Diagnosis Of T2D Research Articles

8513 Toxic Metals Are Associated With Increased Diabetes And Obesity Through Gut Microbiota Changes In Five African-Origin Populations

Abstract Disclosure: J. Jorgensen: None. C. Choo-Kang: None. L. Issa: None. J.A. Gilbert: None. G. Ecklu-Mensah: None. A. Luke: None. K. Bedu-Addo: None. T. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. M. Argos: None. Y. Dai: None. R.M. Sargis: None. L.R. Dugas: None. B.T. Layden: None. Obesity is associated with an increased risk for cardiometabolic diseases, such as type 2 diabetes mellitus (T2D). Prior research has shown an association between toxic metals/metalloid (hereafter, “metals”) exposures, including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), and increased T2D risk. Importantly, metal exposure has been suggested to impact the gut microbiome. Gut microbiome composition and metabolism are key to the development and progression of obesity and diabetes, thus we propose a potential novel interaction via the gut microbiota between metals and T2D, although the exact pathway remains unclear. We studied a large African-origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US (n=188, 51% female, mean age=43.0±6.5 yr). Analyzing 16S rRNA Amplicon sequencing, anthropometrics, and creatinine-adjusted urinary metal levels, we observed metal levels were significantly associated with country of origin and in most countries were significantly associated with decreased microbial diversity. Metal levels were highest in Ghana and lowest in the US, and were significantly different between Ghana and the US for As and Pb (p-value < 2.2e-16). Individually, Pb levels were significantly associated with fasting blood glucose and BMI, As levels were associated with T2D diagnosis, and Hg levels were associated with obesity diagnosis. Pb levels were significantly associated with a lower proportion of potential acetate- and butyrate-producing microbial strains. Similarly, As levels were associated with decreased proportion of potential butyrate-producing genera. Microbial strains in individuals with high Pb levels showed significant association with obesity and T2D risk and strains in individuals with significant high As levels were associated with only T2D risk. Hg and Cd were not significantly associated with microbes and clinical status. These taxa are significantly associated with increased heme metabolism. With this study, we aimed to begin to describe the effect of metals and the risks for obesity and diabetes through its action within the gut microbiome. We demonstrate that toxic metal exposures were associated with differences in the gut microbiome and predicted metabolism that may also be associated with increased obesity and T2D risk. Presentation: 6/1/2024

Association between neighbourhood poverty and type 2 diabetes risk. Does moving from a high to lower poverty neighbourhood reduce diabetes risk?

ObjectivesDiabetes, a pressing global public health crisis, Diabetes, a global health crisis, is significantly impacted by social determinants, including neighborhood characteristics. This study aims to to assess whether relocation from a high poverty to lower poverty neighbourhood is associated with a reduction in T2D incidence. Methods and ResultsThis population-based, propensity-matched cohort study will use linked administrative health to examine the association between neighborhood relocation and T2D incidence. The study population will include adults (age ≥20 years) residing in high poverty urban neighborhoods between April 1st, 2002, to March 31st, 2021, as defined by an area Low-Income Measure - After Tax value of 38,730 dollars for a household size 4 based on the Canadian Census. Individuals will be followed for a new diagnosis of T2D using a validated algorithm based on hospitalization and physicians’ claims data. Propensity score matching will used to match individuals who moved from high-to-lower poverty neighbourhoods to one of two comparison groups: those moving from high-to-high poverty areas and those who remain in their original neighbourhood. Time-to-event analysis utilizing Cox proportional hazards regression with a robust variance estimator will be used to compare T2D incidence between matched groups. As a sensitivity analysis, non-propensity score modeling will be conducted using neighbourhood of residence as a time-varying covariate. The results of the aforementioned analyses will be presented during the conference. ImplicationsBy clarifying the link between neighborhood poverty and T2D incidence, the results will guide focused interventions to alleviate health inequalities in socioeconomically disadvantaged areas.

