American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm - 2023 Update.

OBJECTIVE: This consensus statement provides (1) visual guidance in concise graphic algorithms to assist with clinical decision-making of health care professionals in the management of persons with type 2 diabetes mellitus to improve patient care and (2) a summary of details to support the visual guidance found in each algorithm. METHODS: The American Association of Clinical Endocrinology (AACE) selected a task force of medical experts who updated the 2020 AACE Comprehensive Type 2 Diabetes Management Algorithm based on the 2022 AACE Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan and consensus of task force authors. RESULTS: This algorithm for management of persons with type 2 diabetes includes 11 distinct sections: (1) Principles for the Management of Type 2 Diabetes; (2) Complications-Centric Model for the Care of Persons with Overweight/Obesity; (3) Prediabetes Algorithm; (4) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Dyslipidemia; (5) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Hypertension; (6) Complications-Centric Algorithm for Glycemic Control; (7) Glucose-Centric Algorithm for Glycemic Control; (8) Algorithm for Adding/Intensifying Insulin; (9) Profiles of Antihyperglycemic Medications; (10) Profiles of Weight-Loss Medications (new); and (11) Vaccine Recommendations for Persons with Diabetes Mellitus (new), which summarizes recommendations from the Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention. CONCLUSIONS: Aligning with the 2022 AACE diabetes guideline update, this 2023 diabetes algorithm update emphasizes lifestyle modification and treatment of overweight/obesity as key pillars in the management of prediabetes and diabetes mellitus and highlights the importance of appropriate management of atherosclerotic risk factors of dyslipidemia and hypertension. One notable new theme is an emphasis on a complication-centric approach, beyond glucose levels, to frame decisions regarding first-line pharmacologic choices for the treatment of persons with diabetes. The algorithm also includes access/cost of medications as factors related to health equity to consider in clinical decision-making.

Gap in Willingness and Access to Video Visit Use Among Older High-risk Veterans: Cross-sectional Study.

BACKGROUND: The recent shift to video care has exacerbated disparities in health care access, especially among high-need, high-risk (HNHR) adults. Developing data-driven approaches to improve access to care necessitates a deeper understanding of HNHR adults' attitudes toward telemedicine and technology access. OBJECTIVE: This study aims to identify the willingness, access, and ability of HNHR veterans to use telemedicine for health care. METHODS: WWe designed a questionnaire conducted via mail or telephone or in person. Among HNHR veterans who were identified using predictive modeling with national Veterans Affairs data, we assessed willingness to use video visits for health care, access to necessary equipment, and comfort with using technology. We evaluated physical health, including frailty, physical function, performance of activities of daily living (ADL) and instrumental ADL (IADL); mental health; and social needs, including Area Deprivation Index, transportation, social support, and social isolation. RESULTS: The average age of the 602 HNHR veteran respondents was 70.6 (SD 9.2; range 39-100) years; 99.7% (600/602) of the respondents were male, 61% (367/602) were White, 36% (217/602) were African American, 17.3% (104/602) were Hispanic, 31.2% (188/602) held at least an associate degree, and 48.2% (290/602) were confident filling medical forms. Of the 602 respondents, 327 (54.3%) reported willingness for video visits, whereas 275 (45.7%) were unwilling. Willing veterans were younger (P<.001) and more likely to have an associate degree (P=.002), be health literate (P<.001), live in socioeconomically advantaged neighborhoods (P=.048), be independent in IADLs (P=.02), and be in better physical health (P=.04). A higher number of those willing were able to use the internet and email (P<.001). Of the willing veterans, 75.8% (248/327) had a video-capable device. Those with video-capable technology were younger (P=.004), had higher health literacy (P=.01), were less likely to be African American (P=.007), were more independent in ADLs (P=.005) and IADLs (P=.04), and were more adept at using the internet and email than those without the needed technology (P<.001). Age, confidence in filling forms, general health, and internet use were significantly associated with willingness to use video visits. CONCLUSIONS: Approximately half of the HNHR respondents were unwilling for video visits and a quarter of those willing lacked requisite technology. The gap between those willing and without requisite technology is greater among older, less health literate, African American veterans; those with worse physical health; and those living in more socioeconomically disadvantaged neighborhoods. Our study highlights that HNHR veterans have complex needs, which risk being exacerbated by the video care shift. Although technology holds vast potential to improve health care access, certain vulnerable populations are less likely to engage, or have access to, technology. Therefore, targeted interventions are needed to address this inequity, especially among HNHR older adults.

