Pre-existing Type 2 Diabetes Mellitus Research Articles

Maternal periconception hyperglycemia, preconception diabetes, and risk of major congenital malformations in offspring.

What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated with an increased risk of CHD, including when HbA1c levels were within euglycemic ranges. Maternal preconception diabetes has been linked with MCMs in the offspring. However, evidence concerning associations with specific periconception serum measures of hyperglycemia, and susceptibility of different organ systems, is inconsistent. Moreover, limited evidence exists concerning the effectiveness of antidiabetic medications in mitigating diabetes-related teratogenic risks. A large Israeli birth cohort of 46534 children born in 2001-2020. Maternal HbA1c test results were obtained from 90 days before conception to mid-pregnancy. Maternal diabetes, other cardiometabolic conditions, and MCMs in newborns were ascertained based on clinical diagnoses, medication dispensing records, and laboratory test results using previously validated algorithms. Associations were modeled using generalized additive logistic regression models with thin plate penalized splines. Maternal periconceptional HbA1c value was associated with CHD in newborns, with the risk starting to increase at HbA1c values exceeding 5.6%. The association between HbA1c and CHD was stronger among mothers with type 2 diabetes mellitus (T2DM) compared to the other diabetes groups. Maternal pre-existing T2DM was associated with CHD even after accounting for HbA1C levels and other cardiometabolic comorbidities (odds ratio (OR)=1.89, 95% CI 1.18, 3.03); and the OR was materially unchanged when only mothers with pre-existing T2DM who had high adherence to antidiabetic medications and normal HbA1c levels were considered. The rarity of some specific malformation groups limited the ability to conduct more granular analyses. The use of HbA1c as a time-aggregated measure of glycemic control may miss transient glycemic dysregulation that could be clinically meaningful for teratogenic risks. The observed association between pre-existing diabetes and the risk of malformations within HbA1c levels suggests underlying causal pathways that are partly independent of maternal glucose control. Therefore, treatments for hyperglycemia might not completely mitigate the teratogenic risk associated with maternal preconception diabetes. The work was supported by NIH grants K99ES035433, R01HD097778, and P30ES000002. None of the authors reports competing interests. N/A.

Association of early post-transplant hyperglycaemia and diabetes mellitus on outcomes following heart transplantation.

Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes. Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia. A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes. EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

Sex Differences in 'Life's Essential 8' cardiovascular health and Type 2 Diabetes Mellitus Risk Across Menopause Stages.

The purpose of this paper is to explore sex-based differences in cardiovascular health (CVH) and the incidence of type 2 diabetes mellitus (T2DM) among women at different menopausal stages and men. A prospective cohort study was conducted, involving 126,818 participants without pre-existing T2DM from the UK Biobank. CVH was assessed using the Life's Essential 8. Absolute risks (ARs) and hazard ratios (HRs) were separately employed to assess the association between increased CVH and T2DM risk. The Accelerated Failure Time model assessed the impact of CVH on the time to T2DM onset. Over a mean follow-up of 168 months, 4,315 cases of T2DM were documented. In men, each one-point increase in CVH was associated with a 0.268% decrease in AR and a 6.4% decrease in HR for T2DM. In premenopausal, perimenopausal and postmenopausal women, each unit increase in CVH resulted in a 0.105%, 0.180% and 0.166% decrease in AR and a 7.7%, 5.2% and 6.4% decrease in HR of T2DM. The adjusted median time to T2DM onset was delayed by 12.46, 9.83, 11.5 and 21.43 months in the highest quintile of men, premenopausal, perimenopausal and postmenopausal women, respectively, compared with the lowest CVH quintile. As CVH improved, the reduction in AR for T2DM was more prominent in men than in women. HR trends for CVH and T2DM were similar in men and postmenopausal women. Increased CVH delayed the onset of T2MD in both men and women, with the most significant delay observed in postmenopausal women.