Exploring protein relative relations in skeletal muscle proteomic analysis for insights into insulin resistance and type 2 diabetes

The escalating prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2D) underscores the urgent need for improved early detection techniques and effective treatment strategies. In this context, our study presents a proteomic analysis of post-exercise skeletal muscle biopsies from individuals across a spectrum of glucose metabolism states: normal, prediabetes, and T2D. This enabled the identification of significant protein relationships indicative of each specific glycemic condition. Our investigation primarily leveraged the machine learning approach, employing the white-box algorithm relative evolutionary hierarchical analysis (REHA), to explore the impact of regulated, mixed mode exercise on skeletal muscle proteome in subjects with diverse glycemic status. This method aimed to advance the diagnosis of IR and T2D and elucidate the molecular pathways involved in its development and the response to exercise. Additionally, we used proteomics-specific statistical analysis to provide a comparative perspective, highlighting the nuanced differences identified by REHA. Validation of the REHA model with a comparable external dataset further demonstrated its efficacy in distinguishing between diverse proteomic profiles. Key metrics such as accuracy and the area under the ROC curve confirmed REHA’s capability to uncover novel molecular pathways and significant protein interactions, offering fresh insights into the effects of exercise on IR and T2D pathophysiology of skeletal muscle. The visualizations not only underscored significant proteins and their interactions but also showcased decision trees that effectively differentiate between various glycemic states, thereby enhancing our understanding of the biomolecular landscape of T2D.

Shedding more than weight: Metabolic and bariatric surgery and the journey to insulin independence in insulin-treated type 2 diabetes

BackgroundType 2 diabetes (T2D) imposes a significant health burden, necessitating lifelong pharmacological interventions, with insulin being one of the cornerstone therapies. However, these regimens are associated with health risks and psychological stressors. This study aimed to examine the rates of insulin-treated T2D remission and cessation or reduction in the dosage of insulin therapy after metabolic and bariatric surgery (MBS). MethodsThis was a retrospective analysis of patients with a preoperative diagnosis of insulin-treated T2D who underwent primary laparoscopic sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) with a minimum of 3 and up to 5 years of follow-up. The average daily dose for each type of insulin, measured in units, was calculated at annual intervals. ResultsAmong 287 patients included, 201 (70%) underwent RYGB, 66 (23%) underwent SG, and 20 (7%) underwent BPD/DS. The average follow-up period was 4.6 ± 0.7 years. At 5 years follow-up, the mean total weight loss was the highest in the BPD/DS subgroup at 37.5% ± 11.6%. Insulin usage decreased significantly from complete dependency at baseline to 36.2% just 1 year postoperatively, and the use of noninsulin antidiabetic drugs decreased from 79.4% initially to 26.1%. These results were sustained throughout the study period. The subgroup analysis indicated that, 5 years after surgery, T2D remission was the highest after BPD/DS (73.7%) compared with RYGB (43.2%) and SG (23.3%) (P < .001). ConclusionMBS is a transformative approach for achieving significant remission in insulin-treated T2D and reducing insulin requirements. Our findings reinforce the efficacy of these surgical interventions, particularly highlighting the promising potential of procedures that bypass the proximal small intestine, such as BPD/DS and RYGB.

Prevalence and incidence of heart failure in type 2 diabetes patients: results from a nationwide prospective cohort—the DIABET-IC study

BackgroundType 2 diabetes (T2D) patients have an increased risk of heart failure (HF). There are limited data on the association between HF and T2D in specific healthcare settings. This study sought to analyse the prevalence and incidence of HF in a contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics.MethodsWe conducted an observational multicentre prospective study (DIABET-IC) that enrolled patients with a T2D diagnosis attending cardiology and endocrinology outpatient clinics in 30 centres in Spain between 2018 and 2019. The prevalence at the start of the study and the incidence of HF after a 3 year follow-up were calculated. HF was defined as the presence of typical symptoms and either: a) LVEF < 40%; or b) LVEF ≥ 40% with elevated natriuretic peptides and echocardiographic abnormalities.ResultsA total of 1249 T2D patients were included in the present analysis (67.6 ± 10.1 years, 31.7% female). HF was present in 490 participants at baseline (prevalence 39.2%), 150 (30.6%) of whom had a preserved ejection fraction. The presence of adverse social determinants and chronic conditions such as chronic kidney disease and atherosclerotic cardiovascular disease were more frequent in HF patients. During the study period, there were 58 new diagnoses of HF (incidence 7.6%) among those without baseline HF. The incidence rate was 3.0 per 100 person-years. Independent predictors of incident HF were smoking, left ventricular ejection fraction, NT-ProBNP, history of tachyarrhythmia and treatment with pioglitazone, oral anticoagulants, or diuretics. Despite an average suboptimal glycaemic control, the use of antidiabetic drugs with cardiovascular benefits was low (30.4% for sodium-glucose cotransporter-2 inhibitors and 12.5% for glucagon-like peptide-1 receptor agonists).ConclusionsIn this contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics, the prevalence and incidence of HF were high, comorbidities were frequent, and the use of antidiabetic agents with cardiovascular benefit was low. Outpatient care seems to be a unique opportunity for a comprehensive T2D approach that encompasses HF prevention, diagnosis, and treatment.Graphical

Decline in case rates of youth onset type 2 diabetes in year three of the COVID-19 pandemic.

