Fasting Serum Glucose Research Articles

INFLUENCE OF FERMENTED MELON SEED (OGIRI) PROTEIN ISOLATE ON POSTPRANDIAL BLOOD GLUCOSE LEVELS IN DIABETIC RATS

ABSTRACT Abstract Introduction Diabetes mellitus is a prevalent endocrine disorder affecting millions worldwide, characterized by chronic hyperglycemia and associated with serious complications. Aim This study aimed to evaluate the anti-diabetic properties of Ogiri Protein Isolate (OPI) derived from fermented melon seeds (Citrullus vulgaris) and its effects on blood glucose levels, lipid profiles, and key organs in alloxan-induced diabetic rats. Methods Forty-two rats were divided into seven groups: positive control, negative control, diabetic group treated with 20% OPI, non-diabetic group treated with 20% OPI, diabetic group treated with 10% OPI, non-diabetic group treated with 10% OPI, and diabetic group treated with 80mg/kg Glibenclamide for 14 days. Fasting serum glucose levels, feed and water intake, weight gain, and plasma HDL-cholesterol and triglyceride levels were measured. Results OPI treatment significantly reduced fasting serum glucose levels in diabetic rats. There was a significant (p<0.05) decrease in feed and water intake in treated groups. Weight gain improved in OPI-treated diabetic rats compared to untreated diabetic rats. Plasma HDL-cholesterol levels increased significantly in all treated groups compared to the control, with the highest levels in non-diabetic and untreated groups. Similar trends were observed in plasma and liver triglycerides. Conclusion The findings suggest that OPI possesses anti-diabetic properties, significantly lowering blood glucose levels and improving lipid profiles in diabetic rats. OPI holds promise as a potential therapeutic agent for diabetes management. Further research is needed to validate these results in human studies. Keywords: Ogiri Protein Isolate (OPI), anti-diabetic, Diabetes mellitus, Postprandial blood glucose and Alloxan.

Prevalence of chronic kidney disease and associated risk factors among people living with HIV in a rural population of Limpopo Province, South Africa.

Limited evidence informs on the prevalence of chronic kidney disease (CKD) in people living with HIV (PLWH) in South Africa. Thus, this study aimed to determine the prevalence of CKD and its associated risk factors among PLWH within the rural province of Limpopo, South Africa. We conducted a cross-sectional study of 143 participants, subdivided into groups of PLWH (n = 103) and individuals without HIV (n = 43). Structured questionnaires were used to collect and capture sociodemographic information including age, sex, alcohol intake, smoking status, and educational status. Basic measurements taken included levels of cluster of differentiation 4 (CD4+) count, body mass index (BMI), blood pressure, plasma cystatin C, and fasting serum glucose levels. Plasma cystatin C-based estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) estimator to determine the prevalence of CKD. The prevalence of CKD was approximately 7% in PLWH. Multivariate logistic regression analysis showed that it was only diabetes mellitus (odds ratio of 5.795, 95% confidence interval, p = 0.034) and age (odds ratio of 1.078, 95% confidence interval, p = 0.039) that were significantly associated with CKD in PLWH. Chronic kidney disease was prevalent in PLWH, and it was further associated with cardiovascular risk factors, diabetes, and ageing. As PLWH age, the burden of CKD may be increased with the increase in cardiovascular-related comorbidities such as diabetes.

Opuntia humifusa stems rich in quercetin and isorhamnetin alleviate insulin resistance in high-fat diet-fed rats.

