Metabolic Risk Markers Research Articles

Effect of an office-based intervention on visceral adipose tissue: the WorkACTIVE-P randomized controlled trial.

Office-based activity reduces sedentariness, yet no randomized controlled trials (RCTs) have assessed how such activity influences visceral adipose tissue (VAT). This study examined the effect of an office-based, multicomponent activity intervention on VAT. The WorkACTIVE-P RCT enrolled sedentary office workers (body mass index: 31.4 (standard deviation (SD) 4.4) kg/m2) to an intervention (n = 20) or control (n = 20) group. For 3 months, the intervention group received an office-based pedal desk, further to an intervention promoting its use and increased walking. The control group maintained habitual activity. At baseline and follow-up, VAT, cardiometabolic disease risk markers, physical activity, and food intake were measured. Steps/day were not altered relative to control (P ≥ 0.51), but the pedal desk was utilized for 127 (SD 61) min/day. The intervention reduced VAT relative to control (-0.15 kg; 95% confidence interval (CI) = -0.29 to -0.01; P = 0.04). Moreover, the intervention decreased fasting glucose compared with control (-0.29 mmol/L; 95% CI = -0.51 to -0.06; P = 0.01), but no differences in other cardiometabolic disease markers or food intake were revealed (P ≥ 0.11). A multicomponent intervention decreased VAT in office workers who were overweight or obese. Though longer-term studies are needed, office-based, multicomponent activity regimens may lower cardiometabolic disease risk. Trial registered at ClinicalTrials.gov (NCT02561611). Novelty: In WorkACTIVE-P, a multicomponent activity intervention decreased visceral adipose tissue relative to control in office workers. The intervention also reduced glucose compared with control, though other metabolic risk markers and food intake were not altered. Such multicomponent interventions could help reduce cardiometabolic disease risk, but longer studies are needed.

Impact of the consumption of ultra-processed foods on children, adolescents and adults' health: scope review.

The aim of this study was to conduct a literature scope review of the association between the consumption of ultra-processed foods and health outcomes. The search was carried out in the PubMed, Web of Science and LILACS databases. Studies that assessed the association between the consumption of ultra-processed foods, identified on the NOVA classification, and health outcomes were eligible. The review process resulted in the selection of 63 studies, which were analyzed in terms of quality using a tool from the National Institutes of Health. The outcomes found included obesity, metabolic risk markers, diabetes, cardiovascular diseases, cancer, asthma, depression, frailty, gastrointestinal diseases and mortality indicators. The evidence was particularly consistent for obesity (or indicators related to it) in adults, whose association with the consumption of ultra-processed foods was demonstrated, with dose-response effect, in cross-sectional studies with representative samples from five countries, in four large cohort studies and in a randomized clinical trial. Large cohort studies have also found a significant association between the consumption of ultra-processed foods and the risk of cardiovascular diseases, diabetes and cancer - even after adjusting for obesity. Two cohort studies have shown an association of ultra-processed foods consumption with depression and four cohort studies with all-cause mortality. This review summarized the studies' results that described the association between the consumption of ultra-processed foods and various non-communicable diseases and their risk factors, which has important implications for public health.

Comparison of serum adiponectin and osteopontin levels along with metabolic risk factors between obese and lean women with and without PCOS.

The objective of this study was to investigate the possible relation between serum adiponectin and osteopontin levels as metabolic risk markers among women with different polycystic ovary syndrome (PCOS) phenotypes. In a University Hospital setting PCOS patients diagnosed according to Rotterdam Consensus Conference criteria with body mass index (BMI) between 18 and 35 were recruited. Overall, 57 PCOS patients and 57 age- and BMI-matched healthy controls were included in the study. Luteinising hormone (LH) to follicle-stimulating hormone FSH ratio (LH/FSH), free androgen index (FAI), and dehydroepiandrosterone sulphate (DHEAS-S) was found to be significantly higher in women with PCOS. There was significant interaction between PCOS status and obesity for serum adiponectin levels. Although mean adiponectin and osteopontin levels were similar among cases and controls, a further two-way ANOVA comparison within lean and obese subgroups revealed adiponectin to be significantly lower in lean PCOS women than in lean controls. LH/FSH ratio and adiponectin levels were all found to differ between lean counterparts; however, they did not show any correlation with metabolic markers [cholesterol, homeostatic model assessment (HOMA) or C-reactive protein (CRP) levels] in overall lean women or in the lean PCOS subgroup. Serum adiponectin levels in lean PCOS women were significantly lower than those in lean controls. On the other hand, mean adiponectin and osteopontin levels were similar in PCOS cases and controls overall.