To determine changes in case rates of youth onset type 2 diabetes in the three years following the COVID-19 pandemic. A single-center, retrospective medical record review was conducted for patients newly diagnosed with T2D between 3/1/18 and 2/28/23 at a pediatric tertiary care center. The number of patients referred to CHLA with a T2D diagnosis date between 3/1/2020 and 2/28/2023 was compared to historical rates between 3/1/2018 and 2/29/2020. χ2 or Fisher's exact test was used to compare categorical variables between each year and 2019. Compared to prepandemic baseline (3/1/19-2/29/20, 11.8±3.7 cases/month), there was a significant increase in new T2D monthly case rates in pandemic year 1 (3/1/20-2/28/21, 20.1±6.0 cases/month, 171 %, p=0.005) and pandemic year 2 (3/1/21-2/28/22, 25.9±8.9 cases/month, 221 %, p=0.002). Case rates declined in pandemic year 3 to 14.5±4.1 cases/month (3/1/22-2/28/23, p=0.43). Compared to prepandemic year 1, the frequency of DKA at diagnosis was higher in pandemic year 1 (13.3 vs. 5.0 %, p=0.009). The DKA rate in pandemic years 2 (6.8 %) and 3 (3.4 %) were comparable to prepandemic year 1 (p=0.53 and 0.58, respectively). Youth onset type 2 diabetes cases and DKA rates in year 3 of the pandemic have returned to prepandemic level.

Recent Patterns and Assessment of Long-term Complications followi ngSARS-CoV-2 Infection and Vaccination in the Context of Diabet esPrevalence among Blood Donors.

Much increasing evidence has suggested that long-term complications post vaccination of SARS-CoV-2 experience a wide range of complication including diabetes. The risk and burden of type 1 diabetes is extensively reported, but type 2 diabetes mellitus (T2D) has yet to be characterized. To address this gap, we aimed to examine trends of long-term complications post SARS-CoV-2 infection and vaccination in diabetes incidence among the Saudi population. In this cross-sectional hospital-based study, we analyzed the blood profile of first-time blood donors from the University Hospital of King Abdulaziz University, Jeddah. Saudi Arabia. Various blood parameters, HbA1c was measured in the month of May 2023. All the donors were non-diabetic and were never diagnosed with T2D before the current blood donation. 203 healthy subjects donated their blood, out of which 104 had abnormally high HbA1c tending towards diagnosis of T2D and 99 had with blood profiles. The study followed the STROBE reporting guidelines. Out of 203 donors 104 (male 50(48.1%), female 54(51.9%)) were diagnosed with increased HbA1c (8.24 in males) compared to 7.61 of HbA1c in females. 35.6% were above ˃65 years, with 52.9% with O+ from the ABO blood group. Liver functions indicated significant p˂0.05, 0.04, increased amount of GGT (46.47 U/L), Alkaline phosphatase (99.93 ±64.26 uL) respectively in HbA1c elevated donors KFT represented significant p˂0.05, 0.02 elevated levels of urea (6.73 ±5.51 mmol/L), creatinine (129.97 ±195.17 umol/L) respectively along with elevated values of Lactate dehydrogenase (LDH) (263.72± 196.70 uL) and triglycerides (1.66 ±0.74mmol/L) when compared to normal value of HbA1c donors. In the present cross-sectional study, significant increase in HbA1c, trending towards increased cases of T2D post SARS-CoV-2 infection and vaccination. Males are much affected compared to females. Further maximum number of cases were from donors above the age of 65 years with altered partial LFT (GGT, Alkaline phosphatase), KFT (urea, creatinine), lipid profile (TG) and LDH in post SARS-CoV-2 and vaccination blood donors. Increase in HbA1c in 50% of donors, irrespective of gender, is an alarming figure for health authorities, with altered LFT, KFT and LDH tests and, in the near future, may increase the incidence of T2D. Large-scale population-based studies are required to prevent future incidences of T2D in young children who will be vaccinated.

