Estimation of Blood Glucose Levels in Diabetic Patients of Different Skin Diseases with the Treatment of Triamcinolone Acetonide and Prednisolone – a Comparative Study.

A Thesis paper submitted to the Department of Pharmacy, East West University in conformity with the requirements for the Degree of Bachelor of Pharmacy.

  A collaborative study between Department of Pharmacy,

East West University and Skin Department, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders.

SummarySteroid, pharmacologically very important & useful that is essential and can be used for different

indications & treatment of diseases.

Steroid has different complications like folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, acneiform eruptions, allergic contact dermatitis, hyperglycemia, growth reterdation, cataract, Cushing’s syndrome, glaucoma etc. For these reasons, use of steroids should be very metticulous & rational to avoid those side effects and complications.

Depending on substitution, subtraction, addition and replacement, pharmacologically steroid has been classified into two groups: a) mineralocorticoids (Aldosterone, Desoxycorticosterone, Corticosterone, Cortisol, Cortisone & 9-alpha fluorocortisol) and b) glucocorticoids (Corticosterone, Cortisol, Cortisone, Prednisone, Methylprednisone & Dexamethasone).

In dermatology prednisolone and triamcinolone acetonide are indicated in different skin diseases, drugs can be used in the same indications like Urticaria, Leprosy, Lichen Planus, sweet syndrome, Seborrheic Dermatitis, Pompholyx, Prurigo Nodularis, Pemphigus vulgaris, Hand Eczema, Bullous, Vasculitis etc.

Our purpose of this study is to see the variation of side effects of prednisolone and triamcinolone acetonide in the skin diseases where both the steroids are indicated.

Continue…Study subjects were divided into two groups: group1 (prednisolone) and group2 (triamcinolone acetonide).

Single dose of triamcinolone acetonide was given to 15 patients and different amount of dose of prednisolone was given to 15 patients. Their glycemic status was measured before steroid (baseline) at 0 week which was compared with the blood sugar during period of week1, week2 and week3 after steroid.

Blood glucose level (fasting & 2h ABF) in both groups (prednisolone and triamcinolone acetonide) rose significantly after week1, week2 & week3.

The study showed, triamcinolone acetonide had little tendency to increase blood glucose level when compared with prednisolone. Fasting blood glucose ≥ 10 mmol/l was considered as an arbitrary line for control of blood glucose. Triamcinolone acetonide did not cross arbitrary line 10 mmol/l but prednisolone crossed the arbitrary line. Thus control of blood glucose level remained static in triamcinolone. However blood glucose in prednisolone might remain uncontrolled. Both groups showed significant improvement of skin diseases.

Thus triamcinolone acetonide is the better choice in the treatment of skin diseases with diabetes mellitus.

 

Introduction

Diabetes is a disease in which the body does not produce or properly use insulin. It has high blood sugar levels which if not well-controlled can lead to long-term complications affecting various organs in the body such as the eye, kidney, nervous system, skin and blood vessels. Skin problems are very common in diabetics and it is a common condition which frequently has skin manifestations. The attachment of glucose to protein may result in a profound effect on structure and function of that protein, and account for clinical manifestations of the disease. It has been suggested that increased cross linking of collagen in diabetic patients is responsible for the fact that their skin is generally thicker than that of non-diabetics. Advanced glycosylation end products are probably responsible for yellowing of skin and nails. Increased viscosity of blood due to stiff red blood cell membranes results in engorgement of the post-capillary venules in the papillary dermis, detected as erythema of the face, or periungual erythema. It is suggested that these skin changes may eventually be used as a reflection of the patient's current as well as past metabolic status (DermAtlas). Diabetic skin conditions include abnormal growths, ulcers, infections and changes in the skin itself (National skin centre). There are many reasons people with diabetes face increased risk of skin problems:

Impaired circulation Hyperglycemia (high glucose) Hyperlipemia (high levels of fats in the blood) Suppressed immune system Diabetic neuropathy (nerve damage) High blood pressure