Impact of Breast Cancer on Cardiometabolic Health in Spanish Women ≥50 Years with Pre-Existing Type 2 Diabetes Mellitus.

During breast cancer (BC), cardiometabolic disorders can worsen prognosis, particularly in women with type 2 diabetes mellitus (T2DM). This study aimed to determine the impact of BC diagnosis on cardiometabolic parameters and the incidence of complication in women over 50 years of age (90% aged ≥ 65 years) with pre-existing T2DM. Using primary care registries from Asturias (Spain), a total of 106 women diagnosed with T2DM followed by BC were selected and matched with women with T2DM (n = 212) in a cohort study. Indicators of cardiometabolic health and microvascular complications associated with T2DM were collected. Women were monitored from two years prior to five years after BC diagnosis. Conditional logistic regressions were used to compare the adjusted odds of staying below each indicator's threshold. During follow-up, women with T2DM+BC had a higher risk of fasting blood glucose ≥126 mg/dL (adjusted odds ratio [aOR] = 1.83; 95% confidence interval [CI95%]: 1.01-3.32) and glycosylated hemoglobin (Hb1Ac) ≥ 48 mmol/mol or 6.5% (aOR: 2.44; IC95%: 1.21-4.91). There was no difference between the groups regarding the incidence of microvascular complications. BC incidence negatively impacted the glycemic control of Spanish women with pre-existing T2DM measured by basal blood glucose and HbA1c, but not cardiometabolic health indicators or T2DM complications.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus

ObjectiveTo assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. MethodsA cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. ResultsThe mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8–315.9) vs 158.1 (113.4–201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. ConclusionPatients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Frequency of Type 2 Diabetes Mellitus among Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) have established themselves as significant global health concerns, with a notable co-prevalence that suggests a potential pathophysiological connection. The increasing incidence of T2DM, particularly in developing countries, alongside the significant burden of HCV, poses challenges for healthcare systems and necessitates deeper understanding of their interrelation. Objective: This study aimed to ascertain the frequency of T2DM among patients with HCV infection and to investigate the potential association between HCV reactivity and the incidence of T2DM. Methods: A cross-sectional analysis was conducted at a molecular pathology laboratory in Lahore, Pakistan. Patients aged 18-60 years without cirrhosis or pre-existing T2DM were consecutively enrolled over a six-month period. Exclusion criteria included liver cancer, interferon therapy, end-stage renal disease, other viral hepatitides, and pregnancy. Data were collected via questionnaires after informed consent, with serum and hemoglobin A1c (HbA1c) levels measured. HCV reactivity was confirmed via real-time polymerase chain reaction (RT-PCR), and the frequency of T2DM was assessed by HbA1c criteria. Statistical analysis involved univariate analysis using SPSS version 25.0. Results: Among the 300 HCV-reactive patients, the frequency of T2DM was found to be 49.33% (148 patients). The mean age of participants was 42.71 ± 6.808 years, with 53.0% males and 47.0% females. Urban and rural participants were nearly equally represented. A significant association was noted between HCV reactivity and T2DM (p=0.001), while no significant relationship was found with gender, residence, marital status, or family history of T2DM. Conclusion: The study highlights a substantial frequency of T2DM in HCV-reactive patients and a significant association between HCV infection and the development of T2DM. Regular HbA1c monitoring in HCV-reactive patients is recommended for the early identification and management of T2DM.