TPE conjugated islet amyloid polypeptide probe for detection of peptide oligomers

Islet amyloid polypeptide (IAPP), also known as amylin, is a polypeptide hormone co-secreted with insulin by pancreatic β-cells. In general, IAPP is soluble and lacks a defined structure. However, under certain conditions, these peptides tend to aggregate into soluble oligomers, eventually forming insoluble amyloid fibrils with typical cross-β-sheet structures. Amylin aggregates, therefore, have been regarded as one of the hallmarks of type II diabetes (T2D). Among these aggregated species, oligomers were shown to exhibit significant cytotoxicity, leading to impaired β-cell function and reduced β-cell mass. Monitoring of oligomer appearance during IAPP fibrillation is of particular interest. In this study, we successfully grafted an aggregation-induced emission molecule, tetraphenylethylene (TPE), at the N-terminus of IAPP. By mixing a small amount of TPE-labeled IAPP with unlabeled IAPP, we were able to detect an increase in TPE fluorescence during the nucleation phase of IAPP aggregation in vitro. It may enable real-time monitoring of IAPP oligomer formation and is further applied in the diagnosis of T2D.

FRI588 Effect Of Covid-19 On Depression In Girls With Obesity And Pcos Or Type 2 Diabetes

Abstract Disclosure: D. Ebedes: None. C.J. Noar: None. J. Benson: None. S. Simon: None. L.D. Gulley: None. L.B. Shomaker: None. L. Pyle: None. M.G. Cree: Consulting Fee; Self; Pollie Inc. Grant Recipient; Self; NIH. Research Investigator; Self; Amino Corp. Objectives: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and is associated with elevated body mass index (BMI), and depression in adolescent girls. Prior to the COVID epidemic, we demonstrated elevated rates of depressive symptoms in adolescent girls with obesity suffering from PCOS or T2D. Studies examining how the mental health of this at-risk group of adolescents has changed since the start of the COVID-19 pandemic is limited. Methods: Data were collected from 70 new girls with obesity and PCOS or T2D, who presented for care in an obesity complications clinic between 6 to 18 months into the COVID epidemic (7/1/2020-6/30/2021). Patients were included if they had Center for Epidemiologic Studies-Depression (CES-D, 20 items) scores obtained within 6 months of PCOS or T2D diagnosis. A chart review was performed to collect data on demographics, physical exam findings, psychiatric care, and metabolic measures. CES-D scores ≥16, indicate elevated depression symptoms, and CES-D scores ≥24, indicate severe depression symptoms. This post COVID data was compared to already collected pre-COVID data. Data from pre vs post were compared within PCOS or T2D with a t-test or Mann Whitney U, and proportions with Chi-squared tests. Results: The pre-COVID-19 cohort included 91 girls (47 with PCOS, 44 with T2D) age 15±2 years and BMI z-scores (2.2±0.4). The post-COVID-19 cohort included 70 girls (33 with PCOS and 37 with T2D) aged 14.2±2.3 years and BMI z-scores 2.1±0.7. Pre-Covid moderate or severe depressive symptoms were observed in 30% and 23% of girls with PCOS vs 24% and 39% post-covid (p=0.306). In those with T2D, pre-COVID 18% and 14% had moderate or severe depressive symptoms, respectively, whereas post-COVID these rose to 27% and 43% (P=0.002). There was no change pre/post COVID in the mean CESD score in those with PCOS (18.8±11.6 vs 22.1±13.6; p=0.253), whereas there was a significant increase in overall CESD scores in T2D (12.9±10.6 vs 21.8±11.8; p&amp;lt;0.001). Dysglycemia was worse post-COVID in T2D only, HbA1c (Pre 7.25%[6.6,9.5] vs Post 8.6[7.7,11.4] p=0.006) but neither group demonstrated changes in systolic blood pressure, high density lipoprotein or alanine aminotransferase. Rates of home schooling were greatly elevated during COVID (PCOS pre 15% vs post 76% and T2D pre 5% vs post 55%). Both post-Covid groups reported high rates of loss of sports activities, social activity and friendships. Conclusions: Girls with PCOS and obesity had double the prevalence of depressive symptoms compared to youth with T2D prior to COVID. 6-18 months into the COVID epidemic, CESD scores remained unchanged in girls with PCOS, but were significantly worse in girls with T2D. Presentation: Friday, June 16, 2023

Diabetes management in older adults who fall: a study amongst older adults presenting to the emergency department.

