Use of Diabetes Technologies and Retinopathy in Adults With Type 1 Diabetes.

Importance: Diabetic retinopathy (DR) is a complication of diabetes that can lead to vision loss. Outcomes of continuous glucose monitoring (CGM) and insulin pump use in DR are not well understood. Objective: To assess the use of CGM, insulin pump, or both, and DR and proliferative diabetic retinopathy (PDR) in adults with type 1 diabetes (T1D). Design, Setting, and Participants: A retrospective cohort study of adults with T1D in a tertiary diabetes center and ophthalmology center was conducted from 2013 to 2021, with data analysis performed from June 2022 to April 2023. Exposure: Use of diabetes technologies, including insulin pump, CGM, and both CGM and insulin pump. Main Outcomes and Measures: The primary outcome was development of DR or PDR. A secondary outcome was the progression of DR for patients in the longitudinal cohort. Multivariable logistic regression models assessed for development of DR and PDR and association with CGM and insulin pump use. Results: A total of 550 adults with T1D were included (median age, 40 [IQR, 28-54] years; 54.4% female; 24.5% Black or African American; and 68.4% White), with a median duration of diabetes of 20 (IQR, 10-30) years, and median hemoglobin A1c (HbA1c) of 7.8% (IQR, 7.0%-8.9%). Overall, 62.7% patients used CGM, 58.2% used an insulin pump, and 47.5% used both; 44% (244 of 550) of the participants had DR at any point during the study. On univariate analysis, CGM use was associated with lower odds of DR and PDR, and CGM with pump was associated with lower odds of PDR (all P < .05), compared with no CGM use. Multivariable logistic regression adjusting for age, sex, race and ethnicity, diabetes duration, microvascular and macrovascular complications, insurance type, and mean HbA1c, showed that CGM was associated with lower odds of DR (odds ratio [OR], 0.52; 95% CI, 0.32-0.84; P = .008) and PDR (OR, 0.42; 95% CI, 0.23-0.75; P = .004), compared with no CGM use. In the longitudinal analysis of participants without baseline PDR, 79 of 363 patients (21.8%) had progression of DR during the study. Conclusions and Relevance: In this cohort study of adults with T1D, CGM use was associated with lower odds of developing DR and PDR, even after adjusting for HbA1c. These findings suggest that CGM may be useful for diabetes management to mitigate risk for DR and PDR.

Machine Learning Models for Prediction of Diabetic Microvascular Complications.

IMPORTANCE AND AIMS: Diabetic microvascular complications significantly impact morbidity and mortality. This review focuses on machine learning/artificial intelligence (ML/AI) in predicting diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). METHODS: A comprehensive PubMed search from 1990 to 2023 identified studies on ML/AI models for diabetic microvascular complications. The review analyzed study design, cohorts, predictors, ML techniques, prediction horizon, and performance metrics. RESULTS: Among the 74 identified studies, 256 featured internally validated ML models and 124 had externally validated models, with about half being retrospective. Since 2010, there has been a rise in the use of ML for predicting microvascular complications, mainly driven by DKD research across 27 countries. A more modest increase in ML research on DR and DN was observed, with publications from fewer countries. For all microvascular complications, predictive models achieved a mean (standard deviation) c-statistic of 0.79 (0.09) on internal validation and 0.72 (0.12) on external validation. Diabetic kidney disease models had the highest discrimination, with c-statistics of 0.81 (0.09) on internal validation and 0.74 (0.13) on external validation, respectively. Few studies externally validated prediction of DN. The prediction horizon, outcome definitions, number and type of predictors, and ML technique significantly influenced model performance. CONCLUSIONS AND RELEVANCE: There is growing global interest in using ML for predicting diabetic microvascular complications. Research on DKD is the most advanced in terms of publication volume and overall prediction performance. Both DR and DN require more research. External validation and adherence to recommended guidelines are crucial.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). METHODS: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. RESULTS: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. CONCLUSIONS: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

People living with type 2 diabetes (T2D) are more likely to develop problems with their heart or blood circulation, known as cardiovascular disease (CVD), than people who do not have T2D. However, it can be difficult to predict which people with T2D are most likely to develop CVD. This is because current approaches, such as blood tests, do not identify all people with T2D who are at an increased risk of CVD. In this study we reviewed published papers that investigated the differences between people with T2D who experienced CVD compared to those who did not. We found some indicators that could potentially be used to determine which people with T2D are most likely to develop CVD. More studies are needed to determine how useful these are. However, they could potentially be used to enable clinicians to provide targeted advice and treatment to those people with T2D at most risk of developing CVD.

