Glucose Homeostasis Parameters Research Articles

New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survival via suppression of TXNIP/NLRP3 pyroptosis signaling in Streptozocin–Induced diabetes mellitestype-1 in rats

BackgroundAn ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass. ObjectivesThe study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats via suppression of TXNIP/NLRP3 signaling. Methods: Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment. ResultsThe STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters. ConclusionsNoteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites via targeting pancreatic TXNIP/NLRP3 signaling pathway.

Genistein mitigates diet-induced obesity and metabolic dysfunctions in gonadectomized mice with some sex-differential effects.

Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome. Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment. Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as Fasn, Srebf1, Saa1, Cd36, Col1a1, Pck1, and Ppargc1a. Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice. Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.

Asymmetric dimethylarginine serum concentration in normal weight and obese CKD patients treated with hemodialysis

IntroductionAsymmetric dimethylarginine (ADMA), a cardiovascular risk factor, increases in renal failure. The aim of this study was to investigate ADMA levels in normal weight and obese patients on hemodialysis.MethodsIn this cross-sectional study, 43 normal weight and 43 obese patients on regular hemodialysis were examined. Malnutrition-inflammation score (MIS), anthropometry, circulating ADMA, lipid profiles including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipid ratios, glucose homeostasis parameters, blood pressure, and high-sensitivity C-reactive protein (hs-CRP) were assessed.ResultsSerum levels of ADMA were significantly lower in the obese compared to the normal weight patients (10268.2 ± 10092.4 vs. 13765.2 ± 9951.3 ng/l, P = 0.03). At the same time MIS score (6.1 ± 2.4 vs. 10.7 ± 3.2, P < 0.001), systolic blood pressure (119 ± 26.8 vs. 134.2 ± 24.7 mmHg, P = 0.018) and mean arterial pressure (91.3 ± 18.6 vs. 100.9 ± 15.9 mmHg, P = 0.028) were significantly lower in the obese than the normal weight group. Fasting blood glucose (P = 0.045), TG/HDL (P = 0.03), TC/HDL (P = 0.019), and LDL/HDL (P = 0.005) ratios, and hs-CRP (P = 0.015) levels were significantly higher in the obese than in the normal weight group.ConclusionCirculating ADMA was significantly lower in obese than in normal weight patients on hemodialysis, which was concomitant with lower MIS, indicating a better nutritional inflammatory status, and lower blood pressure.

Changes in pancreatic steatosis by computed tomography 24 months after sleeve gastrectomy in youth with severe obesity

BackgroundPancreatic steatosis has been associated with obesity and the metabolic syndrome. Studies in adults have demonstrated improvement in pancreatic steatosis following sleeve gastrectomy (SG) with concomitant improvement in glucose homeostasis. ObjectivesTo examine changes in pancreatic steatosis in youth with severe obesity 24 months following SG. SettingAcademic hospital system. MethodsForty-seven youth (13–24 years) with severe obesity (37 females) were followed for 24 months; 23 had SG and 24 were nonsurgical (NS) controls. Attenuations of the pancreas and spleen were measured using computed tomography (CT) at baseline, 12- and 24-month follow-up. Subjects underwent magnetic resonance imaging (MRI) for subcutaneous and visceral adipose tissue (SAT, VAT), dual energy x-ray absorptiometry (DXA) for body composition, blood sampling for glycated hemoglobin (A1C), and fasting and postprandial insulin and glucose. Linear mixed effects (LMEs) models were used to compare within- and between-group changes over 24 months. ResultsAt baseline, SG had higher body mass index (BMI) versus NS (P = .033). Over 24 months, significant reductions were noted in weight, BMI, VAT, SAT, fat mass (FM), and lean mass (LM) in the SG versus NS groups (P ≤ .0001). There was a significant 24-month decrease in pancreatic steatosis in the SG group (P = .006). In the whole group, 24-month reductions in pancreatic steatosis correlated with BMI and FM decreases. No associations were found between pancreatic steatosis and glucose homeostasis parameters. ConclusionsPancreatic steatosis measured by CT improved after SG in youth. Further studies are needed to understand the relationship between pancreatic steatosis and glucose homeostasis.