Type 2 diabetes mellitus (T2D) is associated with poor health outcomes whilst tight glycaemic targets are questionable in those aged over 70years with increased frailty. Our aim was to examine whether people with T2D admitted to hospital with a fall, were more likely to have greater frailty, increased mortality and co-morbidity burden, or risk factors for falls than people without T2D, and whether these differences were associated with medications used for the treatment of T2D. The Older Persons Assessment Service (OPAS) is a local emergency department (ED) service, which accepts patients on frailty criteria. The OPAS accepts patients primarily aged over 70years who present with frailty and geriatric syndromes such as falls, with retrieval from the ED department directly to the service from triage. The OPAS databank was analysed for people with T2D admitted with a fall between June 2020-September 2022. We examined clinical outcomes relating to medication, age, Charlson co-morbidity index (CCI) and clinical frailty score (CFS). 1081 patients were included: 294 (27.2%) with T2D and a mean HbA1c of 53.9 (± 15.8) mmol/mol [7.1%]. People with T2D had a similar mean CFS and age compared to those without T2D, but higher mean CCI (7.0 ± 2.2 vs 5.9 ± 2.1, p < 0.001). Of those people with T2D, 175 (59.5%) and 240 (81.6%) had a HbA1c ≤ 53mmol/mol [7.0%] and ≤ 64mmol/mol [8.0%], respectively. In total, 48 (16.3%) people with T2D were identified to have a capillary blood glucose below 4.0mmol/L on admission to the ED. At 12months' follow-up, 831 (76.9%) patients were alive and 250 (23.1%) had died. People with T2D treated with insulin and/or gliclazide had a greater 1-year mortality (36.6% vs 23.6%, p < 0.05), greater frequency of hypoglycaemia (35.4% vs 11.8%, p < 0.001), and greater HbA1c (65.5 ± 17.2mmol/mol [8.2] vs 48.9 ± 12.1mmol/mol [6.6%]) compared to those who used other agents. Logistic regression confirmed a diagnosis of T2D was associated with 1-year mortality, but mortality was not significantly associated with hypoglycaemic-inducing agents. People with T2D were not more likely to live in deprived areas. A diagnosis of T2D is associated with greater 1-year mortality, and may be influenced by use of hypoglycaemia-inducing diabetes medications. Clinician awareness can support de-prescribing for patients with frailty and HbA1c < 64mmol/mol.

Sex-specific associations of serum selenium and selenoprotein P with type 2 diabetes mellitus and hypertension in the Berlin Aging Study II

BackgroundSelenium is essential for expression and proper function of a set of redox active selenoproteins implicated in aging-relevant diseases, e.g. type 2 diabetes mellitus (T2D) and hypertension. However, data in cohorts of older adults, particularly with respect to different Se biomarkers and sex-specific analyses are sparse. ObjectiveTo assess associations of serum Se and selenoprotein P (SELENOP) concentrations with T2D and hypertension in a cohort of older females and males. MethodsThis study included 1500 participants from the Berlin Aging Study II. Diagnosis of T2D was made in case of antidiabetic medication, self-reported T2D, or laboratory parameters. Diagnosis of hypertension was based on self-report, blood pressure measurement, or anti-hypertensive medication. Se was measured by spectroscopy, and SELENOP by ELISA. Multiple adjusted regression models quantified dose-dependent associations. ResultsParticipants had a median(IQR) age of 68 (65,71) years, and 767 (51%) were women. 191 (13%) participants had T2D and 1126 (75%) had hypertension. Se and SELENOP correlated significantly (r = 0.59, p < 0.001), and were elevated in those with self-reported Se supplementation. Serum Se and SELENOP were not associated with T2D in the whole cohort. In men, SELENOP was positively associated with T2D, OR (95%CI) for one mg/L increase in SELENOP was 1.22 (1.00,1.48). Se was non-linearly associated with hypertension, comparing to the lowest quartile (Q1), and participants with higher Se levels (Q3) had a lower OR (95%CI) of 0.66 (0.45,0.96), which was specific for men. SELENOP positively associated with hypertension, and OR (95%CI) per one mg/L increase was 1.15 (1.01,1.32). ConclusionsThe data suggest a sex-specific interrelationship of Se status with T2D and hypertension, with apparent biomarker-specific associations.

