CORRELATION BETWEEN MEAN PLATELET

VOLUME AND FASTING PLASMA GLUCOSE LEVELS

IN PREDIABETES AND NORMOGLYCEMIC
INDIVIDUALS

D R .SURIYA.K.K.N
REG. NO: 1801091016

A DISSERTATION SUBMITTED TO
SRI BALAJI VIDYAPEETH (DEEMED TO BE UNIVERSITY)
IN PARTIAL FULFILLMENT FOR THE AWARD OF
DEGREE OF M.D. GENERAL MEDICINE (BRANCH X)

MAHATMA GANDHI MEDICAL COLLEGE AND RESEARCH INSTITUTE

PONDICHERRY – 607402, INDIA

MAY 2021
 MAHATMA GANDHI MEDICAL COLLEGE AND RESEARCH INSTITUTE,
PONDICHERRY -607402

CERTIFICATE

This is to certify that the dissertation entitled “CORRELATION BETWEEN MEAN

PLATELET VOLUME AND FASTING PLASMA GLUCOSE LEVELS IN

PREDIABETES AND NORMOGLYCEMIC INDIVIDUALS” is a bonafide record of

original work carried out by DR. SURIYA K.K.N UIN: 1801091016 in the Department of

General Medicine, under our guidance and supervision during the period of his

postgraduate study for M.D. General Medicine from May 2018 to April 2021.

Dr. SIVA RANGANATHAN GREEN

Professor,
Department of General Medicine
Guide

[Link] .S
Professor of General Medicine
Head of Department of General Medicine

Prof. SEETESH GHOSE

DEAN I/c
MGMCRI

ii
 MAHATMA GANDHI MEDICAL COLLEGE AND RESEARCH INSTITUTE,
PONDICHERRY - 607402

DECLARATION OF THE CANDIDATE

I hereby declare that this dissertation entitled “CORRELATION BETWEEN

MEAN PLATELET VOLUME AND FASTING PLASMA GLUCOSE LEVELS IN

PREDIABETE AND NORMOGLYCEMIC INDIVIDUALS.” is a bonafide and

genuine research work carried out by me,Dr. SURIYA KKN , UIN: 1801091016 in

Department of GENERAL MEDICINE, under guidance [Link] RANGANATHAN

GREEN, Professor, DEPARTMENT OF GENERAL MEDICINE, Mahatma Gandhi

Medical College and Research Institute, Pondicherry.

Date:

Place: IIIrd yr. PG Student

Department of General Medicine
MGMCRI

iii
 ACKNOWLEDGEMENTS

I take this opportunity to express my respect to my beloved teacher and guide

[Link] RANGANATHAN GREEN., Associate Professor, Department of General

Medicine, Mahatma Gandhi Medical College and Research Institute for lending his

expertise throughout my post graduate study and also towards completion of my

dissertation.

I would also like to thank my HOD PROF. [Link] his consistent

encouragement, guidance and parently support throughout the PG training. I expressmy

heartiest gratitude to my Unit Chief Prof. Dr.T.K. DUTTAfor his encouragement, guidance

and moral support throughout my PG program.

I sincerely thank [Link] M. Dean, Mahatma Gandhi Medical College and

Research Institute and [Link] N. Dean (Faculty), and Mahatma Gandhi

Medical College and Research Institute for lending their expertise towards writing of this

dissertation.

I would like to thank the entire faculty of Department of General Medicine for their

guidance and support all along. I want to acknowledge all my fellow postgraduates from

the department of General medicine, who helped me compile this study.

I would like to thank all the patients who volunteered to be a part of my study,

without them this study would not have been possible.

I thank the Chairman and Vice Chancellor of our Medical College and Hospital for

their every help in making this dissertation possible.

Last but not least, I would like to thank my parents who have been pillars of

strength and support during my post graduate studies.

DR. SURIYA K K N

iv
 CONTENTS

CERTIFICATE ............................................................................................................ ii
DECLARATION BY THE CANDIDATE ................................................................. iii
ACKNOWLEDGEMENT ...........................................................................................iv
CONTENTS .................................................................................................................. v
LIST OF TABLES .......................................................................................................vi
LIST OF FIGURES.................................................................................................... vii
LIST OF ABBREVIATIONS ................................................................................... viii
1. INTRODUCTION ................................................................................................. 1
2. AIM AND OBJECTIVES...................................................................................... 3
3. REVIEW OF LITERATURE ................................................................................ 4
4. RESEARCH QUESTION .................................................................................. 28
5. MATERIAL AND METHODS ........................................................................... 29
6. RESULTS........................................................................................................... 35
7. DISCUSSION ...................................................................................................... 55
8. LIMITATIONS AND RECOMMENDATION................................................... 60
9. SUMMARY ......................................................................................................... 61
10. CONCLUSION .................................................................................................... 63
11. ABSTRACT ........................................................................................................ 64
12. REFERENCES .................................................................................................... 66
13. ANNEXURE
13.1. ETHICAL COMMITTEE CERTIFICATE ............................................... 76
13.2. PROFORMA .............................................................................................. 77
13.3. PATIENT INFORMATION SHEET ......................................................... 78
13.4. MASTER CHART ..................................................................................... 85
13.5. PLAGIARISM CHECK CERTIFICATE .................................................. 90
13.6. PLAGIARISM BONAFIDE CERTIFICATE ............................................ 91

v
 LIST OF TABLES

1. Distribution of age among study groups (n = 110) ...................................................................... 35

2. Distribution of mean age among study groups (n = 110) ............................................................ 36

3. Distribution of gender among study groups (n = 110) .................................................................. 37

4. Distribution of mean BMI among study groups(n = 110) ............................................................. 38

5. Distribution of obesity among study groups based on BMI (n = 110) ......................................... 39

6. Distribution of participants with history of dyslipidemia between the study groups .. ............... 40

7. Distribution of participants with history of alcohol intake among the study groups ................... 41

8. Distribution of participants with history of amoking between the study groups......................... 42

9. Distribution of FBS among the study groups (n = 110) ................................................................. 43

10. Distribution of mean FBS among the study groups(n = 110) ...................................................... 44

11. Distribution of PPBS between the study groups (n = 110).......................................................... 45

12. Distribution of mean PPBS between the study groups (n=110) ................................................. 46

13. Distribution of HbA1c among the study groups (n=110) ............................................................ 47

14. Distribution of mean HbA1c among the study groups(n=110) .................................................... 48

15. Distribution of Platelet count among study groups(n=110) ....................................................... 49

16. Distribution of mean Platelet count among study groups based(n=110)................................... 50

17. Distribution of mean Hemoglobin levels among study groups based (n=110)........................... 50

18. Distribution of Mean platelet volume among study groups(n=110) ........................................... 52

vi
 LIST OF FIGURES:

[Link] of age among study groups(n = 110) ...................................................................... 35

[Link] of mean age among study groups n=110) ............................................................ 36

[Link] of gender among study groups (n = 110) .............................................................. 37

[Link] of mean BMI among study groups(n = 110) ......................................................... 38

[Link] of obesity among study groups based on BMI (n=110) ......................................... 39

[Link] of participants with dyslipidemia between the study groups(n=110) .................... 40

[Link] of participants with history of alcohol intake among the study groups (n = 110). 41

[Link] of participants with history of smoking among study groups (n = 110) ................ 42

[Link] of FBS among the study groups (n = 110) ............................................................... 43

[Link] of mean FBS among study groups(n = 110) ......................................................... 44

[Link] of PPBS among study groups (n = 110) ................................................................. 45

[Link] of mean PPBS among study groups(n=110).......................................................... 46

[Link] of HbA1c among study groups (n=110) ............................................................... 47

[Link] of mean HbA1c among the study groups (n=110) ................................................ 48

[Link] of Platelet count among study groups(n=110) .................................................... 49

[Link] of Haemoglobin levels among study groups (n=110) ........................................... 51

17. Distribution of mean platelet volume among study groups (n=110) ...................................... 52

[Link] between FBS and MPV in normoglycemic group (n=55) ...................................... 53

[Link] between FBS and MPV in prediabetes group (n=55)............................................. 54

vii
 LIST OF ABBREVIATIONS:

Abbreviation Expansion

DM Diabetes Mellitus

CHD Coronary Heart Disease

CRP c-Reactive Protein

IL Interleukin

TNF Tumour Necrosis Factor

SPSS Statistical Package for Social Sciences

MS Microsoft

IGT Impaired glucose tolerance

IFT Impaired levels of fasting glucose

HbA1C Glycated Haemoglobin

OGTT Oral glucose tolerance tests

T2DM Type 2 Diabetes Mellitus

MPV Mean Platelet Volume

FPG Fasting plasma glucose

ICA Islet cell antibodies

ADA American Diabetic Association

LDL Low Density Lipoprotein

HDL High Density Lipoprotein

GLUT Glucose Transporter

BMI Body Mass Index

VWF Von Willebrand Factor

GP Glycoprotein

ADP Adenosine diphosphate

viii
 1. INTRODUCTION

Diabetes mellitus is a common chronic disease with high morbidity and

mortality.1 Diabetes is a disorder of metabolism clinically presented by chronic

hyperglycemia and blood lipid and protein disorders that have been widely reported as

related to several complications causing morbidity and mortality.2 Long-term problems

of diabetes comprise retinopathy with probable loss of vision; nephropathy causing

renal failure; peripheral neuropathy with risk of foot ulcers, amputations, and Charcot

joints. In addition, it causes autonomic neuropathy causing gastrointestinal,

genitourinary, and cardiovascular symptoms and sexual dysfunction. Patients with

diabetes have a higher risk of developing atherosclerotic cardiovascular, peripheral

arterial and cerebrovascular disease.3 Patients with type-2 diabetes mellitus (DM) have

a two to four times more risk of coronary heart disease (CHD) morbidity and mortality,

a four-to eight-fold increased risk of congestive heart failure, a two- to six-fold more

risk of stroke, and a worse prognosis of cardiovascular events than subjects without

diabetes.4,5 It is stated that cardiovascular mortality risk is connected with blood glucose

concentration in cases with type 2 DM.6,7Based on the data obtained from large

epidemiologic studies, diabetes has been classified as CHD and cerebrovascular risk

equivalent.8,9

It is nowadays commonly recognized that chronic inflammation has a

noteworthy role in the development and development of diabetes mellitus and the

pathogenesis of its problems. Numerous studies have described an increase in the levels

of inflammatory cytokines such as c-reactive protein (CRP), interleukin (IL)-1, IL-6

and tumour necrosis factor (TNF)-α in patients with diabetes.10,11 Inflammatory

cytokines are formed by various cell types, released into circulation and have local,

central and peripheral effects on different tissue types.12 Two of the main conditions of

1
prediabetes are impaired levels of fasting glucose (IFG) and impaired glucose tolerance

(IGT). IFG is defined as the fasting plasma glucose level ranging from 100 mg/dL (5.6

mmol/L) to 125 mg/dL (6.9 mmol/L). IGT is a condition characterized by a 2-hour

plasma glucose value in the oral glucose tolerance test, ranging from 140 mg/dL (7.8

mmol/L) to 199 mg/dL (11.0 mmol/L). Another prediabetic ailment is glycated

haemoglobin (HbA1C) that ranges from 5.7% to 6.4%.13Macrovascular complications

are twice as common in people with IGT as in normoglycemic individuals.14 It has

been described that patients with IGT have a high risk of developing type 2 diabetes

mellitus (T2DM) but the development of this disorder can be decelerated through

lifestyle modifications related to diet and physical activity.15 So, it is important to do an

oral glucose tolerance tests (OGTT) on persons with a risk of diabetes to identify the

presence of increased levels of IGT or identify manifest diabetes.

