Diabetes Syndrome Research Articles

Effects of green tea catechin on the blood pressure and lipids in overweight and obese population-a meta-analysis

BackgroundOverweight and obesity as main health problems harm human beings worldwide. The number of people diagnosed with overweight and obese is gradually increasing. Green tea catechin has been reported to effectively help control body weight in overweight and obese population, and is protectively against the blood pressure and lipids in people with type 2 diabetes and metabolic syndrome. MethodsWe retrieved 4 English databases (PubMed, Web of science, Cochrane, Scoups) from inception to April 20, 2023. Two reviewers independently determined eligibility, assessed the reporting quality of included studies, and extracted the data. Data were extracted from eleven studies. The results were presented with the weighted mean differences (WMDs), and the confidence intervals (CIs) was 95 %. The random-effects or fixed-effects model was applied according to the heterogeneity. The subgroup analysis was used to identify the source of heterogeneity. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. ResultsEleven randomized controlled trials (RCTs) inclusion studies were screened from 3072 literature articles, involving 613 overweight and obese patients. After combining all studies, it was found that in overweight and obese people green tea catechin could reduce waist circumference (WC) (pooled WMD = −1.37 cm, 95 % CI: −2.52 to −0.22 cm, p = 0.019), and triglyceride (TG) (pooled WMD = −0.18 mmol/L, 95 % CI: −0.35 to −0.02 mmol/L, p = 0.032), and increase high density lipoprotein cholesterol (HDL-c) (pooled WMD = 0.07 mmol/L, 95 % CI: 0.01–0.14 mmol/L, p = 0.031). ConclusionGreen tea catechin supplement effectively reduced WC and TG levels and improved HDL-c levels. However, it did not show the significant effect on the blood pressure in overweight and obese people. The present meta-analysis showed a moderate benefit of green tea catechin supplementation on lipid profiles in overweight and obese people.

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.

A clinical case of fatty liver disease. How the new nomenclature can be applied in practice

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is an urgent problem, as this condition is diagnosed in about 35% of the world’s population. Manifestations of metabolic dysfunction in MASLD include excessive body weight (abdominal obesity is the most dangerous), manifestations of dyslipidemia, hepatomegaly, signs of diabetes, arterial hypertension, and moderate alcohol consumption (> 20 g/30 g of alcohol per day in women and men, respectively). According to a new meta‑analysis, MASLD significantly increases the risk of cardiovascular, metabolic, oncological and reproductive consequences. This disorder was associated with a significantly increased risk of cardiovascular outcomes (hazard ratio [HR], 1.43), metabolic outcomes such as incident hypertension (HR, 1.75), prediabetes (HR, 1.69), diabetes (HR, 2.56) and metabolic syndrome (HR, 2.57), chronic kidney disease (HR, 1.38), and various liver‑related outcomes (HR, 3.92). MASLD is also associated with all types of cancer (HR, 1.54); the highest risk is observed for hepatocellular carcinoma (HR, 4.37). Currently, there are no FDA‑approved drugs for the treatment of MASLD, but there are some drugs to treat comorbidities with potential benefit in MASLD that may be considered in the appropriate clinical setting. It is important to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to diagnostics and treatment, in addition to the approach of a gastroenterologist‑hepatologist alone. The increasing MASLD prevalence will remain a major global health threat that requires the implementation of effective mechanisms of the disease management.
 The authors present a clinical case of metabolic dysfunction‑associated steatohepatitis, associated with the I degree obesity. Liver dysfunction, metabolic and asthenovegetative disorders were revealed on the basis of complaints, anthropometric and anamnestic data, and the results of laboratory studies. Treatment with the use of S‑adenosylmethionine (Agepta, manufactured by Italy, developed by the company Omnifarma, Ukraine) was proposed, which contributed to the stabilization of indicators, according to the data of repeated clinical examinations. The lifestyle changes, physical activity, compliance to the treatment scheme and doctor’s recommendations enabled improving the patient’s state of health.

