Discussion

Diabetes mellitus is a major public health problem world-wide. In 1997, the World Health Organization (WHO) estimated its global prevalence to be more than 135 million , and projections for the year 2025 estimate a 120% increase in the number of people with diabetes throughout the world (WHO,1998). Diabetes mellitus is a major emerging clinical and public health problem in Egypt (Herman et al,1995). As regards diabetes mellitus as a health hazard several scientific research around the world had been carried out to identify newly rising risks of diabetes mellitus which are related to modernization and industry.The environmental threats to human health are numerous . These threating hazards are related to development that lacks health-and environment-safeguards, and to unsustainable consumption of natural resources. One of these threats is air pollution and its impact on human health is increasingly becoming an important subject for consideration and indeed concern throughout the world (WHO ,1992 . This includes several emissions which are emitted from Nitrogen fertilizers industrial plants mainly Nitrogen oxides and ammonia (Bojanic et al,1977; Spuzic et al,1977 and Wilkie et al,1995) . Our study is based on the alarming risk factors of diabetes mellitus in a nitrogenous fertilizes plant. It is one of these research studies which shows the exposure to nitrogenous compounds and job stress in nitrogenous fertilizers factory as a risk factor for diabetes mellitus .It was found that the maximum prevalence of diabetes mellitus among the factory workers and employees was found to be 469/4500 with a percentage of (10.4%), while the prevalence of diabetes mellitus among the whole Egyptian population is ( 8.69%) according to the reports of the

Egyptian Diabetic Association WHO , (2003) and Arab et al.,(2003) . This high prevalence of diabetes among the workers in the fertilizers factory can be associated with the exposure to high concentrations of nitrogenous fertilizers as ammonia,urea , nitrates and nitrogen oxides. This study is enforced by Parslow et al.,(1997) and Van Maanen et al., (2000) who found that associations between regional water nitrate levels and the incidence of type 1 diabetes have been reported as following : Parslow et al.,(1997) reported that the rate of diabetes was 30% higher among those in water supply zones with average nitrate levels of 14.9-40 mg/L compared with those in areas with means less than 3.2 mg/L. Van Maanen et al. (2000) reported a 50% increase in rates when nitrate levels exceeded 25 mg/L, compared with levels less than 10 mg/L . Those studies concluded that the toxic concentration of nitrites and nitrates were due to nitrosamines triggered free -radical production, which in turn damaged the insulin producing cells of the pancreas . As regards the distribution of the diabetic workers among the different departments of the factory it was found that the highest percentage of diabetic workers is present in the Ammonia departments with a percentage of (16.1%) of the whole workers in this department and this agreed with Kostraba et al.(1992 ) who found a positive correlation even though the range of average nitrate levels was relatively limited and also agreed with Parslow et al. (1997) and Van Maanen et al. (2000) . The average nitrate concentrations in all areas of all the three studies were below the current World Health Organization standard (50 mg/L) . Virtanen et al. (1994) disagreed with the results of our study and estimated the intake of nitrate and nitrite from drinking water and found no relation with risk . As regards the socio-demographic characteristics of the studied group, It revealed that there was no significant difference between the diabetic

workers and the control group in all the socio-demographic characteristics i.e. the control group was matched with the exposed group. Regarding the age, the mean age for the fertilizers factory diabetic workers was (46.9) years and for the control group the mean age was (49.2) years . As regarding the marital status, (55.9%) and (44%) of the exposed group (cases) and the control groups were married respectively. Concerning the residence (41.3%) and (44%) of the cases and controls respectively were from urban areas. As regards the educational level, the majority of the exposed group (38%) reached secondary level of education, while the majority to control group (38%) reached the university level of education.

As regards the presence of symptoms of diabetes among the fertilizers factory diabetic workers it was found that polyuria was found in (18.1%) of the diabetic workers followed by polydepsia and polyphagia with a percentage of (9.8%) and (2.26%) respectively indicating that there were uncontrolled cases of diabetes in agreement with Chuang et al. , (2002) who found that about (55%) of diabetic patients in 198 study from 230 diabetes centers in Asia were uncontrolled. According to the type of treatment our study showed that (53.1%) of the fertilizers factory diabetic workers were treated with oral anti-diabetic drugs (NIDDM) and the remaining (46.9%) of the fertilizers factory diabetic workers were treated with insulin (IDDM) . This result agreed with The National diabetes data group,1979 which classified the two major types of diabetes mellitus according to treatment

