Use Of Glucose-lowering Agents Research Articles

Diabetic Nephropathy: Pathogenesis and Drug Delivery System

Diabetic nephropathy is the leading cause of chronic kidney disease. The pathogenesis of diabetic nephropathy consists of four main pathways that indicate intracellular metabolic abnormalities identified in diabetic nephropathy, namely the activation of polyol and protein kinase C pathways, formation of advanced glycation end products, increased oxidative stress, and intraglomerular hypertension. Conventional treatment approaches for diabetic nephropathy that have been through clinical trials are, among others, the use of glucose-lowering agents, reduction of blood pressure, reduction of capillary permeability, and antioxidants. Although such treatments have been proven to slow the severity of diabetic nephropathy which leads to chronic kidney failure, their effectiveness does not cure diabetic nephropathy in patients. Thus, the modification of drug delivery systems and the widely-performed gene therapy need to be reviewed for their effectiveness with the previous treatments of diabetic nephropathy. This review article discusses the perspective of implementing the most effective diabetic nephropathy treatment system in order to achieve the therapeutic goals of diabetic nephropathy. The modification of drug delivery system and the gene therapies are expected to be able to increase the effectiveness of the drugs and guarantee their safety. The characteristics of the therapeutic targets in each kidney cell need to be understood more deeply so that the therapeutic goals can be achieved. It is hoped that the testing in the clinical phase of diabetic nephropathy by modifications of the drug delivery system and gene-based therapies will be widely carried out in the future.

Stroke Prevention by Antihyperglycemic Drugs in Type 2 Diabetes Mellitus

ObjectivesThe American Heart Association/American Stroke Association and the American Association of Clinical Endocrinology provided guidelines for patients with transient ischemic attacks or strokes (TIA/stroke) and diabetes mellitus with the use of glucose-lowering agents (GLA) effective in preventing major adverse cardiovascular events (MACE). This review evaluated GLA for specific differences in TIA/stroke prevention. MethodsPrevious reviews and meta-analyses were evaluated for outcomes of MACE, cardiovascular death (CVD), hospitalization for heart failure, and TIA/stroke. The GLA were glucagon-like peptide 1-receptor agonists (GLP-1RA, 6-trials, n = 46 541), sodium-glucose transport 2 inhibitors (SGLT2i, 5-trials, n = 46 959), insulin-providing regimens (IP, 4-trials, n = 26 223), and thiazolidinediones (TZD, 1-trial, n = 5238). ResultsThere were reductions in MACE for each class. Relative risk (rr) reductions for TIA/stroke were found with GLP-1RA (rr = 0.840, 95% CI: 0.759, 0.936, P =.001) but not with SGLT2i, IP, or TZD. Cardiovascular deaths were decreased with GLP-1RA (rr = 0.873, CI: 0.804, 0.947, P =.001) and SGLT2i (rr = 0.835, CI: 0.706, 0.987, P =.034), but not with TZD or IP. Hospitalizations for heart failure were decreased only with SGLT2i (rr = 0.699, CI: 0.626, 0.781, P <.001). Increased CVD correlated with aggressive lowering of A1c (r = −0.611, P =.012) and showed a trend with the relative risk of hypoglycemia (r = 0.447, P =.08). For GLP-1RA, there was no increase in hypoglycemia and a direct correlation with a decreased rr for stroke with decreases in A1c (r = 0.917, P =.010). ConclusionImprovements in A1c with GLP-1RA were associated with stroke prevention in patients with diabetes and with TIA or stroke. Reductions in cardiovascular mortality include therapy with GLP-1RA and SGLT2i. Aggressive lowering of A1c, however, was associated with increased CVD.

Use of diabetes medications in adults with T2D and CVD in Japan: secondary analysis of the CAPTURE study.

