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Biomedicines
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New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition
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New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 4595

Special Issue Editor

Dr. Tomislav Bulum

E-Mail Website
Guest Editor
1. Vuk Vrhovac Univerity Clinic, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia
2. Medical Faculty, University of Zagreb, Šalata 2, 10000 Zagreb, Croatia
Interests: diabetes type 1; diabetes type 2; metabolic syndrome; diabetic nephropathy; diabetic retinopathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The discovery of insulin in 1921 represented a milestone in the treatment of diabetes. In 1923, the Nobel Prize for Medicine was awarded for its discovery, and it was one of the most important discoveries in the history of medical science, affecting hundreds of millions of people worldwide. Thousands of lives have been saved, and the life expectancy of people with diabetes has been significantly extended. Since its discovery, insulin has been continuously improved through pharmacological development and optimized for therapeutic purposes, including the development of intermediate- and long-acting insulins, the ability to produce human insulin, and finally, the development of insulin analogs with improved properties using recombinant DNA technology.

Despite increasing awareness, diabetes is still one of the most challenging health problems in the 21st century. In the last 15 years, the number of people diagnosed with type 1 diabetes has increased by 45%, and the number of people diagnosed with type 2 diabetes has increased by 95%. Recently, the focus in the treatment of diabetes has been on new therapeutic options; however, insulin is still one of the most potent therapeutic options for patients with type 2 diabetes and is the only one for patients with type 1 diabetes.

Considering this context, this Special Issue will focus on the roles of insulin and insulin action in a broad sense. We welcome submissions related to new knowledge about insulin secretion and action, as well as the development and action of insulin analogs and their effects on glycemic control and chronic complications in diabetes.

Dr. Tomislav Bulum
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • insulin action
  • insulin analogs
  • type 1 diabetes
  • type 2 diabetes
  • complications
  • glucose homeostasis

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Related Special Issue

Published Papers (4 papers)

