An Association between Work Stress and Serum Cortisol with the development of Type 2 Diabetes Mellitus among Industrial Workers

Veena Prabavathy J, Sangeetha R*

Department of Biochemistry, Vels Institute of Science, Technology and Advanced Studies, Chennai 600117

*Corresponding Author E-mail: sara_dna@yahoo.co.in

ABSTRACT:

Objective: The main purpose of this study was to find out the interrelationship between stress and development of Type 2 DM using stress hormone Serum Cortisol as a marker among the industrial workers as work related stress was found to be an analogue between the environment and the individual. Method: A total of 250 Non diabetic Industrial workers have been chosen to conduct this cohort study in relation to their perceived stress which was measured through perceived stress scale PSS 10 and GHQ 12 questionnaire and their stress hormone, Serum cortisol level was assessed using Architect CLIA method as serum Cortisol will be secreted in higher levels during the body’s fight or flight response to stress and is also responsible for several stress related changes in the body mainly metabolic path way. The altered blood glucose levels were estimated using blood plasma by regular Glucose Oxidase method using fully automated chemistry analyser. Result: Study among 250 Industrial workers of age group ranging from 25-55yrs with the number of years of service ranging from 2- 30 years revealed a positive association between stress score and cortisol levels varying with work experience. the work group with 0-10 years of work experience had a cortisol value of 27+2.1µg/dl with fasting blood sugar 108 + 2.6 mg/dl and PPBS being 135+1.7 mg/dl and their perceived stress score 20+1 however for the work group with 11 to 20 years of experience their cortisol level was 22+1.3 which is almost little lesser in comparison to the first work group with fasting and post prandial values almost showing an average of 109 + 3.8 and PPBS 135 + 2.6 with a less degree of stress score of 16+2 and the work group with the work experience of 21 to 30 years showed a cortisol value of 24+3.1 with fasting blood sugar 109 +4.2 and Post prandial 135 +3.6 with a significant correlation to the stress score of 21+2 . Existence of correlation between parameters using Pearson’s correlation revealed statistically significant low correlation with age of workers and their fasting blood sugars. Their fasting blood glucose and post prandial blood glucose levels were statistically significant ( p<0.05) and highly correlated and the increase in cortisol levels could be correlated with increased fasting blood glucose and post prandial blood glucose levels with the correlation being ( p<0.01). Conclusion: From this cohort study it is evidently proven that work stress plays a major role in the development of Type 2 diabetes among industrial workers apart from other factors that could cause diabetes. And it is also evident from this study that release of high Cortisol by the body in relationship to its stress mechanism can influence the regulation of blood glucose resulting in an increased risk of Type 2 DM.

KEYWORDS: Type 2 DM, Serum Cortisol, Perceived Stress, work stress, Glucose.

INTRODUCTION:

Diabetes Mellitus is a metabolic disease which is characterised by the inability to maintain normal glucose homeostasis which may depend on the alteration of the secretion of the hormones like insulin which is responsible for the uptake of glucose in the body.¹

Blood glucose may also get altered by the secretion of stress hormone like cortisol which is said to increase during high stress level of the individual thereby resulting in high blood glucose and persistent high Cortisol level may lead to the development of Type 2 DM. However the association between work stress and Type 2 diabetes are said to be inconsistent.²

Cortisol which is said to be steroid hormone belonging to glycocorticoid class of hormones is produced by the zona fasiculata of adrenal cortex of humans within the adrenal glands. The hormone is released in response to stress. The blood sugar level increases through gluconeogenesis and suppress the immune system.³

Increased levels of Cortisol puts a strain on the body health, though it is normal for Cortisol levels to rise during the times of acute stress it becomes abnormal if these levels continuous to remain high. This prolonged elevated level of this steroid hormone affect immune function, metabolic pathways for the use of energy and the risk of chronic disease. If the individual is in stressful situation the stress hormone immediately provides glucose to the body by utilising the protein source through gluconeogenesis in the liver, and this quick delivery of glucose prepares the body for the fight or flight mechanism hence if the body is in persistent stressful state then cortisol obtains glucose consistently thereby leading to high blood sugar.⁴

