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State-of-the-art biostatistics methods allow for the simultaneous modeling of several correlated non-fatal disease processes over time, but there is no clear guidance on the optimal analysis in most settings. An example occurs in diabetes, where it is not known with certainty how microvascular complications of the eyes, kidneys, and nerves co-develop over time. In this article, we propose and contrast two general model frameworks for studying complications (sequential state and parallel trajectory frameworks) and review multivariate methods for their analysis, focusing on multistate and joint modeling. We illustrate these methods in a tutorial format using the long-term follow-up from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study public data repository. A formal comparison of prediction error and discrimination is included. Multistate models are particularly advantageous for determining the order and timing of complications, but require discretization of the longitudinal outcomes and possibly a very complex state space process. Intermittent observation of the states must be accounted for, and discretization is a probable disadvantage in this setting. In contrast, joint models can account for variations of continuous biomarkers over time and are particularly designed for modeling complex association structures between the complications and for performing dynamic predictions of an outcome of interest to inform clinical decisions (eg, a late-stage complication). We found that both models have helpful features that can better-inform our understanding of the complex trajectories that complications may take and can therefore help with decision making for patients presenting with diabetes complications.
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Complicações do Diabetes , Diabetes Mellitus , Humanos , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Probabilidade , Ensaios Clínicos como AssuntoRESUMO
Award programmes that acknowledge the remarkable accomplishments of long-term survivors with type 1 diabetes have naturally evolved into research programmes to determine the factors associated with survivorship and resistance to chronic complications. In this review, we present an overview of the methodological sources of selection bias inherent in survivorship research (selection of those with early-onset diabetes, incidence-prevalence bias and bias from losses to follow-up in cohort studies) and the breadth and depth of literature focusing on this special study population. We focus on the learnings from the study of longstanding type 1 diabetes on discoveries about the natural history of insulin production loss and microvascular complications, and mechanisms associated with them that may in future offer therapeutic targets. We detail descriptive findings about the prevalence of preserved insulin production and resistance to complications, and the putative mechanisms associated with such resistance. To date, findings imply that the following mechanisms exist: strategies to maintain or recover beta cells and their function; activation of specific glycolytic enzymes such as pyruvate kinase M2; modification of AGE production and processing; novel mechanisms for modification of renin-angiotensin-aldosterone system activation, in particular those that may normalise afferent rather than efferent renal arteriolar resistance; and activation and modification of processes such as retinol binding and DNA damage checkpoint proteins. Among the many clinical and public health insights, research into this special study population has identified putative mechanisms that may in future serve as therapeutic targets, knowledge that likely could not have been gained without studying long-term survivors.
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Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Projetos de Pesquisa , Humanos , Sistema Renina-Angiotensina/fisiologiaRESUMO
INTRODUCTION/AIMS: The purpose of this study was to evaluate the clinical profile of myasthenia gravis (MG) in older patients and determine the impact of medical comorbidities on their MG status and outcome. METHODS: This was a retrospective chart review of patients with a symptom onset of MG at or after 65 years of age. Correlations were made between demographics, clinical characteristics, the Myasthenia Gravis Foundation of America (MGFA) severity scale scores, and Myasthenia Gravis Impairment Index (MGII) scores with two outcome measures: MGFA Post-Intervention Status (MGFA-PIS) and Simple Single Question (SSQ). RESULTS: The study population included 109 patients, with 90 of them having more than one follow-up visit. Their mean age was 75.3 ± 6.9 years and sex distribution was even. Of these patients, 67.7% had generalized MG. Nine-one percent of patients had one comorbidity. None of the demographic factors or comorbidities showed an association with MGFA-PIS, SSQ, or MGII after correction for multiple comparisons. Seventy-one percent of the patients improved with treatment, 12.4% remained unchanged, and 16.6% showed worsening at their last follow-up visit. DISCUSSION: Our study shows that patients with very-late-onset MG had a good prognosis and treatment response. None of the comorbidities had an impact on the severity of myasthenic symptoms or on outcome in these patients.
