30 Jan 2016

Role of Pharmacist in Counseling Diabetes Patients



Role of Pharmacist in Counseling Diabetes Patients

Introduction

The role of pharmacist has changed dramatically over the past three decades. Traditionally pharmacists were viewed as individuals who dispensed medicine to the public. This role slowly got transferred into one which involved more of development of drugs. The later stage of 1960s revealed the growth of a new development that changed the concept of pharmacy from a product oriented to a patient focused one, called clinical pharmacy. Pharmacists are now becoming indispensable in monitoring patient drug therapy.1 The clinical pharmacy grew with the concept of pharmaceutical care, the responsible provision of drug therapy for the purpose of achieving definite outcomes which improve the patients' quality of life. It involves the pharmacist's decision to avoid, initiate, maintain, or discontinue drug therapy, both of prescription and non- prescription drugs. It is thus practiced in collaboration with patients, physicians, nurses, and other health care workers. The ultimate goal of pharmaceutical care is to optimize a patient's quality of life. These outcomes can be achieved by influencing the cure of the disease, elimination or reduction of symptoms, arresting or slowing the disease progress, prevention and diagnosis of disease or desired alterations in the physiological process.

Patient counseling is an important means for achieving pharmaceutical care. It is defined as providing medication related information orally or in written form to the patients or their representatives, on topics like direction of use, advice on side effects, precautions, storage, diet and life style modifications.3 Patient counseling is interactive in nature and involves a one-to–one interaction between a pharmacist and a patient and/or caregiver. It should include an assessment of whether or not the information was received as intended and that the patient understands how to use the information to improve the probability of positive therapeutic outcomes.4 The ultimate goal of counseling is to provide information directed at encouraging safe and appropriate use of medications, thereby enhancing therapeutic outcomes.5 Several guidelines specify the points to be covered by the pharmacist while counseling the patients. 

Diabetes: A Major Global Burden

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia. It is associated with abnormalities in carbohydrate, fat and protein metabolism, and results in chronic complications including micro-vascular, macrovascular, and neuropathic disorders.7 The worldwide prevalence of DM has risen dramatically over the past two decades. It has been projected that the number of individuals with DM will continue to increase in the near future. Between 1976 and 1994, for example, the prevalence of DM among adults in the United States increased from 8.9% to 12.3%.8 Approximately 8 million Americans are known to have diabetes. Every year, on average 6,25,000 new cases of diabetes are diagnosed, and more than 178,000 deaths result from the disease and its related complications.9 Most cases of type 2 DM do not have a well- known cause; therefore it is uncertain whether it represents a few or many independent disorders manifesting as hyperglycemia.
Diabetes has been implicated as the underlying cause of 12% of all new cases of legal blindness, over one third new cases of end- stage renal disease (ESRD), and nearly half of non traumatic lower – extremity amputations. Evidence has also shown that people with diabetes are two to four times more likely to die from heart disease or suffer stroke.8 Prevalence of diabetes in adults worldwide was estimated to be 4.0% in 1995 and expected to rise to 5.4% by the year 2025. It is higher in developed than in developing countries.

The number of adults with diabetes in the world is estimated to rise from 135 million in 1995 to 300 million in the year 2025. The major part of this numerical rise will occur in developing countries. There will be a 42% increase, from 51 to 72 million in the developed countries and a 170% increase, from 84 to 228 million in the developing countries. The countries with the largest number of people with diabetes are, and by the year 2025 will be India, China, and the US. Majority of diabetics are in the age range of 45- 64 years in the developing countries and ? 65 years in developed countries. This pattern will be accentuated by the year 2025, and diabetes will be increasingly concentrated in urban areas.