Risk factors associated with severity, prognosis, and evolution of patients with tropical diabetic hand syndrome

Risk factors associated with severity, prognosis, and evolution of patients with tropical diabetic hand syndrome

Ketogenic diet influence on the elemental homeostasis of internal organs is gender dependent

The ketogenic diet (KD) is a low-carbohydrate and high-fat diet that gains increasing popularity in the treatment of numerous diseases, including epilepsy, brain cancers, type 2 diabetes and various metabolic syndromes. Although KD is effective in the treatment of mentioned medical conditions, it is unfortunately not without side effects. The most frequently occurring undesired outcomes of this diet are nutrient deficiencies, the formation of kidney stones, loss of bone mineral density, increased LDL (low-density lipoprotein) cholesterol levels and hormonal disturbances. Both the diet itself and the mentioned adverse effects can influence the elemental composition and homeostasis of internal organs. Therefore, the objective of this study was to determine the elemental abnormalities that appear in the liver, kidney, and spleen of rats subjected to long-term KD treatment. The investigation was conducted separately on males and females to determine if observed changes in the elemental composition of organs are gender-dependent. To measure the concentration of P, S, K, Ca, Fe, Cu, Zn and Se in the tissues the method of the total reflection X-ray fluorescence (TXRF) was utilized. The obtained results revealed numerous elemental abnormalities in the organs of animals fed a high-fat diet. Only some of them can be explained by the differences in the composition and intake of the ketogenic and standard diets. Furthermore, in many cases, the observed anomalies differed between male and female rats.

Multifactorial Aspects of Adiponectin in Non- Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a significant worldwide health issue strongly associated with obesity and metabolic syndrome. It underscores the critical role of adiponectin, a significant adipokine, in the disease's intricate progression. NAFLD's complexity stems from its interplay with factors like obesity, diabetes, and metabolic syndrome, with reduced adiponectin levels commonly observed in NAFLD patients, influenced by age, gender, lipid profiles, and insulin resistance. Adiponectin's versatility in mitigating insulin resistance, inflammation, and liver fibrosis makes it a focal point in NAFLD research, while recent studies introduce spexin, a neuropeptide, as a potential correlate, adding to the understanding of metabolic disorders. To tailor treatment approaches, recognizing the factors affecting adiponectin levels, such as genetics, lifestyle, and comorbidities, is crucial. Lifestyle changes and specific medications offer promise in improving NAFLD outcomes by modulating adiponectin. The article underscores adiponectin's central role in the complex NAFLD landscape and the need for further research to fully grasp its mechanisms and therapeutic potential in managing this prevalent liver disease, emphasizing the importance of rebalancing adipokines and enhancing metabolic health.

Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study

BackgroundIt is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study.MethodsWe used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex.ResultsIndividuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20–1.25) for hypertension to λFDR of 2.48 (95% CI 2.15–2.86) for T2D. Most of these were higher than in spouses (λSpouses < λFDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h2CRP: 0.26 to h2HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λFDR obesity-MetS: 1.28 (95% CI 1.24–1.32) to λFDR MetS-T2D: 1.61 (95% CI 1.52–1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from rg HDL-Triglycerides: − 0.53 to rg LDL-Apolipoprotein B: 0.94).ConclusionsThere is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.

The Effect of a Period of Resistance Training on Some Apoptotic Markers in Kidney Tissue of Diabetic Male Rats with Morphine Withdrawal Syndrome

Background and Objective: The objective of this study was to investigate the effect of resistance training on some apoptotic markers of kidney tissue with morphine withdrawal syndrome in diabetic rats. Materials and Methods: In this experimental study, 32 male Wistar rats were randomly divided into 4 groups of 8, including: diabetes, morphine diabetes, diabetes + resistance training, diabetes morphine + resistance training. After implementing the diabetes induction protocol, the addicted groups received morphine orally for 21 days, and then the training groups participated in the resistance training protocol for 8 weeks. Then all the mice were killed and dissected and their kidney tissue was removed. ELISA kits were used to evaluate apoptotic factors. Results: Cytochrome-C variable results showed a significant decrease in the morphine diabetes (P=0.002) and diabetes + resistance training (P=0.001) and morphine diabetes + resistance training (P=0.001) groups compared to the diabetes group. The results of the caspase-8 variable also showed that the diabetes + resistance training group had a significant decrease compared to the diabetes group (P=0.004) and the morphine diabetes group (P=0.012). Also, the reduction of caspase 3 variable results in the morphine diabetes group (P=0.001), diabetes + resistance training (P=0.001) and morphine diabetes + resistance training (P=0.002) was significant compared to the diabetes group. Conclusion: Resistance training has reduced apoptotic indices in kidney tissue and can be a suitable treatment strategy for diabetes and withdrawal syndrome diabetes.