The effect of microbiome-modulating therapeutics on glucose homeostasis in metabolic syndrome: A systematic review, meta-analysis, and meta-regression of clinical trials

BackgroundMetabolic syndrome (MetS) is a chronic disorder featuring overweight/obesity, high blood pressure, and dysfunction of lipid and carbohydrate metabolism. Microbiome-modulating probiotics, prebiotics, synbiotics and fecal microbiota transplant (FMT) are promising adjunct therapies for improving parameters of glucose homeostasis and insulinemia. MethodsWe conducted a comprehensive systematic review, meta-analyses, and meta-regressions to investigate the effect of the abovementioned microbiome therapies on various biomarkers after screening clinical trials published through April 2023. We pooled data using random effects meta-analyses, reporting them as mean differences (MDs) with 95 % confidence intervals (CIs), and conducting univariate linear model meta-regressions. ResultsData from 21 trial comparisons across 19 studies (n = 911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03 mg/dL [95%CI: 6.93; −1.13]; p effect = 0.006, I2 = 89.8 %), and fasting insulin (MD: 2.56 μU/mL [95%CI: 4.28; −0.84]; p effect = 0.004, I2 = 87.9 %), but not insulin resistance or sensitivity indices and HbA1c. Age, baseline BMI, baseline biomarker value, pro/synbiotic dosage, trial duration, nutraceutical type, and WHO region were factors affecting the efficacy of these interventions at producing changes in biomarkers, signaling the potential role of personalized precision medicine adjunct therapy for deranged glucose homeostasis in patients with MetS. Nevertheless, presence of heterogeneity calls for further investigation before their clinical application. ConclusionsProbiotics, prebiotics, synbiotics and FMT supplementation improved fasting glucose and insulin in patients with MetS. Further large-scale and high-quality trials are required before potential clinical applications.

Serum Levels of Adipolin and Adiponectin and Their Correlation with Perinatal Outcomes in Gestational Diabetes Mellitus.

Objectives: This study aimed to investigate the serum level of adipolin and adiponectin in healthy pregnant women and pregnant women with gestational diabetes mellitus (GDM) during the second trimester, the prepartum period, and in the newborns of these patients. Methods: A total of 55 women diagnosed with GDM and 110 healthy pregnant women were included in this study. Pearson's and Spearman's correlation coefficients were calculated to determine the association of adipolin and adiponectin with anthropometric markers of obesity (body mass index (BMI), mid-upper arm circumference (MUAC), tricipital skinfold thickness (TST)), inflammation markers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)), and maternal glucose homeostasis parameters (fasting glucose, insulin, C peptide, glycosylated hemoglobin A1c (HbA1c), Insulin Resistance-Homeostatic Model Assessment (IR HOMA)). Results: There were no statistical differences between the adipolin value in patients with GDM compared to healthy patients (p = 0.65 at diagnosis and p = 0.50 prepartum) and in newborns from mothers with GDM compared to healthy mothers (p = 0.24). Adipolin levels are significantly higher in patients with GDM who gave birth via cesarean section (p = 0.01). In patients with GDM, the adipolin level correlates positively with HgA1c in the prepartum period. We found a positive correlation between the maternal adipolin values at diagnosis and prepartum and neonatal adipolin (respectively: r = 0.556, p = 0.001; r = 0.332, p = 0.013). Adiponectin levels were significantly lower in patients with GDM at diagnosis and prepartum (p = 0.0009 and p = 0.02), but their levels increased prepartum (5267 ± 2114 ng/mL vs. 6312 ± 3150 ng/mL p = 0.0006). Newborns of mothers with GDM had lower adiponectin levels than newborns of healthy mothers (p < 0.0001). The maternal adiponectin value correlates negatively with maternal BMI, MUAC, and IR HOMA in both groups at diagnosis and prepartum. There were no differences between the groups in terms of cesarean rate (p > 0.99). The relative risk of occurrence of adverse events in patients with GDM compared to healthy ones was 2.15 (95% CI 1.416 to 3.182), and the odds ratio for macrosomia was 4.66 (95% CI 1.591 to 12.69). Conclusions: There was no difference in adipolin levels between mothers with GDM and healthy mothers during the second trimester and the prepartum period. Adipolin is known to enhance insulin sensitivity and reduce inflammation, but unlike adiponectin, it does not appear to contribute to the development of GDM.

