Increased Incidence Of Diabetes Research Articles

Increased genetic risk for β-cell failure is associated with β-cell function decline in people with prediabetes.

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the influence of T2D pPS on diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin or placebo arms. Associations were tested using general linear models and Cox regression adjusted for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher β-cell pPS was associated with lower insulinogenic index and corrected insulin response at one year follow-up adjusted for baseline measures (effect per pPS standard deviation (SD) -0.04, P=9.6 x 10-7; -8.45 uU/mg, P=5.6 x 10-6, respectively) and with increased diabetes incidence adjusted for BMI at nominal significance (HR 1.10 per SD, P=0.035). The liver/lipid pPS was associated with reduced one-year baseline-adjusted triglyceride levels (effect per SD -4.37, P=0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the β-cell cluster pPS had worsening in measures of β-cell function.

Incidence of Type 2 Diabetes Mellitus in Transgender Individuals Undergoing Gender Affirming Hormonal Therapy: A Systematic Review.

Gender-affirming hormonal therapy (GAHT), which includes estrogen, testosterone, androgen agonists, is commonly used in transgender individuals to change their secondary sexual characteristics to align with their gender identity. However, this treatment could result in metabolic side effects that could increase the chances of acquiring type 2 diabetes mellitus. Thus, this study aims to compare differences in body mass index (BMI), insulin resistance, and the incidence of type 2 diabetes mellitus between cisgender and transgender individuals undergoing GAHT. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review searching through PubMed, Google Scholar, Medline (Medical Literature Analysis and Retrieval System Online), and ResearchGate for articles published between 2014 and 2024. The final search was conducted in February 2024. Out of the 3,934 articles reviewed, 11 were selected, focusing on insulin sensitivity/resistance, diabetes incidence, and BMI changes with GAHT. Although our result findings did not show clear evidence of increased diabetes incidence among GAHT patients, it was observed that GAHT does increase BMI and insulin resistance in transgender individuals. Notably, compared to transgender men, transgender women on GAHT were found to be more prone to insulin resistance. We recommend regularly monitoring insulin sensitivity parameters and HbA1c during GAHT to monitor metabolic side effects. Further research and more clinical trials are needed to confirm the GAHT's impact on insulin resistance and to evaluate its role in the onset of type 2 diabetes mellitus.

The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 (IFIH1A946T) and confers an increased risk for several autoimmune diseases, including T1D. We hypothesized that the IFIH1A946T risk variant, (IFIH1R) would promote T1D pathogenesis by stimulating type I interferon (IFN I) signaling leading to immune cell alterations. To test this, we developed Ifih1R knock-in mice on the non-obese diabetic (NOD) mouse background, a spontaneous T1D model. Our results revealed a modest increase in diabetes incidence and insulitis in Ifih1R compared to non-risk Ifih1 (Ifih1NR) mice and a significant acceleration of diabetes onset in Ifih1R females. Ifih1R mice exhibited a significantly enhanced interferon stimulated gene (ISG) signature compared to Ifih1NR, indicative of increased IFN I signaling. Ifih1R mice exhibited an increased frequency of plasma cells as well as tissue-dependent changes in the frequency and activation of CD8+ T cells. Our results indicate that IFIH1R may contribute to T1D pathogenesis by altering the frequency and activation of immune cells. These findings advance our knowledge on the connection between the rs1990760 variant and T1D. Further, these data are the first to demonstrate effects of Ifih1R in NOD mice, which will be important to consider for the development of therapeutics for T1D.

Ongoing Increase in Incidence of Diabetes in Austrian Children and Adolescents (1989–2021): Results from a Nationwide Registry