Low-grade endotoxemia and risk of recurrent thrombosis in primary antiphospholipid syndrome. The multicenter ATHERO-APS study

IntroductionLow-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as “second hit” in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. PurposeTo evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. MethodsBaseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H2O2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. ResultsIn the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H202 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H2O2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. ConclusionLow-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts.

SAT674 Lipodystrophy: A Hidden Culprit In Uncontrolled Diabetes

Abstract Disclosure: F. El Sayed: None. A. Banka: None. Introduction: Lipodystrophies are rare disorders with selective absence/accumulation of fat tissue. The “common” genetic forms include Congenital Generalized Lipodystrophy or Familial Partial Lipodystrophy (FPLD). Non-genetic factors like autoimmune disorders, chronic infections, or malnutrition can also contribute to a lipodystrophy phenotype. Clinical case: A 49-year-old female with diabetes mellitus, hypertriglyceridemia, gait disturbances, hypertension, hereditary hemorrhagic telangiectasias, asthma, presents with suspected lipodystrophy. She notes truncal obesity as a child, with progression as an adult and subsequent loss of volume from her arms and legs around age 30. Family history is significant for multiple family members with diabetes mellitus. On physical exam, the patient has a BMI of 22.86 kg/m2. She walks with a cane and has abdominal fat deposition, a dorsocervical fat pad, and reduced fat and muscle mass in her lower extremities. Her diabetes is poorly controlled with multiple complications including retinopathy, microalbuminuria, neuropathy, CVA, and CAD. Her medications include metformin, pioglitazone, detemir, aspart, and an insulin sliding scale for diabetes management, and rosuvastatin, fenofibrate, and omega-3-acid ethyl esters for hyperlipidemia. Her last A1C was 12.7%, and urine analysis was positive for glucosuria and ketonuria. Her lipid panel revealed high triglycerides (800s) and low HDL levels. Other pertinent labs include elevated GDF15 at 761 pg/mL. and lactate elevation at 3.4 mml/L. Given suspicion for hypercortisolism, she underwent a dexamethasone suppression test which was negative for Cushing’s disease. She subsequently underwent exome sequencing with mitochondrial deletion testing, which led to the diagnosis of FPLD. Discussion: FPLD results in loss of fat from the extremities starting around puberty, often leading to metabolic complications. Although both sexes are affected, women usually present with more severe disease. Currently, multiple genes are associated with FPLD, most commonly LMNA and PPARG which both follow autosomal dominant inheritance. Conclusion: Presently, there is no cure for lipodystrophy syndromes. However, in patients with diabetes and resistant metabolic syndrome features, a diagnosis of lipodystrophy should be considered. Further evaluation with genetic testing is warranted and has implications for family planning and medical management. Presentation: Saturday, June 17, 2023

THU334 Trends In GLP-1 Agonist Utilization In Diabetics With And Without Vascular Disease

