Diabetes mellitus is a group of metabolic diseases characterised by high blood sugar (glucose) levels that result from defects in insulin secretion, or its action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with “sweet urine,” and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycaemia) lead to spillage of glucose into the urine, hence the term sweet urine.
According to the World Health Organisation (WHO), an estimated 17.3 million people died from cardiovascular diseases in 2008, representing 30 per cent of all global deaths. Of these deaths, an estimated 7.3 million were due to coronary heart disease and 6.2 million were due to stroke.
Medical experts, assembled by Pfizer Nigeria & East Africa Region (Pfizer NEAR), have identified hypertension, diabetes mellitus, hyperlipidaemia (high fat/cholesterol level), cigarette smoking, obesity and sedentary living as modifiable risk factors; and family history, age and gender as the non-modifiable risk factors.
The team of medical experts led by consultant nephrologist and medical director of Ibadan Hypertension Clinic, Emeritus Professor Oladipo Akinkugbe, at the Cardiovascular Summit organised recently by Pfizer Nigeria, Ghana and East Africa Region, recommended preventive strategies, which include control of high cholesterol levels and high blood pressure through the modification of dietary habits and government‘s support, especially in the discouragement of western dietary habits through its food and health regulatory agencies.
Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalise the glucose level. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycaemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.
Impact of diabetes
Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the result of damage to small vessels, referred to as microvascular disease. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. This is referred to as macrovascular disease.
From an economic perspective, the total annual cost of diabetes in 2011 was estimated to be 174 billion dollars in the United States. This included 116 billion in direct medical costs (healthcare costs) for people with diabetes and another 58 billion in other costs, due to disability, premature death, or work loss. Medical expenses for people with diabetes are over two times higher than those for people who do not have diabetes. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.
Diabetes was the 7th leading cause of death in the United States listed on death certificates in 2007.
Specific causes of diabetes
Insufficient production of insulin (either absolutely or relative to the body’s needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycaemia and diabetes.
This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as insulin resistance. This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin-producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycaemia develops.
Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilised. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells’ inability to utilise glucose gives rise to the ironic situation of “starvation in the midst of plenty”. The abundant, unutilised glucose is wastefully excreted in the urine.
Insulin is a hormone that is produced by specialised cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body’s needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycaemia).
Types of diabetes
There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also formerly called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body’s immune system. The patient with type 1 diabetes must rely on insulin medication for survival.
In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells that are directed against and cause damage to patients’ own body tissues. In persons with type 1 diabetes, the beta cells of the pancreas, which are responsible for insulin production, are attacked by the misdirected immune system. It is believed that the tendency to develop abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood.
Exposure to certain viral infections (mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. Some of the antibodies seen in type 1 diabetes include anti-islet cell antibodies, anti-insulin antibodies and anti-glutamic decarboxylase antibodies. These antibodies can be detected in the majority of patients, and may help determine which individuals are at risk for developing type 1 diabetes.
At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age, however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the people with diabetes, only approximately 10 per cent have type 1 diabetes and the remaining 90per cent have type 2 diabetes.
Type 2 diabetes was also previously referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately for their body’s needs, particularly in the face of insulin resistance as discussed above. In many cases, this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells).
In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis, despite elevated glucose levels. The control of gluconeogenesis becomes compromised.
While it is said that type 2 diabetes occurs mostly in individuals over 30 years old and the incidence increases with age, we are seeing an alarming number patients with type 2 diabetes who are barely in their teen years. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise.
While there is a strong genetic component to developing this form of diabetes, there are other risk factors – themost significant of which is obesity. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20 per cent increase over desirable body weight.
Regarding age, data shows that for each decade after 40 years of age, regardless of weight, there is an increase in incidence of diabetes. The prevalence of diabetes in persons 65 years of age and older is around 27 per centtype 2 diabetes is also more common in certain ethnic groups. Compared with a 7 per cent prevalence in non-Hispanic Caucasians, the prevalence in Asian Americans is estimated to be 8 per cent, in Hispanics 12 per cent, in blacks around 13 per cent, and in certain Native American communities 20 per cent to 50 per cent. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy (gestational diabetes).
Diabetes can occur temporarily during pregnancy, and reports suggest that it occurs in 2per cent to 10 per cent of all pregnancies. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 35to 60 per cent of women with gestational diabetes will eventually develop type 2 diabetes over the next 10 to 20 years, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Patients with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth, to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to the patient’s future risk for developing diabetes.
