Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals.

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

Effect of interpregnancy interval on the risk of gestational diabetes mellitus during a second pregnancy.

BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study.

BACKGROUND: Type 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population. METHODS: This was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1ß and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes. RESULTS: Prediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1ß and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1ß and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05). CONCLUSIONS: SFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Genetic causality between type 1 diabetes and arrhythmia identified by a two-sample Mendelian randomization study.

BACKGROUND: Clinical studies have shown that cardiovascular diseases in patients with type 1 diabetes (T1D) are often atypical or asymptomatic. The link between T1D and arrhythmia remains unclear. To infer causality between T1D and arrhythmia at the genetic level, we conducted a Mendelian randomization study through the genetic tools of T1D. METHODS: In this study, we used genetic variables and summary statistics from genome-wide association studies of T1D and arrhythmia. Single nucleotide polymorphisms were selected based on the assumptions of instrumental variables. The inverse variance-weighted method was used as the primary analysis to summarize the causal effects between exposure and outcome. The weighted median and weighted mode methods were used as secondary methods. We tested for horizontal pleiotropy using the MR-Egger method and detected heterogeneity using the Q-test. A leave-one-out sensitivity analysis was performed. Scatter plots, forest plots, and funnel plots were used to visualize the results of the MR analysis. RESULTS: In this study, we selected 28 T1D-related SNPs as instrumental variables. The IVW [odds ratio (OR) = 0.98, 95 % confidence interval (CI) = 0.97-1.00, P = 0.008], weighted median (OR = 0.98, 95 % CI = 0.96 - 0.99, P = 0.009), and weighted mode (OR = 0.98, 95 % CI = 0.96-0.99, P = 0.018) analysis methods suggested a causal effect of T1D on arrhythmia. The MR-Egger method indicated no horizontal pleiotropy (P = 0.649), and the Q-test showed no heterogeneity (IVW, P = 0.653). CONCLUSIONS: Our MR analysis revealed a causal association between T1D and the development of arrhythmia, indicating that patients with T1D had a higher risk of arrhythmia.

An improved linear systems model of hydrothermal isometric tension testing to aid in assessing bone collagen quality: Effects of ribation and type-2 diabetes.

This study sought to further develop and validate a previously proposed physics-based model that maps denaturation kinetics from differential scanning calorimetry (DSC) to the isometric tension generated during hydrothermal isometric tension (HIT) testing of collagenous tissues. The primary objectives of this study were to verify and validate two physics-based model parameters: α, which indicates the amount of instantaneous isometric tension developed per unit of collagen denaturation, and ß, which captures the proportionality between temperature and the generated isometric tension post denaturation initiation. These parameters were used as measures of bone collagen quality, employing data from HIT and DSC testing of human bone collagen from two previous studies. Additionally, given the physical basis of the model, the study aimed to further validate Max.Slope, the rate of change in isometric tensile stress with change in temperature, as an independent measure of collagen network connectivity. Max.Slope has previously been positively correlated with measures of cortical bone fracture resistance. Towards this verification and validation, the hypotheses were a) that α would correlate strongly with HIT denaturation temperature, Td, and the enthalpy of melting (ΔH) from DSC, and b) that ß would correlate positively and strongly with Max.Slope. The model was employed in the analysis of HIT-DSC data from the testing of demineralized bone collagen isolated from cadaveric human femurs in two prior studies. In one study, data were collected from HIT-DSC testing of cortical bone collagen from 74 donors. Among them, 38 had a history of type 2 diabetes +/- chronic kidney disease, while the remaining 36 had no history of T2D again with or without CKD. Cortical bone specimens were extracted from the lateral mid-shaft. The second study involved 15 donor femora, with four cortical bone specimens extracted from each. Of these four, two specimens underwent a 4-week incubation in 0.1 M ribose at 37 °C to induce non-enzymatic ribation and advanced glycation endproducts, while the other two served as non-ribated controls. The examination involved investigating correlations between the model parameters α and ß and various measures, such as Max.Slope, Td, ΔH, age, and duration of type 2 diabetes. The results revealed positive correlations between the model parameter ß and Max.Slope (r = 0.55-0.58). The parameter α was found to be associated with Td, but also sensitive to the shape of the HIT curve around Td resulting in difficulties with variability and interpretation. As a result, while both hypotheses are confirmed, Max.Slope and ß are better indicators of bone collagen quality because they are measures of the connectivity or, more generally, the integrity of the bone collagen network.

