THE RELATIONSHIP BETWEEN LEPTIN AND ANTHROPOMETRIC PARAMETERS IN TYPE 2 DIABETIC PATIENTS


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THE RELATIONSHIP BETWEEN LEPTIN AND ANTHROPOMETRIC PARAMETERS IN TYPE 2 DIABETIC PATIENTS  

ABSTRACT

Obesity, a state of hyperleptinemia and leptin resistance, may play a role in the aeitiopathogenesis of type 2 diabetes mellitus. Leptin hormone which was originally recognized for its role as a satiety factor has now been implicated in a wide variety of multisystem biological functions, including the regulation of glucose homeostasis. However, there is paucity of information regarding leptin and its effect on the West African population. This study was therefore aimed at studying the relationship between leptin, obesity and insulin levels in type 2 diabetes mellitus. One hundred and eighty- three diabetics (183) and 96 control non-diabetics were studied. Pulse, blood pressure and anthropometric parameters of all the respondents were measured. Fasting blood sugar (FBS) was analyzed using the glucose oxidase method and lipid profile was determined using enzymatic method. Serum leptin and serum insulin were also analysed using enzyme linked immunoassay (ELISA) method. Homeostasis Model Assessment was used to determine insulin resistance. Type 2 diabetes mellitus patients and non- diabetic controls that were normotensive with no disease complications or associated chronic illness were used for the study. The mean serum leptin levels for the diabetics and non diabetics was observed to be 4.57 ± 0.17 ng/ml and 4.70 ± 0.25ng/ml respectively (p > 0.05) and the mean insulin level for the diabetic and non diabetic groups are 4.70 ± 0.25 μU/mL and 4.49 ± 0.01 μU/mL respectively (p < 0.05). A positive correlation was observed between leptin and body mass index (BMI) in both type 2 diabetic patients (r = 0.36, p < 0.05) and non-diabetics (r = 0.48, p < 0.05). A positive correlation was also found between leptin and waist circumference (WC) in both type 2 diabetic patients (r = 0.32, p < 0.05) and non-diabetics (r = 0.39, p < 0.05). Hip circumference (HC) also correlated positively with leptin in both the diabetics (r = 0.33, p < 0.05) and non-diabetics. The study also found a positive correlation between leptin and FBS in the non-diabetic group (r = 0.21, p < 0.05) but a negative correlation in the diabetic group(r = - 0.18, p < 0.05). A correlation was also found between leptin and HOMA-IR in both the diabetic (r = - 0.018, p < 0.05) and non-diabetics (r = 0.20, p < 0.05). However there was no significant relationship between leptin and insulin in both type 2 diabetic patients (r = 0.11, p > 0.05) and non-diabetics (r = - 0.06, p < 0.05). Age, BMI and WC emerged as the independent predictors of leptin in the diabetic group while BMI, WC and HC emerged as independent predictors of leptin in the non-diabetics.

TABLE OF CONTENT

Page Cover page …………………………………………………………………………. i Title Page..................................................................................................... ........ iii

Declaration ................................................................................................... ......... iv

Certification.................................................................................................. ......... v

Dedication .................................................................................................... ......... vi

Acknowledgement......................................................................................... ......... vii

Abstract ......................................................................................................... .......... viii

Table of contents ............................................................................................. .......... x

List of tables xv

List of figures xvii

List of appendices xix

Abbreviations xx

1.0 INTRODUCTION 1

1.1 Statement of research problem ..................................................................... 3

1.2 Rationale/ justification ....................................................................................... 4

1.3 Missing link ...................................................................................................... 5

1.4 Aim and objectives ............................................................................................. 5

1.4.1 Aim ..................................................................................................................... 5

1.4.2 Objectives ............................................................................................................ 5

1.5 Research hypothesis 6

2.0 LITERATURE REVIEW 7

2.1 Blood glucose homeostasis .................................................................................. 7

2.1.1 Blood glucose regulation ....................................................................................... 7

2.1.2 Insulin hormone and blood glucose homeostasis ................................................. 10

2.1.3 Mechanism of action of insulin ............................................................................ 15

2.1.4 Role of insulin in metabolism ............................................................................... 15

2.1.5 Insulin resistance ................................................................................................... 16

Role of catabolic hormone in blood glucose homeostasis ....................................17