Need for counseling in diabetes
Diabetes is a chronic, incurable condition that has considerable impact on the life of each individual patient. Patient involvement is paramount for the successful care of diabetes. The principal task of the health care team is to give each patient knowledge, self- confidence and support. Patients with diabetes and their families provide 95% of their care themselves,12,13 and, as a consequence, educational efforts to improve self- management are central components of any effective treatment plan.
The role of self-management behavior is clear even in studies that address relationships between pharmacologic treatment and outcomes at the physiologic level. For example, both the Diabetes Control and Complications Trial (DCCT) 14 and the United Kingdom Prospective Diabetes Study, (UKPDS)15 required patients to adhere to complex and intensive treatments over long periods of time. The primary goals of DM management are to reduce the risk for microvascular and macrovascular disease complications, to ameliorate symptoms, to reduce mortality, and to improve quality of life.16 Appropriate care requires goal setting for glycemia, blood pressure, and lipid levels, regular monitoring for diabetic complications, dietary and exercise modifications, appropriate medications, appropriate self monitoring of blood glucose (SMBG), and laboratory assessment of the aforementioned parameters.

Studies have confirmed that the complications of diabetes can be reduced by proper control of blood glucose.15,17 The proper control is dependent on the patient's adherence to medications, life style modifications, frequent monitoring of blood glucose, etc and can be influenced by proper education and counseling of the patient.18 Pharmacists, being one of the indispensable members of the health care team, have an immense responsibility for counseling these patients.
Diabetes, if untreated, can lead to various complications such as neuropathy, nephropathy, retinopathy, hyperlipidema, diabetic foot ulcers, infections, etc.19 These complications adversely affect the quality of life of the patient. Quality of life is a multidimensional concept referring to a person's total well being, including his or her psychological, social, and physical health status.20 It is also well established that pharmacist provided patient counseling improves the quality of life of the diabetic patients.

Role of pharmacists in diabetes management
Because of the rapid expansion of available therapeutic agents to treat diabetes, the pharmacist's role in caring for diabetic patients has expanded. The pharmacist can educate the patients about the proper use of medication, screening for drug interactions, explain monitoring devices, and make recommendations for ancillary products and services.
The pharmacist, although not the health care professional to diagnose diabetes, is important in helping the patient maintain control of their disease. The pharmacist can monitor the patient's blood glucose levels and keep a track of it. During their contact, the patients can ask the pharmacist any questions they did not ask the physicians and can get further information regarding diabetes. The pharmacist can also counsel the patients regarding insulin administration regularly so that the onset of complications can be postponed by having tight glycemic control. Another important role of pharmacist is always being available to answer the questions of the patients. Overall, it is the pharmacist's role to help a diabetic patient in the best possible way to cope with their disease.

Essential components of diabetic counseling
Since diabetes is a chronic complication affecting the diabetic patient at various levels, the counseling should focus on the nature of the disease, lifestyle modifications, medications, and acute and chronic complications.

I. Counseling 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.
II. Counseling regarding lifestyle modifications: While counseling regarding the life style modifications, the pharmacist should focus on the key areas including diet, exercise, smoking and alcohol intake.

A. Diet: Dietary control is the mainstay of treatment in type 2 diabetes and an integral part in type 1 diabetes. Among the dietary counseling, importance should be given for the dietary content including carbohydrate, fat and fiber intake.
1.     Carbohydrates: The blood glucose level is closely affected by the carbohydrate intake. Daily intake should be kept fairly constant and the amount given should be appropriate to the level of physical activity. Most young people will require 180 g of carbohydrate per day, whereas 100 g may suffice for an elderly patient. If fiber rich food such as whole meal bread, jacket potatoes, etc. are eaten, then the carbohydrate content of the diet make up to 50% to 55% of the calories. People with diabetes should limit their sugar intake, but total exclusion of sugar from the diet is impractical and unnecessary.
2.     Fat: Since there is an increased risk of death from coronary artery disease in diabetics, it is wise to restrict saturated fats and to substitute them with unsaturated fats. Furthermore, obesity is a major problem in diabetes, and fats contain more than twice the energy content per unit weight than either carbohydrate or proteins. More severe restrictions may be indicated for individuals with hypercholesterolemia.
3.     Fiber: Dietary fiber has two useful properties. Firstly it is physically bulky and increases satiety. Secondly, fiber delays the digestion and absorption of complex carbohydrates, thereby minimizing hyperglycemia. For an average person with NIDDM, 15gm of soluble fiber (from fruits, pulses and vegetables) is likely to produce a 10% improvement in fasting blood glucose, glycated hemoglobin and low- density lipoprotein cholesterol.

