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Group 1 consisted of 7 patients with non-autoimmune, sporadic PNDM, negative to the most common PNDM genes (i.e. KCNJ11, INS, ABCC8) or to a targeted panel of 27 monogenic diabetes genes (Supplementary Table 1). They found biallelic I ONECUT1 i mutations in 2 patients with syndromic, permanent neonatal diabetes mellitus (PNDM) from unrelated consanguineous families; family members carrying heterozygous I ONECUT1 i mutations showed hyperglycemia ranging from IFG to diabetes [[2]]. It is thus conceivable that in our patient G81D, coupled with another not yet identified variant in non coding regions of I ONECUT1 i or in another gene, contribute to causing PNDM. [Extracted from the article]

Background: Although the MODY12 subtype, caused by ABCC8 mutations, is rare, it is highly sensitive to sulfonylureas. The identification of ABCC8 mutations in patients clinically diagnosed with MODY has the ability to contribute to the precise management of diabetes., Methods: Genetic analysis of two families with MODY were conducted using whole-exome sequencing (WES) and Sanger sequencing. The spatial structures of the mutant proteins were constructed using MODELLER and PyMOL software to provide further evidence of pathogenicity., Results: The heterozygous missense mutations V357I and R1393H in ABCC8 were found in probands of two unrelated MODY pedigrees, which co-segregated with the hyperglycemic phenotypes in these two pedigrees. Detection of the V357I mutation enabled the proband of family A to successfully transfer from insulin to sulfonylurea (SU). After 3 months of follow-up for the SU trial, the HbA1c level of proband A improved from 12.4% at the initial diagnosis to 7.20%. Proband B was treated with insulin because of pregnancy and poor islet function. In silico analysis indicated that the R1393H mutation resulted in a longer hydrogen bond distance to L1389 and cleavage of carbon-hydrogen bonds to V1395, A1390, and L1389., Conclusions: We have described two pathogenic missense mutations in ABCC8 in Chinese families with MODY. Our findings support the heterogeneity in the clinical features of MODY12 caused by ABCC8 mutations., Competing Interests: Declarations Conflict of interest None. Ethical approval The human studies were approved by The Ethics Review Committee of First Affiliated Hospital of Zhengzhou University. Informed consent Written informed consent for participation in this study was provided by the participants’ legal guardians., (© 2024. The Author(s).)

Aims: The precision medicine approach of tailoring treatment to the individual characteristics of each patient has been a great success in monogenic diabetes subtypes, highlighting the importance of accurate clinical and genetic diagnoses of the type of diabetes. We sought to describe three unique cases of childhood-onset diabetes in whom skeletal manifestations led to the revelation of a rare type of diabetes. Methods : Case-scenarios and review of the literature. Results: Case 1: A homozygous mutation in TRMT10A, a tRNA methyltransferase, was identified in a 15-year-old boy with new-onset diabetes, developmental delay, microcephaly, dysmorphism, short stature and central obesity. The progressive apoptosis of pancreatic beta cells required insulin replacement therapy, with increased demand due to an unfavorable body composition. Case 2: Congenital generalized lipodystrophy type 1 was suspected in an adolescent male with an acromegaloid facial appearance, muscular habitus, and diabetes who presented with a pathological fracture in a cystic bone lesion. A homozygous mutation in AGPAT2, an acyl transferase which mediates the formation of phospholipid precursors, was identified. Leptin replacement therapy initiation resulted in a remarkable improvement in clinical parameters. Case 3: A 12-year-old boy with progressive lower limb weakness and pain was diagnosed with diabetic ketoacidosis. Diffuse diaphyseal osteosclerosis compatible with the diagnosis of Camurati-Engelmann disease and a heterozygous mutation in TGFβ1 were identified. Preservation of euglycemia by insulin replacement relieved pain, suggesting that the diabetic milieu may have augmented TGFβ1 overexpression. Conclusion: Unraveling the precise genetic cause for the clinical manifestations led to the prediction of phenotypic manifestations, and enhanced the clinical outcomes. [ABSTRACT FROM AUTHOR]

Aims: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern. The diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of next-generation sequencing in the Tunisian population. Methods: We performed a targeted sequencing of 27 genes known to cause monogenic diabetes in 11 phenotypically suspected Tunisian patients. We retained genetic variants passing filters of frequency in public databases as well as their probable effects on protein structures and functions evaluated by bioinformatics prediction tools. Results: Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice-site variants were identified in ABCC8 gene. Conclusions: Our study is the first to investigate the clinical application of targeted next-generation sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population. [ABSTRACT FROM AUTHOR]

