Sex differences in cardiovascular risk factors of children and adolescents with type 1 diabetes mellitus: A role for diet?

BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of morbidity and mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk is higher in women with diabetes than in men. With this study, we wanted to determine whether female children and adolescents with T1DM are more prone to cardiovascular risk factors (CVRFs) and an atherogenic diet than boys. METHODS AND RESULTS: For this cross-sectional study, anthropometric, clinical, biochemical, and dietary intake data of 314 children with diabetes (3-18 years; 178 boys) were analysed according to age and sex. Linear and binary logistic regression was performed to test independent associations between sex, dietary intake, and CVRFs. Low-density lipoprotein -cholesterol (LDL-c), triglyceride (TG), fibre, monounsaturated fatty acid levels (all p < 0.01), and lipid (p = 0.022) intake were higher in the girls than in the boys. Multiple regression analysis showed that LDL was associated with sex, glycated haemoglobin (HbA1c), and lipid intake percentage (R (Kannel, 1979) [2] = 0.130; p = 0.0004) independent of age, pubertal stage, body mass index (BMI), duration of diabetes, energy, and fibre intake. Logistic regression analysis showed that high LDL-c levels were present more often in girls [odds ratio, OR; confidence interval, CI = 2.569 (1.178-5.604); p = 0.018] who had a higher dietary lipid intake percentage [OR (CI) = 1.089 (1.011-1.173); p = 0.025]. CONCLUSIONS: Girls with diabetes have higher LDL-c levels associated with higher dietary lipid intake. Our findings suggest that young people with diabetes, especially girls, may benefit from early dietary interventions to reduce their cardiovascular risk.

Long chain fatty acids metabolism and cardiovascular risk factors in youth with type 1 diabetes.

BACKGROUND AND AIMS: Fatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D. METHODS AND RESULTS: We recruited 154 adolescents with T1D (aged 17.3 ± 2 years, 82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r = -0.32,p = 6.6∗10-5) and directly with triglycerides (r = 0.24, p = 0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r = -0.26, p = 0.002). We found some weak (r ≤ 0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing. CONCLUSION: In youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.

Lipid and saturated fatty acids intake and cardiovascular risk factors of obese children and adolescents.

OBJECTIVE: To test the hypothesis that lipid intake is associated with triglycerides to HDL-cholesterol ratio (TG/HDL-cholesterol), a predictor of the development of cardiovascular disease, in obese children and adolescents, independently from the level of overweight, insulin resistance, blood pressure, and non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: One hundred and eighty non-diabetic obese children/adolescents (age range 6-16 years) were enrolled. Diet (3-day weighed dietary record), physical and biochemical parameters and liver ultrasonography were measured. The impact of lipid intake on TG/HDL-cholesterol ratio >2.2 was measured by regression models, adjusting for covariates (age, gender, height, weight, systolic and diastolic blood pressure, NAFLD positivity, HOMA-IR, and total energy intake). RESULTS: Independently from covariates, children consuming a diet with a fat content higher than 35% of total energy had a significantly higher chance [OR = 3.333 (95% CI: 1.113-9.979), P = 0.031] to have a TG/HDL-cholesterol >2.2 than children consuming less than 35% of fat. Moreover, if saturated fatty acids (SFA) intake was higher than 13% of total energy, children had a significantly higher chance [OR = 4.804 (95% CI: 1.312-17.593), P = 0.018] to have a TG/HDL-cholesterol >2.2 than children consuming less than 13% of SFA in their diet. CONCLUSIONS: High fat intake, especially SFA intake, is associated with TG/HDL-cholesterol levels of obese children and adolescents, independently from other cardiovascular risk co-factors. Further intervention studies will contribute to clarify the potential role of changes in the composition and amount of fat in the diet of obese children and adolescents, on their cardiovascular risk factors.

13C/12C breath test ratio after the ingestion of a meal naturally enriched with (13C)carbohydrates is a surrogate marker of insulin resistance and insulin sensitivity in children and adolescents with Type 1 Diabetes.

AIMS: To test the hypotheses that exogenous carbohydrate oxidation affects postprandial glycaemic profiles and 13C/12C breath test could be used for estimating insulin resistance (IR) and insulin sensitivity (IS) in youths with Type 1 Diabetes (T1D). METHODS: Non-randomized, cross-sectional study for repeated measures; fifteen youths (11-15 years) with T1D were enrolled. Respiratory exchanges were measured by indirect calorimetry after the ingestion of a mixed meal [13% protein, 29% fat, 58% carbohydrate (CHO; naturally enriched with [13C]carbohydrates)]. Total and exogenous CHOs oxidation was calculated by indirect calorimetry and 13C/12C breath test. IR and IS were calculated using estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS). RESULTS: The blood glucose Area Under the Curve (BG-AUC) was significantly associated with the amount of exogenous CHOs oxidized (r = -0.67, p < 0.02) when adjusting for CHOs intake and %fat mass. A direct correlation between eGDR and ISS with exogenous CHOs oxidized (r = 0.70, p < 0.02; r = 0.61, p < 0.05 respectively) and with the differential of 13C/12C enrichment in the expired at breath test (r = 0.59, p < 0.05; r = 0.62, p < 0.05), was found. CONCLUSIONS: Assessing the capacity to oxidize exogenous CHOs (estimated by the differential of 13C/12C enrichment in the expired air at the breath test) could be used as a non-invasive surrogate marker of IR and IS in youths with T1D.