Abstract Disclosure: P. Sargin: None. M. Barahona: None. H. Rubayet: None. G. Leef: None. GLP-1 agonists (GLP1) have emerged as a breakthrough class of drugs for the management of Type 2 Diabetes (T2DM). Data from cardiovascular outcomes trials has shown benefits in patients with known atherosclerotic vascular disease, including reduced cardiovascular mortality and stroke. These agents are now considered preferred therapy, however, prior studies have shown low rates of utilization. We hypothesized that recent guidelines and provider education may lead to increased prescribing of GLP1. We analyzed a large, multicenter database to investigate recent trends in GLP1 utilization in patients with T2DM and vascular disease. We extracted all patients from the database with T2DM and excluded patients with diagnoses of Type 1 Diabetes, thyroid cancer, pancreatitis, or MEN syndrome type 2, or age &amp;gt;90. We then stratified the cohort to compare patients with a diagnosis of ischemic heart disease, peripheral vascular disease, or cerebrovascular disease since January 1st, 2021 against diabetic patients without these diagnoses. Patients were compared for rates of prescription of diabetes medications and baseline characteristics including age, sex, race, BMI, HgA1c, and creatinine. Our search generated a total of 408553 patients with T2DM and vascular disease (defined as at least one of the following: ischemic heart disease, peripheral vascular disease, cerebrovascular disease), and 520383 with T2DM and no known vascular disease. The vascular disease cohort was 56% male, 68% white, mean age 70±13. Ischemic heart disease was present in 78%, cerebrovascular disease in 43%, and peripheral vascular disease in 22%. The non-vascular disease cohort was 54% female, 57% white, mean age 63±16. In the vascular disease cohort, 56% were prescribed insulin, 47% metformin, 17% SGLT2, and 14% GLP1. In the non-vascular disease cohort, 43% were prescribed metformin, 32% insulin, 11% GLP1, and 8% SGLT2. The P-value was less than 0.001 for all comparisons. Rates of the utilization of GLP1 agents in our database are still relatively low, but higher than has been reported before. This might suggest a favorable trend compared with prior studies on this topic, although they are not directly comparable due to different patient populations. With only 14% of the T2DM-vascular disease population receiving one of these agents (after excluding those with a documented contraindication), more work needs to be done to enable all patients who would benefit from these medications to access them. Presentation: Thursday, June 15, 2023

THU301 Natural History Of Pregnancy And Pregnancy Outcomes In Subjects With Lipodystrophy

Abstract Disclosure: T.J. Neal: None. M.S. Startzell: None. E. Cochran: None. M. Lightbourne: None. R.J. Brown: None. Lipodystrophy syndromes are a group of rare heterogenous disorders characterized by deficiency of adipose tissue in a regional distribution (Partial Lipodystrophy, PL) or all of the body (Generalized Lipodystrophy, GL), leading to severe insulin resistance, diabetes, hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. During pregnancy in patients with lipodystrophy, insulin resistance worsens during late gestation, leading to pregnancy complications that may threaten the lives of the fetus and mother. Case reports have suggested increased risk of pregnancy complications such as pre-eclampsia in patients with lipodystrophy. We sought to systematically examine pregnancy complications and offspring outcomes in lipodystrophy through a prospective study involving structured interviews with patients with known lipodystrophy and past pregnancy. Data were collected in 7 patients with PL (2 LMNA, PPARG, 4 unknown genetic cause) and 1 with GL (AGPAT2). These 7 patients had 21 pregnancies (mean 2.6), including 19 singleton and 2 twin gestations. 14 pregnancies (67%) were spontaneous and 7 (33%) required fertility treatment. 10 pregnancies (48%) in 6 patients resulted in 12 live births (7 term, 3 preterm; 3 vaginal and 8 C-section delivery) and 11 (52%) resulted in miscarriage (9 first trimester, 2 second trimester in 1 patient due to cervical insufficiency). There were no episodes of acute pancreatitis during pregnancy. Among the 10 pregnancies resulting in live birth, 100% were complicated by diabetes. 5 (50%) had pre-gestational diabetes and 5 (50%) had gestational diabetes that resolved after delivery. 8 (80%) required insulin during pregnancy (of whom none required insulin pre-pregnancy). 5 (50%) of these pregnancies were complicated by pre-eclampsia. Among all 21 pregnancies, metformin was used in 8 (38%), insulin in 8 (38%), metreleptin in 4 (19%) pregnancies (all 4 of which were in 1 patient with GL), and fenofibrate in 2 (9.5%). Among 12 offspring, 1 (8%) was small for gestational age (GA), 8 (67%) were appropriate for GA and 3 (25%) were large for GA. 6 (50%) had neonatal hypoglycemia. In summary, pregnancies in women with lipodystrophy showed high complication rates, including very high rates of miscarriage, diabetes, and pre-eclampsia. Larger studies are needed to determine how management of these patients during pregnancy, including with newer treatments such as metreleptin for GL, affects pregnancy and offspring outcomes. Presentation: Thursday, June 15, 2023

