Use of Plant Foods including Bitter Gourd and Fenugreek in...

Use of Plant Foods including Bitter Gourd and Fenugreek in

managing type 2 diabetes mellitus

Paturi V Rao MB BS (Andhra), MD Med (Madras, Dip Diiab (Zagreb), PhD Endo (AIIMS), FRCP (London)

Fellow, American College Endocrinology

Senior Professor and Head

Department of Endocrinology and Metabolism,

Nizam’s Institute of Medical Sciences University, Hyderabad, India

diabetes.org.in diabetes-india.com diabaid.org rssdi.in [email protected]

International Journal of Diabetes in

Developing Countries

Vol. 9 • October 1989

Editorial

Indigenous plant drugs for diabetes mellitus

Satyavati GV, Tandon N and Sharma M

Update Articles

Indigenous drugs in diabetes mellitus : prospect and

retrospect

Mukherjee SK

Traditional remedies for diabetes mellitus : trials,

trials and trilateral quest

Vaidya Ashok B, Antarkar DS and Joshi BS

Perspectives for clinical trials with indigenous drugs for

control of diabetes

Ahuja MMS

http://www.rssdi.org/1989_october/article1.pdf

. . . 48 plants http://www.rssdi.org/1989_october/article1.pdf

Table III

Major Chemical Constituents of Plants Showing Hypoglycaemic Activity

S. No. Chemical Principle Plant

1 Aminoacids Blighia sapida (Hypoglycin A) (Hypoglycin B)

2. Alcohol Bougainvillea spectabilis (Pinitol)

3. Alkaloids Catharanthus roseus (Catharanthine) (Leurosine)

(Lochnerine) (Vindoline etc.)

4. Flavonoid Pterocarpus marsupium (Epicatechin)

5. Glycosides Ficus bengalensis (Bengalenoside)

Launaea nudicaulis

6. Glycans Anemarrhena asphodeloide (Anemarans A,B,C,D)

Atractylodes japonica (Atractans A,B,C)

Dioscorea japonica (Dioscoran A,B,C,D,E,F)

Ephedra distachya Ephedrans (A,B,C,D,E)

7. Glycoproteins Moms alba (Moran A)

8. Gum guar Cyamopsis tetragonolobus

9. Mucilage Planiago asiatica

Althaea officinalis

Abelmoschus esculentus

Dioscorea batatas

10. Neutral substance Azadirachta indica (Nimbidin)

11. Oil Allium cepa

12. Peptides Momordica charantia (P-insulin)

13. Proteins Acacia melanoxylon

14. Polysaccharides Gymnema sylvestris

15. Sulphides Allium cepa (Allicin) (Allylpropyldisulphide)

16. Triterpenoids Poterium ancisroides (Tormantic acid)

http://www.rssdi.org/1989_october/article1.pdf

Individual biotinylated lectins chosen to probe glycan structures were incubated in PBS for 1 hour. Plates were washed with 1.65 ml PBST and incubated with Streptavidin-HRP (Pierce) added at a concentration of 0.1 mg/ml in PBS for 1 hour. Plates were developed with 3,3’,5,5’ tetramethylbenzidine substrate (Neogen Corporation) followed by incubation at room temperature for 5-15 min for color development. The reaction was stopped by the addition of 100 μl of 2N H2SO4. Absorbance at 450 nm was measured on a Spectramax plus microplate reader (Molecular Devices Corporation). A standard curve was generated for every ELISA plate by plotting concentrations of the known proteins samples against their absorbance values, using Softmax Pro (Molecular Devices Corporation) to estimate the concentrations. Normalized concentrations were then transformed to natural log scale. Those subjects with adequate overall protein in their samples, but ELISA values under the detectable limit for a particular protein, were assigned a value of 0.5 rather than 0 to facilitate log-transformation. When transformed to log scale, the value of -0.69 corresponded to those without any protein detected.

Direct lectin ELISA of urine: prediabetic subjects In order to determine changes in specific glycosylation patterns in the urine proteome, we have developed a direct ELISA platform. In this platform, urine samples are coated onto an ELISA plate, and global changes in particular saccharide motifs (glycotopes) are assessed by probing with biotinylated plant lectins. In the current study, we first conducted a preliminary screen of urine using lectins directed at glycotopes from different parts of glycans. Preliminary direct lectin ELISAs were conducted on pooled urine samples from each condition (control, IFG, IGT, and NDM). Relatively weak signals were observed for GSL-2 (GlcNAc-GlcNAc), HHL (polymannose), LTL (a-1,2 fucose), and VVL (O-linked GalNac). Strong signals were observed for lectins that recognized chitobiose, lactosamine, a-1,3 or a-1,6 fucosylation, and a- 2,6 sialylation.

Direct lectin ELISA of urine: prediabetic subjects We next probed a panel of urine from control subjects and patients with IFG, IGT, or newly diagnosed T2DM (NDM). When normalized for total protein concentration, a significantly greater amount of reactivity was seen in both IFG and IGT samples compared to controls using PHA-E and LEL biotinylated lectins; (p=0.0444 and 0.0039, respectively). PHA-E recognizes lactosamine (Gal-b1,4 GlcNAc), and LEL preferentially binds to trimers and tetramers of N-acetyl glucosamine 22 or lactosamine 23. LEL reactivity between control and NDM samples was marginally significant (p=0.0533). Data that was not normalized by concentration indicated that other lectins that recognize polylactosamine, such as ECL and DSL, also had large differences in reactivity between control and IGT groups.

Direct Lectin ELISA

TMB* (catalyzed by HRP)

Streptavidin HRP

Glycans

Biotinylated Lectin

Serum protein

TMB

Lectin reactivity normalized

for total protein concentration. Geometric mean for each group

IFG vs. control

IGT vs. control

NDM vs. control Control IFG IGT NDM

Lectin n=42 n=16 n=24 n=24 p-value p-value p-value

PHA-E 6129 14453 18729 11461 0.0444 0.0039 0.0657

MAL1 669 615 550 983 0.8936 0.7544 0.3426

LEL 1548 3896 4867 3007 0.0395 0.0045 0.0533

ECL 1611 1819 1212 1696 0.7776 0.5749 0.8795

Con A 3552 4815 14478 14643 0.8021 0.1683 0.1647

DSL 106840 66084 213639 259890 0.6315 0.3729 0.1254

AAL 104772 58338 162156 146063 0.5546 0.5513 0.6424

SNA 5481 4983 7235 6676 0.9115 0.6975 0.7794

Reactivity to the lectins LEL and PHA-E was significantly different when normalized for total protein concentration between subjects with

impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and control subjects.