Introduction. Since there is no uniform global diabetes trend in childhood and adolescence, regional epidemiological surveys of diabetes incidences are important. In Austria, the incidences of type 1 diabetes (T1D), type 2 diabetes (T2D), and other forms of diabetes have been recorded for decades. Methods. To analyze recent developments of diabetes incidence within the decades long-standing Austrian nationwide prospective population-based incidence study for diabetes in children aged <15 years. We estimated time trends of age-standardized rates from 1989 to 2021 for T1D and T2D by joinpoint analysis. Annual percent changes (APCs) were calculated. Case ascertainment was 97%. Results. We observed an unusual increase of T1D incidence in the year 2021, reaching a peak of 28.7/100,000/PY (person years). From 2011 to 2020, there had been a constant plateau phase in the total cohort (APC 0.78, 95% CI [−0.99, 2.58], p = 0.379 ), which had followed a steep increase of T1D incidence (APC 4.6, 95% CI [3.94, 5.19], p < 0.001 ) from 1989 to 2011. Age-specific differences in T1D incidence development were observed. For the first time, we observed a statistically significant constant increase in T2D during the observation period (APC 3.47, 95% CI [0.76, 6.26], p = 0.014 ). Other forms of diabetes are two times more common than T2D in this age group. Conclusion. The incidence of T1D in Austrian children <15 years is still increasing and showed a peak in 2021. For the first time, a significant increase in pediatric T2D was observed in Austria.

Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4–8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

Hurricanes Irma and Maria and Diabetes incidence in Puerto Rico

ObjectiveTo evaluate the impact of Hurricanes Irma/Maria on diabetes incidence in Puerto Rico. Mortality increased substantially after the hurricanes, but morbidity was not assessed.MethodsWe recruited 364 participants from the San Juan Overweight Adults Longitudinal Study (SOALS) aged 40–65 years who completed a three-year follow-up and were free of diabetes. We conducted additional questionnaires 1.7–2.5 years after hurricanes. Glycosylated hemoglobin (HbA1c), fasting glucose and insulin were assessed at all three visits. We compared diabetes incidence between pre-hurricane visits and between visits spanning the hurricanes using Generalized Estimating Equation (GEE) adjusting for within person repeated measures, age, and body mass index (BMI).ResultsDiabetes incidence was significantly higher spanning the hurricanes than pre-hurricane (multivariate GEE model: IRR = 2.1; 95% CI: 1.4–3.1). There was a significantly higher increase spanning the hurricanes compared to pre-hurricanes for Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (median: 0.3 uIU/mL vs. 0.2 uIU/mL). HbA1c levels increased by 0.4% spanning the hurricanes.ConclusionIncreases in diabetes incidence, HOMA-IR and HbA1c were higher spanning the hurricanes compared to the pre-hurricanes period. The increase in diabetes incidence remains significant after adjusting for age and BMI.

Multifunctional porous poly (L-lactic acid) nanofiber membranes with enhanced anti-inflammation, angiogenesis and antibacterial properties for diabetic wound healing

With increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.

Effects of COVID-19 shelter-in-place confinement on diabetes prevention health behaviors among US adults with prediabetes: A cross-sectional survey

The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant lifestyle changes due to shelter-in-place confinement orders. The study’s purpose was to assess if the COVID-19 pandemic affected self-reported diabetes prevention behaviors among American adults with prediabetes. As part of a randomized clinical trial among adults with prediabetes and overweight/obesity, questions were added to existing study surveys to assess the effect of the COVID-19 pandemic on diabetes prevention behaviors and stress. Survey responses were summarized using frequencies. 259 study participants completed seven COVID-19 survey questions from June 2020 to June 2021. Participants were 62.9% female, 42.5% White, 31.3% Black, 11.6% Asian, 8.1% Hispanic, and 6.6% Other. Over 75% of participants reported that the COVID-19 pandemic affected physical activity levels, with 82.1% of those affected reporting decreased physical activity; 70.3% reported that the pandemic affected their eating habits, with 61.7% of those affected reporting their eating habits became less healthy; 73.7% reported that the pandemic affected their level of stress, with 97.4% of those affected reporting that their level of stress had increased; 60% reported that the pandemic affected their motivation to adopt/maintain healthy habits, with 72.9% of those affected reporting their motivation decreased. A high percentage of study participants with prediabetes reported decreases in health promotion behaviors and increases in stress due to the COVID-19 pandemic. Consequently, the pandemic could lead to increased diabetes incidence. Strategies to improve diabetes prevention behaviors and address mental health concerns among those at-risk for diabetes are critical during and after the COVID-19 pandemic.

Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A.