Obesity, characterized by abnormal fat accumulation and metabolic disturbances, presents a significant health challenge. Opuntia humifusa Raf., commonly known as Korean Cheonnyuncho, is rich in various beneficial compounds and has demonstrated antioxidant and anti-inflammatory effects. However, its potential impact on glucose and lipid metabolism, particularly in obese rats, remains unexplored. We aimed to investigate whether O. humifusa stems and fruits could beneficially alter glucose metabolism and lipid profiles in a rat model of high-fat diet (HFD)-induced obesity. Thirty-two rats were allocated into 4 groups: normal diet (NF), HFD control (HF), HFD treated with 2% O. humifusa stems (HF-OS), and HFD treated with 2% O. humifusa fruits (HF-OF). Experimental diets were administered for 6 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. The major flavonoid from O. humifusa stems and fruits was identified and quantified. After 6 weeks of treatment, the serum fasting glucose concentration in the HF-OS group was significantly lower than that in the HF group. Serum fasting insulin concentrations in both HF-OS and HF-OF groups tended to be lower than those in the HF group, indicating a significant improvement in insulin sensitivity in the HF-OS group. Additionally, the HF-OS group exhibited a tendency towards the restoration of adiponectin levels to that of the NF group. The 2% O. humifusa stems contain abundant quercetin and isorhamnetin, which alter fasting blood glucose levels in rats fed a HFD, leading to a favorable improvement in insulin resistance.

Characterization of the oxidative stress and inflammatory markers in metabolically healthy obese individuals

Introduction and Objectives:
 Obesity has emerged as a global health problem. Although various studies have linked obesity to a wide spectrum of diseases mainly diabetes and cardiovascular disease, little is known concerning involvement of oxidative stress and inflammation in non-diseased conditions. The current study aims to explore the feasibility of inflammatory markers and oxidative stress markers in sera of metabolically healthy obese individuals. 
 Methods:
 The current study involved one hundred healthy participants. Following obtaining relevant clinical data, sera were taken for further laboratory investigations including lipid profile, fasting serum glucose and HbA1c. Samples were also investigated for determining inflammatory and oxidative stress markers including highly sensitive C - reactive protein (hs-CRP), malondialdehyde (MDA) and gamma glutamyl transferase (GGT).
 Results: 
 Total cholesterol, triglyceride and fasting blood glucose levels were statistically significantly higher in study group compared to controls (p < 0.0001, 0.009 and < 0.0001 respectively). The hs-CRP, MDA and GGT were also statistically significantly higher in healthy obese (p < 0.001, 0.005 and 0.001 respectively). Moreover, MDA was positively correlated with GGT and was statistically significant (p < 0.001). 
 Conclusion:
 The obtained findings suggest that, there may be an existence of a low grade chronic inflammation consistent with oxidative stress which might be considered as a risk factor for developing metabolic diseases and cardiovascular disturbances mainly diabetes mellitus, hypertension and stroke.

Assessment of Serum Caspase-1, IL-10, and IL-18 Levels in Baghdad's Medical City in Women with Polycystic Ovary

Background: Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women. Caspase-1 is implicated in several important inflammatory diseases and controls adipocyte differentiation and insulin sensitivity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and plays an important role in chronic inflammatory conditions. This study was planned to investigate the association between insulin resistance in (PCOS) and serum levels of caspase-1, IL-10, and IL-18. Methods: Fifty women with PCOS and forty healthy controls were evaluated in this controlled clinical study. Caspase-1 and IL-18, IL-10 levels, serum lipid sub-fractions, fasting glucose, fasting insulin, and other hormone levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Results: Regarding levels of obesity, the BMI of patients and controls was significantly different . The tests of insulin, fasting glucose, HOMA, testosterone, progesterone, prolactin, LH, estradiol, SHBG, cholesterol, triglycerides, LDL, HDL, and VLDL all showed statistically significant changes. Research participants' serum FSH levels were greater than controls, but this difference was statistically insignificant. There was a highly significant difference in IL 10 and IL 18 levels. Additionally, PCOS patients had considerably greater Caspase-1 levels than controls. A significant positive link between age and caspase-1 , a significant positive relationship between BMI and IL-18 , and a significant positive relationship between IL-10 and VLDL levels . Conclusion: There was an association between caspas-1, IL-10, IL-18 and polycystic ovary syndrome-related insulin resistance. Many recent proteins and interleukins are now considered potential new markers of insulin resistance in diagnostic and therapeutic polycystic ovary syndrome.