Aleuria aurantia (Orange Peel Fungus)

Artocarpus integrifolia (Jackfruit)

Concanavalin A (Jack bean)

Sambucus nigra (Elder)

Urinary Proteome Glycosylation in Type 2 Diabetes Mellitus without

albuminuria n:10

with macroalbuminuria

n:7

with CRF n:9

Vs. controls n:7 (-fold change) Albumin 0 24% 300

Lectin ELISA Aleuria aurantia 2.2 3.1 3.0

Artocarpus integrifolia

1.7 2.3 7.5

Concanavalin A 1.9 2.3 34 Sambucus nigra 1.6 2.2 63

While albumin itself only manifested a significant increase in CRF samples, lectin reactivity exhibited significant and progressive increases comparing T2DM without albuminuria and macroalbuminuria vs control. Significant and easily detectable global alterations in the glycosylation profile of the urinary proteome occur in the development of nephropathy.

Lectin reactivity may represent a simple and robust alternative to albuminuria as a biomarker of incipient and established renal complications.

Herbs for Diabetes Since antiquity, diabetes has been treated with plant medicines.

Recent scientific investigation has confirmed the efficacy of many of

these preparations, some of which are remarkably effective. Active

ingredients have been isolated from plant products, evaluated for

safety and efficacy in animals and studied in human volunteers. Few

examples of such plant extracts used for treating Hyperglycemia are:

Syzygium Cumini - Neredu - Black Plum (Blue Berry)

Fenugreek - Trigonella Foenum Graecum - Menthi

• Fenugreek,

Trigonella foenum

graecum is an annual

herb belonging to

family Leguminasaea

and is extensively

cultivated in many

parts of India.

• The hypoglycemic

action of fenugreek

seeds has been

studied in both

Alloxan recovered

and severely diabetic

rabbits as well as in

humans.

Fenugreek

In rabbits it increased glucose induced serum insulin levels and

improved glucose tolerance in GTT. After treatment with a dose of

100 mg/kg for 15 days in rabbits there was improvement in

GHbA1c and lipid profile.

Sharma RD. Effect of fenugreek on blood glucose and serum lipids

in type-1 diabetes. European Journal of Clinical Nutrition.

1990;44:301–306.

42 patients were chosen and divided into three groups. Group 1

were fed 10 gm of powdered fenugreek seeds per day, Group 2

were given 20 gm per day and Group 3 were not given any

fenugreek powder but continued on the same drug and diet

regimen as earlier. At the end of 6 weeks it was observed that there

was no significant difference in the fasting blood sugars in Group 1

but in Group 2 who were given larger doses (20 gms /day) there

was a significant reduction in fasting blood sugars.

Raghuram TC, Sharma RD, Pasricha S, Menon KK, Radhaiah G. Int

J Diab Dev Countries. 1992;12(1):1-4.

Fenudiet (debitterized, defatted,

deodorized dietary fiber from fenugreek

seeds) and metformin are equally effective

in improving insulin sensitivity in well

controlled type 2 diabetes mellitus

Paturi V Rao*, Neelima Gundupalle, Renuka Damarasingu,

Madhav Pavuluri, Raghunath B Murakonda, Gayatri Ratan,

Deepthi Alapati, Bhanu T Paturi


Nizam’s Institute of Medical Sciences University, Hyderabad, India

diabetes.org.in diabetes-india.com diabaid.org rssdi.org nims.info * [email protected]

Introduction

Fenugreek is a food and a spice commonly eaten in many parts of the world,

and has been used for centuries by practitioners of Ayurvedic and

Traditional Chinese Medicine. The beneficial effects of soluble dietary fiber

fraction of Trigonella foenum graecum on insulinemic and lipidemic status in

type 2 diabetes were well established. But it remains unclear whether these

benefits, accrue from glycemic control per se or specific to Fenugreek

therapy.

Fenugreek, clinically recognized as anti hyperglycemic like biguanides, is

devoid of hyperlactatemia or lactic acidosis rarely associated with metformin

albeit the tolerable gastro intestinal symptoms. Since publication of UKPDS

results, metformin is reinvented as the insulin sensitizer (for insulin

resistance even in non diabetics), preventive of coronary artery disease and

weight reducing agent in type 2 diabetes mellitus.

In this context, comparing Fenugreek with metformin, an anti hyperglycemic

agent gains more importance. Present study appraised any possible

differences in insulin sensitivity (HOMA, fasting insulin and glucose),

pancreatic B cell function (C peptide) and lipid levels, after 3 months of

treatment with Fenugreek and metformin in type 2 diabetes mellitus.

Open labeled, randomized and parallel group comparative study of

Fenudiet and metformin in well controlled type 2 diabetes mellitus on

metformin monotherapy.

Gender, age, duration of diabetes, body mass index (BMI), waist-to-

hip ratio (WHR), glycemic and lipidemic control, diet and activity

patterns were matched in 17 subjects given Fenudiet (5 g twice a day)

and 19 metformin (0.5 to 3.5 g in a day) for a period of 3 months.

Renal and liver functions, hemogram, electrocardiogram,

fundoscopy, chest x-ray were normal before and after the study in

both groups. There were no treatment emergent adverse events,

hypoglycemic episodes or other adverse events during the study.

Glycemic control

In well controlled type 2 diabetes mellitus, Fenudiet and metformin

are equally effective in maintaining glycemic control. Fenudiet

regulated plasma glucose in fasting state better than metformin.

Fenudiet may have beneficial effects on hepatic output of glucose

and/or pancreatic beta cell secretion, which needs further evaluation

in long term studies.

Insulin sensitivity

Significant reduction in serum insulin levels and HOMA-IR units,

was consistent and comparable between Fenudiet and metformin

therapies. It can be inferred that Fenudiet and metformin are

equally effective in improving insulin sensitivity. The improvements

in insulin resistance noticed after Fenudiet as well as metformin

therapy, were independent of their known benefits on

anthropometry, glycemia and lipemia.

Pancreatic beta cell function

C-peptide concentration in serum rose significantly after 3 months

of treatment with Fenudiet and metformin. Change in c-peptide

levels after Fenudiet therapy were significantly associated with

decreasing BMI, increasing HbA1c, reduction in triglycerides and

rising HDL cholesterol. Not only the peripheral utilization of insulin

but also the pancreatic beta cell secretion has improved in both

groups of subjects. Fenudiet and metformin demonstrated similar

benefits in restoring beta cell function.

