Prevalence and factors associated with thyroid autoimmunity among children newly diagnosed with type 1 diabetes before and during the COVID-19 pandemic: Evidence from Kuwait.

AIMS: This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID-19 pandemic in Kuwait. MATERIALS AND METHODS: This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID-19 pandemic from the official declaration of the first identified positive COVID-19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID-19 pandemic, 1 January 2017 to 23 February 2020. RESULTS: One thousand twenty-four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID-19 pandemic, compared with 14.5% during the pre-pandemic period (p = 0.015). Children with positive COVID-19 status were more likely to present with thyroid antibodies (p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID-19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024). CONCLUSIONS: Incident cases of T1D during the COVID-19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID-19 in the onset and progression of T1D and on thyroid autoimmunity and disease.

Factors Affecting Mode of Birth in Women With Preexisting Diabetes and Gestational Diabetes: A Retrospective Cohort at a Tertiary Referral Center.

Women with preexisting diabetes and gestational diabetes mellitus (GDM) are at higher risk for adverse maternal and neonatal outcomes. However, there is no consensus on a uniform approach regarding mode of birth (MOB) for all forms of diabetes. The aim of the study is to compare MOB in women with preexisting diabetes and GDM and possible factors influencing it. A retrospective cohort study of women with GDM and preexisting diabetes between 2015 and 2021 at a tertiary referral center was conducted. One thousand three hundred eighty-five singleton pregnancies were included. One thousand twenty-two (74.4%) women had a vaginal birth (VB) and 351 (25.6%) a caesarean section. Preexisting diabetes was significantly associated with caesarean section compared to GDM (OR 2.43). Five hundred fifty-one (40.1%) women underwent induction of labor, and 122 (22.1%) women had a secondary caesarean after IOL. Women induced due to spontaneous rupture of membrane (SROM) achieved the highest rate of VB at 93%. The lowest rates of VB occurred if indication for induction was for preeclampsia or hypertension. IOL was significantly less successful in preexisting diabetes with a VB achieved in 56.4% for type 1 diabetes and 52.6% of type 2 diabetes compared to GDM (78.2% in GDM; 81.2% in IGDM; OR 3.25, 95% CI 1.70-6.19, p < 0.001). The rate of VB was higher who were induced preterm compared to women with term IOL (n = 240 (81.9%) vs. n = 199 (73.2%); p < 0.05). Parity, previous VB and SROM favored VB after IOL, whereas preexisting diabetes, hypertension, and IOL after 40 + 0 weeks are independent risk factors for caesarean delivery.

Are soluble E-selectin, ICAM-1, and VCAM-1 potential predictors for the development of diabetic retinopathy in young adults, 15-34 years of age? A Swedish prospective cohort study.

The aim of this study was to determine plasma levels of three adhesion molecules that may contribute to the development of diabetic retinopathy; soluble endothelial selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), in young adults, aged 15-34 years at diagnosis of diabetes, to find potential predictors for development of retinopathy, and to evaluate their relation to diabetes associated autoantibodies. Participants with type 1 (n = 169) and type 2 diabetes (n = 83) were selected from the complications trial of the Diabetes Incidence Study in Sweden and classified in two subgroups according to presence (n = 80) or absence (n = 172) of retinopathy as determined by retinal photography at follow-up 8-10 years after diagnosis of diabetes. Blood samples were collected at diagnosis in 1987-88. The levels of sE-selectin, sICAM-1, and sVCAM-1 were analysed by enzyme-linked immunosorbent assay and islet cell antibodies by a prolonged two-colour immunofluorescent assay. Mean HbA1c (p<0.001) and clinical characteristics: mean body mass index (p = 0.019), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.003), male gender (p = 0.026), and young age at diagnosis of diabetes (p = 0.015) remained associated with development of retinopathy in type 1 diabetes. However, in a multivariate analysis only HbA1c remained as a risk factor. sE-selectin was significantly higher in the group with type 2 diabetes and retinopathy, compared to the group with type 2 diabetes without retinopathy (p = 0.04). Regarding sE-selectin, sICAM-1, and sVCAM-1 in participants with type 1 diabetes, no differences were observed between the groups with or without retinopathy. This trial confirmed the role of HbA1c and clinical characteristics as predictors for development of retinopathy in type 1 diabetes. sE-selectin stands out as a potential predictor for development of retinopathy in type 2 diabetes, whereas a predictive role for sICAM-1 and sVCAM-1 could not be identified neither for type 1 nor type 2 diabetes.

