, significantly decreased by 53-55% on average with TZP and 15 mg doses compared with SEMA (48%) . All TZP doses improved insulin sensitivity as reflected by a significant decrease by 16-24% on average of HOMA2-IR, calculated with insulin, compared to a decrease by 5% with SEMA. Fasting insulin levels were also significantly reduced by 9-21% on average with all TZP doses compared to an increase of 0.6% with SEMA. Dual GIP/GLP-1 receptor agonist TZP significantly improved markers of islet cell function and insulin sensitivity compared to selective GLP-1 RA SEMA in people with T2D. Disclosure K. Brown: Employee; Eli Lilly and Company. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.K. Thomas: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Liu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

715-P: Tirzepatide as Monotherapy Improved Markers of Beta-Cell Function and Insulin Sensitivity in People with Type 2 Diabetes (SURPASS-1)

Tirzepatide (TZP) , a novel dual GIP/GLP-1 receptor agonist, led to greater HbA1c, fasting serum glucose and body weight reductions vs. placebo (PBO) in people with early T2D (baseline mean T2D duration 4.7 y and 54% no prior diabetes medications) from the 40-wk SURPASS-1 trial. In a Phase 2b trial, TZP also improved β-cell function and insulin sensitivity (IS) vs. PBO and selective GLP-1 receptor agonist, dulaglutide 1.5 mg. Similarly, in SURPASS-1, TZP improved β-cell function, as indicated by a 75-80% increase in HOMA2-B, and insulin resistance, as indicated by a 2-12% decrease in fasting insulin and 8-20% decrease in HOMA2-IR. In this analysis, we aimed to explore changes in additional biomarkers of β-cell function and IS after TZP monotherapy (5, and 15 mg) . At 40 wks, proinsulin/C-peptide ratios, a marker of insulin processing, β-cell stress and β-cell function improved with decrease by 47-49% with TZP vs. -0.1% with PBO (p&amp;lt;0.001, all doses) (Table) . Fasting proinsulin decreased by 49-55% with TZP vs. no change with PBO (p&amp;lt;0.001, all doses) . Decreases in fasting C-peptide by 3-9% with TZP did not differ vs. PBO. TZP vs. PBO improved biomarkers of IS evidenced by increases in adiponectin (16-23% vs. -0.2%; p≤0.028, all doses) and IGFBP-2 (38-70% vs. 4.1%; p&amp;lt;0.001, all doses) . As a monotherapy for early T2D, TZP achieved significant improvement in markers of β-cell function and IS. Disclosure C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. H.Mao: Employee; Eli Lilly and Company. V.Thieu: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

197-LB: Adipocyte ZAG Improves Obesity-Triggered Insulin Resistance by Reshaping Macrophages Populations in Adipose Tissue

Adipose tissues macrophages (ATMs) serve as critical effectors in the mediating occurrence of metabolic inflammation to impact whole-body insulin sensitivity in obesity. Discovering the key adipokines mediating crosstalk of adipocyte-macrophage and understanding the molecular mechanism of ATMs polarization and function have become hot topic issues in the immunometabolism fields. Zinc-α2-glycoprotein (ZAG) as an anti-inflammatory adipokines plays important roles in obesity-related metabolic diseases. We attempt to explore the precise role of adipose ZAG in metabolic inflammation and obesity-associated insulin resistance. Here we showed that Omental ZAG was positively associated with insulin sensitivity and M2 macrophages markers. ZAG-specific ablation in adipocyte aggravated insulin resistance and adipose tissues inflammation as evidenced by enhanced M1 macrophages proportion and inhibited AKT signaling pathway in mice fed with a high-fat diet. ZAG overexpression attenuated insulin resistance and accumulation of pro-inflammatory macrophages. Exogenous ZAG inhibits PA-induced M1 macrophage polarization via β3-AR/PKA/STAT3 signaling in RAW264.7 macrophages. These findings suggest that adipocyte ZAG maintains insulin sensitivity via the cross talk with adipose-resident macrophages. Keywords: ZAG; inflammation; insulin resistance; obesity; adipose tissue macrophages Disclosure X. Xiao: None. Z. Liao: None. Y. Wang: None. X. Qi: None. Funding National Natural Science Foundation of China (82070873, 82000813) , Natural Science Foundation of Hunan province (2020JJ8097, 2021JJ40496) and Major special projects of Hunan provincial health and family planning commission (A2017011)

A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial

BackgroundA spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual’s health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI.MethodsThis single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant’s home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety.DiscussionWe anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI.Trial registrationClinicalTrials.gov: (NCT03576001).Prospectively registered: July 3, 2018.

The Use and Effectiveness of Selected Alternative Markers for Insulin Sensitivity and Secretion Compared with Gold Standard Markers in Dietary Intervention Studies in Individuals without Diabetes: Results of a Systematic Review.