SAT083 Comparing Grit, Anxiety, And Social Responsiveness In KCNJ11-NDM And Their Sibling Controls

Abstract Disclosure: J. Desai: None. L. Letourneau-Freiberg: None. M. Msall: None. M. Scott: None. R.N. Naylor: None. L. Philipson: None. S.W. Greeley: None. Background: Neonatal diabetes mellitus (NDM), diabetes with onset before 6-12 months of age, is most commonly caused from mutations in the ATP-dependent Potassium (KATP) channel genes: KCNJ11 (KCNJ11-NDM) or ABCC8. Because of brain expression of mutant KATP channels, a spectrum of neurodevelopmental difficulties have been described, such as developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, learning disorders, and Attention-deficit/hyperactivity disorder (ADHD). In order to understand more about specific challenges, we compared self- and parent/caregiver-reported grit, anxiety, and social responsiveness among participants with KCNJ11 mutations and their sibling controls. Methods: We recruited 12 families (12 KCNJ11-NDM participants and 10 sibling controls) through the University of Chicago Monogenic Diabetes Registry (www.monogenicdiabetes.org). Affected participants and sibling controls, and in some cases their parent/caregiver, completed the SCARED/SCAARED (anxiety), SRS-2 (social responsiveness) and Grit Scale (grit) surveys. Nonparametric analyses were performed using the Mann-Whitney U-test for group comparisons. Results: Individuals with KCNJ11-NDM had significantly worse social responsiveness scores compared to sibling controls in both Total Social Responsiveness and 4/5 subscales including Social Awareness, Cognition, Communication, and Restricted Interests and Repetitive Behavior (p&amp;lt;0.05), but no difference for Motivation. In terms of deficits in social interaction, 20% of KCNJ11-NDM participants had total SRS-2 T-scores in the mild range, 30% with scores in the moderate range, and 40% with scores in the severe range. 80% of control participants had total SRS-2 T-scores in normal range. Grit results were not significantly different between groups. Total anxiety scores and anxiety subscale scores were not significantly different between groups. Nevertheless, both participants with KCNJ11-NDM and sibling controls revealed greater levels of anxiety as a whole; 50% of KCNJ11-NDM participants (n=6) and 40% of unaffected controls (n=4) had mean total anxiety scores ≥ 25, indicating the possible presence of a clinical anxiety disorder. Conclusion: The prevalence of social interaction challenges was high among KCNJ11-NDM participants, highlighting the importance of early clinical assessment and support for such problems. Results of the SRS-2 Motivation subscale and Grit, which measure more intrinsic levels of personality, may suggest that individuals with KCNJ11-NDM exhibit intrinsic motivation and grit. Elevated overall anxiety levels in both KCNJ11-NDM participants and sibling controls suggest the need for early assessment and supportive interventions for families affected by KCNJ11-NDM. Presentation: Saturday, June 17, 2023

Fetal sex and the development of gestational diabetes mellitus in gravidae with multiple gestation pregnancies.

There is an increasing incidence of pregnancies with twin gestations. One outcome more likely to occur with multiple gestations is gestational diabetes mellitus. Studies have suggested that in singleton pregnancies, fetal sex may affect insulin resistance. However, the effects of fetal sex in twins and the development of gestational diabetes mellitus are unknown. We hypothesized that rates of gestational diabetes mellitus and degree of insulin resistance might vary in twin gestations based on the fetal sex pairing: male-male, male-female or female-female. We aimed to employ a large population-based database to ascertain any correlations between fetal sex and gestational diabetes mellitus in multifetal gestations. A two-hospital, single academic institution database comprised of over 39 000 participants with pregnancy data from August 2011 to January 2022 was employed. All twin deliveries of live-born neonates >24 weeks' gestational age from gravidae without preexisting diabetes or twin-twin transfusion syndrome were included. Entries were then grouped based on the fetal sex of the pairing. The presence or absence of gestational diabetes and type of gestational diabetes - diet-controlled (gestational diabetes mellitus classification A1) vs medication-controlled (gestational diabetes mellitus classification A2) - were identified. Statistical analysis was performed using a generalized linear mixed method, and a P-value ≤0.05 was considered statistically significant. We identified 1924 twin deliveries that met the inclusion criteria in our database (male-male =652; male-female = 638; female-female = 634). We found no association between fetal sex pairing and the development of gestational diabetes mellitus. There was a significant association between the fetal sex pairing and the type of gestational diabetes mellitus developed, with 32.0% of male-male twins, 33.3% of male-female twins and 58.3% of the female-female twin deliveries associated with medication-controlled gestational diabetes classification A2: male-female vs female-female (P = 0.05) and male-male vs female-female (P = 0.046). While gestational diabetes mellitus is of multifactorial origin, we found a significant association between the fetal sex pairing and the treatment needed for gravidae with twins who develop gestational diabetes mellitus. A higher proportion of female-female twins was associated with gestational diabetes classification A2 compared with male-female or male-male deliveries. Further research on the physiology driving this association is warranted.