A cross-sectional questionnaire study: Impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia.

OBJECTIVE: Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors. METHODS: Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records. RESULTS: 189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04). CONCLUSION: Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.

Suicidal Ideation, Suicide Attempts, and Suicide Deaths in Adolescents and Young Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence is lacking on the risk of suicide-related behaviors (suicidal ideation, suicide attempt, suicide death) in youth with type 1 diabetes (T1D). PURPOSE: We aimed to 1) determine the prevalence of suicidal ideation, suicide attempts, and suicide deaths in adolescents and young adults (AYA) with T1D aged 10-24 years; 2) compare suicide-related behavior prevalence in youth with and without T1D; and 3) identify factors associated with suicide-related behaviors. DATA SOURCES: A systematic search was conducted in MEDLINE, Embase, and PsycInfo up to 3 September 2023. STUDY SELECTION: We included observational studies where investigators reported the prevalence of suicide-related behaviors among AYA aged 10-24 years with T1D. DATA EXTRACTION: We collected data on study characteristics, data on prevalence of suicide-related behaviors, and data on associated factors. DATA SYNTHESIS: We included 31 studies. In AYA with versus without T1D, pooled prevalence of suicidal ideation was 15.4% (95% CI 10.0-21.7; n = 18 studies) vs. 11.5% (0.4-33.3; n = 4), respectively, and suicide attempts 3.5% (1.3-6.7; n = 8) vs. 2.0% (0.0-6.4; n = 5). Prevalence of suicide deaths ranged from 0.04% to 4.4% among youth with T1D. Difficulties with T1D self-management were frequently reported to be associated with higher rates of suicide-related behaviors. However, findings on the association of glycemic levels and suicide-related behaviors were inconsistent. LIMITATIONS: There was a considerable level of heterogeneity in meta-analysis of both suicidal ideation and suicide attempts. CONCLUSIONS: Suicidal ideation and suicide attempts are prevalent in AYA with T1D. Current evidence does not suggest that these rates are higher among AYA with T1D than rates among those without.

Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study.

OBJECTIVES: To estimate the burden, trends, and inequalities of type 1 diabetes mellitus (T1DM) among older adults at global, regional, and national level from 1990 to 2019. DESIGN: Population based study. POPULATION: Adults aged ≥65 years from 21 regions and 204 countries and territories (Global Burden of Disease and Risk Factors Study 2019)from 1990 to 2019. MAIN OUTCOME MEASURES: Primary outcomes were T1DM related age standardised prevalence, mortality, disability adjusted life years (DALYs), and average annual percentage change. RESULTS: The global age standardised prevalence of T1DM among adults aged ≥65 years increased from 400 (95% uncertainty interval (UI) 332 to 476) per 100 000 population in 1990 to 514 (417 to 624) per 100 000 population in 2019, with an average annual trend of 0.86% (95% confidence interval (CI) 0.79% to 0.93%); while mortality decreased from 4.74 (95% UI 3.44 to 5.9) per 100 000 population to 3.54 (2.91 to 4.59) per 100 000 population, with an average annual trend of -1.00% (95% CI -1.09% to -0.91%), and age standardised DALYs decreased from 113 (95% UI 89 to 137) per 100 000 population to 103 (85 to 127) per 100 000 population, with an average annual trend of -0.33% (95% CI -0.41% to -0.25%). The most significant decrease in DALYs was observed among those aged <79 years: 65-69 (-0.44% per year (95% CI -0.53% to -0.34%)), 70-74 (-0.34% per year (-0.41% to -0.27%)), and 75-79 years (-0.42% per year (-0.58% to -0.26%)). Mortality fell 13 times faster in countries with a high sociodemographic index versus countries with a low-middle sociodemographic index (-2.17% per year (95% CI -2.31% to -2.02%) v -0.16% per year (-0.45% to 0.12%)). While the highest prevalence remained in high income North America, Australasia, and western Europe, the highest DALY rates were found in southern sub-Saharan Africa, Oceania, and the Caribbean. A high fasting plasma glucose level remained the highest risk factor for DALYs among older adults during 1990-2019. CONCLUSIONS: The life expectancy of older people with T1DM has increased since the 1990s along with a considerable decrease in associated mortality and DALYs. T1DM related mortality and DALYs were lower in women aged ≥65 years, those living in regions with a high sociodemographic index, and those aged <79 years. Management of high fasting plasma glucose remains a major challenge for older people with T1DM, and targeted clinical guidelines are needed.