Diabetes Treatment in the Elderly: Incorporating Geriatrics, Technology, and Functional Medicine.

PURPOSE OF REVIEW: The current approach to diabetes in the elderly incorporates components from the comprehensive geriatric approach. The most updated guidelines from the American Diabetes Association reflect influence from the consensus made in 2012 with the American Geriatrics Society. Notably, the framework included the evaluation for geriatric syndromes (falls and urinary incontinence), functional and cognitive abilities. The goal for this review is to provide an updated summary of treatment strategies for community-dwelling older adults. We identified the need to expand our approach by addressing innovative approaches and scientific concepts from telemedicine, functional medicine, and geriatrics. RECENT FINDINGS: Findings on cardiovascular protection with sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and some glucagon-like peptide 1 receptor agonists (GLP-1RA) support their use for older patients with diabetes. However, careful consideration for agent selection must incorporate the presence of geriatric issues, such as geriatric syndromes, or functional and cognitive decline, as they could increase the risk and impact adverse reactions. Telemedicine interventions can improve communication and connection between older patients and their providers, and improve glycemic control. Functional medicine concepts can offer additional adjuvant strategies to support the therapeutic interventions and management of diabetes in the elderly. A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult, but multiple reports highlighted the risk for vitamin B12 deficiency. Randomized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly, including some with longer duration and lesser risk for hypoglycemia. Randomized clinical trials showed cardiovascular protection with SGLT-2i (empagliflozin, canagliflozin) and GLP-1RA (liraglutide, semaglutide). The most current guidelines recommend addressing for geriatric syndromes, physical and cognitive function in the elderly, in order to individualize targets and therapeutic strategies. Clinicians managing diabetes in the elderly can play a major role for the early detection and evaluation of geriatric issues in their patients. Telemedicine interventions improve glycemic control, and certain functional medicine strategies could be adjuvant interventions to reduce inflammation and stress, but more studies focused on the elderly population are needed.

Metformin and ageing: improving ageing outcomes beyond glycaemic control.

In a world where the population is ageing, there is growing interest and demand for research evaluating strategies that address the ageing process. After 60 years of successful use of metformin in our pharmaceutical armamentarium, we are learning that, beyond improving glycaemic control, metformin may have additional mechanisms and pathways of action that need further study. Although, metformin's effect on clinical ageing outcomes may still be considered speculative, the findings from studies into cellular and animal models and from observational and pilot human studies support the existence of beneficial effects on ageing. At present, progress for human research, using randomised clinical trials to evaluate metformin's clinical impact, has just started. Here, we present a review on the ageing process and the mechanisms involved, and the role that metformin may have to counter these. We go on to discuss the upcoming large randomised clinical trials that may provide insight on the use of metformin for ageing outcomes beyond glycaemic control.

Weight loss and physical activity for disease prevention in obese older adults: an important role for lifestyle management.

Weight loss in older adults has been a controversial topic for more than a decade. An obesity paradox has been previously described and the issue of weight status on health outcomes remains a highly debated topic. However, there is little doubt that physical activity (PA) has a myriad of benefits in older adults, especially in obese individuals who are inactive and have a poor cardiometabolic profile. In this review, we offer a critical view to clarify misunderstandings regarding the obesity paradox, particularly as it relates to obese older adults. We also review the evidence on PA and lifestyle interventions for the improvement of cardiorespiratory fitness, which can prevent disease and provide benefits to obese older adults, independent of weight changes.