Diabetes is a metabolic disease that currently affects nearly half a billion people worldwide. β-cells dysfunction is one of the main causes of diabetes. Exposure to endocrine-disrupting chemicals is correlated with increased diabetes incidence. We hypothesized that treatment with bisphenol A (BPA) induces endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR), leading to impaired function of the β-cells, which over time, can cause diabetes. In this study, we aimed to evaluate UPR pathways activation under BPA treatment in β-cells and possible recovery of ER homeostasis. MIN6 cells (mouse insulinoma cell line) and isolated pancreatic islets from NOR (non-obese diabetes resistant) mice were treated with BPA. We analyzed the impact of BPA on β-cell viability, the architecture of the early secretory pathway, the synthesis and processing of insulin and the activation of UPR sensors and effectors. We found that the addition of the chemical chaperone TUDCA rescues the deleterious effects of BPA, resulting in improved viability, morphology and function of the β-cells. In conclusion, we propose that modulators of UPR can be used as therapeutic interventions targeted towards regaining β-cells homeostasis.

Abstract C074: Racial disparities in diabetes prevalence in prostate cancer patients on androgen deprivation therapy

Abstract Background Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostate cancer and has been shown to prolong survival. However, the use of ADT is associated with many side effects, most notably an increase in diabetes incidence for patients on ADT. African American men have higher prevalence and mortality rates from prostate cancer than Caucasian men. However, it is unclear how prostate cancer treatment such as ADT affects these disparities. This study examines racial differences in the prevalence of Diabetes mellitus in prostate cancer patients based on their ADT status in the US. Methods This is a retrospective cohort study. Data were sourced from US Collaborative Network TriNetX, a real-time EHR database providing patient data from 49 health care organizations (HCOs). Our cohorts of interest were diabetic prostate cancer patients PCA group identified by ICD-10 code C61, E08-E13 without ADT and PCA+ADT group – identified by ICD-10 code C61, E08-E13 and with ADT (AN500). Descriptive statistics. Prevalence and prevalence ratios were calculated for both PCA and PCA+ADT groups and followed by subgroup analysis by race. Results PCA group included 166,818 diabetic prostate cancer patients with a mean age of 73.5 (SD=13.7). PCA+ADT group included diabetic prostate cancer patients on ADT with a mean age of 75.9 (SD=10.5). The lifetime prevalence of diabetes mellitus in the PCA group is 25 per 100 patients, 69% (White), 14% (African American), and 1% (Asian). In the PCA+ADT group, the prevalence of diabetes is 28 per 100, 66% (White), 22% (African American), and 2% (Asian). Further subgroup analysis showed the prevalence of diabetes in the White population to be 26 per 100 patients in the (PCA+ADT) group, 37 per 100 patients in the African American population, and 34 per 100 patients in the Asian population. The prevalence ratio (PR) of having diabetes in the PCA+ADT group in comparison to the PCA group is PR=1.10 (95% CI=1.089-1.115), P<0.001, Z=15.76. Further, the prevalence ratio (PR) comparing racial groups to the (PCA+ADT) was calculated. In the White group PR=0.938 (95% CI=0.921-0.955), P<0.001, Z=7.059. In the African American group, PR=1.33 (95% CI= 1.296-1.362), P<0.001, Z=22.24. In the Asian group, PR=1.204 (95% CI= 1.107-1.310), P<0.001, Z=4.33 Conclusion The prevalence of diabetes is 10 % higher in the PCA+ADT group than in the PCA group, and further subgroup analysis demonstrated a racial difference in the prevalence of diabetes. In the African American group, diabetes prevalence was higher by 33 % than in the PCA+ADT group. In the Asian group, it was higher by 20%. The white group had a lower prevalence of diabetes by 6.2 % than the PCA+ADT group. The results suggest racial disparities necessitating increased screening efforts and urgent diabetes mellitus management and control. Citation Format: Sameh Gomaa, Kevin Kelly, Edith Mitchell, Grace LuYao, Tingting Zhan, Kuang-Yi Wen. Racial disparities in diabetes prevalence in prostate cancer patients on androgen deprivation therapy [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C074.

Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes.

Since early times, being overweight and obesity have been associated with impaired glucose metabolism and type 2 diabetes (T2D). Similarly, a less frequent adult-onset diabetes in low body mass index (BMI) people has been known for many decades. This form is mainly found in developing countries, whereby the largest increase in diabetes incidence is expected in coming years. The number of non-obese patients with T2D is also on the rise among non-white ethnic minorities living in high-income Western countries due to growing migratory flows. A great deal of energy has been spent on understanding the mechanisms that bind obesity to T2D. Conversely, the pathophysiologic features and factors driving the risk of T2D development in non-obese people are still much debated. To reduce the global burden of diabetes, we need to understand why not all obese people develop T2D and not all those with T2D are obese. Moreover, through both an effective prevention and the implementation of an individualized clinical management in all people with diabetes, it is hoped that this will help to reduce this global burden. The purpose of this review is to take stock of current knowledge about the pathophysiology of diabetes not associated to obesity and to highlight which aspects are worthy of future studies.