Early versus late time‐restricted feeding in adults at increased risk of developing type 2 diabetes: Is there an optimal time to eat for metabolic health?

AbstractTime‐restricted feeding (TRF) is a novel dietary approach where energy intake is limited to a set number of hours in the day (typically ≤12 hours), which leads to an extension of the daily fast that generally occurs overnight. Human pilot studies (based on animal experiments) have demonstrated that TRF has the potential to reduce risk factors for type 2 diabetes (T2DM): mediating weight loss, the reduction of low‐density lipoprotein (LDL) cholesterol and improving insulin sensitivity. However, it remains unclear whether it is better to restrict food intake to earlier in the day (early‐TRF) or later in the day (late‐TRF). The aim of this study is to investigate the effects of TRF on established risk factors for T2DM and its application to wider society. The primary hypothesis is that 10 weeks of daily TRF will reduce food intake, bodyweight and adiposity while improving markers of metabolic disease risk, such as LDL‐cholesterol and insulin sensitivity. The secondary hypothesis is that early‐TRF will induce larger metabolic changes in comparison to late‐TRF. Eligible volunteers will be randomised to either the early‐TRF (7 am to 3 pm), late‐TRF (12 pm to 8 pm) or control group (unrestricted eating window) for 10 weeks. Changes in fasting markers, diet, bodyweight and body composition will be assessed throughout the experiment, as well as the effects on psychological wellbeing and social and family interactions.

Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS.

Polycystic ovary syndrome (PCOS) is characterized by elevated androgen production and subclinical changes in cardiovascular and metabolic risk markers. Total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin appear to increase specifically in PCOS compared with fertile women. PCOS also confers an increased risk of cardiometabolic disease in later life. Novel biomarkers such as serum’s cholesterol efflux capacity and blood-derived macrophage activation profile may assist in more accurately defining the cardiometabolic risk profile in these women. Aldosterone antagonists, androgen receptor antagonists, 5α-reductase inhibitors, and synthetic progestogens are used to reduce hyperandrogenism. Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction. The naturally occurring inositols display insulin-sensitizing effects and may be also used in this context because of their safety profile. Combined oral contraceptives represent the drug of choice for correction of androgen-related symptoms. Overall, PCOS management remains focused on specific targets including assessment and treatment of cardiometabolic risk, according to disease phenotypes. While new options are adding to established therapeutic approaches, a sometimes difficult balance between efficacy and safety of available medications has to be found in individual women.

Association of hyperuricemia and gamma glutamyl transferase as a marker of metabolic risk in alcohol use disorder

Excessive alcohol consumption leads to overproduction of urates and renal function plays a critical role in serum uric acid levels. We aimed to assess associations of hyperuricemia in patients with alcohol use disorder (AUD) and comparable Glomerular Filtration Rate (GFR). A total of 686 patients undergoing treatment for AUD between 2013 and 2017 were eligible (77% men); age at admission was 47 years [interquartile range (IQR), 40–53 years], age of onset of alcohol consumption was 16 years [IQR, 16–18 years] and the amount of alcohol consumed was 160 g/day [IQR, 120–240 g/day]. Body Mass Index was 24.7 kg/m2 [IQR, 21.9–28.4 kg/m2], eGFR was 105 mL/min/1.73 m2 [IQR, 95.7–113.0 mL], 9.7% had metabolic syndrome and 23% had advanced liver fibrosis (FIB-4 > 3.25). Prevalence of hyperuricemia was 12.5%. The eGFR-adjusted multivariate analysis showed that relative to patients with GGT ≤ 50, those with GGT between 51 and 300 U/L and those with GGT > 300 U/L were 4.31 (95% CI 1.62–11.46) and 10.3 (95% CI 3.50–29.90) times more likely to have hyperuricemia, respectively. Our data shows that hyperuricemia in the context of AUD is strongly associated with serum GGT levels and suggest an increased cardio-metabolic risk in this population.

