Efficacy of a phone reminder to improve adherence to post-partum glucose tolerance testing after gestational diabetes and clinical predictors of post-partum follow-up compliance.

AIM: To assess the effectiveness of a phone reminder to improve adherence to post-partum glucose tolerance testing in women with gestational diabetes mellitus (GDM) and to identify clinical predictors of adherence to post-partum follow-up. METHODS: Retrospective study including 543 women with GDM. We assessed the adherence rate to post-partum glucose tolerance testing in women who received a phone reminder (n = 297) compared to women not alerted (n = 246). Demographic and clinical variables were collected to identify the predictors of adherence to the post-partum oral glucose tolerance test (OGTT). RESULTS: The adherence to post-partum OGTT was higher in women who received the phone reminder compared to those not alerted (60.6 % vs. 35.4 %, p < 0.001). Women less compliant compared to those more compliant, had a higher pre-pregnancy body mass index (BMI) (29.3 ± 7.9 vs. 27.0 ± 6.1 Kg/m2, p = 0.03). The adherence was lower in pre-pregnant obese compared to non-obese women (42.7 % vs. 52.0 %, p < 0.05), in women with only one, compared to multiple OGTT alterations during pregnancy (44.5 % vs. 57.8 %, p < 0.05), and in women non-insulin treated compared to those insulin-treated (40.0 % vs. 57.1 % vs, p < 0.001). CONCLUSIONS: The phone reminder improved post-partum follow-up adherence. Pre-pregnancy BMI, number of OGTT alterations and type of therapy could identify poorly adherent women.

Endocrine-metabolic assessment checklist for cancer patients treated with immunotherapy: A proposal by the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE) and Italian Society of Pharmacology (SIF) multidisciplinary group.

Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy.

Associations between continuous glucose monitoring (CGM) metrics and psycholinguistic measures: a correlational study.

AIM: Recently, the relationship between diabetes and mental health has been widely studied. With the advent of continuous glucose monitoring (CGM), some researchers have been interested in exploring the association between glucose-related metrics and psychological aspects. These studies have primarily relied on self-report questionnaires which present some limitations. Therefore, the present multicenter study aims at testing potential associations between CGM metrics and affective processes derived from narratives about using a CGM sensor. METHODS: An exploratory correlational design was used. Fifty-eight adults with type 1 diabetes using CGM were enrolled and invited to complete an online survey, where they replied to an open-ended question regarding their personal experience with the CGM sensor. Texts derived from the answers were analyzed through Linguistic Inquiry and Word Count, a widely used text analysis tool that can automatically identify and quantify linguistic patterns related to various psychological dimensions. Psycholinguistic measures were correlated with CGM metrics. RESULTS: Higher levels of sadness/depression correlated with lower %TIR (r = - 339; p < .01) and higher %TAR (r = .342; p < .01). CONCLUSIONS: The study highlights the relationship between CGM metrics and psychological variables derived from patients' narratives. In particular, it is possible to hypothesize a positive role of %TIR in reducing depressive feelings in individuals with diabetes, as well as a negative role of depressive feelings in achieving desirable CGM outcomes. Additionally, there is a potential role of glycemic variability, particularly hyperglycemia, in the expression of depressive and sad feelings, which has been less studied compared to the effects of hypoglycemia.

Polybrominated Diphenyl Ethers (PBDEs) and Human Health: Effects on Metabolism, Diabetes and Cancer.

There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways.

Commentary from the Italian Association of Medical Diabetologists (AMD) and Italian Society of Diabetology (SID) Interassociative Diabetes and Pregnancy Study Group on the screening and diagnostic methods for gestational diabetes: An open debate.

The current board of the interassociative Italian association of medical diabetologists (AMD)/Italian society of diabetology (SID) Diabetes and Pregnancy Italian Study Group commented about two recent papers published in the New England Journal of Medicine that investigated the screening and diagnostic methods for gestational diabetes mellitus (GDM). It is well recognized that effective screening and accurate, early diagnosis of GDM contributes to better management of these women in order to reduce adverse maternal and fetal/neonatal outcomes. However, there is worldwide controversy concerning which screening (selective or universal; one step or two steps) and which diagnostic criteria (glucose thresholds) are appropriate. The main findings of these papers are discussed along with their implications for the management of pregnant women.

