Association between fear of hypoglycemia and physical activity in youth with type 1 diabetes: The SEARCH for diabetes in youth study.

BACKGROUND: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (ß (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

Socio-economic, demographic, and clinical correlates of poor glycaemic control within insulin regimens among children with Type 1 diabetes: the SEARCH for Diabetes in Youth Study.

AIM: To examine the distribution and association of sociodemographic, adherence, and barriers-to-care factors in relation to glycaemic control within insulin regimens in US children with Type 1 diabetes in the SEARCH for Diabetes in Youth Study. METHODS: Self- or parent-reported data from 1095 children with Type 1 diabetes aged 10-17 years were collected on insulin regimen, sociodemographics, diabetes self-management, diabetes-related family conflict and barriers to care. Multivariable logistic regression analysis identified poor glycaemic control correlates within each insulin regimen. RESULTS: Participants included 694 children on insulin pump therapy, 188 receiving basal-bolus injections, and 213 on a mixed insulin regimen. Of these, 28.5%, 45.2% and 51.2%, respectively, had poor glycaemic control [HbA1c ≥ 80 mmol/mol (9.5%)]. Family conflict between parent and child regarding diabetes management was the only factor significantly associated with poor glycaemic control in all insulin regimens (insulin pump, P≤ 0.0001; basal-bolus injections, P=0.0002; mixed insulin regimen, P=0.0103). For children on insulin pump, poor control was significantly associated with non-white race (P=0.0008), living in multiple households (P=0.0331), having Medicaid insurance (P=0.0090), and decreased insulin adherence (P<0.0001). For children on a mixed insulin regimen, living in multiple households (P=0.0256) and not spending enough time with healthcare provider (P=0.0058) correlated with poor control. CONCLUSIONS: A high percentage of US children with Type 1 diabetes had poor glycaemic control, especially those not using an insulin pump. Early identification of children with risk factors associated with poor glycaemic control within insulin regimens and addressing diabetes-related family conflict may allow interventions to improve diabetes management.

Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework.

As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will 'close the loop' between blood glucose monitoring and automated insulin delivery and may transform day-to-day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed-loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed-loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed-loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non-restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed-loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long-term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management.

Diabetes nutrition therapy and dietary intake among individuals with Type 1 diabetes in China.

AIMS: To describe the contribution of diabetes nutrition therapy to disease self-management among individuals with Type 1 diabetes in China and to estimate the association of diabetes nutrition therapy with dietary intake. METHODS: The 3C Study was an epidemiological study of the coverage, cost and care of Type 1 diabetes in China. The data reported in the present study are from the 3C Nutrition Ancillary Study, a follow-up study conducted a mean ± sd of 1.6 ± 0.2 years later. Diabetes nutrition therapy was assessed by an interviewer-administered questionnaire. Dietary intake was assessed using three 24-h recalls. The association of diabetes nutrition therapy with dietary intake was estimated using ancova. RESULTS: Participants (n = 100; 54% male) had a mean ± sd age of 41.7 ± 16.3 years and a mean ± sd diabetes duration of 11.8 ± 9.7 years. Fewer than half of the participants reported that they had 'ever' met with a dietitian. While 64% of participants were taught carbohydrate counting, only 12% 'ever' use this tool. Participants on insulin pumps and those testing ≥ 1 time/day reported greater dietary flexibility and higher fruit intakes compared with participants on other insulin regimens and testing less frequently. After adjustment for confounding by age and occupation, there were no consistent differences in dietary intake across subgroups of diabetes nutrition therapy. CONCLUSIONS: In this sample of individuals with Type 1 diabetes in China there is little dietitian involvement or carbohydrate counting. Increased frequency of nutrition education in conjunction with intensified self-monitoring of blood glucose is needed to improve care.

Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial.

