A Review On Type 2 Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels. Type 2 diabetes affects how your body uses sugar (glucose) for energy. It stops the body from using insulin properly, which can lead to high levels of blood sugar if not treated. T2DM also known as Non-Insulin Dependent Diabetes Mellitus (NIDDM)/Adult or Maturity onset Diabetes Mellitus. Over time, type 2 diabetes can cause serious damage to the body, especially nerves and blood vessels. Type 2 diabetes is often preventable. Although type 2 DM predominantly affects older individuals, it is now known that it also occurs in obese adolescent children; hence the term MOD for it is inappropriate. Moreover, many type 2 DM patients also require insulin therapy to control hyperglycaemia or to prevent ketosis and thus are not truly non-insulin dependent contrary to its former nomenclature. The various signs and symptoms are hunger, polyphagia, weight loss, wasting, polyuria etc. The various complications are acute metabolic and late systemic complications. Treatment usually involves pharmacological therapy like insulin therapy, oral hypoglycaemic agents and non pharmacological therapy. Patient counselling is defined as providing medication information orally or in written form to the patients or their representatives on directions of use, advice on side effects, precautions, storage, diet and life style modifications.

Keywords

Introduction

Type 2 diabetes affects how your body uses sugar (glucose) for energy. It stops the body from using insulin properly, which can lead to high levels of blood sugar if not treated. Over time, type 2 diabetes can cause serious damage to the body, especially nerves and blood vessels. Type 2 diabetes is often preventable. This type comprises about 80?ses of DM. Although type 2 DM predominantly affects older individuals, it is now known that it also occurs in obese adolescent children; hence the term MOD for it is inappropriate. Moreover, many type 2 DM patients also require insulin therapy to control hyperglycaemia or to prevent ketosis and thus are not truly non-insulin dependent contrary to its former nomenclature[1].

       
           
       
    Fig 1: Diagrammatic representation of type 2 DM

ETIOLOGY

Type 2 diabetes mellitus (T2DM) is by far the more common type of diabetes and is characterized by insulin resistance resulting from defects in the action of insulin on its target tissues (muscle, liver, and fat), but complicated by varying and usually progressive failure of beta cells’ insulin secretary capacity. T2DM involves a more complex interplay between genetics and lifestyle. There is clear evidence suggesting that T2DM is has a stronger hereditary profile as compared to T1DM. The majority of patients with the disease have at least one parent with T2DM [2].

EPIDEMIOLOGY

Globally, 1 in 11 adults has DM (90% having T2DM) [3]. The onset of T2DM is usually later in life, though obesity in adolescents has led to an increase in T2DM in younger populations. T2DM has a prevalence of about 9% in the total population of the United States, but approximately 25% in those over 65 years. The International Diabetes Federation estimates that 1 in 11 adults between 20 and 79 years had DM globally in 2015. Experts expect the prevalence of DM to increase from 415 to 642 million by 2040, with the most significant increase in populations transitioning from low to middle-income levels [4].T2DM varies among ethnic groups and is 2 to 6 times more prevalent in Blacks, Native Americans, Pima Indians, and Hispanic Americans compared to Whites in the United States [5][6].While ethnicity alone plays a vital role in T2DM, environmental factors also greatly confer risk for the disease. For example, Pima Indians in Mexico are less likely to develop T2DM compared to Pima Indians in the United States (6.9% vs. 38% )[7].

PATHOPHYSIOLOGY

A patient with DM has the potential for hyperglycaemia. The pathology of DM can be unclear since several factors can often contribute to the disease. Hyperglycaemia alone can impair pancreatic beta-cell function and contributes to impaired insulin secretion. Consequentially, there is a vicious cycle of hyperglycaemia leading to an impaired metabolic state. Blood glucose levels above 180 mg/dL are often considered hyperglycaemic in this context, though because of the variety of mechanisms, there is no clear cutoff point. Patients experience osmotic diuresis due to saturation of the glucose transporters in the nephron at higher blood glucose levels. Although the effect is variable, serum glucose levels above 250 mg/dL are likely to cause symptoms of polyuria and polydipsia. Insulin resistance is attributable to excess fatty acids and proinflammatory cytokines, which leads to impaired glucose transport and increases fat breakdown. Since there is an inadequate response or production of insulin, the body responds by inappropriately increasing glucagon, thus further contributing to hyperglycaemia. While insulin resistance is a component of T2DM, the full extent of the disease results when the patient has inadequate production of insulin to compensate for their insulin resistance.  Chronic hyperglycaemia also causes nonenzymatic glycation of proteins and lipids. The extent of this is measurable via the glycation haemoglobin (HbA1c) test. Glycation leads to damage in small blood vessels in the retina, kidney, and peripheral nerves. Higher glucose levels hasten the process. This damage leads to the classic diabetic complications of diabetic retinopathy, nephropathy, and neuropathy and the preventable outcomes of blindness, dialysis, and amputation, respectively [8].