Prediabetes is an autonomous risk factor for cardiovascular disorders. Mean

platelet volume (MPV) can describe platelet activity, and increased MPV is associated

with thrombogenic activation and a high risk of developing cardiovascular disease. In

diabetic patients, MPV is higher when compared with normal individuals. Though, the

relationship between MPV and prediabetes is not well understood. The purpose of the

present study was to compare MPV in prediabetic and normoglycemic subjects, and to

evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in

these two groups.

2
 2. AIM AND OBJECTIVES

1.1. Aim:

 To study the relationship between Mean platelet volume and fasting plasma

glucose values in prediabetes and normoglycemic individuals.

1.2. Objectives:

 To study the mean platelet volume in pre-diabetic patients and normoglycemic

individuals.

 To study the fasting plasma glucose levels in prediabetes and normoglycemic

individuals.

 To evaluate the correlation between mean platelet volume and fasting plasma

glucose levels in pre-diabetics and normoglycemic population.

3
 3. REVIEW OF LITERATURE

a. DIABETES MELLITUS

TYPE 1 DIABETES:

Type 1 diabetes is characterized by annihilation of the pancreatic beta cells,

leading to complete insulin deficiency. This is usually due to autoimmune destruction

of the beta cells (type 1A). Testing for islet cell antibodies (ICA) or other islet

autoantibodies (antibodies to glutamic acid decarboxylase [GAD65], insulin, and to the

tyrosine phosphatases, IA-2 and IA-2β, and zinc transporter ZnT8) in serum may be

accommodating if finalizing the diagnosis is important; a positive result is suggestive of

immune-mediated or type 1A diabetes.16Though, some patients with complete insulin

deficiency have no sign of autoimmunity and have no other known cause for beta-cell

obliteration. They are supposed to have idiopathic or type 1B diabetes mellitus.

The present American Diabetes Association (ADA) classification of diabetes

mellitus does not show the clinical heterogeneity of patients with diabetes and the rise

of the concept that early beta cell dysfunction is probably a primary fault in the

pathophysiology of diabetes, regardless of "type." Other classification schemes have

been anticipated, showing beta cell autoimmunity, beta cell function, clinical features,

and body weight. The increased prevalence of overweight/obesity in the population has

additional complicated classification systems with an added component of insulin

resistance even in type 1 diabetes.

4
TYPE 2 DIABETES:

Type 2 diabetes is by far the most common type of diabetes in adults and is

characterized by hyperglycemia and variable degrees of insulin deficiency and

resistance. It is a common disorder whose prevalence rises noticeably with higher

degrees of obesity. Insulin resistance and insulin deficiency can rise through genetic or

environmental influences, making it hard to govern the precise cause in an individual

patient. In addition, hyperglycemia itself can impair pancreatic beta cell activity and

worsen insulin resistance.

PATHOGENESIS OF TYPE 2 DM

Considering the pathogenesis of type 2 diabetes is complicated by several

factors.17 Subjects present with a combination of varying degrees of insulin resistance

and relative insulin deficiency, and it is probable that both subsidize to type 2

diabetes.18 Also, each of the clinical features can rise through genetic or environmental

effects, making it difficult to determine the precise cause in an individual patient.

Moreover,hyperglycemia itself can damage pancreatic beta cell activity and exacerbate

insulin resistance, leading to a vicious cycle of hyperglycemia leading to a worsening

metabolic state.19

Type 2 diabetes is frequently accompanied by added conditions, including

hypertension, high serum low-density-lipoprotein (LDL) cholesterol concentrations,

and low serum high-density-lipoprotein (HDL) cholesterol concentrations that, alike

type 2 diabetes, rise cardiovascular risk. This collection of clinical conditions is

mentioned to as the metabolic syndrome.20 Hyperinsulinemia taking place in response

to insulin resistance might play an important role in the origin of these abnormalities.

Higher free fatty acid levels, inflammatory cytokines from fat, and oxidative factors,

5
have all been implicated in the pathogenesis of metabolic syndrome, type 2 diabetes,

and their cardiovascular complications.

Impaired insulin secretion and insulin resistance

The comparative importance of impaired insulin release and insulin resistance in

the pathogenesis of type 2 diabetes has been assessed in several studies.21 As an

example, in a prospective study of over 6500 British civil servants without diabetes at

baseline, 505 subjects were diagnosed with diabetes during 9.7 years (median) of

follow-up.22 In those who developed diabetes compared with those who did not, there

was a noticeable reduction in insulin sensitivity during the five years before the

diagnosis. Beta cell function (insulin secretion) increased three to four years prior to

diagnosis and then decreased until diagnosis.

Insulin secretion

Insulin secretion by beta cells needs glucose transport into the cell, which is at

minimum mediated by the glucose transporter 2 (GLUT-2). A mouse model with a

genetic alteration affecting GLUT-2 expression produced mice with glucose

intolerance; similar changes in GLUT-2 could be induced in normal mice fed a high-fat

diet and suggests a possible mechanism for the link between high-fat diet and the

development of diabetes.23

Impaired insulin secretion has also been described to occur in mice lacking

Abca1, a cellular cholesterol transporter.24 Mice with inactivation of Abca1 in beta cells

have defective insulin secretion, impaired glucose tolerance, but normal insulin

sensitivity.

6
Insulin resistance

Insulin resistance may be the best predictive factor of type 2 diabetes.25The huge

majority of patients seem to have a genetic risk for type 2 diabetes. It is possible, for

instance, that insulin resistance becomes more severe with growing age and weight,

thereby exposing a concurrent defect in insulin secretion in vulnerable patients to cause

impaired glucose tolerance and ultimately overt hyperglycemia. In normal-weight

nondiabetic patients at high risk for type 2 diabetes, both fasting and post-glucose

hyperinsulinemia predict future weight gain, which in turn inclines to

hyperglycemia.26,27 Hyperglycemia itself may subsidize to further progression by a

toxic effect on beta cells, perhaps by reducing insulin gene expression.

Insulin action

Insulin applies its effects by first binding to a precise insulin receptor that is

present on many cells through the body. The insulin receptor is a huge transmembrane

protein composed of two extracellular alpha subunits and two transmembrane and

intracellular beta subunits that have intrinsic tyrosine kinase function. When insulin

binds to the extracellular portion of the receptor, the tyrosine kinase is activated,

initiating a sequence of intracellular responses mediated in part by insulin receptor

substrates.28,29

ROLE OF DIET, OBESITY, AND INFLAMMATION

The prevalence of impaired glucose tolerance and type 2 diabetes has increased

dramatically in the US population in the past two decades. The most striking features in

these groups and of most patients who develop type 2 diabetes are increased weight

gain and decreased physical activity, each of which increases the risk of diabetes.

7
Free fatty acids

Plasma FFA concentrations are high in obese patients. A high plasma FFA

concentration is a risk factor for type 2 diabetes (relative risk 2.3), may inhibit insulin

secretion and can inhibit insulin-stimulated glucose uptake in patients with type 2

diabetes.30

Pattern of fat distribution

Upper body or male-type obesity has a much greater connection with insulin

resistance and impaired glucose tolerance than lower body or female-type obesity.

Other factors

 Interleukin-1 beta

 Uncoupling protein 2

 Obestatin

LIFETIME RISK/PREVALENCE

The projected prevalence of diabetes among adults in the United States ranges

from 4.4 to 17.9 percent (median 8.2 percent).31 The community-based Framingham

Heart Study, in a predominantly non-Hispanic white population, found a doubling in the

incidence of type 2 diabetes over the last 30 years.

FAMILY HISTORY

The importance of family history in predicting diabetes was highlighted in a

Finnish study.32 Patients with type 2 diabetes who had no family history of type 1 or

type 2 diabetes were older at onset and had conservation of endogenous insulin

8
secretion as compared with patients who had a family history of diabetes. Those with a

family history of only type 2 diabetes were more obese, had more endogenous insulin

secretion, and were less expected to have islet-cell autoantibodies than patients with a

family history of both type 1 and type 2 diabetes.

ETHNICITY

Data from the prospective Nurses' Health Study collected over 20 years found

that the risk for developing diabetes, corrected for BMI, was increased for Asians,

Hispanics, and blacks (RR 2.26, 1.86, and 1.34, respectively) compared with whites.33

OBESITY

The risk of impaired glucose tolerance (IGT) or type 2 diabetes rises with

increasing body weight. The risk of diabetes associated with body weight appears to be

modified by age. In a prospective cohort study of over 4000 men and women >65 years

of age, the risk of diabetes associated with BMI in the highest percentile was greater in

subjects less than 75 years of age compared with those 75 years and older (HR 4.0

versus 1.9).34

LIFESTYLE FACTORS

Though insulin resistance and impaired insulin secretion in type 2 diabetes have

a considerable genetic component, they can also be predisposed, both positively and

negatively, by social factors, such as physical activity, diet, smoking, alcohol

consumption, body weight, and sleep duration. Improving these lifestyle factors can

lessen the chance of developing diabetes mellitus.35

9
Exercise

A deskbound lifestyle reduces energy expenditure and promotes weight gain and

increases the risk of type 2 diabetes. Amongst sedentary behaviors, increased television

watching is reliably associated with the progress of obesity and diabetes.36 Physical

activity of reasonable intensity reduces the incidence of novel cases of type 2 diabetes,

irrespective of the presence or absence of impaired glucose tolerance.

Smoking

While a absolute causal association has not been recognized, a relationship between

cigarette smoking and diabetes mellitus is biologically conceivable based upon a

number of observations:

 Smoking increases the blood glucose concentration after an oral glucose

challenge.

 Smoking may impair insulin sensitivity.

 Cigarette smoking has been linked to increased abdominal fat distribution and

greater waist-to-hip ratio that, as mentioned above, may have an impact upon

glucose tolerance.37

The effect of smoking termination on diabetes risk is inconstant and may depend

upon individual patient factors. Smoking cessation may lower diabetes risk by lessening

systemic inflammation. On the other hand, smoking cessation is often related with

weight gain, which will increase the risk of diabetes.

Sleep duration

Quantity and quality of sleep may foresee the chance of development of type 2

diabetes mellitus, as demonstrated by the findings of a meta-analysis of 10 prospective

10
studies.38 Compared with approximately 8 hours/day of sleep, short (≤5 to

6 hours/day) and long (>8 to 9 hours/day) duration of sleep were significantly

associated with an increased risk of type 2 diabetes (RR 1.28 and 1.48, respectively).

DIETARY PATTERNS

Dietary patterns affect the risk of type 2 diabetes mellitus. A healthy diet (high

in cereal fiber and polyunsaturated fat, and low in trans-fat and glycemic load) had

more impact on diabetes risk in minorities than among whites (RR 0.54 versus 0.77) in

a large 20 year prospective study.

