Evaluation of a mathematical model of diabetes progression against observations in the Diabetes Prevention Program

2012 ◽  
Vol 303 (2) ◽  
pp. E200-E212 ◽  
Author(s):  
Thomas Hardy ◽  
Eyas Abu-Raddad ◽  
Niels Porksen ◽  
Andrea De Gaetano
Keyword(s):  
Mathematical Model ◽  
Prevention Program ◽  
Diabetes Prevention ◽  
Diabetes Prevention Program ◽  
Diabetes Incidence ◽  
Cell Protection ◽  
Data Set ◽  
Diabetes Progression ◽  
The Impact

The seminal publication of the Diabetes Prevention Program (DPP) results in 2002 has provided insight into the impact of major therapies on the development of diabetes over a time span of a few years. In the present work, the publicly available DPP data set is used to calibrate and evaluate a recently developed mechanistic mathematical model for the long-term development of diabetes to assess the model's ability to predict the natural history of disease progression and the effectiveness of preventive interventions. A general population is generated from which virtual subject samples corresponding to the DPP enrollment criteria are selected. The model is able to reproduce with good fidelity the observed time courses of both diabetes incidence and average glycemia, under realistic hypotheses on evolution of disease and efficacy of the studied therapies, for all treatment arms. Model-based simulations of the long-term evolution of the disease are consistent with the transient benefits observed with conventional therapies and with promising effects of radical improvement of insulin sensitivity (as by metabolic surgery) or of β-cell protection. The mechanistic diabetes progression model provides a credible tool by which long-term implications of antidiabetic interventions can be evaluated.

scholarly journals Long-term metformin adherence in the Diabetes Prevention Program Outcomes Study

2020 ◽  
Vol 8 (1) ◽  
pp. e001537
Author(s):  
Elizabeth Arquin Walker ◽  
Jeffrey S Gonzalez ◽  
Mark T Tripputi ◽  
Samuel Dagogo-Jack ◽  
Margaret J Matulik ◽  
...  
Keyword(s):  
Prevention Program ◽  
Diabetes Prevention ◽  
Proportional Hazards ◽  
Diabetes Prevention Program ◽  
Cox Proportional Hazards ◽  
Diabetes Incidence ◽  
Open Label ◽  
Program Outcomes ◽  
Outcomes Study

IntroductionTo investigate long-term metformin adherence in the Diabetes Prevention Program Outcomes Study (DPPOS) by examining: (1) predictors of long-term adherence to study metformin and (2) whether metformin adherence was associated with incident type 2 diabetes.Research design and methodsDPPOS was an open-label continuation of the randomized clinical trial (Diabetes Prevention Program (DPP)) in which eligible participants randomized to the metformin group were offered study metformin and followed over 11 years. A brief structured adherence interview was administered semiannually. Metformin adherence was assessed by pill counts. Predictors of metformin adherence were examined in multivariate regression models. Incident diabetes associated with metformin adherence and other variables was assessed in Cox proportional hazards models.ResultsOf 868 participants eligible to continue taking study metformin, 664 (76%) took at least some metformin over 11 years, with 478 of them reporting problems with adherence. DPPOS cumulative adherence showed significant associations of higher adherence (≥80%) with early adherence at 3 months in DPP (p<0.001) and lower depression scores during DPPOS (p<0.001); significant differences were also seen by race/ethnicity (p<0.004). Predicting adherence by multivariate modeling showed odds of adherence significantly lower for Black participants and for participants reporting more than one barrier. Odds for adherence were significantly higher for those adherent early in DPP and those reporting at least one planned strategy to improve adherence. Higher metformin adherence was significantly associated with a lower diabetes risk (p=0.04), even after adjustment for demographic variables, depression, and anxiety scores.ConclusionsIn this long-term diabetes prevention study, early metformin adherence and planned strategies to promote adherence improved long-term adherence over 11 years; higher adherence to metformin was related to lower diabetes incidence. Incorporating strategies to promote adherence when initially prescribing metformin and counseling to support adherence over time are warranted.

scholarly journals The Impact of a Yearlong Diabetes Prevention Program-Based Lifestyle Intervention on Cardiovascular Health Metrics

2021 ◽  
Vol 12 ◽  
pp. 215013272110298
Author(s):  
Susan M. Devaraj ◽  
Bonny Rockette-Wagner ◽  
Rachel G. Miller ◽  
Vincent C. Arena ◽  
Jenna M. Napoleone ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Lifestyle Intervention ◽  
Prevention Program ◽  
Diabetes Prevention ◽  
Cardiovascular Health ◽  
Diabetes Prevention Program ◽  
Behavioral Risk ◽  
Community Based ◽  
The Impact

Introduction The American Heart Association created “Life’s Simple Seven” metrics to estimate progress toward improving US cardiovascular health in a standardized manner. Given the widespread use of federally funded Diabetes Prevention Program (DPP)-based lifestyle interventions such as the Group Lifestyle Balance (DPP-GLB), evaluation of change in health metrics within such a program is of national interest. This study examined change in cardiovascular health metric scores during the course of a yearlong DPP-GLB intervention. Methods Data were combined from 2 similar randomized trials offering a community based DPP-GLB lifestyle intervention to overweight/obese individuals with prediabetes and/or metabolic syndrome. Pre/post lifestyle intervention participation changes in 5 of the 7 cardiovascular health metrics were examined at 6 and 12 months (BMI, blood pressure, total cholesterol, fasting plasma glucose, physical activity). Smoking was rare and diet was not measured. Results Among 305 participants with complete data (81.8% of 373 eligible adults), significant improvements were demonstrated in all 5 risk factors measured continuously at 6 and 12 months. There were significant positive shifts in the “ideal” and “total” metric scores at both time points. Also noted were beneficial shifts in the proportion of participants across categories for BMI, activity, and blood pressure. Conclusion AHA-metrics could have clinical utility in estimating an individual’s cardiovascular health status and in capturing improvement in cardiometabolic/behavioral risk factors resulting from participation in a community-based translation of the DPP lifestyle intervention.

scholarly journals Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study

2016 ◽  
Vol 101 (4) ◽  
pp. 1754-1761 ◽  
Author(s):  
Vanita R. Aroda ◽  
Sharon L. Edelstein ◽  
Ronald B. Goldberg ◽  
William C. Knowler ◽  
Santica M. Marcovina ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Prevention Program ◽  
Diabetes Prevention ◽  
Vitamin B12 Deficiency ◽  
Diabetes Prevention Program ◽  
Open Label ◽  
Metformin Group ◽  
B12 Deficiency ◽  
Outcomes Study

Abstract Context: Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use. Objective: To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). Design: Secondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years. Setting: Twenty-seven study centers in the United States. Patients: DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively. Interventions: Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS). Main Outcome Measures: B12 deficiency, anemia, and peripheral neuropathy. Results: Low B12 (≤ 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P &lt; .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use, 1.13; 95% confidence interval, 1.06–1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels. Conclusions: Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.

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