The ability of pGCD59 to predict adverse pregnancy outcomes: a prospective study of non‑diabetic pregnant women in Ireland

Delia Bogdanet1  · Michelle Toth Castillo2  · Helen Doheny3  · Louise Dervan1  · Miguel Angel Luque‑Fernandez4,5 ·Jose A. Halperin2  · Paula M. O’Shea1,3 · Fidelma P. Dunne1

Received: 12 July 2022 / Accepted: 27 September 2022 / Published online: 29 October 2022 © The Author(s) 2022

Abstract

Aim Even though most pregnancies are uneventful, occasionally complications do occur. Gestational diabetes is linked to an increased risk of adverse pregnancy outcomes. Early identification of women at risk of experiencing adverse outcomes, ideally through a single blood test, would facilitate early intervention. Plasma glycated CD59 (pGCD59) is an emerging biomarker which has shown promise in identifying hyperglycaemia during pregnancy and has been associated with the risk of delivering an LGA infant. The aim of this study was to explore the ability of the first- and second-trimester pGCD59 to predict adverse pregnancy outcomes.

Methods This was a prospective study of 378 pregnant women. Samples for pGCD59 were taken at the first antenatal visit and at the time of the 2 h 75 g OGTT (24–28 weeks of gestation). Adjusted receiver operating characteristic curves were used to evaluate the ability of pGCD59 to predict maternal and neonatal outcomes.

Results First-trimester pGCD59 levels were higher in women with gestational diabetes who delivered a macrosomic infant (4.2±0.7 vs. 3.5±1.0 SPU, p<0.01) or an LGA infant (4.3±0.3 vs. 3.6±1.0 SPU, p=0.01) compared to women with GDM that did not experience these outcomes. Second-trimester pGCD59 levels were higher in women that developed polyhydramnios (2.9±0.4 vs. 2.5±1.1 SPU, p=0.03). First- and second-trimester pGCD59 predicted pregnancy-induced hypertension with good accuracy (AUC:0.85, 95%CI:0.78–0.91; AUC: 0.80, 95%CI: 0.73–0.88, respectively) and neonatal hypoglycaemia with fair to good accuracy (AUC:0.77, 95%CI: 0.54–0.99, AUC:0.81, 95%CI:0.62–0.99).

Conclusions This study has shown that pGCD59 has the potential to predict adverse pregnancy outcomes. Prospective studies with a larger number of cases are necessary to fully explore and validate the potential of this emerging biomarker in predicting adverse pregnancy outcomes.

Keywords Pregnancy outcomes · Gestational diabetes · Biomarker · pGCD59

This article belongs to the topical collection Pregnancy and Diabetes, managed by Antonio Secchi and Marina Scavini.

* Delia Bogdanet

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Michelle Toth Castillo

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Helen Doheny

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Louise Dervan

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Miguel Angel Luque-Fernandez

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Jose A. Halperin

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Paula M. O’Shea

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Fidelma P. Dunne

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1 College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland, Galway, Ireland

2 Divisions of Haematology, Brigham & Women’s Hospital, Harvard Medical School, Boston, USA

3 Department of Clinical Biochemistry, Saolta University Health Care Group (SUHCG), Galway University Hospitals, Galway, Ireland

4 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

5 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK

On the occasion of the centennial of insulin therapy (1922–2022), II‑Organotherapy of diabetes mellitus (1906–1923): Acomatol. Pancreina. Insulin.

Alberto de Leiva‑Hidalgo1,2  · Alejandra de Leiva‑Pérez2

Received: 2 October 2022 / Accepted: 30 November 2022 / Published online: 31 December 2022 © The Author(s) 2022

Abstract

Aims The general objective has been the historiographical investigation of the organotherapy of diabetes mellitus between 1906 and 1923 in its scientific, social and political dimensions, with special emphasis on the most relevant contributions of researchers and institutions and on the controversies generated on the priority of the "discovery" of antidiabetic hormone.