The Effects of Resveratrol Supplementation on the Quality of Life of Diabetic Patients with Neuropathy: Small Randomized Clinical Trial

The diabetic neuropathy complication exerts a considerable decline in the level of patient’s well-being. The main approaches to hamper the progression of diabetic complications and improve patient’s life quality are controlling the glycemic levels and amelioration of the hyperglycemia-induced neuroinflammation, oxidative stress and pain. Supplementation of appropriate anti-inflammatory and anti-oxidants such as resveratrol may therefore be effective in the management of diabetic complications. The aim of this trial was to assess resveratrol’s impact on improving life quality of patients with the neuropathic complication of diabetes. Sixty-one patients with diabetic neuropathy were recruited in this double-blinded placebo-controlled trial. Patients were randomized into the resveratrol (n=31) group; who received a 500mg resveratrol capsule once daily concomitantly with the conventional hypoglycemic agents for three months, and the placebo (n=30) group. From each group 25 patients completed the study. The quality of life (QoL) of the patients was estimated utilizing RAND 36-item survey questionnaire. Fasting blood glucose levels were analyzed at the baseline and on the last day of the 3rd month. There was a significant decrement (p< 0.001) in the fasting serum glucose level of the patients supplemented with resveratrol at the end of the 3rd month, in comparison with the patient using the placebo. There was also a significant improvement in patient’s severity of pain (p<0.001) as shown in the bodily pain score of the RAND 36 scale and a remarkable (p < 0.05) improvement in physical functioning, physical health, social functioning, emotional well-being, energy/fatigue, and health change subscales of the questionnaire. The study concluded that resveratrol is the polyphenol that has a positive effect on reducing pain associated with diabetic neuropathy and improving the overall QoL of the patient.

Consuming Mushrooms When Adopting a Healthy Mediterranean-Style Dietary Pattern Does Not Influence Short-Term Changes of Most Cardiometabolic Disease Risk Factors in Healthy Middle-Aged and Older Adults

BackgroundMushrooms are a nutritious food, though knowledge of the effects of mushroom consumption on cardiometabolic risk factors is limited and inconsistent. ObjectiveWe assessed the effects of consuming mushrooms as part of a healthy United States Mediterranean-style dietary pattern (MED) on traditional and emerging cardiometabolic disease (CMD) risk factors. We hypothesized that adopting a MED diet with mushrooms would lead to greater improvements in multiple CMD risk factors. MethodsUsing a randomized, parallel study design, 60 adults (36 females, 24 males; aged 46 ± 12 y; body mass index 28.3 ± 2.84 kg/m2, mean ± standard deviation) without diagnosed CMD morbidities consumed a MED diet (all foods provided) without (control with breadcrumbs) or with 84 g/d of Agaricus bisporus (White Button, 4 d/wk) and Pleurotus ostreatus (Oyster, 3 d/wk) mushrooms for 8 wk. Fasting baseline and postintervention outcome measurements were traditional CMD risk factors, including blood pressure and fasting serum lipids, lipoproteins, glucose, and insulin. Exploratory CMD-related outcomes included lipoprotein particle sizes and indexes of inflammation. ResultsAdopting the MED-mushroom diet compared with the MED-control diet without mushrooms improved fasting serum glucose (change from baseline −2.9 ± 1.18 compared with 0.6 ± 1.10 mg/dL; time × group P = 0.034). Adopting the MED diet, independent of mushroom consumption, reduced serum total cholesterol (−10.2 ± 3.77 mg/dL; time P = 0.0001). Concomitantly, there was a reduction in high-density lipoprotein (HDL) cholesterol, buoyant HDL2b, and apolipoprotein A1, and an increase in lipoprotein(a) concentrations (main effect of time P < 0.05 for all). There were no changes in other measured CMD risk factors. ConclusionsConsuming a Mediterranean-style healthy dietary pattern with 1 serving/d of whole Agaricus bisporus and Pleurotus ostreatus mushrooms improved fasting serum glucose but did not influence other established or emerging CMD risk factors among middle-aged and older adults classified as overweight or obese but with clinically normal cardiometabolic health. Trial registration numberhttps://www.clinicaltrials.gov/study/NCT04259229?term=NCT04259229&rank=1

Cardiometabolic-related dietary patterns and thyroid function: a population-based cross-sectional study

BackgroundLittle is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function.MethodsThis cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively.ResultsThe two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function.ConclusionsA diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.

Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

An Assessment of Heme Oxygenase-1 and Glutathione-S-transferase in Obese Iraqi Patients

This study aimed to detect the relation of Heme oxygenase-1(HO-1) and Glutathione-S-transferase (GST) in obese patients, against oxidative stress. The study included 139 samples of people with age range of 35-65 years divided in two groups according gender (female and male) groups while four gropes according body mass index (BMI). Blood samples were collected from AL-Yarmouk Hospital at the period between September/2022 to January/2023. Some biochemical parameters were measured for all study groups, which include: -determination of serum HO-1 levels by using the ELISA-technique, lipid profile, GST activity, and fasting serum glucose (FSG) assessed manual. The BMI, waist hip ratio(WHR) and low density lipoprotein (LDL) were found to be significant [(38.83±0.44b) (32.03±0.26a) (26.40±0.22d) (23.10±0.28c)],,[(1.01±0.03b) (0.92±0.02ab) (0.93±0.01ab) (0.88±0.01a)] ,[(80,42±7.47a) (99.74±6.63ab) (112.93±10.12b) (83.94±8.95ab)] respectively and not significant with other parameters of lipid profile, FSG, and Atherogenic index. Also, it appeared that the HO-1 levels were higher in obese groups compared with healthy groups [(2.06 ± 0.09b)(1.95 ± 0.04ab) (1.88 ± 0.04ab)(1.75 ± 0.05a)] ng/ml respectively . It was shown that the increasing of GST level in healthy compared with obese groups [(6.10± 0.57c)(4.120 ± 0.69b)(2.44 ± 0.21a)(2.71± 0.30ab)]IU/L respectively .The result showed that the increase in BMI,WHR and HO-1 in obese female and BMI,TG,HO-1 and VLDL in obese male ,compared with female and male healthy groups ,while the results showed an increase in GST levels in healthy female and male groups .We conclude from this study that high levels of heme oxygen-1 synchronized with low of glutathione-S- transferase , clearly indicating their primary role in detoxification, protection of the against oxidative stress, and prevention of the development of metabolic diseases.

Cardiac and Metabolic Effects of Bariatric Surgery Among Obese Patients in a Malaysian Tertiary Hospital: A 6-month Prospective Cohort Study.

Obesity is known to be associated with left ventricular diastolic dysfunction due to its effect on blood pressure and glucose tolerance. We aimed to investigate whether weight loss after bariatric surgery might improve diastolic dysfunction through in-depth echocardiographic examination. We recruited twenty-eight patients who were about to undergo bariatric surgery by purposive sampling. They underwent echocardiography at baseline and 6 months after surgery with a focus on diastolic function measurements and global longitudinal strain (GLS). They also had fasting serum lipid and glucose measurements pre- and post-surgery. The mean weight loss after surgery was 24.1 kg. Out of the 28 subjects, fifteen (54%) initially had diastolic dysfunction before surgery. Only two had persistent diastolic dysfunction 6 months after surgery. The mean indexed left atrial volume 6 months post-surgery was 27.1 from 32 ml/m2 prior to surgery. The average E/e' is 11.78 post-surgery from 13.43 pre-surgery. The left ventricular GLS became (-)25.7% after surgery from (-)21.2% prior to surgery. Their post-surgery fasting serum lipid and glucose levels also showed significant improvement. Our study reinforced the existing evidence that bariatric surgery significantly improved echocardiographic parameters of diastolic function and left ventricular global longitudinal strain, along with various metabolic profiles.

Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study.

Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. Obesity (body mass index ≥ 30kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. Analyses with exposures measured < 60, 60 to < 70, and ≥ 70years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2years respectively. In analyses of individual components, obesity before 60years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70years or ≥ 70years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70years.