Lipids

The triglyceride lowering effect of Fenudiet was more pronounced

than in subjects who received metformin. Fenudiet and metformin

were equally effective in regulating total cholesterol and HDL

cholesterol.

Obesity

There were no significant differences in the measurements of body

weight or body mass index in the subjects before and after

interventions with Fenudiet and metformin.

Waist and hip circumference

A moderate decrease in the waist and hip circumferences were

equally noted in both groups of subjects on Fenudiet and

metformin therapy.

Safety Parameters

Fenudiet is as safe as metformin, as there were no significant

adverse effects, treatment emergent adverse events or

hypoglycemic episodes during the study.

Vijaysar –

Pterocarpus Marsupium

Vijaysar is extracted from the bark of

Pterocarpus Marsupium. Experimental studies

demonstrated its hypoglycemic action. Its

heartwood, bark and water stored in tumblers

made from the bark have shown anti diabetic

actions.

ICMR undertook a multi centric trial to test its

efficacy in human volunteers in 4 ICMR

collabarating centres India.

Blood glucose control was achieved in 67 out

of 93 newly diagnosed type 2 DM patients. In

73% this was achieved at a daily dose of 2 gm.

Hb A1c level was controlled in only 7%

Probably because of short duration of study.

Indian Council of Medical Research. Flexible

dose open trial of Vijayasar in cases of newly

diagnosed non-insulin-dependent diabetes

mellitus. Indian Council of Medical Research

(ICMR), Collaborating Centres, New Delhi.

Indian J Med Res 1998 Nov;108:253.

Cyamopsis Tetragonolobus

- Cluster Beans 44 patients having different diet

habits, body weights were

included in this study and their

PPBS, serum cholesterol and

body weights were recorded

before Guar gum therapy. No

alteration in the mode of therapy

(whether parenteral insulin or oral

hypoglycemic agents was made.

Patients were given 5 gm of Guar

gum in a glass of water either

before lunch or before dinner.

Inspite of continuing the same

dosage schedule a definite

reduction in PPBS was noticed in

patients who were administered

Guar gum.

Trivedi BB, Maniyar KT, Patel B.

Effect of fibre diet (guar) on

cholesterol, blood glucose and

body weight. Int J Diab Dev

Countries 1999;9(1):31-33.

Dry powder from fresh fruits was extracted using

benzene. Four major fractions Kakara I ,II , III , IV

were obtained out of which I and III yielded 3

fractions I b, III a and IV b. Kakara I b (400mg/kg) and

III a (100mg/kg) had no effect on fasting blood

sugars but improved glucose tolerance 20% and 30%

in a single dose in Alloxan recovered (AR) rabbits.

Multiple doses (Ib for one week and III a for 2 weeks)

seemed to act by suppressing circulating free fatty

acids without affecting other serum lipids

(cholesterol, triglycerides and phospholipids). Both

could increase glucose induced serum insulin levels

during GTT. III b in a single dose (300 mg/kg)

produced only a transient but not a sustained fall in

FBG and improved glucose tolerance. In multiple

doses for 1 week there was improvement in glucose

tolerance and increase in serum insulin during GTT

indicating pancreatic effect. Thus Mimordia

charantia contains atleast 3 non steroidal orally

active hypoglycemic principles having pancreatic (III

b) as well as extra pancreatic (I b and III a)

mechanism of action.

Pugazhenthi S. Murthy PS. Studies on the isolation

and effect of three orally active hypoglycemic

principles kakara Ib, IIIa and IIIb, from bitter gourds

(Momordica Charantia LINN). Int J Diab Dev

Countries 1989;9(2):73-6.

Momordica Charantia -

Kakara - Bitter Gourd

(Melon)

http://diabetes.org.in/journal/vol.3no.5dec.htm

. . . The indigenous drugs employed have conceptually based

effectiveness, depending on their taste (rasas) and since diabetes is

considered to be a disease of sweets, sugary, foods, agents with bitter

and astringent effect have been in vogue for centuries. In the natural or

extract forms, bitter principles exist in the following - Natural. Azidirace

water indica (neem), Momordica charantia (karela), Cocinia indica

(kundra). Swertia chirata (chiretta), Alegle marmelos (Begl root).

Extracts. Colocynthbitter – apple, bitter cucumber, bitter gourd,

Benzaldehyde - bitter almonds, Quinine from cinchona afficinalis.The

hypoglycaemic effect of this type of bitter can be speculative and based

on its astringent properties, or the absorptive capacity of glucose

is being modified from the gut either due to gut hormones or plasma

insulin response.

Sharma R. Efficacy of the Bitter principles on post-glucose blood

glucose values


Sharma R. Efficacy of the Bitter principles on post-glucose blood

glucose values


Group II 100 G. glucose tolerance was done after withdrawing the prior

antidiabetic medication. 2-3 days later, extracted juice of 250 g of fresh

Momordica charantia was administered in fasting state, 1½ hour later

100 G GTT repeated. Blood glucose values were assessed at fasting; 1

hour and 2 hours intervals. Results Group II (NIDDM-Momordica

charantia)-A mean average percent drop in blood glucose by 15% at 1

hour level and 26% at 2 hour levels was observed.

Percentage fall of blood sugar with Momordica charantia (mc)

http://diabetes.org.in/journal/1988_dec/article33.pdf

STUDIES ON THE ISOLATION AND HYPOGLYCEMIC EFFECT OF THREE ORALLY ACTIVE

COMPOUNDS KAKARA Ib, KAKARA IIIa AND KAKARA IIIb FROM BITTER GOURDS

S. PUGAZHENTHI AND P. SURYANARAYAN MURTHY

Department of Biochemistry, University College of Medical Sciences, Shahdra, Delhi-110 032

. . . Three principles called Kakara Ib, Kakara IIIa and Kakara Illb, possessing

hypoglycemic activity have been isolated from the benzene extract of bitter gourds by

silicic acid column chromatography and gel filtration. They are not steroids and

therefore different from charantin reported by earlier workers. Their activity was tried

both in severely diabetic (SD) rabbits and in alloxan recovered (AR) rabbits with nearly

normal or slightly elevated fasting blood glucose (FBG) levels but impaired glucose

tolerance. la AR rabbits given orally either Kakara Ib (300 mg/kg) or Kakara IIIa1 (100

mg/kg) there was significant improvement in GTT pattern for a long time even after

the withdraw! of the drug (2 weeks for Kakara Ib) without changing the FBG levels or

increasing the glucose induced insulin release in glucose tolerance test (GTT). Thus

Kakara Ib and Kakara IIIa improve glucose utilization by extra pancreatic mechanism

and their effect was comparable to tolbutamide (300 mg/kg). On the other hand

Kakara Illb brought down FBG levels and increased the glucose induced insulin release

in AR rabbits indicating that its action is through pancreas. A proper combination of

the 3 principles is likely to have more favourable effect because of both pancreatic and

extra pancreatic effects.