into "insulin-dependent diabetes mellitus" (IDDM) and "noninsulindependent diabetes mellitus" (NIDDM). This result disagreed with Mooradian (1996) who found that insulin is a treatment for both IDDM and NIDDM : for survival in IDDM while it is used to control the blood sugar and complications by time in those who are NIDDM . As regards the distribution of the complications of diabetes mellitus (Microvascular , Macrovascular and Mixed complications) among the fertilizers factory diabetic workers by, age, residence, smoking, education and the type treatment it was found that was no significant difference among diabetic workers by residence, education level and type of treatment except for the age and smoking as complications were found to increase by increasing age and smoking this was accepted by (Rimm et al., 1993 and et al., 1998 ). From our study it is found that the most common complications were microvascular complications including polyneuropathy , nephropathy and retinopathy in agreement with Ramchandran et al.,(1999). As regards the distribution of complications of diabetes mellitus according to the duration of diabetes it was found that the longer the duration of diabetes in years the more common the occurrence of complications with statistical significant difference at p value (< 0.05).It is also found that some diabetic workers had more than single complication with the increase of the diabetes duration . The present results agreed with National Diabetes Data Group (1995) who reported that the longer the duration of diabetes the more common chronic Chuang et al. , (2002) and Rimm et al., 1995) ,but others have failed to show this association (Stolk et al., 1993; Perry et al., 1995 and Njolstad

problems affecting multiple organ systems which will eventually arise in patients with poor glyceamic control . As regards the chemical emissions released in the fertilizers factory it was found that these chemical emissions (NO,NO2&ammonia) were at high levels in the air of the fertilizers factory when compaired with the Egyptian standards for the ambient air quality (Law4/1994) or WHO standards: (50 ug/m for NO&ammonia) and (6 ug/m for NO2) according to the WHO, (1987) and there was significant difference between the levels of these chemical emissions in the fertilizers factory and Mansoura University . As regards the distribution of the diabetic workers (cases) in the fertilizers factory according to the workplace mean annual concentration of ammonia in the different departments of the factory the present study found that the highest concentration of ammonia is present in the ammonia and urea departments with XSD =354.1761.53 and as regards the type of DM in the distribution of the workers it was found that the highest percentages of IDDM (9.1 %) was present in the ammonia department and this result agreed with Elliot et al, ( 2001) who found that higher intake of nitrates, nitrites and N-nitroso compounds, had been associated with increased risk of IDDM as these chemicals are toxic to pancreatic beta cells. This is also was accepted with Sauter et al., (1990) who found that exposure to toxic hazards in the work environment increases the level of job stress. So these chemical emissions contributes to diabetes development both physically and psychologically. As regards the risk factors for diabetes mellitus among the study population it was found that there was no significant statistical difference between the cases and the control group in the risk factors for diabetes mellitus as regard : Age , family history,

consanguinity , diet , overweight ,obesity , Hepatitis C virus, and lack of exercise.The present (1995) and Arab(1992) result agreed with Herman et al., who found that age , family history,

consanguinity , diet , overweight ,obesity , Hepatitis C virus, and lack of exercise had the highest risk for DM in Egypt. The present study found that diabetes increased with age as 44% of cases were > 50years in age and this agreed with the WHO, (1999)who found that the incidence of diabetes increases with age . The present study found that about 45% of the cases were overweight and 36% were obese and this agreed with Chan et al., 1994 and Colditz et al.,( 1995 ) who indicated that there was a general relationship between the prevalence of diabetes and the average weight of the populations in their studies . Within those populations, the risk of developing diabetes (predominantly type 2) was related to increasing obesity and also to a central distribution of fat and the rate of weight gain during life. This study agreed with Lemieux et al.,(1996) and Chan et al., (1994) who found that the risk of developing type 2 diabetes rises steadily above surprising low levels of BMI, but above a BMI of 30 kg/ m2 this risk rises exponentially ;at the highest levels (BMI >40 kg/ m2) the risk is increased 40-80 fold above a BMI <21kg/ m2 , equating to a lifetime risk of 50% . Shaten et al., (1993) accepted also with them as the risk of diabetes almost doubled for each 5 kg /m2 increase in body mass index . As regards the family history the present study considered it a risk factor for diabetes mellitus which agreed with Ohson et al., (1988) and Kawakami et al., (1997) who found that the first degree

relatives of people with diabetes(type 2 DM) have a two fold increased risk of diabetes. As regards the diet the present study found that 45% of cases had fatty diet and 47% had rich CHO diet and only 8% of the cases had healthy balanced diet which is accepted by Salmeron et al., (1997) who found that a diet containing both a high glyceamic load and low cereal fiber content ,increased the risk of selfreported type 2 DM up to 2.5 fold . As regards lack of exercice and sedentary life our present study found that only 7.4% of cases practice exercice and this agreed with Helmrich et al., (1991) and Perry et al.,( 1995) who found that the amount of daily physical risk activity appears to have a continuous inverse relationship with the risk of type 2 DM ,with a reduction in of 6% for each 500-Kcal increase in leisure time energy The present study found also that hepatitis C infection was present among the fertilizers factory diabetic workers with a percentage of (9%) and among the control group with a percentage of (3%) and this was in agreement with Szopa et al.,( 1993) who evidenced that chronic hepatitis C virus infection has been associated with an increased incidence of diabetes, and also with Yang et al., (2003) who found that the occurrence of anti HCV antibodies blood levels was higher in diabetic patients than in healthy adults and therefore HCV may play a role in the development of diabetes mellitus .This result also was accepted with ElZayadi et al., (1998) who reported that chronic hepatitis C patients in Egypt are three times more likely to develop DM than HCV seronegative patients. expenditure.