Western versus prudent diet

In a study of over 42,000 male health professionals, a western diet

(characterized by high consumption of red meat, processed meat, high fat dairy

products, sweets, and desserts) was associated with an increased risk of diabetes

independent of BMI, physical activity, age, or family history (RR 1.6, 95% CI 1.3-

1.9).39 The risk was markedly increased (RR 11.2) among subjects who ate a western

diet and were obese (BMI ≥30 kg/m2 versus <25 kg m2). In contrast, men who ate a

prudent diet (characterized by higher consumption of vegetables, fruit, fish, poultry, and

whole grains) had a moderate reduction in risk (RR 0.8, 95% CI 0.7-1.0). Comparable

results have been described in women.40

CLINICAL MARKERS

Abnormal glucose metabolism can be recognized years beforehand the onset of

obvious diabetes. Patients with impaired fasting blood sugar (IFG) and impaired

glucose tolerance (IGT) are at higher chance of developing diabetes and cardiovascular

disease. However, other clinical markers may also be predictive of diabetes.

11
  Markers of inflammation

 Retinal arteriolar narrowing

 Endothelial dysfunction

 Endogenous sex hormones

SCREENING

The following five criteria define the optimal conditions for screening for a

particular disorder:41

 The disorder should be an important public health problem

 An early asymptomatic stage should exist

 There is a suitable screening test

 An accepted treatment should be available

 There is evidence that early treatment during the asymptomatic stage improves

long-term outcome

TYPE 2 DIABETES

Arguments for screening It has not been recognized that early discovery of type 2

diabetes and intervention improve long-term results. Though, the arguments for

widespread screening to recognize undiagnosed cases of type 2 diabetes are much

robust than for type 1 diabetes.

 Type 2 diabetes is a major public health issue affecting around 8 percent of the

United States (US) population and with as many as 25 percent of the population

remaining undetected. Data from the Framingham Heart Study specify that the

incidence of type 2 diabetes has doubled over the last 30 years. The global

prevalence of type 2 diabetes continues to rise.42

12
 Screening tests - The usually used screening tests for type 2 diabetes comprise

measurement of fasting plasma glucose (FPG), two-hour plasma glucose during

an oral glucose tolerance test (2-h OGTT), and glycated hemoglobin (A1C).

The sensitivity and specificity of FPG and A1C as screening tests vary

conferring to the population tested and the threshold used to define diabetes. Using a

two-hour blood glucose >200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test as

the reference standard, the specificity of a fasting blood glucose

≥126 mg/dL (7.0 mmol/L) was greater than 95 percent; the sensitivity was about 50

percent, and may be lower for people over the age of 65. Using the same reference

standard, the specificity and sensitivity of an A1C cut point of 6.5 percent were 79 and

44 percent, respectively. However, the presence of diabetic retinopathy correlated better

with A1C ≥6.5 percent than with FPG or OGTT criteria.

Blood glucose

Blood glucose values are disseminated over a range in the population, although

there are some approximate thresholds above which the risk of future contrary events is

considerable. An Expert Committee on the Diagnosis and Classification of Diabetes

Mellitus recommended placing individuals in one of three categories based upon the

fasting plasma glucose concentration, A1C, or 2-h OGTT (75 gram glucose load).43

Normal -Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L). Fasting is

defined as no caloric intake for at least eight hours.

 Increased risk for diabetes

 Impaired fasting glucose (IFG) -Fasting plasma glucose between 100 and

125 mg/dL (5.6 to 6.9 mmol/L).

13
  Impaired glucose tolerance (IGT) -Two hour plasma glucose value during a 75

gram oral glucose tolerance test between 140 and 199 mg/dL (7.8 to

11.0 mmol/L).

 Diabetes mellitus -FPG at or above 126 mg/dL (7.0 mmol/L), A1C ≥6.5 percent,

a two-hour value in an OGTT (2-h PG) at or above

200 mg/dL (11.1 mmol/L), or a random (or "casual") plasma glucose

concentration ≥200 mg/dL (11.1 mmol/L) in the presence of symptoms. The

diagnosis of diabetes must be confirmed on a subsequent day by repeat

measurement, repeating the same test for confirmation.

Effectiveness of early detection

Cost-effectiveness analyses have recommended that diabetes screening in older

patients is cost-effective. As an instance, in a computer simulation model, eight

screening plans were compared with a no-screening control plan in a simulated

population of 325,000 people aged 30 years without diabetes. In other cost-

effectiveness analyses, screening targeted to individuals with hypertension was better

cost-effective than worldwide screening, and screening for impaired glucose tolerance

(prediabetes) and undiagnosed type 2 diabetes, followed by intervention (lifestyle or

pharmacological), was more cost-effective than no screening. In one model, the most

cost-effective strategy was targeted screening at age 55 to 75 years.44

14
Calculating a risk score

Risk factor assessment scoring systems have been inspected as a strategy to

guide screening, but most have not been authenticated in varied populations, and they

are not in widespread use.45 The majority of these risk valuation tools involve simple

questionnaires about significant diabetes risk factors (eg, age, weight, family history of

diabetes, personal history of hypertension, physical activity). A score is allotted for

each risk factor and the whole score used to recognize subjects for laboratory screening.

Depending upon the cut-point used, sensitivity and specificity for predicting

undiagnosed diabetes are approximately 80 and 70 percent, respectively.

PREVENTION

Three factors have been assessed in an effort to prevent type 2 diabetes:

exercise, weight loss, and drug therapy. Smoking termination may also be significant.

Lifestyle modification (predominantly exercise and weight loss) successfully reduces

the expansion of diabetes. Thus, we promote lifestyle changes (healthy diet and regular

exercise) to all our patients. In addition, we measure A1C or fasting plasma glucose

(FPG) in adults >45 years of age with BMI >25 kg/m2 who have one or more additional

risk factors for diabetes (eg, family history diabetes mellitus in a first-degree relative,

habitual physical inactivity, gestational diabetes, hypertension, dyslipidemia).

LIFESTYLE MODIFICATION

Variations in lifestyle, including diet modification, weight loss, and workout

slow progression of impaired glucose tolerance to overt diabetes. The helpful effects of

such intervention seem to continue after the original intervention. The reputation of

factors such as diet, body weight, and exercise can also be inferred from the findings in

15
certain societies that have undergone rapid change towards a westernized lifestyle. In

these societies, the prevalence of IGT and type 2 diabetes often increase greatly,

correlated with both weight gain and decreased physical activity.46

Insulin therapy in type 2 Diabetes Mellitus

The importance of glycemic control in minimizing complications related to

diabetes has been well established in type 1 diabetes. Similarly, the United Kingdom

Prospective Diabetes Study (UKPDS) demonstrated that strict glycemic control in

patients with type 2 diabetes results in a similar reduction in risk of microvascular

disease; though the impression on prevention of macrovascular complications in type 2

diabetes remains uncertain.

Based upon the results of the UKPDS, normoglycemia is now the goal for many

patients with type 2 diabetes. Though, target A1C levels in patients with type 2 diabetes

should be custom-made to the individual, balancing the development in microvascular

complications with the risk of hypoglycemia. The A1C goal must also be set somewhat

higher for older individuals and those with an inadequate life expectancy.

COMBINATION ORAL AGENT AND INSULIN THERAPY

Patients with persistent hyperglycemia in spite of oral hypoglycemic therapy might

add insulin to oral medication or may stop the oral drug(s) and begin insulin. The basis

for mixture oral hypoglycemic drug and insulin therapy is that, by suppressing hepatic

glucose production, the patient can retain the suitability of oral agents, while

diminishing total insulin requirements and consequently the degree of

hyperinsulinemia.47

16
 b. PLATELET AND ITS FUNCTIONS

The platelet is a circulating disc-shaped cell without any nucleus, responsible for

commencement of the hemostatic mechanisms that restore the injury to the vascular

endothelium. The four major platelet functions include the following:

 Platelet adherence

 Platelet activation and secretion

 Platelet aggregation48

 Interaction with coagulation factors

OVERVIEW OF PLATELET FUNCTION

Circulating platelets do not normally come across the connective tissue matrix

that lies underneath vascular endothelial cells. Once a break within the integrity of this

vascular lining ensues, platelets are exposed to, and interact with, collagen fibrils.

Platelet contacts with collagen not only delivers a surface for platelet adhesion, but also

serve as a provokes platelet activation. This marks in signaling pathways that induce

platelets to change their shape, spreading along the collagen fibrils and to secrete

thromboxane A2 and ADP into the circulation. The released thromboxane A2 and ADP

stimulate neighboring platelets, causing them to become activated and in turn to secrete

supplementary thromboxane A2 and ADP.

Platelet adherence

Platelet-mediated hemostasis is started by exposure of the vascular sub-

endotheliumsubsequent to the trauma to the endothelial surface. Circulating platelets

are recruited to the site of injury and bind to exposed components of the sub-

endothelium, together with collagen, fibronectin, von Willebrand factor (VWF),

17
fibrinogen, and thrombospondin via glycoprotein (GP) receptors on the platelet surface

(eg, GPIb/IX, GPIa/IIa, GPIIb/IIIa).49,50,51

Platelet activation

Receptor-ligand binding leads to platelet activation, mediated through calcium-

dependent cytoskeletal variations in the platelet. This outside-in signaling afterward

causes the release of substances from two sources. Platelet alpha granules (VWF,

platelet factor 4, thrombospondin, fibrinogen, beta-thromboglobulin, and platelet-

derived growth factor)

 Platelet dense granules (adenosine diphosphate (ADP) and serotonin)

ADP, in turn, facilitates inside-out signaling leading to a structural change

in GPIIb/IIIa on the platelet surface.

Platelet aggregation

The GPIIb/IIIa conformational change permits the third step in platelet-

mediated hemostasis: platelet aggregation. Fibrinogen fixes to the structurally

altered GPIIb/IIIa receptor on two or more adjacent platelets, resulting in platelet

aggregation and accumulation at the site of the vascular injury. Other platelet agonists

including thrombin (via the platelet thrombin receptor), epinephrine, and collagen

enhance this aggregation phenomenon.

Interaction with coagulation factors

Lastly, platelets interact with circulating coagulation factors by providing a

framework for the activation of phospholipid-dependent coagulation factors. Activation

18
of platelets alters their phospholipid membranes, permitting enhanced binding of

coagulation factor complexes, including the prothrombinase complexes.

Ailments of platelet function comprise of numerous rare congenital disorders,48

besides a myriad of common acquired conditions (eg, aspirin use, effects of other drugs,

liver disease, uremia). The consultant Hematologist is often asked to assess patients

with a bleeding disorder with clinical features suggesting the existence of a

qualitative and/or quantitative platelet disorder (eg, mucocutaneous bleeding and

petechiae).

ASSESSMENT OF PLATELET FUNCTION

CBC and peripheral smear examination

Since functional platelet disease conditions may be related with normal,

reduced, or elevated platelet counts, the early assessment of a patient assumed to have a

functional platelet disorder should comprise a complete blood count, including a

platelet count, white blood cell differential, and investigation of the peripheral blood

smear.

The presence of large platelets on the peripheral smear suggests faster platelet

turnover, although the presence of exceedingly large platelets, often as large as, or

larger than, a normal red cell, in a patient with thrombocytopenia

(macrothrombocytopenia) can be seen in patients with Bernard-Soulier disease or in

other giant platelet syndromes. Small platelets are representative of other congenital

disorders, such as Wiskott-Aldrich syndrome.

