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From the Metabolic Syndrome to a Normal Status
Aurelian Udristioiu¹, Manole Cojocaru²
¹Clinical Laboratory, Department of Hematology, Emergency County Hospital Targu Jiu & UCB University, Romania, E-mail: email@example.com
²Titu Maiorescu University, Faculty of Medicine, Physiology Department, Bucharest, Romania; E-mail: firstname.lastname@example.org
Corresponding author Aurelian Udristioiu
Objective: The aim of this study was to determine the effectiveness of a standard physical exercise protocol in terms of returning patients with signs of metabolic syndrome (MS) to a normal metabolic status.
Methods: Patients showing signs of MS (45 adult females and 35 adult males, 20-50 years old) without any disability applied a combined treatment consisting of a hypocaloric diet (<2,500 kcal/day) and a program of physical exercise using a fitness bicycle.
Results: Prior to the exercise program and without any treatment, 23% showed a healthy lipid metabolism, 28% presented high LDL and low HDL, 14% showed an atherosclerotic index and LDL/HDL >3.5 for males and >2.5 for females, 5% exhibited values predictive of coronary risk (CHOL/HDL >5), and the remaining 30% had dyslipid syndrome types 2-4, with high cholesterol and triglyceride levels. After 3 months of standard physical effort, 64 patients (80%) exhibited normalized biochemical results and a normal health status. Of the patients who failed to respond to this standard physical exercise regimen, 16 (20%) might require drug-based treatment in addition to exercise and dieting.
Conclusions: The diet/exercise combination presented in this study was effective for treatment of MS.
Keywords: Metabolic Syndrome, Qualitative Index HOMA, Waist-to-hip Ratio, Metabolic Equivalents, Body Mass Index.
In all developed and some developing countries, the numbers of obese individuals diagnosed with insulin resistance (IR) have increased rapidly to >40% in recent years. IR is a patho-physiological state characterized by a subnormal physiological response to insulinconcentrations. This state precedes the development of metabolic syndrome (MS). Insulin resistance is often considered a pre-diabetic condition . However, studies have shown that the progression of pre-diabetes to diabetes can be prevented by a combination of weight loss and increased physical activity . Although IR can be determined using a variety of methods, these are difficult to apply in everyday clinical practice; thus it is easier to monitor other parameters of MS.
MS consists of multiple, interrelated risk factors of metabolic origin that appear to promote the development of atherosclerotic cardiovascular disease (ASCVD) and which are strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state .
Over the past decade, various criteria for the diagnosis of MS have been proposed. In 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) proposed a simple set of diagnostic criteria based on common clinical measures, including waist circumference, triglycerides, HDL-C, blood pressure, and fasting glucose level. The presence of defined abnormality in any three of these five measures constitutes a diagnosis of MS. The ATP III criteria for MS have been widely used in both clinical practice and epidemiological studies.
The World Health Organization (WHO) has slightly different criteria for metabolic syndrome, including high insulin levels, elevated fasting blood glucose, or elevated post-meal glucose alone with at least two of the following criteria: abdominal obesity (defined as a waist-to-hip ratio greater than 0.9), a body mass index of ≥30 kg/m2 or a waist measurement >37 inches, lipid l panel showing a triglyceride level ≥150 mg/dl or an HDL cholesterol >35 mg/dl, blood pressure ≥ 140/90 (or receiving treatment for high blood pressure) .
The aim of this study was to determine the effectiveness of a standard physical exercise protocol that would return patients with clinical and paraclinical signs of MS to a normal metabolic status without any specific treatment for dyslipid syndromes. The patients were randomly selected outpatients who were aiming to obtain a normal body mass index (BMI), waist-to-hip ratio (WHR), and normal levels of lipid parameters.
