Indicator Of Glycemic Control Research Articles

Dual impact analysis of GSTT1 polymorphisms on the metformin response and cardiovascular risk: A novel integrated approach in type 2 diabetes mellitus management

Although genetic variations in glutathione S-transferase (GST) have been linked to type 2 diabetes mellitus (T2DM), the relationships among GSTT1 polymorphisms, metformin effectiveness, and cardiovascular risk remain unclear. This study investigated the association between the GSTT1 null genotype and the metformin monotherapy response while simultaneously assessing its impact on atherosclerotic cardiovascular disease risk. This case-control study examined 84 T2DM patients aged 30-70 years, categorized into metformin therapy responders and nonresponders. This study employed multiplex PCR for GSTT1 genotyping and utilized the pooled cohort equation for cardiovascular risk assessment, offering a comprehensive analysis of both genetic and clinical parameters. GSTT1 genetic variations were not significantly associated with metformin response (odds ratio [OR] 1.773, p=0.306) or cardiovascular risk (OR 1.086, 95% CI: 0.46-2.56, p=1.000). The analysis revealed distinct patterns in clinical parameters between the GSTT1 null and wild-type genotypes, particularly in terms of glycemic control indicators and lipid profiles, although these differences did not reach statistical significance. This study presents a novel approach by simultaneously examining both the therapeutic response and cardiovascular risk in relation to GSTT1 polymorphisms, distinguishing it from previous studies that typically focused on either aspect in isolation. These findings suggest that while genetic variations in GSTT1 may influence metabolic parameters, their direct impact on metformin effectiveness and cardiovascular risk may be more complex than previously thought.

Comparative Effectiveness of Oral Hypoglycemic Agents for Glycemic Control and Glycemic Variability in Patients with Type 2 Diabetes Mellitus: Using Flash Glucose Monitoring.

The study aimed to compare the effectiveness of oral hypoglycemic agents (OHAs) as monotherapy, dual and quadruple therapy for glycemic control (GC) and glycemic variability (GV) in patients with type 2 diabetes (T2DM) using flash glucose monitoring system (FGM). Diabetes management largely relies on HbA1c monitoring. Glycemic variability has been an evolving glycemic target for preventing complications related to type 2 diabetes mellitus. The purpose of the study was to compare glycemic control measures and glycemic variability measures among study groups and to study the relationships between GC and GV indices. Retrospectively, FGM data were collected from 50 T2DM patients. The patients were classified based on prescribed number of OHAs as monotherapy [group 1: Dipeptidyl peptidase- 4 (DPP-4) inhibitors (n=10), group 2: Sodium-glucose co-transporter-2 (SGLT2) inhibitors (n=10), group 3: Sulphonylureas (n=10), group 4: Dual therapy (n=10), and group 5: Quadruple therapy (n=10)]. Measures of GC and GV were evaluated. Significant differences between study groups were observed in GC and GV measurements. The SGLT2 inhibitors monotherapy group demonstrated optimal GC [eA1c (%): 6.5 ± 2.2; MBG: 140.80 ± 63.94; TIR: 60.60 ± 19.96] and GV (SD: 42.38 ± 34.57; CV: 27.85 ± 6.68; MAGE: 96.76 ± 52.47; MODD: 33.96 ± 22.91) in comparison to other study groups. On using Pearson correlation analysis, mean blood glucose (MBG) and mean amplitude of glycemic excursion (MAGE) showed moderate correlation (r = 0.742)(r2 = 0.551), depicting distinct glucose variabilities at the same mean blood glucose levels. The monotherapy group of SGLT2 inhibitors demonstrated glucose-lowering effects with reduced glycemic variability. Hence, optimum glycemic control is associated with decreased glycemic variability.

Differential effects of liraglutide naltrexone/bupropion, and caloric restriction on metabolic parameters and beta-cell regeneration in type 2 diabetic rat model: role of beta arrestin 1.

Traditional antidiabetic treatments often carry the risk of beta-cell exhaustion, highlighting the need for therapies that promote beta-cell regeneration. This study investigates the comparative effects of Liraglutide, naltrexone/bupropion (NTX + BUP), and caloric restriction on metabolic control and beta-cell regeneration in a rat model of obese type 2 diabetes. Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + caloric restriction (50%), diabetic + NTX + BUP (4mg/45mg /kg/day orally), and diabetic + liraglutide (0.3mg/kg/day, S.C). Body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 were assessed. All interventions significantly improved body weight, BMI, glycemic control, lipid profiles (except HDL), and atherogenic indices compared to the diabetic control group. NTX + BUP and caloric restriction resulted in greater weight loss compared to liraglutide. Of note, liraglutide significantly decreased β-arrestin-1 levels compared toboth NTX + BUP and caloric restriction. Furthermore, liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 indicating beta-cell regeneration, whileNTX + BUP showed insignificant effects. Thus we can conclude that,while NTX + BUP demonstrates efficacy in improving metabolic parameters in obese type 2 diabetic rats, it shows limitations in promoting beta-cell regeneration compared to liraglutide and caloric restriction.