Methods We have analyzed the experimental procedures and determination of biological parameters used by researchers during the investigated period (1906–1923): pancreatic ablation techniques, induction of acinar atrophy with preservation of pancreatic islets, preparation of pancreatic extracts (PE) with antidiabetic activity, clinical chemistry procedures (glycemia, glycosuria, ketonemia, ketonuria, etc.). The field investigation has included on-site and online visits to cities, towns, buildings, laboratories, universities, museums and research centers where the reported events took place, obtaining documents, photographic images, audiovisual recordings, as well as personal interviews complementary to the documentation consulted (primary sources, critical bibliography, reference works). The documentary archival sources have been classified according to theme, including those consulted in situ with those extracted online and digitized copies received mainly by email. Among the many archives contacted, those listed below have been most useful and have been consulted on site and on repeated visits: National Library of Medicine-Historical Archives (Bethesda, MD, USA); Archives, University of Toronto and Thomas Fisher Rare Books Library (Toronto, Ontario, Canada); Francis A. County Library of Medicine, Harvard University (Boston, Mass, USA); Zentralbibliothek der Humboldt-Universität (Berlin, DE), Geheimarchiv des Preuβischen Staates (Berlin, DE); Landesamt für Bürger—und Ordnungsangelegenheiten (LABO) (Berlin, DE); Arhivele Academiei Române şi Universitǎții Carol Davila (Bucharest, RO).

Main results and conclusions A) The European researchers Zülzer (Z Exp Path Ther 23:307–318, 1908) and Paulescu (CR Seances Soc Biol Fil 85:558, 1921) meet the requirements of the priority rule in the discovery of the antidiabetic hormone. B) Factors of socioeconomic and political nature related with the First World War and the inter-war period delayed the process of purification of the antidiabetic hormone in Europe. C) The Canadian scientist J. Collip, University of Alberta, temporarily assimilated to the University of Toronto, and the American chemist and researcher G. Walden, with the expert collaboration of Eli Lilly & Co., were the main authors of the purification process of the antidiabetic hormone. D) The scientific evidence, reflected in the heuristics of this research, allows to assert that the basic investigation carried out by the Department of Physiology of the University of Toronto, directed by the Scottish J. Macleod, in conjunction with the clinical research undertaken by the Department of Medicine of the University of Toronto (W. Campbell, A. Fletcher, D. Graham) made it possible in record time the successful treatment of patients with what was until then a deadly disease.

Keywords Pancreatic extracts · Organotherapy · Acomatol · Pancreina · Insulin · Patents

Managed by Antonio Secchi.

Alberto de Leiva-Hidalgo and Alejandra de Leiva-Pérez have

contributed equally.

Extended author information available on the last page of the article

Monogenic diabetes clinic (MDC): 3‑year experience

Novella Rapini1  · Patrizia I. Patera1  · Riccardo Schiafni1  · Paolo Ciampalini1  · Valentina Pampanini1  ·

Matteoli M. Cristina1  · Annalisa Deodati1  · Giorgia Bracaglia2  · Ottavia Porzio2,3 · Rosario Ruta4  · Antonio Novelli4  ·

Mafalda Mucciolo4  · Stefano Cianfarani1,5,6  · Fabrizio Barbetti2

Received: 30 May 2022 / Accepted: 6 September 2022 / Published online: 30 September 2022 © The Author(s) 2022, corrected publication 2022

Abstract

Aim In the pediatric diabetes clinic, patients with type 1 diabetes mellitus (T1D) account for more than 90% of cases, while monogenic forms represent about 6%. Many monogenic diabetes subtypes may respond to therapies other than insulin and have chronic diabetes complication prognosis that is different from T1D. With the aim of providing a better diagnostic pipeline and a tailored care for patients with monogenic diabetes, we set up a monogenic diabetes clinic (MDC).

Methods In the first 3 years of activity 97 patients with non-autoimmune forms of hyperglycemia were referred to MDC. Genetic testing was requested for 80 patients and 68 genetic reports were available for review.

Results In 58 subjects hyperglycemia was discovered beyond 1 year of age (Group 1) and in 10 before 1 year of age (Group 2). Genetic variants considered causative of hyperglycemia were identified in 25 and 6 patients of Group 1 and 2, respectively, with a pick up rate of 43.1% (25/58) for Group 1 and 60% (6/10) for Group 2 (global pick-up rate: 45.5%; 31/68). When we considered probands of Group 1 with a parental history of hyperglycemia, 58.3% (21/36) had a positive genetic test for GCK or HNF1A genes, while pick-up rate was 18.1% (4/22) in patients with mute family history for diabetes. Specific treatments for each condition were administered in most cases.