Pregnancy Outcomes in Women with Poorly Controlled Pregestational Diabetes Mellitus.

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Modifiable lifestyle risk factors for overweight and obesity in children and adolescents with type 1 diabetes: A systematic review.

This review aims to identify and report epidemiological associations between modifiable lifestyle risk factors for overweight or obesity in children and adolescents with type 1 diabetes (T1D). A systematic literature search of medical databases from 1990 to 2023 was undertaken. Inclusion criteria were observational studies reporting on associations between dietary factors, disordered eating, physical activity, sedentary and sleep behaviours and measures of adiposity in children and adolescents (<18 years) with T1D. Thirty-seven studies met inclusion criteria. Studies were mostly cross-sectional (89 %), and 13 studies included adolescents up to 19 years which were included in this analysis. In adolescents with T1D, higher adiposity was positively associated with disordered eating behaviours (DEB) and a higher than recommended total fat and lower carbohydrate intake. A small amount of evidence suggested a positive association with skipping meals, and negative associations with diet quality and sleep stage. There were no published associations between overweight and physical activity, sedentary behaviours and eating disorders. Overall, the findings infer relationships between DEB, fat and carbohydrate intake and adiposity outcomes in people with T1D. Prospective studies are needed to determine causal relationships and to investigate sleep stages. High quality studies objectively measuring physical activity and include body composition outcomes are needed.

Burnout Among Young Adults With Type 1 Diabetes.

PURPOSE: The purpose of this qualitative descriptive study was to describe the experience of diabetes burnout in young adults with type 1 diabetes (T1DM). In addition, aims included participant perspectives of risk and protective factors associated with burnout and ways to balance everyday life with diabetes self-management (DSM). METHODS: Young adults with T1DM (N = 11) were recruited through social media platforms and modified snowball sampling and interviewed. Informational redundancy was achieved. Qualitative thematic coding and analysis were conducted within and across transcripts. RESULTS: Diabetes burnout was described as the willingness to put diabetes and DSM on the "back burner" and let things slide due to exhaustion, frustration, apathy, and the desire to be like everyone else for a while. Risk and protective factors were identified along with strategies to achieve balance of DSM in everyday life. CONCLUSIONS: This study identified a clear definition of diabetes burnout and acknowledges this concept as distinct and separate from other psychosocial conditions. Health care providers can utilize this information to identify individuals at risk for diabetes burnout and offer more effective support to lessen the overall burden associated with T1DM.

Concomitant autoimmunity and risk of multiple sclerosis disability worsening.