Continue..The key to prevention of many types of diabetic skin conditions is regular good hygiene and control of risk

factors. Treatments depend on the particular disorder but often include surgical incision or debridement (removal of damaged tissue) and antibiotics, antifungals or other medications (National skin centre). Some common skin diseases associated with Diabetes Mellitus are Urticaria, Leprosy, Lichen Planus, sweet syndrome, Seborrheic Dermatitis, Pompholyx, Prurigo Nodularis, Pemphigus vulgaris, Hand Eczema, Bullous, Vasculitis etc. (ANDREWS’). Shortly after the synthesis of hydrocortisone in 1951, topical glucocorticoids and mineralocorticoids were recognized as effective agents for the treatment of skin diseases. It is also used to treat many inflammatory skin diseases. Maibach and Stonghton, 1973 have divided 20 dermatological disorders that are very responsive and those that require concentrations of steroids, occlusion or intralesional administration. Various side effects of these preparations are also associated with its different uses. So attention must be paid to the concentration of steroid used. In clinical trial found that glucocorticoids increase blood glucose level and cause hyperglycemia. As a result physicians do not use corticosteroids due to the metabolic deterioration of blood glucose level with diabetes. Glucocorticoids work on carbohydrate, lipid, and protein and produce glucose. As a result hyperglycemic episode occur (Goodman, Gilman). If our diabetes is well controlled, many of these skin problems can be averted. This requires compliance with a diabetic diet, medication and regular check-ups with our doctor. When there are serious complications such as bacterial skin infections, gangrene, seek immediate medical attention. Consult doctor early. We may need hospitalization. If left untreated, these complications may lead life-threatening. Infected ulcers and skin infections need to be treated with antibiotics, antifungals and glucocorticoids (prednisolone and triamcinolone acetonide) (Reza B Zaid, 1996). Now, most commonly used drugs are corticosteroids, especially glucocorticoids (prednisolone and triamcinolone acetonide) and others as a combination therapy. The aim of this controlled study was to determine the efficacy of steroids in treating diabetic with different dermatoses as well as to see the effects on glucose metabolism.

Materials and MethodsA randomized, parallel- group study was conducted from March 2008 through December 2008 at

the Bangladesh Institute of Research and Rehabilitation for Diabetes, Skin Department (BIRDEM), Shahbagh, Dhaka, Bangladesh.

Patients

In the study, 30 patients (both male and female) with NIDDM (cases) were taken between 30-70 years as healthy volunteers. They were selective and subdivided grouped as 1) group1; prednisolone (15 patients), the standard drug and 2) group2 (15 patients), the study, triamcinolone acetonide. Blood sugar levels were estimated for different skin diseases (Urticaria, Leprosy, Lichen Planus, sweet syndrome, Seborrheic Dermatitis, Pompholyx, Prurigo Nodularis, Pemphigus vulgaris, Hand Eczema, Bullous, Vasculitis etc.) where steroid was indicated in every weekly for four weeks. Pregnant, nursing women were excluded from the study. Patients with other clinical complication other than type2 diabetes and skin diseases were excluded from the study. Their state of blood pressure, weight was recorded before starting of steroid therapy. Their glycemic status as well as individual’s diet and exercise habit were recorded at the base line and every week for four weeks. To avoid other factors that are responsible for raising individual’s blood sugar all the patients were instructed to continue the same diet and exercise habit as they were in basal state.

 

Statistical Analysis:

Data were analyzed by manually. All the data of the study sample was entered from each patient’s history sheet and data of standard sample was entered from all enquiry sheets. Descriptive statistics were done for major variables of interest, including the population, age distribution, drug for skin diseases, drug for diabetes and different concentration of blood sugar levels using Student’s t-test. A probability level of 0.05 was considered statistically significant.

