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Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: 15 February 2027 | Viewed by 13403

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Dr. Katarzyna A. Majewska

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Department of Pediatric Diabetes, Auxology and Obesity, Poznan University of Medical Sciences, Poznań, Poland
Interests: short stature; growth hormone; growth hormone therapy; obesity; insulin resistance; dysglycemia; type 1 diabetes; prediabetes; autoimmune thyroiditis
Special Issues, Collections and Topics in MDPI journals

Dr. Agnieszka Zawada

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Guest Editor

Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
Interests: type 1 diabetes mellitus; type 2 diabetes mellitus; diabetic complications; diabetes treatment; autoimmune diabetes

Special Issue Information

Dear Colleagues,

Diabetes mellitus remains a leading global health challenge, with rising prevalence among adults and children. Due to acute and chronic complications, it has profound implications for morbidity, mortality, and healthcare systems. Beyond glycemic control, diabetes is closely linked with cardiovascular disease, kidney dysfunction, neuropathy, retinopathy, infections, and impaired wound healing. The complexity of these complications underscores the need for a multidisciplinary approach to care, involving endocrinology, cardiology, nephrology, neurology, ophthalmology, and primary care. Diabetes can also affect cognitive functions and psychological well-being, thus requiring additional targeted support.

This Special Issue, titled “Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective”, aims to highlight advances in clinical management, prevention strategies, and integrated care models. Topics of interest include novel therapeutic approaches, biomarker-driven diagnostics, lifestyle interventions, comorbidity management, and health system responses to the diabetes epidemic.

We welcome original research, clinical studies, and reviews that contribute to improving outcomes and fostering holistic, patient-centered diabetes care.

Dr. Katarzyna A. Majewska
Dr. Agnieszka Zawada
Guest Editors

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Keywords

diabetes mellitus
type 1 diabetes
type 2 diabetes
diabetic complications
prediabetes
diabetes treatment
autoimmune diabetes

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Published Papers (9 papers)

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Research

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13 pages, 628 KB

Open AccessArticle

Dietary Vitamin K Intake and Insulin Resistance Markers in U.S. Adults: NHANES 2001–2018

by Wojciech Matuszewski, Mikołaj Madeksza, Michał Szklarz, Paulina Włodarczyk, Patrycja Waśniewska and Judyta Juranek

J. Clin. Med. 2026, 15(10), 3763; https://doi.org/10.3390/jcm15103763 - 14 May 2026

Viewed by 446

Abstract

Background: Vitamin K (VK) has emerging roles beyond coagulation, including potential involvement in glucose metabolism. While large cohorts report inverse associations between VK status and incident type 2 diabetes, less is known about its relationship with insulin resistance markers in general populations. Methods: We conducted a cross-sectional analysis of 23,247 adults from the National Health and Nutrition Examination Survey (NHANES) 2001–2018. Dietary VK intake was assessed using a single 24 h recall and modeled as energy-adjusted nutrient density (µg/1000 kcal). Fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose, and HbA1c were analyzed using survey-weighted linear regression; models were adjusted for demographic, socioeconomic, lifestyle, and adiposity-related factors. Effect modification by baseline metabolic status was evaluated, and sensitivity analyses assessed robustness. Results: Higher energy-adjusted VK intake was modestly associated with lower fasting insulin and HOMA-IR, but not with fasting glucose or HbA1c in primary linear models. Each SD increase in VK intake was associated with 1.4% lower fasting insulin (95% CI: −2.4% to −0.4%) and 1.3% lower HOMA-IR (95% CI: −2.3% to −0.3%) in fully adjusted models. Associations were attenuated following adjustment for adiposity. Effect modification by baseline metabolic status was observed, with stronger associations among normoglycemic individuals. Findings were consistent across sensitivity analyses, although effect sizes were small. Conclusions: In this nationally representative sample of U.S. adults, higher VK intake was modestly associated with lower insulin resistance markers. Prospective studies incorporating objective VK biomarkers and dynamic measures of insulin sensitivity are needed to clarify these associations. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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14 pages, 864 KB

Open AccessArticle

The First Selective Screening for Type 1 Diabetes in a Pediatric Population in Bulgaria

by Natasha Yaneva, Meri Petrova, Adelina Yordanova, Trifon Popov, Margarita Arshinkova, Dobroslav Kyurkchiev and Ekaterina Kurteva