So-called "gray" platelets appear pale and hypogranulated on the blood smear

and can specify a congenital deficiency in alpha granules.52 They are also often seen in

acquired disorders, including the myelodysplastic syndrome.

19
Bleeding time

The bleeding time (BT) has extensively been used as a screening test for platelet

function.53 Unfortunately, there are many variables that can affect its precision. In

addition, it is not useful as a preoperative screening test in patients without a history of

bleeding and it cannot precisely assess platelet dysfunction in the presence of

thrombocytopenia.

There is general belief that the BT should not be regularly used preoperatively.

Newer tests described below are increasingly changing the BT for evaluating platelet

function, but their role as preoperative screening tests in patients without a clinical

history of bleeding remains unverified.

Platelet aggregation assays

Conventional platelet aggregation assays employ a panel of platelet agonists to

assess the platelet activation and accumulation in vitro. Either whole blood or platelet-

rich plasma is used depending on the technique. Since many common medications can

affect platelet function, care must be taken to avoid their use in patients prior to testing.

Common agonists used in these tests include ADP, arachidonic acid, collagen,

epinephrine, thrombin, and ristocetin.

Normal platelet aggregation in vitro in response to ADP and epinephrine

includes a biphasic response. The first wave of aggregation shows activation

of GPIIb/IIIa and succeeding cross-linking of platelets via fibrinogen binding. The

second wave reflects platelet degranulation and heightened aggregation due to the

release of platelet agonists. Arachidonic acid, collagen and thrombin provoke only a

single burst of aggregation.

20
Automated platelet function screening tests

There are numerous fresher technologies in current clinical use gauging many

aspects of platelet function. 54,55,56 They are increasingly substituting the bleeding time

for precise clinical indications.

Platelet Function Analyzer (PFA-100)

The most broadly tested is the PFA-100 device. This device uses two discrete

cartridges that differentiate between an aspirin -induced defect and more severe platelet

dysfunction.

One study compared results with the PFA-100 and standard platelet

aggregometry in subjects with abnormal platelet function. The sensitivity (94 versus 95

percent) and specificity (88 versus 89 percent) of the two tests were remarkably similar.

An aspirin -induced defect was detected with a sensitivity of 96 versus 100 percent and

von Willebrand disease and Glanzmann thrombasthenia were established with

sensitivities of 96 percent for the PFA-100 versus 80 percent with standard

aggregometry. The PFA-100 is less sensitive to other precise platelet diseases such as

storage pool disease.56

In a study involving 113 patients, both the bleeding time (BT) and PFA-100

were used and showed concurring results in 74 percent of patients.57 In the 29 patients

with conflicting results, 23 had anomalous findings with the PFA-100 but a normal BT.

When platelet aggregometry was done, 17 of these 23 patients had a defect constant

with aspirin effect. A second study resolved that the PFA-100 was as sensitive to the

effects of aspirin on platelet function as the template BT, with less inconsistency and

less false positive results.58

21
 There are abundant studies evidently showing superior sensitivity of the PFA-

100 versus the BT in screening for VWD. In several studies, the sensitivity of the PFA-

100 was consistently higher than the BT (84 to 97 percent versus 48 to 66 percent),

though the sensitivity of the PFA-100 varied with the severity of the VWD.59,60

THERAPEUTIC ANTIPLATELET AGENTS

The most common clinical conditions leading to disordered platelet function

comprise either a anticipated therapeutic effect or an adverse medication effect. Until

lately, the only drug that has been well recognized to cause increased bleeding related

with changed platelet function was aspirin .61 However, the newer GPIIb/IIIa inhibitors

also can lead to bleeding problems, due to their higher inhibition of platelet

aggregation. Thrombocytopenia has also been described following use of these agents,

with an incidence of 2 to 13 percent.

MEAN PLATELET VOLUME

Platelets play a significant role in the normal haemostasis; the mean platelet

volume (MPV) and a precise assessment of the platelet size are considered markers and

determinants of platelet function. Larger platelets with advanced MPV are

hemostatically more sensitive and produce more amounts of the prothrombotic factor

Thromboxane A2, increasing a tendency to thrombosis.62

Circulating platelets differ significantly in size, metabolism, and functional

activity, the largest being more reactive and producing a more amount of thrombogenic

factors.63 All modern automated hematologyanalyzers deliver platelet counts and

produced both the mean platelet volume (MPV) and the size inconsistency as platelet

distribution width (PDW). The excessive dispersion of platelet volumes, also in normal

22
subjects (log-normal distribution), depends on the process of platelet production,

through the disintegration of cytoplasm of megakaryocytes and proplatelet (proPLT)

formation. In healthy subjects there is a non-linear opposite association between MPV

and platelet concentration: MPVs incline to decrease in subjects with higher platelet

counts;64 this implies that PLT number and size are ruled by preservation of mass. MPV

should consequently be expressed as a function of platelet concentration. Furthermore,

in elderly patients a significantly greater platelet volume has been detected, with a

direct correlation between age and MPV for both sexes, or only for men. This reflection

is, still, a debated issue as no significant differences were observed in other studies.

MPV values are reportedly elevated in patients with type 2 diabetes, and change in

some infections, such as acute appendicitis, infective endocarditis and septic shock

although the latter finding is presently a matter of dispute.65 An increase in MPV with

respect to the baseline is related with mortality in patients with severe sepsis.66

Unpredictably, high MPV is related with a decreased risk of venous thromboembolism

in cancer patients, unlike in cancer-free patients.67 The anticoagulant suggested for a

complete blood count (CBC) including platelet indices is K2 -EDTA.68 When blood

comes into contact with EDTA, platelets rapidly change in shape – from disks with

diameter of 2–4 μm to spheroids covered with threadlike extensions. This

transformation, initially isovolumetric, is accompanied by progressive increase in

volume within 1 or 2 h, to reach an equilibrium condition, albeit not definitive. Thus,

MPV increases with time if assessed with impedance methods.

Lately, bigger MPV is developing as an independent risk factor for

thromboembolism, stroke, and myocardial infarction. In patients suffering from

diabetes, MPV was higher compared with the normal glycemic controls; furthermore, it

has been proposed that a rise in MPV may play a role in the micro- and macro-vascular

23
complications related to diabetes. Also, platelet activity recovers with better glycemic

control.

MPV is altered by numerous biosocial and lifestyle factors such as race, gender,

age, blood pressure, smoking habits, and alcohol consumption.

MEAN PLATELET VOLUME AND DIABETES

The definition of IFG is not steady worldwide. Conferring to the American

Diabetes Association (ADA) criterion, IFG is defined as FPG levels of 100–125 mg/dL;

this threshold was lowered in 2003 for better prediction of future diabetes incidence.

Other organizations, including the European Diabetes Epidemiology Group (EDEG)

and the Japan Diabetes Society (JDS), have retained the original diagnostic range for

IFG at FPG levels of 110– 125 mg/dL.

The term “prediabetes” has substituted the clinical definitions recognized as

borderline or chemical diabetes, conventionally used to classify the individuals at high

risk of progression to overt diabetes. Prediabetes has been connected to an uncertain

increase in overall cardiovascular events and has been associated with a higher risk of

stroke. Furthermore, it has been reported that in prediabetic subjects, the von

Willebrand factor levels, vital for platelet aggregation and adhesion, is significantly

higher than in the controls, and Willebrand factor levels were positively correlated with

MPV in the prediabetic group.

A study using a large multi-ethnic cohort has established that the risk of

cardiovascular accidents or death in normoglycemic and prediabetic subjects rises

gradually with increasing FPG levels. A 1 mmol/l (18 mg/dl) increase in FPG has been

associated with a 17% increase in the risk of future cardiovascular events or death.69

Even within the normoglycemic range, elevated cardiovascular risk is strongly and

24
independently associated with glucose levels. Patients with fasting glucose levels in the

high normal range (95–99 mg/dL) have an increased cardiovascular risk when

compared with subjects in low-normal range (< 80 mg/dL).70

Although the basic mechanism of higher MPV in diabetes remains uncertain, it

has been recommended that increased MPV may be due to osmotic swelling as a

consequence of hyperglycemia.71 One more postulated mechanism from a study in mice

established that insulin induces megakaryocytes to produce larger platelets.72

Hyperglycemia rises platelet reactivity directly and by increasing glycation of

platelet protein; increased MPV has also been described in diabetes, IGT and

gestational diabetes. It has been previously reported that MPV is positively and

independently correlated with FPG levels, not only in prediabetic subjects, but also in

normoglycemic subjects, after correcting for the confounding variable.

A positive correlation between MPV and 2 h-PG during OGTT in modest IGT

subjects was reported by Coban et al. However, they did not assess the confounding

factors that are thought to have a pronounced impact on MPV, such as blood pressure,

dyslipidemia, high-sensitivity C-reactive protein or smoking status.

Obesity is a risk factor of cardiovascular diseases, partly due to more oxidative

stress and inflammation, which are related with increased reactive oxygen species

(ROS) manufacture and decreased NO bioavailability. Lately, Monteiro et al73 showed

that metabolic anomalies, as a result of high-fat diets, cause platelet hyper-agregability

involving enhanced intra-platelet ROS production and decreased NO bioavailability. In

slightly hyper-triglyceridemic subjects, n-3 polyunsaturated fatty acids elevated the

MPV values slightly. In obese subjects, MPV was positively correlated with BMI and a

positive correlation was also shown between weight loss and reduction in MPV. A

higher BMI value was positively associated with increased insulin levels and insulin

25
resistance. In patients with cardiovascular disorders, MPV was significantly high in

those with insulin resistance when compared to insulin-sensitive subjects.74

Nevertheless, MPV was positively related with insulin level in polycystic ovary

syndrome, which is related to high insulin levels and the incidence of obesity. So,

hyperinsulinemia that go together with obesity may influence platelet reactivity in

obese patients.

ASSOCIATION OF MPV WITH OTHER CONDITIONS

Atherosclerosis results in about 80% of all deaths from type 2 diabetes mellitus,

of which approximately 75% are due to coronary artery disease.75 Platelets and their

interaction with the vessel wall play a significant role in atherogenesis and in the

development of the coronary thrombus.76 Mean platelet volume (MPV), a basis of

platelet activation, is a newly evolving risk factor for athero-thrombosis.77 Elevated

MPV levels have been recognized as an independent risk factor for myocardial

infarction in patients with coronary heart disease78 and for death or recurrent vascular

accidents after myocardial infarction.79 Furthermore, increased platelet size has been

described in subjects with vascular risk factors such as diabetes mellitus, in patients

with acute ischemic stroke, hypercholesterolaemia, obesity, smoking and in patients

with renal artery stenosis.

ST-elevation myocardial infarction (STEMI) characteristically is triggered by

occlusive coronary thrombus development superimposed on a ruptured or eroded

atherosclerotic plaque.80 Platelets play a pivotal role in thrombus formation. Antiplatelet

therapy is an important constituent of the treatment in STEMI. In spite of a proper

therapy, a population of patients signifying high platelet activity still exists. These

patients are mainly at risk of major cardiovascular accidents. The association between

26
erythrocyte count, leukocyte count and STEMI has been extensively studied.81-84 The

experimental data suggests the significant role of platelets. Nevertheless, most clinical

studies have used sophisticated platelet function test. Meanwhile, the methods of testing

platelet activity may be very time consuming, expensive, and technically difficult.85 The

mean platelet volume (MPV) is a universally available parameter with routine blood

counts by automated hemograms and, therefore, is an attractive index to study in

clinical scenarios. It has been linked to many cardiovascular risk factors. MPV is a

marker of platelet size and activity and has been linked to poor prognosis following

STEMI.86

27
 4. RESEARCH QUESTION

Is there a relationship between mean platelet volume and the fasting plasma glucose

levels in prediabetes and normoglycemic individuals?

