Diabetes Prevention Study Research Articles

Is Weight Loss the Most Effective Method for the Prevention of Type 2 Diabetes? A Discussion in View of Evidence from Landmark Studies

Type 2 Diabetes mellitus (T2DM) and obesity are a continuum and intertwined in a complex way. Both these chronic conditions pose a significant challenge to the global health system, if the current trend continues, it is estimated that by 2045 the number of people affected globally will increase by almost 700 million. Considering the above, effective strategies have to be implemented to tackle this global pandemic. The main strategies discussed in the literature are lifestyle intervention (ESI) with or without weight loss and medication. This article looked at the evidence from the various landmark studies which include the Diabetes Prevention Program (DPP) and Diabetes Prevention Study (DPS) Outcomes of these studies suggest that ELSI with loss is superior to ELSI without weight loss and metformin in risk reduction of T2DM. The evidence from the Swedish obese subject study also concludes that weight loss achieved through bariatric surgery reduces the risk. Lifestyle modification programmes even without weight loss have greater health benefits but as far as risk reduction for T2DM the evidence is not conclusive. This review article concludes that reducing weight is paramount for preventing T2DM, especially in high-risk individuals, compliance plays a vital role in overcoming these challenges and stresses the importance of tailored strategies for person-to-person characteristics to overcome those challenges.

Covariate-constrained randomization in cluster randomized 2 × 2 factorial trials: application to a diabetes prevention study

BackgroundCluster randomized trials (CRTs) are randomized trials where randomization takes place at an administrative level (e.g., hospitals, clinics, or schools) rather than at the individual level. When the number of available clusters is small, researchers may not be able to rely on simple randomization to achieve balance on cluster-level covariates across treatment conditions. If these cluster-level covariates are predictive of the outcome, covariate imbalance may distort treatment effects, threaten internal validity, lead to a loss of power, and increase the variability of treatment effects. Covariate-constrained randomization (CR) is a randomization strategy designed to reduce the risk of imbalance in cluster-level covariates when performing a CRT. Existing methods for CR have been developed and evaluated for two- and multi-arm CRTs but not for factorial CRTs.MethodsMotivated by the BEGIN study—a CRT for weight loss among patients with pre-diabetes—we develop methods for performing CR in 2 × 2 factorial cluster randomized trials with a continuous outcome and continuous cluster-level covariates. We apply our methods to the BEGIN study and use simulation to assess the performance of CR versus simple randomization for estimating treatment effects by varying the number of clusters, the degree to which clusters are associated with the outcome, the distribution of cluster level covariates, the size of the constrained randomization space, and analysis strategies.ResultsCompared to simple randomization of clusters, CR in the factorial setting is effective at achieving balance across cluster-level covariates between treatment conditions and provides more precise inferences. When cluster-level covariates are included in the analyses model, CR also results in greater power to detect treatment effects, but power is low compared to unadjusted analyses when the number of clusters is small.ConclusionsCR should be used instead of simple randomization when performing factorial CRTs to avoid highly imbalanced designs and to obtain more precise inferences. Except when there are a small number of clusters, cluster-level covariates should be included in the analysis model to increase power and maintain coverage and type 1 error rates at their nominal levels.

Food Consumption and Risk of Islet Autoimmunity and Type 1 Diabetes in Children at Increased Genetic Susceptibility for Type 1 Diabetes

BackgroundProspective longitudinal evidence considering the entire childhood food consumption in relation to the development of islet autoimmunity (IA or) type 1 diabetes is lacking. ObjectivesWe studied the associations of consumption of various foods and their combinations with IA and type 1 diabetes risk. MethodsChildren with genetic susceptibility to type 1 diabetes born in 1996–2004 were followed from birth up to ≤6 y of age in the prospective birth cohort type 1 diabetes prediction and prevention study (n = 5674). Exposure variables included 34 food groups covering the entire diet based on repeated 3-d food records at ages 3 mo to 6 y. Endpoints were islet cell antibodies plus biochemical IA (n = 247), multiple biochemical IA (n = 206), and type 1 diabetes (n = 94). We analyzed associations between longitudinally observed foods and risk of IA/type 1 diabetes using a Bayesian approach to joint models in 1-food and multi-food models adjusted for energy intake, sex, human leukocyte antigen genotype, and familial diabetes. ResultsThe final multi-food model for islet cell antibodies plus biochemical IA included oats [hazard ratio (HR): 1.09; 95% credible interval (CI): 1.04, 1.14], banana (HR: 1.07; 95% CI: 1.03, 1.11), and cruciferous vegetables (HR: 0.83; 95% CI: 0.73, 0.94). The final model for multiple biochemical IA included, in addition to the above-mentioned foods, fermented dairy (HR: 1.42; 95% CI: 1.12, 1.78) and wheat (HR: 1.10; 95% CI: 1.03, 1.18). The final multi-food model for type 1 diabetes included rye (HR: 1.27; 95% CI: 1.07, 1.50), oats (HR: 1.15; 95% CI: 1.03, 1.26), fruits (HR: 1.05; 95% CI: 1.01, 1.09), and berries (HR: 0.67; 95% CI: 0.50, 0.93). ConclusionsHigher consumption of oats, gluten-containing cereals, and fruits was associated with increased that of cruciferous vegetables with decreased risk of several type 1 diabetes-related endpoints when considering all the foods in combination. Further etiological and mechanistic studies are warranted.

Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.

The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

1270-P: Evolution of Stroke Incidence over 34 Years Follow-up among People with Newly Diagnosed Diabetes and Impaired Glucose Tolerance in the Da Qing Diabetes and Diabetes Prevention Study 1986–2020

1270-P: Evolution of Stroke Incidence over 34 Years Follow-up among People with Newly Diagnosed Diabetes and Impaired Glucose Tolerance in the Da Qing Diabetes and Diabetes Prevention Study 1986–2020

Maternal gluten, cereal, and dietary fiber intake during pregnancy and lactation and the risk of islet autoimmunity and type 1 diabetes in the child

Maternal gluten intake in relation to child's risk of type 1 diabetes has been studied in few prospective studies considering the diet during pregnancy but none during lactation. Our aim was to study whether gluten, cereals, or dietary fiber in maternal diet during pregnancy and lactation is associated with the risk of islet autoimmunity or type 1 diabetes in the offspring. We included 4943 children with genetic susceptibility to type 1 diabetes from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study, born between 1996 and 2004. Maternal intake of gluten, different types of cereals, and dietary fiber were derived from a semi-quantitative validated food frequency questionnaire covering the eighth month of pregnancy and the third month of lactation. Children were monitored for islet autoantibodies up to age of 15 years and type 1 diabetes until year 2017. Risk of islet autoimmunity and clinical type 1 diabetes were estimated using Cox regression model, adjusted for energy intake, child's sex, HLA genotype, and familial diabetes. Altogether 312 children (6.4%) developed islet autoimmunity at median age of 3.5 (IQR 1.7, 6.6) years and 178 children (3.6%) developed type 1 diabetes at median age of 7.1 (IQR 4.3, 10.6) years. Gluten intake during pregnancy was not associated with islet autoimmunity (HR 0.96; 95% CI 0.68, 1.35), per 1g/MJ increase in intake nor type 1 diabetes (HR 0.96; 95% CI 0.62, 1.50) in the offspring. Higher barley consumption during lactation was associated with increased risk of type 1 diabetes (HR 3.25; 95% CI 1.21, 8.70) per 1g/MJ increase in intake. Maternal intake of other cereals or dietary fiber was not associated with the offspring outcomes. We observed no association between maternal intake of gluten, most consumed cereals, or dietary fiber during pregnancy or lactation and the risk of islet autoimmunity or type 1 diabetes in children from a high-risk population.

Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies

Previous studies have revealed heterogeneity in the progression to clinical type 1 diabetes in children who develop islet-specific antibodies either to insulin (IAA) or glutamic acid decarboxylase (GADA) as the first autoantibodies. Here, we test the hypothesis that children who later develop clinical disease have different early immune responses, depending on the type of the first autoantibody to appear (GADA-first or IAA-first). We use mass cytometry for deep immune profiling of peripheral blood mononuclear cell samples longitudinally collected from children who later progressed to clinical disease (IAA-first, GADA-first, ≥2 autoantibodies first groups) and matched for age, sex, and HLA controls who did not, as part of the Type 1 Diabetes Prediction and Prevention study. We identify differences in immune cell composition of children who later develop disease depending on the type of autoantibodies that appear first. Notably, we observe an increase in CD161 expression in natural killer cells of children with ≥2 autoantibodies and validate this in an independent cohort. The results highlight the importance of endotype-specific analyses and are likely to contribute to our understanding of pathogenic mechanisms underlying type 1 diabetes development.

Long-term cumulative incidence of clinically diagnosed retinopathy in the Finnish Diabetes Prevention Study.

