Fasting Serum Research Articles

Association of systemic immune-inflammation index with insulin resistance and prediabetes: a cross-sectional study.

Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation. Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes. After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (β: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (β: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (β: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001). Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes.

Evaluation of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in patients with inflammatory bowel disease: gene expression of TNF-α as a marker of disease severity

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of unknown etiology and unpredictable course. The aim of the work was to assess the levels of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in IBD patients compared to controls and evaluate the gene expression of TNF-α as a marker of disease severity.MethodsAdropin, fasting serum FGF-1 levels, TLR1, and TNF-α were measured in 60 IBD patients. They were also compared with 58 healthy controls matching age and gender. Moreover, the blood cells cDNA copy number of TNF-α were determined as a marker of severity.ResultsAdropin and TLR1 levels were significantly lower in patients than controls. FGF-1 was reduced but not statistically significant. The expression of TNF-α gene in the IBD patients was significantly increased (42%) in comparison with control samples (P < 0.001).ConclusionsAdropin, IGF-I, and Toll-like receptor-1 biomarkers may have a role in the intricate pathophysiology of IBD and may possibly operate as predictors of disease activity. Thus, they may be therapeutic targets for IBD. Moreover, the expression of TNF-α gene can be used as a marker of severity.

Associations between time in range and insulin secretory capacity in Japanese patients with type 2 diabetes

Impaired insulin secretory capacity is associated with high glycemic variability in patients with type 2 diabetes (T2DM). However, there are no existing reports on the association between insulin secretory capacity and time in range (TIR). This retrospective study involved 330 T2DM admitted for diabetes education who underwent intermittently scanned continuous glucose monitoring (isCGM) and had their fasting serum C-peptide immunoreactivity (S-CPR) measured within 5 days of admission. The baseline characteristics were as follows: age, 60.2 years; glycated hemoglobin (HbA1c), 9.2%; S-CPR, 2.2 ng/mL; S-CPR index (S-CPR [ng/mL]/fasting plasma glucose [mg/dL] × 100), 1.6; and TIR, 60.3%. TIR correlated significantly with the S-CPR index, which was confirmed by multivariate analysis that included various factors such as HbA1c. Receiver operating characteristic (ROC) analysis showed that 1.88 was the optimal S-CPR index level to predict TIR ≥ 70%. In addition to HbA1c and biguanide use, the S-CPR index was a significant factor associated with TIR > 70%. S-CPR index values of ≥ 1.88 also correlated significantly with TIR > 70%. In conclusion, insulin secretory capacity is associated with TIR in Japanese T2DM, suggesting that the S-CPR index might be a potentially useful biomarker insulin secretory capacity, in association with TIR.Trial registration UMIN0000254333.

Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population.

To investigate three features of dietary cooking oil intake, namely, the consumption, cooking style, and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population. The elderly (≥ 65 years) participants for this study were recruited from two community health centers in the urban area of Shanghai. A questionnaire was administered to collect information on dietary oil consumption (low, medium and high) and cooking styles (fry or stir-fry vs. others) and the composition of fatty acids (poly-unsaturated vs. mono-unsaturated). The cardiometabolic measurements included anthropometry, blood pressure, fasting plasma glucose and serum lipids. The 1186 study participants had a mean age of 70.9 ± 5.4 years. The mean dietary oil consumption was 35.0 g/d, being low (< 25 g/d), medium (25-49 g/d) and high (≥ 50 g/d) in 485,467 and 234 participants, respectively. The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4% and 27.4%, respectively. Both before and after adjustment for sex, age, current smoking and alcohol intake, dietary oil consumption was significantly (P ≤ 0.02) and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration. With similar adjustments as above and additional adjustment for dietary oil consumption, the fry or stir-fry cooking style was significantly (P ≤ 0.048) and positively associated with body mass index, but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol, and the dietary intake of oils rich in mono-unsaturated fat acids was significantly (P ≤ 0.02) and positively associated with diastolic blood pressure, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol, and the prevalence of hypertriglyceridemia and hypercholesterolemia. This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in an elderly Chinese population.

The Comparison of Irisin, Subfatin, and Adropin in Normal-Weight and Obese Polycystic Ovary Syndrome Patients.