1101-P: Cardiovascular Risk Factors and Intraoperative Hypotension Predicted Development of Insulin Deficiency and Diabetes after Pancreatectomy

Objective: Ischemia in pancreatic islets is critical to beta cell function, however, clinical evidences on the implications for diabetes are lacking. Pancreatectomy can induce diabetes, but the mechanisms are not clearly elucidated. Therefore, we examined if cardiovascular disease (CVD) risk factors and intraoperative ischemia, which could cause perfusion insufficiency in pancreatic islets, are associated with insulin deficiency and diabetes after pancreatectomy. Methods: From 2 prospective cohorts of pancreatectomy since 2007, participants were enrolled who had pre-operative HbA1c < 7% without antidiabetes. As for proximal pancreatectomy, those were selected whose HOMA-R increased after surgery. Insulin secretion was assessed by changes in HOMA-B for 1 year (ΔB) . The participants were divided into low- and high-ΔB groups, with stratification by operation type, pre-operative HbA1c, HOMA-B, HOMA-R, and ΔR. Then CVD risk factors and intraoperative ischemic events were compared between the 2 groups, and evaluated for diabetes incidence. Results: A total of 237 patients were enrolled (men 44%, age 56 years, HbA1c 5.6% in average) . Low-ΔB (median -32% of baseline) and high-ΔB (5%) groups showed comparable baseline metabolic variables. According to logistic regression analyses and Cox regression model, a composite of IGT, hypertension, dyslipidemia and a reduction in intraoperative systolic BP significantly decreased HOMA-B after 1 year (RR, 9.52; 95% CI, 1.14-79.3) , and increased diabetes incidence (HR, 3.3; 95% CI, 1.2-8.9) , after adjustment with age, sex, BMI, HbA1c and operation. Conclusion: We observed that chronic ischemia suggested by CVD risk factors and intraoperative ischemic insult were linked to development of insulin deficiency and diabetes after pancreatectomy. Disclosure S.Moon: None. K.Park: None. H.Jang: None. J.Jang: None. H.Jung: Advisory Panel; Novo Nordisk, Research Support; Jeil Pharmaceutical Co., Novo Nordisk. J.Lee: None. H.Sohn: None. Y.Han: None. H.Kim: None. W.Kwon: None. Y.Yoon: None. H.Han: None. T.Oh: None. Funding National Research Foundation of Korea (2019R1A2C1007397)

Consumption of home-prepared meal at workplace as a predictor of glycated haemoglobin among people with type 2 diabetes in Hong Kong: a mixed-methods study

ObjectivesThere is increasing attention on association between eating patterns and diabetes control following global changes in eating patterns. There had been very limited research on the eating patterns of diabetic patients with employment, although working age population has seen the highest increase in diabetes incidence. This study aimed to identify workplace eating patterns in relation to glycaemic control among type 2 diabetic patients with employment.MethodsThis is a sequential mixed-methods study. The exploratory qualitative study involved focus group interviews with 31 type 2 diabetic patients with employment, which guided the design of a subsequent cross-sectional investigation involving 185 patients with employment. Thematic analysis was conducted on the qualitative data to identify workplace eating patterns most relevant to glycaemic control. Hierarchical multiple linear regression was performed to examine association between workplace eating pattern and glycaemic control, proxied by HbA1c.ResultsThe focus group interviews identified frequency in the consumption of home-prepared meals (HPM) and meal hours as the major workplace eating patterns that affected glycaemic control. The cross-sectional study confirmed that regular consumption of HPM at workplace could explain variance of HbA1c, independent of socio-demographic factors, lifestyle factors and disease condition, with R2 = 0.146, F(14, 170) = 2.075, p = 0.015; adjusted R2 = 0.076. Patients who were female, in non-skilled occupation, on shift, with fixed work location and had break during work were more likely to consume HPM.ConclusionsConsumption of HPM at workplace should be promoted to facilitate better glycaemic control by type 2 diabetic patients with employment, possibly through more practical dietary advice, and workplace accommodation in terms of space and facilities. In the context of COVID-19 pandemic, consumption of HPM also meant additional protection for diabetic patients through reducing close contact exposures in restaurants.

