Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Artery Disease Events Among Common Haptoglobin Phenotype Groups with Type 2 Diabetes
The present ADVANCE analysis suggests that not having HbA1c equal to or above 8.0%, rather than achieving HbA1c less than 7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
KEY FINDINGS: The present ADVANCE analysis suggests that not having HbA1c >=8.0%, rather than achieving HbA1c <7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
BACKGROUND: This study sought to determine whether the association between attaining specific glycated hemoglobin (HbA1c) targets (<7.0% (<53 mmol/mol) and >=8.0% (>=64 mmol/mol) compared with 7.0%-7.9%) over time and risk of incident coronary artery disease (CAD) was dependent on haptoglobin (Hp) phenotype in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.
DETAILS: Prospectively collected HbA1c data from the ADVANCE biomarker case-cohort study, updated at 6 months and every 12 months thereafter over a median of 5.0 (IQR 4.5-5.3) years, were analyzed in relation to incident CAD in the Hp2-2 (n=1323) and non-Hp2-2 (n=2069) phenotypes separately using weighted multivariable-adjusted Cox regression models. Additional a priori stratifications by sex, race, previous cardiovascular disease (CVD), and type 2 diabetes duration were performed. Mean HbA1c was similar in each phenotype group throughout the study. Compared with HbA1c of 7.0%-7.9%, HbA1c <7.0% was not associated with CAD risk for any phenotype group or subgroup. HbA1c >=8.0% compared with 7.0%-7.9% over time was associated with higher CAD risk for the Hp2-2 phenotype only (HR 1.53, 95% CI 1.01 to 2.32; no significant association in the non-Hp2-2 type: 1.26, 0.89 to 1.77, p-interaction=0.71); this was pronounced when those with previous CVD at baseline were excluded (Hp2-2: 2.80, 1.41 to 5.53, p-interaction=0.03). Compared with HbA1c of <8.0%, having HbA1c >=8.0% was associated with a 59% higher CAD risk among participants with the Hp2-2 phenotype (1.59, 1.12 to 2.26) and a 39% higher CAD risk among participants without the Hp2-2 phenotype (1.39, 1.03 to 1.88, p-interaction=0.97).
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Copyright © BMJ Publishing Group Ltd. All rights reserved.
Source: Cahill, L. E., Warren, R. A., Lavallée, S. K., et al. Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Artery Disease Events Among Common Haptoglobin Phenotype Groups With Type 2 Diabetes: The ADVANCE Study. BMJ Open Diabetes Research & Care. 2025; 13(3): e004713. Published: May 6, 2025. DOI: 10.1136/bmjdrc-2024-004713.
Continuous Glucose Monitoring with Geriatric Principles in Older Adults with Type 1 Diabetes and Hypoglycemia
In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion.
KEY FINDINGS: In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion.
BACKGROUND: Continuous glucose monitoring (CGM) use in older adults with type 1 diabetes (T1D) has shown benefits. However, the impact of CGM use, coupled with simplified treatment regimens and personalized glycemic goals that are better suited for older patients with multiple comorbidities and hypoglycemia, is not known.
DETAILS: Older adults (>=65 years) with T1D with hypoglycemia (two or more episodes of hypoglycemia [blood glucose <70 mg/dL for >=20 min over 2 weeks]) who were CGM naive or CGM users were randomized to intervention and control groups. The intervention consisted of the combined use of CGM with geriatric principles (i.e., adjusting goals based on overall health, and simplification of regimens based on CGM patterns and clinical characteristics) over 6 months. The control group received usual care by their endocrinologist. The primary end point was change in time when blood glucose was <70 mg/dL from baseline to 6 months. Cost-effectiveness was calculated using a health care sector perspective. Authors randomized 131 participants (aged 71 ± 5 years; 21% >=75 years old) to the intervention (n = 68; CGM users = 33) or the control (n = 63; CGM users = 40) group. The median change in hypoglycemia from baseline to 6 months was -2.6% in the intervention group and -0.3% in the control group (median difference, -2.3% [95% CI -3.7%, -1.3%]; P < 0.001). This improvement was seen in both CGM naive (-2.8%; 95% CI -5.6%, -0.8%) and CGM users (-1.2%; 95% CI -2.7%, -0.1%). The HbA1c did not differ between the groups (7.5% vs. 7.3%). The intervention was cost-effective (incremental cost-effectiveness ratio $71,623 per quality adjusted life-year).