BACKGROUND: Few studies have examined the effect of concomitant autoimmune diseases on multiple sclerosis (MS) disability worsening. We set out to examine whether concomitant Crohn's Disease (CD), Ulcerative Colitis (UC), or Type 1 Diabetes (T1D) affect MS disability worsening in a nationwide cohort of MS patients as defined by reaching expanded disability scale status (EDSS) scores 3.0, 4.0 and 6.0. METHODS: Patients with MS onset between January 2004 and January 2019 were identified from the Swedish MS registry and the Swedish National Patient Register. Kaplan-Meier analysis was used to estimate the median time to reach sustained disability milestones. Adjusted Cox proportional hazard regression models were used to calculate the risk of reaching disability milestones among persons with and without CD, UC, or T1D. RESULTS: Out of 8972 persons with MS, 88 (1.0 %) had T1D, 47 (0.8 %) had UC, and 78 (0.9 %) had CD. There was a significantly higher risk of disability progression, for persons with MS and T1D for reaching EDSS 6.0, hazard ratio (HR) = 2.21 (95 % confidence interval (CI) = 1.48 -3.31) and persons with MS and comorbid CD for reaching EDSS 3.0, HR = 2.30 (95 %CI = 1.74-3.04) and 4.0, HR = 1.59 (95 %CI = 1.09-2.32), and persons with MS and comorbid UC for reaching EDSS 3.0 HR = 1.57 (95 %CI = 1.15-2.14). As defined by Charlson's comorbidity index, the co-existence of other co-morbidities conferred a significant increase in the risk of reaching all endpoints, with HR ranging from 1.23 to 1.62. CONCLUSION: Comorbidity is associated with a significantly increased risk of reaching disability end-points, and T1D, CD, and UC increase the risk further. Thus, there appears to be a need for increased vigilance of comorbidites in persons with MS in order to optimise the long-term outcome of MS.

[Diabetes-related skin lesions : a frequently underdiagnosed problem]. / Lésions cutanées liées au diabète : une problématique souvent sous-diagnostiquée.

Skin disorders are common in diabetes, affecting both patients with type 1 and type 2 diabetes. These cutaneous manifestations can be classified into three categories: dermatoses associated with the presence of diabetes, cutaneous complications of diabetes (acute and chronic) and dermatoses linked to antidiabetic treatments. These conditions vary considerably in terms of severity (from insignificant cosmetic problems to life-threatening) and prevalence (from relatively frequent to rare). Despite the high prevalence of diabetes and associated skin disorders, the dermatological manifestations of diabetes are generally neglected and often under-diagnosed. Failure to diagnose and treat skin disorders at an early stage can lead to clinical worsening, whereas early detection and treatment can reduce the risk of serious complications.

Chez les personnes atteintes d'un diabète de type 1 ou 2, les atteintes cutanées sont fréquentes. Elles peuvent être classées en trois catégories : les dermatoses associées à la présence du diabète, ses complications cutanées (aiguës et chroniques) et les dermatoses liées aux traitements antidiabétiques. Ces atteintes varient considérablement en gravité (allant de préoccupations esthétiques banales à potentiellement mortelles) et en prévalence (relativement fréquentes à rares). Malgré la prévalence élevée du diabète et des atteintes cutanées associées, les manifestations dermatologiques sont généralement négligées et souvent sous-diagnostiquées. L'absence de diagnostic et de traitement à un stade précoce peut entraîner une aggravation clinique dermatologique. La détection et le traitement précoces de ces atteintes peuvent réduire le risque de complications graves.

Early increase in HbA1c trajectory predicts development of severe microangiopathy in patients with type 1 diabetes: the VISS study.

INTRODUCTION: To study the HbA1c trajectory from the time of diagnosis to examine if patients at the greatest risk for severe microangiopathy can be identified early allowing clinicians to intervene as soon as possible to avoid complications. RESEARCH DESIGN AND METHODS: In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age, 1983-1987, were followed from diagnosis until 2019. Mean HbA1c was calculated each year for each patient. Severe diabetic microangiopathy was defined as proliferative diabetic retinopathy (PDR) or macroalbuminuria (nephropathy). RESULTS: After 32 years, 27% had developed PDR and 8% macroalbuminuria. Patients with weighted HbA1c (wHbA1c); <57 mmol/mol; <7.4% did not develop PDR or macroalbuminuria. The HbA1c trajectories for patients developing PDR and macroalbuminuria follow separate courses early on and stay separated for 32 years during the follow-up. Patients without severe complications show an initial dip, after which HbA1c slowly increases. HbA1c in patients with severe complications directly rises to a high level within a few years. Mean HbA1c calculated for the period 5-8 years after diabetes onset strongly predicts the development of severe complications. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and higher prevalence of PDR. CONCLUSIONS: The HbA1c trajectory from diabetes onset shows that mean HbA1c for the period 5-8 years after diagnosis strongly predicts severe microangiopathy. Females with childhood-onset diabetes exhibit a high peak in HbA1c during adolescence associated with higher wHbA1c and a higher prevalence of PDR.