Glucagon17

Cortisol17

Epinephrine18

Adipocyte hormone leptin18

Mechanism of action of leptin22

Role of Leptin in blood glucose homeostasis26

Obesity and type 2 diabetes mellitus28

Pathophysiology of obesity29

Role of adipose tissue in obesity31

Pathogenesis of type 2 diabetes mellitus33

Relationship between leptin, insulin and obesity in type 2 diabetes mellitus34

MATERIALS AND METHOD.37

Materials.37

Instrument for data collection37

Method38

Study area38

Study population40

Study design40

Sample size estimation40

Sampling method41

Inclusion and exclusion criteria41

Procedure for data collection.42

Ethical considerations42

Measurement of vital signs42

Anthropometric measurements.43

Laboratory procedures44

Data analysis47

Limitation.49

RESULTS50

Socio-demographic characteristics of the respondents50

4.1.1 Age and sex distribution ……………………………………………………… 50

4.1.2 Educational status …………………………………………………………….. 52

4.1.3 Respondents‘ occupations …………………………………………………… 52

4.1.4 Respondents‘ ethnicity ………………………………………………………. 52

Smoking and alcohol status of the respondents ……………………………..56

Physical exercise of the respondents56

Physiologic and biochemical parameter of respondents60

Weight, height, body mass index, waist circumference, hip circumference

and waist hip ratio of the respondents 60

Mean values of pulse rate, systolic, diastolic and mean arterial pressure of

the respondents 64

Mean serum leptin, insulin and glucose levels of the respondents68

Serum leptin levels of the respondents ……………………………………….68

Serum insulin levels of the respondents ………………………………………80

Serum lipid levels of the respondents …………………………………………87

Relationship between serum leptin, insulin, lipids, blood glucose and anthropometric parameters of the respondents ………………………………….94

Relationship between leptin, obesity and type 2 diabetes mellitus114

Discussions118

Weight, height, body mass index, waist circumference, hip circumference

and waist hip ratio of the respondents 118

Serum leptin, insulin and glucose levels of respondents120

Serum leptin levels of respondents ……………………………………………120

Serum insulin levels of respondents122

Serum lipids levels of respondents …………………………………………….128

Relationship between leptin, insulin, fasting blood glucose and

anthropometric parameters of respondents 130

SUMMARY, CONCLUSION AND RECOMMENDATIONS135

Summary136

Conclusion137

Recommendations138

REFERENCES 139

APPENDICES 163

CHAPTER ONE INTRODUCTION

Leptin is a 167-amino-acid protein transcribed from the obese (ob) gene of mice and human subjects (Zhang et al., 1997; Brennan et al., 2006). The hormone is expressed and secreted from the adipose tissue of mice and humans, and the quantity secreted is highly correlated with body fat mass and adipocyte size (Maffei et al., 1995; Considine et al., 1996). Obese people have been shown to have higher leptin levels than normal weight in people (Maffei, 1995).

Figure 1.1: Structure of Leptin

Leptin hormone was initially thought to play a vital role only in the regulation of food intake, energy expenditure, and whole-body energy balance in rodents and humans (Janechova et al., 2001). Since the discovery that leptin replacement improves insulin sensitivity and diabetes in mice homozygous for mutations of the obesity gene (ob gene), it is now been implicated in the pathophysiology of obesity and is shown to play a significant role in insulin resistance related to obesity (Harris et al., 1996). Leptin is also shown to play a role in blood glucose homeostasis (Heather et al., 2012). It has also been reported to normalize blood glucose and insulin levels in ob/ob mice with type 2 diabetes mellitus (Pellymounter, et al., 1995). Leptin has roles in insulin secretion by the β cells of the pancreas, and in the regulation of insulin action and energy metabolism in adipose tissue and skeletal muscle (Houseknecht et al., 1998). Reports from several studies also

demonstrated that obese people with type 2 diabetes mellitus have high leptin levels (Mehmet et al., 2004; Mohti et al., 2005). Similarly, Ramazan et al., (2010) showed high leptin levels in obesity and metabolic syndrome, including type 2 diabetes mellitus.

Diabetes Mellitus results from insulin deficiency, or impaired insulin response resulting in excess glucose in the blood (Guyton and Hall, 2003a). Type 1 is an autoimmune disease that often starts early in life and involves near total destruction of the β cells over time. Eventually, little or no insulin is produced, leading to a complete dependence on exogenous insulin. On the other hand, type 2 diabetes mellitus is characterized by insulin resistance in insulin dependent tissues, which may lead to a compensatory increase in insulin production and release in the blood. Persistent high levels of insulin will result in β cell damage and hence little insulin formation (Bakari and Onyemelukwe, 2005) However both hyperinsulineamia and hypoinsulinemia have been reported among type 2 diabetes mellitus patients (Bakari and Onyemelukwe, 2002). Type 2 diabetes mellitus is the most common form of diabetes mellitus and account for approximately 90-95% of cases of diabetes. Type 2 diabetes mellitus patients are vulnerable to varied forms of both short and long term complications, which often lead to disability (Thévenod et al., 2008).

Obesity, especially visceral obesity is an established risk factor for type 2 diabetes mellitus (Haffner, 2006). Data emerging over the past several years reported a worldwide increase in the number of obese people (Must et al., 1999). The increasing prevalence of obesity has resulted in similar increase in the number of persons with type 2 diabetes Mellitus (Hu, 2011).   There is currently a body of knowledge corroborating the fact that obesity is the major risk factor for insulin insensitivity in type 2 diabetes

mellitus (Khan and Flier, 2000; Petersen and Shulman, 2006). However, not all obese people have type 2 diabetes mellitus implying that other factors may also contribute to the pathology.

