Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2008 Mar 31.
Published in final edited form as: J Cardiovasc Nurs. 2006;21(1):47–55.

Total Homocysteine, Diet, and Lipid Profiles in Type 1 and Type 2 Diabetic and Nondiabetic Adolescents

Melissa Spezia Faulkner 1, Wei-Hsun Chao 2, Savitri K Kamath 3, Laurie Quinn 4, Cynthia Fritschi 5, Jack A Maggiore 6, Robert H Williams 7, Robert D Reynolds 8
PMCID: PMC2276696  NIHMSID: NIHMS40855  PMID: 16407737

Abstract

Background and Research Objective

Limited research is available on the possible differences in the cardiovascular risk factors of total homocysteine (tHcy), dietary energy, and lipids among adolescents with type 1 diabetes mellitus (DM), type 2 DM, or healthy controls. This study’s primary aim was to compare the dietary energy and the intake of macronutrients and micronutrients of folate, and vitamins B6 and B12, as well as lipids and tHcy for adolescents with type 1 DM, type 2 DM, and healthy non-DM controls.

Subjects and Methods

This secondary analysis of the merging of 2 datasets included the following adolescents: 50 with type 1 DM, 14 with type 2 DM, and 53 controls. Mean ages for those with type 1 versus type 2 DM were 15.2 ± 1.9 versus 16.1 ± 1.9 years, respectively. Mean age for the controls was 16.5 ± 1.0 years. Variables included fasting tHcy and lipids, and 24-hour dietary recalls for macronutrients and micronutrients. Hemoglobin A1c was obtained for those with DM. Statistical analyses included one-way analyses of variance, Pearson correlations, and stepwise regression.

Results and Conclusions

Adolescents with type 1 DM had the lowest tHcy values (P < .05), which were reflective of the limited extant research with this population. Lipid profiles and dietary energy did not differ significantly among the 3 groups. Hemoglobin A1c was related to total cholesterol and triglycerides in those with type 1 DM, confirming the importance of promoting better metabolic control in lipid management for these youth. Future research should continue to explore the validity of tHcy and lipids as predictors of CV risks for youth with type 1 and type 2 DM.

Keywords: adolescents, diabetes, diet, lipid profiles, total homocysteine

Cardiovascular disease (CVD) is increased 2 to 4 times in persons with diabetes mellitus (DM) compared to those without it, regardless of the type of DM, and claims the lives of approximately 55% of affected individuals.1 With an increasing incidence of both type 1 and type 2 DM in children and adolescents, there is mounting concern regarding a greater occurrence of risks for earlier onset of CVD.2 In adults, long-standing DM contributes to the development of microvascular and macrovascular complications. Total plasma homocysteine (tHcy), dietary practices, and lipid profiles are clinical parameters that are frequently assessed in determining CVD risks in adult patients with DM. Longitudinal research of dietary patterns of adolescents indicates that diets high in saturated fats and cholesterol promote a negative CVD risk profile.3 Numerous investigators have reported that elevated levels of tHcy, an amino acid formed during methionine metabolism, are related to CVDs.4–6 Elevated levels of tHcy have been found to be associated with an increased risk of atherothrombotic events,4 as well as the acute phase of myocardial infarction when there is an elevation of reactant proteins.5 Although the direction of the causality between elevated tHcy and CVD is not definitive, increasing clinical and epidemiological research supports the hypothesis of tHcy as an independent risk factor.7,8 Similar to linkages of dietary intake of saturated fats to serum lipid levels, the intake of certain B vitamins can influence plasma tHcy levels. Specifically, decreased consumption of folate and vitamins B6 and B12 is associated with higher tHcy levels.9 Currently, there are insufficient data to support specific lipid abnormalities in youth with type 1 DM, whereas youth with type 2 DM tend to exhibit patterns of dys-lipidemia similar to adults that include elevated triglycerides, normal to slightly elevated LDL cholesterol, and decreased HDL cholesterol.10 The extent to which CVD risk factors of tHcy, diet, and lipid profiles differ among adolescents with type 1 DM, type 2 DM, or healthy controls is unknown.

Limited research is available on tHcy concentrations in children and adolescents.11 Studies exploring the association of tHcy in youth with parental or family histories of CVD reveal conflicting results. The Bogalusa Heart Study12 reported that black and white children with a positive parental history of coronary artery disease (CAD) had significantly higher tHcy levels in both gender groups than those without CAD. Alternatively, Glowinska et al13 did not find a relationship between family history of CVD and plasma tHcy. In several studies of youth with type 1 DM, tHcy levels were either not significantly different or were significantly lower than control values.14–17 One important finding noted by Glowinska et al14 was a significantly higher tHcy concentration for those youth with duration of type 1 DM greater than 10 years or with arterial hypertension. Similar to studies in adults with diabetes, Chiarelli et al18 found significantly higher tHcy concentrations associated with diabetic complications of nephropathy (albumin excretion rate >70 μg/min) and proliferative retinopathy in adolescents (mean age = 18.3 ± 2.4 years).

Although a number of prospective studies of adults report that elevated levels of tHcy are associated with the development of CVD,19–21 a recent meta-analysis of the tHcy literature published from 1966 through 1998 found that elevated plasma tHcy levels are not predictive of CVD. This meta-analysis suggested that elevated tHcy levels are related to previously established vascular disease.22 However, data are conflicting regarding the relationship of plasma tHcy levels to CVD in adults with diabetes. Studies indicate that adults with type 1 DM without evidence of nephropathy have plasma tHcy levels lower than, comparable to, or higher than healthy non-DM controls.23–27

Renal status varies in persons with DM related to hyperglycemia, duration of diabetes, and progression of nephropathy, reflecting periods of glomerular hyperfiltration and impaired renal function. In a recent study of adults with type 1 DM, plasma tHcy levels were noted to be significantly lower in the subjects with diabetes than in the subjects with diabetic renal disease and elevated creatinine levels or the non-DM healthy controls.25 Wollesen et al28 identified an inverse relationship between glomeru-lar filtration rate (GFR) and tHcy in adults with type 1 or type 2 DM who had hyperfiltration, resulting in lower tHcy than in those individuals with a normal GFR. Additionally, Neugebauer et al29 reported an inverse relationship between GFR and tHcy in type 1 DM subjects whose GFR was decreased below 75 mL/min, reflecting elevated levels of tHcy in this instance. Glycosylated hemoglobin (HbA1c) was similar in those with GFR<75 mL/min and those with GFR >75 mL/min (9.5% ± 1.6% vs. 9.0% ± 1.3%).