SIGNS AND SYMPTOMS

• Hunger
• Polyphagia                                                
• Weight loss                                                                               
• Wasting                                                       
• Vulvitis
• Polyuria
• Polydipsia
• Tachycardia
• Hypotension

RISK FACTORS

• Family history of type 2 DM
• Obesity
• Habitual physical inactivity
• Race and ethnicity (Blacks, Asians, Pacific Islanders)
• Previous identification of impaired fasting glucose or impaired glucose tolerance
• History of gestational DM or delivery of baby heavier than 4 kg
• Hypertension
• Dyslipidaemia (HDL level < 35> 250 mg/dl)
• Polycystic ovary disease and acanthosis nigricans
• History of vascular disease

COMPLICATIONS

Broadly classified into two major groups;

1. Acute metabolic complications

2. Late systemic complications

1. Acute metabolic complications:

• Diabetic ketoacidosis
• Hyperosmolar nonketotic coma
• Hypoglycaemia

2. Late systemic complications:

• Atherosclerosis
• Diabetic microangiopathy
• Diabetic nephropathy
• Diabetic neuropathy
• Diabetic retinopathy
• Infections

DIAGNOSIS

The following investigations are helpful in establishing the diagnosis of diabetes mellitus:

1. URINE TESTING:

Urine tests are cheap and convenient but the diagnosis of diabetes cannot be based on urine testing alone since there may be false-positives and false-negatives. They can be used in population screening surveys. Urine is tested for the presence of glucose and ketones.

1. Glucosuria:

Benedict’s qualitative test detects any reducing substance in the urine and is not specific for glucose. More sensitive and glucose specific test is dipstick method based on enzyme-coated paper strip which turns purple when dipped in urine containing glucose. The main disadvantage of relying on urinary glucose test alone is the individual variation in renal threshold. Thus, a diabetic patient may have a negative urinary glucose test and a nondiabetic individual with low renal threshold may have a positive urine test.  Besides diabetes mellitus, glucosuria may also occur in certain other conditions such as: renal glycosuria, alimentary (lag storage) glucosuria, many metabolic disorders, starvation and intracranial lesions (e.g. cerebral tumour, haemorrhage and head injury).

2. Ketonuria:

Tests for ketone bodies in the urine are required for assessing the severity of diabetes and not for diagnosis of diabetes. However, if both glucosuria and ketonuria are present, diagnosis of diabetes is almost certain. Rothera’s test (nitroprusside reaction) and strip test are conveniently performed for detection of ketonuria.

2. SINGLE BLOOD SUGAR ESTIMATION:

For diagnosis of diabetes, blood sugar determinations are absolutely necessary. Folin-Wu method of measurement of all reducing substances in the blood including glucose is now obsolete. Currently used are O-toluidine, Somogyi-Nelson and glucose oxidase methods. Whole blood or plasma may be used but whole blood values are 15% lower than plasma values. A grossly elevated single determination of plasma glucose may be sufficient to make the diagnosis of diabetes. A fasting plasma glucose value above 126 mg/dl (>7 mmol/L) is certainly indicative of diabetes. In other cases, oral GTT is performed.

3. SCREENING BY FASTING GLUCOSE TEST:

Fasting plasma glucose determination is a screening test for DM type 2. It is recommended that all individuals above 45 years of age must undergo screening fasting glucose test every 3-years, and relatively earlier if the person is overweight or at risk because of the following reasons:

• Many of the cases meeting the current criteria of DM are asymptomatic and do not know that they have the disorder.
• Studies have shown that type 2 DM may be present for about 10 years before symptomatic disease appears.
• About half the cases of type 2 DM have some diabetes related complication at the time of diagnosis.
• The course of disease is favourably altered with treatment.

