Palliative care in a Graduate Entry Medical Curriculum: exploring students' attitudes on the importance of receiving teaching in palliative care.

BACKGROUND: As people live longer with life-limiting illnesses, there is greater need for skills and knowledge in palliative care (PC). Medical students should acquire the knowledge, attitudes, and confidence during training for future decision-making. However, most graduates across Europe feel unprepared to provide PC. To develop PC training for medical students, we must gain perspective on their understanding of PC and their learning needs. OBJECTIVES: The aim was to investigate graduate entry medical students' views on the importance of education in PC and how well PC topics were covered within their curriculum. The objective was to highlight areas that could be reviewed for future PC curricula. METHODS: In this prospective quantitative study, penultimate and final-year students were recruited from a graduate entry medical school. Ethical approval was granted. Students completed an online questionnaire. RESULTS: From 281 recruited students, 82 responded. Ninety-five percent of respondents felt everyone should have a PC rotation. The aspects of education perceived to be most important were knowledge of symptom control, communication, ethical issues, self-care, and grief. The only aspect considered well covered within the curriculum was ethical issues. Ninety-six percent of penultimate and 75% of final years wanted more teaching in PC. CONCLUSION: Graduate entry medical students view PC as a vital subject within their medical school training. The study highlights challenges in providing education and sufficient placement in PC to correlate with the respondents' perceived needs. The findings contribute to the growing literature surrounding the importance of PC education within the medical school curriculum.

Post-Civil War modernity and the nurse training movement: The "Experiment" of the Boston Training School for Nurses.

BACKGROUND/PURPOSE: This paper describes the origins of the Boston Training School for Nurses (1873), later named the Massachusetts General Hospital School of Nursing, and the role played by a Boston civic group, the Woman's Education Association, in its founding. METHODS: Social and political forces in the post-Civil War modern era and the challenges the founders encountered in establishing and managing a nursing school are delineated. DISCUSSION: Themes that highlight the significance of the Boston Training School's creation relative to the nurse training movement in America are identified. CONCLUSION: The long-term implications of the initial agreement for a 1-year experiment to train nurses in a formal educational setting are discussed.

GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study.

Context: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels. Context: In this study, we aimed to better characterize islet autoantibodies in this T2D cohort. This is an ancillary study to NCT01794143. Methods: We stringently defined GAD65Ab positivity with a competition assay, analyzed GAD65Ab-specific epitopes, and measured GAD65Ab-specific anti-Id in serum. Results: Competition assays confirmed that 5.9% of the patients were GAD65Ab positive, but beta-cell function was not associated with GAD65Ab positivity, GAD65Ab epitope specificity or GAD65Ab-specific anti-Id. GAD65-related autoantibody responses in GRADE T2D patients resemble profiles in healthy individuals (low GAD65Ab titers, presence of a single autoantibody, lack of a distinct epitope pattern, and presence of anti-Id to diabetes-associated GAD65Ab). In this T2D cohort, GAD65Ab positivity is likely unrelated to the pathogenesis of beta-cell dysfunction. Conclusion: Evidence for islet autoimmunity in the pathophysiology of T2D beta-cell dysfunction is growing, but T1D-associated autoantibodies may not accurately reflect the nature of their autoimmune process.

The Use of Rescue Insulin in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: To describe rescue insulin use and associated factors in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS: GRADE participants (type 2 diabetes duration <10 years, baseline A1C 6.8%-8.5% on metformin monotherapy, N = 5,047) were randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin and followed quarterly for a mean of 5 years. Rescue insulin (glargine or aspart) was to be started within 6 weeks of A1C >7.5%, confirmed. Reasons for delaying rescue insulin were reported by staff-completed survey. RESULTS: Nearly one-half of GRADE participants (N = 2,387 [47.3%]) met the threshold for rescue insulin. Among participants assigned to glimepiride, liraglutide, or sitagliptin, rescue glargine was added by 69% (39% within 6 weeks). Rescue aspart was added by 44% of glargine-assigned participants (19% within 6 weeks) and by 30% of non-glargine-assigned participants (14% within 6 weeks). Higher A1C values were associated with adding rescue insulin. Intention to change health behaviors (diet/lifestyle, adherence to current treatment) and not wanting to take insulin were among the most common reasons reported for not adding rescue insulin within 6 weeks. CONCLUSIONS: Proportionately, rescue glargine, when required, was more often used than rescue aspart, and higher A1C values were associated with greater rescue insulin use. Wanting to use noninsulin strategies to improve glycemia was commonly reported, although multiple factors likely contributed to not using rescue insulin. These findings highlight the persistent challenge of intensifying type 2 diabetes treatment with insulin, even in a clinical trial.