Fructosamine as an Indicator forGlycemic Control inthe Veteran Community.

Glycemic monitoring via Hemoglobin A1(HbA1c) proves to be inaccurate when a patient is diagnosed with a hemoglobinopathy/erythrocyte disorder. Moreover, any acute changes of glycemic intake within 6 weeks of blood sampling have been noted to impart a greater effect on HbA1c than the remaining days of the supposed overall 3-to-4-month average of glycemic control. Fructosamine, an alternative to HbA1c, allows physicians to analyze glycemic control in the presence of an underlying hemoglobinopathy/erythrocyte disorder. Fructosamine analyzes glycemic control over a two-to-three week period, compared to a 3-to-4-month period with HbA1c. Studies indicate that fructosamine is significantly correlated with HbA1c in various population types. Given the increased likelihood of hemaglobinopathies/erythrocyte disorders in the veteran population accompanied by the the necessity for tighter glycemic evaluation, fructosamine offers an assay for physician when analyzing glycemic control in veterans. The aim of our study was to evaluate the correlation of HbA1c and fructosamine in the veteran community. We hypothesize that fructosamine is significantly correlated with HbA1c in the veteran community and therefore can be used as an alternative assay in the Veterans Affairs. Following institutional review board review and exemption, a retrospective chart review was conducted at the Northport Veterans Affairs between the dates of December 2007 and December 2018. Inclusion criteria consisted of veterans above the age of 18 years with a HbA1c and fructosamine assay drawn from the same blood sample. Exclusion criteria consisted of veterans with an underlying hemoglobinopathy, erythrocyte disorder, or serum protein altering pathology. Linear regression analysis was conducted between HbA1c and fructosamine values. Linear regression equation, correlation coefficient, and coefficient of variance were reported. A paired t-test was conducted between assay HbA1c and predicted HbA1c from the determined regression equation. A total of 156 veterans were included in this study. A correlation coefficient and coefficient of variance of 0.75 and 0.56 were calculated from regression analysis (P < 0.05). A regression equation of the following was determined: HbA1c{%} = 0.0154*Fructosamine (mmol/L)+ 3.121. Paired t-test of assay HbA1c (M = 8.17, standard deviation = 1.64) and predicted HbA1c (M = 8.21, standard deviation = 1.53) returned without significance for difference of paired values. Given that both correlation coefficient and coefficient of variance were considered significantly strong and the paired t-test indicated no significant difference between assay HbA1c and predicted HbA1c, fructosamine can be considered as an alternative assessment of glycemic control compared to HbA1c in the veteran community. We advise physicians at the Veterans Affairs to use fructosamine as an assessment of glycemic control when a veteran is diagnosed with an underlying hemoglobinopathy/erythrocyte disorder or requires stringent analysis of glycemic control. Yet, at this point of time, fructosamine does not have the necessary data to indicate complete replacement of HbA1c with fructosamine.

Comparative analysis of bone health and glycemic control in postmenopausal women: insights from clinical data

Abstract Background Menopause leads to significant physiological and biochemical alterations that impact different aspects of health, such as bone mineral metabolism and glycemic control. It is imperative to comprehend these alterations in order to identify potential health hazards and develop preventative measures. This comparative cross-sectional study aimed to evaluate bone-associated markers and glycemic control indices in postmenopausal women (PMP). Methods A sample of 100 women aged 30 years or older was randomly selected and categorized into three groups: PMP (n = 60), premenopausal (PRM) (n = 20), and women in the reproductive age group (RWA) (n = 20). Venous blood samples were collected, and fasting blood glucose (FBG), calcium, phosphorus, uric acid, and alkaline phosphatase (ALP) levels were analyzed using standard laboratory techniques. The insulin and estrogen levels were evaluated using enzyme-linked immunosorbent assay (ELISA), and Homeostasis model assessment of insulin resistance (HOMA-IR), Quantitative insulin sensitivity check index (QUICKI), and Fasting insulin resistance index (FIRI) were calculated. A significance level of p &lt; 0.05 was used in the statistical analysis conducted using SPSS version 25.0. Results The PMP and PRM groups showed significantly greater mean values of FBG, insulin, and HOMA-IR when compared to RWA (p &lt; 0.05), while these groups had lower QUICKI levels. Similar trends were noted for bone-associated markers, with significant differences among the groups (p &lt; 0.05). The correlation results showed that QUICKI had positive correlations with both ALP and phosphorus, while FBG and FIRI had negative connections with both. Conclusion Postmenopausal women demonstrated higher levels of glycemic control indices and bone-related markers compared to premenopausal and reproductive-age women, indicating potential risks for osteoporosis and obesity.