Background: The gold-standard techniques for measuring insulin sensitivity and secretion are well established. However, they may be perceived as invasive and expensive for use in dietary intervention studies. Thus, surrogate markers have been proposed as alternative markers for insulin sensitivity and secretion. This systematic review aimed to identify markers of insulin sensitivity and secretion in response to dietary intervention and assess their suitability as surrogates for the gold-standard methodology. Methods: Three databases, PubMed, Scopus, and Cochrane were searched, intervention studies and randomised controlled trials reporting data on dietary intake, a gold standard of analysis of insulin sensitivity (either euglycaemic-hyperinsulinaemic clamp or intravenous glucose tolerance test and secretion (acute insulin response to glucose), as well as surrogate markers for insulin sensitivity (either fasting insulin, area under the curve oral glucose tolerance tests and HOMA-IR) and insulin secretion (disposition index), were selected. Results: We identified thirty-five studies that were eligible for inclusion. We found insufficient evidence to predict insulin sensitivity and secretion with surrogate markers when compared to gold standards in nutritional intervention studies. Conclusions: Future research is needed to investigate if surrogate measures of insulin sensitivity and secretion can be repeatable and reproducible in the same way as gold standards.

Dietary Assessment Tools and Metabolic Syndrome: Is It Time to Change the Focus?

Metabolic syndrome (MS) is associated with a range of chronic diseases, for which lifestyle interventions are considered the cornerstone of treatment. Dietary interventions have primarily focused on weight reduction, usually via energy restricted diets. While this strategy can improve insulin sensitivity and other health markers, weight loss alone is not always effective in addressing all risk factors associated with MS. Previous studies have identified diet quality as a key factor in reducing the risk of MS independent of weight loss. Additionally, supporting evidence for the use of novel strategies such as carbohydrate restriction and modifying the frequency and timing of meals is growing. It is well established that dietary assessment tools capable of identifying dietary patterns known to increase the risk of MS are essential for the development of personalised, targeted diet and lifestyle advice. The American Heart Association (AHA) recently evaluated the latest in a variety of assessment tools, recommending three that demonstrate the highest evidence-based and clinical relevance. However, such tools may not assess and thus identify all dietary and eating patterns associated with MS development and treatment, especially those which are new and emerging. This paper offers a review of current dietary assessment tools recommended for use by the AHA to assess dietary and eating patterns associated with MS development. We discuss how these recommendations align with recent and novel evidence on the benefits of restricting ultra-processed food and refined carbohydrates and modifying timing and frequency of meals. Finally, we provide recommendations for future redevelopment of these tools to be deployed in health care settings.

Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial.

Inconsistent evidence showed that folate supplementation may be associated with reduced risk of cancer due to improved metabolic profiles and reduced markers of oxidative stress and inflammation. The aim of this investigation was to quantify the effects of folate supplementation on the recurrence and other metabolic factors of women with cervical intraepithelial neoplasia grade 2/3 (CIN2/3). This randomized, double-blind, placebo-controlled clinical trial was performed among 60 overweight/obese women with CIN2/3. Definitive CIN2/3 confirmation was done via biopsy, pathological diagnosis, as well as colposcopy. Participants were randomly assigned to the intervention group to take 5 mg/day folate supplements or placebo group (n = 30 in each group) for 12 weeks. The results of the current study showed a non-significant decrease in recurrence of CIN2/3 in the folate group in comparison with the placebo group (3.3% vs. 16.7%, P = 0.08). Compared with the placebo, folate supplementation significantly decreased plasma homocysteine (Hcy) levels (P < 0.001), serum insulin values (in the crude model) (P = 0.01), and homeostasis model assessment of insulin resistance (P = 0.01). Also, folate supplementation resulted in a significant improvement in the quantitative insulin sensitivity check index (P = 0.002) and total antioxidant capacity (P = 0.04) and a significant reduction in high-sensitivity C-reactive protein (P = 0.015) in comparison with the placebo group. In conclusion, folate supplementation for 12 weeks among overweight/obese women with CIN2/3 showed a non-significant decrease in its recurrence and had beneficial effects on insulin sensitivity, inflammation, and oxidative stress markers.