BMI, insulin sensitivity, and cognition in early type 2 diabetes: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study.

OBJECTIVE: This study explored the association of BMI and insulin sensitivity with cognitive performance in type 2 diabetes. METHODS: A cross-sectional analysis of data from the baseline assessment of the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE) was conducted. BMI was used as a surrogate of adiposity and the Matsuda index as the measure of insulin sensitivity. Cognitive tests included the Spanish English Verbal Learning Test, the Digit Symbol Substitution Test, and the letter and animal fluency tests. RESULTS: Cognitive assessments were completed by 5018 (99.4%) of 5047 participants aged 56.7 ± 10.0 years, of whom 36.4% were female. Higher BMI and lower insulin sensitivity were related to better performance on memory and verbal fluency tests. In models including BMI and insulin sensitivity simultaneously, only higher BMI was related to better cognitive performance. CONCLUSIONS: In this study, higher BMI and lower insulin sensitivity in type 2 diabetes were cross-sectionally associated with better cognitive performance. However, only higher BMI was related to cognitive performance when both BMI and insulin sensitivity were considered simultaneously. The causality and mechanisms for this association need to be determined in future studies.

Transitions for older people with intellectual disabilities and behaviours that challenge others: A rapid scoping review.

BACKGROUND: People with intellectual disabilities and behaviours that challenge others are living longer. This review aimed to explore what is known about the health and social care needs, experiences, service interventions and resources of and for this population as they transition to different care contexts in the UK. METHOD: A rapid scoping review of published and unpublished literature was conducted based on collaborative working with key stakeholders and using systematic methods of data searching, extraction and analysis. RESULTS: Consistent social work support, skilled staff, suitable accommodation, creative engagement with individuals and families to plan ahead, and timely access to quality healthcare are all required to promote successful transitions as people age, and to avoid unwanted/inappropriate transitions at points of crisis. CONCLUSIONS: More research is needed to assess the types of services that this population can and do access as they age, the quality of those services, and the extent to which local commissioners are planning ahead for people with intellectual disabilities and behaviours that challenge others.

Palliative care services for children with life-limiting conditions.

BACKGROUND: Palliative care (PC) for children with life-limiting conditions (LLC) is a holistic approach to achieve the best quality of life. AIMS: Highlighting collaboration between pediatric and PC services is essential in providing seamless care. METHODS: Retrospective data obtained including patient cohort, disease profile, place of death, and the resource requirements for children with a LLC in the Mid-West region of Ireland over a 7-year period. RESULTS: Seventy-seven patients were identified (n = 77); five still receiving care, four discharged, and 68 have died. The cohort ranged in age from 1 day to 17 years with a mean of approximately 6 years. Thirty-five percent of patients were less than 1 year old. Fifty-one percent were male. Seventy-one percent were referred initially to PC for end-of-life care and 29% for symptom management. Forty-four percent had home support services in place prior to referral to PC. An advanced care plan was created for 65%. Of those that died (n = 68), 70.5% died at home, 25% in hospital, and 4.4% in residential care or a children's hospice. The clinical nurse coordinator for children with life-limiting conditions (CNCCLLC) was involved with 88% of patients. The specialist PC teams were involved with 87%; 65 patients had community support, 31 patients had in-hospital support, and 29 patients were seen by both hospital and community services. CONCLUSIONS: Our study highlights the growing number of LLCs and current pediatric and PC services require further resources and development.

Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.

Importance: The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. Objective: To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Design, Setting, and Participants: This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. Exposure: During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. Main Outcomes and Measures: Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. Results: A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; ß = -0.43 [SE, 0.16]; P = .006), waist circumference (ß = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: ß = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: ß = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (ß = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (ß = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (ß = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). Conclusions and Relevance: These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.

Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.

BACKGROUND: Data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to microvascular and cardiovascular disease outcomes in persons with type 2 diabetes. METHODS: We assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with type 2 diabetes. The randomly assigned therapies were insulin glargine U-100 (hereafter, glargine), glimepiride, liraglutide, and sitagliptin. Prespecified secondary outcomes with respect to microvascular and cardiovascular disease included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area, diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, cardiovascular events (major adverse cardiovascular events [MACE], hospitalization for heart failure, or an aggregate outcome of any cardiovascular event), and death. Hazard ratios are presented with 95% confidence limits that are not adjusted for multiple comparisons. RESULTS: During a mean 5.0 years of follow-up in 5047 participants, there were no material differences among the interventions with respect to the development of hypertension or dyslipidemia or with respect to microvascular outcomes; the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9, and of diabetic peripheral neuropathy 16.7. The treatment groups did not differ with respect to MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3), or all deaths (0.6). There were small differences with respect to rates of any cardiovascular disease, with 1.9, 1.9, 1.4, and 2.0 in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively. When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group. CONCLUSIONS: In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups. The findings indicated possible differences among the groups in the incidence of any cardiovascular disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes.

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain. METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%. RESULTS: A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P<0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups. CONCLUSIONS: All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

Development and evaluation of a clinical research nursing module for undergraduate nursing schools: expanding Clinical Research Nurses' outreach.

Background: Clinical Research Nurses (CRNs) care for study participants and manage clinical research studies; yet the CRN practice role is rarely covered in undergraduate nursing curricula in the United States. Despite a burgeoning need for CRNs, the pipeline of clinical research nurse positions remains sparse. The International Association of Clinical Research Nurses's (IACRN) strategic goal to "engage with nursing schools to heighten awareness and inclusion of the CRN role competencies in nursing education" prompted the development of an educational lecture module to be disseminated to nursing schools. This project is a pilot launch of the module. Methods: A task force of IACRN was formed to develop educational materials that could be used as outreach to undergraduate nursing schools. The content included a slide presentation covering an overview of clinical research, the CRN practice, three embedded videos showing CRN and study participant perspectives, and coverage of the care of participants of research by staff nurses. Due to COVID-19 we revised our live lecture approach using either a live synchronous webinar presentation, or an embedded asynchronous course module with YouTube videos for course learning management systems. We presented the content to 408 nursing students attending three academic programs. To evaluate effectiveness and satisfaction, an anonymous, post-presentation survey using web-based QualtricsXM was distributed to students. Results: Content and delivery of the module was positively evaluated. There was an improvement in knowledge in each topic. Evaluation responses showed that the content could likely or very likely improve care for their patients (87.4%) and improve patient education for patients in clinical trials (95%). Conclusions: Delivering a synchronous or asynchronous module about the CRN practice role to nursing students in academic nursing programs is valuable to increasing awareness of the care of patients in clinical trials, the CRN role, and future professional development.

Promoting a gender-affirming environment in research: implications for research nurses.

Background: Approximately 25 million people around the world identify as transgender, and the numbers are growing. While visibility of transgender communities has increased, significant healthcare disparities remain. Transgender individuals report being less inclined to share their sex assigned at birth due to fear of stigmatization and mistrust of the medical community. The mistrust and inequity experienced by transgender individuals are not limited to clinical care and may extend to clinical research as well. Aim and method: The aim of this paper is to start a conversation about barriers to participating in research and the role of research staff, specifically the Clinical Research Nurse, in promoting engagement of transgender individuals in clinical research trials. Discussion and conclusions: A discussion of safety considerations, data integrity, and implications for data management is included. Because disparities may result in large part from lack of education and knowledge on best practices for providing care for this population, recommendations for fostering a culture of competence and gender-affirming care among research professionals featuring the role of the research nurse will be discussed.