Nutrition habits of children and adolescents with type 1 diabetes changed in a 10 years span.

BACKGROUND: Diet plays a key role in the treatment of type 1 diabetes (T1D). Dietary habits changed rapidly in the last decades and few data are available on recent dietary changes in children and adolescents with T1D. OBJECTIVE: To test the hypothesis that diet composition changed in a 10-year period in children and adolescents with T1D. METHODS: Two hundred and twenty-nine T1D subjects (M/F:121/108) aged 6 to 16 years were recruited: 114 (group A) enrolled in 2009, not using CGM and/or CSII, and 115 (group B) enrolled in 2019. Anthropometric biochemical (HbA1c, lipid profile), diet, and insulin therapy parameters were compared between the two groups. Multivariate logistic regression analysis was performed with HbA1c as dependent variable (HbA1c > 58 mmol/mol = 1) and nutritional variables and technology use as independent ones. RESULTS: Energy intake of group A was not statistically different from that of group B. Group B had a significantly (P < 0.001) higher protein and lipids intake and lower total carbohydrate and fiber intake than group A. HbA1c was significantly (P < 0.01) lower in group B than in group A. Logistic regression analysis showed that MUFA (OR 0.83, 95%CI:0.693-0.998), fiber intake (OR 0.82, 95%CI:0.699-0.0969), and technology use (OR 0.15, 95%CI:0.031-0.685), adjusted for age, gender, BMI, energy intake and diabetes duration, were associated with a HbA1c higher than 58 mmol/mol) (R2 = 0.27, P < 0.05). CONCLUSIONS: In a 10-year period, diet composition of children and adolescents with T1D changed and glucometabolic control improved. Fiber and MUFA intake showed a positive effect on HbA1c, independent from technology use, supporting the importance of educating children with T1D and families to maintain healthy eating habits.

Glucose-independent association of adiposity and diet composition with cardiovascular risk in children and adolescents with type 1 diabetes.

AIMS: To test the hypothesis that diet composition, adiposity and glycometabolic control could independently contribute to an increase in the cardiovascular risk (CVR) for children/adolescents with type 1 diabetes (T1D). METHODS: One hundred and eighty children/adolescents with T1D (age range 5-18 years) were enrolled. Diet (3-day weighed dietary record), physical (height, weight, waist circumference, bioelectrical impedance analysis) and biochemical (HbA1c, lipid profile) parameters were recorded. Regression models, using non-HDL cholesterol (a gross index of CVR) as the dependent variable and HbA1c (mmol/mol), fat mass (FM) %, lipid-to-carbohydrate intake ratio as independent ones, were calculated. RESULTS: Non-HDL cholesterol was significantly associated with adiposity (FM%; r = 0.27, 95% CI 0.13-0.43), body fat distribution (waist-to-height ratio; r = 0.16, 95% CI 0.02-0.31), lipid intake [% of energy intake (EI)] (r = 0.25, 95% CI 0.11-0.41), carbohydrate intake (% EI; r = -0.24, 95% CI 0.10-0.40), lipid-to-carbohydrate intake ratio (r = 0.26, 95% CI 0.12-0.42) and blood glucose control (HbA1c; r = 0.24, 95% CI 0.10-0.40). A p value cutoff of 0.10 was used for covariates to be included in the regression analysis. Multiple regression analysis showed that adiposity (FM%), blood glucose control (HbA1c) and lipid-to-carbohydrate intake ratio independently contributed to explaining the inter-individual variability of non-HDL cholesterol (R 2 = 0.163, p < 0.05). CONCLUSIONS: Adiposity and lipid-to-carbohydrate intake ratio affect non-HDL cholesterol, a gross index of CVR, regardless of HbA1c, in children and adolescents with T1D. Intervention to reduce CVR in T1D patients should focus not only on glycometabolic control but also on adiposity and diet composition.

Bias in food intake reporting in children and adolescents with type 1 diabetes: the role of body size, age and gender.

BACKGROUND: An assessment of total daily energy intake is helpful in planning the overall treatment of children with type 1 diabetes (T1D). However, energy intake misreporting may hinder nutritional intervention. AIMS: To assess the plausibility of energy intake reporting and the potential role of gender, body mass index (BMI) z-score (z-BMI), disease duration and insulin requirement in energy intake misreporting in a sample of children and adolescents with T1D. METHODS: The study included 58 children and adolescents aged 8-16 yr with T1D. Anthropometry, blood pressure and glycated hemoglobin (HbA1c) were measured. Subjects were instructed to wear a SenseWear Pro Armband (SWA) for 3 consecutive days, including a weekend day and to fill out with their parents a weighed dietary record for the same days. Predicted energy expenditure (pEE) was calculated by age and gender specific equations, including gender, age, weight, height and physical activity level (assessed by SWA). The percent reported energy intake (rEI)/pEE ratio was used as an estimate of the plausibility of dietary reporting. RESULTS: Misreporting of food intake, especially under-reporting, was common in children and adolescents with T1D: more than one-third of participants were classified as under-reporters and 10% as over-reporters. Age, z-BMI and male gender were associated with the risk of under-reporting (model R2 = 0.5). Waist circumference was negatively associated with the risk of over-reporting (model R2 = 0.25). CONCLUSIONS: Children and adolescents with T1D frequently under-report their food intake. Age, gender and z-BMI contribute to identify potential under-reporters.

