Andrea MacIntosh

Metabolic Consequences of Hepatic Steatosis in Overweight and Obese Adolescents

OBJECTIVE To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness. RESEARCH DESIGN AND METHODS This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge. RESULTS The presence of hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU ⋅ kg−1 ⋅ min−1, P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (β = −0.24, t = −2.29, P < 0.025), metabolic syndrome (β = −0.54, t = −5.8, P < 0.001), and glucose area under the curve (β = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome. CONCLUSIONS Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass.

Dietary determinants of hepatic steatosis and visceral adiposity in overweight and obese youth at risk of type 2 diabetes

BACKGROUND Dietary determinants of hepatic steatosis, an important precursor for nonalcoholic fatty liver disease, are undefined. OBJECTIVE We explored the roles of sugar and fat intake as determinants of hepatic steatosis and visceral obesity in overweight adolescents at risk of type 2 diabetes. DESIGN This was a cross-sectional study of dietary patterns and adipose tissue distribution in 74 overweight adolescents (aged: 15.4 ± 1.8 y; body mass index z score: 2.2 ± 0.4). Main outcome measures were hepatic steatosis (≥5.5% fat:water) measured by magnetic resonance spectroscopy and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥0.25) measured by magnetic resonance imaging. Main exposure variables were dietary intake and habits assessed by the Harvard Youth Adolescent Food Frequency Questionnaire. RESULTS Hepatic steatosis and visceral obesity were evident in 43% and 44% of the sample, respectively. Fried food consumption was more common in adolescents with hepatic steatosis than in adolescents without hepatic steatosis (41% compared with 18%; P = 0.04). Total fat intake (β = 0.51, P = 0.03) and the consumption of >35% of daily energy intake from fat (OR: 11.8; 95% CI: 1.6, 86.6; P = 0.02) were both positively associated with hepatic steatosis. Available carbohydrate (β = 0.54, P = 0.02) and the frequent consumption of soda were positively associated with visceral obesity (OR: 6.4; 95% CI: 1.2, 34.0; P = 0.03). Daily fiber intake was associated with reduced odds of visceral obesity (OR: 0.82; 95% CI: 0.68, 0.98; P = 0.02) but not hepatic steatosis. CONCLUSION Hepatic steatosis is associated with a greater intake of fat and fried foods, whereas visceral obesity is associated with increased consumption of sugar and reduced consumption of fiber in overweight and obese adolescents at risk of type 2 diabetes.

Cardiorespiratory fitness and adiposity in metabolically healthy overweight and obese youth.

OBJECTIVE: Controversy exists surrounding the contribution of fitness and adiposity as determinants of the Metabolically Healthy Overweight (MHO) phenotype in youth. This study investigated the independent contribution of cardiorespiratory fitness and adiposity to the MHO phenotype among overweight and obese youth. METHODS: This cross-sectional study included 108 overweight and obese youth classified as MHO (no cardiometabolic risk factors) or non-MHO (≥1 cardiometabolic risk factor), based on age- and gender-specific cut-points for fasting glucose, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and hepatic steatosis. RESULTS: Twenty-five percent of overweight and obese youth were classified as MHO. This phenotype was associated with lower BMI z-score (BMI z-score: 1.8 ± 0.3 vs 2.1 ± 0.4, P = .02) and waist circumference (99.7 ± 13.2 vs 106.1 ± 13.7 cm, P = .04) compared with non-MHO youth. When matched for fitness level and stratified by BMI z-score (1.6 ± 0.3 vs 2.4 ± 0.2), the prevalence of MHO was fourfold higher in the low BMI z-score group (27% vs 7%; P = .03). Multiple logistic regression analyses revealed that the best predictor of MHO was the absence of hepatic steatosis even after adjusting for waist circumference (odds ratio 0.57, 95% confidence interval 0.40–0.80) or BMI z-score (odds ratio 0.59, 95% confidence interval 0.43–0.80). CONCLUSIONS: The MHO phenotype was present in 25% of overweight and obese youth and is strongly associated with lower levels of adiposity, and the absence of hepatic steatosis, but not with cardiorespiratory fitness.