No studies focusing on tHcy in adolescents with type 2 DM were found during this literature review. However, much of the most convincing evidence supporting elevated tHcy as a risk factor for CVD in adults with type 2 DM was derived from the Hoorn study.30,31 This population-based study was a cross-sectional survey of glucose tolerance and other CVD risk factors in a group of middle-aged and elderly men and women residing in the Netherlands. This study demonstrated that an elevated tHcy level was a stronger risk factor for CVD in subjects with type 2 DM compared to subjects with normal or impaired glucose tolerance.30 In particular, the risk of a coronary event increased by 28% for each μmol/L increase in tHcy among the subjects with type 2 DM.31

Although much is known about the connection between diabetes and dyslipidemia as a risk factor for CVD in adults, there are many questions that remain regarding the effects of type 1 or type 2 DM on lipid levels in youth. Teens with diabetes often partake in eating behaviors similar to their peers who consume high-fat diets that are low in fruits, vegetables, and calcium-rich products.32 Dietary recommendations for adolescents emphasize fat intake that is less than 30% of the total calories per day.33 Results of the Bogalusa Heart Study reveal that the majority of US children exceed the national recommendations for total and saturated fat; these youth also have total energy intake that surpasses energy expenditure.34 There is a paucity of longitudinal studies exploring dietary patterns and CVD risks in youth in their transition to young adulthood. The Amsterdam Growth and Health Study followed 98 females and 84 males from 13 to 27 years of age and found that with increasing age and minimal decline in total daily fat intake, the saturated fat and cholesterol intake related significantly and positively to serum total cholesterol (TC).3

There are few observational studies on the relationships among lipoproteins and CVD in adults with type 1 DM. These investigations have reported lipid abnormalities occurring in type 1 DM when accompanied by overweight or obesity, similar to characteristics seen in persons with type 2 DM.35 However, lipid abnormalities specific to youth with type 1 DM have not been thoroughly explicated.10 One prospective study of patients with childhood-onset type 1 DM reported increases in the relative risk for CAD and mortality in patients with poorly controlled lipid levels, thus providing support for the recommendation of more stringent lipid management in patients younger than 18 years.36 Poorer metabolic control was found to be a significant predictor of TC in youth with type 1 DM who had TC levels above the 75th percentile for age, race, and sex.37 Recent research indicated significantly higher lipid levels in youth with type 1 DM than their non-DM counterparts.38

Abnormal lipid levels also have been associated with youth who have type 2 DM, possibly related to the accompanying insulin resistance and overweight/obesity seen in these children.39 However, such abnormal lipid values have been correlated with insulin resistance and overweight/obesity in studies of youth without diabetes as well.40,41 In the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, young persons between 15 and 34 years who died of external causes were found to have a body mass index (BMI) and postmortem glycohemoglobin levels exceeding 8% that were positively linked to the development of fatty streaks and raised lesions in the right coronary artery. These higher glycohemoglobin levels were also related to increased LDL and VLDL cholesterol levels. Results of the PDAY study indicated that atherosclerosis in young adults is associated with a prediabetic or early diabetic state and with obesity.42

Based upon this review of literature on the state of knowledge regarding tHcy, dietary intake, and lipid levels in youth with type 1 or type 2 DM, there was an identified need to explore whether differences exist in the CVD risk profiles for them. Given the relative dearth of information on these variables in general youth populations, we also wanted to compare results to a healthy control group. Therefore, this article presents the data and subsequent analyses derived from the merging of 2 separate datasets so that the necessary comparisons could be made. These datasets include subjects enrolled in an investigation focusing on cardiovascular risks in adolescents with diabetes conducted by Faulkner and colleagues at the University of Illinois at Chicago (UIC) and an investigation focusing on cardiovascular risks in adolescents of Southeast Asian and European origin conducted by Kamath and colleagues, also at UIC. Secondary analysis of existing datasets is possible when scientific rigor is maintained such that the operational variables, including reliability and validity of measures, are congruent and samples are comparable across datasets.43 The purpose of this study was to compare the dietary energy (kilocalories), the intake of macronutrients and micronutrients of folate, and vitamins B6 and B12, as well as the serum lipid profiles and tHcy levels for adolescents with type 1 DM, type 2 DM, and healthy non-DM controls. Sodium intake among the 3 groups was also evaluated. Comparisons of lipid profiles included TC, LDL-C, HDL-C, and triglycerides. Based upon the hypothesized inverse relationship among several of the B vitamins and tHcy, we assessed the specific relationships among dietary intake of folate, vitamins B6 and B12, with tHcy concentrations in each of the groups of adolescents with DM and healthy non-DM controls. The influence of age, gender, and BMI on tHcy and lipid profiles was explored for all 3 groups. For those with diabetes, metabolic control of glucose levels and duration of disease were evaluated for their effects on tHcy and lipid profiles.

Research Design and Methods

Following Institutional Review Board approval, a cross-sectional descriptive design was used to explore CVD risks in both samples of adolescents. Consent was provided by all participants who were 18 years or older. Permission to participate was obtained from a parent or guardian if the teen was younger than 18 years and child assent was obtained.

