Effect of Dietary Treatment on Growth and plasma IGF-1 and IGFBP-3 Levels of Children with Familial Hypercholesterolemia

doi:10.21203/rs.3.rs-5184991/v1

Download PDF

Article

Effect of Dietary Treatment on Growth and plasma IGF-1 and IGFBP-3 Levels of Children with Familial Hypercholesterolemia

https://doi.org/10.21203/rs.3.rs-5184991/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background/Objective: This study aims to determine the effects of dietary treatment on growth and the biochemical markers of growth in children with primary familial hypercholesterolemia.

Subjects/Methods: The study was conducted with 30 children aged 5-10 years diagnosed with familial hypercholesterolemia at Cukurova University Hospital. Sociodemographic characteristics and dietary habits of patients were queried, and anthropometric measurements were taken. Specific dietary treatments were arranged, detailed dietary education was provided, and monthly follow-ups were conducted. At the beginning and in the end of the study, 3-days (24-hour) food consumption records were collected, and biochemical parameters were recorded. The International Physical Activity Questionnaire-Short Form (IPAQ-Short Form) was used to assess the general physical activity levels of the patients.

Results: It was found that 53.3% of the patients were female, and 46.7% were male. The average age of patients was 92.93±19.89 months. A moderate negative relationship was observed between the 6^thmonth IGFBP-3 Z-scores and BMI Z-scores (r=-0.460). A moderate negative relationship was found between the initial IGF-1 Z-scores and the percentage of consumed dietary carbohydrates (r=-0.417). When the change in protein intake was examined, a moderate positive relationship was observed between Delta (∆) total protein and Delta (∆) animal protein, Delta (∆) plant protein, and Delta (∆) IGF-1 values (r=0.693; r=0.392; r=0.356, respectively).

Conclusion: To ensure adequate growth in children diagnosed with primary familial hypercholesterolemia, the amount and the content of protein together with the percentage of daily carbohydrate consumption should be considered in dietary treatment planning. Compliance with the diet should be closely monitored through food consumption records, and adherence to physical activity recommendations should be encouraged.

Health sciences/Health care/Nutrition

Health sciences/Health care/Paediatrics

Primary familial hypercholesterolemia

Linear growth

Diet

IGFBP-3

IGF-1

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism caused by pathogenic variants of the low-density lipoprotein receptor (LDLR) and related genes, resulting in elevated low-density lipoprotein cholesterol (LDL-C) levels. As lifelong exposure to high LDL-C levels increases the risk of atherosclerosis, early diagnosis and intervention is crucial [1]. The global prevalence of FH is 1 in 500, however a higher prevalence is reported in United States and some countries of Europe [2]. It is estimated that out of 35 million familial hypercholesterolemia patients, 20–25% are children and adolescents [3].

Lipid-lowering drugs are recommended in the treatment of children and adolescents with familial hypercholesterolemia [3, 4]. In addition to medical approaches, persistent lifestyle changes such as a cholesterol-poor diet, regular physical activity, avoidance of alcohol and smoking, and regular sleep pattern is recommended [5, 6]. The goal of the nutritional therapy is to maintain sustainable and healthy eating habits, ensure adequate energy intake to support linear growth, and avoid excessive restrictions [7]. Total cholesterol (TC) and LDL-C levels can partially be modulated by dietary intake of fatty acids and cholesterol. In nutritional therapy of familial hypercholesterolemia dietary cholesterol intake should be less than 200 mg per day, saturated fats should be less than 7%, and maximum 20–30% of total energy intake comes from fats. Additionally, consumption of fiber, whole grains, low-fat dairy products, legumes, fish, lean meats, fruits, and vegetables be increased [8].

Insulin-like growth factor 1 (IGF-1) is the primary regulator of postnatal somatic growth and mediates the effects of growth hormone (GH) [9, 10]. Moreover, IGF-1 has metabolic effects of increasing glucose uptake and promoting protein synthesis [11]. Insulin-like growth factor binding protein-3 (IGFBP-3) is the primary protein that binds IGF in the serum, acting as a reservoir for circulating IGF. Approximately 99% of IGF-1 in the bloodstream is bound to IGFBP-3 [12].