Correlation between Epicardial Fat Thickness and Clinical and Anthropometric Variables in an Elderly Population

Abstract Background Epicardial fat (EF) thickness is a marker of visceral adiposity and consequently considered an important predictive marker of cardiovascular and metabolic risk. Objective To describe echocardiographic features of the heart in an elderly population and to study the correlation between EF thickness and clinical and anthropometric variables. Methods A sample of 34 individuals (25 women) aged between 65 and 92 years, who attended a private institution in the central region of Continental Portugal, was analyzed. A standardized sociodemographic [...]

Relationship Between Elevated Hair Mercury Levels, Essential Element Status, and Metabolic Profile in Overweight and Obese Adults.

The objective of the present study was to evaluate hair essential and trace element levels and metabolic risk markers in overweight and obese subjects in relation to body mercury burden. According to 2 × 2 factorial design a total of 440 adults were distributed to four groups: (i) low-Hg normal-weight subjects (n = 114); (ii) high-Hg normal weight subjects (n = 113); (iii) low-Hg overweight (BMI > 25) subjects (n = 110); (iv) high-Hg overweight (BMI > 25) subjects (n = 110). Hg-exposed groups consisted of subjects characterized by frequent seafood consumption (> 4 times/week) subsequently evaluated by hair analysis (> 0.58μg/g). Dietary-exposed subjects were characterized by a more than 3-fold higher hair Hg content irrespectively of body weight values. Both low-Hg and high-Hg overweight subjects were characterized by significantly higher ALT activity, as well as elevated serum glucose, LDL, and triglyceride levels as compared to the respective groups of normal weight subjects. High Hg body burden had a more significant effect on metabolic parameters in overweight and obese adults. Particularly, high-Hg overweight subjects were characterized by significantly higher serum creatinine and uric acid levels, as well as increased GGT and CK activity as compared to low-Hg overweight counterparts. In addition, hair Mg, Mn, and Sr content in high-Hg overweight subjects was significantly lower than that in low-Hg normal weight and overweight examinees. In turn, high Hg levels in overweight subjects were associated with significantly higher hair Se and Zn levels when compared to unexposed overweight adults. Generally, the obtained data demonstrate that increased hair Hg levels in overweight and obese subjects is associated with adverse metabolic profile. It is proposed that observed metabolic alterations may be at least partially mediated by Hg-associated disturbances in essential trace element and mineral metabolism.

Adiponectin, HOMA-Adiponectin, HOMA-IR in Children and Adolescents: Ouro Preto Study.

To examine the association and predictive capacity of adiponectin levels, HOMA-AD and HOMA-IR indexes with metabolic risk markers in children and adolescents. A cross-sectional study was conducted with 691 children and adolescents (7-14 y), of both sexes. Demographic (sex, age), anthropometric (weight, height, body mass index, waist circumference, body fat), biochemical [total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fasting glycemia, insulin and adiponectin] and clinical parameters (arterial blood pressure) were analyzed. In multiple linear regression models, metabolic risk were analyzed in relation to adiponectin levels, HOMA-AD and HOMA-IR. ROC curve analysis was used to define the cut-off for metabolic syndrome for each method studied. Adiponectin level was inversely correlated with weight (r = -0.12; p = 0.01), waist circumference (WC) (r = -0.12; p = 0.01), and triglycerides (r = -0.11; p = 0.02); it was directly correlated with HDL (r = 0.10; p = 0.03) only in the adolescents. In the final linear regression model, after adjustment, only triglycerides (p = 0.03) and HDL (p = 0.04) remained significant. However, HOMA-AD and HOMA-IR were associated with metabolic risk and were the most suitable methods for metabolic syndrome screening in both age groups. For children, independent variables explained 16.0% and 14.5% of HOMA-AD and HOMA-IR, respectively. For adolescents, R2 was higher in HOMA-AD and HOMA-IR models (R2adjusted = 31.9% and R2adjusted = 29.6%, respectively). HOMA-AD and HOMA-IR are better explained by metabolic markers than adiponectin levels.

Interaction of Neighborhood and Genetic Risk on Waist Circumference in African-American Adults: A Longitudinal Study.