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Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Feminino , Seguimentos , Humanos , Masculino , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/terapia , Miastenia Gravis/terapia , Estudos RetrospectivosRESUMO
AIM: To examine the impact of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes. MATERIAL AND METHODS: Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8-week, open-label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis. RESULTS: Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P < .0001), biosynthesis of unsaturated fatty acids (P = .0045), butanoate (P < .0001), propanoate (P = .0053), and alanine, aspartate and glutamate (P < .0050) metabolites were increased after empagliflozin treatment under clamped euglycaemia. Of the urine metabolite groups, only butanoate metabolites (P = .0005) were significantly increased. Empagliflozin treatment also attenuated the increase in a number of urine metabolites observed with acute hyperglycaemia. CONCLUSIONS: Empagliflozin was associated with increased lipid and TCA cycle metabolites in participants with type 1 diabetes, suggesting a shift in metabolic substrate use and improved mitochondrial function. These effects result in more efficient energy production and may contribute to end-organ protection by alleviating local hypoxia and oxidative stress.
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Diabetes Mellitus Tipo 1 , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Glucosídeos/uso terapêutico , Humanos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto JovemRESUMO
AIM: To assess whether adding empagliflozin to closed-loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control. MATERIALS AND METHODS: In an open-label, crossover, non-inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared with no meal announcement with empagliflozin (in the primary non-inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non-inferiority comparison). RESULTS: Participants were aged 40 ± 15 years, had 27 ± 15 years diabetes duration and HbA1c of 7.6% ± 0.7% (59 ± 8 mmol/mol). The system with no meal announcement and empagliflozin was not non-inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0 ± 1.6 vs. 8.5 ± 1.5 mmol/L; non-inferiority p = .94), while simple meal announcement and empagliflozin was non-inferior (8.5 ± 1.4 mmol/L; non-inferiority p = .003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in the target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22 ± 0.18 vs. 0.13 ± 0.11 mmol/L; p < .001). CONCLUSIONS: Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting and improves glycaemic control in conjunction with carbohydrate counting, but does not allow for the elimination of meal announcement.
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Diabetes Mellitus Tipo 1 , Pâncreas Artificial , Adulto , Compostos Benzidrílicos , Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucosídeos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Projetos Piloto , Resultado do TratamentoRESUMO
Objectives: Diabetic kidney disease (DKD) is an independent predictor of cardiovascular morbidity and mortality in type 1 diabetes (T1D). We aimed to explore clinical and biochemical factors, including the achievement of American Diabetes Association (ADA) recommended targets associated with DKD in people living with T1D for ≥50 years. Methods: This was a post hoc analysis of a cross-sectional study of 75 participants enrolled in the Canadian Study of Longevity in T1D. We explored diabetes-related complications, including neuropathy, retinopathy, cardiovascular disease, and DKD. Study participants were dichotomized based on the achievement of ADA recommended targets as the low-target group (achieving ≤4 targets, n = 31) and high-target group (achieving >4 targets, n = 44). The outcome of interest was DKD defined by estimated glomerular filtration rate (eGFR) values <60/mL/min/1.73 m2 and/or 24-h albumin excretion >30 mg. Multivariable logistic regression models were employed to estimate odds ratios (ORs) for DKD with 95% confidence intervals (CIs). Results: Of the 75 participants with prolonged T1D duration (45% male, mean age 66 years), 25 participants had DKD and 50 did not. There was no statistical difference between the high- and low-target groups in terms of age and body mass index. eGFR was significantly higher and the prevalence of diabetic retinopathy was significantly lower in the high-target group. Older age at diagnosis of T1D and lower frequency component to high-frequency component ratio increased the odds of having DKD. Conclusions: In adults with prolonged T1D duration, older age at diagnosis and lower heart rate variability may be associated with DKD.