Position paper of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), and the Italian Study Group of Diabetes in pregnancy: Metformin use in pregnancy.

OBJECTIVE: This document purpose is to create an evidence-based position statement on the role of metformin therapy in pregnancy complicated by obesity, gestational diabetes (GDM), type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS) and in women undergoing assisted reproductive technology (ART). METHODS: A comprehensive review of international diabetes guidelines and a search of medical literature was performed to identify studies presenting data on the use of metformin in pregnancy. The document was approved by the councils of the two scientific societies. RESULTS: In condition affecting the fertility, as PCOS, metformin use in pre-conception or early in pregnancy may be beneficial for clinical pregnancy, even in ART treatment, and in obese-PCOS women may reduce preterm delivery. In obese women, even in the presence of GDM or T2DM, metformin use in pregnancy is associated with a lower gestational weight gain. In pregnancy complicated by diabetes (GDM or T2DM), metformin improves maternal glycemic control and may reduce insulin dose. Neonatal and infant outcomes related to metformin exposure in utero are lacking. Metformin use in women with GDM or T2DM is associated with lower birth weight. However, an increased tendency to overweight-obesity has been observed in children, later in life. CONCLUSIONS: Metformin may represent a therapeutic option in selected women with obesity, PCOS, GDM, T2DM, and in women undergoing ART. However, more research is required specifically on the long-term effects of in utero exposition to metformin.

Do Nutrients and Nutraceuticals Play a Role in Diabetic Retinopathy? A Systematic Review.

Diabetic retinopathy (DR) is a multifactorial neuro-microvascular disease, whose prevalence ranges from 25% to 60% of subjects affected by diabetes mellitus, representing the main cause of legal blindness in adults of industrialized countries. The treatment of advanced stage of DR is based on invasive and expensive therapies, while few strategies are available for the early stage or prevention. The mechanisms underlying DR involve a complex interplay between the detrimental effects of hyperglycemia, dyslipidemia, hypoxia, and oxidative stress, providing several pathways potentially targeted by nutrients and nutraceuticals. In this study, we conducted a systematic review of observational and interventional studies, evaluating the effect of nutrients and/or nutraceuticals on the risk of DR and their potential use for the treatment of patients with DR. The analysis of the 41 included studies (27 observational and 14 interventional studies) suggests a promising preventive role of some nutrients, in particular for vitamins B (i.e., B1 and B12), D, and E. However, further investigations are necessary to clarify the potential clinical application of nutraceuticals in the prevention and treatment of DR.

Knowledge, attitude, and practice of the 2009 Institute of Medicine (IOM) recommendations on the nutritional management of diabetes in pregnancy: an online national survey.

AIMS: As recommended by the Institute of Medicine (IOM), health practitioners should encourage a healthy nutrition and adequate weight gain during pregnancy in order to ensure favorable pregnancy and fetal outcomes, and to prevent diseases later in life for both mother and child. The purpose of this online survey was to determine the knowledge, attitude, and practice of the 2009 IOM recommendations among healthcare professionals managing nutritional therapy in pregnancies complicated by diabetes in Italy. METHODS: A cross-sectional survey was conducted by using an online self-administered questionnaire undertaken between October and December 2021. RESULTS: Of the 220 participants 89% were diabetologists/endocrinologists/internal medicine specialists and 11% dietitians/nutritionists. The survey found that the 53% of respondents provide a personalized diet to pregnant women with diabetes, while 32% a standard diet plan and only 15% healthy dietary advice. The 69% of the participants investigated for appropriate gestational weight gain, mainly based on pre-pregnancy BMI (96%), gestational weight gain (GWG) at first prenatal visit (80%) and presence of twin pregnancy (58%). Maternal weight gain was evaluated at each regularly scheduled prenatal visit and compared with IOM recommendations for the 87% of healthcare professionals. Diet plan was periodically re-evaluated and/or modified (90% of participants), based on inadequate maternal weight gain and/or fetal growth abnormalities (78%), trimester transition (53%), changes in physical activity and/or a "feel hungry" (50%). CONCLUSIONS: This survey reported the knowledge and attitude of IOM guidelines and the nutritional knowledge and practice of Italian professionals on the nutritional management of diabetes in pregnancy. The application of these recommendations seemed more feasible in clinics/team dedicated to "Diabetes in Pregnancy".