Abstract 13255: Cardiac and Generalized SGLT2 Deficiency Does Not Protect Against Development of Heart Failure With Reduced Ejection Fraction in Mice

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally designed for the treatment of diabetes, exert profound cardiovascular benefit and are now the standard-of-care in all forms of heart failure (HF). The mechanism of their benefit in HF is unknown. We hypothesized SGLT2i act via an on-target, extra-cardiac mechanism to promote ketosis and improve myocardial energetics. Generalized- (gKO) and cardiac-specific (csKO) SGLT2 knockout mice were generated by breeding SGLT2 floxed mice with EIIa or αMHC Cre recombinase lines, respectively. While csKO grew and developed normally, gKO mice were slightly smaller compared to WT littermates. There was no baseline cardiac phenotype in either group. The gKO mice exhibited profound glucosuria, decreased fasting serum glucose and augmented fasting ketosis compared to controls, and comparable in magnitude to the metabolic effects of 14 days of treatment with empagliflozin (Empa, 50mg/kg/day orally) in WT mice. Targeted metabolomic analysis of gKO and Empa-treated WT mice identified increased circulating and myocardial levels of the ketone body 3-hydroxybutyrate (1.9-2.3x, p&lt;0.01), along with an increase in a subset of tricarboxylic acid cycle intermediates and C4-OH, a ketone oxidation by-product. Empa treatment in WT mice following trans-aortic constriction with apical myocardial infarction (TAC/MI) improved LV dysfunction and pathological remodeling at 6 weeks (left ventricular ejection fraction (EF) 36±6 vs 28±9, p&lt;0.03; tibia length-normalized biventricular weight 9.6±0.4 vs 11.3±1.6, p&lt;0.001). In contrast, csKO and gKO mice subjected to TAC/MI had no difference in EF, strain, ventricular hypertrophy or dilation compared to WT controls. In conclusion, generalized SGLT2 deficiency phenocopies the metabolic effects of SGLT2i treatment but neither gKO nor csKO afford cardiac protection in an established HF model. These results suggest an off-target mechanism for beneficial effects of SGLT2i in HF.

Association between urinary fluoride concentrations and the prevalence of metabolic syndrome in adult individuals from the Central Region of Mexico

ABSTRACT Emerging scientific studies have supported the hypothesis that exposure to environmental chemicals increases the incidence of diverse human metabolic disorders. Therefore, this study aimed to evaluate the association between fluoride exposure and metabolic syndrome (MetS) prevalence in people from the Central Region of Mexico. This research included 575 adult individuals. Urinary fluoride concentrations were determined using a potentiometric method. Anthropometric measurements and blood pressure were also acquired. Serum fasting glucose and lipid levels were quantified. For the MetS screening, we used the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The mean urinary fluoride levels were 3.50 ± 2.50 mg/L. The prevalence of MetS was approximately 27 and 25% according to NCEP ATP III and IDF criteria, respectively. A multivariate logistic regression analysis showed significant associations (p < 0.05) between urinary fluoride concentrations and MetS occurrence using NCEP ATP III criteria (OR = 1.60; 95% CI 1.05–2.10) and IDF criteria (OR = 1.35; 95% CI 0.95–1.45). These findings emphasize the need to discover the underlying mechanisms that fluoride exposure has on MetS pathogenesis.

The evaluation of fetal interventricular septum with M-mode and spectral tissue Doppler imaging in gestational diabetes mellitus: a case-control study.

To demonstrate possible functional changes in the frequently affected fetal interventricular septum (IVS) with spectral tissue Doppler imaging (TDI) and M-mode imaging to compare gestational diabetes mellitus (GDM) and control groups. A total of 63 pregnant women with GDM, 30 on diet (A1 GDM) and 33 on treated with insulin (A2 GDM), and 63 healthy pregnant women randomly selected and matched to the case group in the control group were included. The GDM fetuses had significantly thickened IVS, increased early diastole (E'), atrial contraction (A'), systole (S'), higher myocardial performance index (MPI'), prolonged isovolumetric relaxation time (IVRT'), shortened ejection time (ET'), and decreased septal annular plane systolic excursion (SAPSE) than the controls. The A2 GDM group fetuses had significantly thickened IVS, increased S' and shortened ET' than the A1 GDM group. In the GDM group, we found a significantly positive low correlation between glycated hemoglobin levels and maternal serum fasting glucose and one-hour postprandial glucose with fetal IVS thickness. We demonstrated a significantly negative low correlation between maternal serum one-hour postprandial glucose, glycated hemoglobin levels, and gestational weight gain with fetal IVS ET'. Fetal IVS diastolic and systolic functions were altered in the GDM group compared to controls, and systolic functions were altered in A2 GDM compared to A1 GDM. This may alert clinicians to possible cardiovascular diseases in the postnatal life, and early preventive strategies and long-term lifestyle changes may provide protection in fetuses with GDM.