Glycemic Control and Adult Height: A Nationwide Swedish Cohort Study on Childhood Type 1 Diabetes

Abstract Context Normal growth throughout childhood and adolescence is considered an indicator of adequate glycaemic control in patients with type 1 diabetes. While it has been suggested that growth in type 1 diabetes is reduced, the literature is conflicting and differences in final adult height and the risk of short stature depending on glycaemic control remain largely unexplored. Objective This work aims to assess adult height outcomes across levels of glycemic control in children and adolescents with type 1 diabetes, as well as to investigate the effect of sex, age at disease onset, and timing of glycemic control in relation to puberty. Methods In this population-based Swedish cohort study, we collected data on glycemic control and height from specialist health-care visits of all individuals with childhood-onset type 1 diabetes in the National Diabetes Register. Using linear and logistic regression, we compared suboptimal (glycated hemoglobin A1c [HbA1c] 53-75 mmol/mol [7.0-9.0%]) and poor (HbA1c &amp;gt; 75 mmol/mol [&amp;gt;9.0%]) to optimal (HbA1c &amp;lt; 53 mmol/mol [&amp;lt;7.0%]) glycemic control in relation to final adult height and the risk of short stature. Results Poor glycemic control was associated with lower final adult height (−2.91 cm [95% CI, –3.48 to −2.33] for males, −1.83 cm [−2.42 to −1.23] for females) as well as a higher risk of short stature in males (odds ratio 1.90 [1.07-3.35]) but not in females (0.73 [0.36-1.51]). For females, adult height was lower only among those with type 1 diabetes since before puberty and if the poor glycemic control occurred before puberty. For males, adult height was lower irrespective of their age at diabetes onset, but only if they had poor glycemic control during or after puberty. Conclusion Poor glycemic control after the onset of type 1 diabetes, compared to optimal control, is associated with lower adult height in males and females. The prepubertal period seems to be more critical for females than males.

Association of serum uric acid levels with glycated haemoglobin in diabetic patients and healthy controls.

Uric acid is formed from purine degradation. Hyperuricemia has emerged as a risk factor for various metabolic diseases including Diabetes mellitus (DM). Uric acid may act as a glucometabolic indicator for Type 2 Diabetes mellitus (T2DM). Glycated haemoglobin (HbA1c) is an indicator of long-term glycaemic control used for diagnosing and monitoring T2DM. However, the association between HbA1c and uric acid is controversial. The present study aimed to study the association of serum uric acid (SUA) levels with HbA1c. This cross-sectional comparative study was conducted in a Tertiary Care Hospital in Northern India after permission from the institutional Ethical committee. The study included patients attending the Outpatient Department of the hospital during the study period. Diagnosed cases of DM as per World Health Organization criteria were included as cases. Controls comprised of apparently healthy subjects of the age group 18-50 years attending OPD Patients and Health Care workers. Both cases and control were divided into two groups those with normal uric acid levels and the hyperuricemia group in both males and females to study the association between HbA1c and uric acid levels. The study constituted 1460 participants of which 880 control and 580 DM. The overall prevalence of hyperuricemia was 17.8%. HUA prevalence was 17.04%-18.9% in the control and diabetic population, respectively. SUA levels in T2DM patients were negatively correlated with glycated HbA1c, and FBS whereas positively correlated with glycated HbA1c in controls. While non-diabetic individuals tend to exhibit higher SUA levels, a decreasing trend has been observed in diabetic individuals. A negative association was observed between SUA level and HbA1c in DM in contrast to controls. Therefore, the utilization of SUA as a marker for assessing glucose metabolism should be approached with careful consideration taking care of these complex dynamics.

Effectiveness and Safety of the TRIO Optimal Health Management Program in Patients with Type 2 Diabetes Mellitus (T2DM) Initiating Basal Insulin Therapy: Real-World Study.

