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On p. 777 of the article cited above, it was incorrectly stated that patients with pancreatic diabetes may have elevated fecal elastase. The correct text is as follows: "In the case of pancreatic diabetes, patients may have low fecal elastase." The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dci23-0038) has been revised.
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Background: A-ß+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved ß-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A-ß+ KPD within this cohort. Methods: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A-ß+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results: Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A-ß+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions: In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A-ß+ KPD. They manifest the key characteristics of obesity, preserved ß-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A-ß+ KPD.
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Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Humanos , Femenino , Masculino , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/etiología , Niño , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Adolescente , Prevalencia , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/fisiología , Células Secretoras de Insulina/metabolismo , Estudios RetrospectivosRESUMEN
OBJECTIVE: The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization. METHODS: Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and regional fat and lean masses at randomization, at Years 1, 4, and 8, and at the final visit. Linear mixed-effects regressions were applied with adjustment for group, clinic, sex, age, race/ethnicity, and baseline body composition. RESULTS: Weight and most body compartments were reduced by 2% to 8% (and BMI 4%) in ILI versus DSE in men but not women. ILI-induced loss of lean tissue did not show a lower percent lean mass versus DSE at 16 years after randomization. CONCLUSION: ILI-related changes in weight, fat, and lean mass were detectable 12 to 16 years after randomization in men but, for unknown reasons, not in women. There was no evidence that the intervention led to a disproportionate loss of lean mass by the end of the study.
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Absorciometría de Fotón , Composición Corporal , Diabetes Mellitus Tipo 2 , Estilo de Vida , Humanos , Diabetes Mellitus Tipo 2/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Índice de Masa CorporalRESUMEN
As our understanding of the pathophysiology of diabetes evolves, we increasingly recognize that many patients may have a form of diabetes that does not neatly fit with a diagnosis of either type 1 or type 2 diabetes. The discovery and description of these forms of "atypical diabetes" have led to major contributions to our collective understanding of the basic biology that drives insulin secretion, insulin resistance, and islet autoimmunity. These discoveries now pave the way to a better classification of diabetes based on distinct endotypes. In this review, we highlight the key biological and clinical insights that can be gained from studying known forms of atypical diabetes. Additionally, we provide a framework for identification of patients with atypical diabetes based on their clinical, metabolic, and molecular features. Helpful clinical and genetic resources for evaluating patients suspected of having atypical diabetes are provided. Therefore, appreciating the various endotypes associated with atypical diabetes will enhance diagnostic accuracy and facilitate targeted treatment decisions.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Autoinmunidad , Secreción de InsulinaRESUMEN
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.
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A survey of advanced practice clinicians (APCs), physicians, residents, and medical students at an academic medical center and community practices in southeastern Texas revealed a gap in knowledge and practice related to testing and treatment for asymptomatic bacteriuria (ASB) in older adults.
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Bacteriuria , Médicos , Humanos , Anciano , Bacteriuria/tratamiento farmacológico , Antibacterianos/uso terapéutico , TexasRESUMEN
OBJECTIVE: To evaluate whether baseline levels of depressive symptoms and diabetes-specific distress are associated with glycemic control in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing the metabolic effects of four common glucose-lowering medications when combined with metformin in individuals with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: The primary and secondary outcomes were defined as an HbA1c value ≥7%, subsequently confirmed, and an HbA1c value >7.5%, subsequently confirmed, respectively. Separate Cox proportional hazards models assessed the association between baseline levels of each exposure of interest (depressive symptoms measured with the eight-item Patient Health Questionnaire and diabetes distress measured with the Diabetes Distress Scale) and the subsequent risk of metabolic outcomes. RESULTS: This substudy included 1,739 participants (56% of whom were non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic, and 68% male; mean [SD] age 58.0 [10.2] years, diabetes duration 4.2 [2.8] years, and HbA1c 7.5% [0.48%]). A total of 1,157 participants reached the primary outcome, with time to event of 2.1 years on average, while 738 participants reached the secondary outcome at 3 years on average. With adjustment for sex, race/ethnicity, treatment group, baseline age, duration of T2DM, BMI, and HbA1c, there were no significant associations between the depressive symptoms or diabetes distress and the subsequent risk of the primary or secondary outcomes. CONCLUSIONS: The current findings suggest that, at least for individuals with diabetes of relatively short duration, baseline levels of emotional distress are not associated with glycemic control over time.