Associations between high-metabolic rate organ masses and fasting hunger: A study using whole-body magnetic resonance imaging in healthy males

BackgroundFat-free mass (FFM) has been shown to be positively associated with hunger and energy intake, an association mediated by resting metabolic rate (RMR). However, FFM comprises a heterogeneous group of tissues with distinct metabolic rates, and it remains unknown how specific high-metabolic rate organs contribute to the degree of perceived hunger. ObjectiveTo examine whether FFM and its anatomical components were associated with fasting hunger when assessed at the tissue-organ level. DesignBody composition (quantitative magnetic resonance and magnetic resonance imaging), RMR and whole-body glucose oxidation (indirect calorimetry), HOMA-index as a marker of insulin sensitivity, nitrogen balance and fasting hunger (visual analogue scales) were assessed in 21 healthy males (age = 25 ± 3y; BMI = 23.4 ± 2.1 kg/m2) after 3 days of controlled energy balance. ResultsFFM (rs = 0.39; p = 0.09), RMR (rs = 0.52; p = 0.02) and skeletal muscle mass (rs = 0.57; p = 0.04), but not fat mass (rs = −0.01; p = 0.99), were positively associated with fasting hunger. The association between the combined mass of high-metabolic rate organs (i.e., brain, liver, kidneys and heart; rs = 0.58; p = 0.006) and fasting hunger was stronger than with FFM as a uniform body component. The strongest individual association was between liver mass and fasting hunger (rs = 0.51; p = 0.02). No associations were observed between glucose parameters, markers of insulin sensitivity and fasting hunger. The encephalic measure, an index of brain-to-body energy allocation, was negatively associated with fasting hunger (rs = −0.51; p = 0.02). ConclusionsFasting hunger was more strongly associated with the combined mass of high-metabolic rate organs than with FFM as a uniform body component, highlighting the importance of integrating individual tissue-organ masses and their functional correlates into homeostatic models of human appetite. The association between liver mass and fasting hunger may reflect its role in ensuring the brain's basal energy needs are met.

Low Birth Weight, β-Cell Function and Insulin Resistance in Adults: The Brazilian Longitudinal Study of Adult Health.

BackgroundAdverse intrauterine environment—reflected by low birth weight (LBW)—has been linked to insulin resistance and type 2 diabetes later in life. Whether β-cell function reduction and insulin resistance could be detected even in middle-aged adults without overt diabetes is less investigated. We examined the association of LBW with β-cell function and insulin sensitivity in non-diabetic middle-aged adults from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).MethodsThis is a cross-sectional analysis of 2,634 ELSA-Brasil participants aged between 34 and 59 years, without diabetes. Participants were stratified according to LBW defined as <2.5 kg and their clinical data were compared. HOMA-IR, HOMA-β, HOMA-adiponectin, TyG index, QUICKI and TG/HDL were calculated and their association with LBW were tested using multiple linear regression including adjustments suggested by Directed Acyclic Graphs and propensity score matching was applied.ResultsThe sample (47.4 ± 6.3 years) was composed of 57.5% of women and 9% had LBW. Subjects with LBW and normal-weight reported similar BMI values at the age of 20 years and current BMI was slightly lower in the LBW group. In average, cardiometabolic risk profile and also indexes of β-cell function and insulin sensitivity were within normal ranges. In regression analysis, log-transformed HOMA-β—but not with the other indexes—was associated with LBW (p = 0.014) independent of sex, skin color, prematurity, and family history of diabetes. After applying propensity-score matching in a well-balanced sample, HOMA-AD and TG/HDL indexes were associated with LBW.ConclusionThe association between LBW and insulin sensitivity markers may occur in healthy middle-aged adults before overt glucose metabolism disturbances. Our data are coherent with the detection of early life events consequent with insulin resistance markers that could contribute to the risk of glucose metabolism disturbances.

The Peripheral Kynurenine Pathway and Psychosomatic Comorbidity in Subjects with Morbid Obesity Undergoing Bariatric Surgery

Background: The Kynurenine pathway (KP) is involved in various disorders, but little is known about the KP and psychosomatic complaints. The aim was to study the peripheral KP and psychosomatic comorbidity in subjects with morbid obesity. Methods: Psychosomatic comorbidity (perceived general health, muscle-skeletal pain, well-being, mood disorders, fatigue, self-esteem, sleepiness, and sense of humour) was registered, and serum samples were collected six months before and after bariatric surgery. Results: A total of 141 subjects (men/women, 116/25) with a mean age of 43.0 (SD 8.7) years and BMI of 42.1 (SD 3.8) kg/m2 were included. No significant associations were seen between the psychosomatic disorders and the KP. There was a significant downregulation of all KP metabolites after surgery, a reduction in CRP, and strong associations between CRP and the KP, particularly with the ratios of Kynurenine/Tryptophan and Quinolinic acid (QA)/Xanthurenic acid (XA). The QA/XA ratio was negatively associated with diabetes. Conclusions: The peripheral KP seemed to be of minor importance for the psychosomatic comorbidity in subjects with morbid obesity. The downregulation of all KP metabolites after bariatric surgery indicated reduced inflammation. The QA/XA ratio seemed to be a marker of insulin sensitivity and favourable glucose control.