Asymptomatic and Symptomatic Hyperuricemia: an Innovative Treatment Strategy

Asymptomatic hyperuricemia is associated with many somatic diseases, the onset and progression of chronic kidney disease (CKD), with an increase in cardiovascular and general mortality. Symptomatic hyperuricemia – gout and various variants of kidney damage, despite the availability of modern rheumatological, urological and nephrological guidelines, does not lose its relevance, as it is characterized by a severe course, significantly worsens the quality of life, increases cardiovascular risk and leads to disability. Hyperuricemia is a persistent increase in the concentration of uric acid (UA) in blood serum (above 360 μmol/l). The appointment of urate-lowering therapy (ULT) for gout is based on the Guidelines of the American College of Rheumatology (ACR, 2020), the European League Against Rheumatism (EULAR, 2016), the National Institute for Health and Care Excellence (NICE, 2022), in the case of urolithiasis – the Guidelines of the European Association of Urology (EAU, 2023) and the American Urological Association (AUA, 2019). Asymptomatic hyperuricemia, from the point of view of the evidence base, requires only the use of lifestyle modification measures. The Austrian Society of Rheumatology and Rehabilitation for patients with gout and hyperuricemia in 2022 proposed dietary and lifestyle recommendations, including sour cherries (Montmorency), which can lower UA levels. Combination of concentrated Montmorency tart cherry powder (1:50) and dry willow extract is an innovative strategy for the treatment of asymptomatic and symptomatic hyperuricemia, a natural hypouricemic agent with an anti-inflammatory effect, which is prescribed as a complementary therapy for gout and hyperuricemia in: cardiovascular diseases, diabetes and metabolic syndrome, CKD, urolithiasis. The appointment of сombination of concentrated Montmorency tart cherry powder (1:50) and dry willow extract will contribute to the achievement of the target value of the UA level in the blood serum of patients with asymptomatic and symptomatic hyperuricemia, the initiation of reno- and cardioprotection, the reduction of the risk of gout attacks, and the achievement of a stable and long interrelapse period.

Evaluating the effect of acupuncture on symptoms of diabetic peripheral neuropathy (DPN) among individuals with diabetic neuropathy: A single-blind, randomized trial study.

This study aimed to investigate the impact of acupuncture on Diabetic peripheral neuropathy (DPN) symptoms among individuals with diabetic neuropathy. In a single-blind, randomized trial conducted between 2019 and 2020, 60 patients diagnosed with diabetic neuropathy were enrolled. These participants were randomly assigned to either the intervention or control group. The intervention group received real acupuncture alongside routine treatment once a week for seven sessions, each lasting 20min. Meanwhile, the control group received sham acupuncture as an adjunct to their routine treatment, following the same schedule. To evaluate treatment efficacy, the study assessed primary outcomes, such as pain intensity measured using the Visual Analogue Scale (VAS). Secondary outcomes included evaluating fatigue severity and diabetic peripheral neuropathy (DPN) side effects, measured using the multidimensional fatigue inventory (MFI-20) and a standard questionnaire after each session. No statistically significant differences in pain and fatigue scores were observed between the two groups throughout all visits, even after adjusting for baseline characteristics, age, sex, type of diabetes, discopathy, and carpal tunnel syndrome parameters (P > 0.05). The findings did not provide strong evidence supporting a significant effect of real acupuncture compared to sham acupuncture on pain and fatigue values (P = 0.267 and 0.634, respectively). However, the 95% confidence interval for pain scores (-0.35, 1.28) was inconclusive, encompassing effect sizes favoring sham acupuncture. Findings suggest that using acupuncture as an adjunctive therapy alongside routine treatment may not lead to a significant reduction in the symptoms of peripheral neuropathy and fatigue severity among individuals with diabetic neuropathy. The online version contains supplementary material available at 10.1007/s40200-023-01314-1.