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Diabetes Mellitus Tipo 2 , Distrés Psicológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/psicología , Hemoglobina Glucada , Control Glucémico , Hipoglucemiantes/uso terapéutico , Investigación sobre la Eficacia ComparativaRESUMEN
OBJECTIVE: To compare the effects of insulin sensitivity and ß-cell function over time on HbA1c and durability of glycemic control in response to dual therapy. RESEARCH DESIGN AND METHODS: GRADE participants were randomized to glimepiride (n = 1,254), liraglutide (n = 1,262), or sitagliptin (n = 1,268) added to baseline metformin and followed for mean ± SD 5.0 ± 1.3 years, with HbA1c assessed quarterly and oral glucose tolerance tests at baseline, 1, 3, and 5 years. We related time-varying insulin sensitivity (HOMA 2 of insulin sensitivity [HOMA2-%S]) and early (0-30 min) and total (0-120 min) C-peptide (CP) responses to changes in HbA1c and glycemic failure (primary outcome HbA1c ≥7% [53 mmol/mol] and secondary outcome HbA1c >7.5% [58 mmol/mol]) and examined differential treatment responses. RESULTS: Higher HOMA2-%S was associated with greater initial HbA1c lowering (3 months) but not subsequent HbA1c rise. Greater CP responses were associated with a greater initial treatment response and slower subsequent HbA1c rise. Higher HOMA2-%S and CP responses were each associated with lower risk of primary and secondary outcomes. These associations differed by treatment. In the sitagliptin group, HOMA2-%S and CP responses had greater impact on initial HbA1c reduction (test of heterogeneity, P = 0.009 HOMA2-%S, P = 0.018 early CP, P = 0.001 total CP) and risk of primary outcome (P = 0.005 HOMA2-%S, P = 0.11 early CP, P = 0.025 total CP) but lesser impact on HbA1c rise (P = 0.175 HOMA2-%S, P = 0.006 early CP, P < 0.001 total CP) in comparisons with the glimepiride and liraglutide groups. There were no differential treatment effects on secondary outcome. CONCLUSIONS: Insulin sensitivity and ß-cell function affected treatment outcomes irrespective of drug assignment, with greater impact in the sitagliptin group on initial (short-term) HbA1c response in comparison with the glimepiride and liraglutide groups.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Metformina , Compuestos de Sulfonilurea , Humanos , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Liraglutida/uso terapéutico , Hemoglobina Glucada , Metformina/uso terapéutico , Fosfato de Sitagliptina/uso terapéutico , Resultado del Tratamiento , Glucemia , Quimioterapia CombinadaRESUMEN
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are associated with excessive weight gain among a subset of persons with HIV (PWH), due to unclear mechanisms. We assessed energy intake (EI) and expenditure (EE) following switch off and onto INSTIs. METHODS: PWH with >10% weight gain on an INSTI-based regimen switched INSTI to doravirine for 12 weeks, then back to INSTI for 12 weeks while keeping their remaining regimen stable. Twenty-four-hour EE, EI and weight were measured on INSTI, following switch to doravirine, and upon INSTI restart. Mixed models analysed changes over time. RESULTS: Among 18 participants, unadjusted 24 h EE decreased by 83 (95% CI -181 to 14) kcal following switch to doravirine, and by 2 (-105 to 100) kcal after INSTI restart; energy balance (EE-EI) increased by 266 (-126 to 658) kcal from Week 0 to Week 12, and decreased by 3 (-429 to 423) kcal from Week 12 to Week 24. Trends toward weight loss occurred following switch to doravirine [mean -1.25 (-3.18 to 0.69) kg] and when back on INSTI [-0.47 (-2.45 to 1.52) kg]. Trunk fat decreased on doravirine [-474 (-1398 to 449) g], with some regain following INSTI restart [199 (-747 to 1145) g]. Fat-free mass decreased on doravirine [-491 (-1399 to 417) g] and increased slightly after INSTI restart [178 (-753 to 1108) g]. CONCLUSIONS: Among PWH with >10% weight gain on an INSTI, switch to doravirine was associated with a trend towards decreases in 24 h EE, weight, trunk fat mass and fat-free mass. Observed changes were not significant, but suggest a mild weight-suppressive effect of doravirine among PWH.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Inhibidores de Integrasa VIH/uso terapéutico , Aumento de Peso , Composición Corporal , IntegrasasRESUMEN
