Trends in anti-diabetic medication use, severe hyperglycaemia and severe hypoglycaemia among American Indian and Alaska Native Peoples, 2009-2013.

AIMS: Type 2 diabetes (T2D) and its complications disproportionally affect American Indian and Alaska Native (AI/AN) peoples. Prescribing decisions for anti-diabetic medications are complicated and require balancing medication benefits, costs and side effects. Little is known about trends in anti-diabetic medication use as well as acute diabetes complications among AI/AN adults. Here, we examined patterns and trends in anti-diabetic medication use and rates of hospital admissions or emergency department (ED) visits due to severe hypoglycaemia and hyperglycaemia among AI/AN adults with T2D. MATERIALS AND METHODS: We conducted a retrospective analysis of Indian Health Service (IHS) Improving Health Care Delivery Data Project. A total of 39 183 AI/AN adults aged ≥18 years with T2D who used IHS or Tribal health services during any of the fiscal years (FYs) 2009-2013 were included. Utilization rates of each class of anti-diabetic medications and rates of severe hypoglycaemia and severe hyperglycaemia in emergency room and/or inpatient discharge diagnoses were calculated for each year. Longitudinal statistical models were fitted to examine time trends of anti-diabetic medication use and complications. RESULTS: During 2009-2013, use of metformin (56.0%-60.5%), insulin (31.4%-35.9%) and dipeptidyl peptidase-4 inhibitors (1.4%-9.0%) increased, whereas the use of sulfonylureas (40.3%-32.9%) and thiazolidinediones (TZDs, 31.6%-8.8%) decreased significantly. Trends in severe hypoglycaemia (1.6%-0.8%) and severe hyperglycaemia (2.0%-1.6%) declined gradually. CONCLUSIONS: There were significant changes in the utilization of different anti-diabetic medication classes during 2009-2013 among AI/AN adults with T2D. Concurrently, there were significant reductions in severe hypoglycaemia and severe hyperglycaemia.

Evaluating Community-Based Translational Interventions Using Historical Controls: Propensity Score vs. Disease Risk Score Approach.

Many community-based translations of evidence-based interventions are designed as one-arm studies due to ethical and other considerations. Evaluating the impacts of such programs is challenging. Here, we examine the effectiveness of the lifestyle intervention implemented by the Special Diabetes Program for Indians Diabetes Prevention (SDPI-DP) demonstration project, a translational lifestyle intervention among American Indian and Alaska Native communities. Data from the landmark Diabetes Prevention Program placebo group was used as a historical control. We compared the use of propensity score (PS) and disease risk score (DRS) matching to adjust for potential confounder imbalance between groups. The unadjusted hazard ratio (HR) for diabetes risk was 0.35 for SDPI-DP lifestyle intervention vs. control. However, when relevant diabetes risk factors were considered, the adjusted HR estimates were attenuated toward 1, ranging from 0.56 (95% CI 0.44-0.71) to 0.69 (95% CI 0.56-0.96). The differences in estimated HRs using the PS and DRS approaches were relatively small but DRS matching resulted in more participants being matched and smaller standard errors of effect estimates. Carefully employed, publicly available randomized clinical trial data can be used as a historical control to evaluate the intervention effectiveness of one-arm community translational initiatives. It is critical to use a proper statistical method to balance the distributions of potential confounders between comparison groups in this kind of evaluations.

Neighborhood characteristics and lifestyle intervention outcomes: Results from the Special Diabetes Program for Indians.

