Diabetology, Volume 6, Issue 6 (June 2025) – 12 articles

Certain pharmacological properties of the methanolic extract of Justicia secunda Vahl leaves (Acanthaceae) were evaluated in Streptozotocin (STZ)-treated albino mice to confirm whether it could be considered an alternative candidate for the treatment of diabetes. Using qualitative phytochemistry, alkaloids, flavonoids, and tannins were detected. In an in vitro DPPH antioxidant activity test, high extract concentrations inhibited the radical by 90% during the first minutes of the reaction. The extract presented a slight genoprotective effect on mouse peripheral blood during the last days of the micronucleus test. Oral administration of the extract at a high dose every two days for 6 weeks caused a hypoglycemic effect in STZ-treated mice, protection against weight loss, and decreased blood triglyceride levels from week 3 of treatment. These effects could be mediated by the antioxidant activity of the detected metabolites and, perhaps, by an inhibitory effect on intestinal α-glucosidase. This renders J. secunda a good candidate for the long-term alternative treatment of diabetes without abandoning allopathic therapy. Full article

Aim: The aim of this study was to evaluate the specificity, sensitivity and accuracy of the Indicator Plaster Neuropad in detecting established Diabetic Autonomic Neuropathy (DAN). Methods: We studied 180 patients with Diabetes Mellitus (DM, mean age 49.5 ± 16 years, 82 with DM type 1). All patients underwent the following Cardiovascular Reflex Tests (CARTs): R-R variation during deep breathing (Mean Circular Resultant (MCR) and standard deviation (SD)), Valsalva maneuver, R-R variability after a rapid change from lying to standing position and postural hypotension. The presence of DAN was established if ≥2 CARTs were abnormal. According to the result the patients were divided into two groups, one with DAN and one without DAN. Assessment with Neuropad was performed also in all patients. Results: Abnormal perspiration with Neuropad (uncompleted or no change in color) was detected in 94 patients. Established DAN was detected in 85 patients. The sensitivity, specificity and accuracy of Neuropad for the diagnosis of established DAN were 87.1%, 78.9% and 82.8%, respectively and area under the curve was 0.846 and 95% CI (0.787, 0.905). Conclusions: Neuropad has high sensitivity, specificity, and accuracy in detecting established DAN, as defined by ≥2 abnormal CARTs. Full article

Background: Two changes to gestational diabetes mellitus (GDM) testing were implemented in the Australian Capital Territory in 2015 and 2017. Aims: We aimed to determine the associations between testing regimes and the prevalence of GDM and large-for-gestational-age (LGA) and small-for-gestational-age (SGA) infants and to compare the prevalence of LGA and SGA infants between women with and without GDM in each testing period. Methods: A total of 23,790 singleton live births with estimated GDM testing and birth dates between June 2012 and December 2019 were stratified into groups: pre-testing changes (June 2012–December 2014, group 1, n = 8069), revised diagnostic criteria (January 2015–May 2017, group 2, n = 8035) and changed pathology centrifugation protocol (June 2017-December 2019, group 3, n = 7686). Women were allocated to groups based on their estimated GDM testing date and stratified by their GDM status. A chi-square test, pairwise z-tests and logistic regression tested the associations. Results: The GDM prevalence significantly increased from 9.5% (group 1) to 19.4% (group 2) to 26.3% (group 3) (all: p < 0.001). The LGA infant prevalence significantly decreased in non-GDM women following revised diagnostic criteria implementation (11.6% vs. 9.7%, p = 0.001). Compared to group 1, women with GDM in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.73, 95% CI of 0.56–0.95 and p = 0.021 and aOR = 0.75, 95% CI of 0.59–0.97 and p = 0.029, respectively). Compared to group 1, non-GDM women in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.83, 95% CI of 0.74–0.92 and p < 0.001 and aOR = 0.88, 95% CI of 0.79–0.99 and p = 0.026, respectively). There were no significant associations for group 3 compared to group 2 nor for SGA infants. Conclusions: While significantly increasing the GDM prevalence, implementing the testing changes was associated with a reduced whole-population LGA infant prevalence without a change in the SGA infant prevalence. Full article