Alcoholic extract of the

bark (1g/kg bw) produced

varied effect on the

glucose tolerance of the

AR rabbits. But the

acetone extract which is

relatively pure has

produced significant

hypoglycemic effect at a

dose of 130 mg/kg body

weight.

Shukla R, Anand K,

Prabhu KM, Murthy PS.

Hypoglycaemic effect of

the water extract of

Ficus bengalensis in

alloxan recovered, mildly

diabetic and severely

diabetic rabbits. Int J

Diab Dev Countries.

1994;14(3):78-81.

Ficus Bengalensis - Marri - Banyan Tree

Glycine Max - Soya

Dolichos Lablab – Chikkudu - Indian Bean

Allium Sativa - Vellulli - Garlic

The plant was ground into powder and

mixed with the standard pellet and fed to

the rats. Blood glucose was recorded

every day.

Consumption of garlic significantly

decreased the FBS and this

hypoglycemic effect may be due to the

action of substances like allyle propyl

disulphide or diallyle disulphide.

Jelodar GA, Malachi M, Motadayen MH,

Sirus S. Effect of fenugreek, onion and

garlic on blood glucose and

histopathology of pancreas of alloxan

induced diabetic rats. Indian J Med Sci

2005 Feb;59(2):64-9.

Effects of three different doses of shilajit (50, 100 and 200 mg/kg/day, orally),

alone for 4 weeks and a combination of shilajit (100 mg/kg/day, orally) with

either Glibenclamide (5 mg/kg/day, orally) or Metformin (0.5 g/kg/day, orally)

for 4 weeks were studied on blood glucose and lipid profile. RESULTS: In the

diabetic rats, all the three doses of shilajit produced a significant reduction in

blood glucose levels and also produced beneficial effects on the lipid profile.

The maximum effect was observed with the 100 mg/kg/day dose of shilajit.

Combination of shilajit (100 mg/kg) with Glibenclamide (5 mg/kg/day) or

Metformin (0.5 gm/kg/day) significantly enhanced the glucose-lowering ability

and improvement in lipid profile than any of these drugs given alone.

CONCLUSION: Shilajit is effective in controlling blood glucose levels and

improves the lipid profile

Trivedi NA, Mazumdar B, Bhatt JD, Hemavathi KG. Effect of shilajit on blood

glucose and lipid profile in alloxan-induced diabetic rats. Indian J

Pharmacology 2004;36(6):373-376.

Shilajit

The effect of Shilajit (a herbo mineral preparation) on

blood glucose and lipid profile in euglycemic and

alloxan-induced diabetic rats in combination with

conventional anti diabetic drugs was studied.

Adathoda Vasica - Saraswathi Bauhinia Purpure - Kanchanam

- Orchid or Butterfly tree

a,

Nymphaea Nouchali -

Kaluva - White Water Lilly

Curcuma Longa -

Pasupu - Turmeric

Curcumin, the active component

in Turmeric Rhizomes (Curcuma

Long Linn), was originally used

in traditional Indian medicine

over 3000 years ago. Several studies

have indicated a beneficial role of

curcumin in terms of antioxidant, anti

tumourogenic, and anti inflammatory

property. A recent study showed that

curcumin-treated diabetic rats had

lower blood glucose and glycated

hemoglobin levels, in association

with lower oxidative stress.

Farhangkhoee H, Khan ZA, Chen S,

Chakrabarti S. Differential effects of

curcumin on vasoactive factors in the

diabetic rat heart. Nutrition &

Metabolism 2006,3:27 (18 July 2006)

Murraya Koenigii –

Karivepaku-Indian curry leaf

Azadirachta Indica - Vepa -

Neem - Margosa

Musa Paradisiaca - Arati -

Banana

Emblica Officinalis – Usiri –

Indian Gooseberry

Cogent db : Herbal preparation

Cogent db a herbo mineral preparation (Cybele herbal laboratories)

has been used in both rats and humans to study its hypoglycemic

actions. Each tablet of cogent db has the following constituents:

• Azadirachta indica bark (neem tree) 3.00 gm

• Phyllanthus Emblica (Indian goose berry) 0.70 gm

• Terminalia Bellerica 0.70 gm

• Terminalia Chebula 0.70 gm

• Tribulus Terrestris (ghokru) 1.00 gm

• Aconitum Heterophyllum 0.10 gm

• Curcuma longa (turmeric) 0.80 gm

• Syzygium Cumini (black plum) 2.00 gm

• Rotula Aquatica (lour) 1.00 gm

Shekhar KC, Achike FI, Kaur G, Kumar P, Hashim R. A preliminary evaluation of

the efficacy and safety of Cogent db (an ayurvedic drug) in the glycemic control of

patients with type 2-diabetes. J Altern Complement Med. 2002 Aug;8(4):445-57.

Oze's Ayurvedic Medical Centre, Kuala Lumpur, Malaysia.

A nonrandomized, non-placebo-controlled clinical trial to evaluate the efficacy of

Cogent db as an adjuvant in the treatment of patients with type 2 diabetes. This study

was conducted in two major peripheral clinics of Kuala Lumpur in the Klang Valley,

Malaysia.

Total of 60 subjects (30 each for control and treatment groups) completed the study.

All subjects in the treatment group were given Cogent db (2 tablets three times daily

after each meal) in addition to the regular allopathic drugs (Daonil, Diamicron ) with

or without Metformin that they took in common with the control group. Thirty two

(32) clinical variables were investigated, including liver enzymes, kidney function

tests, hematologic parameters, blood glucose, insulin, and C-peptide assays.

At the end of 3 months it was found that there was a significant decrease in the levels

of fasting and postprandial blood glucose, cholesterol, triglycerides, glycated

hemoglobin (Hb A(1C)) and fasting insulin in the treatment group compared to the

controls. Cogent db did not alter the liver function tests, hematologic parameters, or

the kidney function tests.