AIM: To determine the potential effect sizes for the Flexible Lifestyle for Youth (FL3X) behavioural intervention to improve glycaemic control (HbA(1c)) and quality of life for at-risk adolescents with Type 1 diabetes. METHODS: Participants [n = 61; age 12-16 years, HbA(1c) 64-119 mmol/mol (8-13%)] were randomized to FL3X (minimum three sessions) or usual care. Effect sizes (Cohen's d), comparing the mean difference between the groups, were calculated. RESULTS: Study retention (95%), attendance at intervention sessions (87% attended all three sessions) and acceptability were high (100% of the adolescents and 91% of parents would recommend the programme to others). Overall, 41% of participants in the intervention group and 24% of participants in the control group were 'responders' [HbA(1c) decreased by > 6 mmol/mol (0.5%); d = 0.37]. HbA(1c) levels decreased (d = -0.18), diabetes-specific quality of life increased (d = 0.29), but generic quality of life decreased (d = -0.23) in the intervention compared with the control group. CONCLUSIONS: The FL3X programme merits further study for improving HbA(1c) and diabetes-specific quality of life in adolescents with Type 1 diabetes. (Clinical trials registry no.: NCT01286350).

Long-term changes in dietary and food intake behaviour in the Diabetes Prevention Program Outcomes Study.

AIMS: To compare change in dietary intake, with an emphasis on food groups and food intake behaviour, over time across treatment arms in a diabetes prevention trial and to assess the differences in dietary intake among demographic groups within treatment arms. METHODS: Data are from the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Participants were randomized to a lifestyle intervention (n = 1079), metformin (n = 1073) or placebo (n = 1082) for an average of 3 years, after which the initial results regarding the benefits of the lifestyle intervention were released and all participants were offered a modified lifestyle intervention. Dietary intake was assessed using a food frequency questionnaire at baseline and at 1, 5, 6 and 9 years after randomization. RESULTS: Compared with the metformin and placebo arms, participants in the lifestyle arm maintained a lower total fat and saturated fat and a higher fibre intake up to 9 years after randomization and lower intakes of red meat and sweets were maintained for up to 5 years. Younger participants had higher intakes of poultry and lower intakes of fruits compared with their older counterparts, particularly in the lifestyle arm. Black participants tended to have lower dairy and higher poultry intakes compared with white and Hispanic participants. In the lifestyle arm, men tended to have higher grain, fruit and fish intakes than women. CONCLUSIONS: Changes in nutrient intake among participants in the lifestyle intervention were maintained for up to 9 years. Younger participants reported more unhealthy diets over time and thus may benefit from additional support to achieve and maintain dietary goals.

Vitamin D in youth with Type 1 diabetes: prevalence of insufficiency and association with insulin resistance in the SEARCH Nutrition Ancillary Study.

AIMS: To determine the prevalence of plasma vitamin D (25-dihydroxyvitamin D) insufficiency in individuals with Type 1 diabetes and to determine the cross-sectional and longitudinal associations of plasma vitamin D with insulin resistance. METHODS: Participants from the SEARCH for Diabetes in Youth Study [n = 1426; mean age 11.2 years (sd 3.9)] had physician-diagnosed Type 1 diabetes [diabetes duration mean 10.2 months (sd 6.5)] with data available at baseline and follow-up (approximately 12 and 24 months after baseline). Insulin resistance was estimated using a validated equation. Cross-sectional and longitudinal multivariate logistic regression models were used to determine the association of plasma vitamin D with insulin resistance, adjusting for potential confounders. RESULTS: Forty-nine per cent of individuals had plasma vitamin D < 50 nmol/l and 26% were insulin resistant. In cross-sectional multivariate analyses, participants who had higher plasma vitamin D (65 nmol/l) had lower odds of prevalent insulin resistance than participants with lower plasma vitamin D (25 nmol/l) (odds ratio 0.70, 95% CI 0.57-0.85). This association was attenuated after additional adjustment for BMI z-score, which could be a confounder or a mediator (odds ratio 0.81, 95% CI 0.64-1.03). In longitudinal multivariate analyses, individuals with higher plasma vitamin D at baseline had lower odds of incident insulin resistance, but this was not significant (odds ratio 0.85, 95% CI 0.63-1.14). CONCLUSIONS: Vitamin D insufficiency is common in individuals with Type 1 diabetes and may increase risk for insulin resistance. Additional prospective studies are needed to determine the association between plasma vitamin D and insulin resistance, and to further examine the role of adiposity on this association.

Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes?