Diabetes, a chronic disease necessitating long-term treatment and self-management, presents significant challenges for patients who spend most of their treatment time outside of hospitals. The potential of digital therapeutics for diabetes has garnered recognition from different organizations. Although some prior studies have demonstrated successful reductions in patients' blood glucose levels and body weight through digital diabetes programs, many studies were limited by including prediabetes patients, patients treated with mostly premixed insulin, or evaluating user engagement outcomes rather than clinical outcomes. Consequently, limited evidence remains regarding the effectiveness of health management mobile applications specifically designed for T2DM patients initiating BI (basal insulin). Based on this, a data-based and artificial intelligence management system named TRIO was developed to provide patients with more personalized intervention methods in stages, groups, and around the clock. TRIO assists doctors and nurses in achieving better blood glucose controls, truly carries out standardized management around patients, and allows them to have a higher quality of life. TRIO represents the three essential pillars in comprehensive diabetes management: physician, nurse, and patient. This prospective observational study evaluated the effectiveness and safety of the TRIO optimal health management program for patients with type 2 diabetes mellitus (T2DM) initiating basal insulin therapy in a real-world setting. Patients aged 18 to 85 with inadequate glycemic control (baseline HbA1c ≥7.0%) starting basal insulin therapy were enrolled in outpatient and inpatient settings. The study was 3 months, with health education and phone-based follow-up assessments. Data collected included patient characteristics, medical history, baseline diabetes conditions, treatment compliance, glycemic control, and safety indicators. A total of 199,431 patients were included, and 118,134 patients completed the 3-month follow-up between Dec 1, 2019, and Dec 31, 2021, involving 574 hospitals in China. The mean baseline HbA1c was 9.2%, the mean duration of diabetes was 7.3 years, and 80.4% of patients were using basal insulin with oral antihyperglycemic drugs. After the intervention, mean HbA1c decreased by -2.59% from baseline, with 55.6% achieving the target HbA1c level of <7.0%. Patients who set lower fasting plasma glucose (FPG) goals (<6.1 mmol/L) showed more significant HbA1c reductions and higher target achievement compared to those with FPG goals≥6.1 mmol/L. Factors such as complications, diabetes duration, and baseline HbA1c levels influenced the magnitude of HbA1c reduction. The presence of complications, shorter diabetes duration, and higher baseline HbA1c were significantly associated with increased hypoglycemia incidence risk. The TRIO optimal health management program effectively improved glycemic control in patients with T2DM initiating basal insulin therapy. Individualized treatment approaches considering patient characteristics and glycemic goals are vital for optimal outcomes. This real-world study was approved by the Ethics Committee of Nanjing Drum Tower Hospital (IRB Review Approval Document, Code: 2019-231-01).

Hypomagnesaemia and Relationship Lipid Profile in Type 2 Diabetes Patients at Janzur Hospital in Libya.

Type 2 diabetes mellitus (T2DM) is associated with increased morbidity and mortality due to the development of complications, especially due to poor glycemic control. Magnesium (Mg) is a crucial element in human health, and its deficiency plays a critical role in the development of lipid abnormalities and the initiation of diabetic complications. The study aimed to evaluate the correlation of hypomagnesemia (Mg) with the alteration of lipid profile patterns and investigate the adverse effects of glycemic control and body mass index (BMI) on magnesium levels among patients with T2DM. A total of 163 subjects whose ages ranged between 35-60 years for both sexes (males and females) were included in this study: 90 type II diabetic patients (40 males and 50 females) and 73 healthy individuals (34 males and 39 females) in Tripoli region, Western Libya. Blood glucose, HbA1c, Magnesium, and lipid profile parameters were biochemically estimated in the study along with the measurement of BMI. All the results were statistically analyzed using SPSS version 25 for applying one-way ANOVA and Person's correlation coefficient tests. The study revealed a significant decrease in serum magnesium levels (1.59 ± 0.47 mg/dL) in T2DM patients compared to the control group (2.21 ± 0.70 mg/dL) (p &lt; 0.01). Significantly elevated levels of blood glucose (140.6 ± 30.95 mg/dL vs. 89.80 ± 12.62 mg/dL, p &lt; 0.01), HbA1c (7.27 ± 2.62% vs. 5.32 ± 0.65%, p &lt; 0.01), cholesterol, triglycerides and LDL cholesterol also observed in T2DM patients compared to healthy individuals. Conversely, HDL cholesterol levels were significantly lower in the T2DM group than in controls (24.44 ± 8.88 mg/dL vs. 47.06 ± 8.75 mg/dL, p &lt; 0.01). There is a relationship between hypomagnesemia, glycemic control, and changed lipid profile in T2DM patients. Further, our results revealed a strong relationship between increased BMI and unfavorable alterations in all biochemical parameters examined.

