A cross-sectional study on the role of stress in hyperglycemia and the effect of Mahatiktaka Kashaya (an Ayurvedic formulation) in its management.

BACKGROUND: Stress is a potential contributer to chronic hyperglycemia. Pitta Prakriti (body constitution) individuals are more prone to stress and the prevalence of type 2 diabetes in stressed out individuals is much more. Aim of study was to evaluate the role of stress in hyperglycemia in individuals of Pitta predominant constitution and to assess the effectiveness of Mahatiktaka Kashaya in stress-induced hyperglycemia.
METHODOLOGY: A cross-sectional study was carried out in 100 Pitta predominant patients having fasting blood sugar level greater than 140 mg/dl, to find the association of stress and hyperglycemia, using International Stress Management Association questionnaire followed by open lebelled clinical trial with Mahatiktaka Kashaya (Decoction). Trial drug was administered at a dose of 15 ml twice daily for 14 days. Assessment was done before and after the treatment. OBSERVATION AND ANALYSIS: 80% of Pitta predominant individuals have reported stress-associated hyperglycemia. Overall effect of Mahatiktaka Kashaya in major domains of Stress Assessment Questionnaire, i.e., symptoms, stability and strategies was significant. Furthermore, the trial drug showed significant improvement in biochemical parameters of diabetes.
CONCLUSION: The study concludes that there is significant association between stress and hyperglycemia in the individuals of Pitta constitution. Mahatiktaka Kashaya is found to be highly significant in stress-associated hyperglycemia in the above said group. Copyright:

Introduction

“Stress” can be defined as any situation which tends to disturb the equilibrium between a living organism and its environment.[1] Stress is a part of life and is necessary for providing challenge to physiological and psychological development. However, too much stress over a period of time combined with poor coping habits may cause physical, chemical and hormonal imbalances in the body, thus leading to disease and death if left unchecked.[2] Stressors can be divided into two categories, external and internal causes. Family and relationship stressors, work stressors, etc., come under external causes and factors such as uncertainty or worries, low self esteem, self criticism, excessive anger and unrealistic expectations come under internal causes.[3] Stress is a potential contributor to chronic hyperglycemia in Madhumeha (type 2 diabetes). Exposure to stress stimulates the hypothalamic–pituitary–adrenocortical (HPA) axis causing release of various hormones, resulting in elevated blood glucose level.[4] It has major effects on metabolic activity as well. Signs of stress can be defined at cognitive, emotional, physical or behavioral level.[5]

In ayurvedic classics, Prakriti (psychosomatic constitution) is the sum total of anatomical, physiological and psychological factors, which plays an important role in the prognosis of disease and response to the treatment. It is a genetically transmitted trait.[6] Pitta predominant constitutions are said to be more vulnerable to psychological stress.[7] The prevalence of type 2 diabetes in stressed individuals is 2.6% in males and 2.1% in females. Significantly larger proportion of type 2 diabetes individuals had severe stress scores (23.4% vs. 10%; P < 0.001) compared to healthy controls.[8]

Mahatiktaka is a Ghrita Yoga (ghee-based formulaton) mentioned in Kushtha Chikitsa.[9] In routine clinical practice also, the Kashaya (decoction) form of this formulation is found to be effective in Madhumeha, especially when associated with stress. Further, it is ideal to prescribe Kashaya form of any preparation for long-term usage, especially in Kleda (excretory portion of body fluids)-predominant clinical conditions. The Kashaya formulation ensures Kleda Shoshana (reduction of Kleda) by virtue of its inherent action of taste. Mahathiktaka Kashaya is also practised for long term effectively in major types of Kushtha (skin disorders) which is also a Kleda (liquid waste prodecct) predominant disease. The Kashaya Yoga is found to be more cost-effective when compared with medicated Ghrita in routine clinical practice. Amalaki juice (Emblica officinalis Gaertn.) is the main ingredient in this formulation and is widely practiced for various mental illness. Details of the formulation are enlisted in Table 1.