The CAPTURE study estimated the global prevalence of established cardiovascular disease (CVD) and characterized the usage of glucose-lowering agents (GLAs) in adults with type2 diabetes (T2D) across 13 countries. The purpose of this secondary analysis of data from the Japanese sites within CAPTURE (NCT03786406, NCT03811288) was to provide data about medication usage stratified by CVD status among Japanese participants with T2D. Data on GLA usage (including those with proven cardiovascular [CV] benefits) in Japanese participants with T2D managed in clinics or hospitals were collected and stratified by CVD subgroups. There were 800 Japanese participants in the CAPTURE study (n = 502 [no CVD group], n = 298 [CVD group], n = 268 [atherosclerotic CVD subgroup]). Oral antidiabetic agents and insulin were used by 88.5% and 23.4%, respectively, of participants overall. Among participants with established CVD, dipeptidyl peptidase-4 inhibitors (65.1%) were most frequently used, followed by biguanides (50.7%) and insulins (26.2%). The pattern was similar among participants with atherosclerotic CVD. A lower proportion of participants in the CVD group used glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) with proven CV benefits versus the no CVD group (GLP-1RAs: 7.0% vs. 8.6%; SGLT-2is: 13.4% vs. 19.1%). This analysis of the CAPTURE study provided a comprehensive overview of prescription patterns for the treatment of T2D in Japan. Use of GLAs with proven CV benefit was low, even in participants with established CVD, which was comparable to the findings from the global cohort. The online version contains supplementary material available at 10.1007/s13340-023-00638-w.

Trends in glycemic, blood pressure, and lipid control in adults with diabetes in Switzerland

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation, GlaxoSmithKline, Faculty of Biology and Medicine of Lausanne. Introduction Good glycemic, blood pressure and lipid control in adults with diabetes reduces complications and improves health outcomes, particularly when achieved simultaneously. Therefore, regular monitoring and successfully achieving control targets are essential in diabetes management. Purpose To assess the 15-year trends in the level of glycemic, blood pressure and cholesterol control in adults with diabetes in Switzerland. Methods Data from a population-based cohort study of 6,733 adults aged 35-75 years in Switzerland was analyzed. Baseline recruitment in 2003-2006 was followed by three subsequent follow-ups between 2009-2012, 2014-2017 and 2018-2021. In adults with diabetes, glycemic control was defined as fasting plasma glucose &amp;lt;7 mmol/L, blood pressure control as systolic and diastolic pressures of &amp;lt;140/90 mmHg, and non-HDL cholesterol control &amp;lt;3.4 mmol/L. Results Rates of glycemic control improved from 23.2% (95% CI, 19.5-27.3) in 2003-2006 to 32.8% (95% CI, 28.1-37.8) in 2018-2021. Blood pressure control also improved, from 51.5% at baseline (95% CI, 46.8-56.2) to 63.3% (95% CI, 58.2-68.1) 15 years later. The largest improvement was in non-HDL cholesterol control, from 29.1% (95% CI, 25.1-33.6) in 2003-2006 to 56.3% (95% CI, 51.1-61.4) in 2018-2021. Overall, simultaneous control of all three improved from 5.5% (95% CI, 3.7-8.1) at baseline to 17.2% (95% CI, 13.7-21.5) 15 years later. Improvements in risk factor control was accompanied by increases in the use of glucose-lowering agents, blood pressure-lowering medication and statins. Men were less likely to achieve blood pressure control but were more likely to achieve non-HDL cholesterol control. Caucasians were less likely to achieve simultaneous control than non-Caucasians. Conclusion Risk factor control in Swiss diabetes patients has improved in the last 15 years.

Trends in glycemic, blood pressure, and lipid control in adults with diabetes in Switzerland: the CoLaus|PsyCoLaus Study

AimTo assess the 15-year trends in the level of glycemic, blood pressure, and cholesterol control in adults with diabetes in a Swiss population-based cohort.Research design and methodsCoLaus|PsyCoLaus is a prospective...