Risk Factors for Corneal Endothelial Decompensation after Penetrating Keratoplasty: A Population-Based Cohort Study

(1) Background: Endothelial decompensation is a common complication after penetrating keratopathy (PK), while the risk factors for endothelial decompensation after PK have not been fully elucidated. Consequently, we aim to investigate the possible risk factors for endothelial decompensation after PK. (2) Methods: This retrospective study was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. The main outcome was the development of endothelial decompensation after PK surgery. The effects of potential risk factors were compared between the patients with endothelial decompensation and the patients without endothelial decompensation via Cox proportional hazard regression, which produced the adjusted hazard ratio (aHR) and a 95% confidence interval (CI). (3) Results: Overall, 54 patients developed endothelial decompensation after PK surgery, with a ratio of 16.12 percent. The pre-existing type 2 diabetes mellitus (T2DM) (aHR: 1.924, 95% CI: 1.257–2.533, p = 0.0095) and history of cataract surgery (aHR: 1.687, 95% CI: 1.328–2.440, p = 0.0026) were correlated with the development of endothelial decompensation. In the subgroup analysis, the correlation between a history of cataract surgery and post-PK endothelial decompensation was more prominent in patients older than 60 years compared to their younger counterparts (p = 0.0038). (4) Conclusions: Pre-existing T2DM and a history of cataract surgery are associated with a higher incidence of post-PK endothelial decompensation.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus

ObjectiveTo assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. MethodsA cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. ResultsThe mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8–315.9) vs 158.1 (113.4–201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. ConclusionPatients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Impact of Pre-existing Type 2 Diabetes Mellitus and Cardiovascular Disease on Healthcare Resource Utilization and Costs in Patients With COVID-19.

Background: The economic burden associated with type 2 diabetes mellitus (T2DM) and concurrent cardiovascular disease (CVD) among patients with COVID-19 is unclear. Objective: We compared healthcare resource utilization (HCRU) and costs in patients with COVID-19 and T2DM and CVD (T2DM + CVD), T2DM only, or neither T2DM nor CVD (T2DM/CVD). Methods: A retrospective observational study in COVID-19 patients using data from the Healthcare Integrated Research Database (HIRD®) was conducted. Patients with COVID-19 were identified between March 1, 2020, and May 31, 2021, and followed from first diagnosis or positive lab test to the end of health plan enrollment, end of study period, or death. Patients were assigned one of 3 cohorts: pre-existing T2DM+CVD, T2DM only, or neither T2DM/CVD. Propensity score matching and multivariable analyses were performed to control for differences in baseline characteristics. Study outcomes included all-cause and COVID-19-related HCRU and costs. Results: In all, 321 232 COVID-19 patients were identified (21 651 with T2DM + CVD, 28 184 with T2DM only, and 271 397 with neither T2DM/CVD). After matching, 6967 patients were in each group. Before matching, 46.0% of patients in the T2DM + CVD cohort were hospitalized for any cause, compared with 18.0% in the T2DM-only cohort and 6.3% in the neither T2DM/CVD cohort; the corresponding values after matching were 34.2%, 26.0%, and 21.2%. The proportion of patients with emergency department visits, telehealth visits, or use of skilled nursing facilities was higher in patients with COVID-19 and T2DM + CVD compared with the other cohorts. Average all-cause costs during follow-up were 7882, and $7277 per-patient-per-month after matching for patients with T2DM + CVD, T2DM-only, and neither T2DM/CVD, respectively. COVID-19-related costs contributed to 78%, 75%, and 64% of the overall costs, respectively. The multivariable model showed that per-patient-per-month all-cause costs for T2DM + CVD and T2DM-only were 54% and 21% higher, respectively, than those with neither T2DM/CVD after adjusting for residual confounding. Conclusion: HCRU and costs in patients were incrementally higher with COVID-19 and pre-existing T2DM + CVD compared with those with T2DM-only and neither T2DM/CVD, even after accounting for baseline differences between groups, confirming that pre-existing T2DM + CVD is associated with increased HCRU and costs in COVID-19 patients, highlighting the importance of proactive management.