Growing evidence reveals various neighborhood conditions are associated with the risk of developing type 2 diabetes. It is unknown, however, whether the effectiveness of diabetes prevention interventions is also influenced by neighborhood characteristics. The purpose of the current study is to examine the impact of neighborhood characteristics on the outcomes of a lifestyle intervention to prevent diabetes in American Indians and Alaska Natives (AI/ANs). Year 2000 US Census Tract data were linked with those from the Special Diabetes Program for Indians Diabetes Prevention Program (SDPI-DP), an evidence-based lifestyle intervention implemented in 36 AI/AN grantee sites across the US. A total of 3394 participants started the intervention between 01/01/2006 and 07/31/2009 and were followed by 07/31/2016. In 2016-2017, data analyses were conducted to evaluate the relationships of neighborhood characteristics with intervention outcomes, controlling for individual level socioeconomic status. AI/ANs from sites located in neighborhoods with higher median household income had 38% lower risk of developing diabetes than those from sites with lower neighborhood income (adjusted hazard ratio = 0.65, 95% CI: 0.47-0.90). Further, those from sites with higher neighborhood concentrations of AI/ANs achieved less BMI reduction and physical activity increase. Meanwhile, participants from sites with higher neighborhood level of vehicle occupancy made more improvement in BMI and diet. Lifestyle intervention effectiveness was not optimal when the intervention was implemented at sites with disadvantaged neighborhood characteristics. Meaningful improvements in socioeconomic and other neighborhood disadvantages of vulnerable populations could be important in stemming the global epidemic of diabetes.

Food choices and distress in reservation-based American Indians and Alaska Natives with type 2 diabetes.

OBJECTIVE: To examine the association between food choice and distress in a large national sample of American Indians/Alaska Natives (AI/AN) with type 2 diabetes. DESIGN: Participants completed a sociodemographic survey, an FFQ and the Kessler-6 Distress Scale. Foods were identified as 'healthy' or 'unhealthy' using a classification grounded in the health education provided by the programme case managers; healthy and unhealthy food scores were calculated using reported intake frequencies. Pearson's correlation coefficients for distress and food scores were calculated for all participants and by gender. Multiple linear regression models stratified by gender assessed the association between distress and food scores, controlling for sociodemographics and duration of type 2 diabetes. SETTING: Rural AI reservations and AN villages. SUBJECTS: AI/AN (n 2484) with type 2 diabetes. RESULTS: Both males (34·9 %) and females (65·1 %) had higher healthy food scores than unhealthy scores. In bivariate analysis, distress level had a significant negative correlation with healthy food scores among female participants, but the association was not significant among males. Significant positive correlations between distress and unhealthy food scores were found in both genders. In the final multivariate models, healthy food scores were not significantly related to distress; however, unhealthy food scores showed significant positive relationships with distress for both genders (females: ß=0·078, P=0·0007; males: ß=0·139, P<0·0001). CONCLUSIONS: Health professionals working with AI/AN diagnosed with type 2 diabetes should offer food choice strategies during difficult times and recognize that males may be more likely than females to select unhealthy foods when distressed.

Obesity and Overweight in American Indian and Alaska Native Children, 2006-2015.

OBJECTIVES: To estimate obesity and overweight prevalence in American Indian and Alaska Native (AI/AN) children across genders, ages, and geographic regions in the Indian Health Service active clinical population. METHODS: We obtained data from the Indian Health Service National Data Warehouse. At least 184 000 AI/AN children aged 2 to 19 years had body mass index data for each year studied, 2006 to 2015. We calculated body mass index percentiles with the 2000 Centers for Disease Control and Prevention growth charts. RESULTS: In 2015, the prevalence of overweight and obesity in AI/AN children aged 2 to 19 years was 18.5% and 29.7%, respectively. Boys had higher obesity prevalence than girls (31.5% vs 27.9%). Children aged 12 to 19 years had a higher prevalence of overweight and obesity than younger children. The AI/AN children in our study had a higher prevalence of obesity than US children overall in the National Health and Nutrition Examination Survey. Results for 2006 through 2014 were similar. CONCLUSIONS: The prevalence of overweight and obesity among AI/AN children in this population may have stabilized, while remaining higher than prevalence for US children overall.

Vital Signs: Decrease in Incidence of Diabetes-Related End-Stage Renal Disease among American Indians/Alaska Natives - United States, 1996-2013.