B-251 Nmr Lipoproteins Help to Reveal Subphenotypes of Phenoreversion from sars-cov-2 Infection

Abstract Background It is estimated that 10% of patients that suffered from severe acute SARS-CoV-2 infection experience symptoms beyond 3 months post-disease onset. Long COVID is a multisystemic condition that comprises more than 200 symptoms. Common new-onset medical conditions include cardiovascular, type-2 diabetes and chronic fatigue syndrome. Whilst progress has been made in characterising the mechanisms underlying long COVID, supported by similarities with other viral infections, available diagnostics are still insufficient. Molecular phenotyping is an established systems medicine tool that provides an integrative profile of an individual’s biological status that results from the cooperative genomic, transcriptomic and proteomic response to environmental stimuli. It exploits spectroscopic platforms based on nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) to generate precise information on a plethora of molecules that can be modelled to explain specific physiological and pathological conditions. Methods A well characterised longitudinal cohort with &amp;gt;200 SARS-CoV-2 positive individuals was collected in Cambridge Hospitals (2020, Wuhan strain). Each individual was classified according to the severity of its respiratory symptoms ranging from A (asymptomatic) to E (external ventilation). For each sample, cellular and immunological parameters, NMR lipoproteins, amino acid, tryptophan and lipidomics assays were measured. Functional PCA models captured latent dynamics in individual trajectories for C-reactive protein, an established marker of inflammation, and metabolic parameters found to be associated with it. Based on these trends, patient heterogeneity was explored using Gaussian mixture modelling and the resulting stratification was used to train personalised predictors of disease outcome using the first time point after onset as input. The addition of a penalty function during training ensured a parsimonious selection of parameters. Patients were asked to complete surveys months (2–6) after infection. Abundance and co-occurrence of symptoms was assessed using latent factor analysis. Results Linear mixed model regression revealed strong associations between C-reactive protein abundance and molecular parameters. Quinolinic acid, VLDL triglycerides and phospholipids, VLDL and IDL cholesterol and glycoprotein related GlycA are positively correlated, while tryptophan, taurine, indole-3-acetic acid, HDL cholesterol, and phospholipids and the supramolecular phospholipid composite (SPC) peak are strongly anti-correlated. Those findings are congruent with prior work on cohorts from Western Australia and Spain. In both cases, strong lipoprotein signatures were observed; GlycA is increased during acute phase, while SPC and HDL subfraction 4 are strongly depleted. The analysis of individual trajectories measured by CRP and associated parameters revealed 3 groups, mildly affected, good recovery and poor prospect. Patients from the last category showed profoundly altered metabolic profiles even weeks after onset, and a higher co-occurrence of neurological related symptoms. Furthermore, disease outcome scores were predicted for each patient in the early stage of infection. The training of these predictors also distilled a panel of most relevant parameters for that purpose. NMR lipoproteins featured excellent predictive capabilities. Conclusion Broad phenotyping, combined with multi-view multivariate analysis, allowed for robust stratification of COVID-19 patients and accurate personalised prediction of disease outcome. It also confirms the critical role played by lipoprotein metabolism in the immune response that is successfully captured by NMR-base lipoprotein parameters.