B. 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 hypoglycemia.
A standard recommendation for diabetic patients, (as for nondiabetic individuals), is that exercise should include a proper warm-up and cool- down period. A warm up should consist of 5-10 min of aerobic activity (walking, cycling, etc.) at a low intensity level. The warm-up session is to prepare the skeletal muscles, heart, and lungs for progressive increase in exercise intensity. After a short warm- up, muscles should be gently stretched for another 5- 10 min. Primarily, the muscles used during the active exercise session should be stretched, but warming up all muscle groups is optimal. The active warm up can either take place before or after stretching. Following the activity session, a cool-down should be structured similarly to the warm-up. The cool- down should last about 5- 10 min and gradually bring the heart rate down to its pre- exercise level.

C. 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.

D. 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. 

III. Counseling regarding medications: Though lifestyle modifications play an important role in diabetes management, it is well established by land mark studies that the chronic complications can be prevented by strict glycemic control. Hence, the pharmacist has an immense role in counseling diabetic patients regarding the drugs. Counseling should be emphasized for oral anti diabetic agents as well as for insulin.
1. Oral hypoglycemic agents (OHAs): If the patient is diagnosed with Type 2 diabetes, he/ she is more likely to be prescribed OHAs. Some of the commonly prescribed oral hypoglycemic agents and the important counseling points are discussed below.
Some general principles to be followed for patients on OHAs:
The patient should be cautioned not to skip meals at any time and to follow regular eating patterns to prevent hypoglycemia. OHAs are comparatively safe drugs. However some patients may develop loss of appetite, nausea and vomiting, abdominal pain, cramps, malaise, diarrhea or weight loss.

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.

IV. Counseling regarding acute complications: Though rare and not directly linked with the quality of life, the acute complications of diabetes can be morbid if not treated properly. The pharmacist should focus on strategies to prevent the occurrence of the acute complications and if they have occurred the methods to overcome and to manage the same. Some of the acute complications of diabetes are discussed below.
1. Hypoglycemia: It is a condition caused by abnormally low level of blood glucose.
Hypoglycemia is caused by taking too much of certain diabetic medicines, missing a meal or delaying a meal, exercising more than usual, or drinking alcohol. The symptoms can be classified as initial, intermediate and advanced symptoms. Initial symptoms may start with sweating, tremulousness, nausea and vomiting, dizziness, mood change, hunger, weakness and progress to the intermediate symptoms of confusion, poor coordination, headache and double vision. The advanced symptoms are unconsciousness and seizures.
The management of hypoglycemia includes taking half a cup of any fruit juice, 2 or 3 glucose tablets, 2 tablespoons raisins, 1 or 2 teaspoons of sugar or honey, half cup of regular soft drink or liquid concentrated glucose. For advanced hypoglycemia, medical intervention is needed with glucagon 1 mg subcutaneously or intramuscularly.
Hypoglycemia can largely be prevented by taking antidiabetic medications properly, eating regular meals, and regular checking of blood glucose.

2. Diabetic keto acidosis (DKA): DKA is a serious complications characterized by hyperglycemia, elevated serum ketones, and an anion gap metabolic acidosis. It mainly affects the individuals with type 1 DM but may also affect type 2 diabetes patients in response to acute stress.
The risk factors include extremes of age, poor glycemic control, poor socioeconomic status, non-compliance etc. In general, insulin omission or non-compliance is identified as an important contributing factor for development of DKA. 25 The pharmacist can counsel the patients regarding the strategies to prevent the occurrence of DKA.

3. Non Ketotic Hyperosmolar Syndrome (NKHS): It is a constellation of severe hyperglycemia, dehydration, and hyperosmolarity in the absence of severe ketosis. It commonly occurs in elderly patients with type 2 DM. Among the various risk factors for NKHS, advanced age, female gender, acute infection and non-compliance are considered important. Hence counseling regarding the important of compliance can be helpful in reducing the occurrence of NKHS. 