Addressing disparities in technology use among patients with type 1 diabetes: a review.

PURPOSE OF REVIEW: The benefits of continuous glucose monitors (CGMs) and insulin pumps in the management of type 1 diabetes (T1D) are widely recognized. However, glaring disparities in access exist, particularly in marginalized and economically disadvantaged groups that stand to benefit significantly from diabetes technology use. We will review recent data describing drivers of these disparities and approaches to address the disparities. RECENT FINDINGS: Several qualitative studies were published in recent years that have investigated the drivers of disparities reported over the past decades. These studies report that in addition to typical barriers seen in the diabetes technology, marginalized patients have unique challenges that make insulin pumps and CGMs less accessible. SUMMARY: Barriers to technology use in these groups include stigmatization, lack of support, financial constraints, provider biases, stringent insurance policies, and clinic infrastructure. To address inequities, multifaceted strategies across community, healthcare, and provider sectors are essential. Key initiatives include enhancing public awareness, refining health policies, ensuring access to high-quality care, and emphasizing patient-centered approaches. The equitable use of technology can narrow the gap in T1D outcomes. The social and economic implications of suboptimal T1D management further underscore the urgency of these efforts for both improved health outcomes and cost-efficient care.

Association of Long-Term, New-Onset, and Postsurgical Diabetes With Survival in Patients With Resectable Pancreatic Cancer: A Retrospective Cohort Study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Identifying modifiable risk factors, such as diabetes, is crucial. In the context of PDAC diagnosis, diabetes manifests as long-term (LTD), new-onset (NOD), or postsurgical (PSD) phenotypes. The link between these diabetes phenotypes and PDAC survival is debated. MATERIALS AND METHODS: We performed a retrospective study on patients with resectable PDAC who underwent pancreatectomy at Johns Hopkins Hospital from 2003 to 2017. We utilized the National Death Index and electronic medical records to determine vital status. We categorized diabetes as LTD, NOD, or PSD based on the timing of diagnosis relative to pancreatic resection. Using multivariable Cox models, we assessed hazard ratios (HRs) for survival times associated with each phenotype, considering known PDAC prognostic factors. RESULTS: Of 1556 patients, the 5-year survival was 19% (95% CI, 17-21). No significant survival differences were observed between diabetes phenotypes and non-diabetic patients. NOD and PSD presented nonsignificant increased risks of death (aHR: 1.14 [95% CI, 0.8-1.19] and 1.05 [95% CI, 0.89-1.25], respectively). LTD showed no survival difference (aHR, 0.98; 95% CI, 0.99-1.31). CONCLUSIONS: No link was found between diabetes phenotypes and survival in resectable PDAC patients. Comprehensive prospective studies are required to validate these results.

Precision Prognostics for Cardiovascular Disease in Type 2 Diabetes: A Systematic Review and Meta-analysis.

Background Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with type 2 diabetes (T2D). Methods We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

Racial Disparities in Access and Use of Diabetes Technology Among Adult Patients With Type 1 Diabetes in a U.S. Academic Medical Center.

OBJECTIVE: Recent studies highlight racial disparities in insulin pump (PUMP) and continuous glucose monitor (CGM) use in children and adolescents with type 1 diabetes (T1D). This study explored racial disparities in diabetes technology among adult patients with T1D. RESEARCH DESIGN AND METHODS: This was a retrospective clinic-based cohort study of adult patients with T1D seen consecutively from April 2013 to January 2020. Race was categorized into non-Black (reference group) and Black. The primary outcomes were baseline and prevalent technology use, rates of diabetes technology discussions (CGMdiscn, PUMPdiscn), and prescribing (CGMrx, PUMPrx). Multivariable logistic regression analysis evaluated the association of technology discussions and prescribing with race, adjusting for social determinants of health and diabetes outcomes. RESULTS: Among 1,258 adults with T1D, baseline technology use was significantly lower for Black compared with non-Black patients (7.9% vs. 30.3% for CGM; 18.7% vs. 49.6% for PUMP), as was prevalent use (43.6% vs. 72.1% for CGM; 30.7% vs. 64.2% for PUMP). Black patients had adjusted odds ratios (aORs) of 0.51 (95% CI 0.29, 0.90) for CGMdiscn and 0.61 (95% CI 0.41, 0.93) for CGMrx. Black patients had aORs of 0.74 (95% CI 0.44, 1.25) for PUMPdiscn and 0.40 (95% CI, 0.22, 0.70) for PUMPrx. Neighborhood context, insurance, marital and employment status, and number of clinic visits were also associated with the outcomes. CONCLUSIONS: Significant racial disparities were observed in discussions, prescribing, and use of diabetes technology. Further research is needed to identify the causes behind these disparities and develop and evaluate strategies to reduce them.