Patients who presented at general practitioners with clinical and paraclinical signs of MS, had no other disability and had not received specialized treatment for this syndrome, and who, based on the advice of their physicians, presented with medical letters to the Department of Endocrinology of the Ambulatory County Hospital Targu Jiu, were considered for inclusion in this study. The patients had been advised by a specialist physician to volunteer for combined treatment consisting of a hypocaloric diet (<2,500 kcal/day) and a program of physical exercise on a fitness bicycle. The fitness bicycle used (Pegas-Pedalux 3, Factory City Brasov, Romania) allowed the investigator to record the intensity of physical effort. During the physical exercise, the average heart rate (HR) was 110-136 bpm. Some patients with advanced obesity (30%) did not agree to participate in the standard exercise regimen; they were not included in the study.
In this experiment were assessed biochemical parameters with signs of MS, ideal weight (IW), the schedule of physical exercise for a cure decreased weight on a fitness bike, combined with the alternative physical exercises and special diet.
Biochemical parameters with signs of MS
1.Blood glucose >120 mg/dl, as a sign of insulin resistance in non-diabetic obese
2.HOMA Qualitative Index (the relationship between liver fat and fasting serum insulin
concentrations) >2, indicating liver fat and insulin resistance. Liver fat was measured by
tomography (Figure 1).
3. Liver enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) levels 20-40 units above normal as a sign of fatty liver, and an AST/ALT ratio <1 in non-alcoholic fatty liver and serum cholinesterase > 9000 U/L, as signs of liverdysfunction .
4. Elevated uric acid, interleukin-18, C-reactive protein , and adipokines [9, 10, 11],and a lipid profile characterized by elevated plasma cholesterol and triglycerides(TGs),increases in cholesterol only (pure or isolated hypercholesterolemia), increases in TGs only (pure or isolated hypertriglyceridemiaor a low high-density lipoprotein level, which contributes to the development of atherosclerosis) .
Ideal weight (IW)
Formerly, ideal weight (IW) was calculated using the Lorenz formula, which was developed in 1929 and exists as two versions, one for males and the other for females. Body weight must be known before its application: For females, IW (kg) = H (cm) – 100 – [H (cm) – 150] / 2; for males, IW (kg) = H (cm) – 100 – [H (cm) – 150] / 4. More recently, ideal weight has been recommended to be calculated as a function of height in centimeters (H) and age (A). Using the new formula (Bull’s algorithm, also known as the EMBED Equation 3 method): for males, IW = 50 + 0.75(H – 150) + [(A– 20) / 4], and for females,IW ´ 0.9.
The schedule of physical exercise was accompanied by a daily dietary energy intake reduction of 400 kcal [Table 1]. The target heart rate (THR), which determined the intensity of the exercise, was generally recommended based on the resting heart rate (HR at rest) and the heart rate during physical effort (HRP), which had to be 60–80% of the values characteristic of aerobic metabolism. The THR ranges were calculated using the Karvonen approach, as follows: THR = (HRP × 50%) + HRR. For a value of 60% of aerobic metabolism, the THR is ((180 − 70) ×0.60) + 70 = 136 bpm . Metabolic equivalents (METs) are useful when walking exercises are recommended by physicians. By definition, a MET is the energy or level of oxygen used at rest (1 MET = 3.5 VO2 mL/kg/min). However, recent studies indicate that the average resting MET level in subjects with coronary heart disease is 23–36% less than the standard value of 3.5 mL/kg/min .
Patients showing signs of MS (45 females and 35 males, aged 20-50 years), were assessed using a biochemical analyzer (Hitachi 912, Roche Diagnostics USA); the principal biochemical parameters for lipid metabolism: total cholesterol (CHOL), triglycerides (TGs), HDL-CO, and LDL- CO were evaluated. This assessment was performed both before and after the physical exercise /diet treatment.
Schedule of physical exercise on fitness bike
The total energy expended, Q (kcal), on the fitness bike, was calculated by the theoretical equation Q (kcal) = oxygen consumption (VO2) ´ isocalorific coefficient (4.83 kcal) = [(5.8 ´ W) + (151 +10.1 ´ P) ´ 4.83], where W represents the patient’s weight (kg) and P is the power of pedaling on the stationary bicycle (Watts/sec) (15). The lipid energetic consumption, QL (kcal) was estimated using the equation Q1 = VO2 – [17.35 ´ 4.83 ´ total muscle mass of body (MSC)]. For efficient exercise, lipid energy consumption exceeds 7 kcal/min, when MSC = 20% from W.