Gestational Diabetes Mellitus pregnancy by pregnancy: early, late and nonrecurrent GDM.

AIMS: To assess the GDM recurrence rate in a cohort of pregnant women with prior GDM, to compare two consecutive pregnancies complicated by GDM, to compare women with nonrecurrent and recurrent GDM and to stratify the latter in women with early and late recurrent GDM. METHODS: Retrospective study including 113 women with GDM in an index pregnancy (G1), at least a postindex pregnancy (G2) and normal glucose tolerance in between. The GDM recurrence rate was assessed, and maternal and neonatal outcomes and pancreatic beta cell function of the index pregnancy were compared with those of the postindex pregnancy (G1 vs. G2). Women with nonrecurrent GDM were compared with those with recurrent GDM. RESULTS: The GDM recurrence rate was 83.2% and the minimum prevalence of early recurrent GDM was 43,4%. The pregravid BMI of women with recurrent GDM increased between the two pregnancies (27.3 ± 5.98 vs. 28.1 ± 6.19 kg/m2, p < 0.05). Women with recurrent GDM had a higher prepregnancy BMI than those with nonrecurrent GDM either at the index (27.3 ± 5.98 vs. 23.1 ± 4.78 kg/m2, p < 0.05) or the postindex pregnancy (27 ± 6vs.24 ± 4,4 kg/m2, p < 0.05). CONCLUSIONS: GDM shows a high recurrence rate in our cohort of slightly overweight women, with an early GDM minimum prevalence of 43.4%.

Body mass index is related to short term retinal worsening in type 2 diabetes patients treated with anticancer drugs.

BACKGROUND: In cancer patients with diabetes, anticancer drugs (ADs) may negatively affect the course of diabetes vascular complications. The short-term effects of ADs on type 2 diabetes (T2D) retinopathy are poorly known. This study evaluated the short-term effects of different classes of ADs on diabetic retinopathy (DR) and clinical risk factors for retinal worsening (RW) in cancer patients affected by T2D. METHODS: Retrospective single-centre study evaluating 168 patients with T2D and cancer. The diagnosis of T2D preceded those of cancer in all patients. We evaluated the retinal short-term effects within the six months after the first-line ADs treatment. RESULTS: After ADs, 6% of patients had a short-term RW. BMI is positively associated with the risk of RW (OR 1.45, 95% confidence interval (CI) 1.1-1.9, p<0.005). Patients treated with alkylating agents and topoisomerase inhibitors have an increased risk of RW (p=0.049 and p=0.057, respectively) and a significantly higher HDL level (p<0.01). CONCLUSIONS: To our knowledge, this study is the first investigating the short-term impact of ADs on DR of T2D patients. Moreover, we provide information arose from a real-world setting. As confirmed by other studies, these findings could help to identify patients at risk for shortterm RW, who should be promptly referred to the ophthalmologist for the prevention of visual impairment.

Influence of Body Mass Index, Cancer Type and Treatment on Long-Term Metabolic and Liver Outcomes in Childhood Cancer Survivors.

In the last decade, the survival of subjects affected by cancer in childhood has significantly improved. The increased lifespan of childhood cancer survivors (CCS) led to a greater risk for long-term, therapy-related morbidity. To identify the clinical predictors of metabolic adverse outcomes in CCS (average off-therapy period: 12 years), we recruited 126 survivors of different childhood cancers (86.5% hematological cancers) who received at least anticancer chemotherapy, consecutively approached during their annual oncohematological outpatient visit. At examination, anthropometric measures and cancer-related history were collected. Moreover, a fasting venous sample was carried out for measuring fasting plasma glucose and insulin, glycated hemoglobin, lipid panel, and transaminases. We calculated the indexes of insulin resistance (HOMA-IR, McAuley, and QUICKI) and secretion (HOMA-ß), liver steatosis (Hepatic Steatosis Index) and fibrosis (FIB-4 and NAFLD fibrosis score), and visceral fat dysfunction (Visceral Adiposity Index). More than one-third of the subjects (37.3%) did not have normal weight, with 11.1% of them affected by obesity. At recruitment, obese subjects were at significantly higher risk for impaired fasting glucose, metabolic syndrome, visceral adipose dysfunction, and liver steatosis/fibrosis. Subjects who received bone marrow transplantation were prone to insulin resistance, while survivors of lymphoma presented a visceral adipose dysfunction These results suggest a carefully metabolic monitoring of CCS, particularly in subgroups at higher risk, to early detect these conditions, promptly begin therapeutic interventions, and mitigate the dysmetabolic-related health burden.

Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review.

Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.

Insulin Receptor Isoforms Differently Regulate Cell Proliferation and Apoptosis in the Ligand-Occupied and Unoccupied State.

The insulin receptor (IR) presents two isoforms (IR-A and IR-B) that differ for the α-subunit C-terminal. Both isoforms are expressed in all human cells albeit in different proportions, yet their functional properties-when bound or unbound to insulin-are not well characterized. From a cell model deprived of the Insulin-like Growth Factor 1 Receptor (IGF1-R) we therefore generated cells exhibiting no IR (R-shIR cells), or only human IR-A (R-shIR-A), or exclusively human IR-B (R-shIR-B) and we studied the specific effect of the two isoforms on cell proliferation and cell apoptosis. In the absence of insulin both IR-A and IR-B similarly inhibited proliferation but IR-B was 2-3 fold more effective than IR-A in reducing resistance to etoposide-induced DNA damage. In the presence of insulin, IR-A and IR-B promoted proliferation with the former significantly more effective than the latter at increasing insulin concentrations. Moreover, only insulin-bound IR-A, but not IR-B, protected cells from etoposide-induced cytotoxicity. In conclusion, IR isoforms have different effects on cell proliferation and survival. When unoccupied, IR-A, which is predominantly expressed in undifferentiated and neoplastic cells, is less effective than IR-B in protecting cells from DNA damage. In the presence of insulin, particularly when present at high levels, IR-A provides a selective growth advantage.

COVID-19 vaccination in pregnant and lactating diabetic women.

AIM: To discuss available information on the opportunity for pregnant women affected by diabetes/obesity to receive COVID-19 vaccine. DATA SYNTHESIS: Pregnant women with SARS-CoV-2 (COVID-19) infection are at high risk for severe acute respiratory syndrome and adverse outcomes. Pregnant women with severe COVID-19 present increased rates of preterm delivery (<37 gestational weeks), cesarean delivery and neonatal admissions to the intensive care unit. Comorbidity such as diabetes (pregestational or gestational) or obesity further increased maternal and fetal complications. It is known that diabetic or obese patients with COVID-19 present an unfavorable course and a worse prognosis, with a direct association between worse outcome and suboptimal glycol-metabolic control or body mass index (BMI) levels. Critical COVID-19 infection prevention is important for both mother and fetus. Vaccination during pregnancy is a common practice. Vaccines against COVID-19 are distributed across the world with some population considered to have a priority. Since pregnant women are excluded from clinical trials very little information are available on safety and efficacy of COVD-19 vaccines during pregnancy. However, it is well known the concept of passive immunization of the newborn obtained with transplacental passage of protective antibodies into the fetal/neonatal circulation after maternal infection or vaccination. Moreover, it has been reported that COVID-19 vaccine-induced IgG pass to the neonates through breastmilk. Therefore, maternal vaccination can protect mother, fetus and baby. CONCLUSIONS: After an individual risk/benefit evaluation pregnant and lactating women should be counselled to receive COVID-19 vaccines.

Efficacy of flash glucose monitoring in pregnant women with poorly controlled pregestational diabetes (FlashMom): A randomized pilot study.