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Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/epidemiologia , Frequência Cardíaca/fisiologia , Fatores Etários , Idoso , Canadá/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Longevidade/fisiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15-19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the proportion with detectable neutralizing antibodies to the Omicron variants was decreased, and the levels were lower. Individuals with hybrid immunity at the baseline visit and those receiving the Original/Omicron bivalent vaccine between the two sampling times demonstrated increased neutralizing antibodies to all strains. Both a higher baseline neutralizing antibody titer to Omicron BA.5 and hybrid immunity were associated with protection against a breakthrough SARS-CoV-2 infection during a 4-month period of follow up during the Omicron BA.5 wave. Neither were associated with protection from a breakthrough infection at 10 months follow up. Receipt of an Original/Omicron BA.4/5 vaccine was associated with protection from a breakthrough infection at both 4 and 10 months follow up. This work demonstrates neutralizing antibody escape with the emerging Omicron variants and supports the use of additional vaccine doses with components that match circulating SARS-CoV-2 variants. A threshold value for neutralizing antibodies for protection against reinfection cannot be determined.
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AIMS: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D). METHODS: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions. The crossover BETWEEN trial (NCT02632747) investigated empagliflozin 25 mg plus ramipril for 4 weeks compared to placebo-ramipril for 4 weeks in 30 adults with T1D. RESULTS: In the glycemic clamp study, hyperglycemia acutely increased levels of NT-proBNP (p = 0.0003) and sTNFR2 (p = 0.003). BETWEEN participants treated with empagliflozin exhibited a paradoxical subacute rise in NT-proBNP (p = 0.0147) compared to placebo, independent of hematocrit. Individuals with higher baseline levels of sST2 and sTNFR1 had greater empagliflozin-associated reductions in systolic blood pressure and greater activation of renin-angiotensin-aldosterone system (RAAS) mediators, whereas those with higher baseline levels of KIM-1 and sTNFR1 had greater glomerular filtration rate (GFR) dip. CONCLUSION: The protective mechanisms of SGLT2 inhibition on blood pressure, RAAS activation, and renal hemodynamics are apparent in the subset of people with uncomplicated T1D with adverse cardiorenal and inflammatory markers.
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Compostos Benzidrílicos , Biomarcadores , Diabetes Mellitus Tipo 1 , Glucosídeos , Hiperglicemia , Inflamação , Humanos , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Masculino , Feminino , Biomarcadores/sangue , Adulto , Hiperglicemia/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/sangue , Pessoa de Meia-Idade , Estudos Cross-Over , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Fragmentos de Peptídeos , Peptídeo Natriurético EncefálicoRESUMO
BACKGROUND: Advancements in treatment have resulted in improved survival among people living with HIV. However, additional years of life are not necessarily spent in good health, as frailty tends to develop at a younger age among people living with HIV. We set out to examine the prevalence of frailty and its correlates among older adults living with HIV in Canada, with a primary interest in nadir CD4 count. METHODS: We performed a cross-sectional analysis of the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV aged 65 years or older. Participants were assessed using the Fried Frailty Phenotype at cohort entry, and those meeting ≥3 criteria were characterized as frail. We used Poisson regression with robust standard errors to estimate the association between nadir CD4 count and frailty, as well as age, gender, time since HIV diagnosis, comorbidities, marital status, and loneliness. RESULTS: Among 439 participants included in this analysis (median age 69 years, interquartile ranges 67-73), prevalence of frailty was 16.6%. Frailty was not associated with nadir CD4 count. Not being in a relationship (aRR 2.09, 95% CI 1.01 to 4.30) and greater degree of loneliness (aRR 1.25 per 10 point increase on UCLA loneliness scale, 95% CI 1.09 to 1.44) were associated with frailty. CONCLUSIONS: Frailty occurred in 16.6% of older adults living with HIV in this cohort. While nadir CD4 count did not correlate with frailty, being single and lonely did, highlighting the importance of recognizing and addressing these social vulnerabilities among people aging with HIV.
