Impaired Glucose Tolerance and Prevention of Diabetes Mellitus Type 2 by Polyherbal Formulation of Eastern Medicine
Conditions: Diabetes Mellitus, Pre Diabetes
Sponsor: Islamia University of Bahawalpur

 
IMPAIRED GLUCOSE INTOLERANCE AND PREVENTION OF 
DIABETES MELLITUS TYPE 2 BY POLYHERBAL FORMULATION OF 
EASTERN MEDICINE 
 
Official Title: Impaired Glucose Tolerance and prevention of diabetes mellitus 
type 2 by polyherbal formulation of Eastern Medicine  
 
Principal Investigator: Hafiz Abdul Sattar Hashmi  
 
Supervisor: Dr Khalil Ahmed Ansari (Ph.D)  
 
Duration : 06 week (March, 20, 2019 –May, 05, 2019)  
 
Responsible Party: Principal Investigator  
 
Ethical Committee Approval No. uccm/01/19  
 
Clinical Trial Registration No. NCT 03884920 (clinicaltrials.gov) 
 
Funding Agency: University College of Conventional Medicine  
 
Location: Pakistan 
University College of Conventional Medicine 
       
     Bahawalpur, Pakistan, 63100 
  
      
Contact: H A Sattar Hashmi, M.Phil 
    +92-345-2115767    sattarhashmi5767@gmail.com 
     Contact: Dr K A. Ansari, Ph.D   
  +92-300-9680920    ansari.khalil@gmail.com 
     Principal Investigator: H A Sattar Hashmi, M.Phil 
 

IMPAIRED 
GLUCOSE 
INTOLERANCE 
AND 
PREVENTION 
OF 
DIABETES MELLITUS TYPE 2 BY POLYHERBAL FORMULATION OF 
EASTERN MEDICINE  
Title: Impaired glucose tolerance and prevention of type 2 diabetes mellitus by 
polyherbal formulation of Eastern Medicine.  
Target population: Model Town A, B of Bahawalpur, City area Khairpur 
Tamewali  
Introduction  
Diabetes mellitus is a severe concern of mankind in the recent years and is a global 
health situation irrespective of the socioeconomic profile and geographic location 
of the population. A variety of statistics across the globe has been clearly 
representing that diabetes mellitus has attained a pandemic form(1). World Health 
Organization (WHO) has indicated that more than 80% of the diabetes deaths 
occur in low and middle revenue countries. It has also been expected that diabetes 
will be the seventh important cause of death in 2030(2). According to International 
Diabetic Foundation (IDF), throughout 2012, more than 371 million people suffer 
from diabetes. The number of people with diabetes is rising in every country and 
about 4.8 million citizens die every year. More than 471 billion USD were used up 
on healthcare for diabetes (3). The increase in type 2 diabetes is related to lifestyle 
changes that have resulted in overweight, obesity, and decreased physical ctivity 
levels. These environmental changes, superimposed on genetic predisposition, 
increase insulin resistance, which, in concert with progressive-cell failure, results 
in rising glycemia in the nondiabetic range. In addition to the risk for diabetes, 
insulin resistance and impaired insulin secretion are accompanied by a host of 
major cardiovascular disease (CVD) risk factors including hypertension and 
dyslipidemia. Further reduction in insulin secretion over time results in increasing 
glycemia and the development of diabetes, which in turn is associated with the 
development of microvascular and cardiovascular complications.  
In the last few years, there has been an exponential increase in the field of herbal 
medicinal study which is ahead of popularity both in the developing and developed 
countries for the reason of their natural origin and less side effects (4). Despite 
extensive progress in the treatment of diabetes by oral hypoglycemic agents, the 
exploration for newer drugs continues because of the several restrictions found in 
the usage of synthetic drugs. Medicinal plants supply a potential source of 
hypoglycemic drugs possessing the dynamic compounds which have been used in 
the treatment of diabetes and they are highly praised for their therapeutic properties 
in the traditional medicine system(5).  