PURPOSE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). METHODS: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. RESULTS: Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. CONCLUSION: Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Sobrepeso/complicaciones , Sobrepeso/terapia , Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina Glucada , Obesidad/complicaciones , Obesidad/terapia , Estilo de Vida , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & controlRESUMEN
Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy, including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy. These conditions may coexist with generalized obesity in PLWH and reflect disturbances of energy balance regulation caused by HIV persistence and antiretroviral therapy drugs. Adipocyte hypertrophy characterizes visceral and subcutaneous adipose tissue depot expansion, as well as ectopic lipid deposition that occurs diffusely in the liver, skeletal muscle, and heart. PLWH with excess visceral adipose tissue exhibit adipokine dysregulation coupled with increased insulin resistance, heightening their risk for cardiovascular disease above that of the HIV-negative population. However, conventional therapies are ineffective for the management of cardiometabolic risk in this patient population. Although the knowledge of complex cardiometabolic comorbidities in PLWH continues to expand, significant knowledge gaps remain. Ongoing studies aimed at understanding interorgan communication and energy balance provide insights into metabolic observations in PLWH and reveal potential therapeutic targets. Our review focuses on current knowledge and recent advances in HIV-associated adipose tissue dysfunction, highlights emerging adipokine paradigms, and describes critical mechanistic and clinical insights.
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Enfermedades Cardiovasculares , Infecciones por VIH , Humanos , Grasa Subcutánea/metabolismo , Tejido Adiposo/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/metabolismo , Adipoquinas/metabolismo , Adipoquinas/uso terapéutico , Enfermedades Cardiovasculares/metabolismoRESUMEN
BACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D. METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n = 15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors. RESULTS: The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p < 0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p < 0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p < 0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p < 0.05). CONCLUSIONS: Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Fabaceae , Niño , Humanos , Adolescente , Glutamina , Proyectos Piloto , Metionina , Racemetionina , Arginina , CitrulinaRESUMEN
OBJECTIVE: To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aß subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and ß+ and ß- define the presence or absence of ß-cell function. RESEARCH DESIGN AND METHODS: We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, ß-cell function, and glycemia. RESULTS: Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+ß- > A+ß+ = A-ß- > A-ß+. GRS of A+ß- KPD was lower than that of a T1D cohort, and GRS of A-ß+ KPD was higher than that of a type 2 diabetes cohort. GRS was lowest among African American patients, with a similar distribution across KPD subgroups. CONCLUSIONS: T1D genetic risk delineates etiologic differences among KPD subgroups. Patients with A+ß- KPD have the highest and those with A-ß+ KPD the lowest GRS.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Células Secretoras de Insulina , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Factores de Riesgo , Células Secretoras de Insulina/fisiologíaRESUMEN
The incidence of type 2 diabetes in children is rising and carries a worse prognosis than in adults. The influence of sex on pediatric type 2 diabetes outcomes has not been well investigated. We studied 715 youth with type 2 diabetes diagnosed at a median age of 13.7 years and compared sex differences in demographic, clinical, and laboratory characteristics within the first year of diagnosis. Females diagnosed with type 2 diabetes were younger and at a higher stage of pubertal development than males, yet presented with lower A1Cs, a lower prevalence of diabetic ketoacidosis, and higher HDL cholesterol levels.