Understanding determinants of metabolic risk has become a national priority given the increasingly high prevalence rate of this condition among U.S. adults. This study's aim was to assess the impact of gene-by-neighborhood social environment interactions on waist circumference (WC) as a primary marker of metabolic risk in underserved African-American adults. Based on a dual-risk model, it was hypothesized that those with the highest genetic risk and who experienced negative neighborhood environment conditions would demonstrate higher WC than those with fewer risk factors. This study utilized a subsample of participants from the Positive Action for Today's Health environmental intervention to improve access and safety for walking in higher-crime neighborhoods, who were willing to provide buccal swab samples for genotyping stress-related genetic pathways. Assessments were conducted with 228 African-American adults at baseline, 12, 18, and 24 months. Analyses indicated three significant gene-by-environment interactions on WC outcomes within the sympathetic nervous system (SNS) genetic pathway. Two interactions supported the dual-risk hypotheses, including the SNS genetic risk-by-neighborhood social life interaction (b = -0.11, t(618) = -2.02, p = .04), and SNS genetic risk-by-informal social control interaction (b = -0.51, t(618) = -1.95, p = .05) on WC outcomes. These interactions indicated that higher genetic risk and lower social-environmental supports were associated with higher WC. There was also one significant SNS genetic risk-by-neighborhood satisfaction interaction (b = 1.48, t(618) = 2.23, p = .02) on WC that was inconsistent with the dual-risk pattern. Findings indicate that neighborhood and genetic factors dually influence metabolic risk and that these relations may be complex and warrant further study. NCT01025726.

Comparing the Keyto App and Device with Weight Watchers' WW App for Weight Loss: Protocol for a Randomized Trial.

BackgroundObesity and being overweight are major contributing factors for many diseases. Calorie restricted diets often fail to result in sustained long-term weight loss. Very low–carbohydrate, high-fat ketogenic diets have been suggested to have superior metabolic and weight loss effects. Keyto is a low-cost, highly scalable mobile health (mHealth) app paired with a noninvasive biofeedback tool aimed at facilitating weight loss through a personalized healthy and predominantly plant- and fish-based ketogenic diet.ObjectiveThis protocol describes a randomized trial comparing the efficacy of the Keyto mHealth app and device intervention to that of Weight Watchers’ WW app in individuals who are overweight or obese. The primary outcome is weight loss after 12 weeks. Secondary and exploratory outcomes, including metabolic and cardiovascular risk factors, will be assessed at 12, 24, and 48 weeks.MethodsA total of 144 participants will be recruited and randomized to either the Keyto program or Weight Watchers program. Study participants will be guided through the study via video conference or phone calls and will undergo a fasting blood analysis performed by a third-party diagnostic lab at weeks 0 and 12 to assess metabolic and cardiovascular risk markers. All participants will be asked to weigh themselves daily on a study-provided Bluetooth-enabled scale. Participants randomized to the Keyto arm will also be asked to measure their breath acetone levels, a measure of ketosis, with the Keyto device 3 times per day.ResultsRecruitment started in December 2019. Rolling recruitment is expected to be completed by July 2020. Data collection and analysis of the primary intervention phase is expected to be completed in October 2020. The 24- and 48-week follow-ups are expected to be completed in January 2021 and July 2021, respectively.ConclusionsThis trial will provide high-quality evidence regarding the efficacy of the Keyto weight loss program in individuals who are overweight and obese in a free-living condition. This study also fills a gap by examining the impact of a ketogenic diet emphasizing plant- and fish-based fats on blood lipid profile and cardiovascular disease risk.Trial RegistrationClinicalTrials.gov NCT04165707; https://clinicaltrials.gov/ct2/show/NCT04165707.International Registered Report Identifier (IRRID)DERR1-10.2196/19053

Impaired CPT1A Gene Expression Response to Retinoic Acid Treatment in Human PBMC as Predictor of Metabolic Risk.