In the original study by Kamath and colleagues, nondiabetic subjects were recruited from a high school located in an affluent suburb of the Chicago metropolitan area which has a high population of persons of South Asian origin. Recruitment was carried out by posting a flyer in the dining hall and announcing the study in classes. Healthy controls were screened for the following inclusion/exclusion criteria: (1) ages between 13 and 19 years; (2) no known conditions requiring diet modifications; and (3) no history of diabetes, CAD, kidney or liver disease, or cancer of any kind.

The nondiabetic adolescents were asked to complete a personal and family medical history form. They were asked to seek advice from their parents or guardians to gather the information as necessary. When in doubt, the research associate talked to the subject/parent to obtain accurate data. The parents of the adolescents with diabetes also completed a demographic information sheet at the time of data collection while in the clinical setting. This information included the date of diagnosis, age of their son or daughter, race or ethnicity, history of smoking for the adolescent, and family history of diabetes and heart disease for first-degree and second-degree relatives.

In the current study by Faulkner and colleagues, adolescents with type 1 or type 2 DM were recruited from a pediatric diabetes clinic at a major medical center in Chicago, IL. Subjects with similar ages to the nondiabetic group were recruited. These adolescents were from families with a wider range of income than the controls. Most teens were in the middle-income range. Adolescents had to have been diagnosed for 1 year and have no other chronic conditions.

Laboratory Assays

Data collection for the determination of fasting biochemical assays was done in the school setting by the school nurse or a member of the research team members for the non-DM subjects and by the nursing staff of the Clinical Research Center of the university hospital for those with diabetes. tHcy was determined by HPLC using the procedure of Williams et al.44 The Beckman Synchron CX-7 Analyzer (Beckman-Coulter, Brea, Calif) was used to determine TC (cholesterol oxidase), triglycerides (glycerophosphate oxidase), HDL-cholesterol (direct, immunoinhibition), and LDL-cholesterol was calculated using the Friedewald equation.45 Glycosylated hemoglobin (HbA1c) was measured using EDTA whole blood analysis with HPLC (BioRad Laboratories, Hercules, Calif). Laboratory procedures included quality control measurements by routine calibration of all assay equipment.

Dietary Intakes

Three-day 24-hour food record was used to assess the daily food intake including supplements, if any. The 3-day food record has been used successfully with adolescents as a valid measure of assessing nutrient intake.46,47 Data from the food record were entered into a nutrition analysis software program, Nutritionist V™ (San Bruno, Calif), which can be used to perform a nutrient analysis of food records, diets, recipes, and menus and compare this information to specific nutrient requirements. The recipe method was used to determine nutrient content of those items, particularly the South Asian foods, which were not in the database. BMI was calculated by the Nutritionist V™ program, using height and weight measurements obtained at the time of data collection at the school or clinic setting.

Statistical Analyses

Statistical analyses were performed using the SPSS statistical program (version 12.0, SPSS, Chicago, Ill). All analyses included 2-tailed tests of significance at an alpha level of .05. One-way analyses of variance with subsequent post hoc Tukey tests were used to test for significant differences among the mean comparisons of height, weight, BMI, dietary energy, macronutrient intake, selected micronutrient intake, and serum concentrations of lipids, lipoproteins, and tHcy for males and for females across the 3 groups: type 1 DM, type 2 DM, and non-DM. Stepwise regression analyses were completed to identify models for predicting plasma tHcy concentration or lipid profiles based upon age, gender, and BMI for each of the groups.

Pearson correlation coefficients were used to determine relationships among dietary folate, vitamins B6 and B12, and tHcy for each of the 3 groups, those with type 1 DM, type 2 DM, and non-DM. Pearson correlation coefficients also were computed to determine relationships among duration of diabetes or metabolic control with tHcy and lipid profiles in those with type 1 DM, type 2 DM, and both types of diabetes combined.

NHANES III Baseline Data

As a means of comparison, means and standard errors for dietary energy, macronutrient and micro-nutrient intakes, serum lipid profiles, and tHcy from our subjects were compared with values for males and females in the general US population age 16 to 19 years, obtained from the Third National Health and Nutrition Examination Survey (NHANES III).48 Dietary intakes of energy, carbohydrate, protein, total fat and saturated fat, sodium, folate, vitamins 48 B6 and B12 were obtained from Bialostoky et al. Serum values for TC, triglycerides, HDL-cholesterol, and LDL-cholesterol were obtained from Hickman et al49 and that of tHcy was obtained from Must et al.50

Results

The total sample included 117 adolescents. There were 49 males and 68 females (Table 1). Subjects included 53 non-DM, 50 type 1 DM, and 14 type 2 DM adolescents. Ages ranged from 13.0 to 18.9 years (mean = 15.9 ± 1.7 years) for the entire sample. The mean age for the non-DM group was 16.5 ± 1.0 years. The mean ages for those with type 1 versus type 2 DM were 15.2 ± 1.9 years and 16.1 ± 1.9 years, respectively. Duration of disease was longer for those with type 1 versus type 2 DM (6.2 ± 3.6 years vs. 2.8 ± 2.1 years, P = .002). Metabolic control measured by HbA1c was better in youth with type 2 versus type 1 DM (7.7% ± 1.8% vs. 8.8% ± 1.5%, P = .03). All of the youth with type 1 DM were receiving insulin, with 66% using multiple injections and the remainder using insulin pumps. Two of the youth with type 1 DM receiving injections were also taking Glucophage® (metformin). Of the 14 adolescents with type 2 DM, 50% (n = 7) used insulin injections in combination with oral therapies: Glucophage® (n = 4); Actos (n = 2); or Glucotrol® (glipizide) (n = 1). Only one adolescent with type 2 DM was using insulin alone. The remaining 6 adolescents with type 2 DM were taking either Glucophage® (n = 5) or Actos® (pioglitazone).