Hepatic Steatosis and Low Cardiorespiratory Fitness in Youth With Type 2 Diabetes

The purpose of this study was to examine the association between cardiorespiratory fitness, ectopic triglyceride accumulation, and insulin sensitivity among youth with and without type 2 diabetes. Subjects included 137 youth ages 13–18 years including 27 with type 2 diabetes, 97 overweight normoglycemic controls, and 13 healthy weight normoglycemic controls. The primary outcome measure was cardiorespiratory fitness defined as peak oxygen uptake indexed to fat free mass. Secondary outcomes included liver and muscle triglyceride content determined by 1H‐magnetic resonance spectroscopy and insulin sensitivity determined by frequently sampled intravenous glucose tolerance test. Despite similar measures of adiposity, peak oxygen uptake was 11% lower (38.9 ± 7.9 vs. 43.9 ± 6.1 ml/kgFFM/min, P = 0.002) and hepatic triglyceride content was nearly threefold higher (14.4 vs. 5.7%, P = 0.001) in youth with type 2 diabetes relative to overweight controls. In all 137 youth, cardiorespiratory fitness was negatively associated with hepatic triglyceride content (r = −0.22, P = 0.02) and positively associated with insulin sensitivity (r = 0.29, P = 0.002) independent of total body and visceral fat mass. Hepatic triglyceride content was also negatively associated with insulin sensitivity (r = −0.35, P < 0.001), independent of adiposity, sex, age, and peak oxygen uptake. This study demonstrated that low cardiorespiratory fitness and elevated hepatic triglyceride content are features of type 2 diabetes in youth. Furthermore, cardiorespiratory fitness and hepatic triglyceride are associated with insulin sensitivity in youth. Taken together, these data suggest that cardiorespiratory fitness and hepatic steatosis are potential clinical biomarkers for type 2 diabetes among youth.

Vigorous intensity exercise for glycemic control in patients with type 1 diabetes.

Regular physical activity has substantial health benefits in persons with type 1 diabetes, including reduced risk of complications and cardiovascular mortality as well as improved self-rated quality of life. Despite these benefits, individuals with type 1 diabetes are often less active than their peers without diabetes. When factors such as time constraints, work pressure and environmental conditions are often cited as barriers to physical activity in the general population, 2 additional major factors may also explain the low rates of physical activity in young people with type 1 diabetes: (1) fear of hypoglycemia both during and after (particularly overnight) exercise and (2) a lack of empiric evidence for the efficacy of physical activity for achieving optimal glycemic control. A number of acute exercise trials recently showed that the inclusion of vigorous intensity physical activity in conventional moderate intensity (i.e. walking and light cycling) exercise sessions may overcome these barriers. No studies have tested the efficacy of high-intensity physical activity on glycemic control (A1C) or post-exercise hypoglycemia in a randomized controlled trial. This article summarizes the literature related to the role of physical activity for the management of blood glucose levels in individuals with type 1 diabetes and provides a rationale for the need of a randomized controlled trial examining the effects of vigorous-intensity physical activity on blood glucose control.

Fitness is a determinant of the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus

The purpose of this prospective cohort study was to determine whether changes in cardiorespiratory fitness are associated with the metabolic response to endurance training in adolescents at risk of type 2 diabetes mellitus (T2DM).