Prediabetes, diabetes and loss of disability-free survival in a community-based older cohort: a post-hoc analysis of the ASPirin in Reducing Events in the Elderly trial

Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. To evaluate disability-free survival (DFS) in older individuals by glycaemic status. This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] < 5.6mmol/l, 64%), prediabetes (FPG 5.6 to <7.0mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three individual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21-1.60), all-cause mortality (1.45, 1.23-1.72), persistent physical disability (1.73, 1.35-2.22), CIND (1.22, 1.08-1.38), MACE (1.30, 1.04-1.63) and cardiovascular events (1.25, 1.02-1.54) but not dementia (1.13, 0.87-1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93-1.12) or other outcomes. Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.

Adjusting the Use of Glucose-Lowering Agents in the Real-World Clinical Management of People with Type 2 Diabetes: A Narrative Review

Despite the availability of new treatment classes, glycaemic control in patients with diabetes remains suboptimal globally. The latter is associated with high risk of premature mortality related to diabetes and its microvascular and macrovascular complications. Practice guidelines typically focus on glycated haemoglobin < 7.0% as a therapeutic goal in type2 diabetes (T2D). Reducing glycated haemoglobin has been proven to reduce the risk of these complications while early attainment of glycaemic goal can have a legacy effect in later life. Both glucocentric and cardiorenal-centric treatment strategies have complementary effects in reducing the trajectory of cardiorenal diseases. In real-word settings, implementation of practice guidelines developed in the USA and Europe may not be applicable to regions such as Asia, where differences in epidemiology, patient phenotypes, cultures, resource availability, and treatment affordability are important considerations. In the present review, we discuss the need to use a pragmatic, albeit evidence-based approach, to combine glucocentric and cardiorenal risk reduction strategies to improve the outcomes in patients with T2D, with particular relevance to Asia Pacific.

Variations in Use of Diabetes Drugs With Cardiovascular Benefits Among Medicaid Patients

Cardiovascular death remains the leading cause of mortality in patients with type 2 diabetes (T2D). A better understanding of the current use and adoption of glucose-lowering drugs with cardiovascular benefit can inform state policies to ensure their appropriate use in patients with T2D. To characterize the use of glucose-lowering agents with known cardiovascular benefit over time and across states. This cross-sectional pharmacoepidemiological study of Medicaid prescription rates of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit was conducted between 2014 and 2019. In 50 states and the District of Columbia, the study focused on nonmetformin, noninsulin glucose-lowering drugs divided into 3 cohorts: (1) sodium-glucose cotransporter 2 (SGLT2) inhibitors, (2) glucagon-like peptide 1 (GLP1) receptor agonists, and (3) all other classes of glucose-lowering drugs. Data were analyzed from January 2014 to December 2019. Number of days supplied of each cohort, use ratios between the aggregated days supplied of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit, and the mean change in use ratios per quarter. Across the 50 states and the District of Columbia, the use ratio of glucose-lowering agents with known cardiovascular benefit ranged from 1.58 to 0.14 (mean [SD], 0.48 [0.27]) in 2019. A lower use ratio was seen in states with a higher prevalence of diabetes (β = -0.049; 95% CI, -0.086 to -0.012; P = .01), a larger total population (β = -0.013; 95% CI, -0.023 to -0.003; P = .01), a greater number of Medicaid enrollees (β = -0.054; 95% CI, -0.096 to -0.014; P = .01), a greater proportion of people enrolled in Medicaid (β = -0.018; 95% CI, -0.030 to -0.007; P = .002), and a greater proportion of Medicaid patients enrolled in managed care organizations (β = -0.0032; 95% CI, -0.0051 to -0.0013; P = .002). Higher Medicaid expenditures per enrollee (β = 0.047; 95% CI, 0.007 to 0.089; P = .03) were associated with a higher use ratio of these agents. The relative use of glucose-lowering agents with known cardiovascular benefit by Medicaid enrollees increased 7.4% per year from 2014 to 2019, with wide variations across state Medicaid programs. In this cross-sectional study, glucose-lowering agents with cardiovascular benefit increased in use during the study period, but also demonstrated considerable variation among states in their relative use. Medicaid programs should try to clarify which factors may be contributing to relative underuse of these potentially life-saving drugs.

