Effect of Weight Loss on Cholesterol Metabolism in Hereditary Hypercholesterolemias and Overweight or Obesity.

Effect of Weight Loss on Lipids Concentration and Cholesterol Metabolism in Overweight and Obese Subjects With Primary Hypercholesterolemia.

Background: Lipid lowering response to weight loss in subjects with genetic hyperlipidemias and overweight or obesity and its effect on cholesterol metabolism has not been studied.

Objective: To explore the effects of weight loss on lipid values and cholesterol metabolism, by measuring circulating non-cholesterol sterols, in overweight or obese subjects with genetic hypercholesterolemias.

Design: The investigators conducted a 6-months weight loss intervention in subjects with the diagnosis of familial hypercholesterolemia (FH) or familial combined hyperlipidemia (FCHL), body mass index >25 kg/m2, steady weight (±3 kg in the last 3 months) and absence of lipid lowering drugs in the previous 5 weeks. They were advised to follow a hypocaloric diet with a deficit of 600 kcal (30% fat, 15% protein, and 55% carbohydrates) per day as calculated from the person's resting energy expenditure and activity level. Anthropometric data, biochemical analysis including lipids, apolipoproteins and non-cholesterol sterols were evaluated at baseline, 3 months and 6 months.

Study Overview

• Status: Completed
• Conditions: Obesity; Weight Loss; Familial Hypercholesterolemias; Familial Combined Hypercholesterolemia
• Intervention / Treatment: Behavioral: Weight loss and dietary intervention

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years.
• Diagnosis of Familial Combined Hyperlipidemia* and Familial Hypercholesterolemia**.
• Body mass index > 25 kg/m2.
• Steady weight (±3 kg in the last 3 months).

• Absence of lipid lowering drugs including sterols supplements in the previous 5 weeks.

  • Familial Combined Hyperlipidemia diagnosis was based on the presence of primary combined hyperlipidaemia in untreated patients whose serum cholesterol and triglyceride concentrations were above the sex- and age-specific 90th percentiles for the Spanish population, serum total apolipoprotein B concentration ≥ 120 mg/dL and there was at least one first-degree relative with hyperlipidemia (total cholesterol and/or triglycerides >90th percentile) (Gómez-Gerique JA et al; 1999).

    • Familial Hypercholesterolemia was diagnosed in subjects with off-treatment LDL cholesterol concentrations above the age- and sex-specific 95th percentile of a Spanish reference population, triglyceride below 200 mg/dL and familial vertical transmission with at least one first-degree relative with LDL cholesterol above age- and sex-specific 95th percentiles (Gómez-Gerique JA et al; 1999).

Exclusion Criteria:

• Alcohol consumption >30 gr/day.
• Uncontrolled type-2 diabetes (HbA1c >8%).
• Any other disease that could interfere with the ability to comply with the study protocol were excluded
• Personal history of cardiovascular disease, very high risk as defined by the presence of ≥ 2 major risk factors, or total cholesterol ≥ 350 mg/dL since lipid-lowering drug were considered highly recommended.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Weight loss and dietary intervention; The weight loss intervention had a total duration of 6 months. Each participant's caloric prescription represented a deficit of 600 kcal per day as calculated from the person's resting energy expenditure and activity level using the Harris-Benedict equation. In general, prescribed energy intake was between 1200 kcal and 1600 kcal/day. Dietary composition consisted on 50-55% of carbohydrates, 15-20% of protein and 30% of fat and included a wide variety of foods typical of a Mediterranean diet. Patients were also provided with recipes and shopping counselling to improve intervention compliance and to achieve the weight loss goal. Individual consultations with a nutritionist were performed twice a month to motivate the weight loss and reinforce the intervention.

Behavioral: Weight loss and dietary intervention; The weight loss intervention had a total duration of 6 months. Each participant's caloric prescription represented a deficit of 600 kcal per day as calculated from the person's resting energy expenditure and activity level using the Harris-Benedict equation. In general, prescribed energy intake was between 1200 kcal and 1600 kcal/day. Dietary composition consisted on 50-55% of carbohydrates, 15-20% of protein and 30% of fat and included a wide variety of foods typical of a Mediterranean diet. Patients were also provided with recipes and shopping counselling to improve intervention compliance and to achieve the weight loss goal. Individual consultations with a nutritionist were performed twice a month to motivate the weight loss and reinforce the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lipids and non-cholesterol sterols concentration	Main outcome it the variation of: Lipids: Total cholesterol, LDL cholesterol, HDL cholesterol, tryglicerides and apolipoprotein B.; Non-cholesterol sterols: Phytosterols (campesterol, stigmasterol and sitosterols) and cholestanol (which are stated as subrogate markers of intestinal cholesterol absorption) and desmosterol, lathosterol and lanosterol (cholesterol synthesis markers).	After 6 months of intervention

Collaborators and Investigators

• Sponsor: Instituto Aragones de Ciencias de la Salud
• Collaborators: Hospital Clinic of Barcelona; Instituto de Salud Carlos III
• Investigators: Principal Investigator: Fernando Civeira, MD, PhD, Unidad de Lípidos/Laboratorio de Investigación Molecular; Hospital Universitario Miguel Servet; Instituto Aragonés de Ciencias de la Salud

Publications and helpful links

General Publications

• Mateo-Gallego R, Perez-Calahorra S, Cofan M, Baila-Rueda L, Cenarro A, Ros E, Puzo J, Civeira F. Serum lipid responses to weight loss differ between overweight adults with familial hypercholesterolemia and those with familial combined hyperlipidemia. J Nutr. 2014 Aug;144(8):1219-26. doi: 10.3945/jn.114.191775. Epub 2014 Jun 4.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): November 26, 2013
• Last Update Submitted That Met QC Criteria: November 25, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Obesity; Lipids; Familial Hypercholesterolemia; Familial Combined Hypercholesterolemia; Weight loss; Lipids; Phytosterols; Overweight.
• Additional Relevant MeSH Terms: Metabolic Diseases; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Body Weight Changes; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Obesity; Weight Loss; Overweight; Body Weight; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: I+CS;CEICA-B80; I+CS-HUMS-B80 (Other Identifier: I+CS/HUMS-B80)