Type 2 Diabetes In Youth Research Articles

Exercise training improves vascular health but not metabolic control in adolescents with type 2 diabetes

Introduction: The rapid increase in childhood obesity has seen the recent emergence of type 2 diabetes (T2D) in teenagers. In Australia, the rate of diagnosis of T2D in youth increased nearly 10-fold in the past last decade and recent data suggesting that 20–25% of obese children and adolescents worldwide are diagnosed with T2D. Vascular disease is a leading cause of disability in patients with T2D, and we have recently reported that youth with T2D have poorer endothelial function than non-diabetic age and BMI matched youth.

Adipocyte-Specific FAK Deletion in Mice Leads to Insulin Resistance but Divergent Adipose Tissue Remodelling Under Lean and Obese Conditions

Insulin resistance and liver fat are both predictors of type 2 diabetes (T2D) in youth. Although lean body mass (LBM) is known to influence insulin resistance, the association of LBM with liver fat has received little attention in youth at risk of T2D. To investigate the association between insulin resistance and liver fat with LBM in youth at risk of T2D. 113 overweight and obese (97.1±3.1 BMI percentile) youth (15.3±1.7 years) participated in this cross-sectional study. The primary outcome measures were insulin resistance (measured by HOMA-IR), liver transaminases (ALT/AST), and liver fat (MRS measured). The primary exposure variable was LBM index [LBMI; lean body mass (kg)/height (m2)]. LBMI was positively associated with fat mass (r=0.56, p=0.0001) and visceral fat mass (r=0.39, p=0.0001). LBMI was negatively associated with HDL-cholesterol (r=–0.28, p=0.006) and positively associated with AST (r=0.27, p=0.002), ALT (r=0.46, p=0.0001), and liver fat (r=0.28, p=0.002). Multiple linear regressions revealed that LBMI was associated with HOMA-IR (ß=0.216 SE 0.061, p=0.0006) and ALT (ß=1.557 SE 0.482, p=0.001) independently of age, sex, ethnicity, visceral fat mass and fitness level, but not with liver fat (p=0.186). These results suggest that LBMI contributes to insulin resistance and liver fat in youth at risk of T2D. Considering that liver fat is the strongest predictor of T2D in youth, LBMI should be considered in risk assessment in youth at high risk of T2D.

The Effects of Type 2 Diabetes on Lipoprotein Composition and Arterial Stiffness in Male Youth

Recent studies suggest HDL exists as numerous subpopulations with distinct protein/lipid compositions that are not reflected in the HDL cholesterol (HDL-C) number. In this study, we sought to evaluate HDL subpopulations in adolescents with type 2 diabetes (T2D) to determine if changes in HDL composition are associated with early vascular disease. T2D (n = 10), lean (n = 9), and obese (n = 11) youth were recruited. Plasma was fractionated using gel-filtration chromatography, and lipid-associated proteins were identified using mass spectrometry. Concurrently, vascular stiffness was assessed using pulse wave velocity (PWV). We found youth with T2D exhibited decreased phospholipid content in fractions containing large HDL particles that was inversely associated with PWV (P < 0.001). No association was noted between HDL-C and PWV. Proteomic analysis revealed changes in 7 of 45 identified proteins in the T2D group, including apolipoprotein (apo) A-II, apoE, and paraoxonase-1 (P < 0.05). Our data demonstrate early changes in the lipid and protein compositions of specific HDL subspecies in adolescents with T2D that are related to early markers of arterial disease. These findings suggest that analyzing the composition of HDL, rather than HDL-C, may be useful in assessing cardiovascular risk in this population.

Abstract 013: High Prevalence and Rapid Increase of Cardiovascular Disease Risk Factors in Youth with Type 2 Diabetes: The TODAY Study Group