Ex vivo human peripheral blood mononuclear cell (PBMC) systems offer the possibility to test transcriptomic effects of food bioactive compounds with potential health effects. We investigated all-trans retinoic acid (ATRA) effect on mRNA expression of key lipid metabolism and inflammatory genes in PBMCs from normal-weight (NW) and overweight-obese (OW-OB) men with different metabolic syndrome-related features. PBMCs were incubated with 10 µM ATRA and mRNA levels of selected genes were analyzed using real-time RT-qPCR. Human ex vivo PBMCs responded to ATRA treatment, but the response for some genes was dependent on body mass index (BMI), with a lower response in PBMC from OW-OB than from NW donors. Moreover, gene expression response was affected by circulating high-density lipoprotein (HDL)-cholesterol levels. Particularly, the response to ATRA of CPT1A, previously reported as a sensitive metabolic risk predictive biomarker, was dependent on HDL levels and not on BMI, being impaired in those individuals with lower HDL levels, specifically in OW-OB. Thus, PBMCs’ insensitivity to ATRA, which can be considered as indicative of impaired metabolism, was observed in individuals with higher metabolic risk (OW-OB with low HDL levels). In conclusion, an ex vivo human PBMC system indicates that ATRA response could be influenced by metabolic syndrome features. Moreover, our study reinforces the role of CPT1A as a marker of metabolic risk and points to plasmatic HDL-cholesterol levels as a parameter to take into consideration when the effects of nutritional factors and/or dietary interventions on humans are under study. Further studies including women are required to detect potential gender differences in the observed effects.

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery

Background and aimsComputed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. Methods and resultsWe examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). ConclusionHigher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. Clinical trial registration numberNCT01373892.

POSSIBLE BENEFICIAL EFFECTS OF VITAMIN K AND OSTEOCALCIN ON GLUCOSE METABOLISM

The role of vitamin K, in bone metabolism and its effects on insulin resistance and Type-2 diabetes, have been discussed. The mechanism of vitamin K’s beneficial effect on insulin sensitivity and glucose homeostasis is not yet known. Various biological active molecules such as adiponectin, leptin, and resistin, which is secreted from adipose tissue and have important roles in glu- cose metabolism, have been proposed to regulate bone metabolism. Some studies have suggested that bone metabolism is also effective on adipose tissue and energy metabolism. It is thought that osteocalcin, a vitamin K dependent protein is effective in glucose metabolism. The role of Vitamin K in glucose metabolism is thought to be partly due to the modulation of diabetes-re- lated cytokines and other metabolic risk markers, as inflammation lies at the bottom of chronic metabolic diseases. The aim of this review is to explain the effect of Vitamin K and osteocalcin on glucose metabolism and its possible mechanisms of action.

1269-P: A Prospective, Population-Based Study of Hypothalamic Gliosis, Obesity, and Weight Gain in Children

Hypothalamic gliosis is a cellular response that, in rodents, is necessary for weight gain and diet-induced obesity. Whether this inflammatory process in the mediobasal hypothalamus (MBH) plays a role in common obesity or change in weight status during growth and development in children is uncertain. Using T2-weighted MRI scans from a longitudinal population-based sample of young children, we measured signal ratios to evaluate evidence of MBH gliosis in relation to obesity and adiposity change over time. We included 169 children from 6 sites recruited as part of the NIH Adolescent Brain Cognitive Development (ABCD) study. Baseline T2-weighted MRI scans were analyzed for evidence of MBH gliosis based on the T2 intensity of the mean bilateral MBH/Amygdala signal ratio. Putamen/Amygdala was used as the control ratio. Models were adjusted for site, age, and sex. At baseline, mean age was 9.9 ± 0.6 y, 50% were female, and 64% were pre-pubertal. Mean BMI z-score was 0.77 ± 1.02 [23% with overweight (OV) and 21% with obesity (OB)]. At 1y assessments (10.8 mo. on average), mean ΔBMI z-score was 0.02 ± 0.36. MBH/Amygdala ratio was positively associated with BMI z-score (r=0.32, P&amp;lt;0.001) and waist/height ratio (r=0.26, P&amp;lt;0.001), a marker of metabolic risk, whereas the control ratio was not (r=-0.02, P=0.52 and r=-0.05, P=0.76). Overall, MBH/Amygdala ratio was not associated with ΔBMI z-score (r=-0.02, P=0.49), but a significant interaction [F(5,158)=5.16; P&amp;lt;0.001] indicated the relationship varied by group. Among children with OV, baseline MBH/Amygdala ratio positively correlated with ΔBMI z-score (r=0.43, P=0.01); this relationship was attenuated in children with OB (r=0.19, P=0.18) and absent among participants of normal weight (r=-0.07, P=0.36). In conclusion, we found evidence that MBH gliosis is associated with excess adiposity in a large pediatric population. In children at risk for obesity, MBH gliosis may be an important predictor of increasing adiposity and metabolic risk. Disclosure L.E. Sewaybricker: None. S.J. Melhorn: None. E. Schur: None. Funding National Institutes of Health (R01DK117623, U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, U01DA041025)