4. ORAL GLUCOSE TOLERANCE TEST:

Oral GTT is performed principally for patients with borderline fasting plasma glucose value (i.e. between 100-140 mg/dl). The patient who is scheduled for oral GTT is instructed to eat a high carbohydrate diet for at least 3 days prior to the test and come after an overnight fast on the day of the test (for atleast 8 hours). A fasting blood sugar sample is first drawn. Then 75 gm of glucose dissolved in 300 ml of water is given. Blood and urine specimen are collected at half-hourly intervals for at least 2 hours. Blood or plasma glucose content is measured and urine is tested for glucosuria to determine the approximate renal threshold for glucose. Venous whole blood concentrations are 15% lower than plasma glucose values[1].

• Normal cut off value for fasting blood glucose level is considered as 100 mg/dl.
• Cases with fasting blood glucose value in range of 100- 125 mg/dl are considered as impaired fasting glucose tolerance (IGT); these cases are at increased risk of developing diabetes later and therefore kept under observation for repeating the test. During pregnancy, however, a case of IGT is treated as a diabetic.
• Individuals with fasting value of plasma glucose higher than 126 mg/dl and 2-hour value after 75 gm oral glucose higher than 200 mg/dl are labelled as diabetics.
• In symptomatic case, the random blood glucose value above 200 mg/dl is diagnosed as diabetes mellitus.

TREATMENT

PHARMACOLOGICAL THERAPY

1.Oral hypoglycaemic agents (OHAs)

OHAs includes Sulfonylureas (First generation includes Acetohexamide, Tolbutamide, Chlorpropamide, Tolzamide and Second generation includes Glyburide, Glimepiride, Glipizide), Biguanides (Metformin), Meglitinides (Repaglinide, Nataglinide), TZDs (Thiazolidinediones -Pioglitazone, Rosiglitazone),Alpha-glucosidase inhibitors (Acarbose, Miglitol) Glucagon like peptide-1-agonist (Exenatide, Liraglutide) Amylinomimetics    (Pramlintide acetate)[9].

2.Insulin therapy

Insulin is a hormone produced by the pancreas to help the body use and store glucose (sugar). Glucose is a source of fuel for the body.

In people with diabetes, the body cannot regulate the amount of glucose in the blood (called glycemia or blood sugar). Insulin therapy can help some people with diabetes maintain their blood sugar levels.

Insulin Doses and Types

Insulin therapy replaces the insulin the body would normally make.

People with type 1 diabetes must take insulin every day. People with type 2 diabetes need to take insulin when other treatments and medicines fail to control blood sugar levels.

Insulin doses are given in two main ways:

• Basal dose –

provides a steady amount of insulin delivered all day and night. This helps maintain blood glucose levels by controlling how much glucose the liver releases (mainly at night when the time between meals is longer).

• Bolus dose –

provides a dose of insulin at meals to help move absorbed sugar from the blood into muscle and fat. Bolus doses can also help correct blood sugar when it gets too high. Bolus doses are also called nutritional or meal-time doses. Sometimes, a bolus dose must also be taken with large snacks.

There are several types of insulin available. Insulin types are based on the following factors:

• Onset –

how quickly it starts working after injection

• Peak –

time when the dose is the strongest and most effective

• Duration –

total time the insulin dose stays in the bloodstream and lowers blood sugar

Types of insulin

• Rapid-acting or fast-acting insulin starts working within 15 minutes, peaks in 1 hour, and lasts for 2 to 4 hours. It is taken right before or just after meals and snacks. It is often used with longer-acting insulin.
• Regular or short-acting insulin reaches the bloodstream 30 minutes after use, peaks within 2 to 3 hours, and lasts 3 to 6 hours. This is taken a half-hour before meals and snacks. It is often used with longer-acting insulin.
• Intermediate-acting insulin starts working within 2 to 4 hours, peaks in 4 to 12 hours, and lasts 12 to 18 hours. This is taken mostly either twice a day or once at bedtime.
• Long-acting insulin starts to work a few hours after injection and works for about 24 hours, sometimes longer. It helps control glucose throughout the day. It is often combined with rapid- or short-acting insulin as needed.
• Premixed or mixed insulin is a combination of 2 different types of insulin. It has both a basal and bolus dose to control glucose after meals and throughout the day.
• Inhaled insulin is a rapid-acting breathable insulin powder that starts working within 15 minutes of use. It peaks 30 minutes after taking it and lasts about 3 hours. It is used just before meals.

Insulin delivery methods

• Insulin syringe –

insulin is drawn from a vial into a syringe. Using the needle, you inject the insulin under the skin.

• Insulin pen –

disposable insulin pens have prefilled insulin delivered under the skin using a replaceable needle.