Increased Risk of Incident Diabetes Among Individuals With Latent Tuberculosis Infection.

In cross-sectional U.S. studies, patients with diabetes had twice the prevalence of latent tuberculosis infection (LTBI) compared with those without diabetes. However, whether LTBI contributes to diabetes risk is unknown. We used longitudinal data to determine if LTBI is associated with increased diabetes incidence. We conducted a retrospective cohort study among U.S. Veterans receiving care in the Veterans Health Administration from 2000 to 2015. Eligibility included all patients without preexisting diabetes who received a tuberculin skin test (TST) or interferon-γ release assay (IGRA). We excluded patients with a history of active TB and those diagnosed with diabetes before or within 2 years after LTBI testing. Patients were followed until diabetes diagnosis, death, or 2015. LTBI was defined as TST or IGRA positive. Incident diabetes was defined by use of ICD-9 codes in combination with a diabetes drug prescription. Among 574,113 eligible patients, 5.3% received both TST/IGRA, 79.1% received TST only, and 15.6% received IGRA only. Overall, 6.6% had LTBI, and there were 2,535,149 person-years (PY) of follow-up after LTBI testing (median 3.2 years). The diabetes incidence rate (per 100,000 PY) was greater in patients with LTBI compared with those without (1,012 vs. 744; hazard ratio [HR] 1.4 [95% CI 1.3-1.4]). Increased diabetes incidence persisted after adjustment for covariates (adjusted HR [aHR] 1.2 [95% CI 1.2-1.3]) compared with those without LTBI. Among patients with LTBI, diabetes incidence was similar in those treated for LTBI compared with those who were not treated (aHR 1.0 [95% CI 0.9-1.1]). Comprehensive longitudinal data indicate that LTBI is associated with increased diabetes incidence. These results have implications for people with LTBI, ∼25% of the global population.

Glucose-responsive multifunctional metal–organic drug-loaded hydrogel for diabetic wound healing

As the incidence of diabetes increases, its complication, diabetic foot ulcers, has become the main type of clinically chronic refractory wounds. Due to the hyperglycemic microenvironment of the diabetic wound, which leads to vascular defects and bacterial growth, the therapeutic effect of wound dressings lacking strategic design is relatively limited. In this study, we designed an injectable, “self-healing”, and glucose-responsive multifunctional metal–organic drug-loaded hydrogel (DG@Gel) for diabetic wound healing. The functionalized hydrogel was prepared by phase-transfer-mediated metallo-nanodrugs, which were made by co-assembling zinc ions, organic ligands, and a small-molecule drug, deferoxamine mesylate (DFO), and the programmed loading of glucose oxidase (GOX). When injected into a diabetic wound, the GOX in DG@Gel changed the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid, which decreased the pH of the wound site. The low pH promoted the release of zinc ions and DFO, which exhibited synergistic antibacterial and angiogenesis activity for diabetic wound repair. In vitro experiments revealed the antibacterial activity and the cell proliferation, migration, and tube formation ability of DG@Gel. Moreover, in vivo experiments showed that DG@Gel can induce re-epithelialization, collagen deposition, and angiogenesis during wound healing in diabetic mice with good biocompatibility and biodegradability. The results suggest that this hydrogel is a promising innovative dressing for the treatment of diabetic wounds. Statement of significanceDiabetic ulcers, as one of the main types of chronic refractory wounds, are not treated effectively in the clinic due to a lack of strategic approach. In this study, we designed a glucose-responsive multifunctional metal–organic drug-loaded hydrogel (DG@Gel), which can change the hyperglycemic wound microenvironment by decomposing excess glucose into hydrogen peroxide and glucuronic acid. This in turn promoted the release of zinc ions and deferoxamine mesylate (DFO) in the hydrogel, which exhibited synergistic antibacterial and angiogenic activity for diabetic wound repair. Furthermore, the DG@Gel exhibited good biocompatibility and biodegradability in vivo. In general, this innovative strategy design may have great application potential in the treatment of various chronic wounds.