Conclusion We conclude that MDC may contribute to provide a better diabetes care in the pediatric setting.

Keywords Monogenic diabetes · GCK · HNF1A · INSR · Glibenclamide · SGLT2i

Managed by Antonio Secchi.

* Fabrizio Barbetti

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1 Diabetology and Growth Disorders Unit, Bambino Gesù Children’s Hospital, IRCCS, 00164 Rome, Italy

2 Clinical Laboratory Unit, Bambino Gesù Children’s Hospital, Piazza S Onofrio 4, 00165 Rome, Italy

3 Department of Experimental Medicine, Univerisity of Rome ‘Tor Vergata’, 00131 Rome, Italy

4 Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy

5 Department of Systems Medicine, University of Rome ‘Tor Vergata’, 00131 Rome, Italy

6 Department of Women’s and Children’s Health, Karolinska Institutet, 17177 Stockholm, Sweden

Evaluation of the prevalence of the most common psychiatric disorders in patients with type 2 diabetes mellitus using the patient health questionnaire: results of the cross‑sectional “DIA2PSI” study

Angelo Emilio Claro1,2  · Clelia Palanza3  · Marianna Mazza1,2  · Andrea Corsello4  · Alessandro Rizzi4  · Linda Tartaglione4  · Chiara de Waure5  · Giuseppe Marano1,2 · Simone Piciollo6  · Giovanna Elsa Ute Muti Schuenemann7  · Marta Rigoni8  · Paola Muti8  · Alfredo Pontecorvi9  · Luigi Janiri1,2  · Gabriele Sani1,2  · Dario Pitocco4

Received: 29 July 2022 / Accepted: 7 October 2022 / Published online: 7 November 2022 © The Author(s) 2022

Abstract

Aims Common Psychiatric Disorders (CPDs) are associated with the development of overweight and obesity, the strongest risk factors for the onset and maintenance of Type 2 Diabetes mellitus (T2D). To the best of our knowledge, this is the frst study to assess the prevalence of CPDs in patients with T2D in Italy.

Methods This is a monocentric cross-sectional study; n=184 T2D patients were screened for CPDs using the Patient Health Questionnaire (PHQ). Primary outcome was to evaluate the prevalence of CPDs. To assess association between CPDs and risk factors, we have utilized univariable logistic regression models.

Results 64.1% were men, median age was 67 (59–64) and median BMI 27 (25–30) kg/m2 . The 42.9% tested positive for one or more mental disorders, 25.6% for depression. Patients with higher BMI (p=0.04) had an increased likelihood of testing positive to the PHQ. Patients who had implemented lifestyle changes (p<0.01) and were aware that mental health is linked to body health (p=0.07) had a reduction in the likelihood of testing positive.

Conclusions Prevalence of CPDs in T2D patients is higher than in the general population. Since CPDs favor the onset and subsistence of T2D, integrated diabetic-psychiatric therapy is required for improvement or remission of T2D in patients with comorbid CPDs.

Keywords Diabetes Mellitus Type 2 · Italy · Mental Disorders · Depression · Feeding and Eating Disorders · Alcohol Induced Disorders

Managed by Massimo Porta.

* Dario Pitocco

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Effect of obesity on fragility fractures, BMD and vitamin D levels in postmenopausal women. Infuence of type 2 diabetes mellitus

J. Gómez de Tejada‑Romero1,2· P. Saavedra‑Santana3  · F. de la Rosa‑Fernández1  · N. Suárez‑Ramírez1  ·Martín‑Martínez1,4· F. Martín del Rosario1  · M. Sosa‑Henríquez1,5

Received: 1 April 2022 / Accepted: 14 June 2022 / Published online: 4 July 2022 © The Author(s) 2022

Abstract

Aims To see the effects of obesity on risk fracture, bone density (BMD), and vitamin D levels in a group of postmenopausal women, and consider how comorbid type 2 diabetes mellitus (T2DM) modifies them.

Methods 679 postmenopausal women were grouped into obese and non-obese. Obese women were grouped into those with T2DM and those without. 25(OH)-vitamin D, PTH and BMD were measured, and prevalent fragility fractures were gathered.