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Fragilidade , Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , Masculino , Feminino , Idoso , Fragilidade/epidemiologia , Prevalência , Estudos Transversais , Canadá/epidemiologia , Contagem de Linfócito CD4 , Estudos de Coortes , Idoso de 80 Anos ou maisRESUMO
Optimizing energy use in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter 2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of 25 mg empagliflozin orally once per day in 40 normotensive normoalbuminuric young adults with T1D. A consecutive 2-day assessment of clamped euglycemia and hyperglycemia was evaluated at baseline and posttreatment visits. Principal component analysis was performed on urinary amino acids grouped into representative metabolic pathways using MetaboAnalyst. At baseline, acute hyperglycemia was associated with changes in 25 of the 33 urinary amino acids or their metabolites. The most significant amino acid metabolites affected by acute hyperglycemia were 3-hydroxykynurenine, serotonin, glycyl-histidine, and nicotinic acid. The changes in amino acid metabolites were reflected by the induction of four biosynthetic pathways: aminoacyl-tRNA; valine, leucine, and isoleucine; arginine; and phenylalanine, tyrosine, and tryptophan. In acute hyperglycemia, empagliflozin significantly attenuated the increases in aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis. Our findings using amino acid metabolomics indicate that hyperglycemia stimulates biosynthetic pathways in T1D. SGLT2 inhibition may attenuate the increase in biosynthetic pathways to optimize kidney energy metabolism.
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Compostos Benzidrílicos , Diabetes Mellitus Tipo 1 , Glucosídeos , Hiperglicemia , Adulto Jovem , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Transportador 2 de Glucose-Sódio , Leucina , Isoleucina , Aminoácidos/metabolismo , Hiperglicemia/tratamento farmacológico , Valina , RNA de TransferênciaRESUMO
STUDY OBJECTIVES: To determine the prevalence of suspected cognitive impairment using the Centers for Disease Control and Prevention (CDC) cognitive question, Ascertain Dementia Eight-item Questionnaire (AD8), Modified Telephone Interview for Cognitive Status (TICS-M), and Telephone Montreal Cognitive Assessment (T-MoCA), the agreement between each tool beyond chance, and the risk factors associated with a positive screen. DESIGN: Multicenter prospective study. SETTING: Remote preoperative assessments. PATIENTS: 307 non-cardiac surgical patients aged ≥65 years. MEASUREMENTS: Prevalence, Cohen's kappa (κ). MAIN RESULTS: The T-MoCA detected the highest prevalence of suspected cognitive impairment (28%), followed by the AD8 (17%), CDC cognitive question (9%), and TICS-M (6%). The four screening tools showed poor agreement beyond chance with one another, with the CDC cognitive question and AD8 approaching the threshold for weak agreement (κ = 0.39). Depression was associated with screening positive on the CDC cognitive question (OR: 2.81; 95% CI: 1.04, 7.68). Obstructive sleep apnea (OSA) (OR: 3.10; 95% CI: 1.26, 7.71) and functional disability (OR: 3.74; 95% CI: 1.34, 11.11) were associated with a positive AD8 screen. Older age (OR: 1.56; 95% CI: 1.01, 2.41), male sex (OR: 3.08; 95% CI: 1.09, 9.40), and higher pain level (OR: 1.21; 95% CI: 1.01, 1.47) were associated with a positive TICS-M screen. Similarly, older age (OR: 1.33; 95% CI: 1.03, 1.73), male sex (OR: 2.02; 95% CI: 1.09, 3.83), and higher pain level (OR: 1.15; 95% CI: 1.02, 1.30) were associated with a positive T-MoCA screen. CONCLUSIONS: The CDC cognitive question, AD8, TICS-M, and T-MoCA were easily implemented during preoperative assessment among older surgical patients. OSA, functional disability, and depression were associated with complaints on the CDC cognitive question and AD8. Older age, male sex, and higher pain level were associated with screening positive on the TICS-M and T-MoCA. Early remote cognitive screening may enhance risk stratification of vulnerable patients.