The energy consumption per minute for jogging was calculated as E (kcal) = 0.8 ´ v + 0.5, where v is the jogging speed (3.5-6.5 km/h). In a parallel study, a control group consisting of 75 young healthy individuals (45 males and 30 females, mean age 21.8 years) who were members of a sporting club (Tennis Club of Bucharest) were assessed using the same type of ergonomic bicycle. The maximum effort capacity (VO2max) and calorie consumption (Q) of the healthy individuals, in comparison with the patients in the cohort study, were determined using an identical physical effort schedule (Table 2).
Before participating in the standard exercise program, based solely on the biochemical tests, 23% of the patients showed a healthy lipid metabolism, 28% presented high LDL (mean 189 mg/dL, SD 2.13) and low HDL (mean 30 mg/dL, SD 2.66), indicating onset of the atherosclerotic process, another 14% showed an atherosclerotic index and LDL/HDL > 3.5 for males, and >2.5 for females, a further 5% showed predictive coronary risk (CO/HDL >5), and the remaining 30% were patients with dyslipid syndrome types 2-4, in conjunction with high cholesterol (360 mg/dL, SD 2.26) and triglyceride (mean 255 mg/dL, SD 3.10) levels. Two 5- to 6-km jogging sessions per week led to the use of an additional 200-300 kcal/session. Energy consumption during exercise according to age was calculated using a mean value 10 kcal/min, (Graphic 2).
After 3 months of following the exercise regimen, 64 (80%) patients obtained a normal BMI and a good WHR (Table 3), a normal health status (normal HOMA Qualitative Index <2), and normalized biochemical results: total cholesterol (mean 169.5 mg/dL, SD 2.13, p = 0.005, reference interval = 114-225 mg/dL), triglycerides (mean 99 mg/dL, SD 2.92, p = 0.04, reference interval = 53-145 mg/dL), HDL (mean 63 mg/dL, SD 2.60, reference interval = 36-60 mg/dL) and LDL (mean 89 mg/dL, SD 2.88, reference interval = 48-130 mg/dL). Sixteen patients (20%) did not respond to the physical exercise regimen and retained high cholesterol or triglyceride levels and a BMI and WHR exceeding the normal limits.
The results described in this report are corroborated by a previous study of sedentary subjects who walked at a self-selected pace (10,000 steps per day, 3 days/week), and exhibited improved lipoprotein profiles and expression of genes involved in reverse lipid transport, without accompanying changes in body weight or total body fat.
Furthermore, a study of 16 pairs of same-sex twins with discordant physical activity patterns found that greater levels of exercise were associated with lower total visceral fat, liver fat, and intramuscular body fat, with the active twin having on average 50% less visceral fat and 25% less subcutaneous abdominal fat than the inactive twin(16). Two comprehensive reviews found little evidence of an intensity threshold for changes in HDL cholesterol, LDL cholesterol, or triglycerides, although most studies did not control for exercise volume, frequency and/or duration, and were conducted using intensities ≥40% VO2max (17).
The American College of Sports Medicine (ACSM) recommends that most adults engage in moderate-intensity cardio-respiratory exercise for at least 30 min/day, at least 5 days per week, for a total of over 150 min of exercise per week. Physical exercise should comprise vigorous-intensity cardio-respiratory exercise for at least 20 min/day on at least 3 days per week (≥75 min/week), or a combination of moderate and vigorous intensity exercise to achieve a total energy expenditure of over 500–1,000 kcal/min per week  (Table 4).
This study focused on a specific treatment method for patients at risk of metabolic syndrome using a standard physical effort of 20 min per day for 5 days per week, according to the recommended activity regimen. This, combined with an appropriate diet, aims to prevent risk factors associated with MS and maintain a normal health status.