Results

Total dose of steroid incase of triamcinolone acetonide group is 69.32 mg/ml, of which 34.66 mg/ml was given IM on “0 week” and 34.66 mg/ml was given at the beginning of 3rd week. Patients with triamcinolone acetonide had blood sugar before steroid was 7.6 mg/dl and 9.9 mg/dl at 1st week, 9.82 mg/dl at 2nd week and 9.05 mg/dl at 3rd week after giving steroid. Though patients were taken steroid, their blood glucose levels still remain controlled (shown in Fig1). Most of skin diseases were well controlled and cured by triamcinolone acetonide. Antidiabetic drugs were no needed to change during treatment.

 

Fig1: Mean value of fasting and 2hABF in triamcinolone in different weeks during treatment period.

Average of fasting and 2hABF in triamcinolone

0

2

4

6

8

10

12

14

16

0 1st 2nd 3rd

Week

Fasting mg/dl

2HABF mg/dl

Total dose of oral prednisolone group is 44.4 mg, of which 18.3 mg was given at 0 week, 13 mg at 1st week, 7.8 mg 2nd week and 5.3 mg was given at 3rd week. Patients with prednisolone had blood sugar before steroid was 8.5mg/dl. After giving steroid blood sugar was 12.13mg/dl at 1st week, 11.54mg/dl at 2nd week and 11.37mg/dl at 3rd week. Here after administered prednisolone, blood glucose level was not controlled (shown in Fig2) but most of the diseases were cured properly. Antidiabetic drugs were changed during treatment.

Fig2: Mean value of prednisolone dose, fasting and 2hABF in prednisolone in different weeks during treatment period.

Average of fasting and 2hABF in prednisolone

0

5

10

15

20

0 1st 2nd 3rd

Week

Mg

/dl

Fasting mg/d

2HABF mg/dl

Significance:

In the study, I considered 95% significance. After giving drugs both prednisolone (15 patients) and triamcinolone acetonide (15 patients), blood sugar level raised significantly from 0 week to 1st week, 0 week to 2nd week and 0 week to 3rd week in all patients. But prednisolone has tendency to increase blood sugar higher than that triamcinolone. In triamcinolone acetonide patients’ blood sugar level rose from 2 to 3 mg/dl whereas in prednisolone patients’ blood sugar level raised 5 to 15 mg/dl than baseline or 0 week.

Comparison between blood sugar level in week 1, 2, 3 with baseline (week0) shown for prednisolone and triamcinolone

Drug type blood sugar level 0 week to 1st week

0 week to 2nd week

0 week to 3rd week

Triamcinolone acetonide

Fasting P<0.01 P<0.01 P<0.05

2h ABF P<0.01 P<0.01 P<0.05

Prednisolone Fasting P≤0.05 P<0.05 P<0.05

2h ABF P<0.05 P<0.05 P<0.05

Tendency to increase blood sugar of prednisolone and triamcinolone acetonide were observed from 0 week to 4th week and blood sugar was highest during 1st week. Later in subsequent weeks the blood sugar level declined gradually.

The fasting blood sugar with group in triamcinolone acetonide did not cross the arbitrary line of controlled blood sugar but prednisolone crossed the urbitary line and was remained uncontrolled state during treatment period. Thus fasting blood sugar control remains good with triamcinolone acetonide when compared with prednisolone.Blood sugar level after breakfast was observed in both triamcinolone acetonide and prednisolone. Pattern of blood glucose levels were similar in prednisolone and triamcinolone acetonide (Fig3).

Thus control of blood sugar in case of prednisolone is more important than triamcinolone actinide. Because prednisolone induced uncontrol state and it crossed the arbitrary controlled line (10 mmol/l) but triamcinolone acetonide did not cross the arbitrary line of controlled blood sugar.

Fasting and 2h ABF in individual patient from week 0, 1, 2 and 3 in triamcinolone acetonide

WeekPatients Baseline 1st week 2nd week 3rd week

Serial No.

