Established Diabetes Research Articles

Digital Health Tools and Behavioral Strategies to Increase Engagement With Diabetes Self-Management Education and Support: Design and Feasibility of DM-BOOST.

The purpose of the study was to describe the development and feasibility of implementing the DM-BOOST program in support of an established diabetes self-management education and support (DSMES) program. A patient panel of 4 adults with type 2 diabetes (T2DM) codesigned DM-BOOST. DM-BOOST is a patient-focused program that includes peer-written text messages about diabetes self-management behaviors and digital health training to improve patient portal use and initiate goal setting prior to a scheduled DSMES appointment. Adults with T2DM and A1C ≥8.0% participated in a 6-month feasibility pilot. Participants were randomly assigned (1:1) to receive either DM-BOOST or usual care. Outcomes included DSMES engagement (scheduled and attended DSMES appointments) and changes in diabetes self-efficacy and treatment satisfaction. Pilot participants (n = 60) were 60.0% female with mean age 45.5 years (SD 8.3) and A1C 10.1% (SD 1.8%). All DM-BOOST participants (30/30, 100%) had DSMES appointments scheduled compared to 86.7% of usual care (26/30). DM-BOOST participants had fewer DSMES appointment no-shows/cancellations (3/30, 10%) compared to usual care (10/26, 35%). There was greater improvement in diabetes self-efficacy in the DM-BOOST group compared to usual care and no difference in treatment satisfaction. DM-BOOST, leveraging peer-written text messaging and digital health training, increased DSMES engagement. Implementation of DM-BOOST was determined to be feasible, with several system-level barriers identified, including obtaining provider referrals and scheduling appointments. An effectiveness trial of DM-BOOST is needed to evaluate the impact on clinical outcomes.

Association between long-term statin use and cataract surgery: a nationwide study on 505 105 cataract surgery patients

AimsTo assess the association between statin use and cataract surgery according to different statin treatment durations in patients with different cardiovascular risk profiles.Methods and resultsWe performed a nested case–control study...

Based on systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for diabetes.

Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies. We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms. Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM. This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.

Cross-sectional associations of self-perceived stress and hair cortisol with metabolic outcomes and microvascular complications in type 2 diabetes.

Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes. The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), β-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator. We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group (F(1,112) = 5.3; p = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness (r = 0.25, p = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control (r = 0.28, p = 0.02), higher insulin resistance (r = 0.26, p = 0.03) and a longer duration of the illness (r = 0.30, p = 0.01). Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness.

Changes in physical activity and diabetes risk after cancer diagnosis: a nationwide cohort study.

Physical activity has the potential to reduce the risk of diabetes after cancer diagnosis. However, current evidence supporting its effects is limited. This study aims to examine the associations between changes in physical activity and subsequent risk of diabetes among cancer survivors. A total of 264,250 cancer survivors (mean age 56.7 (12.5) years, 44.2% males) without a prior history of diabetes were assessed for adherence to physical activity both before and after their diagnosis. The primary outcome was incident diabetes. The Fine-Gray proportional sub-distribution hazards model was used to calculate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for diabetes risk, considering death as a competing risk. Over a follow-up of 1,065,802 person-years, maintaining regular physical activity from pre-diagnosis was associated with a 10% reduced risk of diabetes after cancer diagnosis (sHR 0.90, 95% CI 0.85-0.96), considering traditional diabetes risk factors, sociodemographics, and primary cancer sites. Cancer survivors who became active and inactive after their cancer diagnosis exhibited a marginally decreased risk of diabetes (sHR 0.98, 95% CI 0.93-1.03; sHR 0.97, 95% CI 0.92-1.03). The strength and direction of the association varied depending on the primary site of cancer. Regular physical activity starting before a cancer diagnosis is associated with a lower risk of diabetes following the diagnosis, independent of established diabetes risk factors. The study underscores the importance of engaging in sufficient physical activity to mitigate the risk of diabetes in cancer survivors.

