This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.
According to the World Health Organisation diabetes mellitus is a state of chronic hyperglycaemia due to genetic and environmental factors. In type 1 diabetes mellitus there is no production of insulin whereas In type 2 diabetes mellitus there is insufficient insulin or cells do not respond to insulin present in the body (insulin resistance) (1). The most frequent form is type 2 diabetes that accounts for more than 85 % of cases , with type 1 diabetes accounting for 10% of cases ,specific and gestational diabetes with 5 % of cases (2).
WHO also estimates that more than 180 million people worldwide have diabetes mellitus and this number will most likely more than double by 2030 without urgent action. In 2005 an estimated 1.1 million people died from diabetes and 80 % of these deaths occurred in low and middle income countries such as Zimbabwe ,half of these people being under the age of 70 and 55 % being women (2).
Before the 1990s, diabetes was considered a rare medical condition in Africa. Epidemiological studies carried out in that decade, however, provided evidence of a trend toward increased incidence and prevalence of type 2 diabetes in African populations (3). Indeed, Africa is experiencing the most rapid demographic and epidemiological transition in world history. It is characterized by a tremendous rise in the burden of noncommunicable diseases (NCDs), underlined by the increasing life expectancy and lifestyle changes resulting from the reduction in infectious diseases and increased fertility, as well as Westernization(4).
Almost all the reports published between 1959 and 1985 showed a prevalence of diabetes below 1.4 percent, except those from South Africa, where higher prevalence was reported.
The prevalence of diabetes in Africa was approximately 3 million in 1994; but the region is due to experience a two-to threefold increase by the year 2010 (5). The highest prevalence is found in populations of Indian origin, followed by black populations and Caucasians. Among the population of Indian origin in South Africa and Tanzania, the prevalence is between 12 and 13 percent (6). The prevalence in blacks follows a Westernization gradient, with that of rural Africa generally below 1 percent but that of urban Africa between 1 and 6 percent. In general the prevalence of type 2 diabetes is low in both rural and urban communities of West Africa except in urban Ghana, where a high rate of 6.3 percent was recently reported (7). Moderate rates have been reported from South Africa: 4.8 percent in a semi-urban community in the Orange Free State, 6.0 percent in an urban community of the Orange Free State, 5.5 percent in Durban (mostly occupied by the Zulu tribe), and 8 percent in Cape Town (mostly occupied by the Xhosa tribe.)
INSULIN AND ITS FUNCTION IN GLUCOSE METABOLISM
The major function of insulin is to maintain low blood glucose levels and counter the concerted action of a number of hyperglycemia-generating hormones . Untreated disorders associated with insulin generally lead to severe hyperglycemia and shortened life span as in diabetes mellitus (1). Insulin is synthesized as a preprohormone in the β-cells of the islets of Langerhans. Its signal peptide is removed in the cisternae of the endoplasmic reticulum and it is packaged into secretory vesicles in the Golgi, folded to its native structure, and locked in this conformation by the formation of 2 disulfide bonds (1,8). Specific protease activity cleaves the center third of the molecule, which dissociates as C peptide, leaving the amino terminal B peptide disulfide bonded to the carboxy terminal A peptide. Insulin secretion from β-cells is principally regulated by plasma glucose levels (8). Increased uptake of glucose by pancreatic β-cells leads to a concomitant increase in metabolism. The increase in metabolism leads to an elevation in the ATP/ADP ratio. This in turn leads to the inhibition of an ATP-sensitive potassium channel (KATP channel). The net result is a depolarization of the cell leading to Ca2+ influx and insulin secretion (8).
(1,3) pecial transporter proteins found in cell membranes allow glucose that is in the blood to enter into a cell. These transporters are controlled indirectly by blood insulin in certain body cell types like muscle cells. Low levels of circulating insulin, or its complete absence, will prevent glucose from entering those cells as in typical type 1 diabetes. More commonly, however, there is a decrease in the sensitivity of cells to insulin for instance the reduced insulin sensitivity characteristic of type 2 diabetes, resulting in decreased glucose absorption. In either case, there is cell starvation and weight loss that is sometimes extreme. In a few cases, there is a defect in the release of insulin from the pancreas. Either way the effect is the same and that is elevated blood glucose levels (1,8).
Insulin receptor activation results in internal cellular mechanisms that directly affect glucose uptake by regulating the number and functioning of protein molecules in the cell membrane that are responsible for transporting glucose into the cell.Muscle cells (myocytes) and fat cells (adipocytes) are the two types of tissues that are most strongly influenced by insulin, as far as the stimulation of glucose uptake is concerned.Myocytes are important because of their central role in movement, breathing and circulation and adipocytes are important because they accumulate excess food energy against future needs. Together they account for about two-thirds of all cells in a typical human body (1,8).