Diabetes prevention  
The transition from the early metabolic abnormalities that precede diabetes, 
impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), to diabetes 
may take many years; however, current estimates indicate that most individuals 
(perhaps up to 70%) with these pre-diabetic states eventually develop diabetes (6-
7). During the pre-diabetic state, the risk of a CVD event is modestly increased (8-
11). With the development of diabetes, however, there is a large increase in risk for 
CVD, as well as for long-term complications affecting the eyes, kidneys, and 
nervous system. The complications of diabetes, which are the cause of major 
morbidity and mortality, are related to its duration, chronic level of glycemia, and 
other risk factors. Although clinical trials have demonstrated the effectiveness of 
intensive glycemic and blood pressure control to reduce the long-term 
complications of diabetes. The public health burden of the disease remains 
enormous. The magnitude of the epidemic, coupled with complex treatment 
requirements that are difficult and costly to implement, make the prevention of 
diabetes a critical public health goal. (12) Between 1997 and 2006, eight major 
clinical trials examined whether lifestyle or pharmacologic interventions would 
prevent or delay the development of diabetes in populations at high risk by virtue 
of having IFG and/or IGT(13-15)  
Impaired Fasting Glucose (IFG) and Impaired Glucose Tolarence (IGT)  
IFG and IGT represent intermediate states of abnormal glucose regulation that 
exist between normal glucose homeostasis and diabetes. IFG is now defined by an 
elevated fasting plasma glucose (FPG) concentration (_100 and _126 mg/dl) (29). 
IGT is defined by an elevated 2-h plasma glucose concentration (_140 and _200 
mg/dl) after a 5-g glucose load on the oral glucose tolerance test (OGTT) in the 
presence of an FPG concentration _126 mg/dl. (16-17)  
Objectives:  
1. To assess Glucose Intolerance in the targeted population  
2. To assess the screened population for prevention of Diabetes Mellitus Type 2.  
3. To assess / screened pre-diabetics and potential benefits attained by the 
polyherbal / test formulation in Pre-diabetics and diabetics. 
4. To evaluate the safety profile for use of polyherbal formulation by assessing the 
effect on various blood markers and to assess its acceptability to proceed for 
further progress to develop preventive phytotherapy (test).  
5. To evaluate the preventive efficacy of polyherbal formulation(test) by assessing 
the effect on Glucose intolerance.  
6. To evaluate effect of polyherbal formulation (test) on the insulin.  

7. To evaluate the potential preventive effect of polyherbal formulation for 
developing a preventive strategy for prevention of DM.  
Material and Method:  
Chemicals:  
Liver function test kit  
Renal function test kit  
Lipid profile kit  
Insulin kit  
Glucose Reagent Kit  
Glucose (pharmaceutical grade) 
Polyherbal formulation:  
In the last few years, there has been an exponential increase in the field of herbal 
medicinal study which is ahead of popularity both in the developing and developed 
countries for the reason of their natural origin and less side effects (4).  
Despite extensive progress in the treatment of diabetes by oral hypoglycemic 
agents, the exploration for newer drugs continues because of the several 
restrictions found in the usage of synthetic drugs. Medicinal plants supply a 
potential source of hypoglycemic drugs possessing the dynamic compounds which 
have been used in the treatment of diabetes and they are highly praised for their 
therapeutic properties in the traditional medicine system.(5) Polyherbal 
formulation of Eastern Medicine used in this research is popularly utilized in 
traditional medicine in various countries to control and treat diabetes. These herbs 
are used extensively. Four important herbs among these are selected for the 
preventive effect of these products. These includes Colosynth seed, Occimum 
tenuiflorum seed, Holarrhena antidysenterica seeds, Gymnemia Sylvester leaves. 
These herbs have proved to produce anti-diabetic effect by modulating beta-cell in 
pancreatic 
islet 
cell, 
enhanced 
insulin 
secretion, 
hypoglycemic, 
anti-
hyperlipidemic, anti-Cholesterolic effects on CVS and diabetes. (18-21)  
 
Study Design: 
Three arm parallel Observational Cross-Sectional and Case-Crossover clinical trial 
(Phase 1) 
 
 
 
 
Groups: 
Groups and Interventions 
 
 

 
 
Study Description: 
Brief description: 
Primary protocol to this study is to develop a natural remedy to prevent diabetes mellitus 
in pre-diabetic state and elaborate the effectiveness of polyherbal formulation for carrying out 
Phase-II, III and IV. It also aimed at to see the level of difference of glucose tolerance and 
impaired fasting glucose and impaired glucose tolerance between pre-diabetic and diabetic to 
evaluate the potential benefit for treatment of insulin resistance and sensitivity. To see the for 
prevention of Diabetes Mellitus (DM) and stopping / delaying the onset of DM. 
 
 
Detailed description: 
 
This study is a clinical trial study to evaluate the potential of prevention in pre-diabetics 
and to prevent onset of diabetes mellitus. For this purpose, volunteers will be enrolled in the 
study by observing the Helsinki Declaration for clinical trials. 
volunteers will be screened for the impaired glucose tolerance or impaired fasting glucose or at 
risk to develop diabetes mellitus type 2. 
On screening, pre-diabetics and early onset diabetics with no previous history of treatment etc 
will be grouped into A and B. 
Biochemical evaluations will be carried out at base line and followed by three weeks intervention 
and evaluation of biomarkers and at sixth week for further evaluation. 
Collected data will be evaluated for primary out comes and secondary out come. statistical 
analysis will be done. 
 