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Disfunção Cognitiva , Humanos , Idoso , Masculino , Feminino , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Idoso de 80 Anos ou mais , Prevalência , Testes de Estado Mental e Demência , Fatores de Risco , Inquéritos e Questionários , Avaliação Geriátrica/métodos , Depressão/diagnóstico , Depressão/epidemiologia , Programas de Rastreamento/métodos , Testes Neuropsicológicos/estatística & dados numéricos , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
OBJECTIVES: Diabetic ketoacidosis (DKA) occurring after diabetes diagnosis is often associated with risk factors for other diabetes-related complications. In this study we aimed to determine the prognostic implications of DKA on all-cause mortality and complications in type 1 diabetes (T1D). METHODS: Previously collected data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were obtained through the the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository. Using Cox proportional hazards models with time-dependent covariates, we examined age- and sex-adjusted, glycated hemoglobin-adjusted, and fully adjusted associations of DKA with all-cause mortality, cardiovascular disease, microvascular, and acute complications over 34 years. RESULTS: Of the 1,441 study participants, 297 had 488 DKA events. Prior DKA was associated with a higher risk of age- and sex-adjusted all-cause mortality (hazard ratio [HR] 8.28, 95% confidence interval [CI] 3.74 to 18.32, p<0.001), major adverse cardiovascular events (MACEs) (HR 2.05, 95% CI 1.34 to 3.13, p<0.001), and all advanced microvascular and acute complications compared with no prior DKA. Most associations except retinopathy were significant even after adjustment for covariates. In our fully adjusted analysis, prior DKA was associated with a significantly higher risk of subsequent all-cause mortality (HR 9.13, 95% CI 3.87 to 21.50, p<0.001), MACEs (HR 1.66, 95% CI 1.07 to 2.59, p=0.03), advanced kidney disease (HR 2.10, 95% CI 1.00 to 4.22, p=0.049), advanced neuropathy (HR 1.49, 95% CI 1.05 to 2.13, p=0.03), severe hypoglycemia (HR 1.53, 95% CI 1.28 to 1.81, p<0.001), and recurrent DKA (HR 3.24, 95% CI 2.41 to 4.36, p<0.001) compared with person-time without DKA. CONCLUSIONS: DKA is a prognostic marker for diabetes complications, including excess all-cause mortality. Intensified clinical interventions, such as cardiovascular prevention strategies, may be warranted after diagnosis of DKA.
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Introduction: Continuous subcutaneous insulin infusion (CSII) in type 1 diabetes has been regarded as a major diabetic ketoacidosis (DKA) risk factor. We aimed to determine secular trends in risk since CSII implementation in the 1980s. Research Design and Methods: We assessed the relationship between time-varying CSII use and DKA events from 1983 to 2017 and by each decade in the 1441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants using crude and adjusted Cox proportional hazards models. Results: Time-varying CSII exposure was associated with significantly higher DKA risk in the 1980s (adjusted hazard ratio [HR] 5.81; 95% confidence interval [CI] 3.28-10.29; P < 0.001), but in the 2010s, this risk was not significantly elevated (adjusted HR 1.24; 95% CI 0.73-2.12; P = 0.43). Conclusions: DKA risk associated with CSII in type 1 diabetes has declined substantially since the 1980s such that the remaining risk in the past decade appears to be of low magnitude.
