The Relationship Between Lipoproteins and Insulin Sensitivity in Youth With Obesity and Abnormal Glucose Tolerance.

CONTEXT: Youth with obesity and abnormal glucose tolerance have an increased risk for atherosclerosis but the relative contributions of insulin resistance and hyperglycemia to dyslipidemia and the development of subclinical atherosclerosis are unknown. OBJECTIVE: This work aims to determine the association between insulin resistance, dyslipidemia, and carotid intimal thickness (cIMT) in adolescents with normal and abnormal glucose tolerance. METHODS: An observational cohort study in 155 youth: 44 obese insulin sensitive (OIS; fasting insulin ≤ 20 µM/mL, body mass index [BMI] ≥ 95th percentile), 35 obese insulin resistant (OIR; fasting insulin > 20 µM/mL, BMI ≥ 95th percentile), 34 obese abnormal glucose tolerant (AGT; BMI ≥ 95th percentile), and 42 Lean (BMI 5th-85th percentile). Lipids, lipoprotein particle size and concentration (-P), insulin sensitivity (SI an intravenous glucose test), and CMIT were compared using linear models adjusted for age, race/ethnicity, biological sex, and Tanner stage. Lipid/lipoprotein profile and CMIT were reevaluated in a subset after 2 years. RESULTS: Compared to OIS and Lean, OIR and AGT had elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) but similar total cholesterol and low-density lipoprotein cholesterol (LDL-C). Among OIS, OIR, AGT, lower SI was associated with atherogenic lipids (higher triglycerides, LDL-C, non-HDL-C, and lower HDL-C) and lipoproteins (higher total LDL-P and small HDL-P, and lower large HDL-P). There was a steeper decline in the association of SI with HDL-C and large HDL-P in AGT compared with OIR and OIS. cIMT was comparable across groups and inversely correlated with SI, with no change after 2 years. CONCLUSION: Among youth with obesity, insulin resistance was associated with an atherogenic lipoprotein/lipid profile and cIMT, regardless of glucose tolerance status. Insulin resistance in AGT youth was associated with a shift to smaller HDL-P compared to normoglycemic youth with obesity. Alterations in HDL-P metabolism may be early adverse manifestations of hyperglycemia in youth with obesity.

A Text Messaging Intervention With Financial Incentive for Adolescents With Type 1 Diabetes.

BACKGROUND: Adolescents with type 1 diabetes (T1D) have higher hemoglobin A1C (HbA1c) levels than others. In general, adolescents engage with text messaging (TM) and financial incentives, both associated with improved diabetes outcomes. This study aimed to assess the impact of a TM intervention with financial incentives on self-care behaviors and HbA1c. METHODS: A six-month randomized controlled trial compared MyDiaText™, a TM education and support application, with standard care. The sample included 166 teens with T1D, 12-18 years old, attending a diabetes clinic. The intervention group received one daily TM and were instructed to respond. Participants who responded to TMs for the most consecutive days were eligible for a financial reward biweekly via lottery. All participants received prompts to complete the self-care inventory (SCI) at baseline, 90, and 180 days. HbA1c was collected at clinic visits. Changes in SCI and HbA1c were analyzed using a multilevel mixed-effects linear regression model. Intention-to-treat and per-protocol analyses were performed. RESULTS: The median TM response rate was 59% (interquartile range 40.1%-85.2%) and decreased over time. After adjustment for baseline characteristics, in per-protocol analysis, there was a statistically significant difference in SCI score increase in those receiving one TM per day vs control (P = .035). HbA1c decreased overall, without significant difference between groups (P = .786). CONCLUSIONS: A TM intervention with financial incentives for adolescents with T1D in suboptimal control was associated with increasing self-care report; however, glycemic control did not differ from controls. Further research is needed to develop digital health interventions that will impact glycemic control.

Pediatric Type 2 Diabetes: Not a Mini Version of Adult Type 2 Diabetes.

Pediatric type 2 diabetes mellitus (T2DM) is increasing in incidence, with risk factors including obesity, puberty, family history of T2DM in a first-degree or second-degree relative, history of small-for-gestational-age at birth, child of a gestational diabetes pregnancy, minority racial group, and lower socioeconomic status. The pathophysiology of T2DM consists of insulin resistance and progression to pancreatic beta-cell failure, which is more rapid in pediatric T2DM compared with adult T2DM. Treatment options are limited. Treatment failure and nonadherence rates are high in pediatric T2DM; therefore, early diagnosis and treatment and new pharmacologic options and/or effective behavioral interventions are needed.

