DIABETES MELLITUS

DEFINITION 

Diabetes mellitus is a metabolic disorder of carbohydrates, protein, fat, water and electrolytes characterized by high blood glucose level (hyperglycemia), Polyuria, polydipsia and polyphagia resulting from defects in insulin secretion or because the body cells do not respond to the insulin that is secreted or both.

INCIDENCE OF DIABETES MELLITUS

The incidence is classified according to the types. In type 1 diabetes mellitus, approximately 50-60% of patients get the condition before 20years of age. Type 2 diabetes mellitus is much common than type 1, accounting for 80-90% of all cases. It occurs after the age of 40years with an insidious onset. It is common in women over 65years and men 60years.

TYPES OF DIABETES MELLITUS

On the basis of aetiology two main categories of diabetes are recognized, namely primary (idiopathic) diabetes and secondary diabetes.

PRIMARY (IDIOPATHIC) DIABETES MELLITUS

The great majority of cases seen belong to this group which consist of two main clinical types;

Type 1 diabetes also known as insulin dependent diabetes mellitus (IDDM) or juvenile-onset result from the destruction of destruction of the insulin producing cell of the pancreases occurring most commonly in childhood or adolescence. This presently requires the person to inject insulin.

Type 2 diabetes (non-insulin dependent diabetes mellitus (MIDDM) or maturity onset diabetes: This is due to insulin resistance, a condition which the cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor cells. However, the specific defects are not known. These types of diabetes mellitus usually occur after the age of 40 years.

SECONDARY DIABETES MELLITUS

A minority of cases of diabetes mellitus occurs as a result of a recognizable pathological process or secondary to treatment of some other conditions.

• Gestational diabetes which occurs temporarily during pregnancy in individuals who have an inherited liability to develop the disorder.
• Iatrogenic diabetes, in those genetically susceptible, may be precipitated by various forms of therapy, notably corticosteroids and thiamine diuretics

AETIOLOGY/PREDISPOSING FACTORS OF DIABETES MELLITUS

Although the precise aetiology is still uncertain, several contributing factors are known to be involved.

MODIFIABLE FACTORS

These are factors that predispose one to the condition and with proper lifestyle the occurrence of the condition can be managed. These are factors include;

1. Age: - the disease may appear at any time but 80% of cases occur after the age of 50years and highest incidence of new patients is in 60-70 age groups.
2. Sex: - There are rather young male diabetic than female; middle age women are more often affected. Repeated pregnancy may add to the likelihood of developing diabetes in middle age.
3. Obesity: - The majority of the middle aged diabetic patients are obese. Most of evidence support the view that obesity is diabetogenic in those genetically predisposed to the disorder and that the rising incidence in older people in related to the increasing prevalence of obesity in the population as a whole.
4. Heredity In diabetes mellitus a familial tendency exists and twins are more often both diabetic when they are identical than when they are non identical. Genetic factors are probably more important in those who develop diabetes mellitus after the age of 40years and evidence of dominant inheritance has been obtained in this condition.
5. Diet: - Overeating, especially when combined with under activity is associated with a rise in the incidence of diabetes mellitus in the middle age and elderly.
6. Stress:- this stimulates secretion of epinephrine, norepinephrine and glucocorticoids and these neurotransmitters increases glucose level in the blood.
7. Autoimmunity:- diabetes mellitus co exists with other autoimmune disease such as pernicious anemia.
8. Infectious:- there is some evidence that viral infections may be involved in the aetiology of diabetes mellitus. Example is coxsackie B4 infection, and bacterial infections such as staphylococcus infections, in particular, are frequently associated with the development of clinical diabetes.

NON – MODIFIABLE FACTOR

Other disease can predispose one to the condition or even the treatment of such disease, can results in contracting the condition, Some of these disease include.

1. Liver disease particularly cirrhosis and hepatitis, may be associated with impaired glucose tolerance.
2. Pancreatic disease such as pancreatitis, haemochromatosis and carcinoma causes destruction of the pancreas and lead to impaired secretion and release of insulin.
3. Administration of growth hormone can produce permanent diabetes and about 30% of patient with acromegaly are diabetes.