J. Clin. Med. 2026, 15(8), 3075; https://doi.org/10.3390/jcm15083075 - 17 Apr 2026

Viewed by 914

Abstract

Background: Screening for presymptomatic type 1 diabetes (T1D) reduces the risk of diabetic ketoacidosis (DKA) and allows for early intervention with disease-modifying therapies. Despite the rising incidence of T1D in Bulgaria, screening initiatives remain limited. This pilot study aims to evaluate the feasibility of selective T1D screening in high-risk children and identify potential clinical associations with islet autoimmunity. Methods: The study targeted a recruitment of 250 children aged 0–18 years (200 with a relative with T1D and 50 without). Screening for islet autoantibodies (AABs), including glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated-2 (IA-2A), zinc transporter-8 (ZnT8A), and islet cell cytoplasmic autoantibodies (ICAs), was performed via chemiluminescence immunoassay (CLIA). Participants testing positive for one or more AABs were scheduled for longitudinal immunological and metabolic follow-up to evaluate the persistence of autoimmunity and disease progression. Results: Between October 2024 and February 2026, the pilot study recruited 210 participants (84% of the 250 target), including 160 children with a relative (target 200) and 50 without a family history of T1D (target 50). Within the high-risk group, seven children (4.4%) tested positive for a single autoantibody (3 GADA, 2 ZnT8A, 1 IA-2A, and 1 IAA), while no autoantibodies were detected in the group without a relative. No cases of multiple autoantibody positivity or stage 3 T1D were identified in either group. Furthermore, no statistically significant associations were observed between autoantibody positivity and secondary factors, including breastfeeding, allergic status, a high-glycemic diet, frequent illness, and personal history of autoimmune disease. Conclusions: The findings validate the feasibility of selective T1D screening in Bulgaria, driven by high public interest and successful recruitment across both high-risk and general population cohorts. While this exploratory study found no significant clinical correlations, it establishes a vital roadmap for larger, longitudinal research. Ultimately, this pilot framework provides a scalable model for implementing standardized early detection to reduce the burden of T1D on the national healthcare system. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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9 pages, 560 KB

Open AccessArticle

Patterns and Clinical Outcomes of Sitagliptin/Metformin Extended-Release in Internal Medicine: A Real-World Multicenter Italian Study

by Mariarosaria De Luca, Michele Arcopinto, Giosiana Bosco, Sebastiano Cicco, Francesco Di Giacomo Barbagallo, Chiara Giacinti, Marialuisa Sveva Marozzi, Maristella Salvatora Masala, Miriam Pinna, Giacomo Pucci, Andrea Salzano, Roberto Scicali, Alberto Maria Marra and Antonio Cittadini

J. Clin. Med. 2026, 15(3), 927; https://doi.org/10.3390/jcm15030927 - 23 Jan 2026

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Background: In internal medicine, the management of type 2 diabetes mellitus (T2DM) is challenged by multimorbidity and polypharmacy. The fixed-dose combination of sitagliptin and extended-release metformin (SITA/MET ER) is a valuable option for frail and comorbid patients. Methods: This multicenter, retrospective, observational study involved five Italian Internal Medicine units. Consecutive patients with T2DM who initiated SITA/MET ER were included. Demographic, clinical, and laboratory data were collected at baseline (T0) and at follow-up (T1, 3–4 months). The primary endpoint was change in HbA1c; secondary endpoints included fasting plasma glucose (FPG), treatment adherence, adverse events, and modifications in concomitant antidiabetic therapies. Results: A total of 292 patients (mean age 70.8 ± 10.6 years; 43% female) were analyzed. At baseline, mean HbA1c was 7.4 ± 1.0% and FPG 150.2 ± 42.5 mg/dL, with significant reductions observed at follow-up (HbA1c 7.0 ± 0.8%, FPG 136.8 ± 29.6 mg/dL; both p < 0.05). SITA/MET ER was predominantly prescribed to patients with a complex clinical profile, as reflected by the high prevalence of microvascular (37%) and macrovascular (42%) complications. The use of sulfonylureas decreased from 11% to 3% (p < 0.001), while SGLT2 inhibitor and insulin use remained stable. Treatment adherence to SITA/MET ER was excellent, with full compliance reported and no adverse events recorded. Conclusions: In this real-world internal medicine study, SITA/MET ER improved glycemic control and was well tolerated among patients with complex clinical profiles. These findings support the role of SITA/MET ER as a flexible and practical therapeutic choice in this setting. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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13 pages, 416 KB