FRI084 The Impact Of COVID-19 On Comorbid Beliefs And Adherence To Self-Management Behaviors Among Breast Cancer Survivors With Type 2 Diabetes

Abstract Disclosure: S. Lambert: None. J.E. Itty: None. L. Guerra: None. M. Goel: None. J.J. Lin: None. Y.T. Harris: None. Introduction: During the first year of the Covid-19 pandemic, anxiety and depression rates increased substantially worldwide. Anxiety and depression can affect self-efficacy and health-related beliefs as well as diabetes self-management behaviors (DSMBs) such as diet, exercise, and medication adherence, which are crucial for glycemic control and preventing complications. Both Type 2 diabetes mellitus (T2DM) and breast cancer pose an increased risk of complications from Covid, which could exacerbate pandemic-related distress in patients with T2DM and a history of breast cancer. We compared diabetes beliefs and adherence to DSMBs in breast cancer survivors with T2DM, before Covid-19 versus during the first Covid-19 surge. Hypothesis: Patients will experience a change in diabetes beliefs and adherence to DSMBs in the setting of the Covid-19 pandemic. Methods: Eligible patients included women ≥ 55 years, diagnosed with Stage 0-IIIA breast cancer in the past 15 years, who had completed chemotherapy and/or were prescribed hormonal therapy, had pre-existing T2DM treated with ≥ 1 oral medication, and had been enrolled in an ongoing study of disease beliefs and cognition in breast cancer survivors with comorbid T2DM. We included patients with a baseline visit prior to Covid and a six-month follow up visit between March - September 2020. We assessed diabetes beliefs with the Illness Perception Questionnaire (IPQ) and DSMB adherence with the Summary of Diabetes Self Care Activities (SDSCA) questionnaire. Self-reported adherence to diabetes medication was assessed with the Medication Adherence Rating Scale (MARS). Signed rank tests were used to compare disease beliefs and DSMB adherence before versus during the first Covid-19 wave. Results: 26 patients completed baseline interviews prior to Covid and a six-month follow up visit during the first Covid-19 surge (mean age: 65 years; 27% White, 35% Black, 11% Asian/Pacific Islander, 27% unanswered). Diabetes beliefs did not differ significantly before versus during Covid (p > 0.05 for all IPQ scales), nor did adherence to DSMBs including diet (days/week following a healthful eating plan: p = 0.87), exercise (days participating in a specific exercise: p = 0.40), and glucose monitoring (days checking blood sugar the number of times recommended: p = 0.84). No significant differences were seen in medication adherence (p = 0.698). Conclusion: In this small sample of breast cancer survivors with T2DM there appears to be no change in diabetes beliefs or DSMB adherence during the first Covid surge compared to baseline. These findings raise the possibility that individual patient factors play a greater role in adherence and disease beliefs than pandemic-related distress. Future analyses will expand the sample size and explore whether the extent to which the Covid-19 pandemic impacted patients moderates their disease beliefs and self-management. Presentation: Friday, June 16, 2023

Exploring diet-induced promoter hypomethylation and PDK4 overexpression: implications for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by limited metabolic flexibility in the body. Such limitation implicates the pyruvate dehydrogenase kinase 4 (PDK4) gene Poor nutrition, frequently observed among Southeast Asians usually involves excessive intakes of carbohydrates and monosodium glutamate (MSG), that have been frequently linked to an increased risk of T2DM. The 14-week study aimed to assess the effects of high-carbohydrate (HC), high-MSG (HMSG), and a combination of high-carbohydrate and high-MSG (HCHMSG) diets on the development of T2DM using male mice. To assess the effects, the male mice were divided into four groups: control (C), HC, HMSG, and HCHMSG for 14weeks. After 14weeks, both the HC and HCHMSG groups showed signs of T2DM (168.83 ± 32.33; 156.42 ± 32.46). The blood samples from the HMSG, HC, and HCHMSG groups (57.67 ± 2.882; 49.22 ± 7.36; 48.9 ± 6.43) as well as skeletal muscle samples from the HMSG, HC, and HCHMSG groups (57.78 ± 8.54; 42.13 ± 7.25; 37.57 ± 10.42) exhibited a gradual hypomethylation. The HC groups particularly displayed significant PDK4 gene expression in skeletal muscle. A progressive overexpression of the PDK4 gene was observed as well in the HMSG, HCHMSG, and HC groups (2.03 ± 3.097; 3.21 ± 2.94; 5.86 ± 2.54). These findings suggest that T2DM can be induced by high-carbohydrate and high-MSG diets. However, the sole consumption of high MSG did not lead to the development of T2DM. Further research should focus on conducting long-term studies to fully comprehend the impact of a high MSG diet on individuals with pre-existing T2DM.