RF28 | PSUN185 The effects of diabetes and glycemic control on cancer outcomes in individuals with metastatic breast cancer

Abstract Background While a well-established relationship between diabetes and breast cancer exists, it remains unclear how diabetes impacts breast cancer outcomes. This study aims to determine the impact/association of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer. Methods Patients with metastatic breast cancer between 2010-2021 were identified using the metastatic breast cancer database at a single academic center. The Research Patient Data Registry, a data warehouse of all patients receiving care in the hospital network was then used to determine the diabetes status of each participant. A participant was categorized as having diabetes if they fulfilled pre-specified criteria (international classification of diseases (ICD) 9 or 10 code for diabetes, or a hemaglobin A1c ≥6.5%, or a random blood glucose (RBG) ≥200 mg/dL and documented use of glucose-lowering agents), while controls were defined as individuals who did not fulfill the previous criteria. We evaluated the effects of diabetes on 1) overall survival (OS) and 2) the interval from initiation of first-line metastatic therapy to initiation of a second-line regimen due to documented progression of disease (a surrogate measure of progression-free survival). The impact of glycemic control on OS and duration of first-line therapy was also assessed. Results We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes, who were matched for age, gender, ethnicity and hormone-receptor (HR) status. OS at 5 years (diabetes: 54%, CI; 47-62% vs. controls: 56%, CI; 49-63%, p=0.65) and freedom from initiating a second-line regimen at 2 years (diabetes: 43%, CI; 36-50% vs. controls: 44%, CI; 36-51%, p=0.33) were not statistically different between groups. However, in an 8-year landmark subgroup analysis, OS was better amongst controls than those with diabetes (diabetes [n=27]: 67%, CI; 48-86% vs. Controls [n=28]: 87%, CI; 73-100%, p=0.047at 10 years). Poor glycemic control (median RBG &amp;gt;180 mg/dL or median HbA1c &amp;gt;7%) was not associated with increased mortality at 5 years but was associated with a trend towards worse freedom from initiating a second-line regimen at 2 years when compared to good glycemic control. In a sub-group analysis based on HR status, there were no differences in OS at 5 years, or freedom from initiating a second-line regimen at 2 years between the two glycemic groups (≤180 mg/dL vs &amp;gt;180 mg/dL on two or more occasions in a month) for any of the HR subgroups. Conclusions These data provide some reassurance that hyperglycemia may not be a major contributor to overall mortality in the first 5 years, in most individuals with metastatic breast cancer. However, amongst longer-term survivors, diabetes was associated with worse survival, suggesting that individualized diabetes and glycemic goals should, therefore, be considered in patients with metastatic breast cancer. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.

Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus

The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

The Prevalence of Cardiovascular Disease in Adults with Type 2 Diabetes in China: Results from the Cross-Sectional CAPTURE Study.

IntroductionCardiovascular disease (CVD) is the leading cause of death in Chinese adults with type 2 diabetes (T2D), and treatment guidelines have increasingly focused on the comprehensive management of T2D and CVD. Here, we report data from the Chinese population within the CAPTURE study, including CVD prevalence in patients with T2D and insights into their management.MethodsCAPTURE (a multinational, non-interventional, cross-sectional study in adults with T2D) included data from eight centers in China from July to September 2019. Overall CVD prevalence estimates were calculated, and descriptive data regarding CVD subtypes and treatment were collected and reported here.ResultsOf 805 adults with T2D enrolled in China (61.9% male, median age 59 years), 273 had established CVD, with an estimated prevalence (95% CI) of 33.9% (30.6%, 37.3%). Most CVD cases were atherosclerotic (94.9%). Coronary heart disease had the highest estimated prevalence (16.0%), followed by carotid artery disease (9.6%) and cerebrovascular disease (7.7%). Use of glucose-lowering agents (GLAs) with proven cardiovascular benefits (glucagon-like peptide-1 receptor agonists and/or sodium-glucose cotransporter-2 inhibitors) was low in the China sample (7.7%). Approximately half of the CVD subgroup in the China sample was receiving cardiovascular medication, but use of guideline-directed agents was low (e.g., statins: 35.9%; angiotensin II receptor blockers: 15%; angiotensin-converting enzyme inhibitors: 2.6%).ConclusionsIn the Chinese CAPTURE population, one-third of patients had established CVD, with atherosclerotic CVD largely accounting for the CVD burden; use of GLAs with proven cardiovascular benefits and cardiovascular medications was low, suggesting an unmet need for optimal management in this group.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01243-x.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

BackgroundSodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents.MethodsThis was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents.ResultsAlmost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup.ConclusionThe impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined.Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

990-P: Use of Glucose-Lowering Agents According to Cardiovascular Risk Factors in People with T2D and with or without CVD in the CAPTURE Study

990-P: Use of Glucose-Lowering Agents According to Cardiovascular Risk Factors in People with T2D and with or without CVD in the CAPTURE Study

Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study.

The identification of individuals at high risk of developing hypertension can be of great value to improve the efficiency of primary prevention strategies for hypertension. The objective of this study was to develop a risk prediction model for incident hypertension based on prospective longitudinal data from a general Japanese population. A total of 982 subjects aged 40-59 years without hypertension at baseline were followed up for 10 years (2002-12) for the incidence of hypertension. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive agents. The risk prediction model was developed using a Cox proportional hazards model. A simple risk scoring system was also established based on the developed model. During the follow-up period (median 10 years, interquartile range 5-10 years), 302 subjects (120 men and 182 women) developed new-onset hypertension. The risk prediction model for hypertension consisted of age, sex, SBP, DBP, use of glucose-lowering agents, body mass index (BMI), parental history of hypertension, moderate-to-high alcohol intake, and the interaction between age and BMI. The developed model demonstrated good discrimination (Harrell's C statistic=0.812 [95% confidence interval, 0.791-0.834]; optimism-corrected C statistic based on 200 bootstrap samples=0.804) and calibration (Greenwood-Nam-D'Agostino χ2 statistic=12.2). This risk prediction model is a useful guide for estimating an individual's absolute risk for hypertension and could facilitate the management of Japanese individuals at high risk of developing hypertension in the future.

Abstract P057: The Association Of Diabetes Duration With Central Artery Stiffness And Its 5-year Change Among Older Adults: The Atherosclerosis Risk In Communities Study (ARIC).

Background: Central artery stiffness is a predictor of cardiovascular risk and mortality among individuals with diabetes. Few studies examined whether the duration of diabetes relates to arterial stiffening and its rate of progression. Objective: To examine the association of diabetes duration from midlife to older adulthood with arterial stiffness and its 5-year change. Methods: Diabetes (defined by fasting glycemia level &gt;126 mg/dl or use of glucose lowering agents or self-reported) was ascertained at visit 1 (1988-1990), on repeated examinations and on telephone follow-up calls of 2,155 ARIC cohort members (58% women, 20% black, mean age 74 years), as well as time since ascertainment of diabetes. Carotid femoral pulse wave velocity (cfPWV), a measure of central artery stiffness, was obtained at cohort visits 5 (2011-13) and 6 or 7 (2016-19). Associations of duration of diabetes with visit 5 cfPWV and the 5-year cfPWV change from visit 5 to visit 6 or 7 were evaluated by multivariable linear regression adjusted for demographic factors. Results: Among study participants with diabetes ascertained from midlife to older adulthood (n=639 (29%)), the mean cfPWV at visit 5 was 78.6, 95%CI (52.9, 104.4) cm/s greater than those without diabetes. Over a mean of 4.9 (SD 3) years of follow-up, cfPWV increased by a median 137 cm/s. The 5-year change in cfPWV was 40.5, 95%CI (12.3, 68.8) cm/s greater among those with diabetes, as compared to those without diabetes. The mean diabetes duration was 8.1(SD 6.8) years for participants with diabetes. After adjusting for demographic factors, we observed a positive association of diabetes duration with the 5-year change in cfPWV in older adulthood (Figure). Conclusion: Duration of diabetes was associated with a greater rate of progression of central arterial stiffness in older adults.

