IABS Delhi 2016

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Clinical Trial

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A Clinical Trial to evaluate the Hypoglycemic, antioxidant and antidyslipoproteinemic Activities of Tinospora cordifolia in Management of Type2 Diabetes Mellitus :

A Clinical Trial to evaluate the Hypoglycemic, antioxidant and antidyslipoproteinemic Activities of Tinospora cordifolia in Management of Type2 Diabetes Mellitus Dr Vishnu Kumar Associate Professor, Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Lucknow-226003 [email protected]

INTRODUCTION:

INTRODUCTION Type 2 Diabetes Mellitus (T2DM) is a cluster of abnormal metabolic paradigms with the essential feature of hyperglycemia and is dubbed as the disease of “premature ageing”. Incidence of T2DM is rising all over the world at worrying rate, despite, comprehensive and coordinated efforts of World Health Organization (WHO), International Diabetes Federation and Several Social Science Agencies.

AIM:

AIM To evaluate efficacy of T. cordifolia in managemnt of diabetic dyslipoproteniemia

OBJECTIVES:

OBJECTIVES To assess fasting glucose in plasma To assess HbA1c and serum antioxidant enzymes in lysate To estimate sub fractions of β and α lipoproteins in serum To assess oxidative stress in serum

MATERIAL AND METHODS:

MATERIAL AND METHODS Selection of Healthy Human Volunteers: 60 healthy control (Male-30, Female-30), age 45 to 55 years, BMI 18-22.9 were served as Control. These individuals attended the outpatient department for their periodical health checkup.

Selection of T2DM Patients :

Selection of T2DM Patients 120 type 2 diabetic patients (Male-60, Female-60) were selected from Diabetes Outpatient Department of, Kaya Chikitsha Vibhag , Rajkiya Ayurvedic Chikitsha Mahavidyalaya , Touriya Ganj , Lucknow . This research program was approved by the Ethical Committee and supervised by Prof. Dharam Raj Singh, HOD, Kaya Chikitsha Vibhag .

Exclusion Criteria:

Exclusion Criteria Patients with evidence of acute or chronic inflammatory conditions, infectious disease, hypertension, cancer, persons on insulin or other medications that could affect glucose metabolism were excluded. Pregnant and lactating women were also not included in the study.

Inclusion Criteria:

Inclusion Criteria Both males and females between 45 - 55 years of age, BMI 23-24.9, fasting blood glucose 145 – 155 mg/dl, were included in the study. All diabetic individuals were subjected to a complete medical evaluation by a physician including recording a full medical history and physical examination.

Study Design :

Study Design Subjects were divided in to three groups of 60 subject each, with the following conditions: Group 1: Healthy Control: 20 minute brisk walk/day with Balance Diet Group 2: Diabetic Control: 20 minute brisk walk/day with low carbohydrate Diet Group 3: Diabetic treated: 20 minute brisk walk/day, low carbohydrate diet with T.cordifolia stem powder (50 mg/ kg body weight/ day/ oral macerate with water) This study was run for 15 days.

Collection of blood samples :

Collection of blood samples Fasting blood samples were collected, before and after the study period, from the ante median cubital vein of the subjects following overnight fasting, using disposable plastic syringes with all aseptic precautions. Blood was transferred immediately in to a dry clean plastic test tube with a gentle push to avoid hemolysis . Blood was collected from all three groups, for biochemical estimations in fluoride (sodium fluoride and potassium oxalate, 5.4 mg NaF and 3.0 mg K-oxalate in each vial), EDTA (3 mg/ vial) and plain vials.

RESULTS:

RESULTS Effect of T. cordifolia stems powder on fasting blood sugar, Glycosylated Hemoglobin, serum Lecithin Cholesterol Acyl Transferase and serum lipid profile in type-2 diabetic patients.