Open AccessFeature PaperArticle

Impaired Attention Functioning in Children and Adolescents with Obesity: Preliminary Results Based on the Computerized Continuous Performance Test

by Katarzyna Anna Majewska, Maia Stanisławska-Kubiak, Paulina Wais, Joanna Budzulak, Ewa Mojs and Andrzej Kędzia

J. Clin. Med. 2025, 14(24), 8656; https://doi.org/10.3390/jcm14248656 - 6 Dec 2025

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Abstract

Background/Objectives: Attention is a fundamental cognitive parameter, essential for developmental processes. It enables the selective processing of environmental stimuli and guides behavioral responses. Obesity, apart from its broad influence on human somatic health, is also associated with mental and cognitive functioning. In childhood obesity, detailed attention assessment could help elucidate the relationship between the condition and cognitive development, and perhaps also help predict specific difficulties during treatment. The aim of the study was to investigate attention functioning in children and adolescents with obesity using the computerized continuous performance test (CPT). Methods: The study involved 71 children, including 23 with obesity and 48 healthy children with normal body weight. The MOXO CPT was used to assess attention parameters in all participants. The test covered four parameters: sustained attention, timing, impulsivity, and hyperactivity. Results: Children with obesity obtained significantly lower CPT results in terms of timing (p = 0.024), hyperactivity (p = 0.001), and impulsivity (p < 0.001), while the difference in sustained attention did not reach statistical significance (p = 0.074). Conclusions: Attention efficiency appears to be reduced in children with obesity compared with their healthy peers. Assessment of attention parameters in this group of patients could be valuable in the context of planning and implementing therapeutic interventions. Children with coexisting obesity and impaired attention functioning would probably require more assistance in following daily behavioral and nutritional recommendations. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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26 pages, 2825 KB

Open AccessReview

The Benefits of Non-Pharmaceutic Interventions on Intrinsic Capacity in Insulin-Resistant Adult and Geriatric Populations—A Narrative Review

by Iulia-Daniela Lungu, Adina Carmen Ilie, Ramona Ștefăniu, Sabinne-Marie Albișteanu, Ana-Maria Turcu, Gabriela Grigoraș, Diana-Gabriela Constantinescu, Anca-Iuliana Pîslaru and Ioana Dana Alexa

J. Clin. Med. 2026, 15(15), 6101; https://doi.org/10.3390/jcm15156101 - 5 Aug 2026

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Abstract

Insulin resistance (IR) is a well-established metabolic disorder characterized by reduced responsiveness of peripheral tissues to insulin, leading to hyperglycemia and compensatory hyperinsulinemia. Background: In older adults, IR tends to develop gradually and may remain undiagnosed for years due to the insidious nature of the condition, which often lacks overt symptoms. Non-pharmacological interventions refer to the sum of all measures taken in order to improve a certain biological determination or physical parameter and they consist of lifestyle and dietary modifications. Although insulin resistance is recognized as a central mechanism involved in the development of numerous chronic diseases associated with aging, its impact on intrinsic capacity and the mechanisms underlying this relationship are insufficiently synthesized in the literature. In this context, the present narrative review aims to integrate the current evidence on the interaction between insulin resistance and intrinsic capacity, highlighting common biological mechanisms and potential therapeutic and preventive strategies to promote healthy aging. Methods: We conducted a literature search in PubMed, Scopus and Web of Science databases, screening the literature published between 2010 and January 2026. The search strategy included keywords and Boolean operators in order to refine the suggestions. Relevant articles, reviews, studies and guidelines were selected based on their relevance to the objective of this review. Results and Conclusions: The results of the review highlight that insulin resistance represents a central mechanism contributing to the decline in intrinsic capacity through chronic inflammation, oxidative stress, mitochondrial dysfunction and alteration of the gut microbiota. Current evidence suggests that nutritional interventions, in particular the Mediterranean diet and the DASH diet, can improve insulin sensitivity by modulating the microbiota and reducing systemic inflammation, with the potential to contribute to maintaining functional capacity and promoting healthy aging. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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24 pages, 646 KB