Lifestyle intervention reduces the incidence of type 2 diabetes (T2D) in people with impaired glucose tolerance. To find out whether participation in the earlier lifestyle intervention had an effect on the occurrence of clinically diagnosed retinopathy during a median of 22 years of follow-up time. The study included 505 individuals from the Finnish Diabetes Prevention Study (DPS) (mean 55, range 40-64 years at the onset of the study) with impaired glucose tolerance who were originally randomized into the intervention (weight loss, healthy diet and physical activity (N=257) and usual care control groups (N=248). The median follow-up was 22 years. Clinical retinopathy diagnoses were obtained from the Finnish national hospital Care Register for Health. Data on glycemic parameters, serum lipids and blood pressure were available from both the intervention (median 4 years) and post-intervention period (until the year 7). No significant difference was found in the cumulative incidence of clinically diagnosed diabetic retinopathy between the original intervention (N=23, 8.9%) and control groups (N=19, 7.7%) during the extended follow-up (Odds ratio: 1.15, 95% confidence interval: 0.61-2.21). A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy (Hazard ratio 1.4; 1.02-1.88, 95% posterior interval, adjusted for group, age and sex). Furthermore, the incidence of retinopathy diagnosis was numerically more common among individuals who had developed diabetes during the follow-up (33/349) compared with those who had not (9/156), however, the comparison was not statistically significant (Odds ratio: 1.86, 95% confidence interval: 0.89-4.28, adjusted for group, age and sex). A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy. No evidence was found for a beneficial effect of a 4-year lifestyle intervention on the long-term occurrence of clinically diagnosed retinopathy during a median of 22-year follow-up.

Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women

IntroductionLifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and...

Combining diaries and accelerometers to explain change in physical activity during a lifestyle intervention for adults with pre-diabetes: A PREVIEW sub-study.

Self-report and device-based measures of physical activity (PA) both have unique strengths and limitations; combining these measures should provide complementary and comprehensive insights to PA behaviours. Therefore, we aim to 1) identify PA clusters and clusters of change in PA based on self-reported daily activities and 2) assess differences in device-based PA between clusters in a lifestyle intervention, the PREVIEW diabetes prevention study. In total, 232 participants with overweight and prediabetes (147 women; 55.9 ± 9.5yrs; BMI ≥25 kg·m-2; impaired fasting glucose and/or impaired glucose tolerance) were clustered using a partitioning around medoids algorithm based on self-reported daily activities before a lifestyle intervention and their changes after 6 and 12 months. Device-assessed PA levels (PAL), sedentary time (SED), light PA (LPA), and moderate-to-vigorous PA (MVPA) were assessed using ActiSleep+ accelerometers and compared between clusters using (multivariate) analyses of covariance. At baseline, the self-reported "walking and housework" cluster had significantly higher PAL, MVPA and LPA, and less SED than the "inactive" cluster. LPA was higher only among the "cycling" cluster. There was no difference in the device-based measures between the "social-sports" and "inactive" clusters. Looking at the changes after 6 months, the "increased walking" cluster showed the greatest increase in PAL while the "increased cycling" cluster accumulated the highest amount of LPA. The "increased housework" and "increased supervised sports" reported least favourable changes in device-based PA. After 12 months, there was only minor change in activities between the "increased walking and cycling", "no change" and "increased supervised sports" clusters, with no significant differences in device-based measures. Combining self-report and device-based measures provides better insights into the behaviours that change during an intervention. Walking and cycling may be suitable activities to increase PA in adults with prediabetes.

Extremely Early Appearance of Islet Autoantibodies in Genetically Susceptible Children