“Secondary” diabetes refers to elevated blood sugar levels from another medical condition. Secondary diabetes may develop when the pancreatic tissue responsible for the production of insulin is destroyed by disease, such as chronic pancreatitis (inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas.
Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing’s syndrome. In acromegaly, a pituitary gland tumour at the base of the brain causes excessive production of growth hormone, leading to hyperglycaemia. In Cushing’s syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation.
In addition, certain medications may worsen diabetes control, or “unmask” latent diabetes. This is seen most commonly when steroid medications (such as prednisone) are taken and also with medications used in the treatment of HIV infection (AIDS).
The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption.
The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein.
A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite. Some untreated diabetes patients also complain of fatigue, nausea and vomiting. Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas. Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.
The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor’s office using a glucose meter.
Normal fasting plasma glucose levels are less than 100 milligrams per decilitre (mg/dl).Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes.
A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes.
When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.
The oral glucose tolerance test
Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose. There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.
For the test to give reliable results:
* The person must be in good health (not having any other illnesses, not even a cold).
* The person should be normally active (not lying down, for example, as an inpatient in a hospital), and
* The person should not be taking medicines that could affect the blood glucose.
* The morning of the test, the person should not smoke or drink coffee.
The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.
People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1 to 5 per cent of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes.
Research has shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians now understand that impaired glucose tolerance is not simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.
Glucose tolerance tests may lead to one of the following diagnoses:
Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
Impaired glucose tolerance: A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.
Gestational diabetes: A pregnant woman has gestational diabetes when she has any two of the following:a fasting plasma glucose of 92 mg/dl or more, a 1-hour glucose level of 180 mg/dl or more, or a 2-hour glucose level of 153 mg/dl, or more.
Chronic complications of diabetes
These diabetes complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys and nerves (microvascular disease), and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart disease (angina or heart attack), strokes, and pain in the lower extremities because of lack of blood supply (claudication).
The major eye complication of diabetes is called diabetic retinopathy. Diabetic retinopathy occurs in patients who have had diabetes for at least five years. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina. Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Spontaneous bleeding from the new and brittle blood vessels can lead to retinal scarring and retinal detachment, thus impairing vision.
To treat diabetic retinopathy, a laser is used to destroy and prevent the recurrence of the development of these small aneurysms and brittle blood vessels. Approximately 50 per cent of patients with diabetes will develop some degree of diabetic retinopathy after 10 years of diabetes, and 80 per cent of diabetics have retinopathy after 15 years of the disease. Poor control of blood sugar and blood pressure further aggravates eye disease in diabetes.
Cataracts and glaucoma are also more common among diabetics. It is also important to note that since the lens of the eye lets water through, if blood sugar concentrations vary a lot, the lens of the eye will shrink and swell with fluid accordingly. As a result, blurry vision is very common in poorly controlled diabetes. Patients are usually discouraged from getting a new eyeglass prescription until their blood sugar is controlled. This allows for a more accurate assessment of what kind of glasses prescription is required.
Kidney damage from diabetes is called diabetic nephropathy. The onset of kidney disease and its progression is extremely variable. Initially, diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste products in the blood leads to the need for dialysis. Dialysis involves using a machine that serves the function of the kidney by filtering and cleaning the blood. In patients who do not want to undergo chronic dialysis, kidney transplantation can be considered.
The progression of nephropathy in patients can be significantly slowed by controlling high blood pressure, and by aggressively treating high blood sugar levels. Angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) used in treating high blood pressure may also benefit kidney disease in diabetic patients.
Nerve damage from diabetes is called diabetic neuropathy and is also caused by disease of small blood vessels. In essence, the blood flow to the nerves is limited, leaving the nerves without blood flow, and they get damaged or die as a result (a term known as ischemia). Symptoms of diabetic nerve damage include numbness, burning, and aching of the feet and lower extremities. When the nerve disease causes a complete loss of sensation in the feet, patients may not be aware of injuries to the feet, and fail to properly protect them. Shoes or other protection should be worn as much as possible. Seemingly minor skin injuries should be attended to promptly to avoid serious infections. Because of poor blood circulation, diabetic foot injuries may not heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and even gangrene, necessitating surgical amputation of toes, feet, and other infected parts.
Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction can also be caused by poor blood flow to the penis from diabetic blood vessel disease.