Maturity Onset Diabetes of the Young (MODY) is a monogenic autosomal dominant disorder affecting 1-5 % of all patients with diabetes mellitus. In Caucasians, GCK and HNF1A mutations are the most common cause of MODY. Here, we report two family members carrying a genetic variant of both GCK and HNF1A gene and their nine year clinical follow-up. Our report urges physicians to be cautious when variants in two genes are found in a single patient and suggests that collaboration with MODY genetics experts is necessary for correct diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Aims: Previous structural, vascular density, and perfusion studies have mostly comprised type 1 and type 2 diabetes, even in the absence of retinopathy. The current study aimed to compare macular vessel density (VD) measurements between maturity-onset diabetes of the young (MODY) patients and controls., Methods: The macular VD of superficial, deep retina, and choriocapillaris (CC), and central macular thickness (CMT), foveal avascular zone (FAZ), FAZ perimetry, VD of the total retina at 300 µm around the FAZ (FD), and acirculatory index (AI) measurements were taken and analyzed via OCT-A (RTVue XR 100-2 Avanti, AngioVue) and were compared between molecularly confirmed MODY (glucokinase (GCK) variants) patients and healthy controls., Results: Twenty-five MODY patients and 30 healthy controls were included in the study. The mean plasma hemoglobin A1c level in the MODY group was 6.39 ± 0.38. The mean age was 13.8 ± 2.1 in the MODY group and was 12.6 ± 2.5 years among controls. There was no significant difference in terms of the age, superficial and deep retinal VD, FAZ, FAZ perimetry, CMT, FD, or AI between the groups. Compared to the healthy controls, a slight but significant increase in the CC-VD was detected in the MODY group, but only in the parafoveal and perifoveal regions (p = 0.034, p = 0.009)., Conclusion: The significant CC-VD increase in the MODY group might be associated with hyperglycemia and/or relatively poor and vulnerable peripheral vascular CC perfusion compared to the central. Previous thickness and VD results of childhood or adolescent diabetes were distributed in a wider range, suggesting that various factors, including some not yet clearly defined, may affect the choroidal vasculature independently of glycemia or as a contributing factor., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: Diabetes in pregnancy may be associated with monogenic defects of beta-cell function, frequency of which depends on ethnicity, clinical criteria for selection of patients as well as methods used for genetic analysis. The aim was to evaluate the contribution and molecular spectrum of mutations among genes associated with monogenic diabetes in non-obese Russian patients with diabetes in pregnancy using the next-generation sequencing (NGS).Methods: 188 non-obese pregnant women with diabetes during pregnancy were included in the study; among them 57 subjects (30.3%) met the American Diabetes Association (ADA) criteria of preexisting pregestational diabetes (pre-GDM), whereas 131 women (69.7%) fulfilled criteria of gestational diabetes mellitus (GDM). A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. The sequence variants were rated according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Results: In total, 23 pathogenic, 18 likely pathogenic and 16 variants of uncertain significance were identified in 59/188 patients (31.4%). The majority of variants (38/59) were found in GCK gene. No significant differences in the number of variants among the two study groups (pre-GDM and GDM) were observed.Conclusions: The study suggests that frequency of monogenic variants of diabetes might be underestimated, which warrants a broader use of genetic testing, especially in pregnancy. [ABSTRACT FROM AUTHOR]

Highlights from the article: The topic of diabetes in pregnancy encompasses the pregnancy of women with any form of diabetes (mainly type 1 or type 2 diabetes) diagnosed prior to conception (pregestational diabetes), as well as forms of diabetes and hyperglycemia diagnosed during pregnancy. Among the latter, the most frequent form is gestational diabetes, usually diagnosed during the second trimester of gestation, and less common are early pregnancy hyperglycemia due to undiagnosed pregestational type 2 or monogenic diabetes and early onset gestational diabetes. Management of diabetes in pregnancy: standards of medical care in Diabetes 2019. Heterogeneity of gestational diabetes (GDM) and long-term risk of diabetes and metabolic syndrome: findings from the RADIEL study follow-up.