V. Counseling regarding chronic complications: Since diabetes is a chronic illness and the chronic complications of diabetes can adversely affect the quality of life, these complications should be emphasised. It is well established that the chronic complications of diabetes can be prevented by strict compliance and suitable lifestyle modifications. Some of the chronic complications and the role of pharmacist in counseling the patients regarding these complications are mentioned below.
1.     Diabetic neuropathy: It is characterized by nerve damage caused by chronic high blood glucose levels. Neuropathy can lead to loss of pain or touch sensations on the feet. It can also cause pain in legs, arms or hands. Nerve damage can progress slowly and most of the time the patients may not even be aware that they have nerve problems. Hence regular check ups to rule out diabetic neuropathy is essential. For prevention of diabetic neuropathy the blood glucose and blood pressure should be kept as close to normal as possible. The other precautions include stopping/limiting alcohol intake, regular checking of feet every day and quitting the smoking.
2.     Diabetic retinopathy: Retinopathy is a disorder of the eye that occurs in majority of the adults with diabetes. The patient suffering from retinopathy may complain of blurring of vision, seeing black spots, flashing lights etc. Once detected proper treatment of diabetes can reduce the progression of retinopathy.
3.     Diabetic nephropathy: Nephropathy (disorder of the kidney) is one of the potential life threatening complications of diabetes. Poor control of diabetes is associated with enlargement of the kidneys and impairment in their function. The development and progression of nephropathy in diabetics can be delayed by tight glycemic control.26
4.     Infections: Many infections are seen commonly in diabetic patients. This is an indication of poor diabetes control. Infections at mild stages, if not treated, can lead to life threatening sepsis in these patients.

VI. Counseling in special populations: Since the progression and the management pattern of diabetes vary significantly among different populations, the pharmacist should also tailor his counseling pattern according to the population. Some of the special populations with diabetes are mentioned below with the outline of the counseling in these patients.
1.     Elderly: Elderly diabetic patients usually have various other comorbid conditions like hypertension, hyperlipidemia etc. They may also have some degree of psychiatric imbalance. The counseling in these patients should also address the emotional impairment due to diabetes.
2.     Children: Children, especially the type-1 diabetes patients, require several special precautions. In addition to other essential counseling points, the pharmacist should also focus on the administration time of insulin during school days, storage of insulin in the school, risk of hypoglycemia while playing etc.
3.     Pregnancy: Since elevated blood glucose is associated with congenital abnormalities, the pregnant patients should be asked to have strict control over the blood glucose.
4.     Multiple disorders: Patients with multiple diseases need special counseling for those diseases other than diabetes. Patients with underlying cardiac problems should be cautioned that they may not experience pain during MI and hence should be advised to have regular cardiac checkup.
5.     Frequent traveling: Diabetes patients who travel frequently should be advised regarding the use of insulin pen. They should be also counseled regarding the importance of food plan during their journey and the possibility of hypoglycemia. They should be warned not to neglect even a simple infection as it may turnout to be fatal. 

VII. Counseling regarding self Monitoring of Glucose: With the availability of Blood glucose monitoring devices for the monitoring of blood glucose, patients can monitor glucose levels more frequently and have a control over blood glucose. Pharmacist can play a vital role in educating the patients regarding the use of blood glucose monitors. Pharmacists can help right from choosing a proper glucose monitor, training them in proper use of glucose meters. Pharmacist can explain the significance of various blood glucose levels and maintaining proper blood glucose levels. As the patients gain confidence in measuring the blood sugar, managing diet and medications better outcomes can be expected.