A low-carbohydrate diet with different fatty acids' sources in the treatment of obesity: Impact on insulin resistance and adipogenesis

The search for nutritional intervention strategies against obesity has grown, highlighting the low-carbohydrate diet model. However, little is known about the impact of the quality of fatty acids consumed in this diet. Thus, we aim to investigate the influence of fatty acid quality on dietary strategy on obesity. Male Swiss mice were diet-induced to obesity. Afterward, mice consume a low-carb diet with different types of fat: saturated, polyunsaturated ω-3, ω-6, and monounsaturated ω-9 fatty acids. Weight gain and food consumption were monitored weekly. An oral glucose tolerance test was performed and blood and tissue samples were collected for analysis of insulin resistance markers. Protein expression of insulin signaling pathway molecules, lipid metabolism, mitochondrial function, macrophage polarization, and cytokine production were analyzed. The high-fat diet was able to induce obesity and glucose intolerance. The switch to a low-carbohydrate dietary pattern reversed the glucose intolerance, with better results in the ω-3 and ω-9 groups. After the low-carbohydrate diet, groups ω-3 and ω-9 presented improved fasting serum glucose, insulin, and HOMA indexes. The low-carbohydrate dietalso increased the activity of insulin pathway proteins such as IR, IRS1, and AKT. Furthermore, the ω-3 diet group showed greater activity of mitochondrial complexes and AMPK signaling pathway proteins. The ω-6 and ω-9 -rich diet induced M2-type macrophage polarization, as well as cytokine production modulation by the low-carbohydrate diet in the ω-3 and ω-9 groups. Consuming a low-carbohydrate diet pattern promotes weight loss and improves glucose intolerance in obesity. Also, the quality of lipids has a direct influence, demonstrating that the consumption of ω-3 polyunsaturated and ω-9 monounsaturated lipids can lead to more favorable outcomes for the improvement of glucose intolerance, lipid metabolism, and anti-inflammatory effects.

Association of Parity With Insulin Resistance Early in Pregnant Women: ECLIPSES Study.

Little is known about whether parity is associated with elevated early-pregnancy insulin resistance (IR), or whether overweight/obesity contributes to increasing the possible effect. We determined the associations between parity and glucose metabolism parameters in the first trimester of pregnancy in a Mediterranean pregnant population, and whether these associations are affected by overweight/obesity. A cross-sectional study was conducted of 264 healthy pregnant women from the ECLIPSES study who were recruited at 12 weeks of gestation. At baseline, details on socioeconomic status, obstetric history (including parity, ie, number of births), lifestyle factors, anthropometry, and blood samples were collected. Fasting serum glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed in the first trimester. Elevated IR was defined as the upper HOMA-IR tertile (≥1.58). Multivariable linear regression and Cox regression model with constant time were performed. Parity ranged from 0 to 4. After multivariable adjustment, the insulin levels (β [% change]: 20.92; 95% CI, 4.08-37.71) and HOMA-IR index (β [% change]: 19.72; 95% CI, 2.43-40.49) were positively associated with parity. Additionally, multiparous women, as compared to nulliparous, were more likely to have higher HOMA-IR levels (primiparous [1 birth], β [% change[: 16.88; 95% CI, -1.00 to 37.99; multiparous [≥2 births), β [% change]: 32.18; 95% CI, 3.56-68.71), and an increased relative risk (RR) of an elevated IR (primiparous [1 birth], RR: 1.55; 95% CI, 1.03-2.36; multiparous (≥2 births), RR: 1.72; 95% CI, 1.05-2.83). The combination of multiparity and overweight/obesity conferred a 3.04-fold increase in the RR of elevated IR, which increased proportionally to the number of parities. This study demonstrates that parity may have a negative effect on early-pregnancy IR and that maternal overweight/obesity appears to further aggravate this relationship.

Mediators of the Effect of Obesity on Stroke and Heart Disease Risk: Decomposing Direct and Indirect Effects.