Background/Objectives: Hormonal fluctuations during the menstrual cycle can affect glycemic control in women with type 1 diabetes (T1D), especially during the luteal phase, when increased insulin resistance may lead to prolonged hyperglycemia. Advanced Hybrid Closed-Loop (AHCL) systems could help manage these hormone-driven fluctuations. This study aimed to assess glycemic control across menstrual phases and explore the role of AHCL systems in counteracting the related glucose variability. Methods: A retrospective study was conducted including women with T1D and regular menstrual cycles (study group) and women on estroprogestin therapy (control group). Each group was subdivided by insulin delivery method (AHCL vs. non-AHCL). Glycemic metrics and insulin requirements were compared between the follicular and luteal phases, and between groups. Results: The study included 94 women (62 in the study group, 32 in the control group). In the study group, glycemic control worsened during the luteal phase, with increased average glucose, glycemic variability, and time above range > 250 mg/dL (+0.93%, p = 0.03) and reduced time in range 70–180 mg/dL. These changes were more pronounced among AHCL users, who also showed a significant increase in bolus insulin. No phase-related differences were observed in the control group or among non-AHCL users. Significantly higher insulin needs during the follicular phase were found in the study group compared with the controls. Conclusions: This study confirmed a worsening in glycemic control in women affected by T1D during the luteal phase of the menstrual cycle, suggesting a need for more tailored management. The clear efficacy of AHCL systems in counteracting hormone-related glycemic fluctuations has not been proved, highlighting the need for further research in larger, more homogeneous cohorts. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs) have transformed disease management, particularly in diabetes and obesity. However, recent shortages have disrupted patient care. This review explores the current evidence regarding their direct impact on patient populations and reviews the mitigation strategies recommended by relevant health organizations. Materials and Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available data to 10 January 2025, using these terms: “GLP-1 AND shortage”, “liraglutide AND shortage”, “dulaglutide AND shortage”, “semaglutide AND shortage”, “exenatide AND shortage”, and “tirzepatide AND shortage”. Eligible studies needed to report measurable outcomes like prescription counts, specific laboratory findings, or the proportion of a study population achieving a defined outcome related to the shortage. Only English-language clinical research was considered, while other manuscripts were not included. The risk of bias was assessed using the Critical Appraisal Skills Programme checklist. Study characteristics and findings were summarized in tables. Results: Out of 295 identified manuscripts, 85 works were retained for further screening. Consequently, 8 studies met the inclusion criteria, covering 1036 participants with type 2 diabetes and 573 treated for obesity. In addition, two studies reported prescription prevalence, and one examined prescription counts. Key findings included reduced prescription rates and shifts in treatment practices. No studies assessed impacts on cardiovascular, renal outcomes, or mortality. Discussion and Conclusions: Evidence on the health effects of these shortages is limited. Existing studies highlight disruptions in diabetes and obesity care, but broader impacts remain unclear. Preventing future shortages requires coordinated efforts among all stakeholders. Therefore, we advocate for ethical planning, sustainable production, and fair distribution strategies to mitigate long-term consequences. Full article

Background/Objectives: The increasing prevalence of diabetes underscores the urgent need for non-invasive, rapid, and cost-effective diagnostic alternatives. This study presents a breath-based multiclass diabetes classification system leveraging only three gas sensors (CO, alcohol, and acetone) to analyze exhaled breath composition. Methods: Breath samples were collected from 58 participants (22 healthy, 7 prediabetic, and 29 diabetic), with blood glucose levels serving as the reference metric. To enhance classification performance, we introduced a novel biomarker, the alcohol-to-acetone ratio, through a feature engineering approach. Class imbalance was addressed using the Synthetic Minority Over-Sampling Technique (SMOTE), ensuring a balanced dataset for model training. A nested cross-validation framework with 3 outer and 3 inner folds was implemented. Multiple machine learning classifiers were evaluated, with Random Forest and Gradient Boosting emerging as the top-performing models. Results: An ensemble combining both yielded the highest overall performance, achieving an average accuracy of 98.86%, precision of 99.07%, recall of 98.81% and F1 score of 98.87%. These findings highlight the potential of gas sensor-based breath analysis as a highly accurate, scalable, and non-invasive method for diabetes screening. Conclusions: The proposed system offers a promising alternative to blood-based diagnostic approaches, paving the way for real-world applications in point-of-care diagnostics and continuous health monitoring. Full article

Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin resistance index and the presence of liver steatosis and fibrosis in individuals with T2D. Methods: This cross-sectional study utilized data from the 2017–2020 National Health and Nutrition Examination Survey. Patients with T2D who did not have chronic viral hepatitis or significant alcohol intake were included. The insulin sensitivity (IS) index was calculated using a formula incorporating body mass index, urine albumin-to-creatinine ratio, triglycerides, and gamma-glutamyl transferase. Liver stiffness and steatosis were assessed through transient elastography. MASLD was defined as a controlled attenuation parameter (CAP) of ≥274 decibels/meter (dB/m), while significant liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥8 kPa. Multivariable logistic regression models, adjusted for potential confounders, were used to evaluate the association between IS and these liver outcomes. Results: A total of 1084 patients with T2D were analyzed. The prevalence of MASLD and significant liver fibrosis was 74.1% (95% CI 68.7–78.9) and 25.4% (95% CI 21.2–30.2), respectively. After adjusting for age, sex, waist circumference, and race/ethnicity, lower IS scores (indicating higher insulin resistance) were independently associated with increased odds of both MASLD (quartile 1 vs. quartile 4: OR 2.66, 95% CI 1.23–5.71) and significant liver fibrosis (quartile 1 vs. quartile 4: OR 3.30, 95% CI 1.45–7.51). These findings remained consistent across subgroups stratified by age, sex, and obesity status. Conclusions: This novel IS model, derived from commonly available clinical and biochemical markers, is independently associated with liver steatosis and fibrosis. Its application may help identify patients with more advanced MASLD, facilitating early intervention and risk stratification. Full article