Impaired Glucose Homeostasis Accompanies Cellular Changes in Endocrine Pancreas after Atorvastatin Administration

Abstract Atorvastatin (ATOR) has been reported to increase the risk for diabetes mellitus. Therefore, in the current study, we focused on studying the effect of ATOR on the structure of islets of Langerhans including their various cellular components as well as on glucose homeostasis. We detected a statistically significant increase (P &lt; 0.05) in β-cell mass and percentage with a significant decrease in α-cell area and percentage in animals that received ATOR compared to control ones. In addition, a statistically significant increase (P &lt; 0.05) in the β-cell proliferation was observed in the ATOR group with negligible change in expression of inflammatory cytokines of the islets. A significant downregulation in apoptosis alongside a significant upregulation in anti-apoptosis were detected in islets of animals treated with ATOR. Moreover, there was a significant impairment in various parameters of glucose homeostasis in the ATOR-treated group. Therefore, ATOR may induce insulin resistance-like state that was demarcated at cellular as well as at biochemical levels with little or no inflammatory response.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population

BackgroundEndocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. ObjectiveTo assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. MethodsMultivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. ResultsCompared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DiscussionThis is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

The BDNF protein is associated with glucose homeostasis and food intake in carriers of common BDNF gene variants.

The brain-derived neurotrophic factor (BDNF) concentrations may differ between BDNF gene genotype carriers. These changes occur in individuals with metabolic and mental disorders. The aim of this study was to assess the associations of glucose homeostasis parameters and the frequency of food consumption with BDNF protein concentrations based on the BDNF single-nucleotide polymorphisms (SNPs). Among the 439 participants, some common rs10835211 BDNF gene variants were analyzed. We evaluated BDNF concentration, fasting glucose and insulin concentrations and during oral glucose tolerance tests. Anthropometric measurements, body composition, and body fat distribution were assessed, and 3-day food intake diary and food frequency questionnaire were completed. We noticed significant differences in concentration of BDNF between AA and AG genotype rs10835211 carriers (p=0.018). The group of AA genotype holders were older, and positive correlation was found between age and BDNF in the whole study population (p=0.012) and in the GG genotype carriers (p=0.023). Moreover, BDNF protein correlated with fasting insulin (p=0.015), HOMA-IR (p=0.031), HOMA-B (p=0.010) , and the VAT/SAT ratio (p=0.026) in the GG genotype individuals. Presence of the GG genotype was negatively correlated with nut and seed (p=0.047), lean pork consumption (p=0.015) and the BDNF protein. Moreover, we observed correlations between the frequency of chicken (p=0.028), pasta (p=0.033) and sweet food intake (p=0.040) and BDNF concentration in the general population. Among carriers of the AA genotype, we observed a positive correlation between the consumption of rice (p=0.048) and sweet food (p=0.028) and the BDNF protein level. Peripheral BDNF may be associated with visceral fat content and insulin concentrations in the GG genotype carriers and may depend on variable food intake, which warrants further investigation.

