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CAPITULO III: AUDITORIA DE LOS SISTEMAS INTEGRADOS NORMA ISO 19011:2002

3.5 INFORME DE AUDITORIA

Data generated from the study was coded and entered into the computer for analysis using the Statistical Package for Social Sciences (SPSS) version 11.0. Values were expressed as mean ± standard deviation. The means of continuous variables were compared using unpaired students t test. Differences with P-values less than or equal to 0.05 were taken to be significant 24, 28.

CHAPTER FIVE RESULTS

A total of 100 metabolic syndrome subjects (selected from 283 subjects) and 100 controls that satisfied the inclusion criteria for the study were recruited. Means of variables of metabolic syndrome subjects were compared with those of controls using the unpaired student’s t test.

5.1 ANTIOXIDANT LEVELS

Details of the antioxidant levels of subjects compared with those of controls using the student’s t test are summarized in Table 2.

5.1.1 VITAMIN C

The mean vitamin C concentration of subjects was significantly higher than that of controls (P=0.0001).

5.1.2 VITAMIN E

The mean vitamin E concentration of subjects was significantly lower than that of controls (P=0.0001).

5.1.3 TOTAL ANTIOXIDANT STATUS

The mean total antioxidant status of subjects was significantly lower than that of controls (P=0.0001).

5.2 BASELINE PARAMETERS

Table 1 summarizes the baseline parameters of subjects compared with those of controls using the student’s t test.

5.2.1 AGE AND SEX DISTRIBUTION

The recruited subjects were made up of 40 males and 60 females and their ages ranged from 21 to 73 years with a mean age of 51.41 ± 10.88 years. Male to female ratio was 1:1.5.

Recruited controls consisted of 45 males and 55 females and their ages ranged from 22 to 78 years with a mean age of 48.57 ± 12.05 years. Male to female ratio was 1:1.2.

There was no statistically significant difference between the mean ages of the subjects and that of controls (P=0.082).

5.2.2 COMPONENTS OF METABOLIC SYNDROME (Fig. 1)

High blood pressure (BP ≥ 130/85mmHg) was the most frequent component of metabolic syndrome, observed in 90% of subjects (37 males, 53 females). It was followed by central obesity (WC > 102cm in men and WC > 88cm in women) in 83% of subjects (27 males, 56 females), hyperglycaemia (FPG ≥ 6.1mmol/L) in 57% (20 males, 37 females), HDL hypocholesterolaemia (HDL < 1.0mmol/L in men and HDL <

1.3mmol/L in women) in 35% (15 males, 20 females) and hypertriglyceridaemia (Triglyceride ≥ 1.7mmol/L) in 30% of subjects (16 males, 14 females).

Frequency of central obesity (92%) and hyperglycaemia (62%) was higher in female subjects compared with 70% and 50% respectively in male subjects (Figure 2). Male subjects had a higher frequency of high blood pressure (93%), hypertriglyceridaemia

(40%) and low HDL (38%) compared with 88%, 23% and 33% respectively in female subjects (Figure 2).

5.2.3 BLOOD PRESSURE

Eighty-one percent of subjects had frank hypertension (BP ≥ 140/90mmHg) 27 and were on antihypertensive drugs. The mean duration of hypertension was 5.3 ± 4.47 years.

The mean diastolic (P=0.0001) and systolic (P=0.0001) blood pressures of subjects were significantly higher than that of controls.

5.2.4 ANTHROPOMETRIC PARAMETERS 5.2.4.1 WAIST CIRCUMFERENCE

The mean waist circumference of subjects was significantly higher than that of controls (P=0.0001).

5.2.4.2 BODY MASS INDEX (BMI)

Fifty-one percent of subjects had high BMI > 30kg/m2. The mean BMI of subjects was significantly higher than that of controls (P=0.0001).

5.3 BIOCHEMICAL PARAMETERS

Details of the biochemical parameters of subjects compared with those of controls using the student’s t test are summarized in Table 1.

5.3.1 FASTING PLASMA GLUCOSE (FPG)

Fifty-five percent of subjects had type 2 diabetes (FPG ≥ 7.0mm0l/L or two hours post-glucose value of ≥ 11.1mmol/L) and they were on dietary therapy and oral hypoglycaemic drugs. The mean duration of diabetes was 7.0 ± 3.95 years.