PATHOPHYSIOLOGY OF DIABETES MELLITUS

Insulin is the principal hormone that regulates uptake of glucose from the blood into most body cells (primary muscle and fat cell) insulin is an anabolic or storage hormone. Typically, when blood glucose level is high insulin is released into the blood by the beta cell (b-cell), found in the islet of langerhans in the pancreas in response to the rising levels of blood glucose. Insulin is used by about two-thirds of the body in cells to absorb glucose from the blood for;

1. Use as fuel by body cells.
2. Conversion to other needed molecules or
3. Storage.

Higher insulin levels increase some anabolic (“building up”) Processes such as cell growth and duplication, Protein synthesis, and fat storage. Insulin is also the principal hormone responsible for the conversion of glucose to glycogen for storage in the liver and muscle cells. When glucose levels in the blood are lowered below normal ranges, insulin release is decreased, the body attempts to restore the blood glucose levels to normal by initiating the conversion of glycogen to glucose (glycogenolysis) in the liver.This is mainly controlled by the hormone glucagon which acts in the opposite manner to insulin. The glucose which was terrible produced from the liver stores re-enter the blood stream. However;

• The amount of insulin available in the blood is insufficient due to defect in it secretion by the beta cells of the islet of longer hands
• The Body cells respond poorly to the effects of insulin(insulin insensitivity or resistance)or
• The insulin itself is defective.

Than the glucose will not have it usual effect that is glucose will not absorbed properly by those body cells that requires it, Nor will be stored appropriately in the liver and muscles. The glucose than accumulates in the blood stream resulting in high blood glucose level (hyperglycemia).the conversion of glycogen to glucose from the liver goes unchecked, in response to low insulin levels in the blood. This further elevates the blood glucose level.

When the glucose concentration in the blood is raised beyond it renal threshold, Selective reabsorption of glucose in the proximal renal tubule becomes incomplete and part of the glucose tend to be excreted in the urine (glycouria).the presence of glucose in the urine increases the osmotic pressure of the urine and inhibits the selective reabsorption of sodium and water by the kidney, resulting in increased urine production (polyuria) and increase in fluid loss. 

The resultant decrease in blood volume will be reduced osmostically by the movement of fluid from the body cells and other body fluid compartment into the blood causing dehydration and the body tries to compensate for the fluid loss by increased thirst and increased fluid intake (polydypsia).The insulin deficiency also results in impaired metabolic of fat and protein. 

This gradually results in protein wasting, weight loss and increased hunger and increase food intake (polyphagia). The metabolism of body fat stores for energy leads to the production of acid by products called ketones, which can be detected in the Urine, (ketonuria). As ketones accumulate in the blood, the associated decreased in the blood PH leads to metabolic acidosis (diabetic ketoacidosis).

SIGNS AND SYMPTOMS OF DIABETES MELLITUS 

1. Frequent urination (polyuria)
2. Increased hunger and food intake (polyphagia) 
3. Increased thirst (polydypsia)
4. Glycosuria as a result of incomplete reabsorption of glucose in the urine
5. Recurrent infections (e.g. banalities)
6. Unexplained weight loss
7. Lost blood volume will be replaced somatically from water held in body cells and other body compartments, causing dehydration.
8. Fatigue
9. Blurred vision as a result of persistent hyperglycemia drawing water into the eyes
10. Headache
11. Confusion
12. Nausea and vomiting
13. Abdominal pains
14. A rapid, deep breathing known as kussmanl breathing (hyperventilation)
15. The production of large quantities of urine at night (nocturia)
16. Scaly skin ad dry skin
17. General body weakness (malaise)
18. A state of semi-unconscious (stupor)
19. Lethargy (drowsiness).
20. Skin lesions or wound that are slow to heal

Diagnostic investigation of Diabetes mellitus

An abnormally high blood glucose level is the basic criterion for the diagnosis of Diabetes mellitus.