The hormone glucocorticoid is produced by the adrenal glands located above the kidneys normally gets released to the responses that depends on daily events like waking up in the morning, doing regular exercise besides high alert situation. Cortisol being a biomarker for stress which consistently remains high in a person with no physical activity and to buffer the effects of chronic stress it may contribute to Type 2 diabetes. The Higher cortisol results the more the insulin resistance which reinforces the pancreas to produce more insulin to get a response, but as the insulin resistance persists insulin producing beta cells quickly gets worn out resulting in Type 2 DM.⁵

The whole body effects of elevated cortisol widely varies, out of which blood sugar imbalance and diabetes is said to be one among the notable metabolic change, theoretically, this mechanism can increase the risk for type 2 diabetes, however the causative factor is not clear since the main function of cortisol is to thwart the effect of insulin voluntarily rendering the cells insulin resistant, and the body remains in this insulin resistant state when cortisol levels are chronically elevated. The pancreas on the other hand struggles to keep up with the high demand for insulin, and glucose levels in the blood remain high, and the cells cannot get the sugar they need, and this cycle continues.⁶

T2DM, though it is a metabolic disease, its metabolic condition is not homogenous in-spite its etiological and clinical difference, they share a characteristic which includes the role played by stress in the occurrence of the disease, its progress and its chronicity. The direct and indirect impact of stress and T2DM is characterised by hyperglycemia, insulin resistance and its secretion defect. Though researchers could not find the exact cause of T2DM related to stress, predictors have found out that obesity, hypertension, physical inactivity, sedentary habits, alterations in the glycemic index and fat metabolism correlates well with T2DM and its diffusion. Stress is very often observed in correlation with the diagnosis of diabetes which alters the glucose metabolism and the immune response. In contrast T2DM itself is a source of stress, because it requires lot of modification in lifestyle, the ability to cope up the challenges can affect the management of the treatment and to keep up the glycemic control.⁷

The purpose of this study is to investigate the interrelationship between occupational stress and cortisol levels in industry workers and to establish a correlation between glucose and cortisol levels in those workers.

METHODS:

Research Design and Method:

This research was mainly focussed to evaluate the association between work stress, and T2DM using Serum cortisol as a stress marker. The subject consist of 250 male workers who are working in an Heavy industrial set up and who are non-diabetic between the age group of 25yrs to 60yrs and who had put up around 2-30yrs of service. These selective workers were recruited for the study from Heavy vehicles Factory, Avadi Chennai after an informed consent. Stress questionnaire containing clear study protocol along with General information were collected. GHQ 12 and PSS 10 based on Cohen Sheldon perceived stress scale was distributed widely to the employees and only those who completed and returned the questionnaire were enrolled for the study, Subjects who enrolled but could not complete the protocol were dropped from the study.

Conforming to Ethics:

Approval from VISTAS Ethics Committee (Vel’s Institute of Science Technology and Advanced studies), was obtained for this study before the commencement of employee identification. All the individuals and sample data were identified by their unique employee personal ID depending on their Age, and number of years of service and work area. Individual questionnaire GHQ 21 and PSS 10 were obtained with the individual’s consent, blood tests and their results were kept confidential.

Inclusion Criteria:

Industrial Employees who are in active mechanical work and working with heat

Industrial employees belonging to the age group 25-55 years.

Employees who have put up 2-30 years of service.

Subject includes Nondiabetic and pre-diabetic individuals.

Employees involved in Production unit with high amount of Physical and Mechanical activity.

Exclusion Criteria:

Industrial Employees exposed to Metal toxins and Chemicals.

Employees who are established Diabetes.

Employees who have already gone into organ failures due to uncontrolled diabetes. (Chronic Condition )

Data collection:

The general questionnaire was distributed to the non-diabetic employees at random and filled in questionnaires were collected with their consent to participate in the study with their signature and contact numbers. The study content and the aim of the study were well explained to the employees before handing over the questionnaire. The collected questionnaires were sorted out according to the age and number of years of service. Their general health was assessed and the suitable 250 employees were selected and called for Blood investigation.

Stress Questionnaire:

Stress questionnaire form was distributed both in English and Tamil as most of the industrial employees were well versed only in regional language. The filled up form were collected and stress scores were made based on Sheldon Cohen formulae

The calculations were made as per the recommended PSS scale recommended by Sheldon and Cohen (1994) : The PSS ranges from 0-40

Scores Ranging from

0-13 : Low stress

14-26 : Moderate Stress

27-40 : Would be perceived Stress.

The answers were compared to derive their stress level.

General Health Questionnaire (GHQ-12) of Goldberg and Paul William (1970) was used

The format of full GHQ 12 (12 items) was distributed and the Data’s were collected.