Age, gender, genetic factors, nutritional status, and other variables are known to affect serum IGF-1 and IGFBP-3 concentrations [13]. Specifically, dietary energy and protein intake can increase circulating IGF-I levels [14]. Animal-derived proteins, known as high-quality protein sources, have positive effect on growth [15]. This well-known statement brings a challenge about the linear growth of children who should go on an obligatory animal protein restricted diet, however the data about the subject was limited. This study was performed to determine the effects of dietary therapy on linear growth and biochemical markers of growth in children and adolescents diagnosed with primary familial hypercholesterolemia.

This cross-sectional descriptive study conducted between February 2022-May 2023, involved 30 children aged 5–10 years diagnosed with genetically proven FH, and monitored at Pediatric Metabolism Department of Çukurova University over a 24-week period as their yearly growth velocity is same. The ethical approval (10.01.2022, 2022/006) obtained from Hasan Kalyoncu University.

Body weight was measured using a SECA 769 digital scale with a weight rod with 0.1 kg precision, and height was measured using the same device according to the Frankfort plane [16] by the same physician. Body mass index (BMI)-Z scores were calculated using the World Health Organization (WHO) Anthro Plus (5–19 years) software [17].

Three-day food consumption records were provided in the beginning and in the 6th months of study and recorded in the Food Consumption Record Form. Using the Nutrition Information System (BeBIS 9.0), the average energy and macronutrient intakes were calculated. The meeting energy requirements according to age and gender was determined by using Turkey Nutrition Guide (TUBER)-2022 [18]. In the beginning and in the 6th months of the study, International Physical Activity Questionnaire-Short Form [19] was administered.

IGF-1 and IGFBP-3 levels were measured using the chemiluminescence immunoassay method with the Maglumi 2000 Plus autoanalyzer in the Central Laboratory of Cukurova University Hospital at the beginning and the 6th months of the study. IGF-1 SDS and IGFBP-3 SDS were calculated according to the age and gender of the patients using the website https://www.ceddcozum.com/ [20].

Specific diet treatments and detailed diet education was provided. In stage 1 diet treatment, ≤ 30% of daily total energy comes from fats, saturated fat intake was limited to < 10% of total energy, and dietary cholesterol was ≤ 300 mg. Different from the first step, in stage 2 diet treatment dietary cholesterol was ≤ 200 mg. Diet education was repeated monthly by clinical visits or phone consultations.

Statistical analysis

For statistical analysis Statistical Package for the Social Sciences (SPSS) version 27.0 was used. Statistical significance was considered at the level of p < 0.05. Shapiro-Wilk test was performed for the parameters showed a normal distribution and the Mann Whitney U test was used for binary group analyses. A paired sample t-test was conducted in comparing the variability between the basal and 6th months values.

Thirty patients, 53.3% (n = 16) female, and 46.7% (n = 14) male diagnosed with FH and followed-up in Department of Pediatric Metabolism and Nutrition, Cukurova University Hospital between February 2022 and May 2023 were included into the study. The current mean age of the patients was 92.93 ± 19.89 months (min-max:60–120 month). The age of FH diagnosis was 68.86 ± 31.09 months (min-max:6-111 month). FH diagnosis was based on fasting lipid profile and genetic analysis. Homozygous mutations detected in 43,3% (n = 13) and heterozygous mutations detected in 56,7% (n = 17) of patients. Family history was significant for hypercholesterolemia in 90% (n = 27) patients.

Sociodemographic characteristics and dietary habits of patients were queried and anthropometric measurements were taken. Specific dietary treatments were arranged, detailed dietary education was provided, and monthly follow-ups were conducted. At the beginning and the end of the study, 3-days (24-hour) food consumption records were collected. The International Physical Activity Questionnaire-Short Form (IPAQ-Short Form) was used to assess the general physical activity levels of the patients. Biochemical parameters were recorded by the researcher from the hospital system at the 0th and 6th months of the study.

The patients had no chronic health problems other than FH. Physical examination revealed only xanthomas that were observed in 33,3% (n = 10) of FH patients.

First level diet was initiated in 43,3% (≤ 300 mg cholesterol) and second level diet was initiated 56,7% (≤ 200 mg cholesterol) of FH patients. Three-day food consumption records and fasting lipid profile was provided in the beginning, 3th and in the 6th months of study. When the biochemical findings of the cases were examined, it was found that the LDL-C and TC levels at the 6th month were significantly lower than at the basal visit (p < 0.05) (Table 1).