Fasting 2hABF Fasting 2hABF Fasting 2hABF Fasting 2hABF

1 7.1 13 9 15.8 9 14.7 8.5 14.72 9.9 11.4 12.1 14.3 11.1 12.7 9.9 12.73 5.4 6.9 4.84 5.3 6.2 7.9 6 7.94 6 6.7 12 16 10 14.9 9.5 14.95 8.8 10 8.2 12 9 12.5 8.1 12.56 12.8 17.1 11.5 14.9 8.9 13.4 8 13.47 7.0 14.5 8.3 17 8 15.9 7.9 15.98 7.5 13 6.2 12.1 13.7 19.2 10 19.29 5.1 8.1 9.5 12.4 8.9 11.1 8.3 11.110 7.7 9.1 11.1 13 9.9 11.5 9.5 11.511 10.1 11.5 13.5 16 11.7 14.3 10.5 14.312 6.7 12 10.3 14.9 10 12.7 9.7 12.713 8.7 13.1 11.5 17.3 10.9 15.3 10 15.314 5.5 13.6 10.5 17.1 10.1 14.3 9.8 14.315 5.9 11.5 10 14 9.9 12.3 10 12.3Mean 7.6 11.43 9.9 14.14 9.82 13.51 9.05 12.653

Fasting and 2h ABF in individual patient from week 0, 1, 2 and 3 in Prednisolone

WeekPatients

Baseline 1st week 2nd week 3rd week

Serial No.

Fasting

2hABF Fasting

2hABF Fasting

2hABF Fasting

2hABF

1 7.4 13.1 11.5 20.7 11 17 10.5 16.52 6.1 14.2 9.1 16.3 9.5 14.7 10 15.93 8 16.3 11.1 20.5 10.9 16 10.5 16.34 14.3 24.7 18.3 27.3 16.1 25 15 25.95 6.4 9.8 9 12.4 9.5 13.5 10 13.36 23.6 25.9 7.1 9.1 10.3 18.5 12.5 19.77 8.6 14,2 5.2 8.2 7.3 10 9.7 10.58 8.9 10.3 10.4 12.2 9.3 10.5 10 12.99 4.2 8 15.1 20.5 13.1 16.5 11.9 14.5310 5.4 13.2 14.9 23 12.5 16 11.5 14.8511 7.2 12.4 13.3 20.5 11.9 16 10.9 15.412 4.6 5.8 10.5 14.9 11 13.7 10.5 1213 6.9 11.1 11.3 20.1 10.7 15.5 10.3 13.514 7.8 9 19.1 22.5 16.3 17.5 14.7 14.715 8.1 9.9 16 20 13.7 16.1 12.5 11.5Mean 8.5 13.19 12.13 17.5 11.54 15.8 11.37 15.17

Graph below is showing, Fasting and 2h ABF in individual patient from week 0, 1, 2 and 3 in prednisolone and triamcinolone acetonide.

Patients of triamcinolone acetonide; when they were in the treatment of skin, dose of antidiabetes drug would not change in most of patients. Dose modification was rare. Among fifteen patients one patient who took insulin, his dose was modified (decreased the dose unit) as his sugar level become controlled. On the other hand in prednisolone patients, antidiabetes drug dose would not change in most of patients but one patient who took insulin; their dose was adjusted by increasing or decreasing dose amount (±2) to control their blood sugar level. In both groups dose frequency was observed by Comparing drug treatment from 0 week to 1st week, 0 week to 2nd week & 0 week to 3rd week. For patients who took Prednisolone, dose adjustment is needed whereas in triamcinolone patients did not need to increase dose to control sugar level .

Efficacy: During the study, signs and symptoms improved in both treatment groups except 7 out of 30 patients.

Tolerability:Complication due to drug with prednisolone and triamcinolone, was followed up. Clinical follow up showed no complications such as peptic ulcer disease, myopathy, depression, acne, nausea, hypertention, osteoporosis, adrenal insufficiency and stria. All diseases were well tolerated by prednisolone and triamcinolone.