Опыт эндоваскулярного лечения пациентов с хронической ишемией, угрожающей потерей конечности

The aim of the study was to assess the technical feasibility of endovascular revascularization of the arteries of the lower extremities in the development of critical ischemia of the lower extremities (chronic ischemia with threatening limb loss), including diabetic foot syndrome. Two clinical cases of endovascular revascularization of lower limb arteries with the development of chronic ischemia with threatening limb loss and diabetic foot syndrome were analyzed. Median age was 61 (60–62) years; there was 1 male (50 %). Upon hospitalization, the risk of limb loss according to the WIfI classification was assessed in one case as high, in the other as medium. The efficiency of revascularization was 100 %. In 1 case (50 %), a second intervention was required. High amputation after surgery during the next year of follow-up was 100 % not necessary. The duration of the operation was 120–150 minutes. The survival rate during the year of follow-up after surgery was 100 %. Clinical observation demonstrates that even with the correct selection of patients, stratification of risk factors for both possible loss of a limb and the risk of surgery, as well as the correctness of the chosen tactics for revascularization of the CPR, only with an increase in the number of procedures performed, routing training and the creation of specialized centers is it possible to achieve satisfactory results in treatment of this problem, which, as the global trend shows, will worsen as the incidence of diabetes increases and the population ages

249-OR: Type 2 Diabetes (T2D) Genetic Clusters for Association with Glycemic Responses to Intervention for Diabetes Prevention

Polygenic scores (PS) of T2D genetic variants based on pathophysiologic mechanisms underlying diabetes have been developed. We investigated whether T2D cluster PS influences response to interventions for diabetes prevention. We examined 2,647 DPP participants with impaired glucose tolerance and genetic data randomized to intensive lifestyle, metformin or placebo arms for diabetes prevention. We generated five PS clusters including β-cell related clusters (β-cell, proinsulin) and insulin resistance clusters (liver/lipid, obesity, lipodystrophy). We examined associations of PS with baseline and 1-year glycemic traits after intervention derived from oral glucose tolerance tests using general linear models, and with diabetes incidence over an average period of 3 years using Cox Regression Models. Models were adjusted for sex, age, and 10 principal components, respective baseline trait, and treatment group. At one-year follow-up, β-cell PS was associated with reduction in the insulinogenic index and corrected insulin response, in each treatment group and, statistically significant, in all combined (P<0.001), with no statistically significant interaction term between treatment groups, a finding consistent with a slightly increased diabetes incidence (HR 1.02 per weighted allele [CI 95% 1.00, 1.03]). The remaining PS were associated with baseline participant features, but not with diabetes incidence or change in glycemic parameters from baseline. We conclude that high genetic burden in β-cell cluster PS is associated with greater risk of diabetes and a decrease in insulin secretion, seen across all treatment groups. Despite interventions with intensive lifestyle and metformin, participants with high β-cell cluster genetic burden had an increased risk of diabetes and worsening in insulin secretion similar to placebo group. These data suggest that alternate therapies may be needed to prevent β-cell decline in this subset of prediabetes patients. Disclosure L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. S. Raghavan: None. S. Srinivasan: None. J. Xu: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. M. Udler: None. D. Research group: None. K. A. Jablonski: None. P. W. Franks: Advisory Panel; Self; Zoe Global Limited, Consultant; Self; Eli Lilly and Company, Novo Nordisk. R. B. Goldberg: None. M. Hivert: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. W. C. Knowler: None. C. Lee: None. J. Merino: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048489)

Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines.

Susceptibility to autoimmune diabetes is a complex genetic trait. Linkage analyses exploiting the NOD mouse, which spontaneously develops autoimmune diabetes, have proved to be a useful tool for the characterization of some of these traits. In a linkage analysis using 3A9 TCR transgenic mice on both B10.BR and NOD.H2k backgrounds, we previously determined that both the Idd2 and Idd13 loci were linked to the proportion of immunoregulatory CD4-CD8- double negative (DN) T cells. In addition to Idd2 and Idd13, five other loci showed weak linkage to the proportion of DN T cells. Of interest, in an interim analysis, a locus on chromosome 12 is linked to DN T cell proportion in both the spleen and the lymph nodes. To determine the impact of this locus on DN T cells, we generated two congenic sublines, which we named Chr12P and Chr12D for proximal and distal, respectively. While 3A9 TCR:insHEL NOD.H2k-Chr12D mice were protected from diabetes, 3A9 TCR:insHEL NOD.H2k-Chr12P showed an increase in diabetes incidence. Yet, the proportion of DN T cells was similar to the parental 3A9 TCR NOD.H2k strain for both of these congenic sublines. A genome-wide two dimensional LOD score analysis reveals genetic epistasis between chromosome 12 and the Idd13 locus. Altogether, this study identified further complex genetic interactions in defining the proportion of DN T cells, along with evidence of genetic epistasis within a locus on chromosome 12 influencing autoimmune susceptibility.