A combination of genetic and environmental factors contribute to the highly common, complex, and varied endocrine condition known as polycystic ovary syndrome (PCOS) in women. PCOS primarily affects women between the ages of 15 and 35 who are in the early to late stages of pregnancy. Thus, this study aimed to evaluate the serum levels of irisin, subfatin, and adropin in PCOS with and without obesity compared to the control group. The present cross-sectional study was conducted in 2022 at Al-Nahrain University/Department of Chemistry (Baghdad, Iraq). The serum levels of irisin, subfatin, and adropin were measured with the enzyme-linked immunosorbent assay (ELISA) method. Body mass index, lipid profile, insulin, fasting glucose, follicle-stimulating hormone, and luteinizing hormone levels were also evaluated. The data were analyzed using one-way analysis of variance (ANOVA) by GraphPad Prism software version 8.0.2. A P<0.05 was considered statistically significant. The study population comprised PCOS patients (n=90, divided into 45 obese and 45 normal weight) and healthy women (n=30). According to the results, the serum levels of irisin were significantly higher (P<0.001) in obese and normal-weight PCOS patients than controls. While adropin and subfatin were significantly lower in PCOS than controls (P<0.001). Moreover, there are higher levels of serum insulin, fasting glucose, and luteinizing hormone in PCOS women than in healthy women. According to the findings, PCOS patients had a higher level of irisin than the controls. In addition, decreased subfatin and adropin levels were observed in PCOS patients compared with healthy women. Further research is required to confirm these results in the future.

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab-paclitaxel plus gemcitabine as second or later-line treatment.

Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS. This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.

A case of tuberculosis of adrenal gland presenting as acute adrenal insufficiency following initiation of anti-tubercular therapy

Adrenal tuberculosis is one important cause of acute or chronic adrenal insufficiency in developing countries like India. There are many random cases in literature describing various clinical situations of adrenal tuberculosis presenting with adrenal insufficiency, especially after initiation of anti-tubercular therapy. A 43-year-old male recently diagnosed patient with pulmonary tuberculosis and chronic coronary syndrome was admitted for acute decompensated heart failure with pulmonary edema. He was taking fixed dose combination anti-tubercular therapy. During admission, he had hyponatremia (serum sodium 96 mEq/L) and during treatment, he developed hypotension and shock, which were appropriately treated. Due to ischemic hepatitis, anti-tubercular treatment (ATT) was modified to streptomycin, ethambutol, and ofloxacin regimen to avoid further hepatotoxicity. Hyponatremia and shock recovered. Rifampicin and isoniazid were restarted. He again developed easy fatigability, nausea, vomiting, and hypotension. Suspecting adrenal insufficiency, fasting serum cortisol, and adrenocorticotropic hormone (ACTH) were done, which revealed a low serum fasting cortisol and high ACTH. Computed tomography abdomen showed enlarged left adrenal gland with calcifications. He was started on prednisolone 2 mg/kg/day with full dose fixed dose ATT, following which his symptoms resolved.

Triglyceride-Fasting Glucose Index and Homeostatic Model Assessment for Insulin Resistance as Predictors of Type 2 Diabetes Mellitus in South Indians With Normal Body Mass Index.

Early detection of type 2 diabetes mellitus (T2DM) is imperative to prevent the complications associated with the disease. Current guidelines for diagnosis rely on the assessment of serum glucose (fasting and post-prandial) and glycosylated hemoglobin (HbA1c) levels. Insulin resistance, a phenomenon associated with T2DM, has been observed before the changes in these metrics. The homeostatic model assessment for insulin resistance (HOMA-IR) has been widely used to assess the degree of insulin resistance. The triglyceride-fasting glucose (TyG) index is a newer marker of insulin resistance that merits further study. Aim: The study aimed to assess the validity of the TyG index and HOMA-IR as markers for the development of T2DM in non-obese individuals. Materials and methods:One hundred eight non-obese patients without T2DM were included in this prospective cohort study and followed up for eight years. Anthropometric and biochemical parameters, including fasting glucose levels, HbA1c, fasting serum insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG), were measured at enrolment and eight years follow-up, and HOMA-IR and TyG index were calculated. Results:Twenty participants out of 108 (18.5%) developed T2DM over eight years. On performing the area under the curve (AUC)-receiver operating characteristic curve analysis, TyG of >8.61 and HOMA-IR of >1.5 had the highest validity (ability) to predict new-onset T2DM in the study population (TyG: AUC: 0.612 (95% CI: 0.514-0.705); HOMA-IR: AUC: 0.529 (95% CI: 0.431-0.626)); however, this was not statistically significant. Conclusion:At an eight-year follow-up, TyG and HOMA-IR were unreliable predictors of the development of T2DM in non-obese individuals.