Results Obese women had higher prevalence of T2DM, than non-obese women. Levels of 25(OH)-vitamin D were lower and those of PTH higher in obese women, BMD values were higher in obese women. Diabetic-obese women had a higher prevalence of non-vertebral fractures than non-diabetic-obese. Multivariate logistic regression model showed association of fragility fractures with age, total hip BMD, BMI and T2DM. Obese women have higher BMD and lower 25(OH)-vitamin D values (and higher PTH) than non-obese, without diabetes.

Conclusions T2DM confers an increased risk of non-vertebral fractures in postmenopausal obese women.

Keywords Obesity · Diabetes Mellitus type 2 · Vitamin D · Fragility fractures · Osteoporosis

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1 Research Group On Osteoporosis and Mineral Metabolism, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

2 Department of Medicine, University of Seville, Seville, Spain

3 Department of Mathematics, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

4 Gynecology and Obstetrics Service, Maternal-Infant Insular University Hospital Complex, Las Palmas de Gran Canaria, Spain

5 Bone Metabolic Unit, Maternal-Infant Insular University Hospital Complex, Las Palmas de Gran Canaria, Spain

Association between lipid trajectories during pregnancy and risk of postpartum glucose intolerance after gestational diabetes mellitus: a cohort study

Zhuofan Yang1  · Zhuyu Li1  · Yunjiu Cheng2  · Peisong Chen3  · Dongyu Wang1  · Haitian Chen1  · Wei Chen1  · Zilian Wang1

Zhuofan Yang, Zhuyu Li, Yunjiu Cheng have contributed equally to this work.

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1 Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Rd II, Guangzhou 510080, China

2 Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

3 Department of Clinical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

Received: 19 February 2022 / Accepted: 12 May 2022 / Published online: 5 July 2022 © The Author(s) 2022

Abstract

Aims To assess lipid trajectories throughout pregnancy in relation to early postpartum glucose intolerance in women with gestational diabetes mellitus (GDM).

Methods This prospective cohort study included 221 Chinese women with GDM who completed plasma lipid test in each trimester of pregnancy and oral glucose tolerance test at 6–9 weeks postdelivery between January 1, 2018 and January 8, 2020. Using the group-based trajectory modeling, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol(HDL-c) were identifed separately as three trajectories: low, moderate, and high trajectory. The associations between lipid trajectories and early postpartum glucose intolerance were all evaluated.

Results Seventy-three participants developed postpartum glucose intolerance. For patients in low, moderate and high trajectory, the incidence of postpartum glucose intolerance was 38.4%, 34.9%, and 17.9%, respectively. GDM women with lower LDL-c trajectories presented a higher risk of postpartum glucose intolerance. The adjusted odds ratio (95% CI) for glucose intolerance was 3.14 (1.17–8.39) in low LDL-c trajectory and 2.68 (1.05–6.85) in moderate trajectory when compared with the high one. However, TC trajectory was not associated with the risk of postpartum glucose intolerance, nor were TG trajectory and HDL-c trajectory. Moreover, a significant difference of insulin sensitivity was observed in participants with different LDL-c trajectories; participants in high LDL-c trajectory had the highest insulin sensitivity, whereas the women in low LDL-c trajectory had the lowest insulin sensitivity (P=0.02).

Conclusions The high trajectory of LDL-c during pregnancy may play a protective role on postpartum glucose intolerance in women with GDM. Further studies are warranted to explore the underlying mechanism. Trial registration The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (reference number: [2014]No. 93). All participants provided written informed consent forms, and the ethics committee approved this consent procedure.

Keywords Lipid trajectory · Glucose intolerance · Gestational diabetes mellitus · Insulin sensitivity

This article belongs to the topical collection Pregnancyand Diabetes, managed by Antonio Secchi and Marina Scavini.

Abbreviations

GDM Gestational diabetes mellitus

GBTM Group-based trajectory modeling

TC Total cholesterol

TG Triglyceride

LDL-c Low-density lipoprotein-cholesterol

HDL-c High-density lipoprotein-cholesterol

PGDM Pregestational diabetes mellitus

OGTT Oral glucose tolerance test

FBG Fasting blood glucose

HOMA-IS Homeostasis model assessment-IS

BIC Bayesian information criterion

AvePP Average posterior probability

NODM New-onset diabetes mellitus

LDLR Low-density protein receptor