From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures.

Background and aim-Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods-Thirty subjects, aged 45-65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results-Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions-The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.

Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis

BackgroundThis study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019.MethodsWe compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1–5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders.ResultsAmong 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61–2.32) but significantly higher 10-year risk of CVD (2.45(1.40–4.29)), 5-year risk of HF (1.94(1.20–3.12)) and 10-year risk of HF (2.84(1.83–4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD.ConclusionsThe study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.

Transfer Learning to improve the Diagnosis of Type 2 Diabetes Mellitus (T2D)

Transfer Learning is a Deep Learning technique that is currently being used in early and non-invasive diagnosis of T2D. The objective of this work is to design and implement a Transfer Learning model trained with images of skin patches belonging to healthy people and diabetic foot patients. The research methodology was constituted by 3 phases (Analysis and Design, Development and Evaluation) composed of 5 steps that comply with the proposed objective. Several convolutional neural network (CNN) models were developed: CNN built from scratch, AlexNet, CNN with data augmentation technique, FE-VGG16, FE-ResNet50 and FT-VGG16. These models were evaluated using a set of metrics derived from the confusion matrix, the Receiver Operating Characteristic curve (ROC) of each model and the value corresponding to the area under the curve (AUC). The best performance corresponded to FT-VGG16 model that fuses VGG-16 pretrained model with a block of fully connected layers. Finally, satisfactory results are reported and allow us to conclude that the application of Transfer Learning models for the classification of diabetic foot images constitutes a viable tool for the non-invasive diagnosis of T2D.

188-LB: Association between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure (HHF)

Background: The relation between age at T2D diagnosis and HHF is unclear. We conducted a population-based cohort study to examine the association between age at diagnosis of T2D and incident HHF in Ontario, Canada. Methods: Using administrative health databases, we identified people with new-onset T2D between April 1, 2005 and March 31, 2015. We matched each person to 3 other people without diabetes according to birth year and sex. We excluded any people with prior HHF. We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) for the association between age at T2D diagnosis and incident HHF (followed up until March 31, 2020). Results: Among 743,053 individuals with T2D and 2,199,539 matches, 126,241 incident HHF events occurred (median follow-up 8.9 years). T2D was associated with a greater adjusted hazard of HHF at younger ages (e.g., HR at age 30 years: 5.71, 95% CI: 5.46-5.96; Figure: Model 1) than at older ages (e.g., HR at age 60 years: 2.51, 2.46-2.55). Additional adjustment for recognized mediators (hypertension, coronary artery disease, chronic kidney disease) marginally attenuated this relation (Figure: Model 2). Conclusion: Younger age at T2D diagnosis is independently associated with a disproportionately elevated risk of HHF relative to age-matched individuals without T2D. This relation may be substantially mediated by novel mechanisms that are inadequately understood. Disclosure C. Ke: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Abbott. B. R. Shah: None. J. Echouffo tcheugui: None. Funding National Heart, Lung, and Blood Institute (K23HL153774 to J.E.T.); University of Toronto (to B.R.S.)

1151-P: Predicting Adverse Events in Patients with DKA or HHS

Background: Management of diabetic ketoacidosis (DKA) in pediatric patients is well established, but optimal management for hyperglycemic hyperosmolar state (HHS) and mixed DKA/HHS is uncertain. Aims: Develop a model to identify patients at increased risk of adverse events and identify management differences associated with adverse outcomes. Methods: Retrospective chart review of 5,346 admissions from 3,104 unique patients with type 1 diabetes (T1D) or T2D at a large children’s hospital from 1/1/2010-7/1/2022 requiring IV insulin to manage DKA (pH &amp;lt;7.3, glucose &amp;gt; 200 mg/dl) and/or HHS (glucose &amp;gt;600 mg/dl). An ICU stay &amp;gt;48 hours (h) was a surrogate for severe adverse events. Risk of death or ICU stay &amp;gt;48 h (high risk [HR] group) was modeled using generalized estimating equations on a training dataset of 3,979 admissions from 2010-2019. Admissions 2020-2022 were the test dataset. Discrimination was assessed with receiver-operator-characteristic (ROC) curves. Using this predictive model, we selected a control (C) group at similar risk of adverse events to identify outcome-related management differences. Results: There were 810 ICU admissions; 90 were &amp;gt;48 h. There were 8 diabetes-related deaths, 5 in 2020-2022. In the multivariate model, risk factors for severe adverse events included initial pH, glucose, absolute value of the deviation of glucose-corrected serum Na from 140, and a diagnosis of T2D. Discrimination was excellent; area under the ROC curve was 0.938 and 0.964 in the training and test datasets respectively. HR and C groups were similar for pH, glucose and sodium on admission, but altered mental status was more frequent in the HR group. Glucose and sodium corrected more slowly in the HR patients. Conclusions: The prediction model accurately identified patients at increased risk of prolonged ICU stay or death. Rates of death and prolonged ICU stay increased during the Covid pandemic, correlated with more severe clinical presentation. Slower correction of metabolic abnormalities was associated with prolonged ICU stay. Disclosure M.Yousif: None. S.Adhikari: None. P.C.White: Consultant; Provention Bio, Inc.