Serum Ghrelin and Glucagon-like Peptide 1 Levels in Children with Prader-Willi and Bardet-Biedl Syndromes

Prader-Willi syndrome (PWS) and Bardet-Biedl syndrome (BBS) are causes of pediatric syndromic obesity. We aimed to investigate a possible role for ghrelin and glucagon-like peptide-1 (GLP-1) in the pathophysiology of PWS and BBS. The study included 12 children with PWS, 12 children with BBS, 13 pediatric obese controls (OC) and 12 pediatric lean controls (LC). Fasting serum ghrelin and GLP-1 levels were measured by ELISA. In the PWS group, no significant difference was detected for median ghrelin levels when compared with OC and LC, which were 0.96 (0.69-1.15), 0.92 (0.72-1.20) and 1.13 (0.84-1.29) ng/mL, respectively. Similarly, there was no difference in PWS median GLP-1 levels when compared with OC and LC; 1.86 (1.5-2.94), 2.24 (1.62-2.78) and 2.06 (1.8-3.41) ng/mL, respectively. In the BBS group, there was no difference in median ghrelin levels when compared with OC and LC; 1.05 (0.87-1.51), 0.92 (0.72-1.20) and 1.13 (0.84-1.29) ng/mL, respectively. Neither was there a significant difference in median GLP-1 levels; 2.46 (1.91-4.17), 2.24 (1.62-2.78) and 2.06 (1.8-3.41) ng/mL for BBS, OC and LC, respectively. There were no differences in median fasting ghrelin or GLP-1 levels when comparing patients with PWS and BBS with obese or lean peers. However, similar studies with larger series are needed.

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Characterization of tirzepatide-treated patients achieving different glycemic control levels in SURPASS-AP-Combo.

The study objective was to characterize subgroups of Asia-Pacific patients with type 2 diabetes who achieved different glycated hemoglobin (HbA1c) targets on tirzepatide treatment. This was a post hoc analysis of the SURPASS AP-Combo study. Baseline characteristics, changes in metabolic markers, and safety were compared between tirzepatide-treated patients achieving HbA1c <7.0% (<53 mmol/mol) and those achieving ≥7.0% (≥53 mmol/mol) at week 40. Among patients achieving HbA1c <7.0% (<53 mmol/mol), further comparisons were conducted among subgroups achieving HbA1c <5.7% (<39 mmol/mol), 5.7% to 6.5% (39 to 48 mmol/mol), and >6.5% to <7.0% (>48 to <53 mmol/mol). Five hundred ninety-eight patients on tirzepatide treatment without rescue medication were included (56.9% male; mean age: 53.1 years; mean baseline HbA1c: 8.7% [71.6 mmol/mol]). Patients achieving HbA1c <7.0% (<53 mmol/mol) versus ≥7.0% (≥53 mmol/mol) were slightly younger with a shorter disease duration and lower HbA1c at baseline, and they had greater improvements in HbA1c, fasting serum glucose, body weight, BMI, waist circumference, waist-height ratio, diastolic blood pressure, lipids, and self-monitored blood glucose at week 40. Patients achieving HbA1c <5.7% (<39 mmol/mol) versus those achieving 5.7% to 6.5% (39 to 48 mmol/mol) and those achieving >6.5% to <7.0% (>48 to <53 mmol/mol) were much younger, had much lower HbA1c, and had further improvements in metabolic markers. Tirzepatide treatment was well tolerated irrespective of the HbA1c level achieved, with a low incidence of hypoglycemic events. These findings may help to inform clinical decisions in Asia-Pacific patients with type 2 diabetes.

Osteocalcin: Beyond Bones.