Oxidative balance score as a useful predictive marker for new-onset type 2 diabetes mellitus in Korean adults aged 60 years or older: The Korean Genome and Epidemiologic Study-Health Examination (KoGES-HEXA) cohort.

BACKGROUND: The oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. METHODS: We assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. RESULTS: A total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47-1.07]) but was significant in T3 at (0.47 [0.30-0.75]) (p for trend = 0.002). CONCLUSIONS: The study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.

Evaluation of a Pharmacist-Led Personal Continuous Glucose Monitor Workflow to Improve Glycemic Management in an Internal Medicine Clinic.

The use of personal continuous glucose monitors (CGMs) in patients with diabetes has increased significantly and is expected to continue to increase as CGMs become more affordable and insurance plans improve coverage. The utilization of CGMs has improved diabetes management and reduced hypoglycemic events. A pharmacist-led personal CGM workflow was created to evaluate the impact on glycemic management in patients with diabetes. This was a prospective, investigator-initiated pilot study conducted at an Atrium Health Internal Medicine clinic over 28 weeks. In this pilot, 42 patients were qualifying candidates with diabetes and personal CGM use. Additionally, 30 patients were followed until study completion and included into final analysis. The average baseline A1c was reduced from 8.3% to 7.1% over a 3 - 6 month period. The pharmacist-led CGM workflow revealed a statistically significant reduction in A1c from baseline by an average of 1.2% (95% CI, -0.6 - -1.8; P = 0.0006). On average, patients were enrolled for 19.9 weeks and had an average of 5 visits during this time. During the study duration, 100 medications changes were implemented under the existing Clinical Pharmacist Practitioner (CPP) agreement between the pharmacists and the provider. The implementation of the CGM workflow led to one less diabetes related hospitalization. Overall, 58 CPT 95251 codes were billed yielding $7,052.00 in billed CGM services for the clinic. This project generated 40.6 provider relative value units (RVUs). The utilization of a pharmacist-led personal CGM workflow can improve diabetes outcomes.

A Crucial Role of Adenosine Deaminase in Regulating Gluconeogenesis in mice.

Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine to inosine and regulates adenosine concentration. ADA ubiquitously expresses in various tissues to mediate adenosine receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus (T2DM). Here we show that elevated plasma ADA activity is a compensated response to high level of adenosine in T2DM and plays an essential role in the regulation of glucose homeostasis. Supplementing with more ADA, instead of inhibiting ADA can reduces adenosine levels and decreases hepatic gluconeogenesis. ADA restores a euglycemic state and recovers functional islets in db/db and high-fat-STZ diabetic mice. Mechanistically, ADA catabolizes adenosine and increases Akt and FoxO1 phosphorylation independent of insulin action. ADA lowers blood glucose at a slower rate and longer duration compared to insulin, delaying or blocking the incidence of insulinogenic hypoglycemia shock. Finally, ADA suppresses gluconeogenesis in fasted mice and insulin-deficient diabetic mice, indicating the ADA regulating gluconeogenesis is a universal biological mechanism. Overall, these results suggest that ADA is expected to be a new therapeutic target for diabetes.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Time With Rapid Change of Glucose.

BACKGROUND: A variety of metrics are used to describe glycemic variation, some of which may be difficult to comprehend or require complex strategies for smoothing of the glucose curve. We aimed to describe a new metric named time with rapid change of glucose (TRC), which is presented as percentage of time, similar to time above range (TAR), time in range (TIR), and time below range (TBR). METHOD: We downloaded glucose data for 90 days from 159 persons with type 1 diabetes using the Abbott Freestyle Libre version 1. We defined TRC as the proportion of time (%) with an absolute rate of change of glucose > 1.5 mmol/L/15 minutes (1.8mg/dL/min) corresponding to a minimum rate of change for glucose in the 3.9-10.0 mmol/L (70-180 mg/dL) range within 1 hour. TRC is related to the other glucose variability metrics: CV within day (CVw) and mean amplitude of glycemic excursion (MAGE). RESULTS: The more than 1.27 million glucose rates were t-location scale distributed with SD 0.91 mmol/L/15 min (1.1 mg/dL/15 min). The median TRC was 6.9% (IQR 4.5%-9.5%). The proportion of TRC with positive slope was 3.9% (2.6%-5.3%) and significantly higher than the proportion with negative slope 2.8% (1.5%-4.4%) P < .001. TRC correlated with CVw and MAGE (Spearman's correlation coefficient .56 and .65, respectively, P < .001). CONCLUSION: TRC is proposed as an easily perceived metric to compare the performance of hybrid or fully automated closed-loop insulin delivery systems to obtain glucose homeostasis.