Interesterified palm oil promotes insulin resistance and altered insulin secretion and signaling in Swiss mice

Interesterified fats have been used to replace trans-fat in ultra-processed foods. However, their metabolic effects are not completely understood. Hence, this study aimed to investigate the effects related to glucose homeostasis in response to interesterified palm oil or refined palm oil intake. Four-week-old male Swiss mice were randomly divided into four experimental groups and fed the following diets for 8 weeks: a normocaloric and normolipidic diet containing refined palm oil (PO group) or interesterified palm oil (IPO group); a hypercaloric and high-fat diet containing refined PO (POHF group) or interesterified PO (IPOHF group). Metabolic parameters related to body mass, adiposity and food consumption showed no significant differences. As for glucose homeostasis parameters, interesterified palm oil diets (IPO and IPOHF) resulted in higher glucose intolerance than unmodified palm oil diets (PO and POHF). Euglycemic-hyperinsulinemic clamp assessment showed a higher endogenous glucose production in the IPO group compared with the PO group. Moreover, the IPO group showed significantly lower p-AKT protein content (in the muscle and liver tissues) when compared with the PO group. Analysis of glucose-stimulated static insulin secretion (11.1 mmol/L glucose) in isolated pancreatic islets showed a higher insulin secretion in animals fed interesterified fat diets (IPO and IPOHF) than in those fed with palm oil (PO and POHF). Interesterified palm oil, including in normolipidic diets, can impair insulin signaling in peripheral tissues and increase insulin secretion by β-cells, characterizing insulin resistance in mice.

Post-Hypoglycemic hyperglycemia are highly relevant markers for stratification of glycemic variability and partial remission status of pediatric patients with new-onset type 1 diabetes.

To evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not. In the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHHAUC]) and glycemic homeostasis markers were studied using adjusted mixed-effects models. PHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratio<0.02; sensitivity = 86% and specificity = 68%). PHHAUC moderately correlated with parameters of glucose homeostasis including TIR (R2 = 0.35, p-value < 0.05), coefficient of variation (R2 = 0.22, p-value < 0.05) and Insulin-Dose Adjusted A1c (IDAA1C) (R2 = 0.32, p-value < 0.05) and with residual β-cell secretion (R2 = 0.17, p-value < 0.05). Classification of patients into four previously described glucotypes independently validated PHH parameters as reliable markers of glucose homeostasis and improved the segregation of patients with intermediate values of IDAA1C and estimated C-peptide (CPEPEST). Finally, a combination of PHH parameters identified groups of patients with specific patterns of hypoglycemia. PHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes.

Increased vascular risk factors, atherosclerosis, and psychological distress among Indian adults with refractory epilepsy in comparison to well-controlled epilepsy

ObjectiveComparison of cardiovascular risk factors, atherosclerosis, and psychological distress among adults with refractory versus well-controlled epilepsy. MethodsThe cross-sectional study consisted of two groups of 40 people each: Group I – People with well-controlled epilepsy, Group II – People with refractory epilepsy. Age- and gender-matched people of 20–50 years were recruited. People who were diabetic, smokers, hypertensive, alcoholic, pregnant, with infections, and lactating women were excluded from the study. Biochemical parameters, fasting glucose, lipid profile, fasting insulin, leptin, adiponectin, Lp[a], hsCRP, TyG INDEX, HOMA1-%S, HOMA1-IR, HOMA1-%B, QUICKI, FIRI, AIP, AC, CLTI, MLTI, CRI-I, CRI-II, and CIMT were estimated. Stress levels [PSS-10, GAD-7 & PHQ-9] were assessed based on the scoring system from the questionnaires. ResultsThe existence of metabolic syndrome, levels of triglycerides, TyG index, MDA, OSI, CIMT, AIP, and stress scores [PSS-10, GAD-7 & PHQ-9] were significantly higher in the refractory-epilepsy group in comparison to the well-controlled group. There were associations between LDL -C and CIMT as well as between GAD-7 and CIMT among all the study subjects. There were no significant differences in the levels of glucose homeostasis parameters, hsCRP, leptin, adiponectin, and Lp[a] between the two groups. Based on the ROC analysis, MDA [AUC = 0.853] and GAD-7 [AUC = 0.900] are useful in the differential diagnosis of the study groups. ConclusionPeople with refractory epilepsy had increased levels of vascular risk factors, atherosclerosis, and stress levels compared to people with well-controlled epilepsy. Suitable disease management and therapeutic approaches to address cardiovascular and psychological distress could be planned out among people with refractory epilepsy to improve their quality of life.

Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis.

There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent. This systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Relevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed independently by two researchers who used the Cochrane meta-analysis checklist and the PRISMA guidelines. Clinical studies and trials that measured SCFAs and reported glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMDs) with 95%CIs were calculated using a random-effects model in the data extraction tool Review Manager version 5.4 (RevMan 5.4). The risk-of-bias assessment was performed following the Cochrane checklist for randomized and crossover studies. In total, 6040 nonduplicate studies were identified, 23 of which met the defined criteria, reported fasting insulin, fasting glucose, or HOMA-IR values, and reported change in SCFA concentrations post intervention. Meta-analyses of these studies indicated that fasting insulin concentrations were significantly reduced (overall effect: SMD = -0.15; 95%CI = -0.29 to -0.01, P = 0.04) in treatment groups, relative to placebo groups, at the end of the intervention. Studies with a confirmed increase in SCFAs at the end of intervention also had a significant effect on lowering fasting insulin (P = 0.008). Elevated levels of SCFAs, compared with baseline levels, were associated with beneficial effects on HOMA-IR (P < 0.00001). There was no significant change in fasting glucose concentrations. Increased postintervention levels of SCFAs are associated with lower fasting insulin concentrations, offering a beneficial effect on insulin sensitivity. PROSPERO registration number CRD42021257248.

Screening for Impaired Glucose Homeostasis: A Novel Metric of Glycemic Control

ObjectiveTo investigate the use of a mathematical model of glucose homeostasis, fit to continuous glucose monitor data, as a metric of dysfunctional glycemic control. Patients and MethodsThree hundred eighty four participants recruited from 2 studies between October 2020 and June 2022 were equipped with a continuous glucose monitor, and interstitial glucose data were automatically collected for 2 weeks. The participants were assessed by a physician and diagnosed as being diabetic, prediabetic, or healthy according to the American Diabetes Association guidelines. A mathematical model of glucose homeostasis was fitted to the glucose data, and model parameter values were obtained. The participants were classified into the following 2 groups on the basis of their glucose homeostasis parameters: effective and impaired. Finally, glycemic variability metrics were compared with glucose homeostasis classification. ResultsThe homeostasis classification resulted in a specificity, sensitivity of individuals with prediabetes, and sensitivity of individuals with type 2 diabetes (T2D) of 0.78, 0.86, and 1.00, respectively, for women and 0.71, 0.86, and 1.00, respectively, for men. This sensitivity was similar to that of glycated hemoglobin A1c measurement (a sensitivity of 0.89 for women and 0.90 for men for prediabetes and a sensitivity of 1.00 for T2D) and superior to that of the oral glucose tolerance test (a sensitivity of 0.18 for women and 0.24 for men for prediabetes and a sensitivity of 0.75 for women and 0.86 for men for T2D). Overall, the individuals classified as impaired had increased glucose variability metrics than the individuals classified as effective (P<.05). ConclusionThe classification of glucose homeostasis on the basis of mathematical modeling of continuous measurements has promising applications as a new metric of dysfunctional glycemic control. Trial Registrationclinicaltrials.gov Identifier: NCT04529239; clinical trial registry identifier: CTRI/2021/08/035957

Association of bone turnover biomarkers with severe intracranial and extracranial artery stenosis in type 2 diabetes mellitus patients