Slide12:

Experimental Schedule BMI (Kg/m 2 ) FBS mg/dl HbA1c LCAT LIPID PROFILE TC mg/dl TG mg/dl LDL-TC mg/dl VLDL-TC mg/dl HDL-TC mg/dl Healthy Control 18-22.9 92.26  9.05 4.98  0.53 79.54  14.97 200.26  21.67 110.06  20.18 127.24  24.57 21.89  7.56 49.80  9.17 Type-2 Diabetic Control 23-24.9 144.40  10.86*** (+ 57%) 6.95  0.78 *** (+ 40%) 65.78  13.18 *** (- 17%) 268.53  11.36*** (+34 %) 175.00  28.01*** (+59 %) 201.17  14.42*** (+58 %) 35.00  5.60*** (+60%) 30.53  4.44*** (-39%) Type -2 Diabetic+ T. cordifolia 23-24.9 130.97  14.14** (-9%) 5.87  0.83NS (- 14%) 71.23  12.74 (+8%) 237.46  13.77* (-13%) 143.23  23.64** (-18%) 178.79  17.10 NS (-11%) 28.60 * *  4.85** (-18%) 34.76  4.36 NS (+12.0%)

Slide13:

Effect of T. cordifolia stems powder on serum lipoprotein profile in type-2 diabetic patients

Slide14:

Experimental Schedule VLDL LDL HDL TC mg/dl PL mg/dl TG mg/dl Apoprotein mg/dl TC mg/dl PL mg/dl TG mg/dl Apoprotein mg/dl TC mg/dl PL mg/dl TG mg/dl Apoprotein mg/dl Healthy Control 21.89  7.56 37.50  3.99 39.10  3.95 16.85  1.04 124.16  14.42 29.55  2.11 27.12  1.11 27.13  1.61 46.80  9.17 82.55  9.35 18.47  1.79 183.83  11.34 Type-2 Diabetic Control 35.00  5.60*** (+ 60 %) 87.50  7.48*** (+ 133 %) 58.76  5.70*** (+ 59 %) 18.00 NS  0.57 (6.8 %) 201.17  14.42 *** (+ 62 %) 70.59  7.43*** (+ 139 %) 33.21  6.29*** (+ 23 %) 30.55  1.46* (12.6 %) 30.53  4.44*** (- 34%) 62.52  6.27*** (- 24.26 %) 16.55 NS  1.28 (-10.39 %) 137.42  12.33*** (-25.31%) Type -2 Diabetic+ T. cordifolia 28.60  4.85** (- 18%) 68.18 ± 6.51 *** (- 22%) 50.29 ± 4.85* (- 14%) 17.36 NS ± 6.80 (- 3.5%) 178.79 ± 17 .0* (- 11%) 53.41 ± 4.90*** (- 24%) 25.66 ± 4.28*** (- 23%) 28.90 ± 1.44 NS (- 5%) 32.76 ± 4.36 NS (+ 7%) 66.82 ± 2.90 NS (+ 7% ) 18.25 ± 1.25 NS (+ 10%) 149.80 ± 13.27 NS (+ 9%)

Slide15:

Effect of T. cordifolia stems powder on GSH, serum lipid peroxide; SOD, Catalase , GPx and GR in type-2 diabetic patients

Slide16:

Experimental schedule BMI (Kg/m 2 ) Fasting Blood sugar Glycosylated Hemoglobin (g%) Serum LCAT ( mmol /L/hr) Serum lipid profile TC (mg/dl) TG (mg/dl) LDL-TC (mg/dl) VLDL-TC (mg/dl) HDL-TC (mg/dl) Healthy Control 18-22.9 92.26  9.05 4.98  0.53 79.54  14.97 200.26  21.67 110.06  20.18 127.24  24.57 21.89  7.56 49.80  9.17 Type 2 Diabetic Control 23-24.9 144.40  10.86*** (+ 57%) 6.95  0.78 *** (+ 40%) 65.78  13.18 *** (- 17%) 268.53  11.36*** (+34 %) 175.00  28.01*** (+59 %) 201.17  14.42*** (+58 %) 35.00  5.60*** (+60%) 30.53  4.44*** (-39%) Type 2 Diabetic+ T. cordifolia (50 mg/kg b.w. p.o.) 23-24.9 130.97  14.14** (-9%) 5.87  0.83NS (- 14%) 71.23  12.74 (+8%) 237.46  13.77* (-13%) 143.23  23.64** (-18%) 178.79  17.10 NS (-11%) 28.60 * *  4.85** (-18%) 34.76  4.36 NS (+12.0%)

DISCUSSION:

DISCUSSION In India which is reeling under population distress, and where more than one third of the population lives below the poverty line with another one third subsisting on compromised economic conditions, regular health check up is not always possible due to financial constraints, lack of health awareness and inadequate health infrastructure.