Table 1

Lipid Profile of Patients with Primary Familial Hypercholesterolemia (n = 30)
Parameters	Reference Ranges	Initial	6th Month	p†
Total Cholesterol (mg/dL)	< 170	470.1 ± 259.4	389.8 ± 225.2	< 0.001**
HDL-C (mg/dL)	< 40	71.9 ± 30.6	63.3 ± 24.8	0.124
LDL-C (mg/dL)	< 110	374.8 ± 232.8	322.0 ± 201.0	0.002*
Triglycerides (mg/dL)	< 75	88.3 ± 57.6	85.2 ± 42.8	0.705
Mean: Mean, SD: Standard deviation. p < 0.05 *p < 0.01 †: Wilcoxon-signed rank

Antropometric evaluation was performed in the beginning and 6th months of study. The changes in weight and height of the cases were found to be statistically significant (p < 0.01). Weight and height increase at the basal visit and at the 6th month were found to be statistically significant in both genders (p < 0.01) (Table 2).

Table 2

Anthropometric Data of Patients
Parameter	Basal (Mean ± SD)	6th month (Mean ± SD)	p
Total (n: 30)
Weight (kg)	27.7 ± 9.1	29.4 ± 9.9	< 0.001**
Weight Z-Score	0.10 ± 1.3	0.11 ± 1.3	0.922
Height (cm)	126.4 ± 12.5	129.6 ± 12.8	< 0.001**
Height Z-Score	-0.13 ± 1.1	-0.001 ± 1.01	0.119
BMI (kg/m²)	16.8 ± 2.8	16.9 ± 2.9	0.479
BMI Z-Score	0.23 ± 1.4	0.19 ± 1.4	0.710
Male (n = 14)
Weight (kg)	25.6 ± 7.6	27.4 ± 8.5	< 0.001**
Weight Z-Score	-0.20 ± 1.3	-0.13 ± 1.3	0.506
Height (cm)	125.8 ± 12.1	128.8 ± 13.1	< 0.001**
Height Z-Score	-0.09 ± 1.0	-0.005 ± 1.0	0.454
BMI (kg/m²)	15.8 ± 2.5	16.2 ± 2.4	0.167
BMI Z-Score	-0.25 ± 1.6	-0.15 ± 1.4	0.606
Female (n = 16)
Weight (kg)	29.5 ± 10.1	31.1 ± 10.9	0.002*
Weight Z-Score	0.38 ± 1.3	0.33 ± 1.4	0.644
Height (cm)	126.9 ± 13.1	130.4 ± 12.9	< 0.001**
Height Z-Score	-0.16 ± 1.2	0.001 ± 1.1	0.168
BMI (kg/m²)	17.7 ± 2.8	17.7 ± 3.2	0.763
BMI Z-Score	0.65 ± 1.0	0.48 ± 1.3	0.245
BMI: Body Mass Index; Mean: Mean, SD: Standard deviation p < 0.05 *p < 0.01 p: Paired Sample t-test

A moderate negative relationship was found between the 6th month IGFBP-3 Z-Scores and BMI Z-Scores (r=-0.460). A moderate negative relationship was found between the basal and 6th month IGFBP-3 levels and weight Z-scores and BMI Z-scores of female cases (r=-0.639; r=-0.678, respectively) (Table 3).

Table 3

IGF-1 and IGFBP-3 Levels and Anthropometric Data of Patients
Parameters	IGF-1 Z-score		IGFBP-3 Z-score
	Basal	6th month	Basal	6th month
	r	p	r	p
Total (n: 30)
Weight Z-Score	-0.214	0.256	-0.177	0.349
Height Z-Score	-0.281	0.132	-0.055	0.771
BMI Z-Score	-0.249	0.184	-0.175	0.356
Male (n = 14)
Weight Z-Score	-0.161	0.583	-0.066	0.822
Height Z-Score	-0.409	0.146	-0.055	0.852
BMI Z-Score	-0.055	0.852	0.084	0.776
Female (n = 16)
Weight Z-Score	-0.215	0.424	-0.185	0.494
Height Z-Score	-0.252	0.347	-0.021	0.939
BMI Z-Score	-0.285	0.284	-0.317	0.231
* p < 0.05 **p < 0.01 r: Spearman’s rho correlation

When the correlations between the basal and 6th month energy and macronutrient intakes and the IGF-1 and IGFBP-3 levels of the cases were evaluated, a moderate negative relationship was found between the initial IGF-1 Z-Score and the percentage of carbohydrates in diet (r=-0.417) (Table 4).