Differential evolution of diabetic ketoacidosis in adults with pre-existent versus newly diagnosed type 1 and type 2 diabetes mellitus

BackgroundDiabetic ketoacidosis (DKA) was once known to be specific to type-1 diabetes-mellitus (T1D); however, many cases are now seen in patients with type-2 diabetes-mellitus (T2D). Little is known about how this etiology shift affects DKA's outcomes.MethodsWe studied consecutive index DKA admissions from January 2015 to March 2021. Descriptive analyses were performed based on pre-existing T1D and T2D (PT1D and PT2D, respectively) and newly diagnosed T1D and T2D (NT1D and NT2D, respectively).ResultsOf the 922 patients, 480 (52%) had T1D, of which 69% had PT1D and 31% NT1D, whereas 442 (48%) had T2D, of which 60% had PT2D and 40% NT2D. The mean age was highest in PT2D (47.6 ± 13.1 years) and lowest in PT1D (27.3 ± 0.5 years) (P < 0.001). Patients in all groups were predominantly male except in the PT1D group (55% females) (P < 0.001). Most patients were Arabic (76% in PT1D, 51.4% in NT1D, 46.6% in PT2D) except for NT2D, which mainly comprised Asians (53%) (P < 0.001). Patients with NT2D had the longest hospital length of stay (LOS) (6.8 ± 11.3 days) (P < 0.001), longest DKA duration (26.6 ± 21.1 h) (P < 0.001), and more intensive-care unit (ICU) admissions (31.2%) (P < 0.001). Patients with PT1D had the shortest LOS (2.5 ± 3.5 days) (P < 0.001), DKA duration (18.9 ± 4.2 h) (P < 0.001), and lowest ICU admissions (16.6%) (P < 0.001).Conclusions/interpretationWe presented the largest regional data on differences in DKA based on the type and duration of diabetes- mellitus (DM), showing that T2D is becoming an increasing cause of DKA, with worse clinical outcomes (especially newly diagnosed T2D) compared to T1D.

The association between diabetic retinopathy, cognitive impairment, and quality of life – a cross sectional study

BackgroundDiabetic retinopathy (DR), a microangiopathy caused by Type 2 Diabetes Mellitus (T2DM), is associated with significant visual disability leading to suboptimal quality of life. Retinal microvasculature changes can reflect similar changes in the grey matter and blood-brain barrier. Microvascular changes in the brain are associated with cognitive dysfunction. The present study aimed to find the association between Diabetic Retinopathy (DR) and Cognitive Impairment (CI) and its relationship with Quality of Life (QoL). MethodologyA cross-sectional observational study was conducted in a tertiary care hospital among patients (aged 18 years and above) with pre-existing T2DM as per Standards of Care in Diabetes-2023 criteria. Patients with visual acuity less than 3/60, or education below 6th grade, or with comorbid mental or neurocognitive disorders illness were excluded from the study. DR grading was done using the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. Cognitive functions and quality of life were measured using Montreal cognitive assessment (MoCA) and World Health Organization – Quality of Life scale – brief version (WHO-QOL BREF). The primary outcome measures (cognitive impairment and quality of life) were compared between patients with DR (DR+) and patients without DR (DR-). A P < 0.05 was considered statistically significant. ResultsDiabetic retinopathy was diagnosed in 48.5% (83 out of 171) of the sample. The DR+ group were predominantly male, significantly older, had comorbid immature cataract and hypertension than the DR- group. Also, the DR+ group had significantly reduced scores in all domains of MoCA and QoL. among patients with DR, those with severe and moderate NPDR had more cognitive impairment than mild NPDR. Age and duration of diabetes did not correlate with MoCA and QoL scores. ConclusionThe presence of diabetic retinopathy is associated with cognitive impairment and reduced quality of life in this study population. The association is independent of the age of patient and the duration of diabetes mellitus.