TABLE 1.

Demographics of Race, Gender, and Body Composition of Subjects

Males
Females
Non-DM Type 1 DM Type 2 DM Non-DM Type 1 DM Type 2 DM
n 18 25 6 35 25 8
White 9 18 20 17
Black 7 5 7 8
Hispanic 1 1
South Asian/Asian 9 15
Age (year) 17.0 ± 0.3a 14.8 ± 0.4b 16.9 ± 0.8a 16.3 ± 0.2 15.5 ± 0.9 15.6 ± 0.6
Height (cm) 178.2 ± 1.4a 168.1 ± 2.0b 178.8 ± 2.4a 162.3 ± 1.3 161.3 ± 1.6 160.7 ± 3.5
Weight (kg) 73.2 ± 2.7a 69.7 ± 3.5a 117.2 ± 12.2b 56.2 ± 1.4a 60.8 ± 1.9a 88.0 ± 78b
BMI (kg/m2) 22.9 ± 0.8a 24.4 ± 1.0a 36.2 ± 2.9b 21.3 ± 0.5a 23.3 ± 0.7a 33.9 ± 2.3b
Open in a new tab

DM indicates diabetes mellitus.

All values are mean ± SE. P values calculated by between-group analysis of variance. Values within a row for each gender with different superscripts are significantly different at P < .05.

Table 2 presents the demographics of family history of heart disease and diabetes for the non-DM, type 1 DM, and type 2 DM groups. The family history for heart disease and DM was separated into 5 discrete categories: no history, 1 parent, 2 parents, aunt/uncle/grandparent, or parents and other family member. Family history data were only available on 45 out of the 53 non-DM subjects and on 12 out of the 14 subjects with type 2 DM. Thirty-two percent of the non-DM group indicated a family history of heart disease, whereas 70% of the type 1 DM and 35% of the type 2 DM group indicated a family history of heart disease. The low percentage of those with type 2 DM reporting a family history of heart disease may be partly related to missing data from 2 participants and the small sample size overall for this group. Forty-two percent of the non-DM group reported a family history of DM. For those with type 1 and type 2 DM, 78% and 71%, respectively, reported a family history of diabetes.

TABLE 2.

Demographics of Family History of Heart Disease and Diabetes Mellitus*

Non- DM Type 1 DM Type 2 DM
No family history of heart disease 28 15 7
1 Parent with heart disease 3 1 1
2 Parents with heart disease 1 1
Aunt/uncle/grandparent with heart disease 6 26 4
Parents and other family member with heart disease 7 7
No family history of diabetes Mellitus 23 11 3
1 Parent with diabetes mellitus 1
2 Parents with diabetes mellitus 1
Aunt/uncle/grandparent with diabetes mellitus 12 34 7
Parents and other family member with diabetes mellitus 9 5 2
Open in a new tab

DM indicates diabetes mellitus.

*

Each subject may have had more than 1 family member with a history of heart disease or diabetes mellitus; some subjects chose not to respond to family disease history.

There was no significant difference in height among the 3 groups of females (Table 1). However, the height of the males with type 1 DM was significantly less than either the non-DM or the type 2 DM males, which can be attributed to the concomitantly younger age of the type 1 DM males. Both type 2 DM males and females had significantly greater body weight than either of their non-DM or type 1 DM counterparts. Accordingly, BMI values of the type 2 DM adolescents for each gender were significantly greater than either that of the non-DM or the type 1 DM adolescents.

Dietary energy, macronutrient and selected micro-nutrient intakes are presented in Table 3. Total energy intakes of the males with type 2 DM were nearly the same as that reported in NHANES III for similar age males. Non-DM and type 1 DM males consumed less energy than that reported in NHANES III or those with type 2 DM. However, the differences were not significant among the males with type 1 DM, type 2 DM, or controls. There were no significant differences among the female groups of our subjects, with non-DM females consuming similar total kilocalories as the age-matched females in the NHANES III report.

TABLE 3.

Dietary Energy, Macronutrient and Selected Micronutrient Intakes

Males
Females
Non-DM Type 1 DM Type 2 DM NHANES Non-DM Type 1 DM Type 2 DM NHANES
Energy (kcal) 2,778 ± 275 2,562 ± 131 3,128 ± 512 3,064 ± 70 1,947 ± 120 1,872 ± 123 1,833 ± 288 1,963 ± 46
Carbohydrate (g) 411 ± 39a 296 ± 17b 352 ± 74a,b 385 ± 11 305 ± 20a 238 ± 18b 217 ± 40b 258 ± 6
Protein (g) 94 ± 9 99 ± 6 122 ± 15 111 ± 3 70 ± 5 67 ± 4 66 ± 11 67 ± 2
Total fat (g) 90 ± 12 115 ± 8 139 ± 22 117 ± 3 54 ± 5a 78 ± 7b 79 ± 12b 76 ± 2
Saturated fat (g) 30 ± 5a 40 ± 2a,b 53 ± 10b 41 ± 1 18 ± 2a 27 ± 2b 26 ± 5a,b 26 ± 1
Sodium (mg) 3,528 ± 358 4,506 ± 278 5,443 ± 543 4,904 ± 138 2,767 ± 234 3,256 ± 287 3,227 ± 513 3,160 ± 91
Folate (μg) 397 ± 49 317 ± 34 447 ± 158 325 ± 15 352 ± 43 240 ± 27 203 ± 25 225 ± 12
Vitamin B6 (mg) 2.0 ± 0.3 1.7 ± 0.2 2.6 ± 0.8 2.4 ± 0.1 1.6 ± 0.2 1.3 ± 0.1 1.2 ± 0.2 1.5 ± 0.1
Vitamin B12 (μg) 6.5 ± 3.2 5.7 ± 0.7 7.3 ± 2.4 7.5 ± 0.5 3.2 ± 0.5 3.4 ± 0.5 3.0 ± 0.3 3.8 ± 0.2
Open in a new tab

NHANES indicates Third National Health and Nutrition Evaluation Survey for ages 16–19 years; DM, diabetes mellitus.