AIMS/HYPOTHESIS: The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China. METHODS: Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18-90 years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG ≥7.0 mmol/l or doctor diagnosis). Sex-stratified multilevel models, clustered at the community and province levels and controlling for individual-level age and household income were used to examine the association between diabetes and: (1) a multicomponent urbanisation measure reflecting overall modernisation and (2) 12 separate components of urbanisation (e.g., population density, employment, markets, infrastructure and social factors). RESULTS: Prevalent diabetes was higher in more-urbanised (men 12%; women 9%) vs less-urbanised (men 6%; women 5%) areas. In sex-stratified multilevel models adjusting for residential community and province, age and household income, there was a twofold higher diabetes prevalence in urban vs rural areas (men OR 2.02, 95% CI 1.47, 2.78; women, OR 1.94, 95% CI 1.35, 2.79). All urbanisation components were positively associated with diabetes, with variation across components (e.g. men, economic and income diversity, OR 1.42, 95% CI 1.20, 1.66; women, transportation infrastructure, OR 1.18, 95% CI 1.06, 1.32). Community-level variation in diabetes was comparatively greater for women (intraclass correlation [ICC] 0.03-0.05) vs men (ICC ≤0.01); province-level variation was greater for men (men 0.03-0.04; women 0.02). CONCLUSIONS/INTERPRETATION: Diabetes prevention and treatment efforts are needed particularly in urbanised areas of China. Community economic factors, modern markets, communications and transportation infrastructure might present opportunities for such efforts.

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study.

AIMS/HYPOTHESIS: Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study. METHODS: Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. RESULTS: Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month). CONCLUSIONS/INTERPRETATION: SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.

The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study.

OBJECTIVE: To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study. SUBJECTS: There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (≥6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years). RESULTS: ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12-26 months (P=0.02), 4-6 years (P=0.03), 6-9 years (P=0.0001) and 9-13 years of age (P<0.0001). CONCLUSION: Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.

Diabetic retinopathy in the SEARCH for Diabetes in Youth Cohort: a pilot study.

AIMS: The aim of this pilot study was to generate an initial estimate of the prevalence and correlates of diabetic retinopathy in a racially and ethnically diverse sample of youth with Type 1 and Type 2 diabetes mellitus. METHODS: A pilot study was conducted among 222 individuals with Type 1 diabetes (79% non-Hispanic white, 21% other) and 43 with Type 2 diabetes (28% non-Hispanic white, 72% other), all of > 5 years duration (mean duration 6.8 years) who participated in the SEARCH for Diabetes in Youth study. Diabetic retinopathy was assessed using non-mydriatic retinal photography of both eyes. RESULTS: The prevalence of diabetic retinopathy was 17% for Type 1 diabetes and 42% for Type 2 diabetes (odds ratio 1.50, 95% CI 0.58-3.88; P = 0.40 adjusted for age, duration, gender, race/ethnicity, parental education and HbA(1c). HbA(1c) was significantly higher among those with any diabetic retinopathy (adjusted mean 79 mmol/mol, 9.4%) vs. no diabetic retinopathy (adjusted mean 70 mmol/mol, 8.6%) (P = 0.015). LDL cholesterol was also significantly higher among those with any diabetic retinopathy (adjusted mean 107.2 mg/dl) compared with those without diabetic retinopathy (adjusted mean 97.9 mg/dl) (P = 0.04). CONCLUSIONS: The prevalence of diabetic retinopathy in contemporary young individuals was substantial, particularly among minority youth and those with Type 2 diabetes. Further long-term study of diabetic retinopathy in youth is needed.

Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth.

AIM/HYPOTHESIS: Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been associated with type 2 diabetes in adults. However, it is not known whether TCF7L2 variation increases the risk of early onset type 2 diabetes. Using a case-control design, we examined whether the reported variants [rs12255372 (T/G) and rs7903146 (T/C)] are associated with type 2 diabetes in SEARCH for Diabetes in Youth study participants. METHODS: Variants were genotyped in 694 non-Hispanic white (NHW) youth (86 cases, mean age 15.5 years, mean BMI 34.8; and 608 controls, mean age 14.4 years, mean BMI 22.3) and 545 African-American (AA) youth (154 cases, mean age 15.9, mean BMI 37; and 391 controls, mean age 14.8, mean BMI 23.8). Logistic regression adjusted for age, sex, BMI and West African ancestry. RESULTS: The association of the risk T allele with case/control status was different in AA and NHW youth (p = 0.025). Among AA youth, each copy of the T allele (rs7903146) was associated with a 1.97-fold (1.37, 2.82) increased odds for type 2 diabetes (p < 0.0001), after adjustment for age, sex, BMI and African ancestry. No significant association was detected in NHW youth (adjusted OR, 1.14; 0.73, 1.79). CONCLUSION/INTERPRETATION: TCF7L2 variation is associated with an increased risk of early-onset type 2 diabetes among AA youth, and the association appears to be stronger in AA than NHW youth. This suggests potential different contributions of genetic and environmental factors to early-onset type 2 diabetes by race.

Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study.

AIMS/HYPOTHESIS: The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n = 85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA. METHODS: Youths with a diagnosis of type 1 (n = 60) or type 2 diabetes (n = 25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg⁻¹ min⁻¹). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA1(c), lipids, blood pressure, urine albumin:creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n = 53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n = 33) and healthy control youths (n = 22). RESULTS: The best model included waist, triacylglycerol (TG) and HbA1(c) levels (R² = 0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r = 0.65, p < 0.0001; r = 0.62, p = 0.002) with GDR on the two validation sets. Based on this analysis, we propose the following formula to estimate insulin sensitivity in youths with diabetes: [Formula: see text]. CONCLUSIONS/INTERPRETATION: Insulin sensitivity can be estimated in adolescents with diabetes using routinely collected measures. This score can be applied to epidemiological studies of youths with diabetes to characterise relationships between dimensions of diabetes type.

Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort.

OBJECTIVE: Previous studies have replicated the association of variants within FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity quantitative traits in populations of European ancestry. Non-European populations, however, have not been so intensively studied. The goal of this investigation was to examine the association of FTO single-nucleotide polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non-Hispanic White American (n=458), Hispanic American (n=373) and African American (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This cohort provides the unique ability to evaluate how variation within FTO influences measures of adiposity and glucose homeostasis in three different ethnicities, which were ascertained and examined using a common protocol. DESIGN: A total of 26 FTO SNPs were genotyped, including those consistently associated in the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and rs3751812), and tested for association with adiposity and glucose homeostasis traits. RESULTS: For the adiposity phenotypes, these and other SNPs were associated with body mass index (BMI) in both non-Hispanic Whites (P-values ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 × 10(-6) to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521, rs8057044 and rs8044769) still showed evidence of association after multiple comparisons adjustment (P-values ranging from 5.0 × 10(-5) to 5.2 × 10(-4)). The historically associated BMI SNPs were not associated in the African Americans, but rs1108102 was associated with BMI (P-value of 5.4 × 10(-4)) after accounting for multiple comparisons. For glucose homeostasis traits, associations were seen with acute insulin response in non-Hispanic Whites and African Americans. However, all associations with glucose homeostasis measures were no longer significant after adjusting for multiple comparisons. CONCLUSION: These results replicate the association of FTO intron 1 variants with BMI in non-Hispanic Whites and Hispanic Americans but show little evidence of association in African Americans, suggesting that the effect of FTO variants on adiposity phenotypes shows genetic heterogeneity dependent on ethnicity.

Determinants of adiponectin levels in young people with Type 1 diabetes.

AIMS: To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non-diabetic controls, and explore potential determinants for this difference. METHODS: Data are from the SEARCH for Diabetes in Youth Case-Control Study. A total of 440 youth with Type 1 diabetes and 191 non-diabetic healthy controls age 10-22 years of non-Hispanic White (NHW), African-American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA(1c)). RESULTS: Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 microg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA(1c) in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity. CONCLUSIONS: Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.

Plasma and dietary vitamin E in relation to insulin secretion and sensitivity.

AIM: In the Insulin Resistance and Atherosclerosis Study (IRAS), we have previously shown a protective effect of plasma alpha-tocopherol concentration against diabetes incidence among persons not taking vitamin E supplements. The biologic mechanism for such a protective effect could involve improvement in either insulin sensitivity (S(I)), insulin secretion or both. Thus, we examined vitamin E in relation to insulin secretion and S(I) among persons not taking vitamin E supplements. METHODS: This analysis included 457 adults aged 40-69 years without a previous diabetes diagnosis or vitamin E supplement use at baseline and seen at the 5-year follow-up examination. Baseline nutrient intake was estimated from a validated 1-year food frequency questionnaire; plasma levels of alpha-tocopherol were also assessed. At follow up, a frequently sampled intravenous glucose tolerance test determined S(I), acute insulin response to glucose (AIR), and the disposition index (DI) was calculated as the sum of the log-transformed AIR and S(I) to reflect pancreatic compensation for insulin resistance. RESULTS: In multivariable regression analyses, no relationship was observed for vitamin E intake and either S(I), AIR or DI. However, plasma alpha-tocopherol concentration was positively associated with log-transformed S(I) (beta= 0.27 +/- 0.09, p < 0.01) and DI (beta= 0.41 +/- 0.14, p < 0.01), but not with log-transformed AIR. CONCLUSIONS: Plasma concentration of alpha-tocopherol may improve S(I) and pancreatic compensation for insulin resistance, although it does not seem to be related to acute insulin response.