A-202 Establishing of Lipid-Apolipoprotein Connectivity Map in Hyperglycemia

Abstract Background Hyperglycemia, a condition characterized by a significantly increased glucose level in the blood, can lead to insulin deficiency and pre-diabetes. Lack of insulin production also interferes with lipid metabolism and increases the risk for cardiovascular disease. Thus, diagnosis and treatment of hyperglycemic patients can benefit from advanced proteomics and lipidomics testing approaches. Methods Disease-focused serum samples from 50 specimens were collected and evaluated, including 29 specimens with a glucose level&amp;gt;180 mg/dL and 21 normal lipidemic specimens. The sample proteomics analysis was conducted with a Perfinity IDP workstation (Shimadzu Scientific, Columbia, MD, USA) using on-line protein digestion with an immobilized enzyme reactor (IMER) directly coupled to a HALO-C18 column (Advanced Materials Technology, Wilmington, DE, USA). Lipidomics data were collected with the Lipidyzer platform (AB SCIEX, Framingham, MA, USA). Statistical analysis was conducted using JMP software (SAS Institute, USA) and custom scripts. Results Using targeted lipidomics and proteomics platforms we identified 20 proteins and 575 lipid species across 10 lipid subclasses. We identified specific lipids and lipoproteins dysregulated in hyperglycemic specimens as compared to the normolipidemic samples and linked them to major metabolic pathways. Lipoprotein particles related-proteins apos A1/B/C2/C3/E and lecithin–cholesterol acyltransferase (LCAT) were significantly dysregulated and associated with changes in HDL-mediated lipid transport, very-low-density lipoprotein particle remodeling, acylglycerol homeostasis, and triglyceride homeostasis. Conclusion The conducted integrated analysis of lipid and protein concentrations in hyperglycemia specimens to provide new insights into molecular changes associated with hyperglycemia that may inform new diagnostic and therapeutic strategies. The network analysis can allow improved categorization of patients that can lead to more effective and individualized therapeutic intervention approaches. This study provides new experimental and informatics approaches to better assess underlying metabolic conditions and related diseases, including cardiovascular disease, diabetes, and metabolic syndrome. Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC.

Protective effect of probiotic Limosilactobacillus reuteri DSM17938 against western diet-induced obesity and associated metabolic alterations

PurposeTo evaluate the possible application of Limosilactobacillus reuteri DSM 17938 as a strategy to prevent Western Diet-induced metabolic alterations and liver dysfunction. MethodsMale Wistar rats of 90 days were divided in three groups and fed a control diet (CD), a high fat - high fructose diet alone (WD) or in combination with the administration of 108 CFU of L. reuteri (WD-R) for 8 weeks. Body composition, energy balance and plasma lipid profile were evaluated, together with hepatic glucose homeostasis and insulin sensitivity. Metabolic inflammation was also assessed at a whole-body level and in the liver, together with mitochondrial function and oxidative stress. ResultsRats that received the WD and L. reuteri administration exhibited a lower body lipid gain and a higher protein gain, underlying a beneficial effect of the probiotic in counteracting the development of obesity. Moreover, the WD-R rats were protected from the development of inflammation at a whole body and liver level and displayed normal glucose homeostasis and insulin sensitivity, a decreased hepatic lipid deposition and a preserved function of the mitochondrial respiratory chain and redox balance. ConclusionsWe demonstrate for the first time that Limosilactobacillus reuteri DSM 17938 has a strong efficacy in preventing the development of the hepatic metabolic derangement elicited by the Western diet administration. These are promising results that open the way for the use of this probiotic as a prevention strategy against the development of diet-related diseases, such as type two diabetes and metabolic syndrome.

Angiogenin Levels and Carotid Intima-Media Thickness in Patients with Type 1 Diabetes and Metabolic Syndrome.

It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic syndrome (MS). Therefore, we analyzed the relationship between angiogenin levels and carotid intima-media thickness (cIMT) in DM1 patients with and without MS. We found that angiogenin concentration was significantly lower in DM1 patients compared to controls, while the cIMT measurements were comparable. Exclusion of patients with MS, patients with hypertension, undergoing treatment, or cigarette smokers did not change these findings. Of note, when comparing the subgroups of DM1 patients with and without MS, there was no significant difference between angiogenin levels. However, we did note a significant difference in these levels after the exclusion of smokers. The comparison of cIMT in these subgroups showed a significant difference between the study subgroups. This difference was no longer observed when the age of the patients was taken into account. In summary, it can be concluded that metabolic syndrome in patients with type 1 diabetes does not appear to impact angiogenin levels or cIMT.