Table 4

IGF-1 and IGFBP-3 Z-Scores and Energy and Macronutrient Intakes of Patients
Parameters	IGF-1 Z-Score		IGFBP-3 Z-Score
	Basal	6th month	Basal	6th month
	r	p	r	p
Energy (kcal)	-0.138	0.467	-0.096	0.615
Energy %	0.042	0.824	-0.114	0.550
Protein (g)	0.114	0.548	0.120	0.529
Protein %	0.195	0.301	0.289	0.122
Carbohydrate (g)	-0.300	0.108	-0.259	0.166
Carbohydrate %	-0.417*	0.022	-0.307	0.099
Fat (g)	0.146	0.442	0.164	0.386
Fat %	0.280	0.134	0.220	0.243
%: Percentage of meeting the recommended intake level according to TUBER 2022 p < 0.05, *p < 0.01, Spearman’s rho correlation

When the protein intakes of the cases at the basal and the 6th month were evaluated, it was found that the changes in total protein intake (% energy), plant protein intake (g/kg), and plant protein intake (% energy) were significant (p < 0.05) (Table 5).

Table 5

Protein Intake of Patients
Parameters	Basal Mean ± SD	6th month Mean ± SD	p
Total protein (g/kg)	1.96 ± 0.58	2.16 ± 0.76	0.084
Total protein (% energy)	13.56 ± 2.48	15.63 ± 3.13	0.015*
Animal protein (g/kg)	1.00 ± 0.45	1.07 ± 0.42	0.596
Animal protein (% energy)	7.15 ± 2.78	8.10 ± 2.89	0.133
Animal protein (%)	51.35 ± 15.51	50.25 ± 11.29	0.245
Plant protein (g/kg)	0.95 ± 0.43	1.08 ± 0.47	0.019*
Plant protein (% energy)	8.10 ± 2.89	7.53 ± 2.11	0.015*
Plant protein (%)	48.64 ± 15.51	49.74 ± 11.29	0.246
Mean: Mean, SD: Standard deviation p < 0.05 Paired sample t-test

Table 6

The Relationship Between the Changes in Protein Intake and Related Parameters
	Delta (∆) Total Protein
	r	p
Delta (∆) Animal protein	0.693**	< 0.001
Delta (∆) Plant protein	0.392*	0.032
Delta (∆) IGF-1	0.356*	0.044
Delta (∆) IGF-1 Z-score	0.245	0.192
Delta (∆) IGFBP-3	0.126	0.508
Delta (∆) IGFBP-3 Z-score	-0.208	0.271
Delta (∆) Height Z-score	-0.300	0.107
Delta (∆) Weight Z-score	-0.126	0.506
Delta (∆) BMI Z-score	0.056	0.770
Delta (∆): Change between 6th month value and 0th month value p < 0.05 *p < 0.01 Spearman’s rho correlation

When the changes in protein intake of the cases were examined, a moderate positive correlation was observed between Delta (∆) total protein and Delta (∆) animal protein, Delta (∆) plant protein, and Delta (∆) IGF-1 values (r = 0.693; r = 0.392; r = 0.356, respectively) (Table 5).

A moderate negative correlation was found between the basal IPAQ scores and baseline HDL-C levels of the cases (r=-0.387). A moderate negative correlation was found between the 6th month IPAQ scores and LDL-C and TC levels (r=-0.539; r=-0.588, respectively) (Supplementary Table 1).

A moderate negative correlation was observed between the baseline LDL-C levels and total fat and monounsaturated fatty acid intake (r=-0.495; r = 0.394). At the 6th month, a moderate negative correlation was found between LDL-C levels and total fat intake; a moderate positive correlation was found between LDL-C levels and saturated fatty acid and cholesterol intake (r = 0.513; r = 0.463, respectively) (Supplementary Table 2).