Table 1

Ingredients of Mahatiktaka Kashaya

Sanskrit name	Botanical name	Part used	Quantity
Saptacchadha	Alstonia scholaris Linn	Twaka (bark)	1 part
Parpata	Hedyotis corybosa Linn	Samoola (whole plant)	1 part
Aragwada	Cassia fistula Linn	Twaka (bark)	1 part
Katuki	Picrorhiza kurrooa Royle ex Benth	Samoola (Whole plant)	1 part
Vacha	Acorus calamus Linn	Kanda (rhizome)	1 part
Haritaki	Terminalia chebula Retz	Phala Twaka (fruit pericarp)	1 part
Amalaki	Emblica officinalis Gaertn	Phala Twaka (fruit pericarp)	2 part
Vibitaki	Terminalia bellirica Roxb	Phala Twaka (fruit pericarp)	1 part
Padmakam	Prunus poddum Franch	Kashta (stem)	1 part
Patha	Cyclea peltata Hook. Fil and Thoms	Kanda (rhizome)	1 part
Haridra	Curcuma longa Linn	Kanda (rhizome)	1 part
Darvi	Coscinium fenestratum (Gaertn) Colebr	Kashta (stem)	1 part
Sariva	Hemidesmus indicus Linn	Mula (roots)	1 part
Shatavari	Asparagus racemosusWilld	KandhaI (rhizome)	1 part
Patola	Trichosanthes lobata Roxb	Patra (leaves)	1 part
Bramhi	Bacopa monnieri Linn	Samoola (Whole plant)	1 part
Vishala	Citrullus colocynthis Linn	Samoola (Whole plant)	1 part
Pippali	Piper longum Linn	Phala (fruits)	1 part
Gajapippali	Scindapsus officinalis Schoott	Mula (roots)	1 part
Nimba	Azadirachta indica A. Juss	Twaka (bark)	1 part
Chandana	Santalum album Linn	Sara (heart wood)	1 part
Yashtimadhu	Glycyrrhiza glabra Linn	Kashta (stem)	1 part
Ashwattha	Ficus religiosa Linn	Twaka (bark)	1 part
Kutaja	Holarrhena antidysenterica Roxb	Twaka (bark)	1 part
Guduchi	Tinospora cordifolia Willd	Kashta (stem)	1 part
Kiratatikta	Swertia chirata Linn	Samoola (whole plant)	1 part
Ushira	Vetiveria zizanioides Linn	Mula (roots)	1 part
Vasa	Adhatoda vasica Nees	Patra (leaves)	1 part
Murva	Andrographis paniculata Wall. Ex Nees	Mula (roots)	1 part
Ativisha	Aconitum heterophyllum wall	Kanda (rhizome)	1 part
Musta	Cyperus rotundus Linn	Samoola (whole plant)	1 part
Duralabha	Fagonia cretica Linn	Samoola (whole plant)	1 part

As stress has a siginificant impact on hyperglycemia, it needs to be addressed. Very limited research works are carried out in relation to Prakriti-based treatment strategy. Hence, a cross-sectional study was planned in this background to find the association between stress and hyperglycemia in individuals of Pitta constitution. A clinical study was also conducted in this milieu to evaluate the effect of Mahatiktaka Kashaya in stress-associated hyperglycemia in Pitta-predominant constitution.

Aims and objectives

To evaluate the role of stress in hyperglycemia in the individuals of Pitta-predominant constitution

To assess the effectiveness of Mahatiktaka Kashaya in stress-induced hyperglycemia.

Methodology

Two types of study design were used in the current work. A cross-sectional study and an open clinical trial were conducted in patients visiting the outpatient department of Kayachikitsa, Vaidyaratnam P.S. Varier Ayurveda College, Kottakal, Kerala, India.

Cross-sectional study design

This was carried out to find the association of stress and hyperglycemia among Pitta-predominant individuals.

Sample size

One hundred patients (25–60 years age group).

Inclusion criteria

Pitta-predominant individuals with fasting blood sugar (FBS) level above 140 mg/dl

Age between 25–60 years irrespective of gender and religion

With informed consent.

Exclusion criteria

Patients having psychiatric illness and undergoing antipsychiatric medication.

Survey tools

Specially formulated questionnaire for Prakriti analysis

It includes 10 major characters of all the three constitutions

International Stress Management Association (ISMA) questionnaire.

To calculate the stress score, ISMA questionnaire containing 25 questions was used. According to the symptoms present in the individuals, the score is given. The score above 14 is suggestive of stress and stress-related diseases.

Open lebelled clinical trial

The trial drug Mahatiktaka Kashaya was given for 14 days in 30 patients. Assessment was done before and after the treatment. Total scores before and after the medication were statistically analyzed.

Study design – Open lebelled randomized clinical trial.

Age group – 30–60 years.

Dose – 15 ml.

Administration – With 45 ml lukewarm water twice daily before food.

Investigations

FBS

Postprandial blood sugar (PPBS).

Patients having blood sugar level (FBS 140–200 mg/dl) fulfilling criteria for Pitta-predominant constitution after getting informed consent

ISMA stress score >14

Age between 30 and 60 years.

Patients having psychiatric illness and under antipsychiatric medications

Gestational diabetes

Juvenile diabetes

FBS >200 mg/dl

Pregnant and lactating women.

Assessment

Evaluation of stress through Stress Assessment Questionnaire (SAQ) before and after the treatment

Assessment of biochemical parameters like FBS and PPBS before and after the treatment.