7941 Comparison of Metformin with Inositol versus Metformin Alone in Women with Polycystic Ovarian Syndrome (PCOS): A Systematic Review and Meta Analysis of Randomized Controlled Trials

Abstract Disclosure: F.A. Kelly: None. A.D. Lôbo: None. I.B. Andrade: None. P.G. Lima: None. I.P. da Silva: None. M.C. Souza: None. V. Morbach: None. M.S. Barros: None. F.A. Moraes: None. M.B. Jardine: None. L.M. Lopes: None. M.P. Lima: None. M.G. Leite: None. R.Y. Ura Sudo: None. J.C. Cardoso: None. A.M. De Almeida: None. F.D. Pessôa: None. Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. It addresses the chronic inflammatory state of PCOS and improves ovulation, metabolic parameters, and fertility.In recent years, inositols, specifically myo-inositol, and D-chiro-inositol, have emerged as potential treatment options for PCOS. These compounds act as a messenger for hormones, including insulin and follicle-stimulating hormones. Inositols effectively address insulin resistance and modulate the insulin signaling pathways.Although inositols have recently been included in the recommendations of the European Journal of Endocrinology's 2023 International evidence-based guideline for improvement in metabolic measures and considered with benefits in ovulation, hirsutism, and weight in patients with PCOS, the confidence in the available evidence supporting their use is considered to be limited. We aimed to perform a meta-analysis to understand the role of inositol, on glycemic control, LH/FSH ratio, hirsutism, HOMA-IR, and body mass index (BMI) in individuals with polycystic ovary syndrome (PCOS).PubMed, Embase, and Cochrane databases were systematically searched for RCTs comparing the use of metformin alone versus metformin and inositol in patients with polycystic ovary syndrome. Statistical analysis was performed in R software 4.3.1. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of &amp;lt; 0.05 was considered statistically significant. Heterogeneity was examined with the Cochran Q test, prediction interval, and I² statistics. A total of 4 RCTs and 277 patients were included, of whom 138 were randomized to metformin alone and 139 to metformin plus myo-inositol. Compared with metformin alone, Myo-inositol plus Metformin significantly reduced hirsutism (MD -0.97; 95% CI -1.53; -0.40; p=0.0008) and LH/FSH ratio (MD -0.15; 95% CI -0.26, -0.03; p=0.02). There was no significant difference between groups for BMI (MD: 0.97; 95% CI -0.37, 2.32; p=0.16) and HOMA-IR (MD -0.17; 95% CI -0.35, 0.01; p=0.07).In this meta-analysis of RCTs of patients with polycystic ovary syndrome, inositol was associated with a reduction in hirsutism and LH/FSH ratio, compared with metformin monotherapy. Further studies are needed to clarify whether there are benefits for the use of inositol in PCOS treatment. Presentation: 6/3/2024

Effects of probiotics supplementation on glycemic profile in adults with type 2 diabetes mellitus: A grade-assessed systematic review and dose–response meta-analysis of randomized controlled trials

BackgroundDisturbed glycemia and the resulting type 2 diabetes (T2D) are significant health concerns. Various approaches have been examined to improve glycemic control in patients with T2D. Modification of gut microbiome via administering probiotics has been extensively studied. The present study aims to sum up the existing literature which investigated the effect of probiotics on glycemic indices in individuals with T2D in the format of randomized controlled trials (RCTs). MethodsOnline medical databases (PubMed, Scopus, and Web of Science) were searched from inception to January 2024. Eligible studies were included using pre-defined inclusion and exclusion criteria. Outcome variables included fasting blood sugar (FBS), insulin, hemoglobin A1c (HbA1c), and homeostatic model of insulin resistance (HOMA-IR). Weighted mean differences (WMDs) were estimated. Subgroup and dose-response analyses were conducted. P-values <0.05 were considered as statistically significant. ResultsOut of 5,636 records retrieved by the initial search, thirty-two RCTs were included in the final analyses. Supplementation with probiotics was observed to significantly improve indices of glycemic control; including FBS (WMD: -13.27 mg/dl; 95% CI: -18.31, -8.22), HbA1c (WMD: -0.44 %; 95% CI: -0.59, -0.28), insulin (WMD: -1.33 μIU/ml; 95% CI: -2.57, -0.08), and HOMA-IR (WMD: -0.95; 95% CI: -1.71, -0.18). Dose-response analysis revealed that increased duration of intervention results in a larger reduction only in FBS. ConclusionSupplementation with probiotics seems to improve indices of glycemic control. Nonetheless, taken into account the notable heterogeneity (with regard to dosage, duration, and the species/strains used) between the included studies and low quality of evidence, caution must be considered, especially when long-term clinical implications are intended.