Maternal prolactin is associated with glucose status and PCOS in pregnancy: Odense Child Cohort.

Low circulating prolactin is a potential marker of metabolic risk during pregnancy. We aimed to investigate associations between prolactin and glucose status in pregnant women with and without gestational diabetes mellitus (GDM) or polycystic ovary syndrome (PCOS). Prospective observational cohort study. From the Odense Child Cohort, 1497 pregnant women were included. Blood samples were assessed during first, second (prolactin, hemoglobin A1c (HbA1c)) and third trimester (fasting prolactin, testosterone, HbA1c, insulin, glucose). Oral glucose tolerance test (OGTT) was performed around gestation week 28 in 350 women with risk factors for GDM and in 272 randomly included women. GDM was defined by 2-h plasma glucose ≥9.0 mmol/L. The median (IQR) prolactin increased from 633 (451-829) mIU/L in first-second trimester to 5223 (4151-6127) mIU/L at third trimester. Prolactin was inversely associated with HbA1c in first (r = -0.19, P < 0.001) and third trimester (r = -0.07, P = 0.014). In third trimester, women with GDM (n = 37; 6.0%) had lower prolactin compared to women without GDM (4269 vs 5072 mIU/L, P = 0.004). Third trimester prolactin multiple of the median (MoM) was inversely associated with risk of GDM in multivariate regression analysis (OR 0.30, P = 0.034). PCOS was diagnosed in 10.0% (n = 146). Early pregnancy prolactin MoM was positively associated to PCOS diagnosis (OR 1.38, P = 0.051). Low prolactin levels during pregnancy were associated with higher HbA1c and risk of GDM. A diagnosis of PCOS was associated with higher early pregnancy prolactin levels.

0131 Decreased Habitual Sleep Efficiency is Associated with Increased Insulin Resistance in Healthy Adult Men

Abstract Introduction Partial sleep deprivation is associated with increased insulin resistance (IR), a metabolic disease risk marker. Little is known about habitual sleep patterns and IR in the absence of acute sleep restriction. We anticipated greater change in habitual sleep over one month would be associated with increased IR. Methods 24 males (age=33.6±6.4 years; BMI=25.7±2.5kg/m2) completed baseline (T1) and follow-up (T2; ≥4 weeks post-T1) study procedures: actigraphy (one week) followed by polysomnography (PSG; one 10h sleep opportunity) and a next morning oral glucose tolerance test (OGTT; homeostatic model assessment insulin resistance [HOMA-IR], β-cell function [HOMA-β], and Matsuda Index). Weekly average actigraphy total sleep time (aTST; 291-511min) and sleep efficiency (aSE; 72–93%) were computed at T1 and T2, as well as across the 1, 2, and 3 days prior to PSG/OGTT. Pearson and Spearman correlations assessed the change (T1-T2) in actigraphy (aSEΔ, aTSTΔ, PSGΔ) or PSG sleep (PSG-TSTΔ, PSG-SEΔ, sleep stages) versus change in metabolic risk (HOMA-IRΔ, HOMA-βΔ, MatsudaΔ). Results There were significant correlations between HOMA-IRΔ and aSEΔ [r(22)=-0.42, p=0.01; rs=-0.45, p=0.03], PSG TSTΔ [r(22)=0.50, p=0.012; rs=0.41, p=.045], and PSG-SEΔ [r(22)=0.49, p=0.015; rs=0.43, p=.037]. No significant associations emerged between change in metabolic risk versus aTSTΔ one week prior to PSG/OGTT, aSEΔ or aTSTΔ across 1–3 days prior to PSG/OGTT, or PSG sleep stages. Conclusion Within-subject T1-T2 decrease in habitual sleep quality, but not TST, was associated with increased IR. T1-T2 PSG TST and SE were associated with following day IR. At home sleep 1–3 days beforehand were not correlated with IR. Although preceding night sleep quality and TST are associated with IR, habitual sleep quality, rather than TST, may be a more important determinant of metabolic risk in community dwelling middle-aged men. Support This work was supported by NIH/NHLBI R01HL124211, NIH/NHLBI K24HL138632, NIH National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant UL1TR001881 (PI: Liu); and NIH/NHLBI K24HL143055 (PI: Martin). Dr. Kelly is supported by the VA Office of Academic Affiliations through the Advanced Fellowship Programs in Geriatrics.

