Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS).

During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates, when compared with the Diabetes Prevention Program (DPP), decreased in the placebo (-42%) and metformin (-25%), groups compared with the rates in the intensive lifestyle intervention (+31%) group. Participants in the placebo and metformin groups were offered group intensive lifestyle intervention prior to entering the DPPOS. The following two hypotheses were explored to explain the rate differences: "effective intervention" (changes in weight and other factors due to intensive lifestyle intervention) and "exhaustion of susceptible" (changes in mean genetic and diabetes risk scores). No combination of behavioral risk factors (weight, physical activity, diet, smoking, and antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in the placebo and metformin groups, whereas weight gain was the factor associated with higher rates of progression in the intensive lifestyle intervention group. Different patterns in the average genetic risk score over time were consistent with exhaustion of susceptibles. Results were consistent with exhaustion of susceptibles for the change in incidence rates, but not the availability of intensive lifestyle intervention to all persons before the beginning of the DPPOS. Thus, effective intervention did not explain the lower diabetes rates in the DPPOS among subjects in the placebo and metformin groups compared with those in the DPP.

The SEARCH for Diabetes in Youth study: rationale, findings, and future directions.

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.

Regression from prediabetes to normal glucose regulation is associated with reduction in cardiovascular risk: results from the Diabetes Prevention Program outcomes study.

OBJECTIVE: Restoration of normal glucose regulation (NGR) in people with prediabetes significantly decreases the risk of future diabetes. We sought to examine whether regression to NGR is also associated with a long-term decrease in cardiovascular disease (CVD) risk. RESEARCH DESIGN AND METHODS: The Framingham (2008) score (as an estimate of the global 10-year CVD risk) and individual CVD risk factors were calculated annually for the Diabetes Prevention Program Outcomes Study years 1-10 among those patients who returned to NGR at least once during the Diabetes Prevention Program (DPP) compared with those who remained with prediabetes or those in whom diabetes developed during DPP (N = 2,775). RESULTS: The Framingham scores by glycemic exposure did not differ among the treatment groups; therefore, pooled estimates were stratified by glycemic status and were adjusted for differences in risk factors at DPP baseline and in the treatment arm. During 10 years of follow-up, the mean Framingham 10-year CVD risk scores were highest in the prediabetes group (16.2%), intermediate in the NGR group (15.5%), and 14.4% in people with diabetes (all pairwise comparisons P < 0.05), but scores decreased over time for those people with prediabetes (18.6% in year 1 vs. 15.9% in year 10, P < 0.01). The lower score in the diabetes group versus other groups, a declining score in the prediabetes group, and favorable changes in each individual risk factor in all groups were explained, in part, by higher or increasing medication use for lipids and blood pressure. CONCLUSIONS: Prediabetes represents a high-risk state for CVD. Restoration of NGR and/or medical treatment of CVD risk factors can significantly reduce the estimated CVD risk in people with prediabetes.

Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH Cardiovascular Disease Study.

OBJECTIVE: To evaluate the effects of smoking on early markers of cardiovascular disease (arterial stiffness) in adolescents with and without type 1 diabetes (T1D) in the SEARCH Cardiovascular Disease Study. STUDY DESIGN: Participants included 606 youth (18.9 ± 3.3 years, 83% non-Hispanic white; 50% male). Six groups were defined: (1) smokers with T1D (n = 80); (2) former smokers with T1D (n = 88); (3) nonsmokers with T1D (n = 232); (4) smokers without T1D (n = 40); (5) former smokers without T1D former (n = 51); and (6) nonsmokers without T1D (n = 115). Arterial stiffness measurements included pulse wave velocity (PWV), augmentation index, and brachial distensibility. Multivariate linear regression was used to assess the independent and joint effects of T1D and smoking on arterial stiffness. RESULTS: Nearly 20% of both youth with and without T1D and T1D were smokers. In youth without T1D, smokers had higher trunk and arm PWV. After adjustment for potential confounders, T1D, but not smoking, was an independent predictor of PWV (P < .05). Moreover, smoking status did not modify the association between T1D and increased arterial stiffness. CONCLUSIONS: We found a high prevalence of smoking among youth with and without T1D; however, smoking status was not independently associated with increased arterial stiffness in youth with T1D.

Glucose control predicts 2-year change in lipid profile in youth with type 1 diabetes.

OBJECTIVE: To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in individuals with type 1 diabetes (T1D). STUDY DESIGN: All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ∼12 and ∼24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], log triglycerides [TG], and non-HDL-c) with adjustment for possible confounders. RESULTS: Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non-HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (-0.29 mmol/L, -11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (-0.23 mmol/L, -9.0 mg/dL), and non-HDL-c (-0.32 mmol/L, -12.4 mg/dL) and an 8.5% decrease in TG (mmol/L). CONCLUSIONS: Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.

The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: the EPOCH study.

OBJECTIVE: To examine associations between exposure to maternal diabetes in utero and body mass index (BMI) growth trajectories from birth through 13 years of age among a diverse cohort of youth. STUDY DESIGN: Mixed linear effects models were constructed to assess differences in BMI and BMI growth velocity from birth through 13 years of age for 95 subjects exposed to diabetes in utero and 409 unexposed subjects enrolled in a retrospective cohort study. RESULTS: The overall BMI growth trajectory (adjusted for sex and race/ethnicity) was not significantly different for exposed and unexposed subjects from birth through 26 months of age (P = .48). However, the overall growth trajectory from 27 months of age through 13 years differed by exposure status (P = .008), adjusted for sex and race/ethnicity. The difference was primarily due to a significantly higher BMI growth velocity among exposed youth between 10 and 13 years, increasing by 4.56 kg/m² compared with 3.51 kg/m² in the unexposed (P = .005). Control for demographic variables, socioeconomic factors, and maternal prepregnancy BMI did not alter the observed associations. CONCLUSIONS: Exposure to maternal diabetes in utero accelerates BMI growth in late childhood, thus increasing long-term obesity risk.

Prevalence of increased arterial stiffness in children with type 1 diabetes mellitus differs by measurement site and sex: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS: Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P

The association between adiponectin/leptin ratio and diabetes type: the SEARCH for Diabetes in Youth Study.

We tested the association of adiponectin/leptin ratio with diabetes type after adjusting for multiple factors in 1156 youths with newly diagnosed diabetes in the SEARCH study. Although adiponectin/leptin ratio is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels.

Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: Assessment of the prevalence of serum lipid abnormalities in US youth with type 1 or type 2 diabetes. STUDY DESIGN: The SEARCH for Diabetes in Youth Study was a cross-sectional, population-based study, conducted in six centers. Subjects were 2448 youth with diabetes who had a study examination. Outcome measures were fasting measures of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and non-HDL-C. Analysis was descriptive. RESULTS: The overall prevalence of high TC concentration (>240 mg/dL) was 5%; the overall prevalence of high LDL-C (>160 mg/dL) was 3%, and the overall prevalence of high triglyceride (>400 mg/dL) was 2%. About half of the participants (48%) had an LDL-C concentration above the optimal level of 100 mg/dL. Among youth ages 10+, the prevalence of abnormal lipids was higher in type 2 (n = 283) than in type 1 diabetes (n = 1963): 33% versus 19% had TC concentration >200 mg/dL; 24% versus 15% had LDL-C concentration >130 mg/dL; 29% versus 10% had triglyceride concentration >150 mg/dL; 44% versus 12% had HDL-C concentration <40 mg/dL. Only 1% of youth were receiving pharmacologic therapy for dyslipidemia. CONCLUSIONS: A substantial proportion of young patients with diabetes have abnormal serum lipids.