Objective. We studied the characteristics of children who developed islet autoantibodies by the age of 0.50 years and hypothesized that the appearance of extremely early islet autoimmunity differs between four birth cohorts within 1994–2019 according to the change in the incidence of Type 1 diabetes (T1D) in Finland. Methods. Data from Finnish children participating in the Type 1 Diabetes Prediction and Prevention (DIPP) study, or the Environmental Determinants of Diabetes in the Young (TEDDY) study were analyzed. These studies follow children with increased HLA-conferred risk for T1D with regular measurements of islet autoantibodies. Maternally transferred antibodies were excluded by comparing islet autoantibodies in cord serum, child’s first follow-up serum and the maternal serum. Results. Among 20,979 Finnish children at increased risk to T1D, 53 (0.25%) developed at least one islet autoantibody at the age of ≤0.50 years. During a mean follow-up of 8.1 years, 15.1% progressed to T1D (median age at diagnosis 2.0 years), 43.4% developed confirmed islet autoimmunity but no T1D, and 41.5% had only transient islet autoantibodies. IAA was the most common first-appearing autoantibody. Among progressors, age at diagnosis was 1.0–2.4 years in children with IAA-initiated autoimmunity and 4.5–16.1 years in ZnT8A-initiated autoimmunity. When comparing children developing autoantibodies either at the age of ≤0.50 years or 0.51–0.75 years, confirmed positivity during follow-up was more common in the older group (81.7% vs. 58.5%; p = 0.002 ). In four birth cohorts within 1994–2019 appearance of islet autoantibodies at the age of ≤0.50 years decreased towards the most recent birth cohorts ( p = 0.016 ). Conclusion. Islet autoimmunity by the age of 0.50 years was rare in genetically susceptible children and was typically initiated with IAA. Confirmed positivity was less common in children with autoantibodies at age ≤0.50 than at slightly older age. The secular decrease of islet autoimmunity before age 0.50 years was observed. This trial is registered with NCT03269084 and NCT00279318.

CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity.

Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), and the coxsackie and adenovirus receptor (CXADR) is one of the ligands used by adenoviruses and enteroviruses for cell internalization. Two CXADR single nucleotide polymorphisms (SNPs), rs6517774 and rs2824404, were previously associated with an increased susceptibility to IA in the international TEDDY study (The Environmental Determinants of Diabetes in the Young). This study aimed to replicate the results by genotyping 2886 children enrolled in the Finnish Diabetes Prediction and Prevention study (DIPP). In our preliminary analysis of the SNPs' allelic distributions, we could not find any association with IA susceptibility. However, a stratified analysis revealed a sex disparity, since the allelic distribution of rs6517774 was different when comparing autoantibody positive females with males; a difference not seen in healthy subjects. By using HLA risk groups and sex as covariates, a Cox regression survival analysis found that the rs6517774 (A/G) SNP was associated with a lower age at seroconversion in females (Female*rs6517774-AA; HR = 1.53, p = 0.002), while introducing a protective effect in males. Accordingly, we propose that rs6517774 alters IA characteristics by modifying the age at seroconversion in a sex-dependent manner. In light of this observation, rs6517774 now joins a limited set on SNPs found to introduce sex-dependent risk effects on the age at IA initiation.

Innovation in diabetes prevention research: The 36-year legacy of China Da Qing diabetes prevention study

Innovation in diabetes prevention research: The 36-year legacy of China Da Qing diabetes prevention study

737-P: A Wearable Device (CGM and Activity Tracker) RCT for Postpartum Women with a History of Gestational Diabetes—Preliminary Findings on Anthropometry Measures and Self-Reported Lifestyle Behaviours

Background: Women with a history of gestational diabetes mellitus (GDM) have a 7-fold increased risk for subsequent development of type 2 diabetes mellitus (T2DM). Continuous glucose monitoring systems (CGMS) and exercise trackers have not been thoroughly explored in any Asian postpartum diabetes prevention studies. Objective: The Integrated Hyperglycaemia Incentivised Postnatal Surveillance (I-HIPS) study aims to investigate the efficacy of a personalized lifestyle intervention programme using wearables along with physical activity (PA) and diet modification to achieve healthy weight loss in postpartum women with history of GDM. Methods: Women were randomized to receive the intervention or standard medical care. The intervention group received a CGM sensor and exercise tracker, along with nutrition, exercise and personalized goal-setting workshops. Anthropometric measures (weight, BMI and waist circumference (WC)) and PA assessed using the International Physical Activity Questionnaire were examined between the two arms at the 6-month follow-up. Changes in dietary behaviors in the intervention group were assessed using a validated 6P tool. Results: Twenty-six recruited women had completed the 6-month follow-up. At 6-month, compared with the controls, women receiving intervention achieved a mean difference in the reduction of weight by 0.5 kg, BMI by 0.2 kg/m2 and WC by 0.8cm (p&amp;gt;0.05). The intervention group had increased PA (mean difference: +990 MET mins/week), compared to the controls (mean difference: +298 MET mins/week) (p&amp;gt;0.05) at 6-month. Between baseline and 6-month, women in the intervention group showed a reduction in the frequency of snack and beverage intakes (p=0.01). Conclusion: Preliminary findings suggest a trend toward better health outcomes in the intervention group with improved dietary behaviour. Disclosure P.Quah: None. N.Razali: None. S.M.H.Chai: None. F.Fadzully: None. L.W.K.Ryan: None. C.Ku: None. S.Loy: None. K.Tan: None. Funding National Medical Research Council of Singapore (MOH-000504-03)