All values are mean ± SE. P values calculated by between-group analysis of variance. Values within a row for each gender with different superscripts are significantly different at P < .05.

NHANES data from Bialostoky et al.48

Carbohydrate consumption of the female non-DM adolescents was significantly greater than female adolescents with either type 1 or type 2 DM. Male non-DM adolescents consumed significantly greater amounts of carbohydrates than did the type 1 DM males. Although the males with type 2 DM had a higher intake of carbohydrates than those with type 1 DM and a lower intake of carbohydrates that non-DM males, the findings were not significant. Total fat consumption by non-DM females was significantly less than that of either type 1 or type 2 DM females; non-DM females also consumed a lesser amount of saturated fat than did females with type 1 DM. Although total fat intake for the males did not differ significantly, male adolescents with type 2 DM consumed the greatest amount for the 3 groups. Male adolescents with type 2 DM had a significantly higher intake of saturated fat than did the non-DM males, whereas there was no significant difference in saturated fat consumption between type 1 and type 2 DM males or between type 1 and non-DM males.

There were no significant differences in plasma TC concentrations among the various groups (Table 4). The plasma triglyceride concentrations for males with type 1 DM were significantly lower than values for the other 2 groups of males. There were no other lipid indices that were different for either sex. Plasma tHcy was significantly lower for both males and females with type 1 DM compared with their non-DM counterparts. However, lower tHcy values between youth with type 1 DM versus type 2 DM were significant only in males and not in females.

TABLE 4.

Serum Concentrations of Lipids, Lipoproteins, and Homocysteine

Males
Females
Non-DM Type 1 DM Type 2 DM NHANES Non-DM Type 1 DM Type 2 DM NHANES
Total cholesterol (mg/dL) 156 ± 6 163 ± 5 176 ± 16 158 ± 2 164 ± 5 174 ± 8 168 ± 12 171 ± 2
Triglycerides (mg/dL) 105 ± 10a 60 ± 7b 120 ± 32a 94 ± 6 82 ± 5 76 ± 13 87 ± 28 96 ± 6
HDL-cholesterol (mg/dL) 48 ± 3 50 ± 2 45 ± 4 46 ± 0.8 54 ± 2 54 ± 3 53 ± 4 52 ± 0.8
LDL-cholesterol (mg/dL) 89 ± 5 101 ± 4 106 ± 9 94 ± 4 93 ± 4 105 ± 6 97 ± 10 103 ± 4
Total homocysteine (μmol/L) 7.3 ± 0.4a 5.1 ± 0.3b 8.1 ± 2.1a 8.7 ± 0.3 6.2 ± 0.3a 4.8 ± 0.2b 5.7 ± 0.2a,b 7.2 ± 0.3
Open in a new tab

NHANES indicates Third National Health and Nutrition Evaluation Survey for ages 16–19 years; DM, diabetes mellitus.

All values are mean ± SE. P values calculated by between-group ANOVA. Values within a row for each gender with different superscripts are significantly different at P < .05.

NHANES data for total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol from Hickman et al.49 NHANES data for total homocysteine from Must et al.50

The intake of the micronutrients of sodium, folate, and vitamins B6 and B12 was not significantly different among the 3 groups for males or females (Table 3). There were no significant relationships among any of the micronutrients of vitamin B6, vitamin B12, or folate with tHcy for those with type 1 DM or type 2 DM. The only significant finding for the non-DM group was a positive correlation between dietary vitamin B12 intake and plasma tHcy concentration (r = 0.40, P = .004), which is counterintuitive and may indicate a limitation of dietary recall.

Regression analyses to determine the effects of age, gender, and BMI on tHcy and lipid profiles for each of the 3 groups, type 1 DM, type 2 DM, and non-DM, revealed several significant findings. Gender had a significant influence on tHcy for the non-DM participants. Healthy male adolescents had higher tHcy than healthy females (beta = −0.30, R2 = 0.09, adjusted R2 = 0.08, P = .03). Age was the only significant predictor for TC, occurring exclusively in those with type 1 DM (beta = 0.40, R2 = 0.16, adjusted R2 = 0.14, P = .02). There were no significant predictors for HDL-C in any of the groups. Additional influences of BMI and age on lipoproteins are indicated in Table 5.

TABLE 5.

Predictors of Lipoproteins in Adolescents with Diabetes and Healthy Controls

Group Predictor Lipoprotein Beta R2 Adjusted R2 P
Non-DM BMI Triglycerides 0.33 0.11 0.09 .02
BMI LDL-C 0.30 0.09 0.07 .03
Type 1 DM Age Triglycerides 0.40 0.16 0.15 .004
Age LDL-C 0.33 0.11 0.09 .02
Type 2 DM Age LDL-C 0.57 0.32 0.27 .03
Open in a new tab

BMI indicates body mass index; DM, diabetes mellitus; LDL-C, low-density lipoprotein cholesterol.

Duration of diabetes did not significantly correlate with TC, triglycerides, HDL-C, LDL-C, or tHcy in either those with type 1 DM or type 2 DM. Although HbA1c was not associated with TC, triglycerides, HDL-C, or LDL-C in adolescents with type 2 DM, higher levels of HbA1c were related to TC (r = 0.30, P = .03) and triglycerides (r = 0.28, P = 0.05), but not HDL or LDL in those with type 1 DM. There was no relationship between tHcy and HbA1c in youth with type 1 or type 2 DM. The only significant associations among tHcy and lipids or lipoproteins were in the group with type 2 DM: TC (r = 0.65, P = 0.01) and triglycerides (r = 0.68, P = 0.008).