The mean plasma glucose of subjects was significantly higher than that of controls (P=0.0001).

5.3.2 PLASMA TOTAL CHOLESTEROL

Forty percent of subjects had hypercholesterolaemia (total cholesterol ≥ 5.2mmol/L).

The mean plasma total cholesterol of subjects was significantly higher than that of controls (P=0.0001).

5.3.3 PLASMA TRIGLYCERIDE

The mean plasma triglyceride of subjects was significantly higher than that of controls (P=0.0001)

5.3.4 PLASMA HIGH DENSITY LIPOPROTEIN (HDL)

The mean HDL of subjects was significantly lower than that of controls (P=0.0003).

5.3.5 PLASMA LOW DENSITY LIPOPROTEIN (LDL)

Thirty-two percent of subjects had high LDL ≥ 3.4mmol/L. The mean plasma LDL of subjects was significantly higher than that of controls (P=0.001).

FIGURE 1: COMPONENTS OF METABOLIC SYNDROME IN ENTIRE STUDY POPULATION

90

83

57

35

30

0 10 20 30 40 50 60 70 80 90 100

High Blood Pressure

High Waist Circumference

High Fasting Plasma Glucose

Low High Density Lipoprotein

High Triglyceride

FREQUENCY %

COMPONENTS OF METABOLIC SYNDROME

FIGURE 2: COMPONENTS OF METABOLIC SYNDROME IN MALE AND FEMALE SUBJECTS

93

70

50

38 40

88

92

62

33

23

0 10 20 30 40 50 60 70 80 90 100

High Blood Pressure

High Waist Circumference

High Fasting Plasma Glucose

Low High Density Lipoprotein

High Triglyceride

FREQUENCY %

COMPONENTS OF METABOLIC SYNDROME

Male Female

TABLE 1: BASELINE AND BIOCHEMICAL PARAMETERS OF SUBJECTS AND CONTROLS COMPARED USING STUDENT’S t TEST

PARAMETER SUBJECTS

(n=100) Mean ± SD

CONTROLS (n=100) Mean ± SD

P-VALUE BASELINE

Age (years) 51.41 ± 10.88 48.57 ± 12.05 0.082

Waist circumference (cm) 102.3 ± 11.47 81.2 ± 9.24 0.0001*

Body mass index (kg/m2) 30.37 ± 5.94 24.08 ± 3.95 0.001*

Systolic blood pressure (mmHg) 143.9 ± 22.29 111.75 ± 10.23 0.0001*

Diastolic blood pressure (mmHg) BIOCHEMICAL

Fasting plasma glucose(mmol/L) Triglyceride (mmol/L)

Total cholesterol (mmol/L)

High density lipoprotein (mmol/L)

Low density lipoprotein (mmol/L)

92.75 ± 14.45

6.45 ± 2.2 1.26 ± 0.62 4.87 ± 1.14 1.37 ± 0.55 2.93 ± 0.97

73.25 ± 7.73

4.1 ± 0.64 0.71 ± 0.31 4.21 ± 0.91 1.6 ± 0.33 2.28 ± 0.82

0.0001*

0.0001*

0.0001*

0.0001*

0.0003*

0.01*

* Statistically significant (P<0.05)

TABLE 2: ANTIOXIDANT LEVELS OF SUBJECTS AND CONTROLS COMPARED USING STUDENT’S t TEST

ANTIOXIDANT SUBJECTS

Mean ± SD N CONTROLS

Mean ± SD N P-VALUE Vitamin C (μmol/L) 27.48 ± 7.36 96 44.26 ± 7.30 95 0.0001*

Vitamin E (μmol/L) 16.85 ± 4.86 94 30.83 ± 6.12 94 0.0001*

Total antioxidant status (mmol/L) 1.23 ± 0.283 40 1.58 ± 0.284 40 0.0001*

* Statistically significant (P<0.05)

CHAPTER 6 DISCUSSION

6.1 ANTIOXIDANT LEVELS

In this study, significantly lower concentrations of vitamins C and E and total antioxidant status were observed in subjects compared with controls.