Association of Fructosamine Levels With Glycemic Management in Children With Type 1 Diabetes as Determined by Continuous Glucose Monitoring: Results From the CGM TIME Trial

ObjectiveOur aim in this study was to determine the correlation between serum fructosamine and average blood glucose, as measured by continuous glucose monitoring (CGM) in children with type 1 diabetes. MethodsNinety-seven blood samples were collected from 70 participants in the Timing of Initiation of continuous glucose Monitoring in Established pediatric diabetes (CGM TIME) Trial. Each eligible participant had 3 weeks of CGM data with at least 60% CGM adherence before blood collection. Ordinary least-squares linear regression incorporating restricted cubic splines was used to determine the association between fructosamine levels and mean blood glucose. ResultsAn association was found between fructosamine and mean blood glucose, with an F statistic of 9.543 (p<0.001). Data were used to create a formula and conversion chart for calculating mean blood glucose from fructosamine levels for clinical use. ConclusionsThere is a complex relationship between average blood glucose, as determined by CGM and fructosamine. Fructosamine levels may be clinically useful for assessing short-term glycemic management when CGM is not available.

A primary care-led weight management intervention for adults with diabetes and obesity: quantitative results from a randomised controlled trial of total meal replacement (DiRECT)

Methods to reduce obesity and type 2 diabetes in Aotearoa New Zealand are desperately needed, with obesity one of the greatest predisposing factors for type 2 diabetes as well as heart disease, and certain cancers.1 A recent New Zealand report2 identified several interventions that might benefit people with established diabetes, the most promising being a period of rapid weight loss, followed by supported weight-loss maintenance. Such weight loss has shown to achieve what was previously thought impossible, diabetes remission,3 as well as appreciably reduce the risk of cardiovascular disease and prevent diabetes-related chronic kidney disease, retinopathy, nephropathy, and lower limb amputation.2 While the findings from the studies of low energy total meal replacement diets have stimulated great interest, their use in Aotearoa New Zealand has not been considered. The purpose of this primary-care led intervention therefore was to consider the acceptability and efficacy of such a weight loss programme, DiRECT, in Aotearoa New Zealand. Te Kāika DiRECT is a 12-month study conducted within a Māori primary healthcare provider in O¯tepoti Dunedin. The DiRECT protocol is three months of total meal replacement for rapid weight loss followed by food reintroduction and a longer period of supported weight loss maintenance. Participants were adults with prediabetes or T2 diabetes and obesity wanting to lose weight. Twenty participants (70% female, age 46 (SD 10), BMI 41 (9), HbA1c 51 (11)) were randomised to receive the DiRECT protocol, twenty more (70% female, age 50 (SD 8), BMI 40 (7), HbA1c 54 (14)) were randomised to receive best practice weight loss support (usual care). All participants had the same number of visits with the in-house Dietitian and free access to the onsite gym. Participants in the control group also received regular grocery vouchers to purchase the foods encouraged by healthy eating guidelines. Recruitment began in February, 2022. After the initial three month study period, DiRECT participants reported consuming 3.0MJ (95% CI 1.2 to 4.8MJ) less energy per day than those in usual care. Mean weight loss was 6kg (2.3-9.6kg) greater for DiRECT participants than usual care participants, while medication use and systolic blood pressure (12mmHg (0-24mmHg)) were lower. Continuous glucose monitoring identified that at baseline, participants on average only spent 10% of the day with a blood glucose reading under 8mmol/L (normoglycaemia). After three months, the usual care group spent on average 48% of the day within the normoglycaemic range, while DiRECT participants spent 78% of the day within the normoglycaemic range. Results at 12 months will enable comment on longer term markers of blood glucose control (HbA1c) and diabetes remission rates, as well as indicate if the body weight, medication, and blood pressure improvements observed at three months are sustained.

Treatment approaches and costs associated with diabetes clinical metrics as measured by Healthcare Effectiveness Data and Information Set (HEDIS)