Protein Intake as a Risk Factor of Overweight/Obesity in 8- to 12-Year-Old Children.

Several studies investigating the relationship between body mass index (BMI), waist circumference (WC), and/or body fat (BF) with macronutrient composition of the diet have suggested that dietary composition may play an important role to overweight/obesity in childhood, but its relation remains inconclusive. The aim was to assess the association between energy intake (EI) and macronutrient diet composition with overweight/obesity among children.Nonrandomized cohort study including 396 Italian children and preadolescents (9-13 years old), 200 overweight/obese and 196 normal-weight. The children's weight, height, WC, and food intake were measured.Reported EI was higher in overweight/obese than in nonoverweight children; however, after body weight was considered, the overweight/obese children had less EI than their leaner counterparts. Percentages of EI from proteins, SFA, MUFA and PUFA (in males), and dietary fiber (g/1000 kcal) were higher in the overweight/obese children than in the leaner ones. EI from carbohydrates and fats was lower in overweight/obese males and females, respectively. Positive correlations between BMI and waist-to-height ratio with EI from proteins were found in males (r = 0.296, P < 0.01 and r = 0.326, P < 0.01; respectively) and females (r = 0.374, P < 0.01 and r = 0.405, P < 0.01; respectively), but negative correlations with fats were found in females (r = -0.240, P < 0.01 and r = -0.188, P < 0.05; respectively). Using binary logistic regression, the highest EI from proteins were associated with higher odds ratio for overweight/obesity, while the lowest EI from carbohydrates was associated with higher odds ratio for overweight/obesity in males.Reported EI of overweight/obese children was higher than nonoverweight peers. Overweight/obese children had higher intakes of proteins compared with nonoverweight ones. Overweight/obese males and females showed lower EI from carbohydrates and fats, respectively, than their leaner counterparts.

Nutritional education and carbohydrate counting in children with type 1 diabetes treated with continuous subcutaneous insulin infusion: the effects on dietary habits, body composition and glycometabolic control.

Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p < 0.001) without changing insulin/kg/day requirement. In the sub-group of patients with a significant HbA1c reduction (ΔHbA1c ≥ 0.5 %, n = 12), the carbohydrate (CHO) intake was significantly higher at follow-up (53.0 ± 4.0 vs 57.6 ± 2.5 %; p < 0.01); on the contrary, fat (31.3 ± 3.6 vs 28.5 ± 1.6 %; p < 0.05) and protein intake (15.4 ± 1.8 vs 13.3 ± 1.6 %; p < 0.01) significantly decreased. Patients without a significant HbA1c reduction did not show any difference. CHC, in combination with nutritional education, does not affect dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.

Diet, physical, and biochemical characteristics of children and adolescents with type 1 diabetes: relationship between dietary fat and glucose control.

BACKGROUND: Nutritional habits may significantly influence glycemic control and cardiovascular risk factors in youth with type 1 diabetes (T1D). AIMS: To assess dietary intake, cardiovascular risk factors, and the association between diet composition and glycemic control in Italian youth with T1D. METHODS: Subjects included 114 youth aged 6-16 yr with T1D receiving a routine treatment program with nutrition counseling and 448 controls. Cross-sectional measures included dietary intake, anthropometry, blood pressure, lipid profile, and, in children with diabetes, HbA1c. RESULTS: In prepubertal children, BMI, subcutaneous skinfolds, the prevalence of overweight/obesity, and LDL cholesterol (LDL-CH) were significantly lower in patients than in controls, whereas HDL cholesterol (HDL-CH) was higher. Pubertal boys with T1D did not differ significantly from controls in either anthropometry or lipid profile. Pubertal girls with T1D had a higher BMI and higher triceps skinfolds than controls but not significantly different prevalence of overweight/obesity or lipid profile. Compared to controls, participants with T1D had a lower intake of lipids and simple carbohydrates, a higher ratio of unsaturated/saturated fats and fibre, and a dietary intake closer to the National Reference Dietary Intakes (RDIs). The odds of having an HbA1c higher than 7.5, adjusted for BMI, lipid, and fibre intake, increases by 53% for every 1% increase of energy intake from saturated fat in the diet and by 30% for every year of duration of diabetes. CONCLUSIONS: Youth with T1D having regular nutritional counseling had a diet closer to RDIs than controls and not different cardiovascular risk factors. High saturated fatty acid intake was associated with poor blood glucose control.