Diabetic neuropathy can also affect nerves to the stomach and intestines, causing nausea, weight loss, diarrhoea, and other symptoms of gastroparesis (delayed emptying of food contents from the stomach into the intestines, due to ineffective contraction of the stomach muscles).
The symptom of diabetic nerve damage may respond to traditional treatments with certain medications such as gabapentin (Neurontin), henytoin (Dilantin), and arbamazepine (Tegretol) that are traditionally used in the treatment of seizure disorders. Mitriptyline (Elavil, Endep) and desipramine (Norpraminine) are medications that are traditionally used for depression. While many of these medications are not indicated specifically for the treatment of diabetes related nerve pain, they are used by physicians commonly.
The pain of diabetic nerve damage may also improve with better blood sugar control, though unfortunately blood glucose control and the course of neuropathy do not always go hand in hand. Newer medications for nerve pain include Pregabalin (Lyrica) and duloxetine (Cymbalta).
Slowing downdiabetes complications
Findings from the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown that aggressive and intensive control of elevated levels of blood sugar in patients with type 1 and type 2 diabetes decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 160 mg/dl after meals; and a near normal haemoglobin A1c level.
Studies in type 1 patients have shown that in intensively treated patients, diabetic eye disease decreased by 76 per cent, kidney disease decreased by 54 per cent, and nerve disease decreased by 60 per cent. More recently, the EDIC trial has shown that type 1 diabetes is also associated with increased heart disease, similar to type 2diabetes. However, the price for aggressive blood sugar control is a two to three fold increase in the incidence of abnormally low blood sugar levels (caused by the diabetes medications). For this reason, tight control of diabetes to achieve glucose levels between 70 to120 mg/dl is not recommended for children under 13 years of age, patients with severe recurrent hypoglycaemia, patients unaware of their hypoglycaemia, and patients with far advanced diabetes complications. To achieve optimal glucose control without an undue risk of abnormally lowering blood sugar levels, patients with type 1 diabetes must monitor their blood glucose at least four times a day and administer insulin at least three times per day. In patients with type 2 diabetes, aggressive blood sugar control has similar beneficial effects on the eyes, kidneys, nerves and blood vessels.
How is diabetes treated?
The major goal in treating diabetes is to minimise any elevation of blood sugar (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, treatment with insulin is considered.
Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol, and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal.
Weight reduction and exercise are important treatments for diabetes. Weight reduction and exercise increase the body’s sensitivity to insulin, thus helping to control blood sugar elevations.
Medications for type 2 diabetes
WARNING: All the information below applies to patients who are not pregnant or breastfeeding. At present the only recommended way of controlling diabetes in women who are pregnant or breastfeeding is by diet, exercise and insulin therapy. You should speak with your doctor if you are taking these medications and are considering becoming pregnant or if you have become pregnant while taking these medications.
Based on what is known, medications for type 2 diabetes are designed to:
* increase the insulin output by the pancreas;
* decrease the amount of glucose released from the liver;
* increase the sensitivity (response) of cells to insulin;
* decrease the absorption of carbohydrates from the intestine; and
* slow emptying of the stomach to delay the presentation of carbohydrates for digestion and absorption in the small intestine.
When selecting therapy for type 2 diabetes, consideration should be given to:
* the magnitude of change in blood sugar control that each medication will provide;
* other coexisting medical conditions (high blood pressure, high cholesterol, etc.);
* adverse effects of the therapy;
* contraindications to therapy;
* issues that may affect compliance (timing of medication, frequency of dosing); and
* cost to the patient and the health care system.
It is important to remember that if a drug can provide more than one benefit (lower blood sugar and have a beneficial effect on cholesterol, for example), it should be preferred. It is also important to bear in mind that the cost of drug therapy is relatively small, compared to the cost of managing the long-term complications associated with poorly controlled diabetes.
Varying combinations of medications also are used to correct abnormally elevated levels of blood glucose in diabetes. As the list of medications continues to expand, treatment options for type 2 diabetes can be better tailored to meet an individual’s needs. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient. Patients with type 2 diabetes should work closely with their physicians to achieve an approach that provides the greatest benefits while minimising risks.
Patients with diabetes should never forget the importance of diet and exercise. The control of diabetes starts with a healthy lifestyle regardless of what medications are being used.
Report compiled by Adebayo Folorunsho-Francis with additional reports from medicinenet.com/diabetes_treament and American Diabetes Association