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Research

27 pages, 1223 KB  
Article
Effects of Recommended Supplementation and Mediterranean Diet Adherence on Post-Metabolic Bariatric Surgery Outcomes
by Jan Dębski, Anna Sabuć, Antonina Spalińska, Józef Przybyłowski, Klaudia Skibiak, Maria Czerwińska, Joanna Dzedzej, Emilia Talarek, Amelia Gierula, Krzysztof Wyszomirski, Maciej Walędziak and Anna Różańska-Walędziak
Biomedicines 2026, 14(3), 513; https://doi.org/10.3390/biomedicines14030513 - 26 Feb 2026
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Abstract
Background/Objectives: Metabolic bariatric surgery is an effective treatment for severe obesity but is associated with an increased risk of postoperative nutritional deficiencies. This study aimed to assess the impact of adherence to the Mediterranean diet on selected laboratory parameters and excess weight loss [...] Read more.
Background/Objectives: Metabolic bariatric surgery is an effective treatment for severe obesity but is associated with an increased risk of postoperative nutritional deficiencies. This study aimed to assess the impact of adherence to the Mediterranean diet on selected laboratory parameters and excess weight loss after bariatric surgery. Methods: Eighty adults with obesity were evaluated before and 6 months after surgery. Based on dietary questionnaires, patients were classified as adhering to the Mediterranean diet (n = 32) or not adhering (n = 48). Laboratory parameters, including vitamin D, vitamin B12, folic acid, iron, ferritin, calcium, hemoglobin, and total protein, were assessed pre- and postoperatively. Excess weight loss percentage (EWL%) was calculated using standard methodology. Results: Postoperatively, vitamin D and total protein levels increased in both groups, with median increases of 9.45 ng/mL and 1.1 g/dL, respectively. A significant increase in iron concentration was observed only in Mediterranean diet adherents (median +24 µg/dL), while a decrease was noted in non-adherent patients (−4 µg/dL). Iron deficiency and iron-deficiency anemia occurred exclusively in the non-Mediterranean diet group (10.4% vs. 0%). Median EWL% was higher in Mediterranean diet adherents (44% vs. 31%), although the difference was not statistically significant. Conclusions: Adherence to the Mediterranean diet may reduce the risk of iron deficiency after bariatric surgery, whereas total protein concentration alone appears insufficient for assessing nutritional status or weight loss effectiveness. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition)
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12 pages, 392 KB  
Article
Transcutaneous Carbon Dioxide Therapy Significantly Accelerates Diabetic Foot Ulcer Healing: A Multicentre Randomised Controlled Trial
by Igor Frangež, Miloš Potkonjak, Skender Veliu, Željko Metelko, Anica Badanjak, Julija Križaj, Helena Ban Frangež, Tamara Poljičanin, Marco Meloni, Nikolaos Papanas and Tomislav Bulum
Biomedicines 2026, 14(2), 422; https://doi.org/10.3390/biomedicines14020422 - 13 Feb 2026
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Abstract
Background/Objectives: Diabetic foot ulcers (DFUs) represent common and severe complications of diabetes mellitus (DM). The aim of our parallel-group, open-label, superiority, multicentre randomised controlled trial (RCT) was to evaluate the effectiveness of transcutaneous gaseous carbon dioxide therapy (hereinafter CO2 therapy) in ulcer [...] Read more.
Background/Objectives: Diabetic foot ulcers (DFUs) represent common and severe complications of diabetes mellitus (DM). The aim of our parallel-group, open-label, superiority, multicentre randomised controlled trial (RCT) was to evaluate the effectiveness of transcutaneous gaseous carbon dioxide therapy (hereinafter CO2 therapy) in ulcer healing in patients with non-healing DFUs. Methods: A total of 115 participants (89 males and 26 females, aged 65.7 ± 10.9 years) with a non-healing DFU were randomised to the intervention (76 participants) and control (39 participants) group. Participants in the intervention group received standard of care, combined with CO2 therapies administered every weekday for four consecutive weeks. Participants in the control group received only standard of care. Results: After 4 weeks, 49 (64.5%) ulcers in the intervention group healed, compared with three (7.7%) in the control group (primary outcome). The percentage ulcer area reduction from baseline (secondary outcome) was significantly larger (p ≤ 0.001) in patients from the intervention group, with the median value 100% (18.4–100%), compared to the patients from the control group, with the median value 40% (−300–100%). Patients receiving CO2 therapy had 35.4-fold higher odds of ulcer healing versus controls (OR 35.4, 95% CI 6.68–187.53; p < 0.001), and in multivariate logistic regression, CO2 therapy remained independently associated with healing, while larger baseline ulcer area was associated with lower odds of healing (OR 0.654, 95% CI 0.438–0.977; p = 0.038). No adverse effects were reported. Conclusions: CO2 therapy significantly contributes to ulcer healing in patients with non-healing DFUs, with no observable adverse effects, demonstrating significant potential as an effective and safe complementary treatment of DFUs in conjunction with standard of care. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition)