Discussion and Conclusions

This study provides seminal information on comparisons of dietary energy intake, macronutrients, select micronutrients, lipids, and tHcy levels in youth with type 1 DM, type 2 DM, and non-DM controls. Although the sample of youth with type 2 DM was small, the findings are particularly relevant given that no other studies included data on this group of adolescents. Additional limitations of merging 2 separate datasets for making comparisons among the three groups must be acknowledged in interpreting findings of the study that relate to the controls. Race and weight-matched controls were not available for making comparisons between controls and youth with type 2 DM. Although both male and female controls were included, African-American or His-panic youth were not represented. Significant differences in BMI for both sexes existed between youth with type 2 DM and each of the other 2 groups. Despite the differences in BMI among these groups, BMI was not a significant predictor of tHcy or lipids except in the non-DM group. Triglycerides and LDL-C were both found to be higher with increasing BMI in these controls.

Family history information of the youth who had either type 1 or type 2 DM supported trends in the incidence of diabetes and heart disease in other family members. Overall dietary intake patterns were very similar to NHANES III data for all groups. Although youth with DM consumed fewer carbohydrates than controls, total and saturated fat intake was higher than controls. Males with type 2 DM, in particular, had the highest saturated fat intake. Clearly, the dietary patterns of controls reflected the tendency toward eating more rice and legumes, characteristic of Asian cultures. However, lipid profiles did not differ among the 3 groups and were comparable to gender-specific NHANES III data.49 The lower triglycerides in males with type 1 DM may have been related to the slightly younger ages of the teens in this group.49 Metabolic control was related to TC and triglycerides in those with type 1 DM, confirming the importance of promoting better metabolic control for lipid management in these youth.10,37,38

Adolescents with type 1 DM had the lowest tHcy values, reflective of the limited extant research with this population.16,17 The lack of association of metabolic control with tHcy for either those with type 1 or type 2 DM was similar to research by Pavia et al.15 However, unlike the study by Pavia et al with youth who had type 1 DM, those with type 2 DM in our investigation had strong linkages between tHcy and TC or triglycerides. Although regression analyses revealed that gender variation predicted 8% of the variance in tHcy values for non-DM subjects only, this finding is consistent with the significant sexual dimorphism of tHcy occurring during puberty reported in NHANES III.50 The lack of associations among dietary intake of folate and vitamins B6 and B12 may have been related to the need to use a more direct measure of these micronutrients through plasma concentrations.

Future research should continue to explore the efficacy of tHcy and lipids as predictors of CV risks for youth with type 1 and type 2 DM. There remains a dearth of information on the CV risks in youth with diabetes. Longitudinal tracking of lipid levels and the influence of dietary practices on lipid management is especially needed to ensure that these youth maintain the optimal levels of LDL-C <100 mg/dL, HDL-C >35 mg/dL, and triglycerides <150 mg/dL recommended by both the American Heart Association and the American Diabetes Association.10,51 Given our understanding that both lipids and tHcy levels during childhood reflect familiar tendencies for CV disease, continued study addressing the influences of gender, race, and cultural preferences in diet is critical to tailoring interventions for adolescents with diabetes predisposed to the potential ravages of hypertension, premature myocardial infarction, or stroke.

Acknowledgments

Partially funded by a grant from the National Institute of Nursing Research R01 NR07719-04 and supported by UIC GCRC NIH M01-RR-13987.

Contributor Information

Melissa Spezia Faulkner, College of Nursing, University of Illinois at Chicago, Chicago, Ill.

Wei-Hsun Chao, Department of Human Nutrition, University of Illinois at Chicago, Chicago, Ill.

Savitri K. Kamath, Department of Human Nutrition, University of Illinois at Chicago, Chicago, Ill.

Laurie Quinn, College of Nursing, University of Illinois at Chicago, Chicago, Ill.

Cynthia Fritschi, College of Nursing, University of Illinois at Chicago, Chicago, Ill.

Jack A. Maggiore, Department of Pathology, University of Illinois at Chicago, Chicago, Ill.

Robert H. Williams, Department of Pathology, University of Illinois at Chicago, Chicago, Ill.

Robert D. Reynolds, Department of Human Nutrition, University of Illinois at Chicago, Chicago, Ill.