Slide18:

Consequently most of the T2DM patients are detected quite late sometimes even 10-20 years after onset. Therefore, in the Indian context, diet and exercise become almost futile in most of freshly detected patients who usually require immediate therapeutic intervention. Due to economic compulsions, many patients cannot afford modern medicines.

Slide19:

Moreover, most of the modern (allopathic) medicines in DMT-2 have undesirable side effects; and no single drug can treat all the multifarious problems with rectitude. In search of a patient’s lean on other traditional systems of medicines and indeed Ayurveda is one of the most popular systems in India for several reasons.

Slide20:

Ayurveda has a centuries old tradition of Ayurvedic practitioners, saints and sages, and largely relies on medicinal herbs which are either available at low cost or available free in fields and gardens. Proven use of these herbs over many centuries certifies item non toxic with no side effects.

Slide21:

We administered the shade dried stem of this plant in hyperglycemic patients for two weeks. Let us explain rationale for two week limited administration therapy. First, it did not seem ethically prudent to keep controls on diet and exercise alone for longer period because lack of any previous health examination and tests the hyperglycemia may be persisting for a prostrated period.

Slide22:

Second, in view of its highly acclaimed value in Ayurveda and proven value in experimental animals and robust in in vitro studies

Slide23:

Interestingly the results are very encouraging. In the present study the average glycosylated hemoglobin (HbA1c) was significantly higher in patients when compare with control (p < 0.001) and so was the fasting blood sugar level, total cholesterol, LDL cholesterol, VLDL cholesterol and triglycerides levels. On the contrary shown HDL cholesterol level and lecithin cholesterol acyl transferase activity (LCAT) were significantly lower.

Slide24:

Lecithin cholesterol aceyl transferase is a vitally important enzyme helping in reverse cholesterol transport. It transfers 2 acyl groups of lecithin to cholesterol resulting in generation of cholesterol esters which are retained in core of HDL particle for final scavenging.

Slide25:

Incidentally glycosylated Hb negatively correlates with LCAT activity in T2DM patients. Apoprotein-1 is quantitatively a major component of HDL. Glycation of apoprotein A-1 in HDL alters and reduces LCAT activity in proportion to the extent of apoprotein A-1 glycation .

Biochemical Parameters :

Biochemical Parameters . Blood glucose Henry et al ., 1974 Lipoproteins:  -Lipoprotein (VLDL + LDL) and  -Lipoprotein (HDL) will be precipitated by polyanionic precipitation method of Burstein et al ., 1982. Total Cholesterol: Zlatkis et al ., 1953. Phospholipids: Fiske and Subbarow , 1952. Triglyceride: Handel et al ., 1965. Apolipoproteins Separation of apolipoproteins by their selective precipitation with TCA, alcohol and acetone method of Radding & Steinberg, 1960. Lipid-peroxides: Ohkawa et al ., 1979. Free Fatty Acids: Mosinger , 1965. Triglyceride Lipase (TGL) Activity: Mayes and Felts, 1968. Lipoprotein Lipase (LPL) Activity: Wing and Robinson, 1968. Superoxide dismutase (SOD) activity: Mc Cord et al ., 1969. Total protein: Lowry et al ., 1951. Catalase activity: Bergmeyer et al ., 1974.

CONCLUSION :

CONCLUSION Our study indicates the pivotal role of oxidative stress in pathogenesis and progression of T2DM. This study shows a significant increase in oxidative stress, β lipoproteins, blood glucose, glycosylated hemoglobin following with decrease in α lipoproteins, antioxidant enzymes, reduced glutathione and lecithin cholesterol acyl trans ferase activities were observed in T2DM patients.

However, treatment with T. cordifolia reverse all these effects.:

However, treatment with T. cordifolia reverse all these effects. Cumulatively taking all the reports on T. cordifolia’s supplement along with ours, we are of validated opinion that T. cordifolia therapy could prove on excellent substitute for multidrug therapy in modern medicine.

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