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Diabetes mellitus is a long term disorder in which patients have raised plasma glucose. There are two types of diabetes; type 1 which is insulin deficient diabetes, insulin is not produced by the body or. Type 2 diabetes is where the function of beta cells in the pancreas is impaired hence insulin is not released and the body looses insulin sensitivity. According to the NHS, diabetes affects 2 million people in England and Wales and a further 750, 000 undiagnosed individuals.1 Treatment of patients with just diabetes is a lot easier then treatment of the associated complications patients may have with diabetes, hence this review will be directed more to the treatment and control of these complications.
These include thirst, polyuria, fatigue and malaise, blurred vision, infections, complications and altered mental state. The last three complications are more specific to type 2 diabetes whereas the first four symptoms are the most common in diabetes.
The diagnosis criteria is where patients do not show normal plasma glucose levels at fasting to be < 7mmol/L and at random to be < 11mmol/L. Diagnosis of diabetes mellitus is made with patients having symptoms and plasma glucose levels at the following levels: at fasting ≥ 7mmol/L and at random ≥ 11mmol/L or patients with plasma glucose ≥ 11mmol/L after 2hours of 75g oral glucose in the oral glucose tolerance test. This test should be repeated on another day to check the similarities or non-similarities.
What causes diabetes is unknown however there are lots of factors through which diabetes occurs. Insulin is a hormone secreted through beta cells in islets of Langerhans in the pancreas. Insulin is released from these cells when plasma glucose levels rise causing a breakdown of glucose restoring plasma levels back to normal. Obesity is the most common cause of diabetes as a result of insulin resistance. Other causes include; genetic and birth factors and can be drug induced, mitochondrial mutations, age and ethnicity. The prevalence of diabetes is more in Asian and African-Caribbean ethnicities.3
It is restored by glucagon secretion.
It is caused by increased glucose breakdown.
It is increased glucose production by; food etc.
It is restored by insulin secretion.
Diagram1. This is an adapted diagram from lecture and school notes.
The diagram illustrates the consequence of an increase and decrease in blood glucose levels. Decreased glucose is caused by glycogenesis, whereas increased blood glucose is caused by food, gluconeogenesis and glycogenolysis.
Aims of Treatment
The first aim is to alleviate symptoms and improve lifestyle, by adjusting the diet of the patients, followed by slowly introducing oral hyperglycaemic agents or insulin, and exercise. The treatment is to be adjusted according to the patient to make sure they are symptom-free. According to the guidelines all patients or carer of patients with diabetes require structured education around the time of diagnosis, with annual reviews or reinforcements.2 The second is to maintain health, reducing risk factors and preventing complications arising; glycated haemoglobin (blood glucose) level to be reached, control or detection of hypertension and hyperlipidaemia, review anti-platelet medication, cessation of smoking and screening of complications regularly. Last, management of long-term complications and other medical conditions affecting the patient.
Diagram2. A treatment strategy for Type 2 diabetic patients adapted from lecture note and the NICE guidelines.
When first diagnosed, a glycated haemoglobin target needs to be set for the patient which needs to maintain for as long as possible unless it interferes with their quality of life. Initially sulfonylurea is only considered for patients who are not overweight with a renal impairment. DDP4-i initially is used in patients with non-routine daily patterns, and thaizolidinedione is only used if sulfonylurea is a potential problem.