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INTRODUCTION: The COVID-19 pandemic has changed the landscape of modern medicine on a global scale. An emerging concern is the recognition of a bidirectional relationship between COVID-19 and diabetes. Diabetes is a risk factor for severe COVID-19 illness. Intriguingly, recent epidemiological and in vitro studies suggest that infection with SARS-CoV-2, the causative viral agent of COVID-19, is associated with new-onset diabetes and worsening diabetes control. These factors have affected the management of diabetes. AREAS COVERED: This review provides an overview of our current understanding of the incidence and prevalence of diabetes in relation to the COVID-19 pandemic, highlights studies evaluating SARS-CoV-2's beta cell tropism and its effects on insulin secretion and sensitivity and evaluates the impact of the pandemic on diabetes management and metabolic control. EXPERT OPINION: Epidemiological studies have noted an increase in the incidence of new-onset diabetes associated with COVID-19 in patients with phenotypes of type 1 diabetes, type 2 diabetes and Ketosis-Prone Diabetes. Prospective studies are needed to fully elucidate the association between COVID-19 and diabetes and to characterize persons at risk of developing diabetes after SARS-CoV-2 infection, identify those who should be screened for diabetes, and determine the natural histories of different forms of diabetes associated with COVID-19.
The COVID-19 pandemic has affected medical care worldwide. Healthcare systems have been overwhelmed during 'surges' of COVID-19 illness, and access to care has been affected during prolonged lockdowns. COVID-19 is caused by the SARS-CoV-2 virus, which is highly contagious. Infection with SARS-CoV-2 can lead to serious illness, primarily in the lungs, but it often affects many other organ systems, leading to disability and death. Recent studies show that persons with diabetes can have a more severe course of illness if infected with SARS-CoV-2. There is also growing evidence that COVID-19 may cause diabetes or worsen preexisting diabetes. In this review, we discuss the findings of studies that show an increase in the frequency of diabetes diagnosed worldwide during the COVID-19 pandemic. We also examine recent data that suggest SARS-CoV-2 can infect and damage the insulin-producing cells in the pancreas. Finally, we provide an overview of the impact of COVID-19 on the management of patients with diabetes, and the emerging use of telemedicine in diabetes care.
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COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Incidencia , Diabetes Mellitus Tipo 1/epidemiologíaRESUMEN
Introduction: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG. Materials and Methods: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible. Results: We enrolled 601 participants with mean age 44 ± 16.8 years, 64.4% female. At Stage 1, 80.6% were White, 7.2% African American (AA), 12.2% other/more than one race, and 8.4% Hispanic. Enrollment of URG was significantly below preset targets across most stages. Referral sources differed by race (p < 0.001) but not ethnicity (p = 0.15). Most AA participants were referred by RADIANT investigators (58.5% vs. 24.5% in Whites), whereas flyers, news, social media, and family or friends were more frequent referral sources for White individuals (26.4% vs. 12.2% in AA). Ongoing initiatives to increase enrollment of URG in RADIANT include engaging with clinics/hospitals serving URG, screening electronic medical records, and providing culturally competent study coordination and targeted advertisement. Conclusions: There is low participation of URG in RADIANT, potentially limiting the generalizability of its discoveries. Investigations into barriers and facilitators for recruitment and retention of URG in RADIANT, with implications for other studies, are ongoing.