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer.

Background Diabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. Methodology We retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results Among 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. Conclusions T2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.

Adolopment of adult diabetes mellitus management guidelines for a Pakistani context: Methodology and challenges.

Pakistan has the highest national prevalence of type 2 diabetes mellitus (T2DM) in the world. Most high-quality T2DM clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local T2DM CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of adult DM in Pakistan. We employed the GRADE-ADOLOPMENT approach utilizing the T2DM CPG of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes - 2021 as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. The source document contained 243 recommendations, 219 of which were adopted without change, 5 with minor changes, and 18 of which were excluded in the newly created Pakistani guidelines. One recommendation was adapted: the recommended age to begin screening all individuals for T2DM/pre-diabetes was lowered from 45 to 30 years, due to the higher prevalence of T2DM in younger Pakistanis. Exclusion of recommendations were primarily due to differences in the healthcare systems of Pakistan and the US, or the unavailability of certain drugs in Pakistan. A CPG for the management of T2DM in Pakistan was created. Our newly developed guideline recommends earlier screening for T2DM in Pakistan, primarily due to the higher prevalence of T2DM amongst younger individuals in Pakistan. Moreover, the systematic methodology used is a significant improvement on pre-existing T2DM CPGs in Pakistan. Once these evidence based CGPs are officially published, their nationwide uptake should be top priority. Our findings also highlight the need for rigorous expanded research exploring the effectiveness of earlier screening for T2DM in Pakistan.

Assessment of Pre-existing Type 2 Diabetes Mellitus Prevalence and Risk Factors Among Colorectal Cancer Patients in King Abdulaziz Medical City, Jeddah.

Diabetes mellitus (DM) and cancer are recognized as non-communicable chronic disorderswhich are among the top ten causes of death globally. In Saudi Arabia, the prevalence of type 2 DM(T2DM) and colorectal cancer (CRC) is alarmingly high. Both T2DM and CRC share common risk factors. In this study, we aim to assess the prevalence of pre-existing T2DM among CRC Saudi patients. In this cross-sectional study, data were collected from the medical records of 275 Saudi adult patients with CRC from 2009 to 2018 at King Abdulaziz Medical City, Jeddah (KAMC-J). Participants had a mean age of 57.0 years, standard deviation (SD) of 13.0, and were mostly males (60.00%) and Saudi (100.0%). Participants had a mean BMI of 26.42 (7.35) kg/m2. The prevalence of pre-existing T2DM in this study was 40.80%. 15.8% of participants were overweight and obese (BMI>30), respectively. The average age of diabetics and non-diabetics was 63.6 (10.64) and 52.73 (12.43), respectively. Diabetic patients are significantly older than non-diabetic patients (p<0.001). The average BMI for diabetics was 26.96 (7.26) kg/m2, whereas the average BMI for non-diabetics was 25.93 (7.48) kg/m2. No significant differences were found between the two groups. This study provides new insight into the high prevalence of pre-existing T2DM in CRC patientsin Saudi Arabia. In particular, the age of diagnosis of CRC in diabetic patients was significantly higher than in non-diabetics.

