1.0 Introduction – What is diabetes Mellitus?
Diabetes mellitus is a progressive disorder of chronic hyperglycaemia due to insulin deficiency or resistance and in some cases both which affects people of all ages. The chronic hyperglycaemia causes a range of macro- and microvascular complications. Macrovascular damage leads to increased prevalence of heart disease, stroke and peripheral vascular disease whereas microvascular complications can cause diabetic retinopathy, neuropathy and nephropathy(1). Over the past 30 years, the prevalence of diabetes mellitus (DM) has rapidly increased as a consequence of obesity, lack of exercise and an ageing population and estimates show that this “diabetes epidemic” will continue. In 2008, the international diabetes federation estimate that 246 million adults had DM worldwide and this number was likely to reach 380 million by 2025(2). Due to this increasing pervasiveness, the World Health Organisation has updated its estimates for the prevalence of DM for the year 2025 in the USA from 21.9 million to 30.3(3)(4). The global death percentage due to DM has increased from 5% in 2000 to 6.8% in 2010(5)(6). This shows the importance of developing an effective treatment.
There are 2 distinct types of DM, type 1 and type 2, with type 2 DM being the more common. Both types represent a spectrum; distinct at the two ends but somewhat overlapping towards the middle and hybrids forms are increasingly common. However, type 1 DM is defined as an autoimmune response against the pancreatic beta cells leading to an inability to produce insulin; an insulin deficiency. On the other hand, type 2 DM is defined as a state of insulin resistance resulting in hyperglycaemia due to increased hepatic glucose production and decreased peripheral glucose uptake. The resulting compensatory hypersecretion of insulin by beta cells causes hyperinsulinaemia and progressively results in beta cell failure. Furthermore, the high glucose level is toxic to beta cells resulting in further beta cell failure(1),(7). Other underlying components of type 2 DM such as, incretin deficiency, accelerated lipolysis, increased renal glucose reabsorption and hyperglucagonemia due to pancreatic α-cell failure are gradually being acknowledged(8,9). These findings have allowed the development of new drugs that target these defects. The purpose of this review is to discuss some of the current as well the new and emerging treatments for type 2 diabetes mellitus but first we must discuss some concepts regarding insulin and the importance of glucose regulation. Types 2 diabetes is caused by a combination of genetic and environmental factors. Genetic predisposition influences the vulnerability of developing type 2 diabetes, weather a person will develop it or not depends largely on their lifestyle.On one hand, genome studies have identified 16 susceptible loci and population studies have shown an increased risk of developing diabetes in identical twins of parents with type 2 diabetes when compared with non-identical twins. On the other hand, low birth weight, lack of education, poor diet and a sedentary lifestyle increase the risk. (1,10). The primary defect in diabetes is hyperglycaemia and the primary aim of any treatment is to achieve good glycaemic control. So, why does a glucose imbalance result in such complications and why is it important to regulate blood glucose levels? 2.0 Insulin and the importance of glucose regulation Although many tissues can utilise proteins and fats for energy in the absence of glucose; only glucose can supply important tissues like the brain and retina with sufficient nutrition. …show more content…
However, abnormally elevated blood glucose will exert a high osmotic pressure in the extracellular fluid resulting in cellular dehydration. High blood glucose will also cause loss of glucose in urine which results in osmotic diuresis further draining the body’s fluids and electrolytes. In addition, long term hyperglycaemia damages the vasculature resulting in the micro and macrovascular complication observed in type 2 DM(11). We have discussed the importance of glucose regulation but how is it regulated? 2.1 Regulation of blood glucose The liver is the main organ for glucose homeostasis and acts like a blood glucose buffer system, for example when the postprandial blood glucose elevation results in insulin secretion, any excess glucose is stored in the liver as glycogen; a phenomenon known as glycogenesis. Conversely, low blood glucose results in the subsequent decrease in insulin secretion by the pancreas resulting in release of glucose by the
Diabetes mellitus is a progressive disorder of chronic hyperglycaemia due to insulin deficiency or resistance and in some cases both which affects people of all ages. The chronic hyperglycaemia causes a range of macro- and microvascular complications. Macrovascular damage leads to increased prevalence of heart disease, stroke and peripheral vascular disease whereas microvascular complications can cause diabetic retinopathy, neuropathy and nephropathy(1). Over the past 30 years, the prevalence of diabetes mellitus (DM) has rapidly increased as a consequence of obesity, lack of exercise and an ageing population and estimates show that this “diabetes epidemic” will continue. In 2008, the international diabetes federation estimate that 246 million adults had DM worldwide and this number was likely to reach 380 million by 2025(2). Due to this increasing pervasiveness, the World Health Organisation has updated its estimates for the prevalence of DM for the year 2025 in the USA from 21.9 million to 30.3(3)(4). The global death percentage due to DM has increased from 5% in 2000 to 6.8% in 2010(5)(6). This shows the importance of developing an effective treatment.