The Glycemia Risk Index (GRI) aims to summarize the overall quality of a patient’s glycemic control in a single number, and it is calculated from the hypo- and hyperglycemia times from continuous glucose monitoring, weighted by coefficients. Despite its recent appearance in 2022, this new parameter has strong international support, with almost half a hundred indexed articles already incorporating this metric into their studies. The following is a breakdown of the main papers that have used GRI, divided according to the type of treatment used, the population studied, the type of diabetes, its association with other parameters, and its relationship with chronic complications and the quality of life of people living with diabetes. Full article

Cellular senescence, a phenomenon characterized by the accumulation of dysfunctional, metabolically active cells, is increasingly recognized to be a key player in aging-related metabolic disorders. It is accelerated by hyperglycemia through various molecular pathways, positioning it as a critical mechanism in the pathophysiology of type 2 diabetes mellitus (T2D) and a potential therapeutic target. Emerging evidence from animal and clinical studies suggests that the usage of senolytic drugs, which selectively deplete senescent cells, can improve blood glucose regulation and mitigate diabetic complications. However, despite the conceptual feasibility of this approach, several challenges remain in their translation to the clinic: the molecular mechanisms underlying the pathogenicity of cellular senescence in vivo remain incompletely understood, and organ-specific effects of senolytic administration are yet to be fully elucidated to ensure their safety and efficacy in clinical applications. This review explores the characteristics of cellular senescence and the senescence-associated secretory phenotype (SASP) in key tissues involved in glucose homeostasis, including the pancreas, liver, adipose tissue, and skeletal muscle and the potential applications of targeting cellular senescence as a therapeutic strategy for T2D management. Full article

Introduction: Managing glycemic fluctuations in critically ill elderly patients with type 2 diabetes mellitus (T2DM) poses significant challenges. This case report presents a unique scenario in which increased intravenous glucose (Glc) infusion, together with insulin therapy, improved glycemic control and reduced insulin requirements during a septic episode. This finding adds to the scientific literature by suggesting that adequate Glc administration may enhance insulin sensitivity in critically ill T2DM patients. Case report: An 84-year-old female patient with T2DM, hypertension, and chronic renal failure was admitted to the intensive care unit with fever, nausea, loss of appetite, and profound weakness. Laboratory findings revealed severe hyperglycemia, electrolyte imbalances, and markedly elevated inflammatory markers, leading to the diagnosis of decompensated T2DM that was complicated by sepsis. The initial treatment consisted of continuous intravenous (IV) insulin, crystalloid infusions, and broad-spectrum antibiotics. Despite insulin therapy and the absence of nutritional intake, the patient experienced extreme fluctuations in their blood glucose levels, ranging from hyperglycemia to hypoglycemia. Due to persistent glycemic instability, IV Glc infusion was initiated alongside continuous insulin therapy. Paradoxically, increasing Glc infusion administration rate led to a reduction in the required insulin doses and stabilization of blood glucose levels below 10 mmol·L⁻¹. The patient’s C-peptide levels were initially elevated but subsequently decreased following Glc administration as well, suggesting a reduction in endogenous insulin secretion and therefore higher insulin sensitivity. The patient’s clinical condition improved, allowing for the transition to a subcutaneous insulin regime and the initiation of oral feeding. She was later transferred to a general medical ward and discharged without further complications. Conclusions: This case highlights the complex interplay between Glc and insulin in critically ill elderly patients with T2DM during sepsis. The main takeaway is that carefully managed Glc infusion, in conjunction with flexible insulin therapy, can enhance insulin sensitivity and stabilize blood glucose levels without causing further hyperglycemia. Frequent glycemia monitoring and adaptable glycemic management strategies are essential in the ICU to address rapid glycemic fluctuations in this patient population. Full article

Background/Objectives: This study investigated factors affecting glycated hemoglobin (HbA1c) levels according to sleep duration in adults with diabetes. HbA1c is an important indicator for the diagnosis and management of diabetes, and lowering this value is important for reducing the risk of complications. Recent studies have shown that sleep duration and quality play important roles in controlling blood sugar levels in patients with diabetes. Therefore, we aimed to analyze the factors affecting HbA1c levels according to sleep duration in adult patients with diabetes and propose a personalized diabetes management strategy. Methods: This was a secondary analysis of data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2022 and 2023. The study included 1363 adults aged ≥30 years who were diagnosed with diabetes by a doctor. The participants were categorized into three groups based on their sleep duration: <7 h, 7–9 h, and ≥9 h. Results: The significant factors affecting HbA1c levels varied according to sleep duration. Age, drinking, and stress were significant for those who slept for <7 h. For those sleeping 7–9 h, energy intake, protein intake, fat intake, and education level were significant. Health checkups and drinking were significant for those who slept for >9 h. Conclusions: This study suggests that sleep duration is an important variable in diabetes management and should be considered in personalized diabetes management strategies. Future studies should explore various factors related to sleep patterns in greater depth. Full article

Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. Methods: Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. Results: We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. Full article