Gut Bacterial Families Are Associated with Body Composition and Metabolic Risk Markers in School-Aged Children in Rural Mexico.

Background: Differences in gut microbiota composition have been associated with obesity and metabolic alterations in children. The aim of this study was to analyze the abundance of the main bacterial families of the gut among children according to their body composition and metabolic markers. Methods: A cross-sectional study was conducted with 93 school-aged children (8.4 ± 1.6 years old). Anthropometric and body composition variables were measured and a blood sample was collected to determine glucose, insulin, lipid profile, C-reactive protein, leptin, and cytokines [interleukin 6, interleukin 10 (IL-10), tumor necrosis factor α (TNFα)]. DNA was extracted from stool samples and the abundance of bacterial families (Bacteroidaceae-Porphyromonadaceae-Prevotellaceae, Lactobacillaceae, Enterococcaceae, and Lachnospiraceae-Ruminococcaceae) was determined by qPCR assays. Results: Children with obesity and high waist/height ratio had lower Bacteroidaceae-Porphyromonadaceae-Prevotellaceae and higher abundance of Lactobacillaceae when compared with normal-weight children. TNFα was negatively associated and IL-10 was positively associated with Bacteroidaceae-Porphyromonadaceae-Prevotellaceae. Triglycerides showed a positive relationship with Lachnospiraceae-Ruminococcaceae whereas high-density lipoprotein-cholesterol was negatively associated with Lactobacillaceae. Conclusion: In rural Mexican school-aged children, a low abundance of Bacteroidaceae-Porphyromonadaceae-Prevotellaceae and a high abundance of Lactobacillaceae are associated with obesity and metabolic disturbances.

SUN-LB113 A Continuous Remote Care Intervention Utilizing Carbohydrate Restriction Including Nutritional Ketosis Improves Markers of Metabolic Risk and Reduces Diabetes Medication Use in Patients With Type 2 Diabetes Over 3.5 Years

Novel lifestyle, pharmaceutical, and/or surgical therapies for type 2 diabetes (T2D) are under study to assess lasting impact on metabolic risk. Among them, carbohydrate restriction including nutritional ketosis (CR) has emerged as a safe and effective nutrition therapy for reducing hyperglycemia in patients with T2D1, yet longer term effects are unknown. At the conclusion of a 2-year study assessing a continuous remote care intervention utilizing CR (CCI) among patients who selected this therapy, intervention participants were offered the opportunity to consent to participate in a 3-year extension assessing outcomes at 3.5- and 5-y following initial enrollment. 143 of 169 extension-consented participants provided data at 3.5-y follow up. Among 3.5-y completers, linear mixed effects models were used to assess change over time in diabetes-related outcomes and McNemar’s tests were used to assess for a difference in the proportion of participants meeting certain criteria at baseline compared to follow-up. At enrollment, 3.5-y completers were (mean±SE) 55±1 y of age, 40.8±0.7 kg/m2, and 8±1 y since diagnosis. Following treatment with the CCI for 3.5 y, significant improvements compared to baseline were observed in HbA1c (-0.6±0.1 from 7.4±0.1%; P = 1.9x10-5), weight (-10.9±1.1 from 117.4 kg; P = 6.9x10-17), nonHDL-C (-10±4 from 139±3 mg/dL; P = 0.005), triglycerides (-41±11 from 189±10 mg/dl; P = 2.1x10-4), and HDL-C (+9±1 from 43±1 mg/dl; P = 3.0x10-11); total cholesterol and LDL-C were statistically unchanged. The percentage of participants prescribed diabetes medication decreased from 84.6 to 67.1% (P = 5.0x10-6), while 50.2% of diabetes medications and 71.4% of diabetes medications other than metformin were discontinued. The percentage of participants treated with no pharmaceuticals or monotherapy increased from 52.5 to 81.9% (P = 1.3x10-8). 45.5% (65/143) of participants achieved HbA1c <6.5% with either no medication (34/65, 52%) or only metformin (31/65, 48%) at 3.5 y; 37.8% of participants maintained this status from 1 through 3.5 y of treatment. 22% of participants achieved diabetes remission at 3.5 y, and 17.5% of participants maintained remission status from 2 through 3.5 y of treatment. This demonstrates that clinically meaningful improvements across multiple markers of metabolic risk can be sustained in patients with T2D who selected treatment with this CCI for 3.5 y. Improvements in metabolic risk markers reduced the need for diabetes medication, allowing some patients to achieve and sustain diabetes remission. This ongoing trial will assess 5-y effects.1. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care. 2020; 43(Supplement 1): S48-S65. 2. Athinarayanan SJ, et al. Front Endocrinol. 2019; 10:348.