Background: This study identifies a new set of salient risk factors that may trigger danger signals of vascular dysregulation in T1D. Vascular abnormalities and impairment of CVD is a major adverse effect of T1D, particularly affecting children, adolescents and young adults., Methods: The patients of T1D were compared with the healthy control (HC) for the risk factors of vascular dysregulation in published studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, relevant to clinical subjects. A random effects model was followed and analysed by RevMan 5.4 and GraphPad Prism software., Results: 80 relevant case-control studies having 7492 T1D patients and 5293 HC were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of < 40 years were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD., Conclusion: Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-c, AI%, sICAM-1, and FMD% which could be evaluated with a simple blood test or non-invasive techniques. These may serve dual purposes as biomarkers of rapid diagnosis that could offer prospective tailor-made therapeutics for T1D. (Protocol registered at https://www.crd.york.ac.uk/prospero/CRD42022384636 )., Competing Interests: Declarations Competing interests No competing interests exist. Ethics approval Not applicable. Consent for publication All authors of this review have consented for publication. Research involving human and animal participants As this article is a meta-analysis and data have been obtained from published studies and no live or dead animal/mouse experiments have been carried out, the requirement for obtaining ethics does not arise for this manuscript., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: The most common pathogenic mitochondrial mutation associated with mitochondrial disease is m.3243A>G. Increased obstetric complications, such as spontaneous abortion, gestational diabetes (GDM), preterm delivery, and preeclampsia, have been reported in women carrying this mutation. We aimed to determine the fetal and maternal outcomes in pregnant women with mitochondrial disease. Methods: We retrospectively studied the obstetric and perinatal outcomes in 88 pregnancies of 26 women with genetically confirmed mitochondrial disease (m.3243A>G in the MTTL1 gene (n = 25); m.12258C>A in the MT-TS2 gene (n = 1)). Outcomes included pregnancy related complications, mode of delivery, gestational age at delivery and birthweight. Results: Mean heteroplasmy rate was 18%. The miscarriage rate was higher than background at 25%. 21 pregnancies (24%) were complicated by GDM; 9 pregnancies (13.6%) had a preterm delivery and 2 of them (3%) an extreme premature delivery < 32 weeks. One woman had preeclampsia and one had a postpartum hemorrhage. The caesarean section (CS) rate was 20%. For every unit increase in maternal heteroplasmy levels there was a 26% increased risk of undergoing an assisted operative vaginal delivery (OR 1.26, 95% CI 1.04–1.53, P = 0.002, Bonferroni corrected P = 0.005) and an 18% increased risk of undergoing a CS (OR 1.18, 95% CI 1.01–1.39, P = 0.01, Bonferroni corrected P = 0.03) compared to a spontaneous vaginal delivery. There was a statistical significant correlation between maternal and offspring heteroplasmy levels. Spearman correlation rho = 0.96, 95% CI 0.78–0.99, P = 0.0002. Conclusion: Women with mitochondrial disease appear to have more frequent obstetric complications including miscarriage and GDM. Pre-pregnancy diagnosis of m.3243A>G will enable the counseling of women and increase awareness of possible obstetric complications. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life. [ABSTRACT FROM AUTHOR]