Anthropometry, including measurement of height (HT), weight (WT), body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) have served as simple, cheap and non-invasive markers of obesity (Adamu et al., 2013). Specifically, body mass index (BMI), a composite measure that compares weight and height, defines people as overweight (pre-obese) if their BMI is between 25 and 29.99 kg/m2; and obese when it is up to 30 kg/m2 (World Health Organization, 2014).

Physiologically, a combination of excessive food intake and inadequate physical activity explain most cases of obesity (Swinburn et al., 2004). However, the cause of obesity is multifactorial comprising of genetic, psychosocial and environmental factors (Nammi et al., 2004). However, the discovery of Leptin by Friedman and colleagues (1994) has lead to a breakthrough in the understanding of body weight regulation and the role of fat tissue as an endocrine organ (Marti et al., 1999).

Statement of the Research Problem

Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels (American Diabetes Association, 2013)

International Diabetes Federation (2014) estimates about 387 million people living with diabetes worldwide with global diabetes prevalence of 8.3% and the number is projected to increase to 592 million by the year 2035. This global trend will occur because of population ageing and growth, obesity, unhealthy diets and a sedentary lifestyle. The number of adult population affected by diabetes in Africa is 22 million with prevalence of 5.1% and is projected to increase to 41.5 million by the year 2035. More importantly however, an estimated additional 13.5 million undiagnosed cases of diabetes mellitus and up to 480.9 thousand diabetes related deaths occurred in the African continent in the year 2014 (American Diabetes Association, 2014). Diabetes mellitus is one of the major threats to economic development confronting the African Region with total diabetes health expenditure of 4.5 billion USD in 2014 (International Diabetes Federation, 2014).

An increasing trend of diabetes mellitus and its complications had been observed in parts of Nigeria, from 0.5% in the 1960s to 1.4% and 1.7% in Kwara and Lagos states respectively in 1988; and to 1.6% in Kaduna state (Adadevoh, 1970, Ohwovoriole et al., 1988, Erasmus et al., 1989, Bakari et al., 1999). A study by Dahiru et al., (2008) reported a prevalence rate of 2% in Zaria, a city in North western Nigeria. A similar study by Nyenwe et al., (2003) from Port Harcourt, South-southern Nigeria, found a prevalence rate of 7.9%. In the same vein, Adeleke et al., (2010), observed a prevalence rate of 3.1 per 1000 in their review of childhood diabetes mellitus in Kano, Nigeria between 1999 and 2006.

Rationale/Justification

Diabetes Mellitus is a major cause of morbidity and mortality worldwide with high prevalence rate worldwide and in the developing countries including Nigeria (Mbanya et

al., 1996). Type 2 diabetic patients are commonly obese and may have insulin resistance and an increase in prevalence of obesity has resulted to increase in type 2 diabetic patients (Bakari et al., 2007). Studies have shown that obese diabetics have higher levels of leptin (Misra et al., 2001; Adil, 2010) indicating that the problem may not be leptin deficiency but its resistance. However, there is paucity of information regarding leptin and its effect on the West African population. This study was therefore aimed at studying the relationship between leptin, obesity and insulin levels in type 2 diabetes mellitus patients. It is also hoped that the findings will be useful to physicians for improved management of type 2 diabetes mellitus.

Missing Link/Data

Data to show the relationship between plasma Leptin, Obesity and type 2 Diabetes Mellitus is scarce in the West African population more especially in Kano, North- western Nigeria where the study took place.

Aim and Objectives

Aim

To determine the relationship between plasma Leptin, Glucose, Insulin and Anthropometric parameters (waist circumference, hip circumference, waist to hip ratio, height, weight, BMI) in known type 2 diabetic patients.

Objectives

i. To assess the height, weight, waist circumference, hip circumference, waist-hip ratio and body mass index (BMI) of known type 2 diabetes mellitus patients and their matched non diabetic subjects.

ii. To estimate serum leptin, glucose, insulin and lipid levels of type 2 diabetic mellitus patients and non- diabetic subjects.

iii. To determine the relationship between serum leptin, obesity and type 2 diabetes mellitus.

iv. To determine the relationship between levels of serum insulin, glucose, leptin, lipid profile, insulin resistance and anthropometric measurements (height, weight, body mass index, waist circumference, hip circumference and waist-hip ratio).

Research Hypothesis

The level of serum leptin and obesity are related to type 2 diabetes mellitus.

.

THE RELATIONSHIP BETWEEN LEPTIN AND ANTHROPOMETRIC PARAMETERS IN TYPE 2 DIABETIC PATIENTS


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