Open AccessReview

Beyond Glycemic Control: GLP-1RA–Based Therapies and Emerging Targets Beyond the Metabolic Axis

by Wojciech Matuszewski, Katarzyna Wołos-Kłosowicz, Paulina Włodarczyk, Patrycja Waśniewska, Robert Modzelewski, Jan Marek Górny, Michał Szklarz, Mikołaj Madeksza and Judyta Juranek

J. Clin. Med. 2026, 15(7), 2786; https://doi.org/10.3390/jcm15072786 - 7 Apr 2026

Cited by 1 | Viewed by 1751

Abstract

Background/Objectives: Modern diabetes therapy extends beyond glycemic control and increasingly focuses on comprehensive risk reduction to prevent long-term complications, improve quality of life, and reduce premature mortality. Accordingly, modern therapeutic approaches address not only glucose metabolism but also cardiovascular, renal, and metabolic consequences of diabetes. Within this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a significant therapeutic class. In addition to their well-known effects on glycemic control and the metabolic-cardiovascular-renal axis, increasing evidence suggests that these agents may exert a range of pleiotropic effects and opening new therapeutic venues, discussed in this review. Methods: A narrative review of the literature was conducted using the PubMed, Scopus, and Google Scholar databases. Publications from 2014 and 2026 were screened using predefined keywords related to GLP-1 RAs and their potential effects across multiple physiological systems and diseases. Notably, more than 80% of the included studies were published between 2020 and 2026, reflecting the recent growth of research in this field. Results: GLP-1 RAs have been associated with beneficial effects across a wide range of conditions, including substance use disorders, mental health disorders, neurodegenerative diseases, obesity-related complications, liver disease, genitourinary disorders, osteoarthritis, and sleep apnea. While they are currently the most effective pharmacological agents for the treatment of obesity, they also significantly reduce hepatic steatosis and are associated with a decreased risk of developing hepatocellular carcinoma. Furthermore, they have also demonstrated positive effects against prostate cancer, polycystic ovary syndrome (PCOS), improved libido and fertility. Conclusions: GLP-1 RAs should no longer be regarded solely as antihyperglycemic agents. Instead, they represent a versatile therapeutic class with expanding clinical relevance across multiple medical disciplines. While current evidence is promising, further large-scale, well-designed clinical trials are required to define their full therapeutic potential. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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27 pages, 1797 KB

Open AccessReview

Diabetes Mellitus as an Integrated Microbiome, Immune, and Metabolic Disorder with Clinical Implications for Multisystem Complications and Public Health

by Ayman Elbehiry, Eman Marzouk, Fahad A. Alhumaydhi and Adil Abalkhail

J. Clin. Med. 2026, 15(5), 1788; https://doi.org/10.3390/jcm15051788 - 27 Feb 2026

Cited by 2 | Viewed by 1235

Abstract

Diabetes mellitus is one of the most common health problems worldwide; however, increased blood glucose alone cannot adequately explain its pathophysiology. Although high blood glucose is a defining feature, evidence increasingly proves that diabetes arises from systemic disturbances involving the gut microbiome, immune system, and metabolic control. From this perspective, diabetes can be viewed as a systemic condition shaped by the dynamic interactions between the gut microbiome, the immune system, and metabolic pathways. Alterations in gut microbiome composition and function can influence nutrient metabolism, microbial metabolite production, bile acid signaling, and intestinal barrier integrity. Any damage of the gut barrier allows movement of microbiome-derived molecules that activate innate immune pathways and provoke chronic low-grade inflammation. This inflammatory state interferes with insulin signaling, contributes to immune maladaptation, and exacerbates metabolic dysfunction. Over time, these processes contribute to the advance of multisystem complications, including cardiovascular disease, diabetic nephropathy, neuropathy with cognitive impairment, delayed wound healing, and increased susceptibility to infection. The review also integrates environmental and public health factors, demonstrating how diet, antibiotic exposure, circadian disruption, and social conditions shape the microbiome, immune function, metabolic regulation, and disease risk across the life course. By bringing together clinical, experimental, and population-based evidence, this review illustrates the limitations of care models that concentrate only on glucose. It also points out how integrated approaches targeting the microbiome, immune system, and metabolic pathways can improve diabetes prevention, management, and guide future research. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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21 pages, 873 KB