742-P: Diabetes Prevention Effect of Practically Applicable Intervention in Clinical Settings Based on the Korean Diabetes Prevention Study (KDPS)

Background: The Korean Diabetes Prevention Study (KDPS, NCT02981121), a national clinical study to prevent T2DM, started in 2016 and is currently ongoing. This study was to evaluate the preventive effect of KDPS intervention for up to 1 year. Methods: The enrollment criteria are adults aged 30-70 with a BMI ≥ 23 kg/m2 at high risk of T2DM. Three Intervention methods are hospital-based lifestyle modification (hLSM) developed by Korean Diabetes Association, metformin (MET, 250mg~1000mg) and control standard management (STM) including a visit to the doctor every 6 months. LSM consists of 4 times individual diet interventions and lifestyle modification to keep 10 healthy habits with 7 times on-site and 8 times on phone-call contact. We assessed FPG and A1c every 6 months and OGTT every 12 months to check DM progression. Results: A total of 1611 subjects at 15 university hospitals performed screening with 75g OGTT (KDPS 1: 2016.11 ~ 2018.12, KDPS 2: 2020.9 ~ 2022.4). Eight hundred forty-four patients (male 44.2%) were randomized. The mean age was 56.1 years, BMI 26.6 kg/m2, WC 91.2 cm, FPG 103.2 mg/dL, PP2G 154.9 mg/dL, A1c 5.9%, and there was no significant difference between the three groups. KDPS 2 had a short follow-up period, thus DM prevention effect of up to 1 year was analyzed in 485 subjects of KDPS 1. Up to 1 year, the cumulative incidence of DM was 12/100 person-years (PY) in the LSM, 18/100 PY in MET, and 27/100 PY in STM (P=0.1440). Compared to STM, HR for T2DM in LSM was 0.51 (P=0.0508), and the HR in the MET was 0.82 (P=0.5205). Conclusion: The KDPS was intended to evaluate the DM prevention efficacy of the intervention methods practically applicable in clinical settings in Korea. The hLSM tended to have a 49% DM prevention effect compared to the STM. However, in the case of the MET, there was no significant difference from the control group. Further full analysis of KDPS results is needed for long term effect. Disclosure S.Chon: None. S.Yun: None. J.Woo: None. The korean diabetes prevention study investigators: n/a. Funding Korean Disease Control and Prevention Agency (2020-ER6402-00)

Eating behavior dimensions and 9-year weight loss maintenance: a sub-study of the Finnish Diabetes prevention study

BackgroundBehavioral processes through which lifestyle interventions influence risk factors for type 2 diabetes (T2DM), e.g., body weight, are not well-understood. We examined whether changes in psychological dimensions of eating behavior during the first year of lifestyle intervention would mediate the effects of intervention on body weight during a 9-year period.MethodsMiddle-aged participants (38 men, 60 women) with overweight and impaired glucose tolerance (IGT) were randomized to an intensive, individualized lifestyle intervention group (n = 51) or a control group (n = 47). At baseline and annually thereafter until nine years body weight was measured and the Three Factor Eating Questionnaire assessing cognitive restraint of eating with flexible and rigid components, disinhibition and susceptibility to hunger was completed. This was a sub-study of the Finnish Diabetes Prevention Study, conducted in Kuopio research center.ResultsDuring the first year of the intervention total cognitive (4.6 vs. 1.7 scores; p < 0.001), flexible (1.7 vs. 0.9; p = 0.018) and rigid (1.6 vs. 0.5; p = 0.001) restraint of eating increased, and body weight decreased (−5.2 vs. −1.2 kg; p < 0.001) more in the intervention group compared with the control group. The difference between the groups remained significant up to nine years regarding total (2.6 vs. 0.1 scores; p = 0.002) and rigid restraint (1.0 vs. 0.4; p = 0.004), and weight loss (−3.0 vs. 0.1 kg; p = 0.046). The first-year increases in total, flexible and rigid restraint statistically mediated the impact of intervention on weight loss during the 9-year study period.ConclusionsLifestyle intervention with intensive and individually tailored, professional counselling had long-lasting effects on cognitive restraint of eating and body weight in middle-aged participants with overweight and IGT. The mediation analyses suggest that early phase increase in cognitive restraint could have a role in long-term weight loss maintenance. This is important because long-term weight loss maintenance has various health benefits, including reduced risk of T2DM.