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OBJECTIVE: Although insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors. METHODS: In a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration ≥50 years) and 75 age- and sex-matched controls. Extensive phenotyping for complications was performed and patient-reported variables were included. C-peptide distributions were analyzed, and multivariable logistic regression was used to assess the variable association in participants with T1D. RESULTS: The 74 participants with T1D had a mean age of 66±8 years, a disease duration of 54 (interquartile range 52 to 58) years, and a glycated hemoglobin (A1C) of 7.4%±0.8% (56.8±9.15 mmol/mol). The 75 controls had a mean age of 65±8 years and an A1C of 5.7%±0.4% (38.4±4.05 mmol/mol). Participants with T1D had lower fasted serum C-peptide than controls (0.013±0.022 vs 1.595±1.099 nmol/L, p<0.001). Of the participants with T1D, C-peptide was detectable in 30 of 73 (41%) serum samples, 32 of 74 (43%) urine samples, and 48 of 74 (65%) for either serum or urine. The variables independently associated with detectable serum or urinary C-peptide were lower total daily insulin requirement (odds ratio 2.351 [for 1 lower unit/kg], p=0.013) and lower hypoglycemia worry score (odds ratio 1.059 [for 1 point lower on the worry subscore of the Hypoglycemia Fear Survey], p=0.030). CONCLUSIONS: Although detectable C-peptide in longstanding diabetes was common, the magnitude of concentration was extremely low when compared with age- and sex-matched controls. Despite minimal detectability, its presence is validated by lower insulin requirements and strongly associated with lower hypoglycemia worry.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 1/complicações , Peptídeo C , Hemoglobinas Glicadas , Longevidade , Estudos Transversais , Canadá/epidemiologia , InsulinaRESUMO
BACKGROUND: We have aimed to assess whether muscle thickness ultrasound (US) shows differences between patients with chronic inflammatory demyelinating polyneuropathy (CIDP), chronic axonal polyneuropathy (CAP), and other neuromuscular (NM) diseases compared to controls and to each other. METHODS: We performed a cross-sectional study from September 2021 to June 2022. All subjects underwent quantitative sonographic evaluation of muscle thickness in eight relaxed muscles and four contracted muscles. Differences were assessed using multivariable linear regression, correcting for age and body mass index (BMI). RESULTS: The study cohort consisted of 65 healthy controls, and 95 patients: 31 with CIDP, 34 with CAP, and 30 with other NM diseases. Both relaxed and contracted muscle thickness in all patient groups were lower than in the healthy controls, after controlling for age and body mass index (BMI). Regression confirmed that the differences persisted between patient groups and healthy controls. Differences between patient groups were not apparent. CONCLUSION: The current study shows that muscle ultrasound thickness is not specific in NM disorders, but shows a global reduction in thickness compared with healthy controls after corrections for age and BMI.
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The Covid-19 pandemic required many clinical trials to adopt a decentralized framework to continue research activities during lock down restrictions. The STOPCoV study was designed to assess the safety and efficacy of Covid-19 vaccines in those aged 70 and above compared to those aged 30-50 years of age. In this sub-study we aimed to determine participant satisfaction for the decentralized processes, accessing the study website and collecting and submitting study specimens. The satisfaction survey was based on a Likert scale developed by a team of three investigators. Overall, there were 42 questions for respondents to answer. The invitation to participate with a link to the survey was emailed to 1253 active participants near the mid-way point of the main STOPCoV trial (April 2022). The results were collated and answers were compared between the two age cohorts. Overall, 70% (83% older, 54% younger cohort, no difference by sex) responded to the survey. The overall feedback was positive with over 90% of respondents answering that the website was easy to use. Despite the age gap, both the older cohort and younger cohort reported ease of performing study activities through a personal electronic device. Only 30% of the participants had previously participated in a clinical trial, however over 90% agreed that they would be willing to participate in future clinical research. Some difficulties were noted in refreshing the browser whenever updates to the website were made. The feedback attained will be used to improve current processes and procedures of the STOPCoV trial as well as share learning experiences to inform future fully decentralized research studies.
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The initial two-dose vaccine series and subsequent booster vaccine doses have been effective in modulating SARS-CoV-2 disease severity and death but do not completely prevent infection. The correlates of infection despite vaccination continue to be under investigation. In this prospective decentralized study (n = 1286) comparing antibody responses in an older- (≥70 years) to a younger-aged cohort (aged 30-50 years), we explored the correlates of breakthrough infection in 983 eligible subjects. Participants self-reported data on initial vaccine series, subsequent booster doses and COVID-19 infections in an online portal and provided self-collected dried blood spots for antibody testing by ELISA. Multivariable survival analysis explored the correlates of breakthrough infection. An association between higher antibody levels and protection from breakthrough infection observed during the Delta and Omicron BA.1/2 waves of infection no longer existed during the Omicron BA.4/5 wave. The older-aged cohort was less likely to have a breakthrough infection at all time-points. Receipt of an original/Omicron vaccine and the presence of hybrid immunity were associated with protection of infection during the later Omicron BA.4/5 and XBB waves. We were unable to determine a threshold antibody to define protection from infection or to guide vaccine booster schedules.