References

  • 1.American Diabetes Association. Diabetes 1996: Vital Statistics. Alexandria, VA: American Diabetes Association; 1996. [Google Scholar]
  • 2.Miller J, Silverstein J. Risk factors for cardiovascular disease in children with diabetes. Pract Diabetol. 2004;23(2):13–18. [Google Scholar]
  • 3.Post GB, Kemper HC, Twisk J, van Mechelen W. The association between dietary patterns and cardio vascular disease risk indicators in healthy youngsters: results covering fifteen years of longitudinal development. Eur J Clin Nutr. 1997;51:387–393. doi: 10.1038/sj.ejcn.1600419. [DOI] [PubMed] [Google Scholar]
  • 4.Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999;354:407–413. doi: 10.1016/S0140-6736(98)11058-9. [DOI] [PubMed] [Google Scholar]
  • 5.Senaratne MP, Griffiths J, Nagendran J. Elevation of plasma homocysteine levels associated with acute myocardial infarction. Clin Invest Med. 2000;23:220–226. [PubMed] [Google Scholar]
  • 6.Mangoni AA, Jackson SH. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med. 2002;112:556–565. doi: 10.1016/s0002-9343(02)01021-5. [DOI] [PubMed] [Google Scholar]
  • 7.Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for health-care professionals from the Nutrition Committee American Heart Association. Circulation. 1999;99:178–182. doi: 10.1161/01.cir.99.1.178. [DOI] [PubMed] [Google Scholar]
  • 8.Rosenberg IH. Is it time to standardize and to measure blood homocysteine levels in patients with heart disease? Am J Med. 2002;112:582–583. doi: 10.1016/s0002-9343(02)01107-5. [DOI] [PubMed] [Google Scholar]
  • 9.Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31–62. doi: 10.1146/annurev.med.49.1.31. [DOI] [PubMed] [Google Scholar]
  • 10.American Diabetes A. Management of dyslipidemia in children and adolescents with diabetes. Diabetes Care. 2003;26:2194–2197. doi: 10.2337/diacare.26.7.2194. [DOI] [PubMed] [Google Scholar]
  • 11.Misra A. Risk factors for atherosclerosis in young individuals. J Cardiovasc Risk. 2000;7:215–229. doi: 10.1177/204748730000700309. [DOI] [PubMed] [Google Scholar]
  • 12.Greenlund KJ, Srinivasan SR, Xu JH, et al. Plasma homocysteine distribution and its association with parental history of coronary artery disease in black and white children: the Bogalusa Heart Study. Circulation. 1999;99:2144–2149. doi: 10.1161/01.cir.99.16.2144. [DOI] [PubMed] [Google Scholar]
  • 13.Glowinska B, Urban M, Koput A. Cardiovascular risk factors in children with obesity, hypertension and diabetes: lipoprotein(a) levels and body mass index correlate with family history of cardiovascular disease. Eur J Pediatr. 2002;161:511–518. doi: 10.1007/s00431-002-1040-7. [DOI] [PubMed] [Google Scholar]
  • 14.Glowinska B, Urban M, Peczynska J, Florys B, Szydlowska E. Elevated concentrations of homocysteine in children and adolescents with arterial hypertension accompanying Type 1 diabetes. Med Sci Monit. 2001;7:1242–1249. [PubMed] [Google Scholar]
  • 15.Pavia C, Ferrer I, Valls C, Artuch R, Colome C, Vilaseca MA. Total homocysteine in patients with type 1 diabetes. Diabetes Care. 2000;23:84–87. doi: 10.2337/diacare.23.1.84. [DOI] [PubMed] [Google Scholar]
  • 16.Salardi S, Cacciari E, Sassi S, et al. Homocysteinemia, serum folate and vitamin B12 in very young patients with diabetes mellitus type 1. J Pediatr Endocrinol Metab. 2000;13:1621–1627. doi: 10.1515/jpem.2000.13.9.1621. [DOI] [PubMed] [Google Scholar]
  • 17.Wiltshire E, Thomas DW, Baghurst P, Couper J. Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes. J Pediatr. 2001;138:888–893. doi: 10.1067/mpd.2001.113708. [DOI] [PubMed] [Google Scholar]
  • 18.Chiarelli F, Pomilio M, Mohn A, et al. Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy. J Pediatr. 2000;137:386–392. doi: 10.1067/mpd.2000.108103. [DOI] [PubMed] [Google Scholar]
  • 19.Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;268:877–881. [PubMed] [Google Scholar]
  • 20.Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE. Serum total homocysteine and coronary heart disease. Int J Epidemiol. 1995;24:704–709. doi: 10.1093/ije/24.4.704. [DOI] [PubMed] [Google Scholar]
  • 21.Taylor LM, Jr, DeFrang RD, Harris EJ, Jr, Porter JM. The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. J Vasc Surg. 1991;13:128–136. doi: 10.1067/mva.1991.24913. [DOI] [PubMed] [Google Scholar]
  • 22.Christen WG, Ajani UA, Glynn RJ, Hennekens CH. Blood levels of homocysteine and increased risks of cardiovascular disease: causal or casual? Arch Intern Med. 2000;160:422–434. doi: 10.1001/archinte.160.4.422. [DOI] [PubMed] [Google Scholar]
  • 23.Hultberg B, Agardh CD, Agardh E, Lovestam-Adrian M. Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus. A five-year follow-up study. Scand J Clin Lab Invest. 1997;57:595–600. doi: 10.3109/00365519709055282. [DOI] [PubMed] [Google Scholar]
  • 24.Hofmann MA, Kohl B, Zumbachjn MS, et al. Hyperhomocyst(e)inemia and endothelial dysfunction in IDDM. Diabetes Care. 1998;21:841–848. doi: 10.2337/diacare.21.5.841. [republished from Diabetes Care. 1997 Dec;20(12):1880–6; PMID: 9405911] [DOI] [PubMed] [Google Scholar]
  • 25.Matteucci E, Rossi L, Mariani S, et al. Blood levels of total homocysteine in patients with type 1 diabetes (with no complications, diabetic nephropathy and/or retinopathy) and in their non-diabetic relatives. Nutr Metab Cardiovasc Dis. 2002;12:184–189. [PubMed] [Google Scholar]
  • 26.Cronin CC, McPartlin JM, Barry DG, Ferriss JB, Scott JM, Weir DG. Plasma homocysteine concentrations in patients with type 1 diabetes. Diabetes Care. 1998;21:1843–1847. doi: 10.2337/diacare.21.11.1843. [DOI] [PubMed] [Google Scholar]