Discussion

Corticosteroids have profound effects on carbohydrate metabolism: stimulating liver to form glucose from amino acids and glycerol [14]. In the periphery, corticoids decrease glucose utilization, increase protein breakdown and activate lipolysis, thereby providing amino acids and glycerol for gluconeogenesis [14]. The net result is increased in blood glucose levels because of these effects on glucose metabolism, treatment with glucocorticoid can worsen control in patients with overt diabetes and can precipitate onset of hyperglycemia in patients who are predisposed [14]. One case study showed that prednisolone 20 mg OD for two months followed by dose tapering to 10 mg OD as maintenance dose was given to a patient as an immunosuppressive agent and patient got steroid induced diabetes mellitus [14, 20]. Our study also showed that prednisolone 18.3 mg OD for one month followed by dose tapering to 5.3 mg OD was given to diabetes patients for the treatment of skin diseases and patients blood sugar levels increased significantly after administration of oral prednisolone. However, effects of glucocorticoids on hyperglycemia usually remit within 48 hours of discontinuation of oral administration [14].

In the study of tapering off prednisolone after renal transplantation showed that reduction in daily prednisolone dose leads to decline in blood glucose level [15]. Weight gain was associated with increasing blood glucose level [15]. Each 1mg reduction of prednisolone dose leads to an estimated decline in 2h ABF of 0.12 mmol/l based on multiple linear regression model [15]. We also observed that tapering off prednisolone dose leads to decline in blood glucose level (fasting and 2h ABF).

Continue..

The safety of steroids in diabetes has been a subject of debate.

 

Skin diseases are very much common with diabetes patients and those are treated by steroids.

Steroids are an effective treatment of different skin diseases in the subjects of diabetes [1]. In our study both groups showed significant improvement of skin diseases. Symptoms and improvement of skin diseases were observed by the physicians.

 

Steroids are used in the treatment of erosive lichen planus with diabetes is of considerable concern because steroids can antagonize the action of insulin, lead to hyperglycemia and need self monitoring during steroid therapy [23]. Triamcinolone acetonide treat oral lichen planus completely [28]. We observed that lichen planus was well treated by the apllication of intramascular injection, triamcinolone acetonide.

 

Systemic corticosteroids are usually chosen first to treat patients with generalized forms of any autoimmune bullous disease [26]. The efficacy of systemic steroids in patients is based on the study of patients with pemphigus vulgaris [26]. Before systemic steroids were available most of the patients with that condition died [26]. Prednisolone causes adverse effect after given high dose [26]. After given low dose patients were benefited [26]. Many early case reports showed that steroids therapy is beneficial as it treat disease by blocking further injury or inhibited the inciting cell mediated immunologic reaction [26]. Bullous disease and pemphigus vulgaris were well treated by the administration of oral prednisolone.

 

Leprosy is a disease caused by Mycobacterium leprae that initially affects the peripheral nervous system with patients exhibiting contrasting clinical, immunological pathological manifestation and well treated by steroids (prednisolone) [31]. During treatment period we observed that reactive leprosy was improved after giving prednisolone.

 

Paravertebral lumbosacral injection of triamcinolone acetonide resulted in statistically significant decrease in pruritis, burning, tingling, and pain and improved quality of life [34]. This is also true for our study. Our study limitation was that we have done our study by taking small number of patients. As a result further large study is necessary to confirm our findings. Some general points were noticed during the study. They are: •Diabetes patients who are in diet can be treated by steroids with weekly observation.

•Diabetes patients who are in oral hypoglycemics can be treated by steroids with careful observation, twice per week.

•Diabetes patients who are in insulin need grate care and daily observation while treating by steroids.

•When increase the dose of steroids may need to modify dose of hypoglycemics either patients will face hyperglycemia.

•When reduce the dose of steroids must reduce the dose of hypoglycemics either patients will face hypoglycemic episode. Effect of steroids on blood glucose level reduces with the improvement of skin diseases and when patients are not in stress.