Sulfonylureas are one of several drugs being used. They act by enhancing insulin secretion hence is effective when beta-cells are still active. A lower dose should be avoided or used in patients with severe hepatic impairment due to hypoglycaemia. Metformin (Biguanides) is the second class of drugs used in treatment. They act by decreasing gluconeogenesis and increase peripheral glucose utilisation in the presence of endogenous insulin thus effective when beta-cells are still active.6
Other antidiabetic drugs include thiazolidinediones and dipeptidylpeptide-4 inhibitors. Thiazolidinediones reduce insulin resistance which reduces plasma glucose concentrations. It can be used alone or in combination. Dipeptidylpeptide-4 inhibitors cause an increase in insulin secretion, decreasing glucagon secretions. They can be used in combination with metformin, sulfonylurea or thiazolidinedione, when treatment with any one of them fails to control glycaemia.6
Short acting insulin is used for plasma glucose maintenance, hence taken before meals due to its rapid onset. Intermediate and long acting insulin is given subcutaneously due to its slow onset of 1-2hours; the maximal effect is 4-6hours later, and can last up to 16-35hours. This type of insulin can be given twice a day or once a day in elderly patients.6
Treatment of complications
Hyperosmolar Hyperglycaemic State (HHS) and Diabetic ketoacidosis are the two most common diabetic complications which are life threatening. HHS describes severe hyperglycaemia (high blood glucose concentrations) and serum hyperosmolarity (high osmotic concentrations) without ketosis. A rise in the glucose regulatory hormones contributes to the lack of use of glucose in peripheral tissues, leading to increased glycogenolysis leading to hyperglycaemia associated HHS.
The factors which cause HHS are inadequate treatment and infections however other factors include myocardial infarction, cerebrovascular injury, pulmonary embolism, alcohol use and drugs. Other signs include sunken eyes, dry tongue and hypotension in severe patients.
Diabetic ketoacidosis is more common in patients with type 1 diabetes however it can occur in patients with type 2 diabetes. Diabetic ketoacidosis results from dehydration during insulin deficiency, with is related to high plasma glucose and ketones (organic acids). The hormones released are glucagon, growth hormone and adrenaline, insulin is not released as the body has insulin deficiency. Patients suffer drowsiness, dehydration, over breathing, acetone in breath, hypotension and gastric slashing.
Tests include a blood test to obtain levels of plasma glucose, sodium, potassium and other electrolytes. A ketone level and kidney function test is also carried out.10
Treatment of HHS and ketoacidosis is done by giving fluid replacement and insulin as intravenous infusion is the initial critical treatment. This therapy allows the patient to rehydrate; also lowering plasma acid, restoring glucose levels and electrolyte balance. Once plasma glucose has fallen below 300mg/dL, glucose can be administered alongside insulin to prevent hypoglycaemia from occurring. In HHS, potassium and electrolyte levels should be corrected, patients should be give low molecular weight heparin, and anticoagulants if serum osmolality exceeds 350mmol/l, start the patient on antibiotics if an infection is present.10
Retinopathy is caused by microangiopathy affecting the retinal precapillary arterioles, capillaries and venules. This damage is caused by microvascular leakage from the breakdown of inner blood-retinal barrier and microvascular occlusion. First signs are small saccular pouches due to swelling in the capillary walls.3
Retinopathy can be pre-proliferative retinopathy or proliferative retinopathy. Proliferative retinopathy is when new vessels are formed at the optical disk or elsewhere in the retina. These new vessels can cause a patient's vision to disappear and by causing vitreous haemorrhage.3
Patients with vision threatening retinopathy can become blind caused by vitreous haemorrhage and Maculopathy. Maculopathy is when the macular densa is affected. It is also caused by deterioration of vision, can be caused by inappropriate laser treatment, by ischemia due to loss of prefoveal capillaries.3
Treatment is by photocoagulation or vitrectomy. Photocoagulation is when short argon laser pulses are used to destroy areas in the retina reducing stimuli for formation of new vessels. Vitrectomy is when surgery is used to clear the eye cavity of blood or tissue which can block vision.