Sample collection and Processing:

Blood samples were collected from the employees in fasting condition to estimate their Fasting blood sugar and cortisol levels, then the employees were asked to have their breakfast and two hours post prandial sample was collected to assess their PPBS. The fasting samples were collected around 9.0am. The employees were made to relax and the sample collection was done with minimal stasis and pain. Blood was drawn aseptically from the antecubital vein using BD 21 G flash back needles and vacutainers, Silica Clot activator plain tube was used for serum cortisol and BD Fluoride Oxalate tube for blood sugar estimations. The blood samples for 250 employees were collected in batches in the time period of One month and the investigations were carried out on the same day of blood collection.

Analytical methods:

Blood sugar estimation was done using Glucose oxidase method using fully automated chemistry analyser Biolis 50i belonging to Tokyo Boeki Japan. Proper quality controls were done using Biorad Qc sera. Level 1 and Level 2 controls were run prior to the test sample. The reference range of Blood sugars were fasting Blood sugar 80-110mg% and PPBS upto 139mg%. The subjects sample was analysed and their results were recorded immediately.

Serum cortisol was estimated quantitatively by chemiluminsence immunoassay (CLIA) technique using Architect i system pertaining to ABBOTT USA.

The ARCHITECT Cortisol assay is a delayed one-step immunoassay for the quantitative determination of cortisol in human serum, plasma or urine using CMIA technology with flexible assay protocols, referred to as Chemiflex. Sample and anti-cortisol coated paramagnetic microparticles are combined to create a reaction mixture. Cortisol present in the sample binds to the anti-cortisol coated microparticles. After incubation, cortisol acridinium-labeled conjugate is added to the reaction mixture. The cortisol acridinium-labeled conjugate competes for the available binding sites on the anti-cortisol coated microparticles. Following a second incubation, the microparticles are washed, and pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of cortisol in the sample and the RLUs detected by the ARCHITECT i System optics.

Proper calibration and Quality control protocols were followed. The reference range for morning Serum cortisol samples taken between 9.0–10.0 am is 3.7– 19.4µg/dl. The Architect Serum cortisol assay kit has the allowable sensitivity and specificity to perform the immunoassay. The patient samples were run according to the recommended protocol and the results were recorded immediately.

Statistical analysis:

The statistical analysis was performed using Pearson correlation 2 tailed test with the 95% Confidence interval for proportion (p) was calculated using the formula p± 1.96√(pq/n) and the 95% confidence interval for mean (μ) was calculated using the formula μ±1.96σ/√n. Relationship between cortisol blood sugar and perceived stress were determined using Pearson correlation analysis.

RESULTS AND DISCUSSION:

Diabetes is a rapidly rising factor globally, and the relation of work stress in workplace to diabetes and Prediabetes need to be well investigated. Diabetes being one of the most common non communicable diseases, its prevalence is increasing day by day worldwide. The International Diabetes federation estimated 366 million people are with diabetes in 2011 and is expected to rise to 552 millions in 2030.⁸

Many emerging literatures suggest that stress plays a role in the aetiology of T2DM as a predictor and also as a prognostic factor. Stress has been identified as an increasingly risk factor for disease onset. The psychological stress induces the biological responses in T2DM thereby releasing glucose and lipids into the circulation, and it also releases the inflammatory cytokine and increase the blood pressure. Chronic stress leads to the dysregulation of glucose metabolism and neuroendocrine function and chronic lowgrade inflammation, this dysregulation may lead to the onset of T2DM. The adverse effect of psychological stress on health behaviour such as the choice of food, physical activity and adhering to medication is also said to contribute to the development of T2DM. Stress contributes to the poor glycemic control and cardiovascular complications among individuals who has established diabetes. However stress management mediation attenuates the stress symptoms in T2DM but its effects on disease progression have not been effective⁹. Hypertension is seen in about 60 % of T2DM cases. Both hypertension and dyslipidaemia in T2DM contributes to the increased risk of coronary artery diseases (CAD). In T2DM patients the risk of CAD is considered 2.3 times in men and 2.9 times in women¹⁰.

The present study was conducted to assess the impact of occupational stress on the blood glucose and cortisol levels in factory workers. The study reveals a positive association between stress score and cortisol levels. The stress score was not found to vary with work experience. Interestingly, workers with less than 10 years experience were found to have comparatively high cortisol levels, indicating that adaptation to work tends to decrease any aggravation in occupation stress.