Yoga in Diabetes

Yoga’s effectiveness at preventing and treating

diabetes is due to its emphasis of a healthy diet and

lifestyle as well as its ability to:

• Reduce blood pressure,

• Correction of dyslipidemia,

• Reduction of insulin resistance,

• Correction of hyperinsulinemia and

• Elimination of stress

The practice of Yoga includes:

• Sun Salutation or Surya Namaskara, Asanas, Pranayama, Meditation, Yoga Nidra and Cleansing Processes

Yoga and its effect on various physical, physiological, metabolic and endocrine

functions and parameters were studied by Indian researchers and Yoga institutions.

Research on the effect of Yogic therapy on type 2 diabetes in India mainly comprised

of cross-sectional, uncontrolled, non-randomized and a few randomized controlled

trials. These studies varied in duration from short term i.e. ranging from 10 days to

40 days to long term projects lasting for 6 months.

Review of original research literature on Yoga therapy in diabetics showed a

significant change in glycemic parameters, plasma lipid parameters, blood pressure,

cardiovascular risk factors, dose of insulin, and dose of oral hypoglycemic drugs,

BMI and quality of life.

Several trials done to study the effect of Yoga on type 2 diabetes in India

demonstrated a significant influence on glycemic parameters but most of the studies

were short term trials with a low power and many used yoga along with other

interventions like diet.

Age group of patients in general in the studies was in between 20 -70 years.

Parameters measures in general were fasting blood sugar (FBS), post prandial blood

sugar, glycosylated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT).

Some of the Indian authors who have researched the effect of yoga on type 2

diabetes are : Malhothra et al (2002, 2005), Agrawal et al (2003), Singh et al, Bijlani et

al, Ramaiah et al, Sahay (1994).

Yoga Asanas previously found to be beneficial in diabetes:

1. Surya Namaskar (sun salutations),

2. Trikonasana (triangle posture),

3. Tadasana (mountain posture),

4. Sukhasana (easy posture),

5. Padmasana (lotus posture),

6. Paschimottanasana (seated forward bend pos..

7. Ardhmatsyendrasana (half spinal twist posture),

8. Pawanmuktasana (wind relieving posture),

9. Bhujangasana (serpent posture),

10. Vajrasana (firm or perfect posture),

11. Dhanurasana (bow posture),

12. Sarvangasana (shoulder stance),

13.Halasana (plough posture) and

14.Shavasana (corpse posture).

Name and duration of various asanas included in yoga. (Singh S, Malhotra V, Singh

KP, Madhu SV, Tandon OP. Role of Yoga in modifying certain cardiovascular

functions in type 2 diabetic patients. J Assoc Phys India 2004;52(3):203-6.)

1. Surya Namaskar Out of 12 asanas of suryanamaskar-4 comfortable postures are done, the pose being maintained for ten seconds.

2. Tadasana ¼ minute to one minute for each side adding ¼ minute per week

3. Trikona-asana ¼ minute to one minute for each side, adding ¼ minute per week

4. Sukhasana ¼ minute to one minute, adding ¼ minute per week

5. Padmasana ¼ minute to one minute, adding ¼ minute per week

6. Bhastrika Pranayama 5 – 15 minutes per day

7. Paschimottanasana ¼ minute to one minute for both sides, adding ¼ minute per week

8. Ardhmatsyendrasana ¼ minute to one minute for each side, adding ¼ minute per week

9. Vajrasana ¼ minute to one minute, adding ¼ minute per week

10. Pawanmuktasana ¼ minute to one minute for both sides, adding ¼ minute per week

11. Naukasana 3 – 7 turns of each, the pose being maintained for ten seconds adding one turn each, every fortnight

12. Bhujangasana 3 – 7 turns of each, the pose being maintained for ten seconds adding one turn each, every fortnight

13. Dhanurasana 3 – 7 turns of each, the pose being maintained for ten seconds adding one turn each, every fortnight

14. Shavasana 2 - 10 minutes, adding 2 minutes per week

Sun Salutation :Suryanamaskaras

Ardha-Matsyendra

Pawanamukta

Bhujanga

Sethu Bhandha

Dhanura

Sarvanga

Meditation

A Multicentric, Randomized,

Controlled trial of Yoga and

Fenugreek in prevention of

type 2 diabetes mellitus –

The Indian Diabetes

Prevention Study (IDPS)

Panchakarma

Acupuncture, the practice of inserting special needles (4-25mm long)

into specific areas of the body to stimulate the functions of the

organs, is also said to help in the treatment of diabetes.

The impacts of diabetic neuropathy may be halted through

acupuncture. Also, importantly, treating the pancreas area (through

several of the 500 acupuncture points located all over the body) with

acupuncture has been shown to reduce the autoimmune component

central to diabetes.

There have been some claims that through the use of acupuncture,

diabetics may need to use less insulin. Acupuncture of the ears may

also be beneficial for type 2 diabetics to stimulate the nervous

system.

Acupuncture An ancient Chinese method

of healing

Acupunture in Diabetes

• In a study conducted in China on 60 pts out of which

38 pts were placed in the acupuncture group ,it was seen that once a day administration of Acupuncture for 30 days reduced the Fasting Blood Sugar to below 130 and post prandial blood sugars to below 150.Further the 24 hr urine sugar was reduced by 30%.

• It was noticed that patients receiving Acupuncture showed a statistically significant decline in Cholesterol,Triglycerides and Beta Lipoproteins.

• Drop in Triglycerides was most significant with a decline from an average value of 151 at the start of the study to 117 ,one month later.

Use for People With Diabetes

Though there has been evidence to prove that oral intake of certain herbs may improve Glucose

tolerance there are no studies to prove that Aromatherapy with the use of Essential oils can cure

diabetes (type 1 or type 2). However, essential oils can be used to reduce the side effects of some

complications (i.e., ulcers, loss of skin integrity) and to reduce infections that often take longer to

resolve than in non diabetic patients.

Essential oils can also ameliorate the stress of coping with a lifelong chronic condition such as

diabetes. Aromatherapy has a long history of use for stress reduction, and aromatics have been used in

many cultures to enhance quality of life.

Reiki

A study is being conducted by the

National Centre for Complementary and

Alternative Medicine to determine if

Reiki will improve glycemic control and

cardiac autonomic function in diabetic

patients with painful neuropathy.

Reiki (pronounced ray-kee) is an

Eastern form of natural medicine that

may have been practiced by Buddhist

monks as many as 2,500 years ago. The

name is Japanese, derived from two

characters—"rei,“which means

universal, and "ki,“which means life

force or energy. Thus, Reiki is a

modality in which practitioners access

the "universal life force" to facilitate

healing.