BACKGROUND: American Indians and Alaska Natives (AI/AN) have the highest diabetes prevalence among any racial/ethnic group in the United States. Among AI/AN, diabetes accounts for 69% of new cases of end-stage renal disease (ESRD), defined as kidney failure treated with dialysis or transplantation. During 1982-1996, diabetes-related ESRD (ESRD-D) in AI/AN increased substantially and disproportionately compared with other racial/ethnic groups. METHODS: Data from the U.S. Renal Data System, the Indian Health Service (IHS), the National Health Interview Survey, and the U.S. Census were used to calculate ESRD-D incidence rates by race/ethnicity among U.S. adults aged ≥18 years during 1996-2013 and in the diabetic population during 2006-2013. Rates were age-adjusted based on the 2000 U.S. standard population. IHS clinical data from the Diabetes Cares and Outcomes Audit were analyzed for diabetes management measures in AI/AN. RESULTS: Among AI/AN adults, age-adjusted ESRD-D rates per 100,000 population decreased 54%, from 57.3 in 1996 to 26.5 in 2013. Although rates for adults in other racial/ethnic groups also decreased during this period, AI/AN had the steepest decline. Among AI/AN with diabetes, ESRD-D incidence decreased during 2006-2013 and, by 2013, was the same as that for whites. Measures related to the assessment and treatment of ESRD-D risk factors also showed more improvement during this period in AI/AN than in the general population. CONCLUSION AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Despite well-documented health and socioeconomic disparities among AI/AN, ESRD-D incidence rates among this population have decreased substantially since 1996. This decline followed implementation by the IHS of public health and population management approaches to diabetes accompanied by improvements in clinical care beginning in the mid-1980s. These approaches might be a useful model for diabetes management in other health care systems, especially those serving populations at high risk.

Diabetes-related mortality among American Indians and Alaska Natives, 1990-2009.

OBJECTIVES: We assessed diabetes-related mortality for American Indians and Alaska Natives (AI/ANs) and Whites. METHODS: Study populations were non-Hispanic AI/AN and White persons in Indian Health Service (IHS) Contract Health Service Delivery Area counties; Hispanics were excluded. We used 1990 to 2009 death certificate data linked to IHS patient registration records to identify AI/AN decedents aged 20 years or older. We examined disparities and trends in mortality related to diabetes as an underlying cause of death (COD) and as a multiple COD. RESULTS: After increasing between 1990 and 1999, rates of diabetes as an underlying COD and a multiple COD subsequently decreased in both groups. However, between 2000 and 2009, age-adjusted rates of diabetes as an underlying COD and a multiple COD remained 2.5 to 3.5 times higher among AI/AN persons than among Whites for all age groups (20-44, 45-54, 55-64, 65-74, and ≥ 75 years), both sexes, and every IHS region except Alaska. CONCLUSIONS: Declining trends in diabetes-related mortality in both AI/AN and White populations are consistent with recent improvements in their health status. Reducing persistent disparities in diabetes mortality will require developing effective approaches to not only control but also prevent diabetes among AI/AN populations.

The Relationship between All-Cause Dementia and Acute Diabetes Complications among American Indian and Alaska Native Peoples.

BACKGROUND: American Indian and Alaska Native people (AI/AN) bear a disproportionate burden of diabetes. Growing evidence shows significant associations between several acute diabetes complications and dementia among diabetes patients. However, little is known about these relationships among AI/AN adults. Here, we aim to investigate these associations among AI/AN adults. METHODS: This cross-sectional study extracted data from the Indian Health Service's (IHS) National Data Warehouse and related administrative databases. A total of 29,337 IHS actual users with diabetes who were 45+ years old during fiscal year 2013 were included. All-cause dementia and diabetes complications were identified using ICD-9 diagnostic codes. Negative binomial regression models were used to evaluate the associations of interest. RESULTS: Nearly 3% of AI/AN diabetes patients had a dementia diagnosis. After controlling for covariates, dementia was associated with a 94% higher rate of severe hypoglycemia (Incidence Rate Ratio [IRR = 1.94, 95% CI:1.50-2.51), 52% higher rate of severe hyperglycemia (IRR = 1.52, 95% CI, 1.11-2.08), and 92% higher rate of any acute complication (IRR = 1.92, 95% CI:1.53-2.41). CONCLUSIONS: AI/AN diabetes patients with dementia suffered from considerably higher rates of acute diabetes complications than their counterparts without dementia. The clinical management of patients with comorbid diabetes and dementia is particularly challenging and may require individualized treatment approaches.