As regards smoking as a risk factor for DM the present study found no significant difference among the study population . Our result agreed with Rimm et al., (1993) and Rimm et al.,( 1995) that smoking may play a role in the development of diabetes mellitus ,but others have failed to show this association (Stolk et al., 1993; Perry et al., 1995 and Njolstad et al., 1998 ). According to the employment duration in this study it was found that the longer the duration of employment , the more severe job stress level and diabetes . It was found that at duration of employment of > 30 years, about (46%) of diabetic fertilizers workers were present compared to (18%) of the control group with no statistical difference and this result agreed with West,(1998) who found that physiological changes enhance the body's ability to cope with the stress, but extended exposure to the stressor can also result in the inability of the body to adapt. This result agreed also with Kai et al.,(2000) who suggested that, blood glucose derangement due to stress is presumably associated not only with changes in counter-regulatory hormones involved in glucose metabolism, but also with stress-induced changes in eating behavior resulting in overweight and obesity ending in NIDDM (type 2 DM). As regards the distribution of the workers in the fertilizers factory according to diabetes and the duration of employment it was found that diabetes mellitus increased with increasing the duration of employment among the workers of the fertilizers factory with significant statistical difference P value < 0.001.This result agreed with Kostraba et al.(1992 ) and Van Maanen et al. (2000) who found a positive correlation between the duration of exposure to nitrates and the occurance of diabetes mellitus. Virtanen et al. (1994) disagreed with this result and found no relation between diabetes mellitus and prolonged exposure to nitrates.

As regards exposure to job stress as a risk factor for diabetes mellitus , this study revealed that severe job stress level was found among the fertilizers factory diabetic workers and the control group with a percentage of (44.1%) and (3%) respectively while absence of job stress level among fertilizers factory diabetic workers and the control group was of a percentage of (4.4%) and (41%) respectively with high significant difference .This result agreed with Chrousos (2000) who found that job stress especially the higher levels had an effect on the hypothalamic-pituitary-adrenal axis and the pathogenesis of diabetes mellitus . As regards job stress level and education our study found that the longer the duration of employment in years the more common was the (job stress level with a high statistical significant difference (p<0.05 and this result agreed with Marmot and Theorell(1988) who found that high educational level (white-collars ) was accompanied with severe job stress . This result was against Siegrist et al.,(1990) who found that workers ( blue-collars) with less education, had a substantially high "job strain". As regards the relation between job stress level and regularity of treatment among fertilizers factory diabetic workers the present study found that the regularity in treatment decreased with increasing job stress level and showed that the fertilizers factory diabetic workers of moderate job stress level were regular in anti-diabetes treatment with a percentage of (34%) and with a highly significant p value =0.000 . This result agreed with Sapolsky ,(1998) who referred that to depression which in most cases accompanied high job stress and lead to inability to

experience pleasure. That explains why there is a loss of interest in hobbies and recreation . The technical term for this symptom is anhedonia, meaning the inability to feel pleasure. This agreed also with Anschuetz , (1999 ) who found that high levels of job stress were associated with Severe Exhaustion Stage which is composed of : Chronic sadness or depression Chronic mental and physical fatigue Chronic stress related illnesses (headache, stomach ache, bowel problems, etc.) Isolation, withdrawal, self-destructive thoughts All the above symptoms attributed to the indirect relationship between job stress level and regularity of treatment .

As regards the relation between job stress level and complications of diabetes , this study found that there was direct relationship between the level of job stress and the complications and showed that the high job stress level the more common the occurrence of micro vascular, macrovascular and mixed complications with significant difference at p.value =0.000. It showed also that there was absent complications at absent job stress among the fertilizers factory diabetic workers. It was found also that at severe job stress level some patients had more than one complication. These complications were of both types : macrovascular and microvascular complications. This agreed with Sapolsky , (1998) who found that chronic stress leads to increased levels of glucocorticoids, which increase the levels of glucose in the blood. Obviously, these increased glucose levels raise the likelihood of damage to the kidneys and

blood vessels, as well as blindness, diabetic coma, or even death. Furthermore, increased levels of glucocorticoids, epinephrine, and norepinephrnine during chronic stress will promote insulin resistance. This means that fat cells in the body become even less responsive to insulin, creating higher levels of glucose in the blood, and greater chances of damage to the kidneys and eyes, through many mechanisms one of them involves the blood vessels in the kidneys which become clogged, cutting off oxygen and glucose to the necessary tissues and another mechanism is about proteins which become linked together in the eyes, forming cataracts and retinopathies thus increasing the complications rate. . Henningsen et al.,(1992) also agreed with the present result as they found that job stress had an effect on the immune system functioning which lead to possible synergistic effects of psychosocial and physical health hazards. Anschuetz , (1999 ) also agreed with this result through the Severe Exhaustion Stage explanation.