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Copyright © American Diabetes Association. All rights reserved.
Source: Munshi, M., N., Slyne, C., Adam, A., et al. Continuous Glucose Monitoring with Geriatric Principles in Older Adults with Type 1 Diabetes and Hypoglycemia: A Randomized Controlled Trial. Diabetes Care. 2025; 48(5):694-702. Published: May, 2025. DOI: 10.2337/dc24-1069.
Interdisciplinary Care for Geriatric Syndromes in CKD
Implementing an interdisciplinary model of care that addresses geriatric syndromes in CKD is possible but will require overcoming policy-related, financial, cultural, and structural barriers. Such a model of care may ultimately benefit patients and nephrologists.
KEY FINDINGS: Implementing an interdisciplinary model of care that addresses geriatric syndromes in CKD is possible but will require overcoming policy-related, financial, cultural, and structural barriers. Such a model of care may ultimately benefit patients and nephrologists.
BACKGROUND: Despite their prevalence, prognostic significance, and prioritization by patients, key geriatric syndromes, such as cognitive impairment, frailty, and depression, are not routinely addressed in CKD care in the United States (US). In an interdisciplinary care model, health professionals with diverse expertise collaborate to address all symptoms and functional impairments occurring alongside a patient's chronic disease. Thus, routinely addressing geriatric syndromes in CKD may require implementing this evidence-based model of care and adapting it to the needs of patients with CKD. In a formative step to understanding how health systems could implement an interdisciplinary model of care to address geriatric syndromes in CKD, we interviewed health professionals around the world with relevant expertise.
DETAILS: Authors conducted a qualitative study informed by the Consolidated Framework for Implementation Research. Authors interviewed nephrologists, administrators, geriatricians, palliative medicine specialists, subspecialists, and allied health professionals working in other interdisciplinary clinics from the United States, United Kingdom, India, and Canada. Authors analyzed results using an inductive-deductive approach. Thematic saturation occurred at 42 experts. Three major domains emerged: barriers to implementation, strategies to mitigate barriers, and benefits of implementation. Barriers were categorized into overarching themes related to (1) aging-friendly policy and workforce availability, (2) organizational culture and structure, and (3) nephrologist and patient perceptions. Strategies to mitigate barriers were categorized into themes related to (1) demonstrating viability, (2) facilitating effective health communication, (3) soliciting support from administrators and clinicians, and (4) expanding the base for patient information and treatment evidence. Proposed benefits of implementation included improved shared decision making and reduced nephrologist burnout.
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Copyright © American Society of Nephrology. All rights reserved.
Source: Subash, A.,Levinson, M., Bonnet, K., et al. (20245). Interdisciplinary Care for Geriatric Syndromes in CKD: A Qualitative Study. Clinical Journal of the American Society of Nephrology. 2025; 20(5): 652-664. Published: May, 2025. DOI: 10.2215/CJN.0000000658.
Adverse Pregnancy Outcomes and Long-Term Risk of Heart Failure in Women
In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for HF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical care to reduce the risk of HF.
KEY FINDINGS: In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for HF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical care to reduce the risk of HF.
BACKGROUND: Adverse pregnancy outcomes, such as preterm delivery and hypertensive disorders of pregnancy, may be associated with higher future risks of heart failure (HF). However, the comparative effects of different adverse pregnancy outcomes on long-term risk of HF, and their potential causality, are unclear. The authors sought to examine 5 major adverse pregnancy outcomes in relation to long-term risk of HF in a large population-based cohort.