Intracranial and extracranial artery stenosis is associated with cerebral infarction. Vascular calcification and atherosclerosis are the main causes of stenosis and major risk factors for cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus (T2DM). Bone turnover biomarkers (BTMs) are associated with vascular calcification, atherosclerosis, glucose, and lipid metabolism. To investigate the association of circulating BTM levels with severe intracranial and extracranial artery stenosis in patients with T2DM. For this cross-sectional study including 257 T2DM patients, levels of the BTMs serum osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (CTX), and procollagen type I N-peptide were measured by electrical chemiluminescent immunoassay, and artery stenosis was assessed by color Doppler and transcranial Doppler. Patients were grouped according to the existence and location (intracranial vs. extracranial) of artery stenosis. Correlations between BTM levels, previous stroke, stenosis location, and glucose and lipid metabolism were analyzed. T2DM patients with severe artery stenosis had a higher frequency of previous stroke and levels of all three tested BTMs (all P < 0.05) than patients without. Some differences in OC and CTX levels were observed according to the location of artery stenosis. Significant associations were also observed between BTM levels and some glucose and lipid homeostasis parameters. On multivariate logistic regression analysis, all BTMs were significant predictors of artery stenosis in T2DM patients with and without adjustment for confounding factors (all P < 0.001), and receiver operating characteristic curve analysis demonstrated the ability of BTM levels to predict artery stenosis in T2DM patients. BTM levels were found to be independent risk factors for severe intracranial and extracranial artery stenosis and were differentially associated with glucose and lipid metabolism in patients with T2DM. Therefore, BTMs may be promising biomarkers and potential therapeutic targets for artery stenosis.

Obesity modifies the association of environmental pyrethroid exposure with glucose homeostasis in the US general adults

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-β). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20–1.01) μg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), −6.59% (−10.72%, −2.28%), and 1.10% (−2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level.

The effects of spirulina intake on clinical and metabolic parameters in Alzheimer's disease: A randomized, double-blind, controlled trial.

The current study aimed to determine the effects of spirulina intake on cognitive function and metabolic status among patients with Alzheimer's disease (AD). This randomized, double-blind, controlled clinical trial was done among 60 subjects with AD. Patients were randomly assigned to receive either 500 mg/day spirulina or a placebo (each n=30) twice a day for 12 weeks. Mini-mental state examination score (MMSE) was recorded in all patients before and after intervention. Blood samples were obtained at baseline and after 12 weeks' intervention to determine metabolic markers. Compared with placebo, spirulina intake resulted in a significant improvement in MMSE score (spirulina group: +0.30 ± 0.99 vs. Placebo group: -0.38 ± 1.06, respectively, p=0.01). In addition, spirulina intake decreased high-sensitivity C-reactive protein (hs-CRP) (spirulina group: -0.17 ± 0.29 vs. Placebo group: +0.05 ± 0.27 mg/L, p=0.006), fasting glucose (spirulina group: -4.56 ± 7.93 vs. Placebo group: +0.80 ± 2.95 mg/dL, p=0.002), insulin (spirulina group: -0.37 ± 0.62 vs. Placebo group: +0.12 ± 0.40 μIU/mL, p=0.001) and insulin resistance (spirulina group: -0.08 ± 0.13 vs. Placebo group: 0.03 ± 0.08, p=0.001), and increased insulin sensitivity (spirulina group: +0.003 ± 0.005 vs. Placebo group: -0.001 ± 0.003, p=0.003) compared with the placebo. Overall, our study showed that spirulina intake for 12 weeks in patients with AD improved cognitive function, glucose homeostasis parameters, and hs-CRP levels.

RF16 | PSUN203 Deep Characterization of Pancreas Volume of New-Onset Type 1 Diabetes Patients Reveals Puberty-Specific Patterns and New Topographic Correlations with Pancreatic Functions.