Apart from basic roles such as supporting the body, protecting internal organs, and storing calcium, the skeletal system also performs hormonal functions. In recent years, several reports have been published on proteins secreted by bones and their impact on the homeostasis of the entire body. These proteins include fibroblast growth factor 23, sclerostin, lipocalin 2, and osteocalcin. Osteocalcin, the most abundant non-collagenous protein in bone tissue, is routinely measured as a clinical marker for diagnosing bone metabolism disorders. Its molecule undergoes numerous transformations, with decarboxylation being the critical process. Decarboxylation occurs in the acidic environment typical of bone resorption, facilitating the release of the molecule into the bloodstream and enabling its hormonal action. Decarboxylated osteocalcin promotes insulin secretion and stimulates the proliferation of pancreatic islet β-cells. It also plays a role in reducing the accumulation of visceral fat and decreasing fat storage in the liver. Furthermore, decarboxylated osteocalcin levels are inversely correlated with fasting serum glucose levels, total body fat, visceral fat area, and body mass index. Apart from its role in energy metabolism, osteocalcin affects testosterone production and the synthesis of glucagon-like peptide-1. It is also actively involved in muscle-bone crosstalk and influences cognitive function.

Etiologies underlying subtypes of long-standing type 2 diabetes.

Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.

Evaluating Serum Adiponectin Levels with Respect to the Results of Oral Glucose Tolerance Test in Dysglycemic Pregnant Females

The hormone adiponectin has antidiabetic and anti-inflammatory effects. Gestational diabetes is hyperglycemia that develops in middle of pregnancy. The oral glucose tolerance test is used to screen for gestational diabetes. As a measure for insulin resistance, the (QUICKI-index), utilizes fasting insulin and fasting glucose levels to evaluate the sensitivity to insulin. Pregnancy is a state of insulin resistance and the role played by the adiponectin in the progression from euglycemia into prediabetes is a matter of conflict. Aim: to evaluate adiponectin levels in pregnancy and to find out if it can be used as a marker for developing GDM. Subjects and methods: a cross-sectional study involved 40 pregnants of 18–40 years of age at their second trimester and having BMI of 25-30 Kg/m2. After performing the OGTT, pregnants were divided into: Impaired glucose tolerance (IGTT) group: 23 pregnant with a mean age of 25.9 ± 6.1 years. B. Gestational diabetes (GDM) group: 13 pregnant with an age of 29.5 ± 3.9 years. The following parameters were measured: FBG, 2-hour RBG, fasting insulin, serum adiponectin, QUICKI-index. Results: There was no significant statistical difference with respect to; age (p= .855), BMI (p= .071), and gestational age (p= .239). Serum adiponectin was significantly lower in the GDM group (p= .028). The FBG was significantly higher in the GDM group, (p&lt;0.0001). Similarly, the 2-hour BG, (p&lt;0.001). The fasting serum insulin was significantly higher in the GDM group, (p&lt;0.0001). Pregnant with GDM had significantly lower QUICKI-index in comparison to those with IGTT (p&lt;0.0001). Finally, the blood level of adiponectin showed positive correlation with QUICKI-index of insulin resistance, r (38) = ,499, p &lt;0.0001. Conclusions: serum adiponectin is reduced in pregnant with insulin resistance and might be an independent risk factor for developing diabetes. It might be of help in predicting the progression from euglycemic into overt diabetic states. Abbreviations: OGTT = oral glucose tolerance test, FBG = fasting blood glucose, RBG = random blood glucose, GDM = gestational diabetes mellitus, IGT = impaired glucose tolerance, BMI = body mass index, T2DM = type 2 diabetes mellitus.

Insulin resistance and secretion change after 3 years follow-up and the risk for developing diabetes in non-diabetic adults

Purpose : To determine 3-years natural change of insulin resistance and secretion in non-diabetic Chinese adults and corresponding risk for developing diabetes. Methods : Population-based cohort study was performed in Chinese adults (35-74 years) from 2009 to 2015. Fasting plasma glucose and serum insulin was determined in 1882 subjects (701 men) at baseline and re-tested in 1087 (377 men). Insulin resistance was estimated with HOMA insulin resistance index (HOMA-IR) and insulin secretion with HOMA insulin secretion index (HOMA-IS). The change of HOMA-IR and HOMA-IS was calculated as: the value at follow-up minus that at baseline

#2572 Sodium-glucose transport protein 2 (SGLT-2) inhibitors in diabetic and non-diabetic kidney transplant recipients