Although diet alone and in combination with exercise improves insulin sensitivity and other cardio-metabolic risk factors in older obese adults, exercise alone shows no such benefits, according to research presented at ENDO 2012: the Endocrine Society 94th Annual Meeting. The results of 93 participants (87%) who completed a trial showed that the insulin sensitivity index, as measured by an oral glucose tolerance test, improved in 70% of participants in the diet group and in 86% of those in the diet plus exercise group, whereas no improvements were observed in the exercise only and control groups (p < 0.05) .
The diet and exercise combination presented in this study proved to be an effective treatment for MS, and this or a similar regimen should be recommend by physicians to patients who show signs of MS. For patients who show limited results from exercising on a stationary bicycle (or other exercising methods), drug treatment, such as specific treatment for dyslipid disorder, administration of leptins, leptin genes, or promoter drugs may be necessary, in addition to physical exercise and maintenance of an appropriate diet.
Further studies, which should include an appropriate control group, are necessary to confirm these findings, which can be regarded at present as only a hypothesis derived from the signs and symptoms of MS.
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- My Book written in Clinical Laboratory Medicine, “ Hematological and Metabolical Aspects from Laboratory Medicine” , confirm the aria of my interest in discovery of carcinogenesis mechanisms, especially in onco-haematology field, Leukemia.
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RECENT WORK OF RESEARCHES
1. Udristioiu A. The Assessment of Uncertainty in Measurement of Cholesterol; A Model of Calculation. Biophysical Journal; Volume 96, Issue 3, Supplement 1, February 2009; Page 504a.
2. Udristioiu A, Florescu Cristina, Popescu Manuela Andrei. “High Concentration of anaerobic ATP implicated in aborted apoptosis from CLL”. LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript 09-08-LM-S-SCI-0122R1, Published in 04-05/2010.
3. Aurelian Udristioiu. First Hematological Signal of Latent Anemia to Aging Population. Nature Publishing Group. Advance Search 0.1038 npre 2009.3285.1. Creative Common Attribution 3.0 License, accepted for the work online posted.
4. Udristioiu A, Cojocaru M, Florescu C. Screening Tests for Latent Anemia in Hospitalized Adults Over 65. LabMedicine, American Journal of Clinical Pathology-ASCP, Manuscript 09-11-LM-S-SCI-0156.R1, Published in 07-05/2010.USA American Journal of Clinical Pathology p-ISSN: 0002-9173 ICV 38.53 LabMedicine ; Ascp Press) , Impact Factor ISI, IF = 2.853 , 18 Index Copernicus Journals Master List 2006.
5. PHENOTYPIC AND GENOTYPIC CHARACTERIZATION OF ANTIBIOTIC RESISTANCE PATTERNS IN ACINETOBACTER BAUMANNII STRAINS ISOLATED IN A ROMANIAN HOSPITAL. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2,SIMONA ENACHE-SOARE3, GABRIELA BANCESCU2, AURELIANUDRISTOIU4, MANOLE COJOCARU5, CODRUTA VAGU6
1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy, Department of Microbiology, Traian Vuia 6, Sect. 2, 020956,Bucharest, Romania. 6“Stefan S. Nicolau” Virology Institute, Bucharest, Romania. FARMACIA 2010; (57); 3: 420-427 IMPACT FACTOR ISI THOMSON 0.144 .
6. Moleular Biological Tchiniques user for identification of Candida SPP. MANUELA-ANDA RADU-POPESCU1*, SILVIA DUMITRIU2, SIMONA ENACHE-SOARE3, AURELIAN UDRISTOIU4. 1 University of Medicine and Pharmacy “Carol Davila, Faculty of Pharmacy. FARMACIA 2010; (58); 4: 422-429
7. Udristioiu A. Role of Mg2+ ion as cofactor ATP in assurance of energetic environment cells( Abstract). Magnesium Research 2011; 24 (1): 22-6.
8. -Aurelian Udristioiu, Radu G. Iliescu, Cristina Popescu. Variability of bilirubin values in serum samples with high triglycerides; interference or congenital liver syndromes. J Biosci Tech Volume 2, Issue 4 (JULY 2011).