Guided Imagery

Guided imagery is a proven form

of focused relaxation that helps

create harmony between the mind

and body.This technique provides

a powerful psychological strategy

that enhances a person's coping

skills. Research has shown that

guided imagery can counteract

the effects of stress, fear, panic,

anxiety, helplessness, and

uncertainty.

Biofeedback: Role in Diabetes

For people with type 2 diabetes, stress can prevent them from being

able to keep their blood glucose at a normal level. This can lead to a

cycle of stress and poor health that can result in long-term problems

related to diabetes.

Stress management can include exercise, meditation, or relaxation

techniques. Biofeedback is a type of therapy that uses a machine to

measure the body's responses to stress. The machine records

changes in the body due to stress, such as a rise in skin temperature

or tense muscles, and helps the patient to learn how to control their

body's reactions to stress.

A total of 30 adults with type 2 diabetes were studied. The study

participants took either 10 individual sessions of biofeedback and

relaxation therapy or 3 individual diabetes education sessions.

Before the survey began, each person recorded their blood glucose

levels two times a day for 4 weeks. Then, the researchers measured

signs of their stress levels, including skin temperature and muscle

tension. Each person completed a survey about their medical

history and exercise habits. They also answered questions about

their mental health to see if they had depression or anxiety. After the

sessions ended, they measured their blood glucose levels again for 4

weeks, and the researchers compared their blood glucose levels

before and after the study.

The people who took the biofeedback and relaxation therapy had

much lower short-term and long-term blood glucose levels than the

people who completed the education sessions. They also lowered

their muscle tension, depression, and anxiety more than the people

in the education session. And, those who took part in biofeedback

and relaxation therapy were able to maintain better glucose levels for

longer times.

ROLE OF FENUGREEK IN THE PREVENTION OF TYPE

2 DIABETES MELLITUS IN NON DIABETIC PEOPLE

WITH IMPAIRED GLUCOSE TOLERANCE (IGT)/IMPAIRED FASTING GLUCOSE (IFG)

G. Arpana M.Pharm


Nizam’s Institute of Medical Sciences,

Hyderabad.

under the guidance of

Dr. P.V. Rao

Doctoral Committee Members

Dr. K. Ramesh Kumar Rao

Former Professor and Head, Executive Registrar

Department of Clinical Pharmacology and Therapeutics

Dr. U. Shoba J.C

Additional Professor and Head, Executive Registrar

Department of Clinical Pharmacology and Therapeutics

Dr. A. Krishna Prasad

Additional Professor, Department of Medicine

Dr. Aruna K. Prayaga

Professor, Department of Pathology

Dr. Priscilla Chandran

Professor and Head, Department of Biochemistry

Mr. B. Limbaiah

Dietitian, Department of Dietetics

Overview

Background

Objectives

Methods

Results

Discussion

Strengths, Limitations and Avenues of the

Study for Future Research

Conclusions

Background

Globally, there are approximately 366 million people with IGT and

this is predicted to rise to 552 million by 2030

In 2011, IDF estimates that India alone has 61.3 million people

living with diabetes; this places India second to China1

Prediabetes: Prediabetes is a category of glucose tolerance

representing an intermediate stage between normal glucose

tolerance (NGT) and diabetes

Within this category are two subcategories: impaired fasting glucose

(IFG: defined as a fasting plasma glucose concentration of 100-125

mg/dl) and impaired glucose tolerance (IGT: defined as a 2-h oral

glucose tolerance test [OGTT] plasma glucose concentration of 140-

199 mg/dl)

Fenugreek

Scientific Name : Trigonella foenum-graecum

Family : Fabaceae

Active Chemical Constituents : 4-Hydroxyisoleucine, Trigonelline, Sterols, Sapogenins and Steroid saponins

Regulatory Status : Official in Ayurvedic Pharmacopoeia of India, British Pharmacopoeia, European Pharmacopoeia

Mechanism of Action:

In humans, fenugreek seeds exert hypoglycemic effects by stimulating glucose-dependent insulin secretion from pancreatic β-cells, as well as by inhibiting the activities of alpha-amylase and sucrase, two intestinal enzymes involved in carbohydrate metabolism2,3

Fenugreek seeds also lower serum triglycerides, total cholesterol (TC), and low density lipocholesterol (LDL-C). These effects may be due to sapogenins, which increase biliary cholesterol excretion, in turn leading to lowered serum cholesterol levels4,5

Fenugreek

Safety/Adverse Effects:

Reported side effects include transient diarrhea and flatulence and dizziness

Decreased body weight has also been reported and attributed to decrease in T36

Due to coumarin derivatives, there is a theoretical risk prothrombin time (PT) or international normalized ratio (INR) might be increased, which in turn increases risk of bleeding7

Should not be used during pregnancy because of its potential uterine stimulating properties observed in early animal studies8

Dose: 3-6 g. of the drug in powder form9

Research Envisaged

Research is uncovering the importance of the “pre-diabetic” state or metabolic syndrome, when insulin resistance gives rise to impairment of glucose metabolism 10,11

Thus, dietary supplements that can modulate glucose homeostasis and potentially improve lipid parameters would be desirable

From the literature it is observed that Fenugreek is a dietary supplement that may hold promise in this regard

Though the hypoglycaemic and hypolipidaemic effect of fenugreek were evaluated in animals and human models with type 2 diabetes mellitus, no study is reported in prediabetes

Research Envisaged

Prospective epidemiologic studies have demonstrated that subjects with isolated IFG and isolated IGT have a 4% to 6% annual risk for progression to T2DM compared with less than 0.5% annual incidence in NGT subjects

Individuals with combined IFG/IGT have approximately 10% annual risk for T2DM inferred by IFG is additive to that of IGT 12,13

The increased risk to T2DM associated with IFG and IGT has led us to start the entitled interventional study “Role of Fenugreek in the prevention of type 2 diabetes mellitus in non diabetic people with impaired glucose tolerance (IGT)/impaired fasting glucose (IFG)”

Objectives

PRIMARY To determine whether Fenugreek can prevent the outcome of type 2

diabetes mellitus (T2DM) in non diabetic people with prediabetes (impaired glucose tolerance (IGT) / impaired fasting glucose (IFG))

SECONDARY To monitor whether IGT/IFG is converted to normal glucose

tolerance or FPG/PPPG and HbA1c levels in non diabetic people with IGT/IFG are reduced

To asses if β-cell function and insulin resistance (by using homeostasis model assessment -HOMA) in people who are at high risk for type 2DM, is reduced

Do these interventions improve hypertension?