The National Clinical Care Commission Report to Congress: Summary and Next Steps.

The U.S. is experiencing an epidemic of type 2 diabetes. Socioeconomically disadvantaged and certain racial and ethnic groups experience a disproportionate burden from diabetes and are subject to disparities in treatment and outcomes. The National Clinical Care Commission (NCCC) was charged with making recommendations to leverage federal policies and programs to more effectively prevent and control diabetes and its complications. The NCCC determined that diabetes cannot be addressed simply as a medical problem but must also be addressed as a societal problem requiring social, clinical, and public health policy solutions. As a result, the NCCC's recommendations address policies and programs of both non-health-related and health-related federal agencies. The NCCC report, submitted to the U.S. Congress on 6 January 2022, makes 39 specific recommendations, including three foundational recommendations that non-health-related and health-related federal agencies coordinate their activities to better address diabetes, that all federal agencies and departments ensure that health equity is a guiding principle for their policies and programs that impact diabetes, and that all Americans have access to comprehensive and affordable health care. Specific recommendations are also made to improve general population-wide policies and programs that impact diabetes risk and control, to increase awareness and prevention efforts among those at high risk for type 2 diabetes, and to remove barriers to access to effective treatments for diabetes and its complications. Finally, the NCCC recommends that an Office of National Diabetes Policy be established to coordinate the activities of health-related and non-health-related federal agencies to address diabetes prevention and treatment. The NCCC urges Congress and the Secretary of Health and Human Services to implement these recommendations to protect the health and well-being of the more than 130 million Americans at risk for and living with diabetes.

The National Clinical Care Commission Report to Congress: Background, Methods, and Foundational Recommendations.

Since the first Federal Commission on Diabetes issued its report in 1975, the diabetes epidemic in the U.S. has accelerated, and efforts to translate advances in diabetes treatment into routine clinical practice have stalled. In 2021, the National Clinical Care Commission (NCCC) delivered a report to Congress that provided recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. In the five articles in this series, we present the NCCC's evidence-based recommendations to 1) reduce diabetes-related risks, prevent type 2 diabetes, and avert diabetes complications through changes in federal policies and programs affecting the general population; 2) prevent type 2 diabetes in at-risk individuals through targeted lifestyle and medication interventions; and 3) improve the treatment of diabetes and its complications to improve the health outcomes of people with diabetes. In this first article, we review the successes and limitations of previous federal efforts to combat diabetes. We then describe the establishment of and charge to the NCCC. We discuss the development of a hybrid conceptual model that guided the NCCC's novel all-of-government approach to address diabetes as both a societal and medical problem. We then review the procedures used by the NCCC to gather information from federal agencies, stakeholders, key informants, and the public and to conduct literature reviews. Finally, we review the NCCC's three foundational recommendations: 1) improve the coordination of non-health-related and health-related federal agencies to address the social and environmental conditions that are accelerating the diabetes epidemic; 2) ensure that all Americans at risk for and with diabetes have health insurance and access to health care; and 3) ensure that all federal policies and programs promote health equity in diabetes.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs for Population-Level Diabetes Prevention and Control: Recommendations From the National Clinical Care Commission.

The etiology of type 2 diabetes is rooted in a myriad of factors and exposures at individual, community, and societal levels, many of which also affect the control of type 1 and type 2 diabetes. Not only do such factors impact risk and treatment at the time of diagnosis but they also can accumulate biologically from preconception, in utero, and across the life course. These factors include inadequate nutritional quality, poor access to physical activity resources, chronic stress (e.g., adverse childhood experiences, racism, and poverty), and exposures to environmental toxins. The National Clinical Care Commission (NCCC) concluded that the diabetes epidemic cannot be treated solely as a biomedical problem but must also be treated as a societal problem that requires an all-of-government approach. The NCCC determined that it is critical to design, leverage, and coordinate federal policies and programs to foster social and environmental conditions that facilitate the prevention and treatment of diabetes. This article reviews the rationale, scientific evidence base, and content of the NCCC's population-wide recommendations that address food systems; consumption of water over sugar-sweetened beverages; food and beverage labeling; marketing and advertising; workplace, ambient, and built environments; and research. Recommendations relate to specific federal policies, programs, agencies, and departments, including the U.S. Department of Agriculture, the Food and Drug Administration, the Federal Trade Commission, the Department of Housing and Urban Development, the Environmental Protection Agency, and others. These population-level recommendations are transformative. By recommending health-in-all-policies and an equity-based approach to governance, the NCCC Report to Congress has the potential to contribute to meaningful change across the diabetes continuum and beyond. Adopting these recommendations could significantly reduce diabetes incidence, complications, costs, and inequities. Substantial political resolve will be needed to translate recommendations into policy. Engagement by diverse members of the diabetes stakeholder community will be critical to such efforts.