Trends in Survival After First Myocardial Infarction in People With Diabetes.

BACKGROUND: The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. METHODS AND RESULTS: Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events. CONCLUSIONS: During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Association between diabetes mellitus and primary biliary cholangitis: a two-sample Mendelian randomization study.

Background: Previous observational studies have demonstrated a link between diabetes mellitus(DM) and primary biliary cholangitis (PBC). Nevertheless, since these relationships might be confused, whether there is any causal connection or in which direction it exists is unclear. Our investigation aimed to identify the causal associations between DM and PBC. Methods: We acquired genome-wide association study (GWAS) datasets for PBC, Type 1 diabetes(T1DM), and Type 2 diabetes(T2DM) from published GWASs. Inverse variance-weighted (IVW), MR-Egger, weighted median (WM), Simple mode, and weighted mode methods were used to determine the causal relationships between DM(T1DM or T2DM) and PBC. Sensitivity analyses were also carried out to ensure the results were robust. To determine the causal relationship between PBC and DM(T1DM or T2DM), we also used reverse MR analysis. Results: T1DM was associated with a higher risk of PBC (OR 1.1525; 95% CI 1.0612-1.2517; p = 0.0007) in the IVW method, but no evidence of a causal effect T2DM on PBC was found (OR 0.9905; 95% CI 0.8446-1.1616; p = 0.9071) in IVW. Results of the reverse MR analysis suggested genetic susceptibility that PBC was associated with an increased risk of T1DM (IVW: OR 1.1991; 95% CI 1.12-1.2838; p = 1.81E-07), but no evidence of a causal effect PBC on T2DM was found (IVW: OR 1.0101; 95% CI 0.9892-1.0315; p = 0.3420). Conclusion: The current study indicated that T1DM increased the risk of developing PBC and vice versa. There was no proof of a causal connection between PBC probability and T2DM. Our results require confirmation through additional replication in larger populations.

Diabetes-Related Macrovascular Complications Are Associated With an Increased Risk of Diabetic Microvascular Complications: A Prospective Study of 1518 Patients With Type 1 Diabetes and 20 802 Patients With Type 2 Diabetes in the UK Biobank.

BACKGROUND: Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications. METHODS AND RESULTS: There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association. CONCLUSIONS: Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

A Causal Relationship Between Type 1 Diabetes and Risk of Osteoporosis: A Univariable and Multivariable Mendelian Randomization Study.

Objective: This Mendelian randomization (MR) analysis aims to investigate the causal relationship between type 1 diabetes (T1D) and osteoporosis (OP). Methods: Single nucleotide polymorphisms (SNPs) associated with T1D were selected from the summary statistics of the genome-wide association study (GWAS) in European ancestry as instrumental variables (IVs) for univariable MR (UVMR) to explore the causal relationship between T1D and OP. Inverse variance weighting (IVW) was the primary method used to assess possible causality between T1D and OP. MR-PRESSO and MR-Egger intercepts were used to assess the horizontal pleiotropy of the IVs, and Q tests and the "leave-one-out" method were used to test for heterogeneity of MR results. Multivariable MR (MVMR) analysis was used to account for potential confounders such as smoking, obesity, drinking, and serum 25-hydroxyvitamin D (25OHD) concentrations. Result: Inverse variance weighted estimates suggest T1D may increase risk of OP (UVMR: OR = 1.06, 95% CI: 1.02-1.10, p = 0.002) (MVMR: OR = 1.50, 95% CI: 1.07-1.90, p < 0.001). Conclusion: Our findings suggest that T1D can increase the risk of OP.