Do these interventions improve dyslipidemia?

Do these interventions reduce weight, W/H ratio and BMI?

Materials and Methods

Selection of the Subjects

Department of Endocrinology and Metabolism at Nizam's Institute

of Medical Sciences in Hyderabad

Inclusion criteria

Male and female aged 30-70 years

Body mass index ≥ 19 kg/m2

Fasting plasma glucose 100-125 mg/dl (IFG)

Post 75 g oral glucose load plasma glucose (OGTT)

140-199 mg/dl (IGT)

Urban population is considered

Willing to give informed consent form

Exclusion Criteria

Those taking drugs known to alter glucose tolerance.

Type1 diabetes mellitus.

Fasting triglycerides >400 mg/dL.

History of cancer, any major illness of the liver, kidney and CNS.

Significant cardiovascular disease defined as - decompensated heart failure (NYHA class III and IV)

- diagnosis of unstable angina pectoris. - recent (within the last 6 months) myocardial infarction

Known hypersensitivity to any drug.

Women who are pregnant, breast feeding or planning a pregnancy during the course of the study.

Patients with Uncontrolled hypertension.

Patients with active tuberculosis or other infectious disease.

Patients with epilepsy, psychosis, personality disorder or suspected drug abuse or alcoholism.

Refusal for written informed consent.

Received any investigational drug within 30 days prior to screening.

Subjects on systemic glucocorticoids, beta blockers, thiazides and nicotinic acid.

Study Design

Fenugreek group

(n=74)

Control group (n=66)

Visit-once in 3 Months (V1-V9)

3 years (Follow-up) Study

close-up

1 year

Randomization

7days

(Window

Screening End of study

A 3-year follow-up of randomized controlled trial of Fenugreek in 66 control and 74 study (Fenugreek) subjects was initiated in nondiabetic people with prediabetes.

Randomization Concomitant illness and concomitant medication Adverse events since visit 1 Dispensing the trial drug Check if any withdrawal criteria Pregnancy test if required

Follow up Visits Body weight, BMI and W/H ratio Vital signs Physical Examination Concomitant illness and concomitant medication Hypoglycemic episodes Blood sampling for HbA1c and lipid profile Urine collection for urine micro albumin Adverse events since last visit Fenugreek powder dispensing and accountability Check if any withdrawal criteria Pregnancy test if required

Termination Visit – Visit 9 End of trial form

Rationale of the Study

Our concern was to find if the usage of fenugreek for long term will

alter the outcome of type 2 diabetes in the people with pre-diabetes

or not?

Intervention of the Subject

• Fenugreek powder 5gms BD is given to the patients along with 200ml of

water half an hour before meals and are asked to follow the same dosage

regime up to the end of the study

• Efficacy and safety parameters (weight, BMI, waist-to-hip ratio,

FPG/PPPG, HbA1c, Lipid profile, Urinalysis, Insulin) were assessed at

visit 1 and at every visit.

Assessments

HbA1c : Once in 3 months

Lipid profile and Urinalysis(microalbuminuria) : Once in every 6 months

Insulin assay, ECG, Ophthalmoscopy: : Once in a year

Pregnancy test : Performed at visit 1

Physical Examination : Weight, W/H ratio, Vital signs

Statistical Analysis

Mean, standard deviation, student t test adjusted for baseline, 6-, 12-,

18-, 24-, 30- and 36- months were calculated.

Sample size Calculation

It was assumed that during a 3-year follow up period, 30% subjects with

prediabetes (IFG or IGT) develop clinical diabetes with annual incidence

rates of conversion ranging from 10-12%12,13,14

The recent Finnish Diabetes Prevention Study, Diabetes Prevention

Program and the Da Qing Study have demonstrated that the use of

intervention strategy including restricted dietary fat was associated with

reduction in the risk of developing type 2 diabetes in at least half of the

people with prediabetes12,13,14

In the proposed 3-year study it was expected that administration of

Fenugreek reduces the risk of diabetes development in 14% study

subjects. The risk errors of α=0.05 and β=0.20 were assumed.

The formula used was based on the normal approximation to the

binominal

n/group = 2(Zα+Zβ)2Π (1-Π)/Δ2

Π= Is the arithmetic average of the 2 proportions

Δ = Is the arithmetic difference between the 2 proportions which

would be considered clinically important (significant) if it exists.

Two sided test was considered.

P1 = 36% P2 = 14%

Zα = 1.960 (for =0.05) Zβ=0.84 (for power (1-β)=0.80(β=0.20))

Π = 0.36+0.14/2 =0.25

Δ=0.36 - 0.14 = 0.22

n/group = 2(1.96+0.84)2 0.25 (1-0.25)/0.222

= (15.68) 0.1875/0.0484

= 60.74

If we consider 20% dropouts during the study 20x61/100=12

12+61=73 subjects per group are required for the study.

Subjects

(N: 140)

Randomization

½ Year

(n: 64) DO: 2

½ Year

(n: 73) DO: 1

1 Year (n: 59)

DO: 0 DM: 7

1 Year (n: 68)

DO: 4 DM: 2

1 ½ Years (n: 50)

DO: 0 DM: 16

1 ½ Years (n: 63)

DO: 6 DM: 5

2 Years (n: 38)

DO: 5 DM: 23

2 Years (n: 60)

DO: 6 DM: 8

2 ½ Years (n: 32)

DO: 5 DM: 29

2 ½ Years (n: 54)

DO: 10 DM: 10

3 Years (n: 27)

DO: 5 DM: 34

3 Years (n: 52)

DO: 10 DM: 12

DO: Drop Outs

DM: Diabetes

Mellitus

Fenugreek group

n: 74

Control group

n: 66

Subject Disposition

Incidence rate of diabetes

during the study period in

controls

Incidence rate of diabetes

during the study period in

Fenugreek group

Relative Risk Reduction rate of

diabetes RRR = Control Event Rate-Study Event Rate

Control Event Rate

Mean changes from baseline to

the end of study period

*p<0.05: between the groups. Change is calculated as post-baseline – corresponding baseline. A negative value in change indicated improvement. BMI: body mass index.



*p<0.05, #p<0.01, †p<0.001: between the groups. Change is calculated as post-baseline – corresponding baseline. A negative value in change indicated improvement. BP: blood pressure.