Evaluation of the systemic-immune inflammation index (SII) and systemic immune-inflammation response index (SIRI) in children with type 1 diabetes mellitus and its relationship with cumulative glycemic exposure.

OBJECTIVES: In this study, the systemic proinflammatory status was assessed using the systemic immune-inflammation index (SII) and SIRI systemic immune-inflammatory response index (SIRI) in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: The study involved 159 patients aged between 6 and 16 years. The SII and SIRI values were calculated based on the complete blood count. Basic blood biochemistry evaluated, and carotid intima-media thickness (cIMT) was measured and recorded. The cumulative glycemic exposure was calculated by multiplying the value above the normal reference range of the HbA1c value. The sum of all these values obtained from the time of diagnosis to obtain the cumulative glycemic exposure. All findings were compared statistically. All statistically significant parameters were evaluated in the multivariate logistic regression analysis. RESULTS: The analysis revealed that only cIMT (Exp(B)/OR: 0.769, 95 % CI: 0.694-0.853, p<0.001), high-density lipoprotein (Exp(B)/OR: 3.924, 95 % CI: 2.335-6.596, p<0.001), monocyte count (Exp(B)/OR: 1.650, 95 % CI: 1.257-2.178, p<0.001), hematocrit (Exp(B)/OR: 0.675, 95 % CI: 0.523-0.870, p<0.001), and SIRI (Exp(B)/OR: 1.005, 95 % CI: 1.002-1.008, p<0.001) were significantly associated with T1DM. A statistically significant positive association was found between cumulative glycemic exposure and SIRI only (r=0.213, p=0.032). To our knowledge, this is the first study to evaluate SII and SIRI in children with type 1 diabetes. CONCLUSIONS: These findings indicate that SIRI could serve as a potential biomarker for detecting early-onset proatherosclerotic processes in diabetic children. However, further clinical studies are required to confirm this.

Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

Corrigendum: NmFGF1-regulated glucolipid metabolism and angiogenesis improves functional recovery in a mouse model of diabetic stroke and acts via the AMPK signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2021.680351.].

MARRIAGE: A Randomized Trial of Moxonidine Versus Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

Integrated biomarker profiling for predicting the response of type 2 diabetes to metformin.

AIM: To explore biomarkers that can predict the response of type 2 diabetes (T2D) patients to metformin at an early stage to provide better treatment for T2D. METHODS: T2D patients with (responders) or without response (non-responders) to metformin were recruited, and their serum samples were used for metabolomic analysis to identify candidate biomarkers. Moreover, the efficacy of metformin was verified by insulin-resistant mice, and the candidate biomarkers were verified to determine the biomarkers. Five different machine learning methods were used to construct the integrated biomarker profiling (IBP) with the biomarkers to predict the response of T2D patients to metformin. RESULTS: A total of 73 responders and 63 non-responders were recruited, and 88 differential metabolites were identified in the serum samples. After being verified in mice, 19 of the 88 were considered as candidate biomarkers. Next, after metformin regulation, nine candidate biomarkers were confirmed as the biomarkers. After comparing five machine learning models, the nine biomarkers were constructed into the IBP for predicting the response of T2D patients to metformin based on the Naïve Bayes classifier, which was verified with an accuracy of 89.70%. CONCLUSIONS: The IBP composed of nine biomarkers can be used to predict the response of T2D patients to metformin, enabling clinicians to start a combined medication strategy as soon as possible if T2D patients do not respond to metformin.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.