There are 2 distinct types of DM, type 1 and type 2, with type 2 DM being the more common. Both types represent a spectrum; distinct at the two ends but somewhat overlapping towards the middle and hybrids forms are increasingly common. However, type 1 DM is defined as an autoimmune response against the pancreatic beta cells leading to an inability to produce insulin; an insulin deficiency. On the other hand, type 2 DM is defined as a state of insulin resistance resulting in hyperglycaemia due to increased hepatic glucose production and decreased peripheral glucose uptake. The resulting compensatory hypersecretion of insulin by beta cells causes hyperinsulinaemia and progressively results in beta cell failure. Furthermore, the high glucose level is toxic to beta cells resulting in further beta cell failure(1),(7). Other underlying components of type 2 DM such as, incretin deficiency, accelerated lipolysis, increased renal glucose reabsorption and hyperglucagonemia due to pancreatic α-cell failure are gradually being acknowledged(8,9). These findings have allowed the development of new drugs that target these defects. The purpose of this review is to discuss some of the current as well the new and emerging treatments for type 2 diabetes mellitus but first we must discuss some concepts regarding insulin and the importance of glucose regulation. Types 2 diabetes is caused by a combination of genetic and environmental factors. Genetic predisposition influences the vulnerability of developing type 2 diabetes, weather a person will develop it or not depends largely on their lifestyle.On one hand, genome studies have identified 16 susceptible loci and population studies have shown an increased risk of developing diabetes in identical twins of parents with type 2 diabetes when compared with non-identical twins. On the other hand, low birth weight, lack of education, poor diet and a sedentary lifestyle increase the risk. (1,10). The primary defect in diabetes is hyperglycaemia and the primary aim of any treatment is to achieve good glycaemic control. So, why does a glucose imbalance result in such complications and why is it important to regulate blood glucose levels? 2.0 Insulin and the importance of glucose regulation Although many tissues can utilise proteins and fats for energy in the absence of glucose; only glucose can supply important tissues like the brain and retina with sufficient nutrition. …show more content…
However, abnormally elevated blood glucose will exert a high osmotic pressure in the extracellular fluid resulting in cellular dehydration. High blood glucose will also cause loss of glucose in urine which results in osmotic diuresis further draining the body’s fluids and electrolytes. In addition, long term hyperglycaemia damages the vasculature resulting in the micro and macrovascular complication observed in type 2 DM(11). We have discussed the importance of glucose regulation but how is it regulated? 2.1 Regulation of blood glucose The liver is the main organ for glucose homeostasis and acts like a blood glucose buffer system, for example when the postprandial blood glucose elevation results in insulin secretion, any excess glucose is stored in the liver as glycogen; a phenomenon known as glycogenesis. Conversely, low blood glucose results in the subsequent decrease in insulin secretion by the pancreas resulting in release of glucose by the