Low concentrations of vitamins C and E have been associated with high oxidative stress as well as low intake of foods rich in antioxidants (particularly fruits and vegetables), cigarette smoking, poor health status and low physical activity 20,22. Dietary intake and degree of physical activity were not assessed in this study but it has been documented that, compared to Caucasians, Africans consume more vegetable fibre and less fat 6,29. The percentage of subjects that had a significant history of cigarette smoking in this study was low (10%).

The finding of lower vitamins C and E and total antioxidant levels in subjects suggest that increased production of free radicals and increased depletion of antioxidant reserves as a result of high levels of oxidative stress may be a contributory factor to the reduced antioxidant concentrations. Inadequate dietary antioxidant intake may further contribute to the reduced concentrations 2,37.

Several studies have been done on the status of various dietary antioxidants including vitamins C, E and A, β-carotene and other carotenoids, and selenium in subjects with metabolic syndrome. There is established evidence of reduced levels of individual as well as total antioxidant status in the metabolic syndrome 2,37,38,39. Ford et al observed lower levels of vitamins C and E in metabolic subjects in the U.S. compared with controls 2. Sharma et al also reported lower concentrations of vitamins C and E in metabolic syndrome subjects in India compared with controls 37. A greater degree of

severity of the metabolic syndrome has been shown to result in increased oxidative stress and lower antioxidant enzymatic capacity. Low antioxidant levels further aggravate the degree of oxidation 12,37.

Individual components of metabolic syndrome have also been shown to be independently associated with antioxidant status. Hypertension, hyperglycaemia, central obesity and serum free fatty acids have been found to be negatively associated with total antioxidant status 2,38.

Antioxidants have been found to play a role not only in the pathophysiology of metabolic syndrome but also in the pathophysiology of diabetes mellitus and cardiovascular disease 24,25. Some studies have shown that total antioxidant status as well as vitamins C and E levels are also reduced in diabetes mellitus and cardiovascular disease 9,24,25,40. This is a significant finding because diabetes mellitus and cardiovascular disease may be a consequence of metabolic syndrome; individuals with metabolic syndrome are known to be at high risk for developing these conditions

37. A high prevalence of metabolic syndrome has been observed among type 2 diabetic patients. Previous studies done in Nigeria have shown a prevalence of 25 to 59% 6,8 and in Caucasians 70-80% 4.

Reduced levels of antioxidants have been shown to increase the risk of diabetes mellitus and cardiovascular disease 12,40,41. Montonen et al also observed that an increased intake of vitamin E and total carotenoids was associated with a reduced risk of type 2 diabetes in a large prospective Finnish population study 14. Pharmacological doses of vitamin E have been shown to reduce indicators of oxidative stress, reduce protein glycosylation, reduce insulin resistance and improve metabolic control in type 2 diabetic patients 40,41. However, the safety and efficacy of antioxidant

In Nigerians, Idogun et al observed lower vitamins C and E levels among type 2 diabetics in Lagos 9 and Nweke et al observed lower total antioxidant levels among type 2 diabetics in Portharcourt 42. Lower total antioxidant status among type 2 diabetics was also reported in Ghana 43. In the U.S. Will et al reported significantly lower vitamin C levels in newly diagnosed diabetic patients compared with controls 24 and in Pakistan Ahmad et al observed lower levels of vitamins C and E in type 2 diabetics compared with controls 25. Increased free radical activity has been demonstrated in diabetes mellitus 24,43. It has been suggested that low antioxidant concentrations found in diabetics are as a result of their increased use in scavenging the increased free radicals 2,9,43. Some researchers have suggested that increased oxidative stress and reduced antioxidant concentrations may have preceded and accelerated the development of diabetes mellitus 24,42. High oxidative stress impairs insulin action and contributes to insulin resistance, which constitutes the core of the metabolic syndrome and plays a primary role in the pathogenesis of diabetes mellitus 12.

Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic changes which include smoking cessation, weight control, adequate exercise and proper diet, inclusion of antioxidant vitamins, fruits and vegetables could be beneficial in preventing or delaying the consequences of metabolic syndrome by reducing free radical formation and oxidative stress associated with this syndrome. Without early intervention by lifestyle modification, subjects with metabolic syndrome may eventually go on to develop diabetes mellitus and cardiovascular disease.