Objective: This meta-analysis aimed to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in overweight/obese and/or type 2 diabetes mellitus (T2DM) adolescents aged <18 years. Methods: Herein, we searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data up to August 2023 for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, P<0.001) than the control group. However, there was no difference in fasting blood glucose (FPG; RD=-2.07mg/dL, P=0.065) between the two groups. Nonetheless, the experimental group that administered exenatide showed a no significant reduction in HbA1c (P=0.253) and FPG (P=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28kg, P=0.002) and BMI (RD=-1.63kg/m2, P=0.002) compared to the control group. The experimental group was adopted with liraglutide (RD=-2.31kg, P=0.038) or exenatide (RD=-2.70kg, P<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. But for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81kg/m2, P=0.260). For the experimental group that was adopted with exenatide, BMI revealed a more significant decline in the intervention group than in the control group (RD=-1.14kg/m2, P<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide is better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide is better than liraglutide.

Effect of Wearable Technology on Metabolic Control and the Quality of Life in Children and Adolescents with Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Background: Type 1 diabetes is one of the most common chronic diseases in children. Wearable technology (insulin pumps and continuous glucose monitoring devices) that makes diabetes management relatively simple, in addition to education and follow-ups, enhances the quality of life and health of individuals with diabetes. Aims: To evaluate the impact of wearable technology on metabolic management and the quality of life in children and adolescents with type 1 diabetes. Study Design: Systematic review and meta-analysis. Methods: The Preferred Reporting System for Systematic Reviews and Meta-Analyses was used to conduct a systematic review and meta-analysis. PubMed, Web of Science, MEDLINE, Cochrane Library, EBSCO, Ulakbim and Google Scholar were searched in July 2022 and July 2023 using predetermined keywords. The methodological quality of the studies was evaluated using the Joanna Briggs Institute's Critical Appraisal Checklists for randomized controlled experimental and cross-sectional studies. The meta-analysis method was used to pool the data. Results: Eleven studies published between 2011 and 2022 were included. The total sample size of the included studies was 1,853. The meta-analysis revealed that the decrease in hemoglobin A1C (HbA1c) level in those using wearable technology was statistically significant [mean difference (MD): -0.33, Z = 2.54, p = 0.01]. However, the technology had no effect on the quality of life [standardized mean difference (SMD): 0.44, Z = 1.72, p = 0.09]. The subgroup analyses revealed that the decrease in the HbA1c level occurred in the cross-sectional studies (MD: -0.49, Z = 2.54, p = 0.01) and the 12-19 (MD = 0.59, Z = 4.40, p < 0.001) and 4-18 age groups (MD: -0.31, Z = 2.56, p = 0.01). The subgroup analyses regarding the quality of life revealed that there was no difference according to the research design. However, the quality of life was higher in the wearable technology group than in the control group in the 8-12 and 4-18 age groups (SMD: 1.32, Z = 2.31, p = 0.02 and SMD: 1.00, Z = 5.76, p < 0.001, respectively). Conclusion: Wearable technology effectively reduces the HbA1c levels in children and adolescents with type 1 diabetes in some age groups. However, it does not affect the quality of life.

Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Insights into the Age-Dependent Variation in Nutrition-Related Trace Elements in Diabetes Blood Using Total Reflection X-Ray Fluorescence.

The prevalence of diabetes has reached alarming levels in India, making it essential to understand the concentration of nutritional-trace elements (Fe, Cu, Zn, Cr. and Se) in blood samples from diabetic adults. In this study, 208 whole blood samples from diabetic (n = 104) and non-diabetic (n = 104) adults across various age groups were analyzed using total reflection X-ray fluorescence (TXRF) spectroscopy with a sample dilution method. Statistical analysis was performed to assess descriptive statistics and determine a significant correlation between elemental concentrations in the blood samples of diabetic and non-diabetic adults. The mean concentration of nutritional-related trace elements in diabetic blood was as follows: Fe (46 ± 5) > Zn (1.28 ± 0.14) > Cu (0.10 ± 0.01) > Cr (0.05 ± 0.004) > Se (0.013 ± 0.001) in mg/L, respectively. Additionally, this study investigated the influence of nutrition-related trace element concentrations across various age groups such as 25-40 years (young adults), 41-55 years (middle-aged adults), and 56-70 years (older adults). In this investigation, Zn (p < 0.001) and Cr (p < 0.05) concentrations differed significantly between diabetic and non-diabetic adults aged 56-70 years. These findings will help us to understand age-dependent changes in element concentrations, clarify their role in diabetes, and improve risk factor management associated with diabetes.