Abstract Background and Aims The beneficial effects of administering sodium-glucose transport protein 2 (SGLT2i) inhibitors in patients with Chronic Kidney Disease, with or without Type 2 Diabetes (T2D), has been proven in large randomized controlled trials. Nevertheless, there is limited data considering Kidney Transplant Recipients (KTRs) with or without albuminuria. The purpose of this study was to evaluate the safety and efficacy of administering SGLT2i to KTRs in association to their kidney function and albuminuria. Method In this retrospective study we examined the effects of treatment with SGLT2i on kidney function (eGFR calculated with CKD-EPI formula), albuminuria (24h urine collection) and fasting serum glucose levels of KTRs. We included KTRs with T2D or without T2D and confirmed albuminuria (ACR &amp;gt;30 mg/gCr) in two consecutive ACR measurements. Kidney function and albuminuria monitoring was performed one month post-treatment initiation and in three month intervals thereafter. Moreover, immunosuppression trough levels were measured in each visit and active surveillance for adverse events was performed. Results Twenty-four KTRs (20 males) with a mean eGFR of 51.1 ± 14.2 ml/min/1.73 m2 were included in this study. Nine patients had T2D. Treatment was initiated 10 ± 5.4 years post transplant and all KTRs received dapagliflozin. Mean follow-up was 9 ± 2 months. Kidney function was non-significantly decreased directly after SGLT2i initiation and remained stable until the end of follow up (51.1 ± 14.2 vs. 51.4 ± 13.8 ml/min/1.73 m2). Overall, we found a significant reduction of albuminuria (371 ± 460 vs 235 ± 294 mg/24 h, p = 0.015). When KTRs were examined separately based on their diabetes status (KTRs with T2D vs. no T2D) we found that only those with T2D showed a significant decrease in albuminuria (450.4 ± 548 vs. 259.8 ± 332.5 mg/24 h, p = 0.008) at the end of follow up. Furthermore, a significant reduction of morning fasting glucose (106.4 ± 19.6 vs 99.9 ± 16.6 mg/dl, p = 0.0006) was noted. Trough levels of immunosuppression agents (tacrolimus, everolimus or cyclosporine) did not show any significant change after the initiation of SGLT2i and two patients had to discontinue the treatment, due to one episode of pyelonephritis and detection of funguria. Conclusion Prescription of SGTL2i in KTRs with T2D and albuminuria, seems to be a reliable option with significant efficacy on the decrease of albuminuria with minimal adverse effects.

Serum 25-Hydroxyvitamin D Level Is Positively Associated with Vascular Reactivity Index in Patients with Type 2 Diabetes Mellitus.

Circulating 25-hydroxyvitamin D (25(OH)D) significantly influences endothelial function. This study assessed the correlation between serum 25(OH)D and endothelial function using the vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples from 102 T2DM participants and VRI were assessed. Patients were divided into three categories based on VRI: low (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0). Among these patients, 30 (29.4%) had poor, 39 (38.2%) had intermediate, and 33 (32.4%) exhibited good vascular reactivity. Higher serum fasting glucose (p = 0.019), glycated hemoglobin (p = 0.009), and urinary albumin-to-creatinine ratio (p = 0.006) were associated, while lower prevalence of hypertension (p = 0.029), lower systolic blood pressure (p = 0.027), lower diastolic blood pressure (p < 0.001), and lower circulation 25(OH)D levels (p < 0.001) were associated with poor vascular reactivity. Significant independent associations between diastolic blood pressure (p = 0.002) and serum 25(OH)D level (p < 0.001) and VRI were seen in T2DM patients according to multivariable forward stepwise linear regression analysis. Serum 25(OH)D positively correlated with VRI values, and lower levels of serum 25(OH)D were linked to endothelial dysfunction in T2DM patients.

Aged garlic extract preserves beta-cell functioning via modulation of nuclear factor kappa-B (NF-κB)/Toll-like receptor (TLR)-4 and sarco endoplasmic reticulum calcium ATPase (SERCA)/Ca2+ in diabetes mellitus