1. Classical clinical symptom (such as polyuria, polydipsia and unexplained weight loss)
2. Random blood sugar higher than 11.1mmol/l
3. Fasting blood sugar = 7.0mmol/l
4. 2- hour post load glucose = 11.1mmol/l
5. Blood urea and nitrogen and serum creatinine level
6. Urine testing; a positive response indicates that the urine glucose exceeds 0.55-1.11mmol/l (glycosuria)
7. Electrocardiogram (ECG)
8. Body mass index to determine if patient is obese.

MANAGEMENT OF DIABETES MELLITUS AIM OF TREATMENT

The ideal treatment for diabetes mellitus would allow the patient to:

1. Lead a complete normal life
2. Remain not only symptom free but in positive good health 
3. Achieve a normal metabolic state
4. Prevent the complication associated with long term diabetes mellitus

TYPES OF TREATMENT

Three methods of treatment are available for diabetic patient: 

• Oral anti-diabetic drugs
• Insulin therapy
• Diet and lifestyle modifications

ORAL ANTI-DIABETIC DRUGS

1. Sulfonylureas: stimulate insulin secretion. First generation: examples, tolbutamide, tolazamide, acetohexamide, cholorpropamide.
2. Second generation; example, glyburide, glipizide, glimepiride 
3. Meglitinide, stimulate insulin secretion examples rapalinid, nateglinide.
4. Biguanides, decrease hepatic glucose production examples, metformin, glucophage XR and phenformin.Alpha-Glucosidase inhibitors: inhibit the activities of the enzyme 
5. Apha-Glucosidase which is responsible for the breakdown of carbohydrate molecules into short sugar chains. Examples, acarbose, miglitol
6. Thiazolidinediones; decrease peripheral insulin resistance example, rosiglitazon, pioglitazone 
7. Canbination; glyburide + metformin

INSULIN: A HORMONE FOR REGULATING BLOOD GLUCOSE LEVELS

1. Rapid acting: on set<0.5hrs, peak0.5-2.5 hrs duration: 3 – 4hrs. Examples: insulin analogues-lispro, aspart, glulisine and soluble insulin
2. Short –acting onset: 0.5 – 1 hrs, peak: 1-4 hrs, duration: 4-8 hrs. Example; insulin regular, insulin lispro, insulin aspart.
3. Intermediate acting: onset: 1-3hrs, peak; 3-8 hrs, durations 7- 14hrs examples, lent, neutral protamine hagedorn (NPH) etc
4. Long-acing: onset 2-4 hrs peak: 6 -12 hrs, duration: 12-30 hrs. Examples, ultralente, insulin glaring, bovine ultralente and insulin analogues glargine 
5. Mixed: Examples, NPH / regular: 70/30, 50/50 and NPH/lispro: 75/25 

Side-effects of insulin therapy

1. Hypoglycemia due to intake of insulin without meals 
2. Weight gain as a result of urge for food and overeating 
3. Peripheral edema (insulin treatment causes salt and water retention in a short term).
4. Insulin antibodies (animal insulin)
5. Local allergy (are)
6. Lipodystroph at injection sites
7. Somogyi effect as a result of a rebound phenomenon (i.e occurrence of hypoglycemia and hypoglycemia) which is overheated with insulin.

DIET AND LIFESTYLE MODIFICATION

Basically there are two types of diet; for diabetic patients.

1. Measured, in which the amount of food to be eaten at each time of the day is specified and  
2. Unmeasured, in which the patient is supplied with foods grouped in categories. Measured diet: in these diets the portion of food may be measured either by weighing with scales or by using household measures. Measured diets are required for two groups of patients:

• Those who require insulin or oral hypoglycemic agents and 
• Those that are overweighed and require a strict reducing regime.

Unmeasured diet: If insulin or oral hypoglycemic agents are not required and marked obesity is not present, it may not be necessary for the patient to follow such an accurate diet.

The following foods can be eaten by a diabetic patient. All meats, fish, eggs, cheese, light soups, tea, cabbage, vegetables, mushrooms, lemon juice, water, soda water, pepper, etc. The following foods should be avoided, sugar, glucose, tinned fruits, sweats, salad cream, chocolate, nuts, soft drinks, cakes, sweets biscuits, pies, thick sauces , all fried foods and alcohol drinks unless permission has been given by the doctor. 