28
 5. MATERIAL AND METHODS

a. Study setting:
The study was conducted in the Department of General Medicine, Mahatma

Gandhi Medical College & Research Institute, Pondicherry.

b. Study Population:
This study was conducted among patients who attended the outpatient and in-patient

department of General medicine

c. Study design:
This study was taken as an observational study

d. Study sample:
Patients who were diagnosed as prediabetes by the diagnostic criteria of

American Diabetes Association87and normoglycemic individuals were included in the

study after obtaining written informed consent.

e. Sample Size estimation:

Based on the results of theICMR–INDIAB, R. M. Anjana et. Al 88, the prevalence

of Prediabetes in India is around 10% hence with the confidence interval of 95% power

of 90% and an alpha error of 0.05 and beta error of 0.10 the sample size of group 1 is 55

and sample size of group 2 is 55.

Total sample size is 110

f. Sampling technique:
Convenience sampling technique was used to select study participants from all

the patients who are eligible to participate in the study.

29
g. Study Period:
January 2019 to June 2020

h. Study Groups:
TOTAL NO OF GROUPS: 2
PREDIABETES GROUP NORMOGLYCEMIC GROUP
FPG 0F 100-125 mg/dl FPG OF 70-99mg/dl
PPG OF 140-200 mg/dl PPG LESS THAN 140mg/dl
HbA1c of 5.7%-6.4% HbA1c less than 5.7%

SELECTION PROCESS
It is case control study where prediabetes was taken as the case group and the

normoglycemic individuals were taken as the control group. The patients presenting to

the outpatient department and admitted in the department of general medicine were

enrolled in the study after obtaining consent from the patient.

American diabetic association criteria for diagnosis of prediabetes and diabetes

STAGE OF DISEASE FBG PPBG HBA1C

NORMOGLYCEMIA Less than 100 Less than 140 Less than 5.7
mg/dL mg/dL %
PREDIABETES 100 mg/dL 140mg/dL to 200 5.7% to 6.5%
to126mg/dl mg/dl
DIABETES More than 126 More than 200 More than
mg/dl mg/dl 6.5%

i. Inclusion Criteria:
 Age more than 18 years.

 FPG value of 70-126 mg/dl

 PPG value of 140-200 mg/dl

 HbA1c value of 5.7% to 6.5%.

30
j. Exclusion Criteria:

• Subjects with abnormal platelet counts

• Subjects who are taking antiplatelet medicines (aspirin, ticlopidine, and

clopidogrel) will be excluded.

• Diabetic subjects with the history of anti-diabetic therapy

• FPG > 126 mg/dL,

• PPG > 200 mg/dL

• HbA1c levels more than 6.5

• Low FPG levels (< 70 mg/dL).

• Male subjects with Haemoglobin levels below 13 g/dl

• Female subjects with haemoglobin levels below 12 g/dl will also be excluded

from the study because nutritional anaemia can cause reactive thrombocytosis

k. Brief Procedure:

After obtaining clearance from Institutional Human Ethics Committee patients

attending the outpatient departments and admitted in the wards was taken into

consideration after re-evaluating the presenting complaints, past history, medication

history,family history, general and systemic examination. Those patients with the

positive family history and presence of risk factors such as obesity, smoking were

invited to take part in the study after obtaining an informed written consent.

The participants were then evaluated for the fasting plasma glucose, post

prandial glucose levels and HbA1c levels. The fasting blood glucose levels in these

subjects was obtained after overnight fasting (8 hours) in EDTA containers and was

tested using automated biochemical analyzer. After 2 hours of 75grams of glucose

intake blood samples was withdrawn in the EDTA containers and tested using the

31
automated biochemical analyzer for obtaining the post prandial blood glucose levels,

HbA1c levels also was obtained by convenient method.

According to the above obtained blood glucose levels the subjects were

classified into normoglycemic and prediabetic groups according to the diagnostic

criteria of American Diabetic Association the case group comprises the prediabetic

individuals and the control group is the normoglycemic individuals with the exclusion

criteria identical to those described for the cases. At least one age matched control (up

to 5 years elder or 5 years younger) was recruited per case according to the above-

mentioned criteria.

The complete blood count of both the groups was done to obtain the hemoglobin

levels, Platelet counts and Mean platelet volume. The blood samples was obtained in

Fluoride vacutainers and was measured using the automatic blood counters in the

central lab of [Link] samples was investigated for blood glucose and complete

blood counts within half an hour to avoid variations relating to old samples.

l. Statistical analysis:
Difference in proportions were tested using chi square test. A p value <0.05 was

considered statistically significant. Students ‘t’ test was applied to find the significance of mean

difference. Data entry was done using MS Excel 2013 and data analysis was done using SPSS

version 22.0.

32
 m. Flow chart to summarize the study

PATIENTS ATTENDING THE OUTPATIENT DEPARTMENT OF MGMCRI AND ADMITTED

UNDER THE DEPARTMENT OF GENERAL MEDICINE IN MGMCRI

HISTORY INCLUDING FAMILY HISTORY, MEDICATION HISTORY,HISTORY OF SMOKING AND

ALCOHOL USING A QUESTIONNAIRE, PATIENTS WITH BMI GREATER THAN 30 Kg/m2
GENERAL AND SYSTEMIC EXAMINATION.

MONITORING OF FASTING PLASMA GLUCOSE, POST PRANDIAL PLASMA

GLUCOSE AND HbA1C LEVELS IN THE SELECTED SUBJECTS

CONTROL(NORMOGLYCEMIC) CASES (PREDIABETICS)

FPG OF 70-99mg/dl FPG 0F 100-125 mg/dl
PPG LESS THAN 140 mg/dl PPG OF 140-200 mg/dl
HbA1c less than 5.7% HbA1c of 5.7 - 6.4 %

TO SEND HAEMOGLOBIN LEVELS, PLATELET COUNT

AND MEAN PLATELET VOLUME

COMPARING THE MEAN PLATELET VOLUME WITH

FASTING PLASMA GLUCOSE IN BOTH THE GROUPS USING
STATISTICAL ANALYSIS

33
n. Ethical Considerations:
Institute ethical committee clearance certification was sought and obtained

before the study was begun. Informed written consent was obtained from all patients

before including them in the study.

34
 6. RESULTS

Table 1. Distribution of age among study groups (n = 110)

Study groups
Age Total
Prediabetes n Normoglycemic p value*
(in years) n (%)
(%) n (%)
25 – 30 1 (1.8) 1 (1.8) 2 (1.8)
31- 40 7 (12.7) 6 (10.9) 13 (11.8)
41 -50 15 (27.3) 13 (23.6) 28 (25.5) 0.888
51 -60 19(34.5) 17(30.9) 36 (32.7)
>60 13(23.6) 18(32.7) 31 (28.2)
Total 55 (100) 55 (100) 110 (100)
* Chi Square test was applied to test statistical difference in proportions

Among the study population of 110 participants maximum of the participants

were in the age group of 51 to 60 years (32.7 %) followed by more than 60 years (28.2

%). Both the study groups were comparable in terms ofage of the participants, no

significant difference was observed between the groups (p value -0.888)

Figure 1. Distribution of age among study groups (n = 110)

Study groups Normoglycemic
Prediabetes
20 19
18
18 17
16 15
14 13 13
12
Frequency

10
8 7
6
6
4
2 1 1
0
25 – 30 31- 40 41 -50 51 -60 >60
Age (in years)

35
 Table 2. Distribution of mean age among the study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference
in mean p value*
Age Mean SD Mean SD (95% CI)

1.34
52.6 10.9 53.9 10.7 0.58
(-2.7 to 5.4)
*Student t test was applied for comparison of means

Mean age of the normoglycemic and prediabetes participants were 53.9±10.7 years

and 52.6±10.9 years respectively. The mean difference among the study groups was not

found to be statistically significant (p value- 0.58).

Figure 2. Distribution of mean Age among study groups (n=110)

70

60

50

40
Mean age

30

20

10
53.9 52.6
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

36
 Table 3. Distribution of gender among the study groups (n = 110)

Study group
Total
Gender p value*
Prediabetes Normoglycemic n (%)
n (%) n (%)
Male 41 (74.5) 38 (69.1) 79 (71.8)
0.525
Female 14 (25.5) 17 (30.9) 31 (28.2)

Total 55 (100) 55 (100) 110 (100)

* Chi Square test was applied to test statistical difference in proportions

Among the study population 71. 8 % were males and the rest 28.2 % were

females, of which Prediabetes group had 74.5% males and 14% females compared to

the normoglycemic group which showed 38% males and 17% females. Both the study

groups were comparable in terms ofgender, no significant difference was observed

between the groups (p value -0.525)

Figure 3. Distribution of gender among study groups (n = 110)

Study groups Normoglycemic
45 Prediabetes
41
40 38

35
30
Frequency

25
20 17
14
15
10
5
0
Male Female
Gender

37
 Table 4. Distribution of mean BMI among the study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
BMIkg/m2 Mean SD Mean SD (95% CI)

1.08
27.2 4.6 26.1 4.6 0.208
(-2.7 to 0.61)
*Student t test was applied for comparison of means

Mean BMI of the prediabetes and normoglycemic participants were 27.2±4.6 kg/m2

and 26.1±4.6 kg/m2 respectively. The mean difference among the study groups was not

found to be statistically significant (p value- 0.208).