The National Institute of Health and Clinical Excellence (NICE) in the UK recommends that in dietary therapy, ≤ 20–30% of energy should come from fats, ≤ 10% from saturated fatty acids (SFA), ≤ 10% from polyunsaturated fatty acids, and cholesterol intake should be ≤ 300 mg/day [21]. It is known that with the increase in the consumption of processed foods in Western societies, the amount of dietary SFA intake has dramatically increased [22]. Each 1% increase in energy from SFAs is associated with an average increase of 0.8 to 1.6 mg/dL of plasma LDL-C levels [23, 24]. In our study, a significant decrease in LDL-C levels was observed after 6 months of follow-up. There was no significant increase or decrease in dietary SFA intake. The reason for the negative correlation between total fat intake and LDL-C was thought to be due to the increase in unsaturated fatty acid intake. A moderate positive correlation was found between 6th month SFA intake and LDL-C (r = 0.463, p = 0.04). It was thought that the increase in saturated fat intake might be due to the increased consumption of fast and packaged foods during the follow-up period of some cases coinciding with the earthquake period.

Dietary therapy and physical activity are considered fundamental components of managing CVD risk in individuals with FH. A daily 25–30-minute walk is associated with a reduction in serum triglyceride levels and an increase in serum HDL-C levels by 3.1-6 mg/dL. Physical activity is thought to have a slight effect on reducing LDL-C levels [25, 26]. Most of the cases included in our study were found to be minimally active. A study showed a positive relationship between increased physical activity and HDL-C, while no statistically significant relationship was observed with LDL-C and TC levels [27]. In our study, similar to the literature, a moderate negative relationship was found between IPAQ 6th month scores and LDL-C and TC levels. As the activity levels of the cases increased, LDL-C and TC levels decreased.

Different from the adults’ studies foreseeing to reduce the cardiovascular risk factors in FH, gaining ideal height and weight like healthy pairs is another essential part of dietary treatment planning of FH children. Various studies in the literature have shown conflicting results about the linear growth in children and adolescents with FH. Growth-related problems put forth in FH patients both with good compliance and insufficient adherence to dietary treatment [28, 29]. In one study, anthropometric data and growth-related biochemical parameters of 663, 8–10 years aged FH children who followed-up with a low-fat dietary therapy were evaluated. It was shown that dietary therapy was safe and did not affect growth [30]. In a different study, when anthropometric data of 261, 4–10 years aged FH children going with a low-fat dietary treatment were compared with healthy children and no significant difference in linear growth was observed [31].

In our study, significant increases were found in both weight and height of the patients at the end of 6-month follow-up (p < 0.05). Also, a significant decrease in BMI Z-Scores indicated us that the ratio of increase in height and weight was ideal. The significant portion of the follow-up period coincided with the physically more active summer months may be a positively contributing factor to the relatively lower weight gain when compared with the increase in height.

Serum IGF-I levels are strongly associated with height Z-Scores. It is known that in cases with short stature, IGF-1 levels are below the reference range[32, 33]. A study involving 1546 children aged 6–23 months found that height-for-age Z-Scores and weight-for-height Z-Scores were positively associated with IGF-1 levels [34]. There is no study in the literature evaluating the relationship between anthropometric measurements and growth biochemical markers of IGF-1 and IGFBP-3 levels in children with primary FH undergoing dietary therapy. Taylor et al. reported a close correlation between the low serum IGF-1 and IGFBP-3 levels and low BMI in patients with cystic fibrosis (CF) [35]. Another study found that serum levels of IGF-1 and IGFBP-3 were lower in CF children with growth retardation compared to those without growth retardation, however, this difference was only significant for IGFBP-3. A study evaluating the growth of 14 children followed with celiac disease put forth a significant positive correlation between BMI and IGF-1/IGFBP-3 levels after gluten-free dietary therapy [36].

IGF-1 levels increased in the 6th month of our study when compared to baseline. There was no significant correlation between IGF-1 Z-scores and height Z-scores at baseline and the 6th month of follow-up. However, a moderate negative correlation was found between 6th month IGFBP-3 Z-scores and BMI Z-scores (r=-0.460), suggesting that weight control has a positive effect on growth [37]. Since a similar relationship was not reported before, it will be a probable issue to investigate in future studies.