BackgroundThe clinical outcomes of diabetes can be influenced by primary care providers’ (PCP) treatment approaches. This study explores the association between PCP approaches to management and performance measured by established diabetes metrics and related costs.MethodsIn phase one, Electronic Medical Records were used to extract diabetes related metrics using Healthcare Effectiveness Data and Information Set (HEDIS), for patients with diabetes who had office visits to 44 PCP practices from April 2019 to March 2020. Using those metrics and scoring system, PCP practices were ranked and then categorized into high- and low-performing groups (top and bottom 25%, n = 11 each), with a total of 19,059 clinic visits by patients with a diagnosis of diabetes. Then extensive analysis was performed to evaluate a correlation between treatment approaches and diabetes outcomes across the top and bottom performing practices. In phase 2, patients with diabetes who were attributed to the aforementioned PCP practices were identified in a local health plan claims data base (a total of 3,221 patients), and the allowed amounts from their claims were used to evaluate differences in total and diabetes-related healthcare costs by providers’ performance.ResultsComparing 10,834 visits in high-performing practices to 8,235 visits in low-performing practices, referrals to certified diabetes care and education specialists and provider-to-provider electronic consults (e-consults) were higher in high-performing practices (Z = 6.06, p < .0001), while traditional referrals were higher in low-performing practices (Z = -6.94, p < .0001). The patient-to-provider ratio was higher in the low-performing group (M = 235.23) than in the high-performing group (M = 153.26) (Z = -2.82, p = .0048). Claims data analysis included 1,825 and 1,396 patients from high- and low-performing providers, respectively. The patient-to-provider ratio was again higher in the low-performing group (p = .009, V = 0.62). Patients receiving care from lower-performing practices were more likely to have had a diabetes-related hospital observation (5.7% vs. 3.9%, p = .02; V = 0.04) and higher diabetes-related care costs (p = .002; d = − 0.07); these differences by performance status persisted when controlling for differences in patient and physician characteristics. Patients seeing low-performing providers had higher Charlson Comorbidity Index scores (Mdn = 3) than those seeing high-performing providers (Mdn = 2).ConclusionsReferrals to the CDCES and e-Consult were associated with better measured diabetes outcomes, as were certain aspects of cost and types of hospital utilization. Higher patients to providers ratio and patients with more comorbidities were observed in low performing group.

Vascular Regenerative Cell Deficiencies in South Asian Adults

BackgroundSouth Asian individuals shoulder a disproportionate burden of cardiometabolic diseases. ObjectivesThe purpose of this study was to determine if vascular regenerative cell content varies significantly between South Asian and White European people. MethodsBetween January 2022 and January 2023, 60 South Asian and 60 White European adults with either documented cardiovascular disease or established diabetes with ≥1 other cardiovascular risk factor were prospectively enrolled. Vascular regenerative cell content in venous blood was enumerated using a flow cytometry assay that is based on high aldehyde dehydrogenase (ALDHhi) activity and cell surface marker phenotyping. The primary outcome was the difference in frequency of circulating ALDHhi progenitor cells, monocytes, and granulocytes between the 2 groups. ResultsCompared with White European participants, those of South Asian ethnicity were younger (69 ± 10 years vs 66 ± 9 years; P < 0.05), had lower weight (88 ± 19 kg vs 75 ± 13 kg; P < 0.001), and exhibited a greater prevalence of type 2 diabetes (62% vs 92%). South Asian individuals had markedly lower circulating frequencies of pro-angiogenic ALDHhiSSClowCD133+ progenitor cells (P < 0.001) and ALDHhiSSCmidCD14+CD163+ monocytes with vessel-reparative capacity (P < 0.001), as well as proportionally more ALDHhi progenitor cells with high reactive oxygen species content (P < 0.05). After correction for sex, age, body mass index, and glycated hemoglobin, South Asian ethnicity was independently associated with lower ALDHhiSSClowCD133+ cell count. ConclusionsSouth Asian people with cardiometabolic disease had less vascular regenerative and reparative cells suggesting compromised vessel repair capabilities that may contribute to the excess vascular risk in this population. (The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion [ORIGINS-RCE]; NCT05253521)

Coronary artery calcium score as independent risk factor of obstructive coronary artery disease.

Aim: To prove an independence of CAC score comparatively to conventional risk factors such as age, and dyslipidemia especially in patients under forty years of age. Materials and Methods: Thirty-four asymptomatic adult patients with no prior established atherosclerotic cardiovascular disease, diabetes mellitus or severe comorbidities, except of complex clinical examination, underwent CT scan with evaluation of coronary artery calcium score. Results: The average total cholesterol level in the group was (5.62±1.02) mmol/l, indicating the presence of dyslipidemia. The average HDL level was (1.26±0.24) mmol/l, suggesting an average risk of atherosclerosis. The average LDL levels were within the borderline range at (3.63±1.01) mmol/l. The average triglyceride level was within the safe range at (1.93±1.08) mmol/l. The atherogenicity coefficient indicated a moderate risk of atherosclerosis with an average value of 3.64±1.31. The average coronary artery calcium score was 56.71±143.85, indicating minor plaques and a moderate risk of coronary artery disease. Correlation analysis revealed no significant correlation between age and the CAC score (r=0.1, p>0.05). However, reliable direct correlation of weak strength was found between the CAC score and LDL level (r=0.35, p<0.05). Direct correlations of weak strength were also observed between age and the levels of total cholesterol, LDL and the atherogenicity coefficient (r=0.43, 0.49, 0.42 respectively, p<0.05). Conclusions: Coronary artery calcium score is a valuable screening tool for identifying potential obstructive coronary artery disease, not only for individuals aged forty and above, but also for younger asymptomatic patients.