The National Clinical Care Commission Report to Congress: Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes.

The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non-health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non-health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

Perceived Discrimination, Retention, and Diabetes Risk Among American Indians and Alaska Natives in a Diabetes Lifestyle Intervention.

Objectives: To examine the association of perceived discrimination with participant retention and diabetes risk among American Indians and Alaska Natives. Methods: Data were drawn from the Special Diabetes Program for Indians-Diabetes Prevention Demonstration Project (N = 2553). Results: Perceived discrimination was significantly and negatively associated with short-term and long-term retention and diabetes risk without adjusting. After controlling for socioeconomic characteristics and clinical outcomes, perceived discrimination was not associated with retention but was significantly associated with less improvement in body mass index (BMI) and high-density lipoprotein (HDL) cholesterol. Every unit increase in the perceived discrimination score was associated with 0.14 kg/m2 less BMI reduction (95% CI: [0.02, 0.26], p = 0.0183) and 1.06 mg/dl lower HDL at baseline (95% CI: [0.36, 1.76], p = 0.0028). Discussion: Among racialized groups, improving retention and health in lifestyle interventions may require investigating perceived discrimination and the broader context of structural racism and colonialism.

Prevalence of diagnosed diabetes in American Indian and Alaska Native adults, 2006-2017.

INTRODUCTION: The objective of this study was to examine recent trends in diagnosed diabetes prevalence for American Indian and Alaska Native (AI/AN) adults aged 18 years and older in the Indian Health Service (IHS) active clinical population. RESEARCH DESIGN AND METHODS: Data were extracted from the IHS National Data Warehouse for AI/AN adults for each fiscal year from 2006 (n=729 470) through 2017 (n=1 034 814). The prevalence of diagnosed diabetes for each year and the annual percentage change were estimated for adults overall, as well as by sex, age group, and geographic region. RESULTS: After increasing significantly from 2006 to 2013, diabetes prevalence for AI/AN adults in the IHS active clinical population decreased significantly from 2013 to 2017. Prevalence was 14.4% (95% CI 13.9% to 15.0%) in 2006; 15.4% (95% CI 14.8% to 16.0%) in 2013; and 14.6% (95% CI 14.1% to 15.2%) in 2017. Trends for men and women were similar to the overall population, as were those for all age groups. For all geographic regions, prevalence either decreased significantly or leveled off in recent years. CONCLUSIONS: Diabetes prevalence in AI/AN adults in the IHS active clinical population has decreased significantly since 2013. While these results cannot be generalized to all AI/AN adults in the USA, this study documents the first known decrease in diabetes prevalence for AI/AN people.

Sustained Lower Incidence of Diabetes-Related End-Stage Kidney Disease Among American Indians and Alaska Natives, Blacks, and Hispanics in the U.S., 2000-2016.