A study performed in healthy children showed that both low and high values of BMI could lead to low IGF-1 levels, emphasizes the importance of maintaining BMI within normal ranges for normal plasma IGF-1 levels [38]. As, compliance to dietary treatment and gaining healthy lifestyle changes prevent inappropriate weight gain for age and gender accompanied with ideal linear growth velocity, BMI was maintained within normal ranges in our FH patients. Therefore, there was no decrease in IGF-1 levels during the 6-month follow-up period; instead, an increase was observed as expected in healthy children.

Lipid restricted diets, healthy lifestyle habits and lipid lowering drugs which should be initiated as early as possible to reduce cardiovascular risk factors is a well-defined treatment option in FH of adults. However, in FH children and adolescents, different from the adults’ dietary treatment also should ensure ideal growth. In preparing dietary treatment, adequate daily energy intake should be provided according to age [6]. Additionally, adequate protein and essential amino acid intake plays an important role in growth of FH children. Compared with plant foods, animal-derived foods are considered higher quality protein sources due to their higher content of proteins and essential amino acids. It is known that dietary protein intake (especially milk protein) can increase circulating IGF-I levels. The relationship between consuming of different protein sources, macronutrients, fiber and IGF-1 levels of HF children are not sufficiently defined in the literature [14, 39, 40]. In our study, no significant relationship was found between IGF-1 Z-scores at baseline and the 6th month and energy, protein, fat, and fiber intake, except for a moderate negative relationship between baseline IGF-1 Z-scores and CHO percentage (r=-0.417) (p < 0.05). This suggested that the CHO percentage should be handled more carefully when planning dietary therapy in children with hypercholesterolemia.

The total protein (g/kg/day), animal derived protein (g/kg/day), and plant protein (g/kg/day) intakes of the FH patients increased in study period. Among these, the increase in plant protein intake was significant. A positive moderate correlation was found between Delta (∆) total protein intake and Delta (∆) animal protein (g/kg/day), Delta (∆) plant protein (g/kg/day), and Delta (∆) IGF-1 values (r = 0.693; r = 0.392; r = 0.356, respectively, p < 0.05). The increase in plant protein intake of FH children’s diet led to similar weight, height, and BMI gain like healthy pairs. Additionally, there was an increase in plasma IGF-1 and IGFBP-3 levels, which are the most important biochemical markers of growth.

The recommended dietary treatment of our FH children with increased in total protein (plant protein g/kg/day) intake and reduced percentage of carbohydrate ensures a decrease in LDL-C levels. The growth velocity of our FH children was similar with the age and sex matched healthy pairs. A decrease in BMI with dietary treatment led to a significant increase in plasma IGF-1 levels. So, when planning a dietary treatment for FH children, it is necessary to consider both the amount and the content of protein intake and the percentage of carbohydrate consumption for ensuring adequate growth. The diet compliance should be closely monitored with food consumption records and physical activity should be encouraged.

Mandatory changes in living conditions effect the dietary and physical activity habits of the patients and the families after the Kahramanmaraş-centered earthquake on February 6, 2023. A 1-year follow-up period is considered more appropriate to demonstrate the role of dietary therapy in improving growth outcomes in the FH population.

DATA AVAILABILITY

All data are available upon reasonable request from the corresponding author.

COMPETING INTERESTS

The authors declare no competing interests.

ETHİCAL APPROVAL

The ethical approval (10.01.2022, 2022/006) obtained from Hasan Kalyoncu University. Informed consent was obtained from the patients or their legal representative.

AUTHOR CONTRIBUTIONS

TK, GK, FDB, DK and NOM contributed to the conceptualization and design of the study; TK recruited the patients and collected the data; TK, FDB and DK contributed to the acquisition and analysis of data; TK, GK, FDB, DK and NOM contributed to the interpretation of data; TK drafted the manuscript. All authors agree to be fully accountable for ensuring the integrity and accuracy of the work. All authors have read and agreed to the published version of the manuscript.