Desafios na avaliação da deficiência cognitiva em diabéticos na República Democrática do Congo

ABSTRACT Dementia is a global public health issue, with 57.5 million people living with at least one type of dementia in 2019 worldwide, and projected to rise to 152 million by 2050. Objective: We assessed the cognitive function in diabetic patients aged 60 or older in Bukavu city, in the eastern Republic of the Congo (DRC). Methods: This case-control study involved 123 patients with established diabetes mellitus (DM) and 123 controls over 60-year-olds also with high rates of illiteracy. Cognitive function was assessed using the Swahili version of the Community Screening Instrument for Dementia (CSI-D). Results: Foremost, our study revealed language-related differences between Swahili spoken in other eastern African countries such as Tanzania and Kenya, where the Swahili CSI-D is readily applied, compared to the Swahili spoken in Bukavu (DRC). Our results also showed that cognitive impairment was present in 18.7% of the total 246 participants. Remarkably, the prevalence rate of cognitive impairment was higher in the non-diabetic group (12.2 versus 25.2%; p=0.009). Participants aged 80 or older were more likely to present with cognitive impairment compared to those aged less than 80 (adjusted odds ratio — aOR=70.27; 95% confidence interval — 95%CI 3.94–125.15; p=0.004). We also found that patients living with DM for more than 20 years were three times more likely to be impaired compared to those who were recently diagnosed with DM (aOR=3.63; 95%CI 1.70–18.81; p=0.026). Conclusion: This study revealed that cognitive impairment was relatively high in Bukavu city. It emphasizes the lack of effective tools to assess cognitive function. This requires, therefore, that research be adapted to the intellect and cultural experiences of the patients.

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Neuropathic diabetic foot ulcers in the elderly: clinical outcomes and healing

There is little evidence on healing outcomes of neuropathic foot ulcers in elderly patients. Aims: To determine the healing rates of neuropathic diabetic foot ulcers at 12 and 24 weeks achieved by standard care provided at an established multidisciplinary diabetes foot clinic in patients aged 65 years and above. Data on the incidence of falls and hypoglycaemia were also collected due to their perceived clinical risk in the group studied. Methods: This was a retrospective observational study looking at clinical outcomes of neuropathic foot ulcers. Patients aged 65 years or more presenting with a non-infected neuropathic ulcer at the time of their initial review were identified and classified into two groups: Group E patients were aged above 80 years and Group Y patients 65-80 years. Results: A total of 97 patients, presenting with 106 ulcer episodes, were identified. Mean HbA1c was 60 mmol/mol in Group Y and 55 mmol/mol in Group E. Healing rates of all ulcers at 12 and 24 weeks in the elderly group lagged behind rates in the younger group (67.6% at 12 weeks and 73% at 24 weeks in Group E vs. 78.2% at both intervals in Group Y). The elderly group had more falls, 11% vs. 2% in Group Y. In all, 50% of the falls in Group E were attributed to their prescribed pressure relief (off-loading) devices. Conclusions: With standard foot care given in a multi- disciplinary foot service, neuropathic diabetic foot ulcers can heal in the elderly despite their age-related skin changes. The rate of healing of neuropathic ulcers noted in our study provides a benchmark for healing outcomes and enables comparison with other age groups and centres. Our study identifies a risk of falls associated with off-loading devices and highlights the need for structured falls risk and mobility assessments in this group.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21–72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, ‘multi-omics analyses’ and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

Real-life use of novel glucose lowering agents after acute myocardial infarction and stable coronary artery disease in patients with diabetes - experience from national use in the SWEDEHEART-registry

