Diabetes Mellitus

Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of insulin.

This can arise in many different ways. Lack of insulin affects the metabolism of carbohydrate, protein and fat, and causes a significant disturbance of water and electrolyte homeostasis. Death may result from acute metabolic disbalance, while long-standing metabolic derangement is frequently associated with permanent and irreversible functional and structural changes in the cells of the body, with those of the vascular system being particularly susceptible.

Transmission and Control of disease (Epidemiology)

Epidemiological studies of whole populations have shown that the distribution of blood glucose concentration is unimodal, with no clear division between normal and abnormal values. However, hyperglycemia represents an independent risk factor for the development of disease of both small and large blood vessels.

Diagnostic criteria for diabetes have therefore been selected on the basis of identifying those who have a degree of hyperglycemia which, if untreated, is associated with a significantly increased risk of developing vascular disease. Diabetes is world-wide in distribution and the incidence of both type 1 and type 2 diabetes is rising. It is estimated that, in the year 2000, 150 million people world-wide had diabetes, and this is expected to double by 2010.

This global pandemic principally involves type 2 diabetes, and is associated with several contributory factors including increased longevity, obesity, unsatisfactory diet, sedentary lifestyle and increasing urbanization. However, the prevalence of both types of diabetes varies considerably around the world, and is related to differences in genetic and environmental factors. 

The prevalence of known diabetes in Britain is around 2-3%. Many more cases of type 2 diabetes remain undetected. In Europe and North America the ratio of type 2:type 1 is approximately 7:3. In northern Europe the prevalence of type 1 diabetes in children has doubled in the last 20 years, with a particular increase in children under 5 years of age. Type 2 diabetes is also commencing at an earlier age in many populations, and in some ethnic groups, such as Hispanic and Afro-Americans, is now being observed in children and adolescents.

Normal Glucose Metabolism and Homeostasis  

In humans, blood glucose is tightly regulated by homeostatic mechanisms and maintained within a narrow range of 3.5-6.5 mmol/l. A balance is preserved between the entry of glucose into the circulation from the liver, supplemented by intestinal absorption after meals, and glucose uptake by peripheral tissues, particularly skeletal muscle. A continuous supply of glucose is essential for the brain, which uses glucose as its principal metabolic fuel.When intestinal glucose absorption declines between meals, hepatic glucose output is increased in response to the counter-regulatory hormones glucagons and adrenaline, and it falls during prolonged starvation as other metabolic fuels derived from fat become more important. The liver produces glucose by gluconeogenesis and glycogen breakdown.  

Insulin is the only anabolic hormone and it has profound effects on the metabolism of carbohydrate, fat and protein. Insulin is secreted from pancreatic beta cells into the portal circulation, with a brisk increase in response to a rise in blood glucose (e.g. after meals). A glucose sensor has been identified in the portal vein which modulates insulin secretion via neural mechanisms. Insulin lowers blood glucose by suppressing hepatic glucose production and stimulating peripheral glucose uptake in skeletal muscle and fat, mediated by the glucose transporter, GLUT 4.

Metabolic Disturbances in Diabetes   

The hyperglycemia of diabetes develops because of an absolute (type 1 diabetes) or a relative (type 2 diabetes) deficiency of insulin, resulting in decreased anabolic and increased catabolic effects. In both type 1 and type 2 diabetes, the actions of insulin are also impaired by insensitivity of target tissues. While this is a fundamental defect in type 2 diabetes, hyperglycemia can also reduce insulin secretion by the effect of glucose toxicity on beta cell function.   

Investigations   

Urine Testing   

• Glucose Testing the urine for glucose is the usual procedure for detecting diabetes, using sensitive glucose-specific dipstick methods. If possible, testing should be performed on urine passed 1-2 hours after a meal since this will detect more cases of  diabetes than a fasting specimen. Glycosuria always warrants full assessment.
• Ketones  Ketone bodies can be identified by the nitroprusside reaction, which is primarily specific for acetoacetate. The test is conveniently carried out using tablets or dipsticks for ketones. Ketonuria may be found in normal people who have been fasting or exercising strenuously for long periods, who have been vomiting repeatedly, or who have been eating a diet high in fat and low in carbohydrate.  

Blood Testing   

• Glucose  When symptoms suggest diabetes, the diagnosis may be confirmed by a random blood glucose concentration greater than 11 mmol/l. When random blood glucose values are elevated but are not diagnostic of diabetes, glucose tolerance is usually assessed either by fasting blood glucose estimation or by the oral glucose tolerance test. 
• Glycated hemoglobin Glycated hemoglobin provides an accurate and objective measure of glycaemic control over a period of weeks to months. This can be utilized as an assessment of glycaemic control in a patient with known diabetes, but is not sufficiently sensitive to make a diagnosis of diabetes and is usually normal in patients with impaired glucose tolerance.

Major Manifestations of Disease  

Hyperglycemia is a very common biochemical abnormality. It is frequently detected on routine biochemical analysis of asymptomatic patients, and is found during conditions which impose a burden on pancreatic beta cells, such as pregnancy, severe illness or treatment with drugs such as corticosteroids ('stress hyperglycemia'). 

The classical symptoms of thirst, polyuria, nocturia and rapid weight loss are prominent in type 1 diabetes, but are often absent in patients with type 2 diabetes, many of whom are asymptomatic or have non-specific complaints such as chronic fatigue and malaise. Uncontrolled diabetes is associated with an increased susceptibility to infection and patients may present with skin sepsis (boils) and genital candidiasis, and complain of pruritus vulvae or balanitis.

Management/Treatment

Three methods of treatment are available for the management of diabetes:

• Diet alone,
• Oral hypoglycemic agents
• Insulin.   

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