Managing patients with diabetes and chronic kidney disease

In late 2020, the nonprofit organization Kidney Disease: Improving Global Outcomes (KDIGO) published a clinical practice guideline in the Annals of Internal Medicine on management of patients with diabetes and chronic kidney disease (CKD). The new guidance focuses on comprehensive care needs, glycemic monitoring and targets, and educational and integrated care approaches. “The 2020 KDIGO clinical practice guideline on diabetes management incorporates recent kidney outcome data to provide specific recommendations on use of glucose-lowering agents to mitigate kidney and cardiovascular risk,” said Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP, vice-chair and Allen I. White Distinguished Associate Professor in the College of Pharmacy and Pharmaceutical Sciences at Washington State University in Pullman. “Recommendations from KDIGO complement current guidance from the endocrine and cardiology communities, but provides a succinct resource related to the specific care needs of patients with diabetes and CKD. Particularly important to pharmacists is the guideline's discussion of risk mitigation strategies and important counseling points to optimize patient safety,” said Neumiller. Patients with diabetes and CKD often have other comorbidities and a higher cardiovascular burden, so a comprehensive management approach is needed. KDIGO recommends use of an ACE inhibitor (ACEi) or an ARB in patients with diabetes, hypertension, and albuminuria, with these medications titrated to the highest approved dose that is tolerated. Use may also be considered in patients with diabetes, albuminuria, and normal blood pressure. Only one of these agents should be used at a time, as combination therapy with an ACEi and an ARB or one of these agents with a direct renin inhibitor may be potentially harmful. Close monitoring of blood pressure, potassium levels, and serum creatinine is needed within 2 to 4 weeks of initiation of therapy or when there is a dose increase. KDIGO recommends that hyperkalemia be managed by implementing measures to reduce potassium levels (e.g., moderating potassium intake, initiating diuretics) rather than by decreasing or discontinuing the ACEi or ARB immediately. In addition, KDIGO recommends continuation of the ACEi or ARB unless creatinine levels increase by more than 30%. The ACEi or ARB dose should be reduced or withdrawn in patients who develop symptomatic hypotension, uncontrolled hyperkalemia (despite interventions), and acute kidney injury. The guideline discusses tobacco cessation as part of the comprehensive care plan, with patients encouraged to avoid using any tobacco products and to reduce their exposure to secondhand smoke. A section on lifestyle intervention is also included, and clinicians are encouraged to review those recommendations in the full publication. KDIGO recommends that A1C levels be used to monitor glycemic control in patients with diabetes and CKD, with an individualized target ranging from <6.5% to <8.0% for those not treated with dialysis. Assessment twice per year is reasonable, but assessments as often as 4 times per year may be needed if glycemic targets are not met or after a change in antihyperglycemic therapy. For antihyperglycemic therapy, KDIGO recommends metformin in combination with a sodium–glucose cotransporter-2 inhibitor for patients with type 2 diabetes, CKD, and an eGFR of 30 mL/min/1.73 m2 or greater. If patients do not reach their individualized glycemic target or are unable to use those medications, the guideline recommends use of a glucagon-like peptide-1 receptor agonist as the next preferred agent. Other antihyperglycemic agents are also listed with a figure (i.e., Figure 4) that helps guide appropriate selection based on patient and provider preferences (e.g., weight loss, avoid injections, avoid hypoglycemia, potent glucose lowering needed), comorbidities (e.g., high-risk atherosclerotic cardiovascular disease, heart failure), eGFR (e.g., dialysis), and cost. KDIGO recognizes that data on use of newer agents in patients with type 1 diabetes and CKD receiving insulin are sparse and makes no special recommendations for these patients. KDIGO discusses the importance of both a self-management education program and a team-based integrated approach to care. The self-education program should consider local context, cultures, and availability of resources and be tailored to individual preferences and learning styles. These programs can be delivered one-on-one or as a group-based model. The team-based approach should include both physician and nonphysician personnel and focus on regular assessments, control of multiple risk factors, and self-management to protect kidney function and reduce the risk for complications.