Diabetes mellitus risks can be reduced in many cases by making changes in diet and increasing physical activity with the goal of keeping both short term and long-term blood glucose levels within acceptable bounds. Lifestyle modification are recommended to control blood pressure in patient with hypertension, maintaining a healthy weight, getting at least 3 times exercise a week, having a modest fat intake, eating sufficient fiber and avoid smoking.

WEIGHT MANAGEMENT

In patients with diabetes, weight management is a key factor, especially people with type 2 diabetes are mostly overweight or obese, and many anti diabetic medications and insulin increases weight gain. Weight loss can be achieved through a reduction in energy (reducing calorie) intake and an increase in energy expenditure through physical activity there should be frequent body weight check.

EXERCISE / ACTIVITY

Apart from reducing obesity, activity promotes the uptake of glucose to muscle for a period several times longer than the period of exercise and hence reduces the blood glucose level. People with diabetes need to exercise to prevent or reduces the risk for cardiovascular and peripheral vascular complications. It also assists in weight control. People with diabetes mellitus need to exercise at the same time (preferably when blood glucose levels are at their peaks) and in the same duration each day. This is to minimize fluctuation in blood glucose concentration. Encourage regular daily exercise, rather than sporadic exercise. Encourage a slow, gradual increase in the exercise period e.g. walking.

COMPLICATIONS OF DIABETES MELLITUS

Diabetic complications can be limited and sometimes prevented altogether if good management occurs from an early stage. The major complications include;

1. Diabetic hypoglycemia occurs when amounts of glucose in the blood become very low (fall below 2.7 to 3.3 mmol/l) due to either two much insulin or oral hypoglycemic agents, two little food or excessive physical activity.
2. Diabetic ketoacidosis: This occurs when there is insufficient or no insulin. This result in the break down of fat stores to release energy with an acid by-product production called ketones which accumulates causing diabetic ketoacidosis.
3. Hyperglycemic hyperosmolar nonketotic syndrome. The occurs when the blood glucose levels rises very high and the body tires to get rid of it, glucose will detected in urine (glycosuria) the patient is also very thirsty, weak and dehydrated. If not treated early can result in seizures, coma and finally death. 
4. Diabetic hyperglycemia, occurs when blood glucose rises above 11.1mmol/l.
5. Damage to the retina from diabetes (diabetic retinopathy) and cataracts is the leading cause of blindness.
6. Damage to the kidneys from diabetes (diabetic nephropathy) is a leading cause of kidney failure.
7. Damage to the nerves in the autonomic nervous system can lead to paralysis of the stomach (gastro- paresis), chronic diarrhea and inability to control heart rate and blood pressure.
8. Diabetes accelerates atherosclerosis (the formation of fatty plagues inside the arteries), which can leads to blockage or a clot (thrombus) leading to heart attack, stroke etc. 
9. Increase risk of heart diseases, peripheral vascular disease, and cerebrospinal disease.
10. Neuropathy, that is symmetrical sensory polyneuropathy (damage to the sensory nerves that commonly presents with tingling, numbers of pain in the feet or hands) a leading cause of foot wounds and ulcers, which frequently lead to foot and leg amputations.
11. Diabetic wound. 

PROGNOSIS OF DIABETES MELLITUS

The prognosis in diabetes mellitus has improved steadily since the introduction of insulin, but even with its use the average expectation of life is still rather less than non-diabetic. It may be difficult to estimate the prognosis of an individual patient because so many variables factors have to be considered. Thus duration of disease, financial status of patient and the body built of the patient can all account for the prognosis of the disease.

PREVENTION

From a public health standpoint the only cost effective way of dealing with diabetes is to prevent it. Diabetes mellitus especially type 2 diabetes is associated with an affluent lifestyle and is likely to rise in genetically predisposed individuals who eat two much and exercise too little. Effective health education has shown promising results in the primary prevention of diabetes mellitus, while screening for diabetes (particularly in high risk groups such as the first degree relatives of known cases and more vigorous and early treatment of impaired glucose tolerance could reduce the incidence of serious vascular disease in these patient. In any event the public should be educated primary against an overall excess of calorie and also to encourage sufficient exercise.