VIII. Miscellaneous: Besides the above mentioned topics, the pharmacist should also provide additional counseling for the patients who need it. Some of the additional points to be counseled are mentioned below.
1. Foot care: Meticulous foot care and the choice of suitable foot wear can prevent serious damage which is likely to occur in diabetics.
Tips for foot care: Wash feet daily with lukewarm water and soap, just as washing hands
·        Dry feet well, also between the toes
·        Keep the skin supple with a moisturizing lotion
·        Use soft socks or stockings, which must neither be too big nor too small
·        Never walk barefoot- neither indoors nor outdoors
·        Examine the shoes every day for cracks, pebbles, nails and other irregularities which may irritate the skin
·        A brisk walk everyday stimulates the circulation and makes the patient feel much better.
2. Eye care: Individuals with diabetes could have underlying eye problems that might not be noticed by the patient early. It is important to recognize eye problems early while they can be treated to prevent blindness.
Tips for eye care: For people with type 2 diabetes should have an eye exam every year, women planning to become pregnant should have an eye exam before becoming pregnant. The patient should keep the blood glucose and blood pressure levels as close to normal as possible. The should be advised to inform the doctor right away in case of any problems like blurring of vision or seeing dark spots, flashing lights, or rings around lights.
3. Oral hygiene: People with diabetes are prone to many changes in the mouth such as dry mouth, burning sensations, painful sores, and loss of taste and coating on the tongue. The most common oral complication of diabetes is gum (periodontal) disease. If un-treated, gum disease can be very serious and lead to tooth loss. Early signs of gum disease include long term bad breath or bad taste, swollen, red, tender, shrinking or bleeding gums, pus between teeth; changes in bite, teeth position or denture fit or tooth loss.
Tips for oral hygiene: Brush teeth after every meal and before bedtime use a soft bristled brush, brush all surfaces of all teeth, lightly brush the tongue, massage gums lightly with finger or brush. The patient should be advised to visit the dentist every three months for cleaning, polishing and inspection.

Strategies to improve counseling in diabetes patients
Since diabetes is a chronic illness and the diabetic patients also suffer from varying degree of cognition impairment, special strategies should be adopted for effective counseling. Some of which are discussed below.
1. Patient information leaflets (PILs): Patient information leaflets can help the patients in getting the information regarding diabetes. The PILs should focus on the lifestyle modifications and the medications.
2. Compliance aids: The compliance aids like medication envelopes and medication calendars can help in making the patient understand the different dosing schedule of the medication, especially the OHAs.
3. Use of audiovisual aids: A study by Wedman and Kahan found that a group of patients with diabetes counseled by a dietitian who used graphic teaching aids, complied with health care advice better than did a control group advised by the same counselor without the use of graphic teaching aids. 27 Similarly the counseling pharmacist can also use audiovisual aids in order to improve the outcome of counseling.
4. Establishing patient counseling center: Establishing a separate counseling area near the dispensing area of the pharmacy can be beneficial for effective counseling. In can also improve the quality and the outcomes of the counseling process.
5. Requirements for the counseling pharmacist: In addition to the desired qualities of a good counseling pharmacist, the pharmacist should also have adequate knowledge about diabetes. Such a pharmacist is a vital member in a diabetes management program. 

