ABSTRACT

Diabetes mellitus is a chronic metabolic disorder in which there are high blood sugar levels over a prolonged period. It is characterized by hyperglycemia and insulin resistance which stems up from the interactions of several genetic and environmental factors. It’s a non-communicable disease. The association of Angiotensin Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) has been studied extensively throughout many different geographic and ethnic populations with marked inconsistencies. Hence, this study is aimed at investigating the association of Angiotensin (ACE) gene polymorphism with diabetes in the Buea municipality. The identification of specific variations in the Buea municipality will help in the early diagnosis of pre-diabetics and diabetics, and create awareness in the population about genetic predisposition to T2DM. Blood samples were collected from 11 subjects (5 diabetics and 6 non-diabetics). DNA was extracted by the non-enzymatic salting out method and the samples were genotyped for ACE I/D polymorphism by a PCR base method followed with visualization by gel electrophoresis. Analysis of the ACE I/D polymorphism with T2DM indicated that there was a statistically non-significant difference in the frequency of the genotypes (p=0.497). This therefore confirmed that ACE I/D polymorphism may not be associated with T2DM risk in the Buea population.

CHAPTER ONE

INTRODUCTION AND LITERATURE REVIEW

1.1 Introduction

Diabetes Mellitus (DM) is a chronic metabolic disease characterized by an abnormal increase in blood sugar and need for continuous care. The World Health Organization (WHO) estimates that 6% of world population is a carrier of DM. The prevalence of disease increases with age in both sexes, and the estimated risk of DM throughout life is 30 to 40%, and is associated with the development of lesions in the pancreas and in the long term, to an increased risk of ophthalmological, renal cardiac, vascular or neuropathic complications.

(Saeed et al., 2019 Depending on its cause, DM can be classified as type 1 diabetes (T1DM), which is autoimmune and is characterized by the death of pancreatic β cells, specifically of the pancreatic islet, responsible for insulin production and type 2 diabetes (T2DM), also known by late diabetes and which begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin production may also develop. Also, in this type of diabetes, there is aggregation of Islet Amyloid PoliPeptides (IAPP) considered as a critical pathological process associated with the death of pancreatic β cells, a situation that also occurs in patients undergoing transplantation of the pancreas. (Akram et al., 2015). These two variants account for 90% to 95% of all diabetic patients (Wu et al., 2014). The severity of symptoms is due to the type and duration of diabetes.   Diabetes may result in even more severe conditions like kidney disease, heart disease, stroke, swollen feet as seen in diabetic neuropathy. Uncontrolled diabetes may lead to stupor, diabetic coma and if not treated death due to ketoacidosis or rare from non-ketotic hyperosmolar syndrome. (ADA; Craig et al.2009; Galtier., 2010). Studies have revealed that prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014 (Sarwar et al.,2010 from Africa (WHO, 2014). According to WHO report 2016, 1.097 million people are living with diabetes in Cameroon. Thus, T2DM is a growing potential threat to health in Cameroon.

Globally, the prevalence of diabetes and the diabetic population has risen from 108million in 1980 to 422million in 2014 and in 2016 an estimated 1.6 million deaths were directly caused by diabetes (WHO. 2018). The Middle East and North Africa region has the highest prevalence of diabetes in adults (10.9) while the Western pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes (37.5%) (Akram et al.,2015). T2DM accounts for over 90% of DM in sub Saharan Africa (Levitt.,2008; Hall et al.,2011) and prevalence is rapidly increasing in South Africa. population, 70% of whom remained undiagnosed (Mbanya et al.,2008).

Risk factors of diabetes include excessive alcohol intake, excessive smoking, obesity, age, family history of diabetes, urban residence and CAPN10, GLUT2, GCGR and ACE genes have been associated with diabetes in some populations (Winter. 2018). The association of angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism with T2DM has been extensively studied throughout various ethnicity but largely with inconsistent findings (Alsafar et al., 2015). Nevertheless, an association between ACE/ID polymorphism and T2DM could be expected in the Emirati population, since it is amongst the population with one of the highest T2DM prevalence (International Diabetes Federation; IDF). As such this study is to illuminate the possible association of angiotensin converting enzyme polymorphism with diabetes in the Buea municipality.

1.2 Rationale

Diabetes is a worldwide public health problem made more acute in Africa by low socio-economic standards. In Cameroon, the prevalence of diabetes in urban areas is currently estimated at 6-8% of people living with diabetes who are currently undiagnosed in the population. Despite numerous reports suggesting a substantial genetic contribution to the susceptibility of T2DM no major susceptibility genes have been identified. Variation in association of T2DM to ACE I/D gene polymorphism is due to geographical location and ethnic groups. Some studies have shown that the association of ACE I/D polymorphism with T2DM yielded contradictory results, hence this study aims at identifying the possible association between ACE I/D polymorphism and T2DM. This will help the people of Buea community to know whether they are prone to diabetes or not and to control their feeding habits and lifestyle and as such avoid developing diabetes in the long run.

1.3 Hypothesis

It is hypothesized that there is an association between the angiotensin converting enzyme gene polymorphism and diabetes mellitus.

1.4 Objectives

1.4.1 Overall Objectives

To investigate the association of angiotensin converting enzyme gene polymorphisms with type 2 diabetes mellitus in the Buea municipality.

1.4.2 Specific Objectives

1. To genotype the individuals in the Buea municipality.
2. To identify the genotype responsible for type 2 diabetes mellitus in Buea municipality.