Abstract Background Recently Sodium Glucose Lowering Transport 2 receptor inhibitors (SGLT2i) and Glucagon Like Peptide Receptor Agonists (GLP-1 RA) have demonstrated preventive effects in patients with established diabetes and evidence of cardiovascular disease, and is recommended in guidelines regardless of glucose control. Less is known about the real uptake of these therapies and the demographic of patients prescribed these drugs. Purpose To explore trends and real-life use of novel glucose lowering agents in patients with diabetes and coronary artery disease (CAD) and these patients’ prognosis in a national perspective. Methods All patients with diabetes and CAD admitted for coronary angiography in 2010-2021 reported in the Swedish angiography and angioplasty registry (SCAAR) were included. Information on glucose lowering agents dispended within 6 months to the coronary angiography was collected from the Prescribed Drug Registry and grouped into classes. Information on comorbidities and death until December 2021 was collected from the National Patient Registry. Mortality was assessed by Cox proportional survival analysis with novel cardioprotective glucose lowering agents as a reference. Results Of 38 671 patients, mean age was 68.6 years (SD 10.6) and 67.3% (n=26 017) were men. Figure 1 depicts trends in use of glucose lowering classes 2010-2021; use of novel glucose lowering agents increased rapidly from the year 2016 with a continuously high rise (proportion 7% to 47%). This was mainly driven by the use of SGLT2i (from 4% to 38%) and less of GLP-1 RA (4% to 15%). In parallel with this, use of insulin and absence of glucose lowering treatment decreased slightly and use of sulfonylurea decreased dramatically while use of metformin slightly increased. Patients who received the new agents (SGLT2; n=3191 and GLP-1 RA; n=1570), compared to patients on other glucose lowering agents than SGLT2i or GLP-1 RA (n=25 967), were younger (mean age 66 [SD 10] vs. 68 years [SD 10]), more often men (72.8%; n=3465 vs. 67.1%; n=17 427) and with less frequent heart failure (5.0%; n=239 vs. 6.8%; n=1770) and previous myocardial infarction (7.7%; n=367 vs. 10.5%; n=2736). Cumulative event rate is depicted in Figure 2. All-cause death within 1 year occurred in 1.7% (n=79) of patients with SGLT2i and/or GLP-1 RA compared to 4.5% (n=1114) in patients without new cardioprotective agents whose adjusted associated risk for all-cause death was higher, HR 1.22 (95% CI 1.09-1.37). Conclusion The fast uptake of novel cardioprotective glucose lowering agents in patients with diabetes in Sweden is encouraging. However, there is a signal that those agents are more often prescribed to a population with lower cardiovascular risk with an associated better outcome and less often to those at high risk for new events. This may be one explanation for the lower mortality rate seen. An increased awareness is needed to use effective cardioprotective treatment also in a high-risk population.Figure 1.Use of glucose lowering agentsFigure 2.Death by glucose lowering drugs

Does prediabetes diagnosed by hemoglobinA1c or oral glucose tolerance test predict coronary artery disease in patients suspected of chronic coronary syndrome?