MyDiaText™: Feasibililty and Functionality of a Text Messaging System for Youth With Type 1 Diabetes.

PURPOSE: The purpose of this study was to determine the feasibility and functionality of MyDiaText™, a website and text messaging platform created to support behavior change in adolescents with type 1 diabetes (T1DM) and to evaluate user satisfaction of the application. METHODS: This study was a nonrandomized, prospective, pilot trial to test the feasibility and user interface with MyDiaText, a text message system for 10- to 17-year-old youths with newly diagnosed T1DM. Feasibility was evaluated by assessing for the user's ability to create a profile on the website. Functionality was defined by assessing whether a subject responded to at least 2 text messages per week and by their accumulating points on the website. User satisfaction of the text messaging system was assessed using an electronic survey. The 4 phases of this study were community engagement-advisory sessions, screening and enrollment, intervention, and follow-up. RESULTS: Twenty subjects (14 male, 6 female) were enrolled. All subjects were able to create a profile, and of these, 86% responded to at least 2 text messages per week. A survey administered during follow-up showed that users enjoyed reading text messages, found them useful, and thought the frequency of messages was appropriate. CONCLUSION: MyDiaText is a feasible, functional behavioral support tool for youth with T1DM. Users of the application reported high satisfaction with text messages and the reward system.

Insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to cardiovascular disease biomarkers in obese adolescents.

CONTEXT: Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 have been linked to cardiovascular disease (CVD) risk and pathophysiology in adults, but there are limited data in youth. OBJECTIVE: The aim of the study was to examine the relationship between IGF and IGFBP-1 with traditional and non-traditional CVD risk factors including inflammatory markers and body composition in an obese pediatric cohort. DESIGN: A cross-sectional study. SETTING: The study was carried out at a university children's hospital. SUBJECTS: Sixty-one obese non-diabetic adolescents. OUTCOMES: Fasting IGF-I, IGFBP-1, lipoprotein profiles, high-sensitivity C-reactive protein (hsCRP), and total adiponectin as well as insulin sensitivity measures, blood pressure (BP), and anthropometrics. RESULTS: IGFBP-1 was negatively associated with insulin sensitivity measures, body mass index (BMI), and diastolic BP in males. IGF-I was negatively associated with hsCRP (r = -0.479, p < 0.0005), and IGFBP-1 was positively associated with adiponectin (r = 0.545, p < 0.0005). The IGF-I/CRP and IGFBP-1/adiponectin associations remained significant when controlling for both BMI and insulin sensitivity index (SI ). Both IGF-I and IGFBP-1 were negatively associated with waist circumference (r = -0.327 and r = -0.275, respectively) and sagittal abdominal diameter (r = -0.333 and r = -0.371, respectively), while IGFBP-1 was negatively associated with fat mass (r = -0.347, p = 0.01) as well as neck circumference and fat-free mass in males. Controlling for BMI z-score and SI , IGFBP-1 remained negatively associated with diastolic blood pressure (r = 0.706, p = 0.001 and neck circumference (r = -0.548, p = 0.15) in males. CONCLUSIONS: IGF-I and IGFBP-1 associate with CVD risk markers and may add to clinical assessments of cardiometabolic dysfunction in youth.

Comparison of oral and intravenous glucose tolerance test derived sensitivity and secretory indices in obese adolescents.

BACKGROUND: Insulin resistance increases type 2 diabetes risk in obese adolescents. Thus, quantitative tools measuring insulin sensitivity and secretion are important for risk assessment. METHODS: Forty-four obese pubertal adolescents underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). We correlated OGTT-derived whole body sensitivity index (WBISI) with FSIGT-derived insulin sensitivity index (Si). Insulinogenic index (IGI) from OGTT was compared with acute insulin response to glucose (AIRg) from FSIGT. RESULTS: Fasting insulin (r = -.64, P < .0005) and glucose (r = -.39 P ≤ .0005) predicted Si. The OGTT-derived index WBISI correlated with the FSIGT-derived Si (r = .608, P < .0005). IGI correlated with AIRg from FSIGT (r = .704, P < .0005). CONCLUSIONS: OGTT-based measures correlated with FSIGT-derived measures of insulin sensitivity and secretion. In particular, we demonstrated that WBISI can be a reliable alternative to FSIGT-derived Si in clinical settings where OGTT is a more feasible option.

Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study.

OBJECTIVE: The study objective was to examine the prevalence of depressive symptoms and relationships to quality of life and demographics in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study's large, ethnically diverse youth with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 704 youth with type 2 diabetes <2 years' duration, aged 10-17 years, and BMI ≥85th percentile completed depressive symptoms and quality of life measures. RESULTS: Some 14.8% reported clinically significant depressive symptoms, and older girls had significantly higher rates than older boys. CONCLUSIONS: Rates of significant depressive symptoms were similar to those of healthy adolescents and lower than those of teens with type 1 diabetes. Elevated depressive symptoms, particularly in older girls, suggest clinicians assess vulnerability.

Parathyroid hormone reserve in 22q11.2 deletion syndrome.

OBJECTIVE: We hypothesized that most patients with 22q11.2 deletion and a history of hypocalcemia have inadequate parathyroid function, manifested by intact parathyroid hormone levels below normal. We aimed to evaluate intact parathyroid hormone levels both during normocalcemia and at hypocalcemia, in this population. STUDY DESIGN: Retrospective chart review of 103 patients with 22q11.2 deletion born since 1997 and cared for at the Children's Hospital of Philadelphia. Calcium and intact parathyroid hormone drawn simultaneously were recorded, along with clinical presentation at hypocalcemia. RESULTS: Forty-seven simultaneous Ca/intact parathyroid hormone values were available. Seventy-nine percent of calcium levels and 81% of parathyroid hormone levels were within normal range. There were 19 patients with a history of symptomatic hypocalcemia, for whom any available simultaneous Ca/parathyroid hormone levels, before, during, or after hypocalcemia were analyzed. In this subgroup, 59% of calcium and 76% of parathyroid hormone levels were normal. None had an intact parathyroid hormone of >39.2 pg/mL at hypocalcemia. Seventy-three percent of hypocalcemic events had a precipitating stressor. CONCLUSIONS: Hypoparathyroidism in 22q11.2 deletion is mild, manifesting as a phenomenon of decreased parathyroid hormone reserve. Subjects are normocalcemic most of the time, but are unable to mount elevated intact parathyroid hormone levels, and therefore unable to correct hypocalcemia, in response to stressors.

Fasting c-peptide and insulin-like growth factor-binding protein-1 levels help to distinguish childhood type 1 and type 2 diabetes at diagnosis.

BACKGROUND: Children with new onset diabetes (n = 175) were evaluated over 12-months. Patients were presumptively diagnosed with type 2 diabetes mellitus (T2DM) (n = 26) based on obesity, a relative with T2DM, the ability to wean from insulin, and absence of glutamic acid decarboxylase-65 (GAD-65) antibodies. We hypothesized that markers of insulinization at diagnosis, including fasting C-peptide and insulin-like growth factor-binding protein (IGFBP)-1, in addition to initial CO(2) levels and urine ketones, would help in distinguishing type 1 diabetes mellitus (T1DM) from T2DM. RESULTS: Children with T1DM (84 male, 65 female) had a mean age of 8.7 +/- 4.3 yr and a racial background of 78% white, 19% black, and 3% other. In contrast, children with T2DM (13 female, 13 male) had a mean age of 14.2 +/- 3.1 yr with a racial background of 58% black, 27% white, and 15% other. Fasting C-peptide level was 0.38 +/- 0.37 ng/mL in T1DM vs. 2.66 +/- 2.14 ng/mL in T2DM; a C-peptide of 0.85 ng/mL had 83% sensitivity in distinguishing T1DM from T2DM. Fasting IGFBP-1 level was 38.1 +/- 39.1 ng/mL (T1DM) vs. 3.6 +/- 4.5 ng/mL (T2DM); a value of 3.6 ng/dL could distinguish the two types of diabetes with 93% sensitivity. Urinary ketones were found in 79% of children with T1DM compared with 56% of those with T2DM, and the magnitude was associated with type of diabetes. Initial CO(2) level for T1DM was 17.9 +/- 6.9 mmol/L vs. 22.7 +/- 5.7 mmol/L for T2DM; a value of 21.5 mmol/L could distinguish the two types of diabetes with 83% sensitivity. CONCLUSIONS: In addition to obesity, family history of T2DM, and absence of GAD-65 antibodies, children with new-onset T2DM may be distinguished from those with T1DM by a combination of biochemical parameters (C-peptide, IGFBP-1, CO(2), and urine ketones).