Disease progression joint model predicts time to type 1 diabetes onset: Optimizing future type 1 diabetes prevention studies.

Clinical trials seeking type 1 diabetes prevention are challenging in terms of identifying patient populations likely to progress to type 1 diabetes within limited (i.e., short-term) trial durations. Hence, we sought to improve such efforts by developing a quantitative disease progression model for type 1 diabetes. Individual-level data obtained from the TrialNet Pathway to Prevention and The Environmental Determinants of Diabetes in the Young natural history studies were used to develop a joint model that links the longitudinal glycemic measure to the timing of type 1 diabetes diagnosis. Baseline covariates were assessed using a stepwise covariate modeling approach. Our study focused on individuals at risk of developing type 1 diabetes with the presence of two or more diabetes-related autoantibodies (AAbs). The developed model successfully quantified how patient features measured at baseline, including HbA1c and the presence of different AAbs, alter the timing of type 1 diabetes diagnosis with reasonable accuracy and precision (<30% RSE). In addition, selected covariates were statistically significant (p < 0.0001 Wald test). The Weibull model best captured the timing to type 1 diabetes diagnosis. The 2-h oral glucose tolerance values assessed at each visit were included as a time-varying biomarker, which was best quantified using the sigmoid maximum effect function. This model provides a framework to quantitatively predict and simulate the time to type 1 diabetes diagnosis in individuals at risk of developing the disease and thus, aligns with the needs of pharmaceutical companies and scientists seeking to advance therapies aimed at interdicting the disease process.

Method of Developing a Culturally Tailored Diabetes Intervention for American Indians.

American Indians have the highest prevalence of type 2 diabetes compared with any other racial or ethnic group. Developing a culturally tailored diabetes prevention and management intervention is one way to reduce diabetes-related health disparities among American Indian populations. The purpose of this article is to describe our approach for developing a diabetes prevention and management intervention study using Kolb's Experiential Learning Theory as the framework. To ensure the intervention study was culturally meaningful and relevant we used community-based participatory principles by partnering with a team of nurse researchers, tribal diabetes educators, tribal leaders, and tribal community members who were involved in all aspects of the study process. We conducted seven focus groups predominantly in rural American Indian communities in Oklahoma. Using focus group findings, the team collaboratively designed and developed a multi-generational diabetes prevention and management intervention study. The intervention group sessions will focus on ways to prevent and manage diabetes while the control group sessions will focus on general health education topics that have been identified by the team as important and relevant. Family interventions that involve multiple generations and provide emotional and behavioral support to those with type 2 diabetes and family members at risk may provide our best chance at improving diabetes-related outcomes and reducing health disparities in this critical population.

Acculturation, Dietary Behaviors, and Macronutrient Intake Among Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Initiative.

The purpose of the study was to examine the influences of sex and acculturation on dietary behaviors, macronutrient intake, and dietary quality in participants enrolled in a diabetes prevention initiative in Starr County, Texas. Baseline data from the Starr County diabetes prevention study (N = 300) were analyzed-acculturation (country of origin, years in Starr County, language and food preferences), depressive symptoms (Patient Health Questionnaire-9), healthy eating self-efficacy (Weight Efficacy Lifestyle Questionnaire-Short Form), diet quality (USDA Healthy Eating Index), fat avoidance (Fat Avoidance Scale, Spanish version), and macronutrients. Descriptive statistics and univariate analysis of covariance were used to examine differences based on acculturation, controlling for sex. Participants were predominantly female (73%) and, on average, 51 years of age. Language and food preferences favored Spanish language and Hispanic foods, respectively. The majority (71%) was born in Mexico but had resided in Starr County for 33 years, on average. Depressive symptoms were moderate, and eating self-efficacy scores suggested low confidence in making healthy food choices, particularly for saturated fats. Spanish language preference was associated with worse dietary habits. The mean dietary quality score was lower than the national average (54 vs 59 nationally); females had slightly higher dietary quality than males and a higher mean fat avoidance score, although differences were not clinically significant. Intakes of carbohydrate, saturated fats, and cholesterol were higher than recommended daily allowances. The overall preference for speaking Spanish and the influence of language on dietary intake should inform future dietary interventions. Accommodating cultural norms and food preferences remain major challenges to improving dietary quality among the diverse Hispanic ethnic groups.

Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study

Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10-18 years with an increased risk of developing type 1 diabetes. Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5-20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34-0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50-0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1-1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6-9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86-95) sensitive, with a positive predictive value of 66% (60-72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89-97) but lowered the positive predictive value to 55% (49-60). Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. JDRF International.