PSAT231 Perceived Cognitive Function Is Associated With Adherence to Diabetes Self-Management Behaviors Among Breast Cancer Survivors

Abstract Introduction In the United States, the annual incidence of breast cancer and comorbid type 2 diabetes mellitus (T2DM) in women is ∼40,000. Both conditions are associated with cognitive decline, which adversely affects self-management behaviors (SMBs) including adherence to medication, dietary and exercise recommendations. Patients with breast cancer also self-report decreased cognitive ability. Such perceptions can result from objective decline in cognitive function as well as factors such as anxiety and depression. Yet, the effect of perceived cognitive function on diabetes SMBs remains unclear. We evaluated the relationship between perceived cognitive function and adherence to SMBs in breast cancer survivors with T2DM. Hypothesis Greater adherence to diabetes SMBs will be associated with higher perceived cognitive function. Methodology We enrolled women ≥ 55 years with pre-existing T2DM who were diagnosed with Stage 0-IIIA breast cancer in the past 15 years, had completed adjuvant chemotherapy and/or prescribed hormonal therapy, and were taking ≥ 1 oral diabetes medication. We measured perceived cognitive function with the Functional Assessment of Cancer Therapy-Cognition (FACT-Cog, version 3) and diabetes SMBs adherence with the Summary of Diabetes Self Care Activities (SDSCA) questionnaire. Adherence to diabetes medications was assessed using an electronic monitoring bottlecap (eCAP). Data were dichotomized into adherent vs non-adherent. Wilcoxon rank-sum tests were used to compare cognition scores between groups. Results 239 patients (mean age: 66.5 years; 28% Black, 39% white, 6% Asian, 7% other, 20% unanswered) completed interviews. Cancer survivors who were non-adherent with their diabetes medication perceived themselves as having lower cognitive function (Total FACT-Cog median (interquartile range; IQR) 102 (36.7) vs. 115 (30), p&amp;lt; 0.05), with lower scores on the perceived cognitive ability and impact of cognitive impairments on quality of life (QOL) subscales (Cognitive-ability median (IQR) 20 (9) vs. 23 (7), p&amp;lt; 0.001; QOL median (IQR) 13 (6) vs 16 (3), p&amp;lt; 0.05). Similarly, those who reported healthy eating for &amp;lt;5 days over the past week and &amp;lt;5 days/week over the past month had lower cognitive self-perception scores (Total FACT-Cog median (IQR) 106 (37) vs. 114 (25), p&amp;lt; 0.05 and 106 (37) vs. 114 (26), p&amp;lt; 0.001 respectively), and significantly differed on the perceived cognitive impairment and comments from others subscales (Cognitive-impairment median (IQR) 55.1 (26) vs. 62 (17), p&amp;lt; 0.01 and 54.5 (25) vs. 62 (17), p&amp;lt; 0.001; Comments median (IQR) 16 (2) vs. 16 (1), p&amp;lt; 0.05 and 16 (2) vs. 16 (1), p&amp;lt; 0.001). Adherence to exercise and to blood glucose testing were not associated with differences in perceived cognitive function. Conclusion Among breast cancer survivors with T2DM, adherence to diet and medication was associated with greater self-perceptions of cognitive function. Future studies will test whether interventions to improve patients’ perceptions of their cognitive abilities can influence self-care. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Prevalence of Impaired Fasting Glucose and Type 2 Diabetes in Kazakhstan: Findings From Large Study.

Type 2 diabetes mellitus (T2DM) is a serious public health problem. A large proportion of patients with T2DM are unaware of their condition. People with undiagnosed T2DM are at a greater risk of developing complications, whereas prediabetes has an elevated risk of becoming T2DM. The aim of this study is to estimate the prevalence of impaired fasting glucose (IFG), undiagnosed and prior-diagnosed T2DM in Kazakhstan. A cross-sectional study was conducted in four geographically remote regions using the WHO STEP survey instrument. The status of T2DM of 4,753 participants was determined using the WHO diagnostic criteria based on fasting plasma glucose (FPG) level. As a result, the survey-weighted prevalence of IFG was 1.9% (95% CI 1.1%; 3.5%) and of T2DM was 8.0% (95% CI 3.8; 15.9). A total of 54% of T2DM have been newly diagnosed with T2DM. Being 55–64 years old (OR = 2.71, 95% CI 1.12; 6.60) and having lowered HDL-C level (OR = 3.72, 95% CI 1.68; 8.23) were found to be independent predictors for IFG. Being older than 45 years, a female (OR = 0.57, 95% CI 0.39; 0.83), having high waist circumference, was associated with newly diagnosed T2DM. Whereas, the age older than 45 years, high waist circumference, and family history of diabetes (OR = 2.42, 95% CI 1.64; 3.54) were associated with preexisting T2DM. This study shows a high prevalence of IFG and a high proportion of newly diagnosed T2DM in Kazakhstan. A series of risk factors identified in the study may be used to strengthen appropriate identification of IFG or undiagnosed patients in healthcare settings to deliver either preventive or therapeutic interventions aimed to reduce the incidence of T2DM or the delay of their complications. Further longitudinal studies are needed to confirm these associations in our population.