1458-P: Challenges for the Diagnostic Classification of Type 1 Diabetes (T1D) among Older Adults in Electronic Health Record (EHR) Data

As T1D treatments improve and the US population ages, there is a growing number of older adults (≥65 years) with T1D. This patient population is distinct from their T2D counterparts yet remains understudied. Analyzing routine health care may yield real-world evidence to augment trial data and inform best practices. Yet, it is essential to properly classify patients with T1D vs. T2D. We aimed to assess the extent to which codes for T1D versus T2D overlap in EHR data among older adults with diabetes and assess the implications for identifying older adults with T1D, specifically. We analyzed electronic health record (EHR) data from a large, public health care system in the southeast US, including 12 affiliated hospitals and over 200 academic and community-based practices. We included data from adults ages 65+ years that had at least one code for T1D or T2D. Of the 7,436 patients withT1D or T2D listed among their medical conditions, 7,253 (97.5%) had a diagnostic code for T2D and 895 (12.0%) had a diagnostic code for T1D. Of those with a T1D code, 787 (87.9%) also had at least one T2D code. Among those with a code for T1D, the mean percentage of codes that indicate T1D is 49.4%. There is a high degree of co-occurring T1D and T2D diagnosis codes in EHR profiles of older adults, with implications for clinical care and research. Cohort classification in diabetes-oriented RWE studies warrants further research. Disclosure J.M.Weinstein: Research Support; Dexcom, Inc. R.Muthukkumar: None. L.A.Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Eli Lilly and Company, Jaeb Center for Health Research, Sanofi, Boehringer-Ingelheim. A.R.Kahkoska: None. Funding National Institutes of Health (KL2TR002490, UL1TR002489)

941-P: Improved Glycemic Control with Real-Time CGM in Adults with Type 2 Diabetes Not Treated with Insulin

Background: Little is known about real-time continuous glucose monitoring (rt-CGM) in adults with T2D who are not using insulin. We analyzed real-world data to evaluate the association of rt-CGM use and glycemic control in this population. Methods: Data from US-based adults who reported a T2D diagnosis, age ≥18 years, not using insulin and who first uploaded Dexcom G6 data from the Dexcom app between 9/2021 and 6/2022 were analyzed. Individuals with follow-up data at 3 months and baseline time in range (TIR, 70-180 mg/dL) &amp;lt;70% were included. Outcomes included change in CGM metrics and percentage of users with TIR ≥70% at follow-up. Results: CGM users (n=3,505) were [mean (SD)] 52.2 (11.2) years of age and 46% female. TIR increased by 16.2 percentage points from 40.2% (21.7) at baseline to 56.4% (28.2) at 3 months (p &amp;lt;0.001), which was largely attributable to reduced hyperglycemia (Table). The proportion of CGM users meeting the consensus target of TIR ≥70% increased from 0% to 37%. Over the course of 3 months, CGM was worn 91.7% of the time. Most CGM users (77.6%) accessed Clarity summary reports of CGM data and most (80.2%) enabled the optional high glucose alert. Conclusion: In adults with T2D not using insulin and not meeting treatment targets, use of rt-CGM was associated with clinically meaningful improvements in glycemic control. Ongoing use of rt-CGM may result in further improvements in glycemic control. Disclosure L.H.Jepson: Employee; Dexcom, Inc., Stock/Shareholder; Dexcom, Inc. J.Welsh: Employee; Dexcom, Inc. C.R.Green: Employee; Dexcom, Inc. R.Thomas: Employee; Dexcom, Inc. J.E.Layne: Employee; Dexcom, Inc., Verily Life Sciences. Funding Dexcom, Inc.