6.2 AGE AND SEX DISTRIBUTION

In this study, the age of metabolic syndrome subjects ranged from 21 to 73 years with a mean age of 51.41 years while that of controls ranged from 22 to 78 years with a mean age of 48.57 years. The male to female ratio of subjects (1:1.5) and controls (1:1.2) in this study showed a slight female preponderance in both groups. Similar findings have been observed in some earlier studies which showed a higher frequency of metabolic syndrome in females compared with males 2,44,45.

In Nigeria, Isezuo et al reported a male to female ratio of 1:1.1 in Sokoto 7, Alebiosu et al observed a slight male to female ratio of 1:1.02 in Sagamu 8, Orluwene et al reported a male to female ratio of 1:5 in Portharcourt 45 and Wahab et al reported a male to female ratio of 1:1.3 in Ilorin 46. In the U.S. Ford et al observed a male to female ratio of 1:1.1 2.

6.3 BLOOD PRESSURE

Systolic and diastolic blood pressures were significantly higher in subjects compared to controls. This is in keeping with findings from earlier studies 2,38. High blood pressure was the most frequent component of metabolic syndrome among subjects in this study and this agrees with findings from previous studies 5,41.

High blood pressure was more frequent in men compared with women. It has been reported that hypertension is more common in men than in women through middle age until menopause in women, and that men have higher mean systolic and diastolic blood pressures compared with women in all ethnic groups 48,49,50. Evidence suggests that oestrogen protects against hypertension via activation of the vasodilator pathway mediated by nitric oxide and prostacyclin, and inhibition of the vasoconstrictor pathway mediated by the sympathetic nervous system and angiotensin 49. Men’s

greater involvement in more stressful activity as well as a higher prevalence of alcohol consumption and cigarette smoking, which are risk factors for hypertension, among men may be contributory factors 36,51.

6.4 ANTHROPOMETRIC PARAMETERS

Waist circumference and body mass index were significantly higher in subjects than in controls. Female subjects had a higher frequency of central obesity than male subjects.

It has been shown by earlier studies that the prevalence of obesity is higher in women than in men 5,44,52. The prevalence of central obesity based on waist circumference was found to be ten times higher in Cameroonian women than men 5. A higher waist circumference in women compared with men has also been reported in the United States 39. Similar findings have also been reported in Nigeria 29,41,45. These findings may be due to genetic and hormonal differences between men and women, pregnancies in women and cultural practices that tend to limit physical exertion by women, resulting in sedentary habits 7,52.

6.5 BIOCHEMICAL PARAMETERS

Fasting plasma glucose, triglyceride, total cholesterol and LDL levels of subjects were observed to be significantly higher than those of controls, while HDL was observed to be lower in subjects compared with controls. These findings are similar to those reported by other researchers 2,5,8.

Higher frequency of dyslipidaemia was also observed in men compared with women.

Before menopause, women are known to have lower total cholesterol, lower LDL, lower triglyceride and higher HDL levels than men because of the protective effect of

oestrogen 51,53. Oestrogens increase HDL by reducing triglyceride lipase activity that catabolises HDL 51,54.

6.6 CONCLUSION This study showed that:

1. The concentrations of vitamins C and E were lower in metabolic syndrome subjects compared to controls.

2. Total antioxidant status was lower in metabolic syndrome subjects compared to controls.

3. Female subjects had a higher frequency of central obesity while male subjects had a higher frequency of high blood pressure and dyslipidaemia.

6.7 RECOMMENDATIONS

1. Proactive screening for metabolic syndrome in patients should be encouraged in the general out-patient and metabolic clinics.

2. Dietary counselling and lifestyle modification should be emphasized and subjects with metabolic syndrome and diabetes should be encouraged to see a dietician.

3. Further studies are required to investigate the concentrations of other antioxidants such as beta-carotene, glutathione peroxidase and selenium in subjects with metabolic syndrome.

4. Further studies are also required to determine the effects of increased intake of antioxidants on metabolic syndrome.

6.8 LIMITATION

Inability to measure oxidative stress.

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