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18 pages, 707 KB  
Article
Prevalence and Risk Factors of MASLD in Prediabetes and Type 2 Diabetes Mellitus in Belgium and The Netherlands
by Leen J. M. Heyens, Francesco Innocenti, Christophe Van Steenkiste, Mathieu Struyve, Sven M. Francque, Ger H. Koek, Geert Robaeys and on behalf of the MASLD Research Group
Biomedicines 2025, 13(11), 2821; https://doi.org/10.3390/biomedicines13112821 - 19 Nov 2025
Cited by 1 | Viewed by 1182
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely intertwined with glucose metabolism status (GMS). Bi-national comparative epidemiological data are lacking; therefore, this study aimed to provide new insights into MASLD and fibrosis prevalence and risk factors in Belgium, while comparing data [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely intertwined with glucose metabolism status (GMS). Bi-national comparative epidemiological data are lacking; therefore, this study aimed to provide new insights into MASLD and fibrosis prevalence and risk factors in Belgium, while comparing data from The Netherlands to uncover cross-country differences. Materials and Methods: A prospective cohort study (2019–2024) in Belgian primary and secondary care was compared with the Dutch Maastricht Study. Liver fat was measured using CAP (FibroScan®), and anthropometric, clinical, and biochemical data were collected. Associations with CAP were analysed using multivariable linear regression, including sex, age, BMI, MetS, high SBP, CVD history, and country. Results: A total of 2436 individuals (Belgium and The Netherlands) were screened, of which 1928 were eligible: MASLD with normal GMS (38.3%), prediabetes (19.2%), and type 2 diabetes mellitus (T2DM; 42.5%). Belgian participants with T2DM had higher BMI and prevalence of MASLD. CAP values were significantly associated with female sex (−7.5 dB/m, 95%CI (−11.834; −3.056), p < 0.001), BMI (5.184 dB/m, 95%CI (4.627; 5.741), p < 0.001), and MetS (13.7 dB/m, 95%CI (8.456; 18.994), p < 0.001). Country-specific interactions showed differing effects of high SBP and CVD on CAP between Belgium and The Netherlands, with only the inverse association of CVD history (−10.756, 95%CI (−17.485; −4.027), p = 0.002) with CAP in The Netherlands being significant. Conclusions: MASLD and fibrosis are common in people with prediabetes and T2DM, underscoring the need for early detection and management. Obesity and metabolic risk were key factors, while a history of CVD appeared protective in the Dutch cohort but not in the Belgian one. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition)
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15 pages, 704 KB  
Article
Fetal Sex Modulates Hofbauer Cells’ Response to Diabetes in Human Placenta
by Zdenek Tauber, Max Mrstik, Adela Burianova, Katerina Koubova and Katerina Cizkova
Biomedicines 2025, 13(11), 2606; https://doi.org/10.3390/biomedicines13112606 - 24 Oct 2025
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Abstract
Background: Hofbauer cells (HBCs) are fetal-origin macrophages in the placental villous stroma that contribute to immune tolerance at the feto–maternal interface. They predominantly display an M2 phenotype, characterized by CD206 expression. Methods: Using immunohistochemistry and morphometric analysis, we quantified HBCs, assessed [...] Read more.
Background: Hofbauer cells (HBCs) are fetal-origin macrophages in the placental villous stroma that contribute to immune tolerance at the feto–maternal interface. They predominantly display an M2 phenotype, characterized by CD206 expression. Methods: Using immunohistochemistry and morphometric analysis, we quantified HBCs, assessed CD206 intensity and morphology, and evaluated apoptotic body accumulation in placental villi. Comparisons were made among pregnancies complicated by type 1 diabetes mellitus (T1DM), gestational diabetes mellitus (GDM), and normoglycemic controls, as well as between male and female fetuses. Results: Significant effects of maternal diabetes and fetal sex on CD206 intensity were observed ([diagnosis: F = 2773.00, p < 0.0001; sex: F = 12.19, p = 0.0005]), with a strong interaction (F = 165.40, p < 0.0001). In controls, CD206 intensity was higher in female than male fetuses (p < 0.0001). Across groups, CD206 intensity decreased progressively from controls to GDM and T1DM, with a more pronounced reduction in females. Reduced CD206 was associated with elongation and irregular HBC morphology and increased IL-1β (r = −0.392, p = 0.003; r = −0.609, p < 0.0001) suggesting less tolerogenic phenotype. For apoptotic bodies, significant main effects of maternal diabetes and fetal sex were detected ([diagnosis: F = 97.16, p < 0.0001; sex: F = 15.88, p = 0.0001]). Accumulation increased progressively from controls to GDM and T1DM, with higher counts in males. Conclusions: Maternal diabetes is associated with reduced CD206 intensity, altered HBC morphology, and accumulation of apoptotic bodies in placental villi. Our results suggest greater HBC plasticity, potentially contributing to a tolerogenic placental environment in females. Full article
(This article belongs to the Special Issue New Advances in Insulin—100 Years Since Its Discovery: 2nd Edition)
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