Glycemic Outcomes of Hospitalized Patients on Ambulatory Humulin-R U-500 Insulin.

OBJECTIVE: Managing hospitalized patients on ambulatory U-500 insulin is challenging because of limited guidance on how to safely adjust insulin doses during admission. We sought to evaluate glycemic outcomes in relation to inpatient insulin doses in patients receiving U-500 prior to hospitalization. METHODS: Retrospective study of hospitalized patients on ambulatory U-500 seen consecutively from January 2015 to December 2019. Primary outcomes were inpatient hypoglycemia, hyperglycemia, and normoglycemia at different insulin dosages expressed as weight-based (unit/kg/d) inpatient total daily dose (TDD) and ratio of inpatient to outpatient TDD. RESULTS: We identified 66 admissions of 46 unique patients. The median (interquartile range) body mass index was 41.0 kg/m2 (35.1, 46.8), home TDD 212 units (120, 300), and home insulin dose 1.6 units/kg/d (1.1, 2.2). The median (interquartile range) inpatient insulin dose was 0.7 unit/kg/d (0.3, 1.0) and the ratio of inpatient to outpatient TDD was 0.4 (0.2, 0.8). Hyperglycemia persisted throughout the hospitalization. For the outcomes of hyperglycemia and normoglycemia, we found no association between increased levels of insulin dosages. For the outcome of hypoglycemia, significantly higher odds were observed when non-fasting patients received an inpatient TDD that was either > 40% of their home TDD or > 0.6 unit/kg/d of insulin. CONCLUSION: Patients on ambulatory U-500 have significant hyperglycemia during admission. Inpatient insulin doses of 40% of home TDD or ≤ 0.6 unit/kg were not associated with increased hypoglycemia risk. Further prospective studies are needed to determine effective doses in these high-risk patients.

Insulinoma mimic: methadone-induced hypoglycaemia.

Methadone use for opioid use disorder and chronic pain has increased since the start of the century with about 4.4 million dispensed prescriptions in 2009. With increased use of methadone, there has been increasing reporting of less commonly reported side effects (ie, hypoglycaemia). Here, we describe a woman in her 70s with history of opioid use disorder on methadone, stage 4 chronic kidney disease and prior hypoglycaemic episodes who initially presented with perforated gastric ulcer requiring surgical repair. Her perioperative course was complicated by profound hyperinsulinaemic hypoglycaemia. Given concern for methadone-induced hypoglycaemia, methadone was discontinued with monitoring of subsequent blood glucose, insulin, C peptide, proinsulin, ß-hydroxybutyrate and blood methadone levels. As the serum methadone levels decreased, insulin levels substantially decreased in parallel. After 21 days off methadone, dextrose infusion was discontinued with restoration of euglycaemia. In a patient with hyperinsulinaemic hypoglycaemia and methadone use, it is important to consider discontinuing methadone and re-evaluate fasting glucose levels prior to an extensive and invasive insulinoma workup.

Immune Checkpoint Inhibitor-Associated Diabetes: A Single-Institution Experience.

OBJECTIVE: To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. RESEARCH DESIGN AND METHODS: Retrospective chart review of 18 patients with new-onset ICI-DM following anti-programmed cell death protein 1 (PD-1)/anti-programmed cell death protein ligand 1 (PD-L1) therapy for advanced carcinomas. RESULTS: Of 18 patients, 9 had diabetic ketoacidosis (median glucose 27.92 mmol/L; median glucose before presentation 6.35 mmol/L). Median C-peptide at ICI-DM diagnosis was low, and it declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23 months). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those patients who were positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically. CONCLUSIONS: ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may occur both earlier following PD-L1 blockade compared with PD-1 inhibition and in those who have positive GAD65 autoantibodies.