9. Aurelian Udristioiu¹*,Radu G. Iliescu², Lucian Udristioiu¹ and Manole Cojocaru. A new approach of abnormal apoptosis as a cause of autoimmunity and malignancy. Biotechnology and Molecular Biology Review Vol. 6(8), pp. 166-171, November 2011 . Available online at < http://www.academicjournals.org/BMBR>
10. Aurelian Udristioiu, Cristina Popescu, Manole Cojocaru, Sorina Comisel, Valentina Uscatescu. Relation between LDH and Mg as Factors of Interest in the Monitoring and Prognoses of Cancer. Journal of Bioanalysis & Biomedicine. Ref.: Ms. No. JBABM-11-48R1 accepted on Jan 27, 2012
11. UDRISTIOIU A. Florescu C, Popescu C, Cojocaru M "Significance of Neutrophil Alkaline Phosphatase versus Isoenzymes ALP in Acute or Chronic Diseases,"accepted for publication in LabMedicine, LabMedicine Manuscript 11-03-LM-U-MR-0052.R2/11/12/2011.
12. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Errors in Counting Platelets in Hemodialysis Patients by Use of Optical Microscopy. Review of Applied Physics (RAP) Volume 2 Issue 1, March 2013; p: 17-22
13. Aurelian Udristioiu¹, Radu Iliescu ², Manole Cojocaru³. Energetic Levels of Metabolic Pathways in Malignant B and T Cells Mini-Review. Advances in Chemical Science Volume 2 Issue 4, December 2013; 2; 90-95
14. Aurelian Udristioiu¹, Manole Cojocaru² Hemolytic Anemia Drugs Induced by Antihypertensive Agents: A case of Laboratory. 13 Scholars Journal of Medical Case Reports ISSN 2347- 6559. Sch J Med Case Rep 2013; 1(1):8-11
15. Aurelian Udristioiu1*, Radu G. Iliescu2, Manole Cojoraru Molecular mechanisms of bone reconstruction in new dental implant technology. Integrated Journal of British. Volume 1 2014 Issue 1(5-6), pg: 1-7; IJBRITISH.
1.Aurelian Udristioiu. Cicloergometrul si Sanatatea. Ed. Medicala 1990, Bucuresti. ISBN: 973-39-01105-9; Formatul 16/10 x 100; Nr pagini: 78.
2.Aurelian Udristioiu. “Bioenergetica Celulara si Maligna” Ed. Academica Brancusi 2002, Targu Jiu, Bun de tipar, Bucuresti, Tipografia Everest 2001; ISBN 973 85342-6-7; Formatul 16/14 x 100; Nr. Pagini: 307.
3. Aurelian Udristioiu, Manole Cojocaru, Radu Iliescu., Hematological and Metabolic Aspects from Laboratory Medicine" (ISBN 978-3-8473-0775-4). LAP LAMBERT Academic Publishing GmbH & Co. KG Heinrich-Böcking-Str. 6-8 , 66121, Saarbrücken, Germany, 2012.
4. Book title: Renal Diseases / Book 2 (ISBN 979-953-307-704-7). Chapter title: Variability of Biological Parameters in Blood Samples between Two Consecutive Schedules of Hemodyalsis
Authors: Aurelian Udristioiu, Manole Cojocaru, Victor Dumitrascu, Daliborca Cristina Vlad, Alexandra Dana Maria Panait and Radu Iliescu, Publishing Group 2011., Volume 2, Issue 4 (JULY 2011)
5. e-BOOK: Hematological and Metabolical Aspects of Laboratory Medicine (Hematological and Metabolical Aspects from Laboratory Medicine) ( Second Edition ) [Large Print] [Paperback].
Publisher: Aurelian Udristioiu, 2 edition (September 9, 2013) Full Color on White paper, 122 pages. ISBN-13: 978-1492186816 (CreateSpace-Assigned) ISBN-10: 1492186813, BISAC: Medical / Laboratory Medicine, USA. Sold by www.amazon.com