Background The natural history of type 2 diabetes (T2D) in youth appears to differ from that in adults in that almost half of T2D youth in the “Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)” study had a rapid decline in beta cell function. The rate of change in risk for cardiovascular disease (CVD) in youth with T2D is not known. We tested the hypothesis that CVD risk factors are highly prevalent and rapidly progress over time in youth with T2D using longitudinal assessments of hypertension (HT), microalbuminuria (MA) and dyslipidemia obtained during the TODAY clinical trial of adolescents with recent onset T2D. Methods A cohort of 699 adolescents, aged 10-17 years, &lt;2 years duration of T2D, body mass index (BMI) ≥85th percentile, Hemoglobin A1c (A1c) ≤8% on metformin therapy were randomized to metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention and followed over an average of 3.9 years. (range 2-6.5 years). Primary outcome was loss of glycemic control. Quarterly BP and annual MA were monitored with initiation and titration of therapy (ACE inhibitor) to maintain BP &lt;130/80 or &lt;95th percentile for age, gender, and height and MA &lt;30 mcg/mg. Statin drugs were begun for LDL cholesterol (LDLC) ≥130 mg/dL or triglycerides ≥300 mg/dL. Change in the prevalence of CVD risk factors was examined accounting for the effect of treatment group, time, glycemic control, gender, and race-ethnicity. Results In this cohort, 319 (45•6%) reached primary glycemic outcome. HTN was observed in 11•6% of subjects at baseline and 33•8% by end of study (average follow-up 3•9 years). MA was found in 6•3% at baseline and rose to 16•6% at study end. Participants with LDLC ≥130 mg/dL or statin use increased from 4.5% to 10.7%. Male gender and higher BMI significantly increased the risk for HTN. Higher levels of hemoglobin A1c correlated with the risk of developing MA and dyslipidemia. Conclusion The prevalence of CVD risk factors increased rapidly among adolescents with T2D regardless of diabetes treatment. The greatest risk for HTN was male gender and higher BMI. The risk for microalbuminuria and worsening of dyslipidemia was related to glycemic control. Measures to address CVD risk are needed early in the disease course in this high risk population.

Management of Pediatric and Adolescent Type 2 Diabetes

Type 2 diabetes (T2D) was an adult disease until recently, but the rising rates of obesity around the world have resulted in a younger age at presentation. Children who have T2D have several comorbidities and complications reminiscent of adult diabetes, but these are appearing in teens instead of midlife. In this review, we discuss the clinical presentation and management options for youth with T2D. We discuss the elements of lifestyle intervention programs and allude to pharmacotherapeutic options used in the treatment of T2D youth. We also discuss comorbidities and complications seen in T2D in children and adolescents.

Glucose Control Predicts 2-Year Change in Lipid Profile in Youth with Type 1 Diabetes

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). 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. 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). 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.

Arterial Stiffness, Lipoprotein Particle Size, and Lipoprotein Particle Concentration in Children with Type 1 Diabetes

To determine if lipoprotein particle abnormalities correlate with arterial stiffness in children with type 1 diabetes (T1D). In this case-control study, we evaluated 70 children, 35 with T1D and 35 controls, ages 10-18 years, matched for age, sex, race, and BMI. Arterial stiffness was assessed by radial tonometry (AI75) and blood was collected for lipoprotein subclass analysis. T1D subjects had increased AI75, decreased small LDL particle concentration (P = 0.0067), increased large LDL particle concentration (P = 0.007), increased large HDL particle concentration (P = 0.0012), increased mean LDL particle size (P = 0.0028), and increased mean HDL particle size (P < 0.0001) compared to controls. No significant correlations were found between lipoprotein subclasses and arterial stiffness in T1D subjects. T1D subjects have increased arterial stiffness when compared to controls, despite a less pro-atherogenic lipoprotein profile, indicating the need to identify other risk factors that correlate with arterial stiffness in T1D youth.

Insulin Resistance in Adolescents with Type 1 Diabetes and Its Relationship to Cardiovascular Function

Cardiovascular disease is the major cause of death in adults with diabetes, yet little is specifically known about the effects of type 1 diabetes (T1D) on cardiovascular outcomes in youth. Although insulin resistance (IR) likely contributes to exercise and cardiovascular dysfunction in T2D, IR is not typically considered a contributor in T1D. We hypothesized that cardiopulmonary fitness would be reduced in T1D youth in association with IR and cardiovascular dysfunction. This cross-sectional study at an academic hospital included 12 T1D adolescents compared with 12 nondiabetic controls, similar in age, pubertal stage, activity level, and body mass index. Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, intramyocellular lipid by magnetic resonance spectroscopy, and body composition by dual-energy x-ray absorptiometry. T1D adolescents had significantly decreased VO(2)peak, peak work rate, and insulin sensitivity compared with nondiabetic adolescents. T1D youth also had reduced vascular reactivity and evidence of diastolic dysfunction and left ventricular hypertrophy. Despite their IR and reduced cardiovascular fitness, T1D youth had paradoxically normal intramyocellular lipid, waist to hip ratio, and serum lipids and high adiponectin levels. In multivariate analysis, IR primarily, and forearm blood flow secondarily, independently predicted VO(2)peak. T1D youth demonstrated IR, impaired functional exercise capacity and cardiovascular dysfunction. The phenotype of IR in T1D youth was unique, suggesting a pathophysiology that is different from T2D, yet may adversely affect long-term cardiovascular outcomes.