Diabetic nephropathy is detected when proteinuria occurs five years after diagnoses. It is associated with severe retinopathy and neuropathy and is a major risk in patients with coronary artery disease. However prevalence of this is more in type 1 diabetes rather than in type 2 diabetes. Administration of medication and a tightly controlled blood pressure can delay renal failure development.3
Nephropathy can be managed with ACE inhibitors, and to maintain blood pressure at 130/80mmHg. Smoking is discouraged in these patients, and patients should be regularly reviewed.3
Diabetic neuropathy is nerve disorder caused by diabetes. Neuropathy develops over time and is caused by a number of factors, high glucose levels, body fat and low levels of insulin which are metabolic factors. Neurovascular factors; blood vessels carrying oxygen and nutrients to nerves are damaged, autoimmune factors, mechanical nerve injury, and Lifestyle factors; smoking and alcohol.11
Symptoms include numbness, tingling or pain in the toes, feet, legs, hands, arms, and fingers, wasting of the muscles of the feet or hands, indigestion, nausea or vomiting, diarrhoea or constipation, dizziness or faintness due to a drop in blood pressure after standing or sitting up, problems with urination, erectile dysfunction in men or vaginal dryness in women and weakness.11
Initial treatment is normalizing plasma glucose, and symptomatic relief. Pain is relieved by antidepressants, anticonvulsants and opioids. Gastrointestinal problems relieved with over the counter medication. Dizziness and weakness relieved by raising the bed head or by wearing elastic stockings some benefit from increasing salt intake. Weakness relieved by physical therapy. Antibiotics can clear urinary problems; erectile dysfunction and vaginal dryness require referral to the GP.11
Diabetic foot is a peripheral vascular disease. Foot care is a very important to diabetic patients and should be taken care off as it can lead to ulcers, infections and many other nasty problems such as gangrene.
The following such be carried out on a daily base:
Feet need to be cleaned daily, using warm (not hot water) and a mild soap, do not soak feet.
Dry feet with a soft towel and carefully between toes.
Inspect feet and toes daily for cuts, blisters, redness, swelling, calluses, or other problems. Notify a pharmacist or GP if any problems occur.
Moisturize feet with lotion, but avoid getting lotion between toes.
After a bath or shower, file corns and calluses gently with a pumice stone.
Each week or when needed, cut toenails and file the edges with an emery board.
Always wear shoes or slippers to protect feet from injuries. Prevent skin irritation by wearing thick, soft, seamless socks.
Wear shoes that fit well and allow toes to move. Break in new shoes gradually by first wearing them for only an hour at a time.
Before putting shoes on, look them over carefully and feel the insides with your hand to make sure they have no tears, sharp edges, or objects that may injure the feet.
If you need help taking care of feet, make an appointment with a podiatrist.11
Cardiovascular disease associated with diabetes is another complication, and is more common in hyperglycaemic diabetic patients. It has been observed that this risk factor is the main cause of death in diabetic patients. The risk is greater in women than in men, and over several years can result in myocardial infarction.
It is mainly caused by blockage of blood vessels going to and fro from the heart due to a build up of fatty deposits (arteriosclerosis) in the vessels causing restricted blood flow to muscles resulting in muscle death and lastly a heart attack.
Cardiovascular disease can be prevented by management of the risk factors such as blood pressure and obviously plasma glucose. Diabetic patients with one risk factor of cardiovascular disease are treated with and ACE inhibitor (angiotensin converting enzyme inhibitor).
The last is cerebovascular disease where similar to cardiovascular vascular disease there is restricted blood flow to the brain, hence causing a stroke (sudden blockage or rupture of blood vessel in the brain) or dementia.
Blockage may be caused by a blood clot forming in the arteries in the brain (thrombosis) or by any material travelling in the blood stream such a tissue or cholesterol (embolism). If the thrombosis or embolism completely blocks, the blood vessel ruptures causing bleeding within the brain causing a stroke. Dementia is caused by repeated blockage of arteries by arthrosclerosis with progressive destruction of the brain tissue to lack of blood reaching these tissues.1
It can be treated by ACE inhibitors or anti-platelet drugs.
Diabetes is a condition which is not curable however is preventable. Patients with diabetes require a lot of care and education which is provided to those who are diagnosed. Patients who think they might have the risk of diabetes should see their GP as soon as they can. Type 2 diabetes is more common but both types of diabetes are serious. Management of complications associated with diabetes is very important as it can cause death of not treated well. Diabetes can therefore be prevented or maintained by correct diet, exercise, and medications. Those who smoke should stop as it can cause advancement or complications of diabetes itself.