Aims: An increase in type 1 diabetes (T1D) incidence has been observed in several countries during the COVID-19 pandemic. The objective of this study is to determine T1D incidence trends in Chilean children between 2006 and 2021, and specifically evaluate the effect of the COVID-19 pandemic in this population. Methods: We reviewed mandatory notifications of T1D in Chile's public and private health system in youth < 20 years between 2006 and 2021, and compared COVID-19 pre-pandemic and pandemic incidence. Results: In Chile, 9472 new T1D cases in children were confirmed between 2006 and 2021. The mean annual T1D incidence in the entire period was 12.7/100,000 inhabitants, with an incidence of 11.7/100,000 between 2006 and 2019 vs. 20.2/100,000 during 2020–2021 (β = 0.691, [95%CI 0.479–0903], p < 0.001.) The highest incidence was observed in the 10–14 years age group, but a significant increasing incidence was observed in all age groups. The second year of the COVID-19 pandemic, 2021, had the highest incidence rate of the study period. While a 5% mean annual increase was observed between 2006 and 2019, in 2021 the T1D incidence jumped 28.5% compared with the two previous years. We found a higher T1D incidence in population with private insurance than public insurance (14.8 vs. 11.7/100.000, respectively, RR = 1.26 [95%CI 1.03–1.53], p < 0.027). Conclusions: T1D incidence rates in Chilean youth doubled between 2006 and 2018, subsequently presenting a striking increase during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Aims: Molecular defects of hepatic nuclear factor 1β (HNF1β) are associated with multiorgan disease (renal disease, pancreatic hypoplasia, and genital tract anomalies) in addition to diabetes. We examined the phenotypic features, insulin secretory response to glucose, and response to treatment in subjects with HNF1β-MODY (MODY 5)., Methods: Twelve subjects with HNF1β-MODY were phenotyped in detail. A 2-h oral glucose tolerance test was performed to establish insulin secretory response with glucose, insulin and C-peptide measurements taken at baseline and 30 min intervals. Clinical follow-up occurred bi-annually., Results: Ten of 12 subjects had diabetes with mean age of onset of 30.2 ± 15.5 years, fasting glucose of 9.7 ± 4.6 mmol/L and HbA1c of 60.9 ± 17.1 mmol/mol (7.7 ± 1.6%). Renal and/or pancreatic morphological abnormalities were found in 9 subjects. Mean fasting C-peptide (0.5 ± 0.4 nmol/L) and AUC C-peptide (1.5 ± 1.0 nmol/L/120 min) were reduced in our cohort with 4 subjects demonstrating marked insulin deficiency. OGIS was reduced at 290.2 ± 67.0 ml min -1  m -2 . 6/10 subjects were on insulin therapy at initial diagnosis and 8/10 at last clinical follow-up. Mean insulin dose at last clinical follow-up was 0.45 ± 0.23units/kg/day. 5 subjects on insulin were trialled on sulphonylurea therapy, and none was successfully weaned off insulin., Conclusions: Diagnosing HNF1β-MODY in a diabetes clinic is challenging due to its variable phenotype and variable age of onset. β-Cell dysfunction and insulin resistance contribute to diabetes in HNF1β-MODY. No subjects successfully transitioned to sulphonylurea. Early initiation of insulin therapy would be suitable to achieve glycaemic control. This emphasizes the importance of genetic testing for monogenic forms of diabetes to guide personalized treatment., (© 2021. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: Neonatal diabetes mellitus (NDM) is a rare disease where diabetes presents during the first six months of life. There are two types of this disorder: permanent neonatal diabetes (PNDM) and transient neonatal diabetes mellitus (TNDM). PNDM occurs due to mutations in genes involved in either beta-cell survival, insulin regulation, and secretion. This study aims to define the genetic aetiology and clinical phenotypes of PNDM in a large Egyptian cohort from a single centre., Methods: Patients with PNDM who were diagnosed, treated, or referred for follow-up between January 2002 and January 2021 were identified and clinically phenotyped. All patients were tested for mutations in EIF2AK3, KCNJ11, ABCC8, INS, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, PDX1, PTF1A, NEUROD1, NEUROG3, NKX2-2, RFX6, SLC2A2, SLC19A2, STAT3, WFS1, ZFP57 using targeted next-generation sequencing (NGS) panel. INSR gene mutation was tested in one patient who showed clinical features of insulin resistance., Results: Twenty-nine patients from twenty-six families were diagnosed with PNDM. Pathogenic variants were identified in 17/29 patients (59%). EIF2AK3, INS, and K ATP channel mutations were the commonest causes with frequency of 17%, 17%, and 14%, respectively. Patients with ABBC8 and KCNJ11 mutations were successfully shifted to sulfonylureas (SU). Paired data of glycosylated haemoglobin before and after SU transfer showed improved glycaemic control; 9.6% versus 7.1%, P = 0.041., Conclusions: PNDM is a heterogenous disease with variable genotypes and clinical phenotypes among Egyptian patients. EIF2AK3, INS, ABCC8, and KCNJ11 mutations were the commonest causes of PNDM in the study cohort. All patients with K ATP channel mutations were effectively treated with glyburide, reflecting the fact that genetic testing for patients with NDM is not only important for diagnosis but also for treatment plan and prognosis., (© 2021. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Aims: Circulating peripheral helper T (Tph) cells are shown to promote the progression of autoimmune diseases. However, the role of Tph cells in inflammatory diseases such as type 2 diabetes mellitus (T2DM) and the differences between T2DM and autoimmune diabetes remain unclear. Methods: We recruited 92 T2DM patients, 106 type 1 diabetes mellitus (T1DM) patients and 84 healthy control individuals. Peripheral blood mononucleated cells were isolated and examined by multicolor flow cytometry. We further evaluated the correlations between circulating Tph cells and clinical biochemical parameters, islet function, disease progression and islet autoantibodies. Results: Circulating Tph cells were significantly higher in both T2DM and T1DM patients than in healthy control individuals. A significant positive correlation was observed between Tph cells and B cells in T1DM patients and overweight T2DM patients. Furthermore, Tph cells were negatively correlated with the area under the C-peptide curve (C-PAUC), and Tph cells were significantly positively correlated with fasting glucose and glycated hemoglobin levels in T2DM patients. However, no correlation was found between Tph cells and the above clinical indicators in T1DM patients. The frequency of Tph cells positively correlated with the titer of GAD autoantibodies and duration of disease in T1DM patients. In addition, we demonstrated that the frequency of Tph cells was decreased after rituximab therapy in T1DM patients. Conclusions: Circulating Tph cells are associated with blood glucose levels and islet function in T2DM patients. In T1DM patients, circulating Tph cells are associated with B cells and islet autoantibodies. This may suggest that Tph cells have different pathogenic mechanisms in the two types of diabetes. Clinical trial information: http://ClinicalTrials.gov NCT01280682 (registered July, 2010). [ABSTRACT FROM AUTHOR]