Islet Autoimmunity is Highly Prevalent and Associated With Diminished ß-Cell Function in Patients With Type 2 Diabetes in the Grade Study.

Islet autoimmunity may contribute to ß-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone. We measured T cell autoreactivity against islet proteins, islet autoantibodies against GAD65, IA2, ZnT8, and ß-cell function. Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. ß-cell function calculated as iAUC-CG and ΔC-peptide(0- 30)/Δglucose(0-30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ΔC-peptide(0-30)/Δglucose(0-30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients. We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished ß-cell function and worse glycemic control.

Continuous Glucose Monitoring and HbA1c in Cystic Fibrosis: Clinical Correlations and Implications for CFRD Diagnosis.

CONTEXT: The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear. OBJECTIVE: We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis-related diabetes (CFRD) from normal and abnormal glucose tolerance. METHODS: This prospective observational study included 77 adults with CF who had CGM and HbA1c measured at 2 to 3 time points 3 months apart. RESULTS: Thirty-one of the 77 participants met American Diabetes Association-recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R2 = 0.71, P < 0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time > 140 mg/dL and 3.4% time > 180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, SD, % time > 140, > 180, and > 250 mg/dL than for HbA1c. CONCLUSION: CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.

Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS: Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST). RESULTS: Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition. CONCLUSIONS: In people with type 2 diabetes of a mean duration of <5 years, lower LDL and statin use were related to modestly better executive cognitive function. SBP levels in the range of 120-139 mmHg and DBP levels in the range of 80-89 mmHg, but not lower levels, were related to modestly better executive function. These differences may not be clinically significant.

Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study cohort.

AIMS: The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry. METHODS: Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications. RESULTS: We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean known T2D duration 4 years (all < 10 years); mean HbA1c 8.0% (∼64 mmol/mol) at screening]. Urinary albumin/creatinine ratio (ACR) ≥ 30 mg/gram was present in 15.9% participants; peripheral neuropathy (by Michigan Neuropathy Screening Instrument) in 21.5%; cardiovascular autonomic neuropathy by electrocardiography-derived indices in 9.7%; self-reported retinopathy in 1.0%. Myocardial infarction ascertained by self-report or electrocardiogram was present in 7.3%, and self-reported history of stroke in 2.0%. CONCLUSIONS: In the GRADE cohort with < 10 years of T2D and a mean HbA1c of 8.0%, diabetes complications were present in a substantial fraction of participants, more so than might otherwise have been expected.

Rationale and Design for a GRADE Substudy of Continuous Glucose Monitoring.

Background: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study has enrolled a racially and ethnically diverse population with type 2 diabetes, performed extensive phenotyping, and randomly assigned the participants to one of four second-line diabetes medications. The continuous glucose monitoring (CGM) substudy has been added to determine whether there are racial/ethnic differences in the relationship between average glucose (AG) and hemoglobin A1c (HbA1c). CGM will also be used to compare time in target range, glucose variability, and the frequency and duration of hypoglycemia across study groups. Methods: The observational CGM substudy will enroll up to 1800 of the 5047 GRADE study participants from the four treatment groups, including as many as 450 participants from each of 4 racial/ethnic minority groups to be compared: Hispanic White, non-Hispanic White, non-Hispanic African American, and non-Hispanic Other. CGM will be performed for 2 weeks in proximity to a GRADE annual visit, during which an oral glucose tolerance test will be performed and HbA1c and glycated albumin measured. Indicators of interindividual variation in red blood cell turnover, based on specialized erythrocyte measurements, will also be measured to explore the potential causes of interindividual HbA1c variations. Conclusions: The GRADE CGM substudy will provide new insights into whether differences exist in the relationship between HbA1c and AG among different racial/ethnic groups and whether glycemic profiles differ among frequently used diabetes medications and their potential clinical implications. Understanding such differences is important for clinical care and adjustment of diabetes medications in patients of different races or ethnicities.