DETAILS: A national cohort study was conducted of all 2,201,638 women with a singleton delivery in Sweden in 1973-2015, followed up for HF identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute HRs for HF associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, while adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 48 million person-years of follow-up, 667,774 women (30%) experienced an adverse pregnancy outcome, and 19,922 women (0.9%) were diagnosed with HF (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with long-term increased risk of HF. With up to 46 years of follow-up after delivery, adjusted HRs for HF associated with specific adverse pregnancy outcomes were: gestational diabetes, 2.19 (95% CI: 1.95-2.45); preterm delivery, 1.68 (95% CI: 1.61-1.75); other hypertensive disorders, 1.68 (95% CI: 1.48-1.90); preeclampsia, 1.59 (95% CI: 1.53-1.66); and small for gestational age, 1.35 (95% CI: 1.31-1.40). All HRs remained significantly elevated (1.3- to 3.0-fold) even 30 to 46 years after delivery. These findings were only partially explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk (eg, up to 46 years after delivery, adjusted HRs associated with 1, 2, or ≥3 adverse pregnancy outcomes were 1.51 [95% CI: 1.47-1.56], 2.31 [95% CI: 2.19-2.45], and 3.18 [95% CI: 2.85-3.56], respectively).
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Copyright © American College of Cardiology Foundation. All rights reserved.
Source: Crump, C., Crump, J., and Crump, K. (20245). Adverse Pregnancy Outcomes and Long-Term Risk of Heart Failure in Women: National Cohort and Co-Sibling Study. J Am Coll Cardiol HF.. 2025; 3(4): 589–598. Published: April, 2025. DOI: 10.1016/j.jchf.2024.11.004.
Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes
CD4+ T cells from patients with type 1 diabetes (T1D) have a significant response to post-translationally modified (PTM) deamidated IA-2 peptides; autoantibodies to these PTM neoepitopes remain to be identified in T1D.
KEY FINDINGS: Study results indicate that PTM and unmodified IA-2ecA are predominantly present at late stages of T1D development in patients with clinical new-onset T1D.
BACKGROUND: Increasing evidence shows that pathogenic T cells in type 1 diabetes (T1D) that may have evaded negative selection recognize post-translationally modified (PTM) epitopes of self-antigens.
DETAILS: Authors have investigated the profiles of autoantibodies specifically targeting the deamidated epitopes of insulinoma antigen-2 extracellular domain (IA-2ec) to explore their relationship with T1D development. Authors compared the characteristics of autoantibodies targeting the IA-2ec Q > E epitopes (PTM IA-2ecA) as well as those targeting the IA-2ec unmodified epitopes (IA-2ecA) in participants across different stages of T1D development and in individuals with other types of diabetes and other kinds of autoimmunity. In patients with new-onset T1D, the prevalence of PTM IA-2ecA (26.1%) was significantly higher than that of IA-2ecA (19.5%; P < 0.0001). In a longitudinal newborn cohort, both IA-2ecAs were present, but they were rare in preclinical stage 1 T1D, and with much lower positivity in individuals with stage 3 T1D who had been closely followed from birth in a clinical study compared with patients diagnosed in routine clinical settings with overt symptoms. In participants with latent autoimmune diabetes in adults, type 2 diabetes, and celiac disease autoimmunity, authors did not observe significant positivity of either IA-2ecAs.
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Copyright © The American Diabetes Association. All rights reserved.
Source: Jia, X., Wenzlau, J. M., Zhang, C., al. (2025). Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes. Diabetes. 2025; 74(4): 544-553. Published: March 20, 2025. DOI: 10.2337/db24-0571.
Tirzepatide for Obesity Treatment and Diabetes Prevention
Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo.
KEY FINDINGS: Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo.
BACKGROUND: Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.
DETAILS: Authors performed a phase 3, double-blind, randomized, controlled trial in which 2,539 participants with obesity, of whom 1,032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified.
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Copyright © Massachusetts Medical Society. All rights reserved.
Source: Jastreboff, A. M., le Roux, C. W., Stefanski, A., et al. (2024). Tirzepatide for Obesity Treatment and Diabetes Prevention. NEJM. 2025; 392(10): 958-971. Published: March, 2025. DOI: 10.1056/NEJMoa241081.
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