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Heterogeneous forms of Ketosis-prone diabetes (KPD) are characterized by patients who present with diabetic ketoacidosis (DKA) but lack the typical features and biomarkers of autoimmune T1D. The A-ß+ subgroup of KPD provides unique insight into the concept of "remission" since these patients have substantial preservation of beta-cell function permitting the discontinuation of insulin therapy, despite initial presentation with DKA. Measurements of C-peptide levels are essential to predict remission and guide potential insulin withdrawal. Further studies into predictors of remission and relapse can help us guide patients with A-ß+ KPD toward remission and develop targeted treatments for this form of atypical diabetes.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/etiología , Cetoacidosis Diabética/terapia , Insulina/uso terapéutico , BiomarcadoresRESUMEN
CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown. OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD. METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with data on age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin (HbA1c) to characterize diabetes subgroups at randomization. Prevalent MCI/PD were centrally adjudicated based on standardized cognitive tests and other health information 10 to 13 years after randomization. We estimated marginal probabilities for prevalent MCI/PD among T2D subgroups with adjustment for potential confounders and attrition and examined whether ILI modified any associations. RESULTS: Four distinct T2D subgroups were identified, characterized by older age at diabetes onset (43% of sample), high HbA1c (13%), severe obesity (23%), and younger age at onset (22%). Unadjusted prevalence of MCI/PD (314 cases, 8.4%) differed across T2D subgroup (older onset = 10.5%, severe obesity = 9.0%, high HbA1c = 7.9%, and younger onset = 4.0%). Adjusted probability for MCI/PD within T2D subgroup was highest for the severe obesity subgroup and lowest for the younger onset subgroup but did not differ by ILI arm (interaction P value = 0.84). CONCLUSIONS: Among individuals with T2D and overweight or obesity, probability of MCI/PD differed by T2D subgroup. Probability of MCI/PD was highest for a subgroup characterized by severe obesity. CLINICALTRIALS.GOV IDENTIFIER: NCT00017953.
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Demencia , Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Sobrepeso/terapia , Hemoglobina Glucada , Obesidad Mórbida/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/terapia , Estilo de Vida , CogniciónRESUMEN
CONTEXT: Some individuals present with forms of diabetes that are "atypical" (AD), which do not conform to typical features of either type 1 diabetes (T1D) or type 2 diabetes (T2D). These forms of AD display a range of phenotypic characteristics that likely reflect different endotypes based on unique etiologies or pathogenic processes. OBJECTIVE: To develop an analytical approach to identify and cluster phenotypes of AD. METHODS: We developed Discover Atypical Diabetes (DiscoverAD), a data mining framework, to identify and cluster phenotypes of AD. DiscoverAD was trained against characteristics of manually classified patients with AD among 278 adults with diabetes within the Cameron County Hispanic Cohort (CCHC) (Study A). We then tested DiscoverAD in a separate population of 758 multiethnic children with T1D within the Texas Children's Hospital Registry for New-Onset Type 1 Diabetes (TCHRNO-1) (Study B). RESULTS: We identified an AD frequency of 11.5% in the CCHC (Study A) and 5.3% in the pediatric TCHRNO-1 (Study B). Cluster analysis identified 4 distinct groups of AD in Study A: cluster 1, positive for the 65 kDa glutamate decarboxylase autoantibody (GAD65Ab), adult-onset, long disease duration, preserved beta-cell function, no insulin treatment; cluster 2, GAD65Ab negative, diagnosed at age ≤21 years; cluster 3, GAD65Ab negative, adult-onset, poor beta-cell function, lacking central obesity; cluster 4, diabetic ketoacidosis (DKA)-prone participants lacking a typical T1D phenotype. Applying DiscoverAD to the pediatric patients with T1D in Study B revealed 2 distinct groups of AD: cluster 1, autoantibody negative, poor beta-cell function, lower body mass index (BMI); cluster 2, autoantibody positive, higher BMI, higher incidence of DKA. CONCLUSION: DiscoverAD can be adapted to different datasets to identify and define phenotypes of participants with AD based on available clinical variables.