Franziska K. Bishop

Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes

The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000—2002, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study applied validated questionnaires for smoking, alcohol and physical activity to 582 type 1 diabetes subjects and 724 non-diabetic subjects. More type 1 diabetes subjects reported current smoking than non-diabetic subjects (12.3% versus 8.6%, p=0.027). Overall, reported physical activity did not differ by diabetes status (p=0.79). More type 1 diabetes subjects reported never having consumed alcohol (10% versus 4%, p<0.0001) and those who drank consumed less alcohol (p=0.0015) than non-diabetic subjects. Physical activity and smoking were significantly associated with the presence of coronary artery calcification (adjusted OR=0.9, 95% CI: 0.8—0.996, p=0.045, and OR=1.7, CI: 1.1—2.6, p=0.03, respectively). Type 1 diabetes was independently associated with increased odds of coronary artery calcification (OR=3.5, 95% CI: 2.5—5.0, p<0.0001). Differences exist in lifestyle-related cardiovascular risk factors in men and women with type 1 diabetes compared with non-diabetic subjects in the CACTI study.

A practical method to measure GFR in people with type 1 diabetes.

AIMS Improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. We hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR) and, second, that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement. METHODS GFR was measured by iohexol clearance in plasma, DBS, and as estimated by the CKD-Epidemiology Collaboration equations in 15 adults with type 1 diabetes at two visits, one euglycemic and one hyperglycemic. RESULTS GFR measured by DBS was more comparable and less biased than GFR cystatin C, serum creatinine, and both combined. GFR was higher during hyperglycemia. Correction for between visit glycemia statistically significantly reduced bias and mean squared error for GFR measured by DBS as compared to gold-standard during euglycemia. CONCLUSIONS Iohexol clearance measured with DBS performed better than eGFR methods. Correction for ambient blood glucose improved precision and accuracy of GFR measurement. This method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes, especially when GFR is >60ml/min/1.73m(2).

Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes

Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement at baseline would be associated with cardiorenal risk factors at baseline and 2 yr follow‐up in adolescents with type 1 diabetes.

Outpatient assessment of determinants of glucose excursions in adolescents with type 1 diabetes: Proof of concept

UNLABELLED Abstract Objective: Controlled inpatient studies on the effects of food, physical activity (PA), and insulin dosing on glucose excursions exist, but such outpatient data are limited. We report here outpatient data on glucose excursions and its key determinants over 5 days in 30 adolescents with type 1 diabetes (T1D) as a proof-of-principle pilot study. SUBJECTS AND METHODS Subjects (20 on insulin pumps, 10 receiving multiple daily injections; 15±2 years old; diabetes duration, 8±4 years; hemoglobin A1c, 8.1±1.0%) wore a continuous glucose monitor (CGM) and an accelerometer for 5 days. Subjects continued their existing insulin regimens, and time-stamped insulin dosing data were obtained from insulin pump downloads or insulin pen digital logs. Time-stamped cell phone photographs of food pre- and post-consumption and food logs were used to augment 24-h dietary recalls for Days 1 and 3. These variables were incorporated into regression models to predict glucose excursions at 1-4 h post-breakfast. RESULTS CGM data on both Days 1 and 3 were obtained in 57 of the possible 60 subject-days with an average of 125 daily CGM readings (out of a possible 144). PA and dietary recall data were obtained in 100% and 93% of subjects on Day 1 and 90% and 100% of subjects on Day 3, respectively. All of these variables influenced glucose excursions at 1-4 h after waking, and 56 of the 60 subject-days contributed to the modeling analysis. CONCLUSIONS Outpatient high-resolution time-stamped data on the main inputs of glucose variability in adolescents with T1D are feasible and can be modeled. Future applications include using these data for in silico modeling and for monitoring outpatient iterations of closed-loop studies, as well as to improve clinical advice regarding insulin dosing to match diet and PA behaviors.

Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps

Purpose of ReviewThis review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.Recent FindingsWeight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited.SummaryThere is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

Influences of gender on cardiovascular disease risk factors in adolescents with and without type 1 diabetes