The prevalence of overweight and obesity are well known risk factors of atherosclerotic cardiovascular disease (ASCVD). We aimed to examine the association between body mass index (BMI) and ASCVD over a 23-year follow-up in young adults. We also qualified how much of the effects of obesity on ASCVD were mediated through blood pressure, cholesterol, and glucose. Data are from the Korean Life Course Health Study, a cohort study of 226,955 Korean young adults aged 20-39. At baseline, the participants undertook routine health assessments where their BMI was measured in 1992-1994; and the metabolic mediators including systolic blood pressure (SBP), fasting serum glucose (FSG), and total cholesterol (TC) were re-measured in 2002-2004. The main outcomes of the study include incident events of ischemic heart disease (IHD), stroke, and ASCVD between 2005 and 2015. Cox proportional model was used to calculate adjusted hazard ratios (HRs) for ASCVD. In both men and women, the direct effect of BMI on ASCVD was greater than the indirect effect. The percentage of excess HR of BMI mediated by all of the metabolic mediators, including SBP, FSG, and TC, was 45.7% for stroke and 18.7% for IHD in men and 27.5% for stroke and 17.6% for IHD in women. High BMI in young adults increases the risk of metabolic mediators in their middle age, and metabolic mediators explain the adverse effects of high BMI on stroke risk than IHD risk.

FRI488 The Effect Of Thyroid Stimulating Hormone On Brown Adipose Tissue In Humans

Abstract Disclosure: L. Salej: None. S.D. Kodani: None. N. Chaves: None. K.N. Youssef: None. R. Monahan-Earley: None. H. Halle: None. H. Shaelah: None. P. Annie: None. J.A. Parker: None. A.M. Cypess: None. G. Kolodny: None. Y. Tseng: None. B.C. James: None. A. Gavrila-Filip: None. Obesity and diabetes are two main public health concerns due to their high impact on global morbidity and mortality. In an effort to find new treatment strategies, highly active metabolic tissues such as brown adipose tissue (BAT) have been studied as potential targets. Animal studies have shown that TSH may have a direct local effect on BAT mass and activity by stimulating local T3 production via increased deiodinase-2 (DIO2) expression and also by increasing the expression of uncoupling protein-1 (UCP-1), the key molecule in BAT thermogenesis. We hypothesized that high circulating TSH levels could increase BAT activity by increasing local T3 production and generating a local tissue "thyrotoxicosis". We studied 7 patients with thyroid cancer who underwent thyroid surgery and required recombinant TSH (rhTSH) administration for standard follow-up procedures. Each patient underwent 2 PET-CT scans for assessment of BAT volume and activity, first one day after the rhTSH administration (high TSH state) and then 1-3 months later on suppressive thyroid hormone (TH) treatment (low TSH state). Indirect calorimetry and serum thyroid function tests, fasting glucose, insulin, HbA1c, and lipid panel were measured. Our results show that there was a statistically significant difference in TSH levels (p = 0.0095), with stable circulating T4 and T3 between the low and high TSH states. There was no statistically significant difference in the BAT volume and activity (SUVmax) between the high TSH and low TSH states. Age was a significant predictor of BAT SUVmax (p = 0.008; coeff = -0.39, CI = -0.65-0.13), while BMI was a significant predictor for resting energy expenditure (REE) (p = 0.04; coeff = -203.95, CI = -396.12 - -10.78). Based on these findings, along with those from our previous study[1] showing that circulating TH levels may not be directly correlated with BAT function, we have extended our study to assess the intracellular thyroid hormone status in BAT. We have collected deep peri-thyroidal adipose tissue and subcutaneous white adipose tissue (WAT) as a control group from patients undergoing thyroid surgery. In these samples, we will measure mRNA expression of TSH receptors, TH receptors, β-adrenergic receptors, DIO2 and UCP-1 and evaluate for correlations with circulating TSH and TH levels as well as different metabolic parameters to get a deeper insight into BAT function in humans. Reference: 1. Gavrila A et al. Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status. Thyroid. 2017 Jan 1;27(1):1-10. Presentation: Friday, June 16, 2023