Patient-centered medical home pharmacists’ impact on composite quality care measures for patients with uncontrolled type 2 diabetes

BackgroundPatients with uncontrolled diabetes are at risk for developing complications. Many health care systems have implemented multidisciplinary care models including pharmacists to help achieve quality care measures to reduce complications. ObjectiveThis study aimed to evaluate whether patients with uncontrolled type 2 diabetes mellitus (T2D) seen at patient-centered medical home (PCMH) clinics affiliated with an academic medical center are more likely to meet a composite of diabetes quality care measures with a pharmacist on their care team than usual care patients without a pharmacist on their care team. MethodsThis is a cross-sectional study. The setting included PCMH primary care clinics affiliated with an academic medical center from January 2017 to December 2020. Included were adults aged 18 to 75 years with a diagnosis of T2D, hemoglobin A1C (A1C) more than 9%, and established with a PCMH provider. The intervention is inclusion of PCMH pharmacist on the patient’s care team for management of T2D per a collaborative practice agreement. The main outcome measures included A1C ≤9% per last recorded value during observation period, a composite A1C ≤9% and completion of yearly laboratory tests, and a composite A1C ≤9%, completion of yearly laboratory tests, and statin prescription for adults aged 40-75 years. ResultsIdentified were 1807 patients in the usual care cohort with mean baseline A1C of 10.7% and 207 patients in the pharmacist cohort with mean baseline A1C of 11.1%. The pharmacist cohort was more likely to have an A1C of ≤9% at the end of the observation period (70.1% vs. 45.4%; P < 0.001), a composite of measures met (28.5% vs. 16.8%; P < 0.001), and a composite of measures met for patients aged 40-75 years (27.2% vs. 13.7%; P < 0.001). ConclusionPharmacist involvement in the multidisciplinary management of uncontrolled T2D is associated with a higher attainment of a composite of quality care measures at the population health level.

Association of HbA1c trajectory and variability with cognitive function

AbstractBackgroundType 2 diabetes (T2D) is an important modifiable risk factor for cognitive decline, and increasing evidence suggests that worse glucose control, in addition to a diagnosis of T2D, may play a role in cognitive function in later life. Despite this increasing concern, evidence regarding the relative contributions of poor glucose control and higher glucose variability to cognitive dysfunction among individuals with overweight or obesity is limited, mostly due to lack of repeated measures in many studies.MethodLook AHEAD MIND Study participants, aged 45‐76 years at baseline (2001‐04) with T2D and overweight or obesity, were randomized to an intensive lifestyle intervention focused on weight loss or a diabetes support and education condition, which were discontinued after ∼10 years. HbA1c levels were evaluated at years 1‐4, 6, 8, and 10. Cognitive function was evaluated up to four times between years 8‐18 with a cognitive battery that assessed memory, attention, and executive function domains. Cognitive scores were binned into four groups based on relative timing of cognitive assessments (8‐9; 10‐11; 12‐14; and 15‐18 years). We classified HbA1c variability according to: Variability Independent of the Mean (VIM), Average Real Variability (ARV), and data‐driven latent trajectories. Mixed linear regression models for standardized composite cognitive scores were adjusted for: repeated measures, order of cognitive test, years from randomization, randomization arm, age, sex, race/ethnicity, years of education, CVD history, and APOE ε4.ResultFour HbA1c trajectories were identified: increasing, decreasing, stable‐high, and stable‐low. Composite cognitive scores were significantly lower for increasing, decreasing, and stable‐high HbA1c trajectories ‐compared to stable‐low HbA1c (Table). In multivariable analysis, higher baseline HbA1c, ARV, and VIM were associated with lower composite cognitive scores, and differences between groups were similar by years since randomization. Estimates for ARV and VIM were attenuated when adjusted for baseline HbA1c (not shown). Estimates were similar for tests from all cognitive domains, with little heterogeneity by randomization arm.ConclusionAmong individuals with T2D, higher HbA1c at baseline and greater HbA1c variability over 10 years were significantly associated with lower cognitive scores, suggesting that maintaining glucose control may be useful for the prevention of cognitive decline.