OBJECTIVE: Diabetes-related end-stage kidney disease (ESKD-D) disproportionately affects U.S. racial/ethnic minority populations compared with whites. However, from 1996 to 2013, ESKD-D incidence among American Indians and Alaska Natives (AIANs) and blacks declined. We assessed recent ESKD-D incidence data to determine whether trends by race/ethnicity have changed since 2013. RESEARCH DESIGN AND METHODS: United States Renal Data System data from 2000 to 2016 were used to determine the number of whites, blacks, AIANs, Asians, and Hispanics aged ≥18 years with newly treated ESKD-D (with diabetes listed as primary cause). Using census population estimates as denominators, annual ESKD-D incidence rates were calculated and age adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and estimate an average annual percent change (AAPC) in incidence rates. RESULTS: For adults overall, from 2000 to 2016, age-adjusted ESKD-D incidence rates decreased by 53% for AIANs (66.7-31.2 per 100,000, AAPC -4.5%, P < 0.001), by 33% for Hispanics (50.0-33.3, -2.1%, P < 0.001), and by 20% for blacks (56.2-44.7, -1.6%, P < 0.001). However, during the study period, age-adjusted ESKD-D incidence rates did not change significantly for Asians and increased by 10% for whites (15.4-17.0, 0.6%, P = 0.01). In 2016, ESKD-D incidence rates in AIANs, Hispanics, and blacks were ∼2.0-2.5 times higher than whites. CONCLUSIONS: ESKD-D incidence declined for AIANs, Hispanics, and blacks and increased for whites. Continued efforts might be considered to reverse the trend in whites and sustain and lower ESKD-D incidence in the other populations.

Recruitment and effectiveness by cohort in a case management intervention among American Indians and Alaska Natives with diabetes.

In real-world settings, eligible populations and intervention effectiveness for a translational intervention likely vary across time. To determine the optimal strategies for effective large-scale implementation of evidence-based interventions, it is critical to investigate these potential variabilities. The purpose of this study is to evaluate whether patient characteristics and intervention effectiveness differed by year of enrollment in a multiyear evidence-based translational intervention. The Special Diabetes Program for Indians Healthy Heart (SDPI-HH) Demonstration Project is an intensive case management intervention designed to reduce cardiovascular disease risk among American Indians and Alaska Natives with diabetes. SDPI-HH participants recruited from 2006 through 2008 were included. Baseline characteristics were compared by year of enrollment. We also evaluated the differences in improvements in clinical and behavioral risk factors for cardiovascular disease among participants recruited in different years. The baseline characteristics of the three cohorts significantly differed in demographics, diabetes duration, health behaviors, level of motivation, and clinical measures. Improvements in 13 clinical and behavioral outcomes also differed by enrollment year with the 2006 cohort having the greatest number of significant improvements and the highest rates of participation and retention. Further investigation into the ways to modify the intensive case management model to address differences in levels of motivation and participation is warranted to improve the management of chronic disease in Indian health. Given the evolving nature of translational initiatives of this kind, our analysis results highlight the need to understand and adapt during the natural progression of health behavioral interventions.

Regression to Normal Glucose Regulation in American Indians and Alaska Natives of a Diabetes Prevention Program.

OBJECTIVE: This study evaluated whether regression from impaired glucose regulation (IGR) to normal glucose regulation (NGR) after 1 year of a lifestyle intervention reduces diabetes risk in American Indians and Alaska Natives (AI/ANs). In addition, we sought to identify predictors for regression to NGR and understand possible mechanisms for the association between NGR and future diabetes risk. RESEARCH DESIGN AND METHODS: Data from participants enrolled from 2006 to 2009 in the Special Diabetes Program for Indians Diabetes Prevention Program with IGR at baseline and an oral glucose tolerance test at year 1 were analyzed (N = 1,443). Cox regression models were used to estimate the subsequent diabetes risk (year 1 to year 3) by year 1 glucose status. Mediation analysis was used to estimate the proportions of the association between year 1 glycemic status and diabetes risk explained by specific factors. RESULTS: Those who reverted to NGR at year 1 (38%) had lower diabetes risk than those with sustained IGR (adjusted hazard ratio 0.28, 95% CI 0.12-0.67). The lower risk associated with regression to NGR was explained by both baseline risk factors and differences in weight loss. Metformin use, weight loss, and an increase in exercise were modifiable risk factors associated with higher odds of regression to NGR. CONCLUSIONS: Patients with prediabetes who reverted to NGR had a reduced risk of developing type 2 diabetes over the next 2 years. Both baseline and modifiable risk factors explained the risk reduction associated with NGR.