BackgroundWomen with type 1 diabetes (T1D) have a four-fold increased risk for cardiovascular disease (CVD) compared to non-diabetic (non-DM) women, as opposed to double the risk in T1D men compared to non-DM men. It is unclear how early in life CVD risk differences begin in T1D females. Therefore, our objective was to compare CVD risk factors in adolescents with and without T1D to determine the effects of gender on CVD risk factors.MethodsThe study included 300 subjects with T1D (age 15.4±2.1 years, 50 % male, 80 % non-Hispanic White (NHW), glycated hemoglobin (A1c) 8.9±1.6 %, diabetes duration 8.8±3.0 years, BMI Z-score 0.62±0.77) and 100non-DM controls (age 15.4±2.1 years, 47 % male, 69 % NHW, BMI Z-score 0.29±1.04). CVD risk factors were compared by diabetes status and gender. Multivariate linear regression analyses were used to determine if relationships between diabetes status and CVD risk factors differed by gender independent of differences in A1c and BMI.ResultsDifferences in CVD risk factors between T1D subjects and non-DM controls were more pronounced in girls. Compared to boys with T1D and non-DM girls, T1D girls had higher A1c (9.0 % vs. 8.6 % and 5.1 %, respectively), BMI Z-score (0.70 vs. 0.47 and 0.27), LDL-c (95 vs. 82 and 81 mg/dL), total cholesterol (171 vs. 153 and 150 mg/dL), DBP (68 vs. 67 and 63 mmHg), and hs-CRP (1.15 vs. 0.57 and 0.54 mg/dL) after adjusting for Tanner stage, smoking status, and race/ethnicity (p <0.05 for all). In T1D girls, differences in lipids, DBP, and hs-CRP persisted even after adjusting for centered A1c and BMI Z-score.Testing interactions between gender and T1D with CVD risk factors indicated that differences were greater between girls with T1D and non-DM compared to differences between boys with T1D and non-DM. Overall, observed increases in CVD risk factors in T1D girls remained after further adjustment for centered A1c or BMI Z-score.ConclusionsInterventions targeting CVD risk factors in addition to lowering HbA1c and maintaining healthy BMI are needed for youth with T1D. The increased CVD risk factors seen in adolescent girls with T1D in particular argues for earlier intervention to prevent later increased risk of CVD in women with T1D.

The effect of insurance status and parental education on glycemic control and cardiovascular disease risk profile in youth with Type 1 Diabetes

BackgroundAdult studies have shown a correlation between low socioeconomic status and Type 1 Diabetes complications, but studies have not been done in children to examine the effect of socioeconomic status on risk for future complications. This study investigates the relationship between insurance status and parental education and both glycemic control and cardiovascular disease (CVD) risk factors in youth with type 1 diabetes.MethodsA cross-sectional study of 295 youth with established type 1 diabetes who underwent examination with fasting blood draw and reported insurance status and parental education.ResultsYouth with type 1 diabetes and public insurance had higher hemoglobin A1c (HbA1c), body mass index, hs-CRP, and blood pressure (p < 0.05) than those with private insurance. Insulin regimen varied between insurance groups, and differences in HbA1c and CVD risk factors, except for diastolic blood pressure (DBP), were no longer evident after controlling for insulin regimen. Parental education was not associated with HbA1c or CVD risk factors.ConclusionsYouth with type 1 diabetes and public insurance have worse glycemic control and elevated CVD risk factors compared to those with private insurance, but this was no longer seen when insulin regimen was controlled for. Further research is needed to look at differences between those with public insurance and private insurance that contribute to differences in type 1 diabetes outcomes, and to identify modifiable risk factors in pediatric patients in order to focus earlier interventions to decrease and prevent future diabetes complications.

Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes

Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12–21 years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.

PCSK9 Is Increased in Youth With Type 1 Diabetes

Type 1 diabetes (T1D) is associated with a 10-fold increase in cardiovascular disease (CVD) risk, due in part to dyslipidemia. Patients with poorly controlled T1D show an increase in total and LDL cholesterol as well as elevated apolipoprotein B (ApoB) levels. Moreover, even patients with well-controlled T1D can show increased levels of ApoB. Dyslipidemia is particularly important in females with T1D, as the atheroprotective lipoprotein profile and reduced risk of CVD usually observed in females without diabetes are lost in females with diabetes (1,2). Proprotein convertase subtilisin/kexin type 9 (PCSK9) has recently emerged as a novel regulator of plasma cholesterol levels: gain-of-function PCSK9 mutations increase LDL cholesterol and CVD risk, whereas inhibitors of PCSK9 lower LDL cholesterol. Although PCSK9 is increased in individuals with obesity and type 2 diabetes (3,4), it is not known whether PCSK9 levels are also changed in individuals with T1D. Here, we measured PCSK9 levels in a subset of a previously described cohort of T1D and control subjects (5). For the current study, subjects with serum available for PCSK9 measurement were matched for age and sex between each group using the frequency matching method. Subjects who reported taking statin medications at the time of the study were excluded from the analyses ( n = 3, all from T1D …

The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: Trial design and baseline characteristics

The Flexible Lifestyle Empowering Change (FLEX) Intervention Study is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management for youth with type 1 diabetes mellitus (T1D). This paper details FLEX design, demographic characteristics of the sample, and outcome variables at baseline. Participants were randomized to either an intervention or control arm after their baseline standardized measurement visit. Baseline data for the primary (glycemic levels) and secondary outcome variables (e.g., motivation and problem-solving, health-related quality of life, risk factors associated with T1D complications) as well as the potential mediator variables (e.g., self-management behavior, family conflict and responsibility) suggest that the study sample was representative of the general population of adolescents with T1D and their parents. The FLEX adaptive intervention is an innovative application of a tailored treatment intervention designed to be readily adopted in real-world practice to meet each adolescents individualized T1D self-management goals.