Figure 4. Distribution of mean BMI among study groups (n=110)

35

30

25

20
Mean BMI

15

10

5
26.1 27.2
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

38
 Table 5. Distribution of obesity among the study groups based on BMI
(n = 110)
Study group
Total
BMI (kg/m2) Prediabetes Normoglycemic p value*
n (%)
n (%) n (%)
Underweight
2 (3.6) 0 (0) 2 (1.8)
(less than 18.5)
Normal
16 (29.1) 24 (43.6) 40 (36.4)
(18.5 -24.9)
Pre- obese
18 (32.7) 23 (41.8) 41 (37.3)
(25.0-29.9)
Obese I 0.021
18 (32.7) 6 (10.9) 24 (21.8)
(30.0-34.9)
Obese II
1 (1.8) 0 (0) 1 (0.9)
(35-39.9)
Obese III
(more than 0 (0) 2 (3.6) 2 (1.8)
40.0)
Total 55 (100) 55 (100) 110 (100)
* Chi Square test was applied to test statistical difference in proportions

Higher proportion of participants were in Pre-obese (32.7%) and obese I

(29.1%) range in prediabetes group compared to the normoglycemic group which

showed a higher proportion in the normal (43.6%) and pre-obese (41.8%). The

association was found to be statistically significant. (p-value- 0.021)

Figure 5. Distribution of obesity among study groups based on BMI (n = 110)

Study groups Normoglycemic

30
24 Prediabetes
25 23

20 18 18
Frequency

16
15

10
6
5 2 2
0 0 1 0
0

BMI

39
 Table 6. Distribution of participants with history of Dyslipidemia between
the study groups (n = 110)
Study group
Total
Dyslipidemia p value*
Prediabetes Normoglycemic n (%)
n (%) n (%)
Present 31 (56.4) 15 (27.3) 46 (41.8)
0.002
Absent 24 (43.6) 40 (72.7) 64 (58.2)

Total 55 (100) 55 (100) 110 (100)

* Chi Square test was applied to test statistical difference in proportions

Among the study population, 46 (41.8%) participants had a history of

dyslipidaemia and 64 (58.2%) had no history of dyslipidaemia. Higher proportion of the

pre-diabetes patients (56.4 %) had a history of dyslipidaemiacompared to

normoglycemic individuals (27.3 %). The association was found to be significant. (p

value -0.002)

Figure 6. Distribution of participants with history of dyslipidaemiabetween

the study groups (n = 110)

Study groups Normoglycemic

45
40
40 Prediabetes
35 31
30
Frequency

24
25
20
15
15
10
5
0
Present Absent
Dyslipidemia

40
 Table 7. Distribution of participants with history of alcohol intake among the
study groups
(n = 110)
Study group
Total
H/o alcohol p value*
Prediabetes Normoglycemic n (%)
n (%) n (%)
Present 21 (38.2) 13 (23.6) 34 (30.9)
0.09
Absent 34 (61.8) 42 (76.4) 76 (69.1)

Total 55 (100) 55 (100) 110 (100)

* Chi Square test was applied to test statistical difference in proportions

Among the study population 34 (30.9%) participants had a history of alcohol

consumption, among the study groups a higher proportion of alcohol intake was seen in

the prediabetes group (38.2 %) compared to normoglycemic group (23.6 %). The

association was not found to be statistically significant.

Figure 7. Distribution of participants with history of alcohol intake among the

study groups (n = 110)
Study groups
45 Normoglycemic 42
40
Prediabetes 34
35
30
Frequency

25
21
20
15 13

10
5
0
Present Absent
H/o Alcohol intake

41
 Table 8. Distribution of participants with history of Smoking among the
study groups (n = 110)
Study group
Total
H/o smoking p value*
Prediabetes Normoglycemic n (%)
n (%) n (%)
Present 17 (30.9) 7 (12.7) 24 (21.8)
0.02
Absent 38 (69.1) 48(87.3) 86 (78.2)

Total 55 (100) 55 (100) 110 (100)

* Chi Square test was applied to test statistical difference in proportions

Among the study population 24(21.8%) participants had a history of smoking,

among the study groups a higher proportion of smokers was seen in the prediabetes

group (30.9 %) compared to normoglycemic group (12.7 %). The association was found

to be statistically significant. (p-value- 0.02)

Figure 8. Distribution of participants with history of smoking among the

study groups(n = 110)
Study groups Normoglycemic

Prediabetes
60

50 48

40 38
Frequency

30

20 17

10 7

0
Present H/o Smoking Absent

42
 Table 9. Distribution of FBS among study groups (n = 110)
Study group
Total
FBS Prediabetes Normoglycemic p value*
n (%)
n (%) n (%)
<100 mg/dl 9 (16.4) 47(85.5) 56 (50.9)
100- 126 mg/dl 45 (81.8) 8 (14.5) 53 (48.2) < 0.00
>126 mg/dl 1 (1.8) 0 (0) 1 (0.9)
Total 55 (100) 55 (100) 110 (100)
* Chi Square test was applied to test statistical difference in proportions

Out of 110 study participants 56(50.9%) participants hadFBS less than 100

mg/dl and 53(48.2%) participants had the FBS between 100 and 126 mg/dl and 1

(1.8%) participant had FBS more than 126 mg/dl. Among the study groups in

Prediabetic group 45(81.8%) participants had FBS between 100 to 126 mg/dl and 9

(16.4%)had their FBS less than 100 mg/dl and 1(1.8%) participant had FBS levels

more than 126 mg/dl. In normoglycemic group 47(85.5%) participants had their FBS <

100 mg/dl (85.5%) and 8(14.5%) participants had their FBS between 100 and 126

mg/dl. The association was found to be statistically significant. (p-value < 0.00)

Figure 9. Distribution of FBS among the study groups (n = 110)

Study groups Normoglycemic

50 47
45
45 Prediabetes
40
35
Frequency

30
25
20
15
9 8
10
5 0 1
0
<100 mg/DL 100- 126 mg/DL >126 mg/DL
FBS

43
 Table 10. Distribution of FBS among study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
FBS (95% CI)
Mean SD Mean SD
(in mg/dl)

16.3
107.36 7.5 91.05 7.7 <0.00
(-19.1 to -13.4)
*Student t test was applied for comparison of means

Mean FBS of the prediabetes individuals was 107.36±7.5mg/dl and that of

normoglycemic was 91.05±7.7 mg/dl. The mean difference among the study groups

was found to be significant (p value <0.00).

Figure 10. Distribution of mean FBS among study groups (n=110)

140

120

100
FBS (in mg/dl)

80

60

40

20
91.05 107.36
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

44
 Table 11. Distribution of PPBS between the study groups (n = 110)
Study group
Total
PPBS Prediabetes Normoglycemic p value*
n (%)
n (%) n (%)
<140 mg/dl 6 (10.9) 55 (100) 61 (55.5)
< 0.00
140- 200 mg/dl 49 (89.1) 0 (0) 49 (44.5)
Total 55 (100) 55 (100) 110 (100)
* Fisher’s exact test was applied to test statistical difference in proportions

Among the study population 61(55.5%) participants had their PPBS less than

140 mg/dl, compared to the remining 49 (44.5%) participants with PPBS in the range of

140-200 md/dl Among the study group, the Prediabetes groups had 6(10.9%)

participants with PPBS < 140 mg/dl while the remaining 49 (89.1%) had PPBS values

in the range of 140-200 mg/dl in comparison to the normoglycemic groups which

showed all the 55(100%) showed the PPBS in the < 140 mg/dl levels. The association

was found to be statistically significant. (p-value < 0.00)

Figure 11. Distribution of PPBS between the study groups (n = 110)

Study groups Normoglycemic
60 Prediabetes
49
50

40
Frequency

30

20

10 6

0
<140 mg/DL 140- 200 mg/DL
PPBS

45
 Table 12. Distribution of PPBS among study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
PPBS (95% CI)
Mean SD Mean SD
(in mg/dl)

45.7
159.5 22.4 114.1 14.7 <0.00
(-52.9 to -38.5)
*Student t test was applied for comparison of means

Mean PPBS of the normoglycemic was 114.1±14.7mg/dl and that of the

prediabetes participants was 159.5±22.4 mg/dl. The mean difference among the study

groups was found to be statistically significant (p value <0.00).

Figure 12. Distribution of mean PPBS between the study groups (n=110)

200
180
160
140
PPBS (in mg/dl)

120
100
80
60
40
20
114.1 159.5
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

46
 Table 13. Distribution of HbA1c among the study groups (n = 110)

Study group
Total
HbA1c p value*
Prediabetes Normoglycemic n (%)
n (%) n (%)
<5.7 % 5 (9.1) 55 (100) 60 (54.5)
< 0.00
5.7 – 6.5 % 50 (90.9) 0 (0) 50 (45.5)

Total 55 (100) 55 (100) 110 (100)

* Fisher’s exact test was applied to test statistical difference in proportions

Among the study population 60(54.5%) participants had their HbA1c less than

5.7%, compared to the remining 50(45.5%) which has their HbA1c in the range of 5.7-

6.5% Among the study group, the Prediabetes group had 50 (90.9%) participants with

HbA1c in the range of 5.7 % to 6.5% while the remaining 5(9.1%) had the HbA1c less

than 5.7% in comparison to the normoglycemic groups which showed all the 55(100%)

with HbA1c less than 5.7%. The association was found to be statistically significant. (p-

value < 0.00)

Figure 13. Distribution of HbA1c among study groups HbA1c (n = 110)

Study groups Normoglycemic
60 55 Prediabetes
50
50

40
Frequency

30

20

10 5
0
0
<5.7 % 5.7 – 6.5 %
HbA1c

47
 Table 14. Distribution of HbA1C among the study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
HbA1C (95% CI)
Mean SD Mean SD
(in
percentage)
0.74
6.0 0.21 5.3 0.22 <0.00
(-0.82 to -0.65)
*Student t test was applied for comparison of means

Mean HBA1C of the normoglycemic and prediabetes participants were 5.3±0.22 %

and 6.0±0.21 %respectively. The mean difference among the study groups was found to

be statistically significant (p value <0.00).

Figure 14. Distribution of HbA1C among study groups (n=110)

5
HbA1C (in %)

1
5.3 6
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

48
 Table 15. Distribution of Platelet count among study groups (n = 110)
Study group
Platelets Total
Prediabetes Normoglycemic n (%) p value*
(in lakhs)
n (%) n (%)
<1.5 0 (0) 1 (1.8) 1 (0.9)
1.5- 4.0 54 (98.2) 53 (96.4) 107 (97.3) 0.604
>4 1 (1.8) 1 (1.8) 2 (1.8)
Total 55 (100) 55 (100) 110 (100)
* Chi Square test was applied to test statistical difference in proportions
Among the study population 107(97.3%) participants were with platelet count

between 1.5 to 4.0 lakhs and 1(0.9%)participant was with Platelet count less than 1.5

lakhs and 2(1.8%) participants had Platelet count more than 4 lakhs of which 54

(98.2%) participants in the Prediabetes group were with Platelet count in the range of

1.5 to 4 lakhs and 1 (1.8%) participant with platelet count more than 4 lakhs. In

normoglycemic group 53(96.4%) participants had platelet count in the range of 1.5 to 4

lakhs and 1(1.8%) participant had platelet count less than 1.5 lakhs and 1(1.8%) patient

had platelet count more than [Link] association was not found to be statistically

significant. (p-value – 0.604)

Figure 15. Distribution of Platelet count among study groups (n = 110)

Study groups Normoglycemic

60 54
53
Prediabetes
50

40
Frequency

30

20

10
1 0 1 1
0
<1.5 1.5- 4.0 >4
Platelet (in lakhs)

49
 Table 16. Distribution of Platelet count among the study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
Platelet (95% CI)
Mean SD Mean SD
count (in
Lakhs)
0.22
2.60 0.59 2.56 0.61 (-0.266 to - 0.604
0.190)
*Student t test was applied for comparison of means

Mean Platelet count of the normoglycemic and prediabetes participants were

2.56±0.61 lakhs and 2.60±0.59 lakhs, respectively. The mean difference among the

study groups was not found to be statistically significant (p value 0.604).

Table 17. Distribution of Hemoglobin among the study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
(95% CI)
Haemoglobin Mean SD Mean SD
g/dl
0.22
13.6 1.3 13.8 1.4 0.39
(-0.29 to -0.74)
*Student t test was applied for comparison of means

Mean HB of the normoglycemic and prediabetes participants were 13.8±1.3 g/dl

and 13.6±1.4 g/dl respectively. The mean difference among the study groups was not

found to be statistically significant (p value- 0.39).