Harada-Shiba M, Ohtake A, Sugiyama D, Tada H, Dobashi K, Matsuki K, et al. Guidelines for the Diagnosis and Treatment of Pediatric Familial Hypercholesterolemia 2022. J Atheroscler Thromb. 2023;30:531-557.
Benito-Vicente A, Uribe KB, Jebari S, Galicia-Garcia U, Ostolaza H, Martin C. Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease. Int J Mol Sci. 2018;19:3426
Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. Familial hypercholesterolemia in children and adolescents: Gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36:2425–2437.
Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-3490a.
Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: Eur Heart J. 2016; 37(39):2999-3058.
Capra ME, Biasucci G, Crivellaro E, Banderali G, Pederiva C. Dietary intervention for children and adolescents with familial hypercholesterolaemia. Ital J Pediatr. 2023;49:77.
Pederiva C, Capra ME, Viggiano C, Rovelli V, Banderali G, Biasucci G. Early prevention of atherosclerosis: Detection and management of hypercholesterolaemia in children and adolescents. Life (Basel). 2021;11:345.
Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128:213-256.
Higashi Y, Gautam S, Delafontaine P, Sukhanov S. IGF-1 and Cardiovascular Disease. Growth Horm IGF Res. 2019;45:6-16
Locatelli V, Bianchi VE. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis. Int J Endocrinol. 2014;2014:235060.
Biadgo B, Tamir W, Ambachew S. Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications-Mechanisms and Metabolic Links: A Review. Rev Diabet Stud. 2020;16(1):24-34.
Rahmawati DA, Aminuddin A, Hamid F, Prihantono P, Bahar B, Hadju V. Malnutrition in children associated with low insulin-like growth factor binding protein-3 (IGFBP-3) levels. Gac Sanit. 2021;35:275–277.
Yu H, Mistry J, Nicar MJ, Khosravi MJ, Diamandis A, van Doorn J, et al. Insulin‐like growth factors (IGF‐I, free IGF‐I, and IGF‐II) and insulin‐like growth factor binding proteins (IGFBP‐2, IGFBP‐3, IGFBP‐6, and ALS) in blood circulation. J Clin Lab Anal. 1999;13:166–172.
Watling CZ, Kelly RK, Tong TYN, Piernas C, Watts EL, Tin Tin S, et al. Associations of circulating insulin-like growth factor-I with intake of dietary proteins and other macronutrients. Clin Nutr. 2021;40:4685–4693.
Lee DH, Tabung FK, Giovannucci EL. Association of animal and plant protein intakes with biomarkers of insulin and insulin-like growth factor axis. Clin Nutr. 2022;41:1272–80.
Pekcan G. Beslenme Durumunun Saptanması. In T Buzgan, C Kesici, E Çelikcan, ve M Soylu. (Eds). Beslenme Bilgi Serisi. T.C. Sağlık Bakanlığı Temel Sağlık Hizmetleri Genel Müdürlüğü Beslenme ve Fiziksel Aktiviteler Daire Başkanlığı. Sağlık Bakanlığı Yayın No: 732. Ankara. Klasmat Matbaacılık, 2008. pp 213-249.
de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85:660-667.
Türkiye Beslenme Rehberi (TÜBER) 2022 Sağlık Bakanlığı, Halk Sağlığı Genel Müdürlüğü, Sağlık Bakanlığı Yayın No:1031, Ankara. 2022.
Saglam M, Arikan H, Savci S, Inal-Ince D, Bosnak-Guclu M, Karabulut E, et al. International Physical Activity Questionnaire: Reliability and Validity of the Turkish Version. Percept Mot Skills. 2010;111(1):278-284.
Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A Comprehensive Online Calculator for Pediatric Endocrinologists: ÇEDD Çözüm/TPEDS Metrics. J Clin Res Pediatr Endocrinol 2017;9:182–184.
Familial hypercholesterolaemia: identification and management: Evidence reviews for case-finding, diagnosis and statin monotherapy. London: National Institute for Health and Care Excellence (NICE); 2017 Nov. (NICE Guideline, No. 71.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK550197.
Lee JH. Polyunsaturated Fatty acids in children. Pediatr Gastroenterol Hepatol Nutr. 2013;16:153–161.
Mensink RP, Zock PL, Kester ADM, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77:1146–1155.
Forouhi NG, Krauss RM, Taubes G, Willett W. Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance. BMJ. 2018;361:k2139.
Kinnear, F.J., Hamilton-Shield, J.P., Stensel, D.J. et al. Nutrition and physical activity intervention for families with familial hypercholesterolaemia: protocol for a pilot randomised controlled feasibility study. Pilot Feasibility Stud. 2020;6:42.
Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med 2002;347:1483–1492.
Maciel E da S, Silva BKR, Figueiredo FW dos S, Pontes-Silva A, Quaresma FRP, Adami F, et al. Physical inactivity level and lipid profile in traditional communities in the Legal Amazon: a cross-sectional study: Physical inactivity level in the Legal Amazon. BMC Public Health. 2022;22:1–9.
Tershakovec AM, Jawad AF, Stallings VA, Zemel BS, McKenzie JM, Stolley PD, et al. Growth of hypercholesterolemic children completing physician-initiated low-fat dietary intervention. J Pediatr. 1998;133:28–34.
Lifshitz F, Moses N. Growth failure. A complication of dietary treatment of hypercholesterolemia. Am J Dis Child. 1989;143(5):537-542.
Obarzanek E, Hunsberger SA, Van Horn L, Hartmuller V V., Barton BA, Stevens VJ, et al. Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC). Pediatrics. 1997;100:51–59.
Obarzanek E, Kimm SYS, Barton BA, Van Horn L, Kwiterovich PO, Simons-Morton DG, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the Dietary Intervention Study in Children (DISC). Pediatrics. 2001;107:256–264.
Wan Nazaimoon WM, Osman A, Wu LL, Khalid BAK. Effects of iodine deficiency on insulin-like growth factor-I, insulin-like growth factor-binding protein-3 levels and height attainment in malnourished children. Clin Endocrinol (Oxf). 1996;45:79–83.
Zhao Q, Jiang Y, Zhang M, Chu Y, Ji B, Pan H, et al. Low-density lipoprotein cholesterol levels are associated with insulin-like growth factor-1 in short-stature children and adolescents: A cross-sectional study. Lipids Health Dis. 2019;18:1–7.
Kjaer TW, Grenov B, Yaméogo CW, Fabiansen C, Iuel-Brockdorff AS, Cichon B, et al. Correlates of serum IGF-1 in young children with moderate acute malnutrition: a cross-sectional study in Burkina Faso. Am J Clin Nutr. 2021;114:965–972.
Taylor AM, Bush A, Thomson A, Oades PJ, Marchant JL, Bruce-Morgan C, et al. Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis. Arch Dis Child. 1997;76:304.
Karami H, Kianifar HR, Khakshour A, Vakili R, Khalighi N, Jafari S, et al. Assessment of Serum Levels of Growth Factors IGF1 and IGFBP3 in Children with Cystic Fibrosis. Iran J Pediatr. 2019;29:e87501.
Federico G, Favilli T, Cinquanta L, Ughi C, Saggese G. Effect of celiac disease and gluten-free diet on growth hormone-binding protein, insulin-like growth factor-I, and insulin-like growth factor-binding proteins. Horm Res. 1997;48:108–114.
Li Y, Zong X, Zhang Y, Guo J, Li H. Association of Body Mass Index with Insulin-like Growth Factor-1 Levels among 3227 Chinese Children Aged 2–18 Years. Nutrients. 2023;15(8):1849.
Richter CK, Skulas-Ray AC, Champagne CM, Kris-Etherton PM. Plant protein and animal proteins: do they differentially affect cardiovascular disease risk? Adv Nutr. 2015;6:712–28.
Lassi Z, Moin A, Bhutta Z. Nutrition in Middle Childhood and Adolescence. In: Bundy DAP, Silva Nd, Horton S, et al., editors. Child and Adolescent Health and Development. 3rd edition. Washington (DC): The International Bank for Reconstruction and Development/The World Bank; 2017 Nov 20. Chapter 11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525242/

There is NO conflict of interest to disclose.

Supplementarytables.docx
ADDITIONAL INFORMATION Supplementary information The online version contains supplementary material. Correspondence and requests for materials should be addressed to Tuğçe Kartal.

Download PDF

Reviewers invited by journal
11 Oct, 2024
Editor assigned by journal
07 Oct, 2024
Submission checks completed at journal
01 Oct, 2024
First submitted to journal
01 Oct, 2024

You are reading this latest preprint version

Effect of Dietary Treatment on Growth and plasma IGF-1 and IGFBP-3 Levels of Children with Familial Hypercholesterolemia

Status:

Version 1

Abstract

INTRODUCTION

MATERIALS AND METHODS

Statistical analysis

RESULTS

DISCUSSION

CONCLUSION

LIMITATIONS

Declarations

COMPETING INTERESTS

AUTHOR CONTRIBUTIONS

References

Additional Declarations

Supplementary Files

Status:

Version 1