Effects of glycaemic control on memory performance, hippocampal volumes and depressive symptomology

BackgroundDiabetes and poor glycaemic control have been shown to negatively impact cognitive abilities, while also raising risk of both mood disorders and brain structural atrophy. Sites of atrophy include the hippocampus, which has been implicated in both memory performance and depression. The current study set out to better characterise the associations between poor glycaemic control, memory performance, and depression symptoms, and investigate whether loss of hippocampal volume could represent a neuropathological mechanism underlying these.Methods1331 participants (60.9% female, age range 18–88 (Mean = 44.02), 6.5% with likely diabetes) provided HbA1c data (as an index of glycaemic control), completed a word list learning task, and a validated depression scale. A subsample of 392 participants underwent structural MRI; hippocampal volumes were extracted using FreeSurfer.ResultsPartial correlation analyses (controlling for age, gender, and education) showed that, in the full sample, poorer glycaemic control was related to lower word list memory performance. In the MRI sub-sample, poorer glycaemic control was related to higher depressive symptoms, and lower hippocampal volumes. Total hippocampus volume partially mediated the association between HbA1c levels and depressive symptoms.ConclusionsResults emphasise the impact of glycaemic control on memory, depression and hippocampal volume and suggest hippocampal volume loss could be a pathophysiological mechanism underlying the link between HbA1c and depression risk; inflammatory and stress-hormone related processes might have a role in this.

Effects of 12-weeks resistance training and vitamin E supplementation on aminotransferases, CTRP-2, and CTRP-9 levels in males with nonalcoholic fatty liver disease: a double-blind, randomized trial

BackgroundNonalcoholic fatty liver disease (NAFLD) involves excessive liver fat accumulation and is closely linked to oxidative stress, which contributes to liver inflammation and damage. This study aimed to evaluate how interventions such as resistance training (RT) and vitamin E supplementation (VES) can modulate markers of NAFLD and key proteins regulating glucose and lipid metabolism, such as C1Q/TNF-related proteins (CTRPs).MethodsForty participants with NAFLD (mean age: 32.4 ± 8.2 years) were randomly assigned to one of four groups for 12 weeks: placebo (PLB), VES, PLB + RT, and VES + RT. VES was administered at 800 IU/day in a double-blind manner. The RT regimen included eight exercises at 60–80% of one-repetition maximum (1RM), with three sets of 8–12 repetitions, performed three times per week. Pre- and post-intervention assessments included body composition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid profile, glycemic control, CTRP-2, CTRP-9, and 1RM evaluations.ResultsFollowing the interventions, there was a significant improvement in body composition, lipid profile, glycemic control, and 1RM indices in the exercise groups compared to non-exercise groups (p < 0.05). AST and ALT levels decreased in all groups (p < 0.05) compared to the PLB group. There was also a significant difference between the VES + RT group and both the VES and PLB + RT groups (p < 0.05). CTRP-2 and CTRP-9 levels decreased in the exercise groups compared to non-exercise groups (p < 0.05), and their changes showed a marked correlation with body composition, lipid profile, and glycemic control indices (p < 0.05).ConclusionsThis study highlights the benefits of RT on various health parameters among NAFLD patients. While adding VES to RT resulted in greater decreases in aminotransferases, it did not provide further improvements in other variables. Additionally, enhancements in body composition, lipid profile, and glycemic control indices were possibly associated with decreased levels of CTRPs.Trial registrationRegistered retrospectively in the Iranian Registry of Clinical Trials (IRCT20220601055056N1) on December 21, 2023. Access at https://irct.behdasht.gov.ir/trial/69231.

Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

CLINICAL SIGNIFICANCE OF FLASH MONITORING GLYCEMIA INDICATORS IN CHILDREN WITH TYPE 1 DIABETES MELLITUS

One of the basic principles of the treatment of type 1 diabetes mellitus, along with insulin therapy and diet therapy, is regular self-monitoring of glycemia. Glucose meters are most often used for daily self-monitoring, and in recent years devices for continuous and flash monitoring of glycemia have been used. The article discusses the clinical aspects of the application of a glycemic monitoring system with periodic scanning (flash monitoring). The principle of operation of the system is described, as well as the main parameters obtained when using this system – time in the target range, time above and below the target range and their sub-ranges, an indicator of glycemic variability and an indicator of glycemic control, their normative levels, as well as their practical significance and relationship with the clinical aspects of the course of diabetes mellitus and the prognosis of chronic complications. The results of major international and domestic studies on the effectiveness of the flash monitoring system in different age groups are presented. The advantages of the second generation of flash glycemia monitoring sensors are described, and the results of clinical studies of the accuracy of this monitoring system in both children and adult patients with diabetes mellitus are presented.