Physical activity intensity and type 2 diabetes risk in overweight youth: a randomized trial

Background:The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood.Objective:To test the hypothesis that high-intensity endurance training (ET) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents.Design and methods:In this randomized trial, 106 overweight and obese adolescents (15.2 years; 76% female; 62% Caucasian) were randomly assigned to high-intensity ET (70–85% of heart rate reserve, n=38), moderate-intensity ET (40–55% heart rate reserve; n=32) or control for 6 months (n=36). The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sampled intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy. Exploratory outcomes were cardiorespiratory fitness, physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity.Results:The study had 96% retention and attendance was 61±21% and 55±24% in the high- and moderate-intensity ET arms. Intention-to-treat analyses revealed that, at follow-up, insulin sensitivity was not different between high-intensity (−1.0 mU kg−1 min−1; 95% confidence interval (CI): −1.6, +1.4 mU kg−1 min−1) and moderate-intensity (+0.26 mU kg−1 min−1; 95% CI: −1.3, +1.8 mU kg−1 min−1) ET arms compared with controls (interaction, P=0.97). Similarly, hepatic triglyceride at follow-up was not different in high-intensity (−1.7% fat/water (F/W); 95% CI: −7.0, +3.6% F/W) and moderate-intensity (−0.40% FW; 95% CI: −6.0, +5.3% F/W) ET compared with controls. Both high intensity (+4.4 ml per kg-FFM (fat-free mass) per minute; 95% CI: 1.7, 7.1 ml kg-FFM−1 min−1) and moderate intensity (+4.4 ml kg-FFM−1 min−1; 95% CI: 1.6, 7.3 ml kg-FFM−1 min−1) increased cardiorespiratory fitness, relative to controls (interaction P<0.001).Conclusions:ET improves cardiorespiratory fitness among obese adolescents; however, owing to lack of compliance, the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear.

The Blood Pressure Response to Exercise in Youth with Impaired Glucose Tolerance and Type 2 Diabetes

Type 2 diabetes is associated with hypertension and an increased risk of cardiovascular disease. In adults, blood pressure (BP) responses to exercise are predictive of these complications. To determine if the hemodynamic response to exercise is exaggerated in youth with dysglycemia (DG) compared with normoglycemic overweight/ obese (OB) and healthy weight (HW) controls a cross-sectional comparison of BP and heart rate (HR) responses to graded exercise to exhaustion in participants was performed. DG and OB youth were matched for age, BMI z-score, height and sex. Systolic (SBP) and diastolic BP (DBP) were measured every 2 min, and HR was measured every 1 min. SBP was higher in OB and DG compared with HW youth at rest (p < .001). Despite working at lower relative workloads compared with HW, the BP response was elevated during exercise in OB and DG. For similar HR and oxygen consumption rates, BP responses to exercise were slightly higher in OB and DG compared with HW. OB and DG youth both display elevated resting and exercise BP relative to HW peers. Obesity may play a greater role than dysglycemia in the exaggerated BP response to exercise in youth.

Vigorous Intervals and Hypoglycemia in Type 1 Diabetes: A Randomized Cross Over Trial

Adding vigorous-intensity intervals (VII) to moderate-intensity exercise prevents immediate declines in blood glucose in type 1 diabetes (T1D) however the intensity required to minimize post-exercise hypoglycemia is unknown. To examine this question, ten sedentary T1D individuals completed four treadmill exercise sessions: a control session of 45 minutes of walking at 45–55% of heart rate reserve (HRR) and three sessions consisting of 60 seconds (VII) at 70%, 80%, or 90% of HRR every 4 minutes during exercise at 45–55% of HRR. We used continuous glucose monitoring (CGM) to measure time ≤3.9 mmol/L, glucose variability, hypoglycemia frequency and area under the curve (AUC) for hypoglycemia and hyperglycemia for 12 hours post-exercise. We also examined growth hormone and cortisol responses during and following exercise. In the 12 hours post-exercise, the percentage of time ≤3.9 mmol/L, glucose variability, and AUC for hypoglycemia and hyperglycemia were similar across conditions. The frequency of hypoglycemic events was highest after the 90% intervals compared to the control arm (12 vs 3 events, p = 0.03). There was a trend towards elevated growth hormone with increasing exercise intensity but cortisol levels were similar across conditions. Adding VII to moderate intensity exercise may increase hypoglycemia risk at higher intensities.