591. A Model for assessing staffing needs for an Outpatient Parenteral Antibiotic Therapy (OPAT) program

BackgroundManagement of patients needing OPAT is complex, and requires a multidisciplinary team for transitioning patients from inpatient to outpatient care, ongoing monitoring of labs, antibiotic levels, managing complications of the drugs and intravenous access, and communicating with patients, family, home infusion pharmacies, home care nursing agencies, and the patients’ physicians and other providers. In addition, documentation of each of these activities in the EMR is necessary. Guidance on how to determine number of staff needed for an OPAT program is lacking.MethodsWe created a detailed step by step list of the various activities done by our OPAT nurse (RN) and determined the time needed to perform each activity. We calculated how many hours of nursing time would be needed per week to perform all the activities for patient care based on our OPAT volume.ResultsIn 2019 we enrolled 767 patients in 835 episodes of OPAT. Our weekly census averages about 120–135 patients. Median duration on OPAT was 30 days. We calculated that our OPAT RN workload was an average of 47.5 hours/week (range of 40–55 hours/week), with time per activity ranging from 5 minutes to 3 hours (table). As this calculated to more than one full time RN position, additional staff were requested.Assessment of Staffing Requirements for an OPAT Program ConclusionWe have assessed the workload for OPAT RN(s) in our program based on our 2019 patient volume. We recommend that one RN can safely manage about 500–550 patients per year. Based on this analysis we were successfully able to justify the need for a second RN for our program.Any OPAT Program can do such analysis to determine their OPAT staffing needs, and also plan for the anticipated increases in OPAT volume because of increasing longevity of the population, increase in diabetes incidence, invasive procedures such as arthroplasties, cardiac devices, etc.LimitationsThis analysis does not include time spent by inpatient staff to arrange for home care and home infusion services. It also does not account for an ID pharmacist time, or the physicians and APP time for management of these patients outside of the billable visit.Disclosures All Authors: No reported disclosures

Global Perspectives in Dialysis: Singapore

The first hemodialysis (HD) in Singapore was conducted in September 1961 for acute kidney failure with the twin-coil artificial kidney. It was not until 1968 when the chronic HD program was instituted (1). Since then, the incidence and prevalence of CKD stage 5 (CKD5) and dialysis have increased significantly. The Singapore Renal Registry is maintained by the National Registry of Diseases Office. On the basis of its Annual Report 2018, the crude incidence rate of CKD5 increased from 341.5 per million population (pmp) in 2009 to 504.1 pmp in 2017 (2). Although the age-standardized incidence rate (ASIR) of CKD5 remained stable (256.6–289.2 pmp), the ASIR of dialysis increased significantly from 159.0 pmp in 2009 to 187.0 pmp in 2018 (Table 1). Eighty percent of the new patients on dialysis were aged 50–79 years in 2018, supporting the notion that the greater incidence of dialysis was related to an aging population. However, the crude incidence rate of dialysis also increased significantly for those aged 30–39 and 40–49 years over a 10-year period, which could possibly be explained by the increase in incidence of diabetes. View this table: Table 1. Age-standardized incidence rate of CKD stage 5 and dialysis (2) The age-standardized prevalence rate of dialysis also increased from 890.6 pmp in 2009 to 1081.7 pmp in 2018 (2). The ASIR of HD was consistently higher compared with that of peritoneal dialysis (PD). Although the ASIR for HD remained relatively stable (2), the ASIR for PD increased significantly over the years (Figure 1). Similarly, the prevalence rates of HD were consistently higher than those of PD across the years. However, the increment in age-standardized prevalence rate for HD was higher than that of PD (2) (Figure 2). Figure 1. Incidence rate (per million population [pmp]) of dialysis by modality from 2009 to 2018. HD, hemodialysis; PD, peritoneal …