Abstract There is a current understanding of type 1 diabetes (T1D) as being the result of a heterogeneous disease of whole pancreas. So far, descriptions of pancreas alterations suggested a global involvement of inflammation throughout the organ, characterized by abnormal age-specific patterns (i.e. &amp;gt; or &amp;lt;7 yo). In our DIATAG study, we thoroughly characterized pancreatic structure modifications in new-onset T1D patients and investigated whether these correlated with pancreatic functions during the first postdiagnosis year. Pediatric patients with new-onset T1D (n=31; 11.2±2.9 years) underwent abdominal MRI scan at diagnosis (i.e. 40±37 days postdiagnosis). Exocrine function (i.e. serum trypsinogen) and residual endocrine secretion estimates (i.e. fasten = CPEPBASAL, stimulated model = CPEPEST (1)) were evaluated on fasten blood tests at diagnosis (Δ) and Δ+3, +12 months, respectively. Clinical parameters of glucose homeostasis (i.e. A1C, insulin daily dose, insulin-dose adjusted A1c [IDAA1C]) were collected at Δ+3, +6, +9 and +12 months. We compared pancreas volumes (i.e. PV, PVHEAD, PVBODY, PVTAIL) and ratios (pancreas volume ratio [PVR] = PVHEAD/PVBODY+TAIL; pancreas index [PI] = PV/body weight) to retrospectively identify age-, BMI- and sex-matched controls (n=29). Compared to control group, T1D patients demonstrated a homogeneous (PVR, 1.39±0.7 vs 1.46±0.4, p&amp;gt;0.05) decrease of PI (0.6±0.2 vs 1.1±0.3 mL/kg, p&amp;lt;0.0001) independently of pancreatic subregion. Interestingly, prepubertal children with T1D (n=15) exhibited greater pancreas atrophy of both the body-tail (10±5.6%, p&amp;lt;0.05) and head (7.2±3%, p&amp;lt;0.05) subregions compared to pubertal group (n=16; PI difference of mean, 0.64 vs 0.48 mL/kg). Next, we evaluated correlations between pancreatic volumes and functions during the natural evolution of T1D using multivariate and univariate linear regressions. PV and PI correlated moderately with exocrine function (trypsinogen; R=0.46, R=0.52, p&amp;lt;0.001) but not with residual endocrine function evaluated at Δ+3 months. Interestingly, we observed using topographical analysis that PVHEAD correlated with trypsinogen (R=0.5, p&amp;lt;0.001) but not with any endocrine estimates (p&amp;gt;0.05). PVTAIL positively correlated with CPEPEST and CPEPBASAL at Δ+3 months (R=0.55, p=0.002; R=0.47, p&amp;lt;0.01) and not with clinical parameters or trypsinogen (p&amp;gt;0.05). PVBODY did not correlate with any pancreatic function. Finally, we identified multivariate models that included PV and predicted pancreatic endocrine function at Δ+6 and +12 months (i.e. IDAA1C, HbA1C). MRI performed early after T1D onset helped us define specific pancreas alterations and demonstrate for the first time: (1) the increased pancreas atrophy in prepubertal children; (2) correlations between pancreatic subregion volumes and their respective residual functions early after diagnosis and (3) the improvement of endocrine function prediction models by adding PV estimates as predictors. (1) Wentworth et al. 2019;62(1): 33–40 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

RELATIONSHIPS BETWEEN NAFLD BIOCHEMICAL SCORES AND LEFT VENTRICULAR GEOMETRIC PATTERN IN NAÏVE ESSENTIAL HYPERTENSIVE PATIENTS

