Diabetes Mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. The major etiological factors of the disease are reduced insulin secretion,decreased glucose utilization and increased glucose production. Polyuria(frequent urination),  polydipsia (increased thirst) and polyphagia (increased hunger)are the main characteristic symptoms of this disease. It is one of the initial diseases described in Egyptian manuscripts. In Ancient Ayurvedic texts this disease is described as Madhumeha, a Vataj sub-type of the disease Prameha, characterized by passing of excessive amount of turbid  urine:- “तत्राविलप्रभूतमूत्रलक्षणा:सर्व एव प्रमेहा:”1

The incidence of Diabetes has risen dramatically in the recent times presumably because of reduced activity levels and increasing obesity,and the aging of the population which are also the main etiological factors for this disease. According to latest WHO data an estimated 422 million people suffer from DM globally.2 The global prevalence of diabetes among adults has risen from   

4.7% in 1980 to 8.5% in 2014.3 The prevalence of this disease increases with the age, however in the recent times it is seen that it has started effecting the younger age groups and even adolescents are suffering from DM. India actually has the highest number of diabetics of any one country in the entire world and is emerging as diabetic capital of the world. According to International Diabetes Federation, there were 69.1 million cases of diabetes in India in 2015.

Hyperglycemia in Diabetes mellitus result either from insulin insufficiency or insulin dysfunction. Type I diabetes (insulin dependent) is caused due to insulin insufficiency because of lack of functional beta cells. Patients suffering from this are therefore totally dependent on exogenous source of insulin while patients suffering from Type II diabetes (insulin independent) are unable to respond to endogenous insulin and can be treated with dietary changes, exercise and medication. Type II diabetes is the more common form of diabetes constituting 90% of the diabetic population. AIMS AND OBJECTIVES: 

The aims and objectives behind conducting this study are:

Primary Objectives:

• To evaluate the clinical efficacy of Tryushnadi Gutika along with Mustadi Kwath in the management of Madhumeha.

• To study the etiopathogenesis of Madhumeha from Ayurveda and Modern point of view.

Secondary Objectives:

• To evaluate the safety of Tryushnadi Gutika along with Mustadi Kwatha in the management of Madhumeha.

• To compare the clinical effect of Tryushnadi Gutika along with Mustadi Kwatha & in the management of Madhumeha (Type II Diabetes Mellitus).

• To develop a safe and effective drug that can be helpful for the Diabetic community to combat the ailment.

TRIAL DRUGS REVIEW: 

Indigenous compound formulation used for the trial is TRYUSHNADI GUTIKA along with MUSTADI KWATH.

1. TRYUSHNADI GUTIKA: This indigenous compound drug formulation is described in Chakradutt for the treatment of Prameha . The contents of the formulations are haritaki,bibhitaki,amalaki,pippali,maricha,shunthi,guggulu processed in gokshura kwatha.

2. MUSTADI KASHAY : The description of this drug is available in  bhaisajya ratnavali..The contents are haritaki,bibhitaki,amalaki,haridra,murva,musta,indravaruni,lodhra.

MATERIALS AND METHODS: 

The study design is as follows: 

• Study type : Interventional

• Sub-type : Control trial

• Purpose : Treatment

• Timing : Prospective

• Masking : Open trial

• Sampling Method : Simple Random

• End Point             : Efficacy and Safety 

• Sample Size : 80 patients (20 in each group)

• Number of groups : 4 groups {A , B , C & D}

Group A: Tryushnadi Gutika 

Group B : Mustadi Kwath

Group C:Tryushnadi Gutika with Mustadi Kwath

Group D: Metformin

• Selection of Cases : O.P.D. /I.P.D.  

• Sample population : Patients from college hospital

• Duration of the Trial :           3 Months

INCLUSION CRITERIA: 

• Patients of either sex aged between 20 to 65 years. 

• If yes in any two of the four:

• Blood sugar –fasting > 126 and ≤ 250 mg/dl.

• PP > 200 mg/dl and ≤350 mg/dl.

• Glycosylated Haemoglobin (HbA1c) > 6.5% and < 10%

• Subjects having classical symptoms of diabetes with random glucose levels ≥200mg/dl (≤350mg/dl).

• Diagnosed cases of Type II Diabetics having Glycosylated Haemoglobin (HbA1c) between 6.5-9% without or {with metformin in a dose1g-1.5g/day (for Group-D)}.

•  Subjects who are able to come for follow up on fixed visits and are well aware about the treatment plan.

• Subjects willing to participate and able to provide written informed consent. 

• Diabetes Mellitus >2 years and <10 years.

EXCLUSION CRITERIA: 

• Age below 20 and above 65yrs.

• Subject of Type-I DM (insulin dependent DM) or Type-II DM on insulin/OHA’s other than metformin/ any other AYUSH medication for glucose control.

• Subjects suffering from the complications of Diabetes mellitus viz., diabetic neuropathy, diabetic nephropathy, diabetic retinopathy etc. which require an urgent treatment. 

• Uncontrolled Hypertensive subjects (BP with or without medication >140/90 mmHg after 5 min. of rest).

• Subjects with any unstable Heart disease or known cases of MI, unstable angina or CHF. 

• Patients with concurrent Hepatic Dysfunction (defined as AST and/or ALT > 2 times of the upper normal limit) or Renal Dysfunction, uncontrolled Pulmonary Dysfunction (asthmatic and COPD subjects).

• Diabetes Mellitus <2 years and >10 years.

• Subjects with current or past diagnosis of malignancy (any malignancy diagnosis in last five years).

• Subjects who have a recent history or who are currently known to abuse of alcohol or drugs. 

• Subjects suffering from major systemic illness necessitating long term drug treatment (Rheumatoid arthritis, Psycho-Neuro-Endocrinal disorders, TB, AIDS etc). 

• Female subject of child bearing potential who do not agree to remain abstinent or use medically acceptable methods of contraception during the study therapy and for 4 weeks after the end of study therapy. 

• Pregnant / Lactating women. 

• Subject on systemic or oral steroids, oral contraceptive pills or estrogen replacement therapy.

• Subjects having hypersensitivity to any of the trial drug.

• Subjects who have completed participation in any other clinical trial during the past six (06) months.

DIAGNOSTIC CRITERIA: Diagnosis will be made on the basis of symptoms given in ancient texts and modern literature. Laboratory investigations and clinical findings shall be considered for making diagnosis.  WHO criteria for diagnosis of DM are as follows:

• Symptoms of diabetes plus random blood glucose concentration ≥ 11.1mmol/L (200mg/dl) or

• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dl)

                                               or 

• Two hour plasma glucose≥11.1 mmol/L (200mg/dl) during an oral glucose tolerance test.

DRUG DELIVERY REGIMEN

*Dose of kwath will be adjusted according to ‘vyadhi Bala’ and ‘rogi bala’ (patient’s strength).

*Timing of kwath administration- 30 mins before breakfast and dinner.

DIET AND EXERCISE:

As they play an important role in the management of disease, they will be explained to the patients in details.

PARAMETERS FOR ASSESSMENT OF STUDY OUTCOMES

PRIMARY END POINT-Improvement in objective symptoms.

SECONDARY END POINT-Improvement in subjective symptoms.