1294-P: Detection and Intervention of Prediabetes in a Large Urban Health System: Systematic Failure or Looming Opportunity?

Efficient early detection of prediabetes is critical in order to intervene and reduce conversion to T2DM since lifestyle interventions and/or metformin are proven to reduce progression. Retrospective data from a nationally-ranked tertiary academic medical center were analyzed to determine diagnosis rates, frequency of lifestyle and prescription interventions, and to assess characteristics of patients who were most likely to be clinically identified or treated. Data from the EpicCare EMR were analyzed using the University of Kansas Medical Center i2b2-based clinical data repository (HERON). Data were collected for 69,781 patients established in academically affiliated primary care clinics between 2015 and 2017. After excluding for previous diabetes/prediabetes diagnoses or use of glucose lowering agents, 46,855 patients remained to assess for incident prediabetes (ADA criteria). Clinical recognition of the prediabetes diagnosis, nutrition or weight management referral, and metformin prescription were assessed. Incident prediabetes occurred in 2,581 patients (5%). Thirty eight percent of those received a charted prediabetes diagnosis, 9% received either a referral to nutrition or weight management, and 4% received a metformin prescription. Females (OR 1.57) or those who had higher BMI (OR 1.02) or A1c values (OR 5.67) had higher odds of receiving clinical recognition (p&amp;lt;0.0001). We conclude that relatively few people with prediabetes are clinically noted and even fewer receive interventions that may reduce the conversion to T2DM. There are gender and weight biases; patients with higher BMI, higher A1c values, and females were more likely to have documentation for diagnosis and treatment for prediabetes. These low rates of recognition and treatment are likely to be similar among health care systems across the country. The low rates of recognizing, documenting, and intervening are opportunities to better utilize the EMR and reduce conversion to T2DM. Disclosure E. Newbold: None. S.E. Carlson: Advisory Panel; Self; DSM. Other Relationship; Self; MeadJohnson Nutrition (RB). D.K. Sullivan: None. D.C. Robbins: None. A. Beltramo: None. M. Lowrance: None. L.R. Waitman: None.

Trends in medication utilization, glycemic control and outcomes among type 2 diabetes patients in a tertiary referral center in Singapore from 2007 to 2017.

Use of glucose-lowering agents is a cornerstone in combating type 2 diabetes (T2DM). Treatment guidelines have changed significantly over the past decade. We report temporal trends in medication utilization, glycemic control and rate of severe hypoglycemia in T2DM patients at a tertiary referral center in Singapore. We analyzed data of 36 924 T2DM patients seen at Singapore General Hospital from 2007 to 2017. Annual age-, sex- and racially-standardized proportions of patients (a) prescribed with each class of glucose-lowering agent, (b) on various glucose-lowering regimens, and (c) had an HbA1c of less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, or 9% or more were estimated using logistic regression. Poisson regression was used to estimate standardized rate of severe hypoglycemia. From 2007 to 2017, use of metformin (45.9% to 59.6%) and insulin (24.4% to 57.9%) increased, while utilization of sulfonylureas (52.0% to 44.9%) decreased (all P < 0.001). Utilization of dipeptidyl peptidase-4 inhibitors (1.2% to 31.2%) and sodium-glucose cotransporter-2 inhibitors (0.5% to 7.4%) increased from 2008 to 2017 and 2012 to 2017, respectively (all P < 0.001). More patients were prescribed a combination of insulin and oral agents (17.3% to 46.0%, P < 0.001). The proportion of patients with HbA1c of 8% or more increased (33.7% to 36.0%, P < 0.001). Rates of severe hypoglycemia (5.0 to 8.4 per 100 patient-years, P < 0.001) also rose. Medication utilization patterns have changed significantly over the past 11 years with a shift towards newer agents. Glycemic control has remained stable, and rate of severe hypoglycemia increased. Further analysis is required before causal relationships can be inferred.