MON-040 11-Oxygenated C19 Steroids in Polycystic Ovarian Syndrome

BACKGROUND: Polycystic ovarian syndrome (PCOS), an endocrine and reproductive disorder consisting of hyperandrogenism, menstrual dysfunction and ovarian changes, affects 6–20% of reproductive aged women worldwide. While hyperandrogenemia is traditionally determined by evidence of elevated testosterone (T), this hormone can be difficult to accurately measure in women with relatively lower circulating levels compared to men. Recent studies have suggested that four adrenal androgens known as 11-oxygenated C19 steroids (11OxyAs), specifically 11-ketotestosterone (11KT), may be good alternative markers for hyperandrogenism in PCOS. Using a multiethnic population seeking evaluation for PCOS symptomatology, we sought (1) to investigate the utility of 11OxyAs to differentiate women with and without NIH PCOS relative to classical androgens such as T, androstenedione (A4) and DHEAS levels, and (2) to evaluate the relationship of 11OxyAs to clinical findings of androgen excess. Methods: Using the University of California, San Francisco PCOS Tissue Bank, serum samples from 131 women seen for a PCOS evaluation were selected sequentially and identified as PCOS or non-PCOS (controls) based on meeting NIH criteria at the time of evaluation. In addition to obtaining gonadotropin and metabolic profiles, classical androgens and 11OxyAs were measured using mass spectrometry. The relationship of these androgens to modified Ferriman-Gallwey (mFG) scores and ovarian morphology were also assessed. Results: Out of 131 women selected, 83 met NIH PCOS criteria at the time of evaluation and 48 did not (controls). Age and BMI did not differ among the two groups. As expected, total T, A4 and LH were all significantly higher in NIH PCOS. A trend towards higher HOMA-IR levels was also seen in NIH PCOS, but this did not reach statistical significance (3±3.9 mg/dL vs. 1.9±1.7 mg/dL, p = 0.12). No difference was seen in all four 11OxyAs between NIH PCOS and controls. Unlike previous studies, we also did not find mean 11KT levels to exceed that of T in both controls (T 393±143 pg/mL vs. 11KT 389±206 pg/mL) and PCOS (T 530±245 pg/mL vs. 11KT 388±201 pg/mL). In addition, no relationship was seen between HOMA-IR and 11β-hydroxyandrostenedione (11OHA4) or 11-ketoandrostenedione (11KA4) levels. Within PCOS, DHEAS and A4 were noted to have a weak but inverse relationship to BMI (r2 0.05 p = 0.05; r2 0.08 p = 0.007), whereas no correlation was seen between any of the four 11OxyAs or T and BMI. Lastly, 11OxyAs, T, and A4 levels did not predict mFG scores or polycystic ovarian morphology. Conclusions: 11OxyAs levels were not statistically higher among women with NIH PCOS compared to at risk women who did not meet NIH criteria. There was no significant relationship between these androgens and mFG scores or ovarian morphology. Further studies are necessary to show the utility of 11OxyAs levels as a marker for hyperandrogenism or metabolic risk.