Aims: To explore the predictive value of ferroptosis-related (FR) biomarkers for diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective observational study enrolled patients with T2DM at the Second Hospital of Jilin University between December 2021 and March 2022. DKD was measured by the urinary albumin-to-creatinine ratio. Receiver operating characteristic curve (ROC) analysis was performed to assess the predictive value of ferroptosis-related biomarkers for DKD.The risk factors for massive proteinuria were performed by multivariable logistic regression analysis. Results: Finally, 118 patients (53.0 ± 12.2 years, 76 males) were enrolled, 52 of them without DKD (had normal proteinuria), while 66 with DKD. (Forty-one had microproteinuria, and 25 had massive proteinuria.) FR biomarkers, including acyl-CoA synthase long chain family member 4 (ACSL4), malondialdehyde (MDA), and reactive oxygen species (ROS), were significantly higher in the massive proteinuria group than in the other groups, while glutathione peroxidase 4 (GPX4) was significantly lower (all P < 0.05). The area under the ROC of the combination of GPX4, ACSL4, MDA, and ROS for predicting DKD was 0.804 (P < 0.001). Additionally, multivariate logistic regression analysis showed that the course of disease and ferritin levels were independent risk factors for massive proteinuria, while high serum iron, transferrin, and GPX4 levels were independent protective factors for massive proteinuria in patients with T2DM (all P < 0.05). Conclusions: The GPX4, ACSL4, MDA, and ROS combination might have a good predictive value for DKD. Additionally, the course of disease, ferritin levels, serum iron, transferrin, and GPX4 were independently associated with massive proteinuria. [ABSTRACT FROM AUTHOR]

Keywords: Insulin resistance; Diabetes mellitus; Rabson-Mendenhall syndrome; Genetics EN Insulin resistance Diabetes mellitus Rabson-Mendenhall syndrome Genetics 449 453 5 02/17/23 20230301 NES 230301 Joanna Chrzanowska and Jagoda Skarul equally contributed to this work. The deficiency or the absence of adipose tissue observed in some patients with RMS is the result of impaired both insulin-induced triglyceride synthesis and adipocyte differentiation [[4]]. There are three main types of insulin receptoropathy related to the characteristic clinical features and type of causative variant found in the insulin receptor gene ( I INSR i ): type A insulin resistance (TAIR), Rabson-Mendenhall syndrome (RMS) and Donohue syndrome (DS). Since insulin signalling is impaired in RMS, it appears that insulin in high concentrations may inhibit GH secretion through cross-talk signalling via the IGF-I receptor. [Extracted from the article]

Background: MODY diabetes includes rare familiar forms due to genetic mutations resulting in β-cell dysfunction. MODY 3 is due to mutations in the gene transcription factor HNF-1α, with diabetes diagnosis in adolescence or early adult life. Few data are available about MODY 3 in pregnancy. Case report: A 36-year-old Italian woman came to our unit at the 5th week of pregnancy. She was diagnosed with diabetes at 18 years, with negative autoimmunity and a strong familiarity for diabetes. She was treated with gliclazide and metformin. She had a previous pregnancy in which she was treated with insulin, giving birth at 38 weeks to a 3.210 kg baby girl, who showed neonatal hypoglycemia. We switched her to insulin treatment according to guidelines. We asked for genetic molecular testing, resulting in a HNF-1α gene mutation. A US examination at 7 weeks revealed a twin, bicorial, biamniotic pregnancy. At 37 weeks of gestation, she gave birth to two normal-weight baby girls; only one showed neonatal hypoglycemia and a genetic test revealed that she was affected by HNF-1α gene mutation. Subsequently, entire family of the woman was tested, showing that the father, the sister and the first daughter had the same HNF-1α mutation. Discussion: A MODY 3 foetus needs a near-normal maternal glycemic control, because the exposure to intrauterine hyperglycemia can lead to an earlier age of diabetes onset. Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1α mutations could lead to a functionally impaired protein that might dysregulate HNF-4α expression determining hypoglycemia. [ABSTRACT FROM AUTHOR]