  
 
Groups/Cohorts 
Interventions 
Group A Pre-diabetic placebo 
Group of pre-diabetics receiving placebo BD for 
six weeks 
 
Group B Pre-diabetic test 
Group of Pre-diabetic receiving polyherbal / test 
candidate 900mg in two divided doses for six 
weeks 
Dietary Supplement: Polyherbal 
formulation  
Test candidate will be administered per oral 
before / with meal in two divided doses 
Group C Diabetic test 
Early onset of Diabetes mellitus receiving 
polyherbal formulation 1800mg in two divided 
doses for six weeks 
Dietary Supplement: Polyherbal 
formulation  
Test candidate will be administered per oral 
before / with meal in two divided doses 

Method:  
Step 1: Consent, observation of Ethical Principles of Declaration of Helsinki, 
questionnaire and screening of targeted population for impaired fasting glucose 
(IFG) and impaired glucose tolerance(IGT), (16-17)  
State FPG Level 2-h plasma glucose  
In OGTT (mg/dl)  
Impaired Fasting Glucose = 100-125 <200  
Isolated IFG = 100-125 <140  
Impaired Glucose Tolerance = <126 140-199  
Isolated IGT = <100 140-199  
Step 2: Individuals with IFG & IGT evaluated for age, family history of diabetes in 
first degree relation, BMI = 35 kg/m3 will be evaluated for following profiles on 
two week basis with baseline  
1. Lipid profile for elevated triglycyrides, low HDL, Cholesterol  
2. Hepatic functions: SGPT, SGOT, ALT,  
3. Renal Function test for Creatinine, Urea  
4. Insulin level  
Step 3: At high risk population with impaired FG & IGT and underlying or 
corresponding diseases ,(8-11) population will be given oral polyherbal 
formulation of Eastern Medicine for six weeks.  
Step 4: data collected and interpreted with statistical significance  
Eligibility Criteria: 
Study Population: 
• 
community samples will be obtained from the area of 
Bahawalpur 
• 
Model Town A, B, and 
• 
remote areas of district Bahawalpur consisting of 
Khairpur Tamewali city population 
Sampling Method: Probability Sample   
Minimum Age: 18 Years   
Maximum Age: 59 Years   
Sex: All   
Gender Based: No   
Accepts Healthy Volunteers: Yes   
Criteria: Inclusion Criteria: 
• 
Age: 18-59 
• 
Impaired Fasting Glucose (100-125mg/dl) 

• 
Impaired Glucose Tolerance (140-199mg/dl) 2h-75gm 
OGTT 
• 
History of Diabetes in first degree relation with one 
condition 
• 
At high risk with BMI > 35% 
• 
Early onset diabetic / accidental on screening (glucose 
>200mg/dl) 
Exclusion Criteria: 
• 
on renal dialysis; 
• 
an acute or terminal illness or serious mental illness; 
• 
history of recent coronary event within the last 12 
months; 
• 
a recent history of acute medical problem or 
admission to hospital; 
• 
any other severe medical conditions that need 
intervention / treatment 
• 
has poor short-term prognosis (expected death in <2 
years); 
• 
is planning to travel for longer than 6 weeks during 
the 6-week intervention period; or 
• 
is with compromised liver / kidney / cardiac function 
• 
older patients of DM taking any form of medication / 
intervention 
 
Out Comes: 
 
Study outcomes will be measured by various biomarkers and beneficial effects / toxic 
effect will be assessed by certain blood biomarkers as followed. 
 
Primary outcomes: 
1. Enhancement of Glucose Tolerance 
2. Enhancement of Impaired Fasting Glucose Tolerance 
3. HbA1c level of reduction 
Secondary Outcomes: 
1. Lipid Profile including 
a. Level of Cholesterol 
b. Triglycyrrhides  
c. Low density lipid (LDL) 
d. High density lipid (HDL) 
Unspecified Outcomes: 
1. Liver Function 
a. Serum Glutamate Oxaloacetate Transaminase (SGOT) level 
b. Serum Glutamate Pyruvate Transaminase (SGPT) level 
c. Alkaline Phosphatase level 

2. Kidney Function 
a. Serum Creatinine level 
b. Blood Urea Nitrogen level 
 Noting of Adverse events: 
Any adverse event /effect observed during study will be categorized by the version of Medical 
Dictionary for Regulatory Activities. 
Contacts: 
Central Contact Person: H A Sattar Hashmi, M.Phil 
   Telephone:   +92-345-2115767 
   Email:   sattarhashmi5767@gmail.com  
Central Contact Backup: Dr K A.Ansari, Ph.D 
   Telephone:   +93-300-9680920 
   Email:   ansari.khalil@gmail.com   
Study Officials:  H A Sattar Hashmi, M.Phil 
Study Principal Investigator 
scholar 
Dr K A.Ansari, Ph.D 
Study Director 
AP   
Location: 
University College of Conventional Medicine 
       
     Bahawalpur, Pakistan, 63100 
  
      
Contact: H A Sattar Hashmi, M.Phil 
    +92-345-2115767    sattarhashmi5767@gmail.com 
     Contact: Dr K A. Ansari, Ph.D   
  +92-300-9680920    ansari.khalil@gmail.com 
     Principal Investigator: H A Sattar Hashmi, M.Phil 
 
 
Machines :  
Centrifuge,  
Microlab,  
Chemistry Analyser  
Weighing machine  
Analysis: Statistical Analysis 
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