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Predicting major outcomes in type 1 diabetes: a model development and validation study.

ABSTRACT: Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts.Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic factors for major outcomes were combined in a Weibull regression model. The performance of the model was tested in three different prospective cohorts: the Pittsburgh Epidemiology of Diabetes Complications study (EDC, n?=?554), the Finnish Diabetic Nephropathy study (FinnDiane, n?=?2,999) and the Coronary Artery Calcification in Type 1 Diabetes study (CACTI, n?=?580). Major outcomes included major CHD, stroke, end-stage renal failure, amputations, blindness and all-cause death.A total of 95 EURODIAB patients with type 1 diabetes developed major outcomes during follow-up. Prognostic factors were age, HbA1c, WHR, albumin/creatinine ratio and HDL-cholesterol level. The discriminative ability of the model was adequate, with a concordance statistic (C-statistic) of 0.74. Discrimination was similar or even better in the independent cohorts, the C-statistics being: EDC, 0.79; FinnDiane, 0.82; and CACTI, 0.73.Our prognostic model, which uses easily accessible clinical features can discriminate between type 1 diabetes patients who have a good or a poor prognosis. Such a prognostic model may be helpful in clinical practice and for risk stratification in clinical trials.

SUBMITTER: Soedamah-Muthu SS

PROVIDER: S-EPMC4399797 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Predicting major outcomes in type 1 diabetes: a model development and validation study.

Soedamah-Muthu Sabita S SS Vergouwe Yvonne Y Costacou Tina T Miller Rachel G RG Zgibor Janice J Chaturvedi Nish N Snell-Bergeon Janet K JK Maahs David M DM Rewers Marian M Forsblom Carol C Harjutsalo Valma V Groop Per-Henrik PH Fuller John H JH Moons Karel G M KG Orchard Trevor J TJ

Diabetologia 20140904 11

<h4>Aims/hypothesis</h4>Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts.<h4>Methods</h4>Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic fac ...[more]

PMID: 25186291

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Project description:BackgroundObesity is closely related to the development of insulin resistance and type 2 diabetes (T2D). The prevention of T2D has become imperative to stem the rising rates of this disease. Weight loss is highly effective in preventing T2D; however, the at-risk pool is large, and a clinically meaningful metric for risk stratification to guide interventions remains a challenge. The objective of this study is to predict T2D risk using full-information continuous analysis of nationally sampled data from white and black American adults age ≥45 years.Methods and findingsA sample of 12,043 black (33%) and white individuals from a population-based cohort, REasons for Geographic And Racial Differences in Stroke (REGARDS) (enrolled 2003-2007), was observed through 2013-2016. The mean participant age was 63.12 ± 8.62 years, and 43.7% were male. Mean BMI was 28.55 ± 5.61 kg/m2. Risk factors for T2D regularly recorded in the primary care setting were used to evaluate future T2D risk using Bayesian logistic regression. External validation was performed using 9,710 participants (19% black) from Atherosclerotic Risk in Communities (ARIC) (enrolled 1987-1989), observed through 1996-1998. The mean participant age in this cohort was 53.86 ± 5.65 years, and 44.6% were male. Mean BMI was 27.15 ± 4.92 kg/m2. Predictive performance was assessed using the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. The primary outcome was incident T2D. By 2016 in REGARDS, there were 1,602 incident cases of T2D. Risk factors used to predict T2D progression included age, sex, race, BMI, triglycerides, high-density lipoprotein, blood pressure, and blood glucose. The Bayesian logistic model (AUC = 0.79) outperformed the Framingham risk score (AUC = 0.76), the American Diabetes Association risk score (AUC = 0.64), and a cardiometabolic disease system (using Adult Treatment Panel III criteria) (AUC = 0.75). Validation in ARIC was robust (AUC = 0.85). Main limitations include the limited generalizability of the REGARDS sample to black and white, older Americans, and no time to diagnosis for T2D.ConclusionsOur results show that a Bayesian logistic model using full-information continuous predictors has high predictive discrimination, and can be used to quantify race- and sex-specific T2D risk, providing a new, powerful predictive tool. This tool can be used for T2D prevention efforts including weight loss therapy by allowing clinicians to target high-risk individuals in a manner that could be used to optimize outcomes.

Project description:Aims/hypothesisWe aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes.MethodsA cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., ≥10%) using the model with the percentage eligible for statins using current guidelines by age.ResultsThe age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer-Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic from 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and ≥ 60 years, respectively (all p values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those ≥40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD ≥10% in 10 years.Conclusions/interpretationA prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention, the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.

Project description:BackgroundExisting predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes.Methods and findingsWe developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R2. CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes -0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants.ConclusionsOur study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes.

Project description:BackgroundDiabetes mellitus is a growing global health challenge and affects patients of all ages. Treatment aims to keep blood glucose levels close to normal and to prevent or delay complications. However, adherence to antidiabetic medicines is often unsatisfactory.PurposeHere, we established and internally validated a medication nonadherence risk nomogram for use in Chinese type 2 diabetes mellitus (T2DM) patients.MethodsThis cross-sectional study was carried out from July-December 2020 on randomly selected T2DM patients visiting a diabetes clinic and included 753 participants. Adherence was analyzed based on an eight-item Morisky Medication Adherence Scale (MMAS-8). Other data, including patient demographics, treatment, complications, and comorbidities, were also collected on questionnaires. Optimization of feature selection to develop the medication nonadherence risk model was achieved using the least absolute shrinkage and selection operator regression model (LASSO). A prediction model comprising features selected from LASSO model was designed by applying multivariable logistic regression analysis. The decision curve analysis, calibration plot, and C-index were utilized to assess the performance of the model in terms of discrimination, calibration, and clinical usefulness. Bootstrapping validation was applied for internal validation.ResultsThe prediction nomogram comprised several factors including sex, marital status, education level, employment, distance, self-monitoringofbloodglucose, disease duration, and dosing frequency of daily hypoglycemics (pills, insulin, or glucagon-like peptide-1). The model exhibited good calibration and good discrimination (C-index = 0.79, 95% CI [0.75-0.83]). In the validation samples, a high C-index (0.75) was achieved. Results of the decision curve analysis revealed that the nonadherence nomogram could be applied in clinical practice in cases where the intervention is decided at a nonadherence possibility threshold of 12%.ConclusionThe number of patients who adhere to anti-diabetes therapy was small. Being single male, having no formal education, employed, far from hospital, long disease duration, and taking antidiabetics twice or thrice daily, had significant negative correlation with medication adherence. Thus, strategies for improving adherence are urgently needed.

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Predicting major outcomes in type 1 diabetes: a model development and validation study.

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Predicting major outcomes in type 1 diabetes: a model development and validation study.

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