50
 Figure 16. Distribution ofHaemoglobin among study groups (n=110)

16
14
12
Haemoglobin(g/dl)

10
8
6
4
2
13.8 13.6
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

51
 Table 18. Distribution of mean platelet volume among study groups (n=110)

Prediabetes Normoglycemic
(n = 55) (n = 55) Difference in
mean p value*
MPV (fL) Mean SD Mean SD (95% CI)

1.1
10.2 0.7 9.1 1.0 < 0.00
(-1.4 to -0.79)
*Student t test was applied for comparison of means

Mean MPV of the normoglycemic and prediabetes participants were 9.1±1.0 fL

and 10.2±0.7 fL respectively. The mean difference among the study groups was found

to be statistically significant (p value- 0.00).

Figure 17. Distribution of mean platelet volume among study groups (n=110)

12

10

6
MPV (fL)

2
9.1 10.2
0
Normoglycemic Prediabetes

*Vertical bars indicate standard deviation

52
 Figure 18. Correlation between FBS and MPV in normoglycemic group (n=55)

12 y = 0.0408x + 5.4204
R² = 0.0963
Pearson correlation coefficient =0.310
p value- 0.021
11

10
MPV

6
70 75 80 85 90 95 100 105 110
FBS (in mg/dl)

There is moderate positivecorrelation between FBS and MPV in the normoglycemic

group, that is as the FBS value increased MPV also increased correspondingly. Also,

the correlation between FBS and MPV among Normoglycemic group is statistically

significant (p value- 0.021).

53
 Figure 19. Correlation between FBS and MPV in prediabetes group (n=55)

11.5 y = 0.0166x + 8.4864

R² = 0.0311
Pearson correlation coefficient =0.176
p value - 0.198
11

10.5

10
MPV

9.5

8.5

8
90 100 110 120 130
FBS (in mg/dl)

There is a mild positive correlation between FBS and MPV among prediabetes,

that is as the FBS value increased MPV also increased correspondingly. Also, this

correlation in the prediabetic group was found to be statistically significant (p value-

0.198).

54
 7. DISCUSSION

In our study the maximum number of participants were in the ae group of 51 to

60 years (32.7 %) followed by more than 60 years (28.2 %). Both the study groups were

comparable in terms of age of the participants, no significant difference was observed

between the groups (p value-0.888). Mean age of the prediabetes and normoglycemic

participants were 52.6±10.9 years and 53.9±10.7 years, respectively. The mean

difference among the study groups was not found to be statistically significant (p value-

0.58).

Similar results were seen in studies done by Kurt89 et al, Sansanayudh90 et al,

Shinichiro Oshima91 et al and Kafrawy92 et al where the mean age was found to be

like our study. In contrast in study done by Ozder93et al the mean age of the diabetic

study population was a decade lesser (43 years) as the mean age of diabetes in Turkish

population is 45.8 ±15.3 years94.

Kafrawy92 et al and Ozder93 et al also found that there was no statistically

significant difference in ages of the participants which supports our results.

Among the study participants 71. 8 % were males whereas the rest 28.2 %

were females. Both the study groups were comparable in terms of gender, no significant

difference was observed between the groups (p value -0.525).Our study group had more

male participants which could be because more males came for hospital visit and more

males are exposed to risk factors such as smoking and alcohol.

In a study by Shetty95 et al showed there were 50.8% females and 49.2%

males, the majority being the females. Coban96 et al, Kafrawy92 et al and Ozder93 et al

found that sex had no statistical significance.

Among both the groups dyslipidaemia is found in higher proportion among

pre-diabetes individuals (56.4 %) compared to normoglycemic patients (27.3 %). The

55
association was found to be significant. (p value -0.002). The result of the study done

by Al Amri97et al showed similar result and a positive association between prediabetes

and dyslipidaemia.

Higher proportion of alcohol intake was seen among prediabetes group (38.2

%) compared to normoglycemic group (23.6 %). The association was not found to be

statistically significant. A study done by Cullmann98 et al concluded that high alcohol

consumption increased the risk of prediabetes in men and women. Higher proportion of

smoking was seen among prediabetes group (30.9 %) compared to normoglycemic

group (12.7 %). The association was found to be statistically significant. (p-value-

0.02).

A study done by Aeschbacher99 et al concluded that Smoking is strongly

associated with pre-diabetes supporting our study.

Higher proportion of participants were in Pre-obese (32.7%) and obese I

(29.1%) range in prediabetes group and normal (43.6%) and pre-obese (41.8%) in

normoglycemic group. The association was found to be statistically significant. (p-

value- 0.021). Mean BMI of the normoglycemic and prediabetes participants were

26.1±4.6 kg/m2 and 27.2±4.3 kg/m2, respectively. The mean difference among the study

groups was not found to be statistically significant (p value- 0.208).The result of a study

done by Ozder93et al also showed similar result of the mean BMI in the diabetic group

was 29.05 ± 4.37 kg/m2 whereas it was 27.37 ± 2.95 kg/m2 in the IFG group and it was

24.44 ± 2.50 kg/m2 in non-diabetic subjects (p = 0.000). The author also did not find

any statistically significant difference in MPV in terms of BMI. This was also supported

by Coban96 et al.

Higher proportion of normoglycemic individuals had their FBS < 100 mg/dl

(85.5%) whereas 81.8 % of the prediabetes participants had their FBS range between

56
100 and 126 mg/dl. The association was found to be statistically significant. (P-value <

0.00). Mean FBS of the prediabetes group was107.36±7.5 mg/dl and that of the

prediabetes group was 91.05±7.7 mg/dl. The mean difference among the study groups

was found to be significant (p value <0.00).

Similarly,Nermin100 et al showed in their study that the mean FBG results were

88.7 ± 8.1 mg/dL, 113.5 ± 5.4 mg/dL, 84.1 ± 7.6 mg/dL, and 97.8 ± 11.4 mg/dL in the

normoglycemic group, IFG, FP-OGL, and IGT groups, respectively. There was a

statistically significant difference between IFG and the other 3 groups. The FBG was

significantly higher in that group. Moreover, the FBG of the IGT group was

significantly higher than those of the control and FP-OGL groups.

According to Bhatta101 et al, the mean FBS in non-diabetic group was 83.83±

11.87 mg/dl, in IFG group was 117.37 ± 3.97 mg/dl and in diabetic group was 176.09 ±

49.35 mg/dl. Ozder93 et al observed that the mean fasting blood glucose level in the

diabetic population was 202.68 ± 63.06 mg/dL while that of the Prediabetes group was

111.07 ± 9.85 mg/dL and it was found as 90.07 ± 6.30 mg/dl in non-diabetic group (p =

0.000) which are having higher values compared to our study.

Higher proportion of prediabetes individuals had their PPBS value between

140 and 200 mg/DL (89.1%) and all the normoglycemic participants had PPBS value

less than 140 mg/DL. The association was found to be statistically significant. (p-value

< 0.00). Mean PPBS of the prediabetic participants was159.5±22.4 mg/dl and that of

the normoglycemic participants was 114.1±14.7 mg/dl. The mean difference among the

study groups was found to be statistically significant (p value <0.00).

Thomas102 et al found that the mean postprandial blood sugar (PPBS) level in

the diabetic population was 252.9 ± 94.85 mg/dl, whereas that of the nondiabetic group

was 133.4 ± 56.75 mg/dl which is higher than our findings.

57
 All the normoglycemic individuals had their HbA1c value less than 5.7 % whereas

around 91 % of the Prediabetes had their HbA1c range between 5.7 and 6.5 %. The

association was found to be statistically significant. (p-value < 0.00). Mean HBA1C of

the prediabetes and normoglycemic participants were 6.0±0.21% and 5.3±0.22%

respectively. The mean difference among the study groups was found to be statistically

significant (p value <0.00). Similar results seen in a study done by Thomas102 et al,

where the mean HbA1c level in the diabetic group was 9.13 ± 2.53%, as compared to

5.95 ± 0.723% in the nondiabetic group. Oshima91et al also found the mean HbA1c

level was 5.5±0.4% in normoglycemic group.

Among the study population majority of the participants 107 (97.3%) had their

platelet count between 1.5 to 4.0 lakhs (normal ranges)of which 54 (98.2%) participants

were in the Prediabetes group and 53(96.4%) participants were in the normoglycemic

group. One patient among the normoglycemic group had Platelet count less than 1.5

lakhs and one patient each in both the study groups had platelet count more than 4

lakhs. The association was not found to be statistically significant. (p-value – 0.604),

Mean Platelet count of the normoglycemic and prediabetes participants were 2.56±0.61

lakhs and 2.60±0.59 lakhs, respectively.

Similar results are seen in study done by Bhatta et al, where the mean platelet

count was 255.06 ± 76.44 x 109 /L in non-diabetic group, 259.95 ± 73.82 x 109 /L in

IFG group and 254.55 ± 87.81 x 109 /L in diabetic group and was found to be non-

significant. In study by Kafrawy et al92 the mean platelet count in the diabetic group

was higher thanthat of the nondiabetic group, that was similar to the studies done by

Demirtunc et103 aland Zuberi104et al. Other studies by Hekimsoy105 et al had observed

the opposite finding with lower platelet counts in the diabetic group compared with the

nondiabetic healthy participants. Hence, the platelet count could be dependent on

58
several variables, that is, mean platelet survival, platelet production rate, and turnover

rate in [Link], in our study, the prediabetic group had significantly higher MPV than

the normoglycemic group. This agreed with the findings seen in studies done by

Ateş106et al. and Papanas107 et [Link] platelet activation is seen in patients with

prediabetes, Platelet activation results in circulating large platelets with increased

expression of membrane receptors CD 63 (GP 53) and CD 62 (GMP-140).14 Hence,

platelet activation leads to increased MPV compared to normoglycemic individuals.

Mean MPV of the normoglycemic and prediabetes participants were 9.1±1.0

fL and 10.2± 0.7 fLrespectively. The mean difference among the study groups was

found to be statistically significant (p value- 0.00).

A study done byShimodaira108et al. also confirmed a relationship between

MPV and FBS in prediabetic patients. This result is consistent with the other previous

study by Kafrawy92, Hekimsoy105et al. which showed positive correlation.

The increased platelet size may be one of the factors in the increased risk of

atherosclerosis associated with prediabetes and associated micro-and macro-vascular

complications.

59
 8. LIMITATIONS AND RECOMMENDATION

Limitations:

 Sample size is one of the limitations of the study, further studies with

higher sample size are required.

 MPV could be positively and independently correlated with the FPGlevels,

not only in the prediabetic subjects but also innormoglycemic subjects,

after correcting for confounding variables.

 Single measurements of the blood glucose and hematological parameters

were subject to intra-individual variability this mighthave caused an

imprecise classification of participants, thusaffecting the results.

Recommendations:

 In the light of our findings, we propose that MPV can be used as a simple

and cost-effective tool to monitor the progression and control of Prediabetes

and thereby in preventing vascular events in primary health care.

60
 9. SUMMARY:

 An observational study was done among 110 participants in which maximum of

the participants was in the age group of 51 to 60 years (32.7 %) followed by

more than 60 years (28.2 %) and 71. 8 % were males whereas the rest 28.2 %

were female.

 Among both, the groups dyslipidemia is found in higher proportion among pre-

diabetes individuals (56.4 %) compared to normoglycemic patients (27.3 %).