Existence of correlation between the parameters studied to evaluate stress induced diabetes was analysed using Pearson’s correlation. The analysis revealed statistically significant low correlation the age of workers and their fasting blood sugar levels. The fasting blood sugar levels and post-prandial blood sugar levels were statistically significant (p˂0.05) and highly correlated.

The increase in cortisol levels could be correlated with increased fasting blood glucose and post-prandial glucose levels. The correlation was found to be statistically significant (p˂0.01).

Thus this study reveals that occupational stress causes Type 2 diabetes and a moderate correlation exists between the levels of cortisol and blood sugar. The results of this study are supported by few other reported studies around the world.

Mental stress in its acute state significantly alters the course of glucose concentration following the intake of a standard meal. In an induced stress study of type 2 DM and normal individuals the glucose concentration on control patients and stress day in patients with type 2 diabetes started to deviate even before the time point at which the stress task was applied, the reason was found out to be the changes in blood pressure and the heart rate in the minutes just before the stress test. This change had an effect on glucose concentration only in the individuals with residual insulin secretion who are said to have T2DM.

In healthy subjects whose metabolic activity is normal acute postprandial psychological stress seemed to induce a temporary insulin resistance.

Table 1. Parameters analysed for stress induced Type 2 diabetes in workers

Parameter	Work experience (years)
Parameter	0-10	11-20	21-30
Cortisol (µg/dl)	27 ± 2.1	22 ± 1.3	24 ± 3.1
Fasting blood sugar (mg/dl)	108 ± 2.6	109 ± 3.8	109 ± 4.2
Post-prandial blood sugar (mg/dl)	135 ± 1.7	135 ± 2.6	135 ± 3.6
Stress score	20 ± 1	16 ± 2	21 ± 2

Table 2. Correlation between age, cortisol and blood glucose levels

		Age	Cortisol	FBS	PPBS
Age	Pearson Correlation	1	-.054	.148^*	.102
	Sig. (2-tailed)		.403	.022	.118
	N	248	243	240	238
Cortisol	Pearson Correlation	-.054	1	.098	.177^**
	Sig. (2-tailed)	.403		.133	.007
	N	243	243	235	233
FBS	Pearson Correlation	.148^*	.098	1	.726^**
	Sig. (2-tailed)	.022	.133		.000
	N	240	235	240	238
PPBS	Pearson Correlation	.102	.177^**	.726^**	1
	Sig. (2-tailed)	.118	.007	.000
	N	238	233	238	238

*. Correlation is significant at the 0.05 level (2-tailed). **. Correlation is significant at the 0.01 level (2-tailed).

This was thought to be attributed to glucose induced reduction in peripheral muscle perfusion followed by impaired peripheral glucose clearance.¹¹ Diabetes Mellitus a chronic metabolic disorder characterised by hyperglycemia either due to defective insulin secretion or resistance to insulin action which alters the metabolic activity of the body.¹².

The Life style pattern remain as the corner stone of diabetes management, individually they are often insufficient to patients to maintain their normal blood glucose levels.¹³, the quality of life that people live in plays a major role in disease management mainly diabetes has a strong impact on quality of life. People with diabetes rate their quality of life significantly less when compared to non diabetic which causes stress and thereby increasing the release of stress hormone serum cortisol.¹⁴

A study conducted on the association of morning serum cortisol with glucose metabolism and diabetes hypothesized that morning serum cortisol was positively associated with glycemic measures and prevalent T2DM. Cross sectional association of morning serum cortisol with fasting plasma glucose and haemoglobin A1c, assessment of insulin resistance, beta cell function was done using linear regression model adjusting age sex, education, occupation, systolic blood pressure, waist circumference, physical activity, smoking and beta blocker hormone therapy and cortisol collection time. The result of which showed that higher morning serum cortisol was associated with higher fasting plasma glucose and HbA1c in participants with diabetes, and among all the participants higher cortisol was associated with higher odds of T2DM and hence proves that high morning serum cortisol had a positive association with impaired glucose metabolism.¹⁵