Abstract Introduction The presence of prediabetes worsens the prognosis of coronary artery disease, as patients with prediabetes are known to have an almost doubled cardiovascular mortality risk compared to normoglycemic patients. In clinical practice, HemoglobinA1c (HbA1c) has replaced the oral glucose tolerance test (OGTT) in the diagnosis of prediabetes. However, the background for the HbA1c threshold is based on the development of microvascular complications and progression to established diabetes. It remains unclear whether the substitution of OGTT with HbA1c results in an underestimation of prediabetics with a high risk of coronary artery disease, or if HbA1c is associated with macrovascular complications in prediabetic patients. Purpose We aimed to investigate whether HbA1c- or OGTT-diagnosed prediabetes could predict presence and severity of coronary artery disease in patients suspected of chronic coronary syndrome. Methods This was a descriptive cross-sectional study of 702 patients referred to a coronary CT angiography due to suspicion of chronic coronary syndrome. Coronary artery calcification (CAC)-score, presence of plaque and significant stenosis (&amp;gt;50%), and plaque characteristics were evaluated. All patients had a fasting OGTT and blood samples performed. Patients were categorized according to glycemic status by HbA1c and OGTT, and compared to their test-specific range. Results Prediabetes was detected by HbA1c 167 (24%) or OGTT 272 (39%), and an overlap in classification by both tests was seen in 98 (22%) of participants. Both classifications of prediabetes showed increased presence of plaques, significant stenosis, calcified plaques, and correspondingly, a low frequency of a CAC-score=0 compared to their test-specific normal. Additionally, the HbA1c-prediabetics had an increased frequency of a high CAC score &amp;gt;400 compared to normal HbA1c (23% vs. 10%, p&amp;lt;0.0001). In the multiple logistic regression analysis the HbA1c-prediabetics had an odds ratio (OR) of 1.5 for plaque presence (confidence interval (CI) 1.0;2.4) and OR 2.1 for a CAC-score &amp;gt;400 (CI 1.3;3.5). None of the associations for the OGTT-prediabetics were significant in the logistic regression analysis. Receiver operating characteristic curves were applied to the significant logistic associations. The HbA1c-prediabetics had an area under the curve (AUC)=0.77 for plaque presence and AUC=0.81 for CAC-score &amp;gt;400. Conclusion Prediabetes defined by HbA1c can predict presence and severity of coronary artery disease. Although OGTT identified more patients as having prediabetes, their risk of coronary artery disease was not attributable to prediabetes. Thus, our results support the replacement of OGTT with HbA1c in clinical practice.

THU346 Repairing Skeletal Deterioration In Diabetes With Bone Anabolic Therapies

Abstract Disclosure: S. Marino: None. N. Akel: None. S. Li: None. M. Cregor: None. B. Perez: None. G. Troncoso: None. J. Meeks: None. S. Stuart: None. A. Sato: None. I. Nookaew: None. T. Bellido: None. Treatments for skeletal fragility in diabetes are sorely needed as antiresorptive agents, the current standard of care, stop bone loss but do not rebuild bone nor restore the deteriorated bone microarchitecture. Herein, we demonstrate bone restoration in a preclinical model of established diabetes by two bone anabolic pathways: activation of the PTH1 receptor, with equimolar doses of either PTH (1-34) or Abaloparatide/ABL (100/95 µg/kg/day), and neutralization of the osteocyte-derived inhibitor of bone formation sclerostin with romosozumab/Scl-Ab (100mg/kg/w). Type 2 diabetes (T2D) was induced in skeletally mature male C57BL/6J mice by high fat diet combined with streptozotocin; and, after established diabetes, mice were treated for 4 weeks with the bone anabolic agents. At the end of the study, T2D mice exhibited decreased total (−5%), femoral (−7%) and spinal (−11%) BMD vs nondiabetic mice. PTH/ABL restored the bone lost and increased BMD to a similar extent: total 8%, femoral 11% and spinal 9% vs vehicle-treated T2D mice. Scl-Ab also increased BMD at all sites, but the effects were superior: total 24%, femoral 26%, and spinal 40%. T2D mice exhibited low bone formation (BF) and high bone resorption (BR) circulating markers throughout the disease progression. However, at the tissue level BF and BR were suppressed as evidenced by histomorphometric indexes (BFR −70%; Oc.S/BS -34%) and bone transcriptome GO profiles. PTH/ABL increased BF (BFR ∼700% and P1NP 130/244%) as well as BR (Oc.S/BS unchanged/34%; TRAP5b ∼200%) and corrected the diabetic low bone remodeling signature towards high bone remodeling with bone gain. In contrast, Scl-Ab increased formation (BFR 500% and P1NP 50%) but drastically decreased resorption (TRAP5b −190% and Oc.S/BS −500%). T2D mice exhibited damaged bone microarchitecture. The reduced femoral and spinal cancellous bone BV/TV (−22 and −10%) was corrected by ABL (40 and 42%), Scl-Ab (130 and 83%), and PTH only in the spine (43%). Further, femoral and spinal trabecular thickness were increased equally by PTH/ABL (35 and 24%) and also by Scl-Ab (60 and 66%). Moreover, the decreased cortical thickness (−7%) and BA/TA (−5%) at the femoral mid-diaphysis of T2D mice were corrected and further increased by PTH/ABL (10 and 11%) and Scl-Ab (23 and 19%). Yet, whereas PTH reduced marrow area, ABL increased tissue area TA, and Scl-Ab exerted both effects, resulting in advantageous bone distribution by ABL and Scl-Ab leading to increased energy to ultimate load (60 and 90%) and toughness (50 and 82%). Nevertheless, all agents corrected the low stiffness of T2D bone (-19%) and also increased ultimate load. These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease by increasing bone formation and improving bone microarchitecture and show the benefit of simultaneously inhibiting resorption to achieve superior bone gain and strength. Presentation: Thursday, June 15, 2023