Insulin binds to the extracellular portion of the alpha subunits of the insulin receptor. This causes a conformational change in the insulin receptor and there is activativation of the kinase domain situated on the intracellular portion of the beta subunits. This activated kinase domain autophosphorylates tyrosine residues on the C-terminus of the receptor as well as tyrosine residues in the IRS-1 protein. Consequently the following steps occur :
1. Phosphorylated IRS-1, in turn, binds to and activates phosphoinositol 3 kinase (PI3K).
2. PI3K catalyzes the reaction PIP2 + ATP → PIP3 + ADP.
3. PIP3 activates protein kinase B (PKB).
4. PKB phosphorylates glycogen synthase kinase (GSK) and thereby inactivates GSK.
5. GSK can no longer phosphorylate glycogen synthase (GS).
6. Unphosphorylated GS makes more glycogen.
PKB also facilitates vesicle fusion, resulting in an increase in GLUT4 transporters in the plasma membrane .After the signal has been produced, termination of signaling is needed and this can be by degradation and endocytosis of the receptor bound to insulin . In addition, signaling can be terminated by dephosphorylation of the tyrosine residues by tyrosine phosphatases. Serine/Threonine kinases are also known to reduce the activity of insulin. Finally, with insulin action being associated with the number of receptors on the plasma membrane, a decrease in the amount of receptors also leads to termination of insulin signaling (1,8,9).
In addition to its role in regulating glucose metabolism, insulin stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells. Insulin also modulates transcription, altering the cell content of numerous mRNAs. It stimulates growth, DNA synthesis, and cell replication, effects that it holds in common with the insulin-like growth factors (IGFs) and relaxin.(1,9).
DIAGNOSIS AND MONITORING OF DIABETES MELLITUS
Different tests can be used to diagnose and monitor blood glucose levels in diabetes mellitus patients and these include random and fasting blood glucose, oral glucose tolerance test, blood urea ,blood hydrogen, urinary protein, blood insulin, blood fructosamine and glycosylated haemoglobin (HbA1c) (1).
For diagnosis the OGTT , fasting and random blood glucose tests are ideal and according to the WHO guidelines, if the plasma glucose is <5.5 mmol/L then diabetes is unlikely. A fasting plasma glucose of 7.0 mmol/L or more, or a random glucose of 11.1 mmol/L or more makes diabetes likely and the diagnosis is confirmed by a repeat abnormal test. If the plasma glucose is between 5.5 and 6.9 mmol/L fasting, or between 5.5 and 11.0 mmol/L non-fasting, an OGTT with 75 g anhydrous glucose is recommended.(1)
Blood hydrogen,blood urea and urinary protein,can also be used in diagnosis of diabetes but only as non specific confirmatory tests for fasting,random blood glucose and OGTT.Blood Insulin is rarely measured in diagnosis of diabetes mellitus (1,8).
In the management and control of diabetes , blood glucose determined at the time of the clinic attendance can only give limited information and may not represent the overall closeness of control at other times therefore it has limitations in monitoring glucose control. The HbA1c test provides a better index of diabetic control than plasma glucose since it is not greatly affected by short-term fluctuations in plasma glucose (8).
GLYCOSYLATED HAEMOGLOBIN AND ITS IMPORTANCE
HbA1c is a form of haemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time (three to four months). In the normal 120 day lifespan of the red blood cell glucose molecules join to haemoglobin in a non enzymatic reaction forming HbA1c.In individuals with poorly controlled diabetes, increases in the quantities of the glycosylated haemoglobin have been noted (10,11). Once a haemoglobin molecule is glycosylated, it remains that way. A build up of HbA1c within the red blood cell reflects the average level of glucose to which the cell has been exposed during its life cycle(1,8).
Measuring HbA1c assesses the effectiveness of therapy by monitoring long term plasma glucose regulation. Monitoring of glycogenic status is considered a cornerstone of diabetes care and affects how physicians and patients adjust medical therapy as well as behavioural therapy (diet and exercise) (11,12). It has been shown in a randomised study that when health care providers and patients are informed about the HbA1c results blood glucose control is improved. Simply knowing the results improves glycemic control, either through improved efforts by the patient or by the provider (10).
GLUCOSE CONTROL IN DIABETICS
In a diet control study done among diabetics with HbA1c results available in the United States it was shown that , 39% had good control (HbA1c <7%) 36% had suboptimal control (HbA1c 7-9%) and 25% had poor control (HbA1c >9%) (13).
Public health laboratories in Zimbabwe do not offer the HbA1c assay for diabetic patients. Many patients are from poor socio-economic background and rely solely on public health facilities as they cannot afford private healthcare facilities. Thus, most Zimbabwean diabetics do not have any form of long term monitoring of their blood glucose levels and are at a risk of having high levels of HbA1c levels without them or their health care providers knowing it.
INCREASED HbA1c AND COMPLICATIONS OF DIABETES MELLITUS
A certain study showed that an average HbA1c level of 7.2% resulted in a 76% reduction in retinopathy , a 60% reduction in neuropathy , a 50% reduction in kidney disease and a 35% reduction in cardiovascular disease. (9,14). Another study in America demonstrated unequivocally that maintaining near normal blood glucose levels significantly lowers a person's risk of developing complications related to diabetes (9).
In a study done to determine the relationship of HbA1c levels to hospital admission of patients , it was found that the likelihood of admission increased with higher HbA1c levels. The number of admissions of diabetic patients with HbA1c levels in the range (10.8 % - 18.4 %) was higher with 5 481 admissions in a 3 year period compared with 2 566 admissions of patients with HbA1c levels in the reference region of 7.7 % - 8.1 %(11).