Evidence for beneficial effects of pharmacist provided counseling in diabetes
Several studies have acknowledged the importance of pharmacist provided counseling in diabetes patients.
The Fremantle Diabetes Study examined the effect of a 12-month pharmaceutical care (PC) program on vascular risk in type 2 diabetes. In this study patients were randomized to PC or usual care. PC patients had face-to-face goal-directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessments and provision of other educational material. The main outcome measure was change in HbA(1c). The study concluded that the 12-month PC program in type 2 diabetes reduced glycemia and blood pressure. Pharmacist involvement contributed to improvement in HbA (1c) independently of pharmacotherapeutic changes.
Cioffi et al conducted the study to determine the effect of a clinical pharmacist-directed diabetes management clinic on glycemic control and cardiovascular and renal parameters in patients with type 2 diabetes. The primary endpoint was the impact of 9-12 months of participation in the clinic on HbA1C. The study demonstrated that a clinical pharmacist can effectively care for patients with diabetes referred by their primary care provider because of poor glycemic control.
Gerber et al conducted a study to assess the impact on healthcare utilization and costs of pharmacist consultations provided to patients with diabetes. The study suggested that pharmacist consultations provided to patients with diabetes can decrease total healthcare costs in a health maintenance organization.
Cranor et al assessed the persistence of outcomes for up to 5 years following the initiation of community-based pharmaceutical care services (PCS) for patients with diabetes. A Quasi-experimental, longitudinal pre-post cohort study was conducted in twelve community pharmacies in Asheville, N.C. The study concluded that patients with diabetes who received ongoing PCS maintained improvement in HbA1c over time, and employers experienced a decline in mean total direct medical costs.
The impact of a specially designed patient education program upon the diabetes-related knowledge and compliance of insulin dependent diabetic patients was investigated by Powell et al. The program was successful in producing improvements in both knowledge and compliance but a need for individualization of patient education efforts was indicated.
Odegard et al evaluated the effect of a pharmacist intervention on improving diabetes control; secondary endpoints were medication appropriateness and self-reported adherence. Seventy-seven subjects, were randomized to receive a pharmacist intervention (n = 43) or usual care (n = 34) for 6 months, followed by a 6-month usual-care observation period for both groups. The study concluded that pharmacist intervention did not significantly improve diabetes control, but did allow for similar HbA (1c) control with fewer physician visits. Medication appropriateness and self-reported adherence compared with usual care in individuals with poorly controlled diabetes were not changed.
Kiel and McCord evaluated the changes in clinical outcomes for patients enrolled in a pharmacist-coordinated diabetes management program. Data collection included baseline and follow-up values for HbA1c and lipids as well as frequency of adherence to preventive care, including annual foot and eye examinations and daily aspirin therapy. The study concluded that the pharmacist-coordinated diabetes management program was effective in improving clinical markers for enrolled patients. Significant improvements were observed in Hb A1C and LDL values as well as the frequency of adherence to preventive care.

Conclusion
Diabetes is a chronic illness that requires a combination of pharmacological and non-pharmacological measures for better control. Patient adherence to medication and lifestyle modifications plays an important role in diabetes management. Pharmacists being an important member of the healthcare system have an immense responsibility in counseling these patients. To be an effective counselor, the pharmacist should update his knowledge regarding the latest developments and should possess adequate verbal and non-verbal communication skills.

References
1. Heidi M, Harper A and Berger BA et al. Pharmacists predisposition to communicate- Desire to counsel and job satisfaction. Am J Pharm Educ 1992; 56: 252- 8
2. Popovich NG. Ambulatory patient care in Gennaro AR editor Remington: The science and practice of pharmacy vol 2. Mack publishing company, Pensylvania, 19th edition, 1995; 1695- 719
3. USP medication counseling behaviour guideline. USP DI update volumes I and II Rockville, the United States Pharmacopeia Convention Inc, 1997, 664-75, 1739-48.
4. Beardsley RS. Review of literature: oral patient counseling by pharmacists. Proceedings of the National Symposium on oral counseling by pharmacists about prescription medicines. 1997 Sep 19-21; Lansdowne, Virginia
5. Dooley M, Lyall H, Galbriath et al. SHPA standards of practice for clinical pharmacy. In: SHPA practice standards and definitions 1996. p. 2-11
6. Omnibus Budget Reconciliation. Act of 1990, Pub. L .no. 101-508, and 4401, 104 stat 1388, 1990
7. American Diabetes Association. Diabetes facts and figures. Available at: http://diabetes.org/diabetes-statistics.jsp. (Accessed on 27th January 2005)
8. Powers AC. Diabetes mellitus. In: Braunwald, Fauci, Kasper et al 'editors'. Harrison's Principles of Internal Medicine. 15 th edition. United States of America: McGraw-Hill 2001; 2109- 37.
9. Cowie CC, Eberhardt MS, eds. Diabetes 1996: vital statistics. Alexandria, VA, American Diabetes Association, 1996.
10. Kahn SE, Porte D Jr. The pathophysiology of type II (non- insulin dependent) diabetes mellitus: Implications for treatment. In Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin's Diabetes Mellitus, 5th ed. Stamford, CT, Appleton & Lange, 1997: 487- 512.
11. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: Prevalence, numerical estimates, and projections. Diabetes care 1998; 21: 1414- 31
12. Glasgow RE, Anderson RM. In diabetes care, moving from compliance to adherence is not enough: something entirely different is

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