SAT121 Challenging Health Disparities In Mental Illness: Addressing Diabetes And Metabolic Disease

Abstract Disclosure: R. Chen: Speaker; Self; Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Eli Lilly &amp; Company. C. Finneran: None. D. Higgins: None. C. Lum: None. J. Allen: None. Introduction: Having a severe mental illness such as schizophrenia confers a substantial increase in the prevalence of diabetes, obesity and premature cardiovascular disease. These health disparities, particularly in diabetes care, have led to a life expectancy in this vulnerable group which is up to 25-30 years less than that of the general population. There are several potential causes for these health disparities. These include poor health literacy, poor recognition by clinicians of the relationship between mental illness and diabetes, the persistent separation of mental and physical health care as well as the adverse metabolic effects of antipsychotics. Despite numerous national and international guidelines, patients frequently have difficulties in accessing appropriate metabolic health care and negotiating health pathways. There is little evidence that these health disparities are being addressed in a systematic way. We sought to challenge the traditional separation of mental and physical health care and to address these health disparities. Aims: To establish an integrated multidisciplinary service to manage metabolic health in this vulnerable population. Methods: A collaborative pilot program between diabetes and mental health units has a clinical team of exercise physiologist, dietitian, endocrinologist, diabetes educator and mental health nurse. A model of care has been developed where all patients assessed by the mental-health unit are routinely screened with a tool which assesses anthropometry (including weight, height, BMI) and biochemistry (including HbA1c. lipids and renal function). Patients are managed in weekly multidisciplinary clinics based in the mental health unit, with defined referral criteria (type 2 diabetes, metabolic syndrome, pre-diabetes, dyslipidaemia, hypertension and weight-gain). Results: From June 2020 to September 2022, we assessed 194 patients with 421 occasions of service. 49 patients (25%) had diabetes, 18 had pre-diabetes and 31 had newly-diagnosed diabetes. 91 had metabolic syndrome, 94 were smokers, 123 had dyslipidaemia and 17 were of first nations background. We have also provided education to mental health staff to upskill knowledge on diabetes. Conclusions: Collaboration between mental health and diabetes clinicians has been essential to coordinate a patient-centred service whereby all patients meeting the referral criteria are assessed. New diagnoses of diabetes would potentially have been missed and patients with established diabetes have been assessed whilst they would not have received any diabetes care without the establishment of this clinic. These diabetes health disparities are particularly startling in light of the benefits of early multifactorial intervention in preventing diabetes related complications. Presentation: Saturday, June 17, 2023

SAT645 Cardiac Autonomic Modulation In Transgender Men Under Gender-affirming Hormone Therapy