  • 27.Robillon JF, Canivet B, Candito M, et al. Type 1 diabetes mellitus and homocyst(e)ine. Diabete Metab. 1994;20:494–496. [PubMed] [Google Scholar]
  • 28.Wollesen F, Brattstrom L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int. 1999;55:1028–1035. doi: 10.1046/j.1523-1755.1999.0550031028.x. [DOI] [PubMed] [Google Scholar]
  • 29.Neugebauer S, Tarnow L, Stehouwer C, et al. Total plasma homocysteine is associated with hypertension in Type I diabetic patients. Diabetologia. 2002;45:1315–1324. doi: 10.1007/s00125-002-0908-4. [DOI] [PubMed] [Google Scholar]
  • 30.Hoogeveen EK, Kostense PJ, Beks PJ, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998;18:133–138. doi: 10.1161/01.atv.18.1.133. [DOI] [PubMed] [Google Scholar]
  • 31.Becker A, Kostense PJ, Bos G, et al. Hyperhomocysteiaemia is associated with coronary events in type 2 diabetes. J Intern Med. 2003;253:293–300. doi: 10.1046/j.1365-2796.2003.01113.x. [DOI] [PubMed] [Google Scholar]
  • 32.Story M, Neumark-Sztainer D, French S. Individual and environmental influences on adolescent eating behaviors. J Am Diet Assoc. 2002;102(3 suppl):S40–S51. doi: 10.1016/s0002-8223(02)90421-9. [DOI] [PubMed] [Google Scholar]
  • 33.Bar-Or O, Foreyt J, Bouchard C, et al. Physical activity, genetic, and nutritional considerations in childhood weight management. Med Sci Sports Exerc. 1998;30:2–10. doi: 10.1097/00005768-199801000-00002. [DOI] [PubMed] [Google Scholar]
  • 34.Berenson GS, Srinivasan SR, Nicklas TA. Atherosclerosis: a nutritional disease of childhood. Am J Cardiol. 1998;82(10B):22T–29T. doi: 10.1016/s0002-9149(98)00719-x. [DOI] [PubMed] [Google Scholar]
  • 35.American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care. 2000;23(suppl 1):S57–S60. [PubMed] [Google Scholar]
  • 36.Orchard TJ, Forrest KY, Kuller LH, Becker DJ. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care. 2001;24:1053–1059. doi: 10.2337/diacare.24.6.1053. [DOI] [PubMed] [Google Scholar]
  • 37.Lipman TH, Hayman LL, Fabian CV, et al. Risk factors for cardiovascular disease in children with Type I diabetes. Nurs Res. 2000;49:160–166. doi: 10.1097/00006199-200005000-00008. [DOI] [PubMed] [Google Scholar]
  • 38.Wiltshire EJ, Hirte C, Couper JJ. Dietary fats do not contribute to hyperlipidemia in children and adolescents with type 1 diabetes. Diabetes Care. 2003;26:1356–1361. doi: 10.2337/diacare.26.5.1356. [DOI] [PubMed] [Google Scholar]
  • 39.Steinberger J, Daniels SR. Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism) Circulation. 2003;107:1448–1453. doi: 10.1161/01.cir.0000060923.07573.f2. [DOI] [PubMed] [Google Scholar]
  • 40.Steinberger J, Moran A, Hong CP, Jacobs DR, Jr, Sinaiko AR. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr. 2001;138:469–473. doi: 10.1067/mpd.2001.112658. [DOI] [PubMed] [Google Scholar]
  • 41.Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics. 1999;103(6 Pt 1):1175–1182. doi: 10.1542/peds.103.6.1175. [DOI] [PubMed] [Google Scholar]
  • 42.McGill HC, Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol. 1995;15:431–440. doi: 10.1161/01.atv.15.4.431. [DOI] [PubMed] [Google Scholar]
  • 43.Orsi AJ, Grey M, Mahon MM, Moriarty HJ, Shephard MP, Carroll RM. Conceptual and technical considerations when combining large data sets. West J Nurs Res. 1999;21:130–142. doi: 10.1177/01939459922043785. [DOI] [PubMed] [Google Scholar]
  • 44.Williams RH, Maggiore JA, Reynolds RD, Helgason CM. Novel approach for the determination of the redox status of homocysteine and other aminothiols in plasma from healthy subjects and patients with ischemic stroke. Clin Chem. 2001;47:1031–1039. [PubMed] [Google Scholar]
  • 45.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502. [PubMed] [Google Scholar]
  • 46.Baer MT, Harris AB. Pediatric nutrition assessment: identifying children at risk. J Am Diet Assoc. 1997;97(10 suppl 2):S107–S115. doi: 10.1016/s0002-8223(97)00741-4. [DOI] [PubMed] [Google Scholar]
  • 47.Ambler C, Eliakim A, Brasel JA, Lee WN, Burke G, Cooper DM. Fitness and the effect of exercise training on the dietary intake of healthy adolescents. Int J Obes Relat Metab Disord. 1998;22:354–362. doi: 10.1038/sj.ijo.0800595. [DOI] [PubMed] [Google Scholar]
  • 48.Bialostoky K, Wright JD, Kennedy-Stephenson J, McDowell M, Johnson CL. Dietary intake of Macro-nutrients, micronutrients, and other dietary constituents: United States, 1984–94: Data from the National Health Examination Survey, the National Health and Nutrition Examination Surveys, and the Hispanic Health and Nutrition Examination Survey. Vol. 245. Hyattsville, Md: Department of Health and Human Service, Centers for Disease Control and Prevention; National Center for Health Statistics; 2002. [PubMed] [Google Scholar]
  • 49.Hickman TB, Briefel RR, Carroll MD, et al. Distributions and trends of serum lipid levels among United States children and adolescents ages 4–19 years: data from the Third National Health and Nutrition Examination Survey. Prevent Med. 1998;27:879–890. doi: 10.1006/pmed.1998.0376. [DOI] [PubMed] [Google Scholar]
  • 50.Must A, Jacques PF, Rogers G, Rosenberg IH, Selhub J. Serum total homocysteine concentrations in children and adolescents: results from the third National Health and Nutrition Examination Survey (NHANES III) J Nutr. 2003;133:2643–2649. doi: 10.1093/jn/133.8.2643. [DOI] [PubMed] [Google Scholar]
  • 51.Kavey RE, Daniels SR, Lauer RM, et al. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation. 2003;107:1562–1566. doi: 10.1161/01.cir.0000061521.15730.6e. [DOI] [PubMed] [Google Scholar]

RESOURCES