The presence of enhanced cortisol secretion was found to be associated with the complications and metabolic control of diabetes and also depends on diabetes duration. A logistic regression analysis proved that this complication was also significantly associated with sex, duration of diabetes and glycated haemoglobin. This glucocorticoids secretion has also been found to have a possible link between insulin resistance and the features of metabolic syndrome and hypothalamic pituitary and adrenal axis function. It was also discussed that the HPA activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and the number of diabetic complications.¹⁶ The poor glycemic control also attributed to incidence of anemia in type 2 DM. The routinue haematological investigations are required for correction of anemia in patients with poor glycemic control.¹⁷

Many studies have proved that depression related to work stress has a clear association with both prevalent and incident diabetes, but the link between measures of stress and diabetes is less clear, this may be due to the difference in the measurement of stress and the altered effects of different form of stress on the HPA axis. This HPA axis dysregulation acts as an important biological link between stress depression and diabetes, and it mainly depends on the flatter or blunted diurnal cortisol curve, this is also an important feature for incident diabetes and cardio metabolic risk. HPA axis dysregulation can be a critical link in the high prevalence of co-existing depression and diabetes. T2DM is characterised by disruption of stress- related process with multiple biological systems and prolonged exposure to life stress. The understanding of association between stress, depression and diabetes can be improved once the appropriate biological targets are identified and the interventions are focussed at the HPA axis.¹⁸

In a cohort study conducted among German industrial workers, where the work stress was measured by Effort – Reward Imbalance (ERI) Questionnaire, and their diabetic status was measured by FBS and glycated hemoglobin A1c, the findings clearly indicated that work stress in terms of ERI is associated with diabetes and prediabetes. The association of work stress is also consistent and robust with heart rate variability, altered blood lipids, risk of metabolic syndrome and also has a significant relationship with blood pressure, variability in immune function, inflammation, and specifically in cortisol release and haemostatic biomarkers.¹⁹

A study conducted among Law enforcement officers to find out the interrelationship among physical activity, perceived stress and metabolic syndrome concentrating to find out if the stress and metabolic syndrome gets modified by physical activity finally it was hypothesized that high perceived stress significantly increases the metabolic syndrome risk factors but high levels of physical activity attenuates this relationship.²⁰ Stress has always been a critical issue with patients suffering with DM the factor which needs to be identified and managed as a part of comprehensive care and physical activity was found to promote feelings of well-being and reduce stress. Studies have shown a positive association between lack of physical activity and poor mental well being such as stress, depression and anxiety. In turn physical activity and recreation becomes a coping strategy to maintain their blood sugar for the patients with DM having stress.²¹

Clinical Conditions and Excessive cortisol secretion is well associated with profound metabolic disturbances which results in abdominal obesity, insulin resistance, and low HDL cholesterol level, and this can lead to diabetes. Diabetes is a common complication having chronic exposure to excess glucocorticoids and it becomes an important factor for the morbidity and the mortality of the patients with endogenous hypercortisolism. These glucocorticoids cause variation in Beta cell functions reducing the insulin sensitivity. Better understanding of the mechanism of glucocorticoids induced glucose alteration can make way to the development of novel therapeutic anti inflammatory drugs with reduced impact on glucose metabolism.²²

In addition to it, type 2 DM being a chronic systemic disease with high level of blood glucose and is only one component of pathological process and cause for other clinical manifestations associated with the disease, preventive measures have to be taken to reduce the occurrence of the diabetes for which structured Teaching program on knowledge regarding T2DM will be effective²³, as diabetes poses as a prime challenge to all the people all over the world prevention measures have to be taken, by frequent screening, proper interventions, life style changes, physical activity and healthy control diet²⁴ and above all should learn to lead a stress free life to avoid the recurring exposure to high cortisol which will impair insulin activity and invariably lead to insulin resistance and beta- cell exhaustion²⁵ and regarding T2DM the public and professional awareness of the risk factors of the disease, its symptoms are the important ladders towards prevention and control.²⁶

CONCLUSION:

This study tried to establish a correlation between work stress and the levels of blood glucose and cortisol levels. The results of this study indicate that stress is not exacerbated by experience and that occupational stress is associated with increase in glucose levels both fasting and post-prandial. Moderate correlation exists between cortisol levels and blood glucose levels. In this study out of 250 employees, around 6.8% of the employees have found to have perceived stress and 64.8% has moderate stress, out of which 18% of the employees showed high cortisol secretion level.

CONFLICT OF INTEREST:

Nil

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Received on 10.06.2019 Modified on 08.07.2019

Research J. Pharm. and Tech. 2020; 13(1): 27-32.

DOI: 10.5958/0974-360X.2020.00005.0