Type 2 diabetes mellitus, brain atrophy, and cognitive decline.

To study longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment, and Alzheimer disease (AD). The sample was derived from the Alzheimer's Disease Neuroimaging Initiative cohort who underwent brain MRI and cognitive tests annually for 5 years. Presence of T2DM was based on fasting blood glucose ≥7.0mml/L or the use of glucose-lowering agents. We used latent growth curve modeling to explore longitudinal relationships between T2DM, cortical thickness, and cognitive function, adjusting for relevant covariates and testing for interactions. There were 124 people with T2DM (mean age 75.5 years, SD 6.2) and 693 without T2DM (mean age 75.1 years, SD 6.9) with at least 1 MRI available. AD and lower cortical thickness at study entry was associated with a lower chance of having a MRI available at each follow-up phase (all p < 0.001). T2DM was associated with lower baseline cortical thickness (p = 0.01). We found no direct effect of T2DM on decline in cortical thickness or cognitive function, but there was an indirect pathway linking T2DM and cognitive decline via baseline cortical thickness (β = -0.17, p = 0.022). There was an interaction between T2DM and education whereby the negative effect of T2DM on baseline cortical thickness was reduced in those with greater education (β = 0.34, p = 0.037). These associations changed minimally when adjusted for baseline cognitive diagnosis. In an older cohort with low cerebrovascular disease burden, T2DM contributes to cognitive decline via neurodegeneration. Prior brain and cognitive reserve may protect against this effect.

Hyperglycaemia is associated with cancer-related but not non-cancer-related deaths: evidence from the IPC cohort.

Hyperglycaemia has been associated with the incidence of all and specific types of cancer, distinct from the risks related to diabetes. The relationships between blood glucose and mortality rates related to all and specific cancers were analysed in comparison with all-cause or non-cancer-related mortality rates in a large, general primary care population in France. Between January 1991 and December 2008, 301,948 participants (193,221 men and 108,727 women), aged 16-95years (mean ± SD 44.8 ± 12.0years for men and 45.1 ± 14.2years for women), had a health check at the IPC Centre. All data collected in standard conditions during the health checks-up were used for statistical analysis All examinations were performed under fasting conditions and included a blood glucose measurement. Participants with known diabetes (<9%) were excluded from the analysis. Participants were classified into quintiles based on their blood glucose measurement and were followed for a maximum of 17years (mean ± SD 9.2 ± 4.7years) to assess all-cause, cancer and non-cancer mortality rates. A non-linear relationship was observed between cancer mortality rates and blood glucose quintile after adjustment for age and sex. There was a significant association between the group with the highest blood glucose level and cancer-related death (multivariate Cox model, HR [95% CI] 1.17 [1.03, 1.34]), while the group with normoglycaemia showed no association with cancer-related deaths. We did not observe a relationship between blood glucose and all-cause or non-cancer mortality rates. An excess risk of death was observed in the highest blood glucose quintile for gastrointestinal cancer and leukaemia. Adjustments for diabetes and aspirin use did not modify the results. However, this excess risk disappeared with use of glucose-lowering agents (HR [95% CI] 1.03 [0.74, 1.43]). Hyperglycaemia is associated with significantly higher rates of cancer-related deaths, particularly in gastrointestinal cancer and leukaemia, but not with non-cancer-related deaths. The association is retained when taking into account confounding factors, including chronic aspirin treatment.