BACKGROUND AND AIMS: Good glycemic control is crucial to reduce the risk of adverse pregnancy outcomes. Our aim was to evaluate the efficacy of Flash Glucose Monitoring (FGM) on glucose control in women with pregestational diabetes. METHODS AND RESULTS: Forty women with inadequately controlled type 1 (T1D, n = 34) and type 2 (T2D, n = 6) diabetes at conception were randomly assigned to two arms: the Flash Glucose group (FG, n = 21) using FGM, and the control group (CG, n = 19) using self-monitoring of blood glucose (SMBG). Glycated hemoglobin (HbA1c, %), time in (TIR), below (TBR) and above (TAR) range, glucose variability as well as the occurrence of maternal and neonatal adverse outcomes, were evaluated. HbA1c decreased significantly (p < 0.01) and similarly (-0.65 ± 0.7 vs. -0.67 ± 0.8 for FG and CG, respectively; p = 0.89) in both groups during pregnancy. HbA1c reduction was positively associated with the number of daily FGM scans (p < 0.01). TBR (12.1 ± 2.0% vs. 19.6 ± 3.9%, p = 0.04) and the mean of the daily serum glucose difference (MODD) index (59.1 ± 5.4 vs. 77.7 ± 4.6, p = 0.02) were significantly lower in FG at second trimester. The rates of perinatal adverse outcomes were not different in the two studied groups. CONCLUSIONS: In women with pregestational diabetes, FGM and SMBG had similar efficacy on glucose control during pregnancy. FGM showed additional advantages in terms of TBR and glucose variability. Achievement of good metabolic results depended on the adequate use of glucose sensor. REGISTRATION: At ClinicalTrials.gov as NCT04666818 on December 14, 2020.

Screening of postpartum diabetes in women with gestational diabetes: high-risk subgroups and areas for improvements-the STRONG observational study.

AIMS: To assess the proportion of women with gestational diabetes (GDM) by performing postpartum Oral Glucose Tolerance Test (OGTT) and to identify GDM phenotypes at high-risk of postpartum dysglycemia (PPD). METHODS: Observational, retrospective, multicenter study involving consecutive GDM women. Recursive partitioning (RECPAM) analysis was used to identify distinct and homogeneous subgroups of women at different PPD risk. RESULTS: From a sample of 2,736 women, OGTT was performed in 941 (34.4%) women, of whom 217 (23.0%) developed PPD. Insulin-treated women having family history of diabetes represented the subgroup with the highest PPD risk (OR 5.57, 95% CI 3.60-8.63) compared to the reference class (women on diet with pre-pregnancy BMI < = 28.1 kg/m2). Insulin-treated women without family diabetes history and women on diet with pre-pregnancy BMI > 28.1 kg/m2 showed a two-fold PPD risk. Previous GDM and socioeconomic status represent additional predictors. Fasting more than post-prandial glycemia plays a predictive role, with values of 81-87 mg/dl (4.5-4.8 mmol/l) (lower than the current diagnostic GDM threshold) being associated with PPD risk. CONCLUSIONS: Increasing compliance to postpartum OGTT to prevent/delay PPD is a priority. Easily available characteristics identify subgroups of women more likely to benefit from preventive strategies. Fasting BG values during pregnancy lower than those usually considered deserve attention.

Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta.

Background: Maternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy. Methods: Placental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or <90 mg/dl, regardless of the diagnosis. Results: In T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p<0.0001) in the placenta of patients with peripartum glucose >90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046). Conclusions: To the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth.

Risk for Coexistent Autoimmune Diseases in Familial and Sporadic Type 1 Diabetes is Related to Age at Diabetes Onset.

OBJECTIVE: Type 1 diabetes (T1D) is frequently associated with other autoimmune diseases (AIDs). Although most of T1D patients are sporadic cases (S-T1D), 10% to 15% have a familial form (F-T1D) involving 2 or more first-degree relatives. This study evaluated the effect of T1D family aggregation and age onset on AIDs occurrence. METHODS: In this observational, cross-sectional, case-control, single center study, we enrolled 115 F-T1D and 115 S-T1D patients matched for gender, age, T1D age onset, and duration. With respect to T1D age onset (before or after 18 years), both groups were further subdivided into young- or adult-onset F-T1D and young- or adult-onset S-T1D. The presence of organ-specific antibodies and/or overt AIDs was evaluated. RESULTS: The F-T1D group had a higher percentage of AIDs (29.8% vs 18.4%, P = .04) and a significant earlier onset of AIDs at Cox regression analysis (P = .04) than the S-T1D group. Based on multivariate analysis, the adult-onset F-T1D subgroup had the highest prevalence of both additional organ-specific antibodies (60.5%) and overt AIDs (34.9%), whereas the adult S-T1D subgroup was the least frequently involved (29.1% and 12.7%, respectively). In F-T1D patients, offsprings develop T1D and AIDs earlier than their parents do. CONCLUSIONS: In T1D patients, familial aggregation and adult-onset of T1D increase the risk for coexistent AIDs. These clinical predictors could guide clinicians to address T1D patients for the screening of T1D-related AIDs.