Association of adherence to a Mediterranean diet with glycemic control and cardiovascular risk factors in youth with type I diabetes: the SEARCH Nutrition Ancillary Study.

BACKGROUND/OBJECTIVES: This study aimed to determine the association between a Mediterranean diet and glycemic control and other cardiovascular risk factors among youth with type I diabetes (TID). SUBJECTS/METHODS: Incident TID cases aged <20 years at diagnosis between 2002 and 2005 were included. Participants were seen at baseline (N=793), 1-year (N=512) and 5-year follow-up visits (N=501). Mediterranean diet score was assessed using a modified KIDMED index (mKIDMED). Multivariate linear regression and longitudinal mixed model were applied to determine the association between mKIDMED score and log-HbA1c, lipids, blood pressure (BP) and obesity. RESULTS: In cross-sectional analyses using baseline data, for individuals with the hemoglobin A1c (HbA1c) of 7.5%, a two-point higher mKIDMED score (1 s.d.) was associated with 0.15% lower HbA1c (P=0.02). A two-point higher mKIDMED score was associated with 4.0 mg/dl lower total cholesterol (TC) (P=0.006), 3.4 mg/dl lower low-density lipoprotein cholesterol (LDL-C) (P=0.004), 3.9 mg/dl lower non-high-density lipoprotein cholesterol (non-HDL-C) (P=0.004) and 0.07 lower LDL-C/HDL-C ratio (P=0.02). Using longitudinal data, a two-point increase in mKIDMED score was associated with 0.01% lower log-HbA1c (P=0.07), 1.8 mg/dl lower TC (P=0.05), 1.6 mg/dl lower LDL-C (P=0.03) and 1.8 mg/dl lower non-HDL-C (P=0.03) than would otherwise have been expected. HbA1c mediated ∼20% of the association for lipids in both cross-sectional and longitudinal models. An unexpected positive association between mKIDMED score and systolic BP was found among non-Hispanic white youth in cross-sectional analyses (P=0.009). Mediterranean diet was not associated with obesity. CONCLUSIONS: Mediterranean diet may improve glycemic control and cardiovascular health in TID youth.

Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with SI after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P = 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance.

Heterogeneity in associations between macronutrient intake and lipoprotein profile in individuals with type 2 diabetes.

OBJECTIVE: To evaluate associations between macronutrient intake and lipoprotein profile among individuals with type 2 diabetes who participated in the San Luis Valley Diabetes Study (SLVDS) or the Insulin Resistance Atherosclerosis Study (IRAS). RESEARCH DESIGN AND METHODS: Diet was assessed by 24-h recall in the SLVDS (n = 421) and by validated food frequency interview in the IRAS (n = 437). Analyses adjusted for kilocalories, age, sex, and other covariates were conducted separately for the two study groups. For the SLVDS, repeated observations were included in mixed model analyses (865 observations). For the IRAS, standard regression analyses were conducted. Recent weight history and time of diabetes diagnosis were evaluated as possible modifiers of associations between nutrient intake and lipoprotein profile. RESULTS: Higher reported intake of total dietary fat was related to significantly higher levels of LDL cholesterol (P < 0.05) in both studies and in all subgroups. Reported intake of total and saturated fat was associated positively with total cholesterol, although statistical significance was not reached for all subgroups. Higher reported carbohydrate intake was associated with increased triglyceride concentrations (P < 0.01) only among individuals with previously undiagnosed diabetes in the SLVDS (n = 69) and only among individuals who gained weight (> 5 lb, n = 87) during the previous year in the IRAS. CONCLUSIONS: Toward the goal of optimizing the lipoprotein profile of individuals with diabetes, these results emphasize the potential importance of reducing fat intake while recognizing that individualized approaches to diet are important to minimize the risk of cardiovascular disease.