Correlation Between Hemoglobin A1c (HbA1c) and High-Sensitivity C-Reactive Protein (hs-CRP) in Myocardial Infarction Patients and Their Six-Month Mortality Follow-Up.

Background Acute coronary syndrome (ACS), encompassing unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI), poses significant global health challenges because of its associated high mortality and morbidity rates. Vascular inflammation plays a crucial role in the pathogenesis of atherosclerosis, and it is often assessed using biomarkers such as high-sensitivity C-reactive protein (hs-CRP). Hyperglycemia, common in myocardial infarction patients, is linked to increased complications and mortality, with glycosylated hemoglobin A1c (HbA1c) serving as a key indicator of long-term glycemic control. Objective This study investigates the correlation between hs-CRP and HbA1c levels in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM) and evaluates their impact on six-monthmortality outcomes. Methods A prospective observational study was conducted with 80 patients diagnosed with AMI. Data collection included demographic information, medical history, clinical assessments, laboratory investigations (including hs-CRP and HbA1c levels), and imaging studies. Patients received standard treatment and were followed up for six months. Statistical analyses were performed to examine the relationships between hs-CRP, HbA1c, and clinical outcomes. Results Higher HbA1c levels at admission were significantly correlated with elevated hs-CRP levels (p < 0.05). Both biomarkers showed a reduction at six months, correlating with improved glycemic control and reduced inflammation. Each unit increase in HbA1c was associated with a 21% increase in the hazard of mortality, and, similarly, each unit increase in hs-CRP was associated with a 17% increase in the hazard of mortality. The positive correlation between HbA1c and hs-CRP suggests that HbA1c can serve as an independent marker for predictingmortality in this patient population. Conclusion The study demonstrates a significant correlation between hs-CRP and HbA1c levels in patients with AMI and T2DM, with both biomarkers serving as strong predictors of six-monthmortality. HbA1c, because of its positive correlation with hs-CRP, could be used as an independent marker for assessing the risk of adverse outcomes in these patients. These findings highlight the importance of managing both glycemic control and inflammation in diabetic patients with ACSs.

Autologous hematopoietic stem cell transplantation as a method of immune prevention of type 1 diabetes mellitus: possibilities and prospects

Type 1 diabetes mellitus (DM) is one of the most common autoimmune disease that is treated with lifelong insulin therapy. Non-target indicators of glycemic control, which are observed in 71% of patients, lead to the formation and progression of diabetes complications, early disability and mortality. In this regard, the search for new approaches to the treatment and prevention of type 1 DM seems to be relevant. Various methods of immunological prophylaxis for the development of type 1 DM have been studied, in particular, the use of monoclonal antibodies. Thus, in November 2022, teplizumab was approved to slow down the clinical progression of the stage of type 1 DM. The prospects for the use of new options for islet cell transplantation are being studied — in June 2023, an allogeneic donor β-cell transplant obtained from the pancreas of donors after death was approved. Another pathogenetically substantiated method for the prevention and treatment of autoimmune diseases is high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT-HSCT). HDIT-HSCT demonstrated its effectiveness and cost-effectiveness in various clinical trials. This review provides up-to-date information on modern methods of immunological prophylaxis of type 1 DM.

Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations: Emulating a Target Trial Using Real-World Data.

Metformin is a first-line pharmacotherapy for type 2 diabetes, but there is limited evidence about its safety in early pregnancy. To evaluate the teratogenicity of metformin use in the first trimester of pregnancy. In an observational cohort of pregnant women with pregestational type 2 diabetes receiving metformin monotherapy before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: insulin monotherapy (discontinue metformin treatment and initiate insulin within 90 days of LMP) or insulin plus metformin (continue metformin and initiate insulin within 90 days of LMP). U.S. Medicaid health care administration database (2000 to 2018). 12 489 pregnant women who met the eligibility criteria. The risk and risk ratio of nonlive births, live births with congenital malformations, and congenital malformations among live births were estimated using standardization to adjust for covariates. A total of 850 women were in the insulin monotherapy group and 1557 in the insulin plus metformin group. The estimated risk for nonlive birth was 32.7% under insulin monotherapy (reference) and 34.3% under insulin plus metformin (risk ratio, 1.02 [95% CI, 1.01 to 1.04]). The estimated risk for live birth with congenital malformations was 8.0% (CI, 5.7% to 10.2%) under insulin monotherapy and 5.7% (CI, 4.5% to 7.3%) under insulin plus metformin (risk ratio, 0.72 [CI, 0.51 to 1.09]). Possible residual confounding by glycemic control and body mass index. Compared with switching to insulin monotherapy, continuing metformin and adding insulin in early pregnancy resulted in little to no increased risk for nonlive birth among women receiving metformin before pregnancy. Under conventional statistical criteria, anything between a 49% decrease and a 9% increase in risk for congenital malformations was highly compatible with our data. National Institutes of Health.