BackgroundPeripheral insulin resistance and compromised insulin secretion from pancreatic β-cells are significant factors and pathogenic hallmarks of diabetes mellitus (DM). NF-κβ/TLR-4 and SERCA/Ca2+ pathways have been identified as potential pathways regulating insulin synthesis by preserving pancreatic β-cell functioning. The current study aimed to evaluate the therapeutic effect of aged garlic extract (AGE) against DM in a streptozotocin (STZ)-induced rat model with particular emphasis on pancreatic β-cell functioning.MethodsAGE was characterized by gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate its physio-chemical characteristics followed by in-vitro anti-diabetic and antioxidant potential. This was followed by the induction of DM in laboratory animals for investigating the therapeutic action of AGE by evaluating the role of NF-κβ/TLR-4 and the SERCA/Ca2+ pathway. The parameters assessed in the present experimental setup encompassed antioxidant parameters, metabolic indicators, insulin concentration, intracellular calcium levels, apoptotic markers (CCK-8 and Caspase Glo-8), and protein expression (P-62 and APACHE-II).ResultsAGE characterization by SEM, GC-MS, and X-ray diffraction (XRD) revealed the presence of phenylalanine, alliin, S-allylmercaptocysteine (SAMC), tryptophan, 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid as major bioactive constituents of AGE. Metabolic studies, including intraperitoneal glucose tolerance test (IPGTT), revealed significantly lower blood glucose levels in the AGE group compared to the disease control group. In contrast, the intraperitoneal insulin tolerance test (ITT) exhibited no significant difference in insulin sensitivity between the AGE supplementation group and the DM control group. Interestingly, AGE was found to have no significant effect on fasting glucose and serum insulin levels. In contrast, AGE supplementation was found to cause significant hypoglycaemia in postprandial blood glucose and insulin levels. Importantly, AGE causes restoration of intracellular Ca2+ levels by modulation of SERCA/Ca2 functioning and inhibition NF-κB/TLR-4 pathway. AGE was found to interact with and inhibit the DR-5/ caspase-8/3 apoptotic complex. Furthermore, microscopic studies revealed degeneration and apoptotic changes in pancreatic β-cells of the DM control group, while supplementation of AGE resulted in inhibition of apoptotic pathway and regeneration of pancreatic β-cells.ConclusionThe current study suggests that AGE enhance glucose homeostasis by exerting their effects on pancreatic β-cells, without ameliorating peripheral sensitivity. Moreover, AGEs promote an increase in β-cell mass by mitigating the apoptosis of pancreatic β-cells. These findings suggest that AGE could aid in developing a viable alternative therapy for diabetes mellitus (DM).

Long-term effects of ipragliflozin and pioglitazone on metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes: 5 year observational follow-up of a randomized, 24 week, active-controlled trial: Effect of ipragliflozin in MASLD.

We conducted a 5 year post-trial monitoring study of our previous randomized 24 week, open-label, active-controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction-associated steatotic liver disease (MASLD), identical to those of pioglitazone. In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. At 5 years, the mean liver-to-spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (-4.0%, P = 0.0075 and -7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB-4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years.

Jiaotaiwan improves brain glucose metabolism in a mouse model of Alzheimer's disease by activating the PI3K/AKT signaling pathway

To investigate the effect of Jiaotaiwan on brain insulin-PI3K/AKT pathway in a mouse model of Alzheimer's disease (AD). Fifty 3-month-old male APP/PS1 double transgenic mice were randomized into AD model group, low-, medium- and high-dose Jiaotaiwan treatment groups, and donepezil treatment group. Cognitive functions of the mice were assessed using water maze and open field tests, and neuronal pathologies were observed with HE staining and Nissl staining; immunohistochemistry was used to detect amyloid Aβ deposition in the brain. Fasting serum insulin levels of the mice were measured, and the expressions of Aβ42, insulin-PI3K/AKT pathway components and downstream glucose transporters in the brain tissue were detected with RT-qPCR and Western blotting. The AD mouse models exhibited obvious impairment of learning and memory abilities, significantly reduced hippocampal neurons, and obvious Aβ amyloid plaques in the brain tissue with increased Aβ42 protein expression (P < 0.05) and insulin resistance index, decreased hippocampal PI3K expressions, lowered expressions of AKT and InR, reduced expressions of GLUT1, GLUT3, and GLUT4, and increased expression of GSK3β in both the hippocampus and cortex. Treatment with Jiaotaiwan and donepezil both effectively improved memory ability of the mouse models, increased the number of hippocampal neurons, reduced Aβ amyloid plaques and increased the expressions of PI3K, AKT, InR, GLUT1, GLUT3 and GLUT4 in the hippocampus and cortex. Jiaotaiwan improves learning and memory abilities of APP/PS1 double transgenic mice and delay the development of AD by activating the PI3K/AKT pathway and regulating the expression levels of its downstream GLUTs in the brain.