Abstract Disclosure: R.M. Allgayer: None. L. Horos Bueno: None. R. Silveira Moraes Filho: None. P. Spritzer: None. Heart hate variability (HRV) spectral indices are associated with age and sex. Men have higher frequency amplitudes, with lower HRV than women, suggesting greater sympathetic activity and, theoretically, greater susceptibility to fatal arrhythmias and development of coronary disease, which may be related to higher testosterone levels in men. Scarce data are available on the sympathovagal balance in transgender men. The objective of the present study was to assess whether heart rate variability (HRV) at rest and during sympathetic stimulation is disturbed in healthy transgender men in comparison to cisgender women. A cross-sectional study was conducted at a university hospital with the evaluation of eleven transgender men under testosterone treatment (for at least 6 months) and eleven age- and BMI-paired cisgender women, by a sample size calculation1. Patients with established cardiovascular disease, hypertension, diabetes, and smoking were excluded. Patients who were using medications other than testosterone that could have an impact on heart hate variability were also excluded. Anthropometric, metabolic, hormonal assessment and analysis of HRV indices (time and frequency domain HRV indices) at rest and after a mental stress test were measured. For HRV analysis, participants underwent a 30-minute electrocardiogram recording with a SEER Light digital. For HRV testing, participants were instructed to abstain from caffeine, stimulants, alcohol, and heavy exercise for 24 hours. In the color-word stress test, the subject is shown the printed names of colors on screens of a different color and is asked to name the color of the screen rather than the word. The median age was 23 [22-26] years in transgender men and 24 [22-26] in cisgender women. Mean BMI was 22.32 (±3) in TM and 21.82 (±2.81) in CW. Systolic blood pressure of transgender group was higher than cisgender group, 113.45 (11.09) versus 101.18 (8.08) mmHg, p&amp;lt;0.008. Other metabolic parameters such as fasting glucose, HOMA-IR, lipids, and diastolic blood pressure did not differ between groups. At rest, no differences in HRV were found between groups. However, during sympathetic stimulation with the mental stress test, transgender men, compared to cisgender women, had a significantly lower increase in normalized low frequency (LF) units (ΔLF= 0.19 ±0.04 vs. ΔLF= 0.35 ±0,05; p=0.025) and LF-to-HF ratio (ΔHF/LF= 1.7 ±0,4 vs. 5.7 ±0,76; p&amp;lt;0,001) in response to the mental stress test, respectively. In conclusion, the present results suggest that transgender men have impaired autonomic modulation in response to sympathetic stimulation when compared to cisgender women. The difference in sympathovagal HRV control after stress testing could reflect the effects of testosterone treatment on cardiac autonomic modulation.1 Resmin E, et al. Sympathovagal imbalance in transsexual subjects. J. Endocrinol. Invest. 2008; 31: 1014-1019. Presentation: Saturday, June 17, 2023

THU354 Enfortumab Vedotin Induced Refractory Hyperglycemia

Abstract Disclosure: M. Hussein: None. Introduction: Immunotherapy has transformed the treatment landscape of cancer therapy and has created promising hope for cancer patients. While immunotherapy has dramatic efficacy it also has unique toxicity profile. A spectrum of adverse events known as endocrinopathies have been reported with immune checkpoint inhibitors. One of the newer medications is Enfortumab Vedotin, an antibody-drug conjugate. This drug is approved for use in advanced urothelial carcinoma. Case: We present a 68-year-old male with advanced urothelial carcinoma who was started on Enfortumab vedotin after he progressed on a different chemotherapy/immunotherapy. His medical history was significant for prediabetes and morbid obesity.2 weeks after the first cycle of treatment he presented to emergency room with worsening dyspnea and fatigue. Vital signs: Temp: 37.3, HR: 90, BP: 122/65, RR 18, SPO2 95% on 3L O2 through nasal canula. BMI 44 kg/m. Biochemical workup revealed elevated Glucose level of 310 and anion gap of 12. He was started on subcutaneous insulin. He continued to be uncontrolled and was transferred to the ICU and switched to intravenous insulin due to hyperglycemia. His total daily insulin dose was close to 900 units to achieve blood glucose &amp;lt;180. It took 48-72 hours of Intravenous insulin use to get controlled blood glucose. Hgba1c was 7.3%. Insulin antibody, GAD65 and Islet cell antibodies were negative, C peptide 38 for a glucose of 428. Unfortunately, the patient developed multiorgan failure, and passed away on day 7 of the admission. Discussion: The mechanism of this drug inducing hyperglycemia is not well understood as of yet. But the presumed theory here is the patient developed severe acute insulin resistance that led to this refractory hyperglycemia, as evident by the high c peptide level. Absence of beta cell antibodies and elevated c peptide go against an autoimmune destructive beta cell pathway. The other theory is that there is a malfunction in the signaling pathway at the cellular level that led to hyperglycemia. Risk of developing hyperglycemia as a side effect to this medication increase with patient’s personal risk factors for developing diabetes mellitus (prediabetes and obesity). In phase 3 trial of Enfortumab vedotinEV301, treatment related hyperglycemia was reported in 6.4 % of patients. Hyperglycemia occurred more frequently in patients with hyperglycemia at baseline or with a body-mass index of 30 or higher. Conclusion: We are in need for further studies to understand the mechanism of refractory hyperglycemia induced by this drug. Patients on this type of therapy should be monitored very closely for developing a new onset of diabetes mellitus or worsening of established diabetes mellitus. Presentation: Thursday, June 15, 2023