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.

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.

Recognizing the Needs of High-Need High-Risk Veterans.

Introduction: Understanding the needs of higher-risk older adult patients can support the delivery of high quality and patient-centered healthcare. We sought to characterize the physical, functional, social and psychological needs of High-Need High-Risk (HNHR) Veterans. We hypothesized that the concept of frailty could be useful in identifying the highest-risk HNHR patients and characterizing their needs. Methods: We conducted a cross-sectional study of Veterans in the Miami Veterans Affairs Healthcare System who were identified as High-Need High-Risk by the Department of Veterans Affairs (VA) using data analytic techniques. We analyzed data of 634 Veterans who completed questionnaires by mail, telephone or in person. We assessed the Veterans' frailty status and needs in the physical, functional, psychological and social domains. Beyond descriptive statistics, we used Chi-square (χ 2) test, one-way ANOVA and Kruskal-Wallis to analyze whether there were differences in Veterans' needs in relation to frailty status. Results: The HNHR Veterans who participated in the questionnaire had complex needs that spanned the physical, functional, psychological, and social domains. We observed a potential mismatch between functional needs and social support; over two-thirds of respondents endorsed having dependence in at least one ADL but only about a third of respondents reported having a caregiver. Patients with frailty had higher levels of functional dependence and were more likely than the other HNHR respondents to report recent falls, recent hospitalizations, depression, and transportation issues. Conclusion: High-Need High-Risk Veterans have complex needs related to the physical, functional, psychological and social domains. Within the HNHR population, HNHR Veterans with frailty appear to have particularly high levels of risk and multidomain needs. Increased attention to identifying members of these groups and aligning them with biopsychosocial interventions that are targeted to their specific needs may support development of appropriate strategies and care-models to support HNHR Veterans.

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.

How to prevent the microvascular complications of type 2 diabetes beyond glucose control.

Microvascular complications (retinopathy, nephropathy, and neuropathy) affect hundreds of millions of patients with type 2 diabetes. They usually affect people with longstanding or uncontrolled disease, but they can also be present at diagnosis or in those yet to have a diagnosis made. The presentation and progression of these complications can lead to loss of visual, renal, and neurologic functions, impaired mobility and cognition, poor quality of life, limitations for employment and productivity, and increased costs for the patient and society. If left uncontrolled or untreated, they lead to irreversible damage and even death. This review focuses on the primary and secondary prevention of diabetic microvascular complications in patients with type 2 diabetes, beyond glycemic control. Interventions discussed include standard of care interventions supported by guidelines from major organizations, as well as additional proposed interventions that are supported by research published in the past decade. High level evidence sources such as systematic reviews and large, multicenter randomized clinical trials have been prioritized. Smaller trials were included where high quality evidence was unavailable.

A new angle for glp-1 receptor agonist: the medical economics argument. Editorial on: Huetson P, Palmer JL, Levorsen A, et al. Cost-effectiveness of the once-daily glp-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway. J Med Econ 2015: 1-13 [Epub ahead of print].

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are relatively new medications for diabetes that offer a weight-loss profile that can be considered desirable for patients with both type 2 diabetes (T2D) and obesity. GLP-1 RA are effective in combination with insulin, and even slightly superior or at least equal to short-acting insulin in T2D; however, since they work in the incretin system, they may not be effective in long-standing disease. Additionally, only recently have publications reported their cardiovascular safety, and there is limited evidence for long-term effectiveness. The work presented by Huetson et al. offers a much needed perspective through a medical economic model for the long term cost-effectiveness of GLP-1 RA. The authors found benefits in quality-adjusted life years and reduced lifetime healthcare costs. While there are a few limitations, this study contributes to the understanding of these agents and their impact on the epidemics of obesity in T2D, where weight management is no longer an option, but an essential component of the diabetes plan of care.