• Insulin pump –

a small machine worn on the body pumps insulin under the skin throughout the day. A small tube connects the pump to a small needle inserted into the skin.

• Inhaler –

a small device you use to inhale insulin powder through your mouth. It is used at the start of meals.

• Injection port –

a short tube is inserted into the tissue under the skin. The port containing tube is adhered to skin using adhesive tape. Fast-acting insulin is injected into the tube using a syringe or pen. This allows you to use the same injection site for 3 days before rotating to a new site.

Insulin is injected into these sites on the body:

• Abdomen
• Upper arm
• Thighs
• Hips

NON-PHARMACOLOGICAL THERAPY

• Dietary management
• Stress management
• Physical activities

PREVENTION

• Eat a healthy diet
• Work to achieve a weight that’s healthy for you
• Manage your stress
• Limit alcohol intake
• Get adequate sleep (typically 7 to 9 hrs) and seek treatment for sleep disorders
• Quit smoking
• Take medications as directed by your healthcare provider to manage existing risk factors
• for heart disorders.

PATIENT COUNSELLING

Patient counselling is defined as providing medication information orally or in written form to the patients or their representatives on directions of use, advice on side effects, precautions, storage, diet and life style modifications.

1. Counselling regarding the disease:

The diabetic patients should be explained that the disease is lifelong, progressive and needs necessary modifications in the lifestyle pattern. They should also stress upon the importance of pharmacotherapy, especially the need for strict compliance with the prescribed medication. The patients should be also explained that the disease may affect the quality of life if not well controlled.

2. Counselling regarding lifestyle modifications: While counselling regarding the lifestyle modifications, the pharmacist should focus on the key areas including diet, exercise, smoking and alcohol intake.

1. Diet:

Dietary control is the mainstay of treatment in type 2 diabetes and an integral part in type 1 diabetes. Among the dietary counselling, importance should be given for the dietary content including carbohydrate, fat and fibre intake.

2. Exercise and physical activity:

Exercise can help to promote weight loss and maintain ideal body weight when combined with restricted caloric intake. In type 2 diabetes, the desired level of exercise is 50% to 80% of maximal uptake of oxygen three to four times a week. In type 1 diabetes, care must be taken to have adequate metabolic control prior to exercise and to monitor blood glucose before and after exercise. Exercise is not recommended if the patient has poorly controlled labile blood glucose level or is at increased risk of diabetic complications. Strenuous exercise is not wise in patients prone to develop hypoglycaemia[10].

3. Alcohol intake:

Even if the blood glucose of the patient is well controlled, modest amount of alcohol will significantly alter blood glucose levels. In general, the same guidelines of alcohol use applicable to the general public apply to patients with diabetes.

4. Smoking:

People with diabetes, especially those over age 40 years, who smoke and have high blood pressure and cholesterol, are at a higher risk for cardiovascular problems. When the large blood vessels (arteries) are blocked, heart attack and stroke often result. This hardening or blockage may also occur in the small arteries that supply blood to the legs and feet. Smoking can also lead to serious complications like infections, ulcers, gangrene, and even amputations. Pharmacist should counsel patients regarding the evil effects of smoking and educate the patients regarding the various strategies to stop smoking. Emphasise should be laid on the pharmacological measures to stop smoking.

3. Counselling regarding medications:

1. 1. Oral hypoglycaemic agents (OHAs):

 If the patient is diagnosed with Type 2 diabetes, he/ she is more likely to be prescribed OHAs. Commonly prescribed drugs are metformin, glibenclamide, acarbose etc. The patient should be cautioned not to skip meals at any time and to follow regular eating patterns to prevent hypoglycaemia. OHAs are comparatively safe drugs. However some patients may develop loss of appetite, nausea and vomiting, abdominal pain, cramps, malaise, diarrhoea or weight loss.

1. 2. Insulin:

All patients with type 1 diabetes require insulin. Some patients with type 2 diabetes who initially respond to dietary modification and/ or oral anti diabetic medications eventually require insulin therapy. There are a wide variety of insulin preparations available now. These may differ in source, onset of action, time to peak effect, and duration of action. The clinician will prescribe the type of insulin which suits an individual best.

CONCLUSION:

Diabetes is a serious life-threatening disease and must be constantly monitored and effectively subdued with proper medication and by adapting to a healthy lifestyle. By following a healthy lifestyle, regular checkups, and proper medication we can observe a healthy and long life.

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