Interpretation of the data

The outcome was measured, and data were statistically analyzed using student “t”-test with two-tailed paired sampling.

Ethical clearance – IEC/CL/06/12 dated 19/05/12.

Observation and analysis

Cross-sectional study

One hundred individuals of Pitta-dominant Doshika constitution were selected for the study. Of the 100 individuals, 55 had FBS in-between 140 and 160 mg/dl, 29 within the range 160–180 mg/dl and 16 within the range of 180–200 mg/dl of FBS. Majority of the individuals were having FBS in-between 140–160 mg/dl. Fifity-five percent had PPBS within the range 200–225 mg/dl, 20% within the range of 225–250 mg/dl, 14% within the range 250–275 mg/dl and 11% within the range of 275–300 mg/dl of PPBS, respectively. Of 100 people, 80% had ISMA stress score >14 and the remaining 20% had stress score <14.

Among 85% of total Pitta predominance Prakriti persons (with Pitta character ≥7), 18% were having FBS >170 and 67% were having FBS between 170 and 120. Among them, 76% were having stress score >14 and 9% <14. Forty-nine percent of the Pitta Prakriti with stress score ≥14 were having FBS ≥170 and 31% of Pitta Prakriti with stress score ≥14 were having FBS between 170 and 120 (mg/dl). In the present study, the association between stress and hyperglycemia and between Pitta Prakriti and hyperglycemia was calculated and a significant association was observed. 80% of Pitta-predominant individuals have reported stress-associated hyperglycemia [enlisted in Tables 2-4].

Table 2

Association between Pitta Prakriti and fasting blood sugar level

FBS	Pitta character		Total	χ2	P
	>7	<7
>170	18	04	22	13.82	<0.001
<170	67	11	78
Total	85	15	100

FBS: Fasting blood sugar

Table 4

Association of blood sugar level with Pitta Prakriti and stress

Parameters	Score (%)	FBS level (mg/dl)
Pitta character >7	49	≥170
Stress score >14	39	120-170

FBS: Fasting blood sugar

Effect of therapy showed significant result in biochemical values. 11.87% and 14.6% relief were observed in FBS and PPBS respectively [Table 5].

Table 5

Percentage of improvement in blood sugar level

Parameters	Mean score		SD	Percentage of relief	t	P
	BT	AT
FBS	166.03	146.33	13.56	11.87	7.96	<0.001
PPBS	232.43	199.17	25.73	14.3	7.08	<0.001

BT: Before trial, AT: After trial, SD: Standard deviation, FBS: Fasting blood sugar, PPBS: Postprandial blood sugar

Overall effect in major domains of SAQ are 5.85% relief in symptoms, 4.76% improvement in stability and 16.34% improvement in strategies, respectively. Mean BT score was reduced from 21.21 to 19.96 with 5.85% relief. The improvement found in this domain is mainly due to the psychological counseling (psycho-education) given to the patient during the period of intervention [Tables 6, 7 and Graph 1].

Table 6

Effects of Mahatiktaka Kashaya in major domains of stress assessment questionnaire

Parameters	Mean score		SD	Percentage of relief	t	P
	BT	AT
Symptoms
Emotion	6.83	5.4	1.22	20.94	6.42	<0.001
Behavior	7.16	5.20	0.99	27.45	10.78	<0.001
Physical	7.33	5.57	0.89	24.11	10.78	<0.001
Stability
Procrastination	7.06	5.73	1.09	17.5	6.68	<0.001
Perfectionism	6.73	5.53	1.09	17.83	6	<0.001
Self-esteem	7.27	5.8	5.8	7.27	7.07	<0.001
Depression	7.43	5.46	0.85	26.47	12.69	<0.001
Anxiety	7.43	5.57	1.07	25.12	9.52	<0.001
Strategies
Social support	4.06	6	1.46	47.89	7.25	<0.001
Self-regulation	4.28	5.93	1.24	39.06	7.36	<0.001
Problem-solving	4.57	6.53	1.33	43.07	8.12	<0.001
Distraction	4.27	6.27	1.44	46.87	7.61	<0.001
Health	4.7	7.7	1.8	63.83	9.12	<0.001

BT: Before trial, AT: After trial, SD: Standard deviation

Table 7

Overall effect of Mahaatiktakam Kashayam on symptoms, stability and strategies

Features	BT	AT	SD	Percentage of relief	t	P
Symptoms	21.21	19.96	0.58	5.85	11.6	<0.001
Stability	35.52	33.82	1.01	4.76	9.06	<0.001
Strategies	21.79	25.34	2.11	16.34	9.05	<0.001