Open AccessReview

Enhancing Primary Care Recognition of Type 1 Diabetes in Children: Diagnostic Challenges and Strategies to Prevent Diabetic Ketoacidosis

by Yung-Yi Lan, Rujith Kovinthapillai, Andrzej Kędzia and Elżbieta Niechciał

J. Clin. Med. 2026, 15(2), 533; https://doi.org/10.3390/jcm15020533 - 9 Jan 2026

Cited by 1 | Viewed by 2160

Abstract

Timely recognition of type 1 diabetes (T1D) in children and adolescents is crucial to prevent acute complications such as diabetic ketoacidosis (DKA). This narrative review examines the pathophysiology, clinical presentation, and diagnostic challenges of childhood T1D, including the young age of onset, clinician training gaps, and overlapping symptomatology between T1D and other common pediatric illnesses. Despite increased awareness, a significant proportion of children still present with DKA at diagnosis due to misinterpretation of symptoms, such as polydipsia, polyuria, and weight loss. This work emphasizes the importance of early recognition, timely intervention, and the use of structured management algorithms for primary care clinicians. Strategies to reduce DKA incidence, based on existing literature, successful real-world examples, and current guidelines, include enhanced screening for high-risk populations, educational initiatives, and improved diagnostic protocols. By implementing systematic approaches and public health campaigns, healthcare providers can improve early T1D detection and prevent severe DKA complications, ultimately enhancing patient outcomes and reducing long-term morbidity. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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18 pages, 1731 KB

Open AccessSystematic Review

Continuous Glucose Monitoring in Non-ICU Hospitalized Adults with Type 2 Diabetes: A Systematic Review

by Darío Lara-Gálvez, Matilde Rubio-Almanza, Yolanda Aparicio-Ródenas, David Sanchis-Pascual, Pilar Masdeu-López-Cerón, Victor Pérez-Cervantes and Juan Francisco Merino-Torres

J. Clin. Med. 2026, 15(1), 34; https://doi.org/10.3390/jcm15010034 - 20 Dec 2025

Cited by 2 | Viewed by 1841

Abstract

Background: Continuous glucose monitoring (CGM) may overcome the limitations of intermittent point-of-care (POC) testing by providing real-time glucose trends and reducing treatment delays. This study aimed to evaluate the efficacy of CGM versus POC capillary testing in improving glycemic control among hospitalized non-Intensive Care Unit (non-ICU) adults with type 2 diabetes mellitus (T2DM). Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed for randomized controlled trials published in English or Spanish that compared CGM with POC testing in hospitalized non-ICU adults ≥ 18 years old with T2DM and assessed risk of bias using the Cochrane RoB2 tool. The primary outcome was time in range (TIR). Secondary outcomes included time below range (TBR), time above range (TAR), mean glucose (MG), and glycemic variability (GV). Results: Seven randomized controlled trials (RCTs) including 1106 patients were analyzed. CGM significantly improved TIR (mean difference [MD] +8.15%; 95% confidence interval [CI]: +5.76, +10.55; p < 0.001) and reduced TAR > 180 mg/dL (MD −7.11%; 95% CI: −9.43, −4.78; p < 0.001) and TAR > 250 mg/dL (MD −3.96%; 95% CI: −5.29, −2.62; p < 0.001) compared with POC testing. MG also decreased with CGM (MD −11.27 mg/dL; 95% CI: −14.74, −7.81; p < 0.001). A modest reduction in TBR <70 mg/dL was observed (MD −0.29%; p < 0.001), whereas no significant differences were found for TBR < 54 mg/dL or GV. Conclusions: CGM improves inpatient glycemic control in non-ICU adults with type 2 diabetes, demonstrating advantages over POC testing across multiple randomized trials. However, further multicenter research is needed to clarify workflow implications, cost-effectiveness, and optimal implementation strategies. Full article

(This article belongs to the Special Issue Diabetes Mellitus and Emerging Health Challenges: A Multidisciplinary Perspective)

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