Time in range prediction using the experimental mobile application in type 1 diabetes

BACKGROUND: Time in range (TIR) is a promising indicator of glycemic control used for evaluation of continuous glucose monitoring (CGM) for patients with diabetes mellitus (DM). The current problem is the assessment and prediction of TIR for patients who use self-monitoring of blood glucose (SМBG) corresponding low CGM availability for the majority of diabetic patients.AIM: To develop a predictive model of TIR for patients with T1DM based on data of the experimental mobile application.MATERIALS AND METHODS: An analysis of 1253 professional CGM profiles of patients with T1DM was performed. On the base of included records, TIR(CGM) was calculated and training models of 7-point SMBG profiles were generated. SMBG profiles’re loaded into the developed experimental mobile application that calculated standard glycemic control parameters. The dataset was divided into main and test samples (80 and 20%). For the main sample, the following methods’re used to develop predictive models: simple linear regression (SLR), multiple linear regression (MLR), artificial neural network (ANN). The effectiveness of the developed models was assessed on the test sample with the calculation of the mean absolute error (MAE), the root mean square error (RMSE).RESULTS: The 568 CGM profiles’re included in the study. TIR in the main group (n=454) — 45 [33; 65]%, in the test group (n=114) — 43 [33; 58]%. The most significant predictors of the regression models were the derived TIR (dTIR), p&lt;0,001; derived time below range level 1 (dTBR1), p&lt;0,001; standard deviation of blood glucose (SD), p=0,007. Determination coefficient for SLR (predictor: dTIR) — 0,844; for MLR (predictors: dTIR, dTBR1, SD) — 0,907. ANN multilayer perceptron models with two and one hidden layers’re developed, with the RMSE on the validation set 4,617 and 6,639%, respectively. The results of the forecast efficiency on the test sample were: dTIR: MAE — 6,82%, RMSE — 8,60%; SLR: MAE — 5,66%, RMSE — 7,34%; MLR: MAE — 4,18%, RMSE — 5,28%; ANN (2 layers): MAE — 4,14%, RMSE — 5,19%; ANN (1 layer): MAE — 4,44%, RMSE — 5,52%.CONCLUSION: ANN with two hidden layers and MLR demonstrated the best ability for TIR prediction. Further studies are required for clinical validation of developed prognostic models.

Positive association of the anti-aging protein α-Klotho with insulin resistance and its inverse L-shaped relationship with glycaemic control in the middle-aged and elderly population.

α-Klotho has been linked to insulin resistance (IR) in basic research. However, experimental evidence is inconsistent, and there is a lack of data from human research. This study seeks to elucidate the association of α-Klotho with IR in a nationwide, multiracial population. A total of 5289 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho was measured using enzyme-linked immunosorbent assays (ELISA), and IR was evaluated by the homeostatic model assessment of insulin resistance (HOMA-IR). Weighted multivariate logistic and linear regression analysis, subgroup analysis stratified by demographic characteristics, medical condition or obesity status, and sensitivity analysis using propensity score matching (PSM) were performed. Restricted cubic splines (RCS) were performed to explore the nonlinear relationship. In the fully adjusted logistic regression model, a significant positive association was observed between log-transformed α-Klotho and IR (OR = 3.63, 95% CI: 1.56, 8.45), particularly in males or nonobese individuals (Pinteraction < 0.05). In the linear regression model, log10(α-Klotho) was associated with fasting blood glucose (FBG, β = 1.25, 95% CI: 0.74, 1.76) and glycosylated hemoglobin (HbA1c, β = 0.49, 95% CI: 0.20, 0.77). RCS revealed an inverse L-shaped dose-response relationship of α-Klotho with FBG and HbA1c (Pnonlinear <0.05). Beyond the inflection point of log10(α-Klotho) at 2.79, β coefficients sharply rose for these glycaemic control indicators. The study provides clinical evidence supporting a positive association between α-Klotho and IR. Moreover, the inverse L-shaped relationship suggests that α-Klotho should reach a certain level to predict glycaemic changes effectively.