BT: Before trial, AT: After trial, SD: Standard deviation

Graph 1

Percentage relief of domains in SAQ (in open trial)

Discussion

Stress and hyperglycemia

Role of stress in the onset of type 2 diabetes in individuals predisposed to diabetes and in blood glucose control in people with established diabetes is already proved.[11] Activation of HPA axis causes release of increased amounts of glucocorticoids, in particular cortisol, enhances gluconeogenesis in the liver and diminishes cellular glucose uptake. It also leads to immunosuppression.[12] Stress-induced release of growth hormone can also decrease glucose uptake and fi-endorphin will suppress insulin secretion and elevate glucose levels.[13] Therefore, stressful stimuli has impact on glucose levels through numerous pathways. Eventually, elevated blood glucose levels by themselves impair the ability of pancreas to respond to glucose stimulus.[14] Stress management and progressive muscle relaxation have been shown to be very effective in the treatment of disorders with a psychophysiological component.[15]

Discussion on demographic data

Among 100 participants, majority of participants (48%) belong to 40–50 years of age group. Female participants accounts for 53% and male participants constitute 47% of survey population. Moreover, the prevalence of moderate stress was estimated to be highest in the 40–44 years age group. The major stress sources were parenting, relationship, incident and work.

A significant association between stress and hyperglycemia was detected in individuals of Pitta constitution. Among the three types of constitution, Pitta Prakriti individuals are more prone to stress and other emotional disturbances, as they are described as Klesha Asahishnava (inability to face difficult situation) and Kshiprakopaprasada (short tempered and easily delighted).[16] Among various types of Pitta, mainly Saadhaka Pitta plays a role in immediate response and has a close association with the psychological functioning of the body.[17] Moreover, in the etiopathogenesis of Paittika Prameha, involvement of Santapa (grief), Shrama (exertion) and Krodha (anger) are explained.[18] Anger, particularly anger temperament, is associated with the onset of type 2 diabetes. Due to the abovesaid reasons, Sadhaka Pitta gets vitiated very faster, which is directly connected with the formation of Ojas and leads to Ojakshaya. In this situation, the person cannot respond appropriately to a given situation, named stress. Continuous stress alters the quality of Apara Ojas (innate immunity). This will result in the faster manifestation of Pittaja Prameha (stress diabetes) due to Ashukaritwa (rapid action) of Pitta.[19]

Clinical trial

Maximum number of patients were in 40–50 years age group. 100% of participants reported fluctuating FBS level and 80% were free from family history of diabetes. 70% had unhealthy food habits and low exercise levels.

Mahatiktakakashaya is found to be highly significant in stress-associated hyperglycemia in Pitta constitution. Mahatiktaka Gritha is effective in various ailments including Unmaada (insanity), Apasmara (epilepsy), Kushtha (skin disease), Hridroga (heart disease), and in all Pitta Vikaara (disorders due to imbalance in Pitta Dosha). This is widely practiced for psychological conditions as well. In a dissertation study on the efficacy of Mahatiktaka Gritha in Krodha (anger) with special reference to Paittika Unmaada (insanity), significant effect was noticed.[20] As the current work is on Madhumeha, it is better to administer the above Yoga in Kashaya form. In Madhumeha (Prameha) where the patient is not suitable for Shodhana (purification), Shamana chikitsa (pacification), in the form of Kashaya or Mantha can be administered.[21] Hence, Mahatiktaka Gritha formulation was modified to Kashaya Kalpana and administered. As the Yoga has Sheeta (cold) and Kleda Shoshana (obserption of waste liquid) property, it can alleviate the Ushna (hot in potency) and Tikshna Gunavriddhi (penetrating property) of Pitta. Furthermore, while addressing the Pitta Kopa (vitiation of Pitta) the correction of Dravarupa Pitta Vriddhi (increased state of Pitta) is met along with Kledasamaavastha. Further Samprapti leading to the development of hyperglycemia can be arrested by normal functioning of Saadhaka Pitta and Ojas.

Conclusion

In this current era, stress has a key role in the etiopathogenesis of diabetes. The present study proves that hyperglycemia which occurs in individuals of Pitta constitution is primarily stress induced. Furthermore, the effectiveness of the trial drug “Mahatiktaka” which is indicated in mental disorders is highly significant in stress-associated hyperglycemia in Pitta constitution. This shows the importance of stress evaluation while treating a diabetic patient. The treatment varies depending on the factors such as nature of the stress and Prakriti of the individuals.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 3

Association between stress and fasting blood sugar level

FBS	Pitta character		Total	χ2	P
	>7	<7
>170	49	04	53	10.82	<0.001
<170	31	16	47
Total	80	20	100

FBS: Fasting blood sugar