The association was found to be significant. (p-value -0.002)

 A higher proportion of alcohol intake was seen among prediabetes group

(38.2 %) compared to normoglycemic group (23.6 %) and a higher proportion of

smoking was seen among prediabetesgroup (30.9 %) compared to

normoglycemic group (12.7 %).

 A higher proportion of participants were in Pre-obese (32.7%) and obese I

(29.1%) range in prediabetes group and normal (43.6%) and pre-obese (41.8%)

in the normoglycemic group.

 A higher proportion of normoglycemic participants had their FBS < 100 mg/DL

(85.5%) whereas 81.8 % of the prediabetes individuals had their FBS range

between 100 and 126 mg/DL. The association was found to be statistically

significant. (p-value < 0.00)

 A higher proportion of prediabetes participants had their PPBS value between

140 and 200 mg/DL (89.1%) and all the normoglycemic individuals had PPBS

value less than 140 mg/DL. The association was found to be statistically

significant. (p-value <0.00)

61
 All the normoglycemichad their HbA1c value less than 5.7 % whereas around

91 % of the Prediabetes individuals had their HbA1c range between 5.7 and 6.5

%. The association was found to be statistically significant. (p-value < 0.00)

 Higher proportion of normoglycemic (96.4 %) andprediabetes individuals (98.2

%) had their platelet range between 1.5 to 4 lakhs. The association was not

found to be statistically significant. (p-value – 0.604)

 Mean FBS of the normoglycemic was 91.05 mg/DL and that of the prediabetes

individuals was 107.36 mg/DL. The mean difference between the study groups

was found to be significant (p-value <0.00).

 Mean PPBS of the normoglycemia was 114.1 mg/DL and that of the prediabetes

participants was 159.5 mg/DL. The mean difference between the study groups

was found to be statistically significant (p-value <0.00).

 Mean HBA1C of the normoglycemicand prediabetes participants were 5.3 and

6.0 respectively. The mean difference between the study groups was found to be

statistically significant (p-value <0.00).

 Mean HBA1C of the normoglycemic and prediabetes participants were 5.3 and

6.0 respectively. The mean difference between the study groups was found to be

statistically significant (p-value <0.00).

 Mean HB of the normoglycemic and prediabetes participants were 13.8 and 13.6

respectively. The mean difference between the study groups was not found to be

statistically significant (p-value- 0.39).

 Mean MPV of the normoglycemic and prediabetes participants were 9.1 and

10.2 respectively. The mean difference between the study groups was found to

be statistically significant (p-value- 0.00).

62
 10. CONCLUSION:

Our study demonstrated MPV in prediabetic subjects was higher than that in

normoglycemic groups. In prediabetic subjects there is a positive correlation between

FBS and MPV, that is as the FBS value increased MPV also increased

[Link] may be suggested that platelets of prediabetic patients become more

aggregable and reactive due to increased MPV. Increased risk of cardiovascular

complications regarding Prediabetic patients in comparison with the normoglycemic

individuals may be a result of high MPV. Therefore, MPV might be a useful prognostic

marker of cardiovascular complications in patients who are diagnosed to have

Prediabetes.

Hence, MPV would be a useful prognostic marker of cardiovascular

complications in Prediabetes. Nonetheless, this study demonstrated that parameters of

glycemic control are associated with MPV at least in the unselected general population

with unrecognized or untreated impaired glycemic state and the clinical significance of

the association warrants further study.

63
 11. ABSTRACT

INTRODUCTION

Diabetes mellitus is a common chronic disease with high morbidity and

mortality.1Two of the main conditions of prediabetes are impaired levels of fasting

glucose (IFG) and impaired glucose tolerance (IGT). Prediabetes is an autonomous risk

factor for cardiovascular disorders. Mean platelet volume (MPV) can describe platelet

activity, and increased MPV is associated with thrombogenic activation and a high risk

of developing cardiovascular [Link] purpose of the present study was to compare

MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship

between MPV and fasting plasma glucose (FPG) levels in these two groups.

MATERIALS AND METHODS

It is an observational study where the participants were divided into two groups based on the FBS,

PPBS and HbA1c levels as prediabetic and normoglycemic group. Mean platelet volume levels

were measured in these patients and correlation between mean platelet volume and fasting plasma

glucose levels in both the groups were done using statistical analysis.

RESULTS
In our study we found out that Mean MPV of the prediabetes group was 10.2±0.7

fL which was higher than the normoglycemic group which was 9.1±1.0 [Link]

the fasting plasma glucose levels with the MPV in both the groups found out that there

was a significant positive correlation in both the groups.

CONCLUSION

Our study demonstratedMPV in prediabetic subjects was higher than that in

normoglycemic groups. In prediabetic subjects there is a positive correlation between

64
FBS and MPV, that is as the FBS value increased MPV also increased

[Link] may be suggested that platelets of prediabetic patients become more

aggregable and reactive due to increased MPV. Increased risk of cardiovascular

complications regarding Prediabetic patients in comparison with the normoglycemic

individuals may be a result of high MPV. Therefore, MPV might be a useful prognostic

marker of cardiovascular complications in patients who are diagnosed to have

Prediabetes.

Hence, MPV would be a useful prognostic marker of cardiovascular

complications in Prediabetes. Nonetheless, this study demonstrated that parameters of

glycaemic control are associated with MPV at least in the unselected general population

with unrecognized or untreated impaired glycaemic state and the clinical significance of

the association warrants further study.

65
 12. REFERENCES:

1. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis:

epidemiology, pathophysiology, and management. Jama 2002;287:2570-81.

2. Demirtas L, Degirmenci H, Akbas EM, et al. Association of hematological

indicies with diabetes, impaired glucose regulation and microvascular complications of
diabetes. International journal of clinical and experimental medicine 2015;8:11420.

3. Mellitus D. Diagnosis and classification of diabetes mellitus. Diabetes care

2005;28:S5-S10.

4. Čabarkapa V, Đerić M, Stošić Z, Sakač V, Davidović S, Eremić N. Determining

the relationship between homocysteinemia and biomarkers of inflammation, oxidative
stress and functional kidney status in patients with diabetic nephropathy. Journal of
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75
 13. ANNEXURE

13.1. ETHICAL COMMITTEE CERTIFICATE

76
 13.2 PROFORMA

Age: Sex:

OP No. IP No.

Complaints:

INFORMATION

H/o Type 2 DM Yes/No

H/o Hypertension Yes/No

H/o Dyslipedemia Yes/No

H/o Obesity Yes/No

H/o Alcohol Yes/No

H/o Smoker Yes/No

H/o Antiplatelet medication Yes/No

General examination

Height

Weight

BMI

BP

Investigations

FBS

PPBS

HBA1C

Hemoglobin

Platelet count

MPV

77
 RESEARCH PROJECT
13.3 PATIENT INFORMATION SHEET
CONSENT FORM
PART 1 OF 2
INFORMATION FOR PARTICIPANTS OF THE STUDY

NAME OF THE RESEARCH PROJECT:Correlation between mean Platelet

Volume and Fasting Plasma Glucose Levels in Prediabetes and

Normoglycemic Individuals.

We welcome you and thank you for having accepted our request to consider whether
you can participate in our study. This sheet contains the details of the study; the possible risks,
discomfort and benefits for the participants are also given.

You can read and understand by yourself; if you wish, we are ready to read and
explain the same to you.

If you do not understand anything or if you want any more details we are ready
to provide the details.

Information to the participants:

We welcome you and thank you for having accepted our request to consider whether
you can participate in our study. This sheet contains the details of the study; the possible risks,
discomfort and benefits for the participants are also given.

What is the purpose of the study?

To compare the mean platelet volume and fasting blood glucose in prediabetes and
normoglycemic individuals

Who / where this study is being conducted?

This study is being conducted by [Link]
Graduate medical student belonging to GENERAL MEDICINE department under the
guidance of [Link] RANGANATHAN GREEN.

78
Why I am being considered as one of the subject?
As your fasting blood glucose level is impaired and may suggest that you are in
Prediabetes stage you are being considered as one of the participants to assess the mean platelet
volume

Should I definitely have to take part in this study?

No. If you do not wish to participate you will not be included in this study. Also, you
will continue to get the medical treatment without any prejudice.

If am participating in this study, what are my responsibilities

You may have to follow some simple rules such as
1. Allow to do simple clinical examination
2. Allow to take blood samples – 3 to 5 ml which is required to evaluate your
underlying disease.
3. Allow me to utilize your clinical data for analysis and publication

Are there any benefits for me / public?

Yes, if you are diagnosed to have abnormalities in your blood examination an
appropriate advise on lifestyle modification, weight reduction, dietary advice will be given.
For public, if the abnormalities are found to be consistent, the result of the present study
will be utilized for early detection, prevention and treatment of patients with similar illnesses.

Will there be any discomfort / risks to me?

Clinical examination done is only for the purpose of underlying illnesss. The blood

sample drawn will be 3 to 5 ml by a trained faculty which might cause slight discomfort.

Will I be paid for the study?

No you will not be paid

Will my participating in this study, my personal details will be kept confidentially?

Yes, confidentiality will be maintained.

Will I be informed of this study’s results and findings?

Yes, if you want you can get the details from us.

Can I withdraw from this study at any time during the study period?
Yes. You can withdraw at any time during the study period without mentioning any
reason. You will continue to receive appropriate treatment without any bias.

79
 PART 2 OF 2
MAHATMA GANDHI MEDICAL COLLEGE AND RESEARCH
INSTITUTE
PUDUCHERRY

FORM FOR GETTING INFORMED CONSENT FOR THOSE

PARTICIPATING IN THE RESEARCH PROJECT
CORRELATION BETWEEN MEAN PLATELET VOLUME AND FASTING PLASMA
GLUCOSE LEVELS IN PREDIABETES AND NORMOGLYCEMIC INDIVIDUALS.

I _______________________ have been informed about the details of the study

in own language.
I have understood the details about the study.
I know the possible risks and benefits for me, by taking part in the study.
I understand that I can withdraw from the study at any point of time and even
then, I will continue to get the medical treatment as usual.
I understand that I will not get any payment for taking part in this study.
I will not object if the results of this study is getting published in any medical
journals, provided my personal identity is not reviewed.
I know what I am suppose to do by taking part in this study and I assure that I
will give my full co-operation for this study.

Signature/Thumb impression of the participant

(Name/Address)
__________________________________
__________________________________
__________________________________

Signature/Thumb impression of the witness (Name/Address)

____________________________________________________________________
__________________________________

Name & Signature of the investigator

__________________________________

80
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13.4 MASTER CHART

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13.5. PLAGIARISM CERTIFICATE

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 PLAGIARISM BONAFIDE CERTIFICATE

This is to certify that the dissertation titled “Correlation between Mean Platelet

Volume and Fasting Plasma Glucose Levels in Prediabetes and Normoglycemic

Individuals” is a bonafide original research work, done by K.K.N. SURIYA, Postgraduate,

Department of General Medicine, 2018-2021. This study has been authenticated under my

supervision and has been subjected to the mandatory plagiarism check using URKUND

anti-plagiarism scanner software, the total plagiarism match has been evaluated to be 6%. I

hereby certify that this original work has been authenticated and endorsed by the faculty

members in the Department of General Medicine.

Date: Dr. SIVA RANGANATHAN GREEN

Professor
Department of General Medicine

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