The effects of somatostatin analogues on glycaemia in the treatment of neuroendocrine tumours.

Long-acting somatostatin analogues (SSAs) are the most commonly used drugs in the management of neuroendocrine tumours (NETs) because of their ability to control symptoms and prolong survival. SSA use is associated with changes in glucose metabolism. However, the impacts on glycaemic control and body mass index (BMI) caused by SSAs in NETs are largely unknown. In the present study, we evaluated the effects of SSA treatment on BMI and glycated haemoglobin (HbA1c) in our cohort of patients with NETs. We also assessed changes in glycaemic control and BMI before and after SSA treatment. In addition, we assessed the incidence of new diabetes or whether there was worsening of glycaemic control for patients with pre-existing diabetes. The study comprised a retrospective study of 279 patients with NETs who were treated with SSAs between January 2014 and January 2019. Glycaemic control was assessed by measuring changes in Hba1c. A number needed to harm analysis was used to look at new cases of diabetes within the study population. Treatment with SSAs was associated with a mean increase in HbA1c of 3.35±6.30mmolmol-1 despite a mean decrease in BMI of -1.04±2.79kgm-2 . There were 19 new cases of type 2 diabetes mellitus (T2DM) in the population of 209 with a number needed to harm of 12.5. Of the 34 patients with pre-existing T2DM, five had worsening of their mean HbA1c. Treatment with SSAs for NETs is associated with an increase in HbA1c, despite a reduction in BMI and, importantly, a risk of developing T2DM with a number needed to harm of 12.5. This project was registered with the National Health Service Clinical Audit and Registries. It has a CARMS number - 17666.

Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis.

Simple SummaryFemale breast cancer continues to be the leading cause of cancer deaths worldwide, and type 2 diabetes mellitus (T2DM) is one of the contributors to the poor prognosis of breast cancer. This raises the issue that T2DM might be associated with aggressive clinicopathological characteristics, which indicate pivotal prognostic values. This study aimed to clarify the differences in breast cancer characteristics at diagnosis between patients with and without pre-existing T2DM. Our meta-analyses showed an increased risk of being diagnosed with a late-stage tumor, large tumor size, and invasive lymph nodes in patients with T2DM. No significant results were observed for grade, estrogen/progesterone receptor, and human epidermal growth factor receptor. These findings indicate an association between T2DM and advanced breast cancer at diagnosis, and suggest that the more active role of breast cancer screening should be further explored for women with T2DM.Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by using a random effects model. T2DM was significantly associated with tumor stages III/IV versus cancers in situ and stages I/II (pooled ORs (pOR), 95% CI: 1.19; 1.04–1.36, p = 0.012), tumor size >20 versus ≤20 mm (pOR, 95% CI: 1.18; 1.04–1.35, p = 0.013), and lymph node invasion versus no involvement (pOR, 95% CI: 1.26; 1.05–1.51, p = 0.013). These findings suggest that women with T2DM are at a higher risk of late-stage tumors, large tumor sizes, and invasive lymph nodes at breast cancer diagnosis.