Objective: The not alcoholic fatty liver disease (NAFLD) is associated with an increased cardiovascular mortality and morbidity. An hypothesis for this association could be the left ventricular (LV) geometric alteration sometime found in hypertension that is a known prognostic factor for cardiovascular events in hypertension. We searched for a relationship between biochemical scores of NAFLD and left ventricular (LV) hypertrophy (LVH) or LV geometric patterns changes in a large group of never treated essential hypertensive (EH) patients. Design and method: In 434 naïve (49 ± 14 years, 234 males) we evaluated BMI, waist circumference, liver steatosis at abdominal echography, the biochemical scores of liver steatosis: Liver Fat Score (LFS), Fatty Liver Index (FLI), Hepatic Steatosis Index (NAÏVE), and the fibrosis scores: NAFLD Fibrosis Score (NFS), APRI, FIB-4, parameters of glucose and insulin homeostasis, liver blood tests, lipids, platelets count, glomerular filtration rate (GFR), reactive C protein. LV mass and relative wall thickness was calculated with echocardiography. Patients were classified in 4 groups of LV geometry: 1 = LV normal geometry, 2 = LV concentric remodeling, 3 = concentric LVH, 4 = eccentric LVH. Results: A LVH was present in 17.3% of patients, and these patients had higher LFS (P &lt; 0.001), FLI (P = 0.008), NAÏVE (P = 0.004) and NFS (P = 0.011) scores than patients without LVH. LVH was independently associated with the FLI score but not with fibrosis scores. The steatosis scores (LFS, NAÏVE, FLI) linearly increased across the four LV geometric patterns (P = 0.007, P = 0.001, P = 0.003, respectively). The fibrosis score NFS was significantly higher in subjects with concentric LVH (P = 0.041). The LFS was independently associated with BMI, GAUC, G120, and triglycerides levels. The NFS was independently associated with waist circumference, GFR and weakly with fasting glucose level. Ultrasound steatosis was not different among the four LV geometric patterns. Conclusions: In naïve EH patients the biochemical steatosis scores show a relationship with LVH and LV geometric changes, while fibrosis is associated with concentric LVH. An accurate investigation to reveal a NAFLD should be done in EH patients with altered LV geometry and to better understanding of mechanisms linking the two conditions.

Effect of Camel Milk on Glucose Homeostasis in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The effects of camel milk (CM) intake on glycemic control in patients with diabetes are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of CM intake on glucose homeostasis parameters in patients with both types of diabetes mellitus; T1DM and T2DM. We searched Google Scholar, PubMed/MEDLINE, EBSCO host, CINAHL, ScienceDirect, Cochrane, ProQuest Medical, Web of Science, and Scopus databases from inception until the end of November 2021. Relevant RCTs were identified, and the effect size was reported as mean difference (MD) and standard deviation (SD). Parameters of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting serum insulin (FI), insulin resistance (expressed in terms of HOMA-IR), insulin dose (ID) received, serum insulin antibody (IA), and C-peptide (CP) were tested. Out of 4054 collected articles, 14 RCTs (total 663 subjects) were eligible for inclusion. The pooled results obtained using a random-effects model showed a statistically significant decrease in HbA1c levels (MD, −1.24, 95% confidence interval (CI): −2.00, −0.48, p < 0.001 heterogeneity (I2) = 94%) and ID received (MD, −16.72, 95% CI: −22.09, −11.35 p < 0.00001, I2 = 90%), with a clear tendency was shown, but non-significant, to decrease FBG (MD, −23.32, 95% CI: −47.33, 0.70, p = 0.06, I2 = 98%) in patients with diabetes who consumed CM in comparison to those on usual care. Conversely, the consumption of CM did not show significant reductions in the rest of the glucose homeostasis parameters. Subgroup analysis revealed that patients with T2DM were more beneficially affected by CM intake than those with T1DM in lowering FBG, while patients with T1DM were more beneficially affected by CM intake than those with T2DM in lowering HbA1c. Both fresh and treated (pasteurized/fermented) CM gave similar beneficial effects in lowering HbA1c. Lastly, a relatively superior effect for longer duration on shorter duration (>6 months, ≤6 months, respectively) of CM intake is found in lowering HbA1c. To conclude, long-term consumption of CM by patients with diabetes could be a useful adjuvant therapy alongside classical medications, especially in lowering the required insulin dose and HbA1c. Due to the high heterogeneity observed in the included studies, more controlled trials with a larger sample size are warranted to confirm our results and to control some confounders and interfering factors existing in the analyzed articles.