Mean changes from baseline

to the end of study period

Only subjects with both baseline and corresponding post-baseline visit values were included. Change was calculated as post-baseline – baseline. A negative value in change indicated improvement.



Only subjects with both baseline and corresponding post-baseline visit values were included. Change was calculated as post-baseline – baseline. A negative value in change indicated improvement.



*p<0.05: between the groups. Only subjects with both baseline and corresponding post-baseline visit values were included. Change was calculated as post-baseline – baseline. A negative value in change indicated improvement; UACR: Urine albumin creatinine ratio.



*p<0.05: between the groups. Only subjects with both baseline and corresponding post-baseline visit values were included. Change was calculated as post-baseline – baseline. A negative value in change indicated improvement.

Compliance reported during the

intervention period

Compliance

½ yr.

(n:73)

1 yr.

(n:68)

1 ½ yrs.

(n:63)

2 yrs.

(n:60)

2 ½ yrs.

(n:54)

3 yrs.

(n:52)

n % n % n % n % n % n %

Poor 3 4.11 6 8.82 6 9.52 1 1.67 2 3.70 9 17.31

Average 8 10.96 7 10.29 3 4.76 5 8.33 9 16.67 7 13.46

Good and

Acceptable 62 84.93 55 80.88 54 85.71 54 90.0 43 79.63 36 69.23

Discussion

Progression to Diabetes

The conversion rate from IFG and IGT to diabetes by the end of 3 years

was 54.55% in controls and 22.97% in Fenugreek group.

Thus the cumulative incidence rate of diabetes reduced significantly in

Fenugreek group when compared to controls (χ2 = 13.47 p<0.01).

At 3 years, glucose levels have normalized in 18.52% of controls and

34.62% of Fenugreek subjects.

In our study the conversion rate from IFG and IGT to diabetes in

controls was similar to a 11-year follow up study which stated that

many people with prediabetes may revert to NGT on long term, and that

only about 50% of people with IGT or IFG will develop diabetes after a

protracted follow-up.15

Anthropometric Measurements

Throughout the study period few differences were observed in waist

and hip circumferences, but body weight and BMI were unaltered in

both control and Fenugreek groups.

Studies by Analava Mitra and Debaprasad Bhattacharya,16 Kumar et

al17 and Sorengarten18 supported that patients weight, BMI and other

clinical parameters were measured and found to be almost stationary.

Hypoglycemic Effects

The hypoglycemic effect of Fenugreek seed powder discussed in our

study was well supported by studies of Shani et al,19 Madar,20 Ribes et

al21 and Khosla et al22 which showed that Fenugreek seeds decrease

fasting as well as two hour blood glucose levels in animals while

Sharma,23,24 Al Hobori,25 Madar et al,27,26 and A. Gupta et al28 showed

hypoglycemic effect in type 1 and type 2 diabetes subjects.

Hypolipidemic Effects

The hypolipidemic effects observed in our study were similar to the

observations found in Sowmya and Rajyalakshmi 29 study where

germinated Fenugreek seed showed a significant reduction in the levels

of total cholesterol and LDLc, but with regard to TG, HDLc and

VLDLc no significant reductions were observed.

Insulinotropic effects

Serum insulin has increased significantly (p<0.01) in Fenugreek group

at 3 years.

Various studies by Petit et al. (1993),30 D. Puri et al.31 Devi et al.

(2003) 32 and Eidi et al. (2007)33 suggested that Fenugreek seeds act as

insulin secretor, as they reported increased insulin secretion in animal

studies.

Strengths of the study

• This study was conducted in men and women, having different life-

styles and socio-cultural backgrounds but satisfying the inclusion and

exclusion criteria mentioned.

• Though the sample size had diversified demographics, their

anthropometric, clinical and biochemical parameters were similar at

baseline.

• This study could target large populations more cost effectively.

• No study until now has reported the incidence conversion rate to

diabetes with the interventional Fenugreek powder in prediabetes.

• The strength of this intervention lies on the depth and complexity of

data which illuminates the statistical correlation between

independent risk factors towards the onset or progression to diabetes.

Limitations of the study

• Despite of supplying debitterized processed Fenugreek powder to

the study group, few subjects have forgone their doses due to its

unacceptable palatability.

• Because of this reason they were advised to consume it along with

some flavoring agents. This perhaps, could alter the plasma glucose

levels and was found to be one of the limitations of the study.

• Though there were many reasons for subject dropouts, one of the

reasons was their unwillingness towards the consumption of

Fenugreek on long term basis due to its undesirable taste.

• In addition, subjects did not receive any incentives during the study

due to which there was a lost to follow-up and the dropout rate in

study group was recorded as 13.5%.

Avenues of the Study for Future

Research • Further the compatibility of Fenugreek can be enhanced by certain

additives like tulsi leaves which can mask the bitterness of

Fenugreek.

• As a future prospective, studies in combination of Fenugreek and

tulsi should be intervened in prediabetes.

• The reproducibility of this intervention is further assured in future.

Thus providing an avenue for future research in finding out the role

of Fenugreek in prediabetes, in different population groups and

forming an auxiliary for evidence based studies.

Summary

• This study provides evidence for the use of Fenugreek to delay the

onset of diabetes in subjects with prediabetes.

• Fenugreek powder is useful to mitigate the blood glucose response

in prediabetes.

• From the results it can be concluded that Fenugreek showed

hypocholesterolemic effects by reducing serum cholesterol and

LDLc levels but without affecting serum TG, HDLc and VLDLc

levels.

• Our results strongly suggest that the enhancement of serum insulin

levels is due to insulinotropic effects of β-cell function.

Conclusion

• In conclusion, our results show that hypoglycemic effects are due to

increasing levels of serum insulin due to β-cell secretion and we

suggest here that the mode of action of Fenugreek may be caused by

their contents of alkaloids through reducing the increased blood

glucose level, thereby preventing hyperglycemia and reducing lipid

profile.

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Acknowledgements

• Dr. P. V. Rao

• Dr. K. Ramesh Kumar Rao

• Dr. U. Shoba J.C

• Dr. A. Krishna Prasad

• Dr. Aruna K. Prayaga

• Dr. Priscilla Chandran

• Mr. B. Limbaiah

• Dean and the Director, Nizam’s Institute of Medical Sciences

• Academic and Administration staff of NIMS

• Indian Council of Medical Research

• G. Chandrakala, Dr. G. Neelima, Dr. T. Sreenivas

• All the subjects and their relatives

Use of Plant Foods including Bitter Gourd and Fenugreek in...

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