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OBJECTIVE: Rather than during illness while diabetic ketoacidosis (DKA) is developing, we aimed to determine if levels of routine point-of-care capillary blood ketones could predict future DKA. RESEARCH DESIGN AND METHODS: We examined previously collected data from placebo-assigned participants in an adjunct-to-insulin medication trial program that included measurement of fasted capillary blood ketone levels twice per week in a 2-month baseline period. The outcome was 6- to 12-month trial-adjudicated DKA. RESULTS: DKA events occurred in 12 of 484 participants at a median of 105 (interquartile range 43, 199) days. Maximum ketone levels were higher in patient cases compared with in control patients (0.8 [0.6, 1.2] vs. 0.3 [0.2, 0.7] mmol/L; P = 0.002), with a nonparametric area under the receiver operating characteristic curve of 0.77 (95% CI 0.66-0.88). Ketone levels ≥0.8 mmol/L had a sensitivity of 64%, a specificity of 78%, and positive and negative likelihood ratios of 2.9 and 0.5, respectively. CONCLUSIONS: This proof of concept that routine capillary ketone surveillance can identify individuals at high risk of future DKA implies a role for future technologies including continuous ketone monitoring.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Cetose , Humanos , Ácido 3-Hidroxibutírico , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/diagnóstico , Cetonas , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
OBJECTIVES: Pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or microvascular complications like albuminuria, retinopathy and pre-eclampsia. In this study we aimed to identify whether mechanistic pathways associated with microvascular complications are active in pregnant women with GDM or microvascular disease. METHODS: Urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism and tubular injury were quantified in 355 pregnant women with and without GDM. Participants underwent fundus photography graded for retinopathy. Adjusted associations between individual biomarkers and each outcome variable of interest, including GDM status, albuminuria and retinopathy, were performed using logistic regression. RESULTS: After adjusting for age, systolic blood pressure, body mass index and ethnicity, significant associations between GDM status and apolipoprotein A1, interleukin (IL)-6, IL-8, soluble tumour necrosis factor receptor-I and -II (sTNFR-I and -II), vascular endothelial growth factor and von Willebrand factor were observed. Increased high-sensitivity C-reactive protein (hsCRP) and sTNFR-II were associated with higher levels of albuminuria. hsCRP and previous GDM were associated with retinopathy. CONCLUSION: Mechanistic pathways associated with microvascular complications appear to be active in pregnant women with GDM or microvascular disease.
Assuntos
Diabetes Gestacional , Doenças Retinianas , Gravidez , Humanos , Feminino , Fatores de Risco , Proteína C-Reativa , Albuminúria , Metabolismo dos Lipídeos , Fator A de Crescimento do Endotélio Vascular , Biomarcadores , Inflamação/complicações , Doenças Retinianas/complicaçõesRESUMO
To determine the prevalence and the associated clinical characteristics of orthostatic hypotension and orthostatic hypertension in patients with diabetic sensorimotor polyneuropathy (DSP). METHODS: A single-center retrospective cross-sectional study was conducted on 200 DSP patients who had 3-minute orthostatic measures as part of the standard clinic evaluation. We measured the heart rate (HR) and blood pressure (BP) supine and again after 3 min of standing. RESULTS: The prevalence of orthostatic hypotension was 19.5% and that of orthostatic hypertension was 23%. Subjects with orthostatic hypotension had significantly longer diabetes duration than subjects who were normotensive and those with orthostatic hypertension. Quantitatively, BP changes from supine to standing correlated with diabetes duration (R = 0.306; P = 0.0582) and age (R = 0.434; P = 0.006) in subjects with orthostatic hypotension. CONCLUSIONS: Orthostatic hypertension and orthostatic hypotension are frequent in patients with DSP. Orthostatic hypertension is associated with shorter diabetes duration than orthostatic hypotension.