To compare the role of glibenclamide and pioglitazone drugs in type 11 non- insulin dependent diabetes mellitus patients. Authors:Raj kumar chohan,Mashori Ghulam Rasool,Bhurgri Ghulam Rasool,Shamim-u-Rehman,DahriGhulam mustafa,Anis-u-rehman. Introduction:- Diabetes comes from the greek word for ‘SIPHON” which one is the first term and implies for a lot of urine is made .The trm “mellitus” comes from a laton word, “met” which means “honey” and was used because the urine was sweet (Wheeler,2004) Diabetic ketaocidosis is one of life threatening condition requiring some data hospitalization and treatment. Recognition of this condition is of almost importance, because even small delays can have an impact on survival (Nattrass, 2006). Hypoglycaemia are involved in insulin induced episodes in individuals with diabetes. Probably the major factor prescribing, insulin treated patient from achieving the glucose targets needed to prevent diabetic complications. The incidence of hypoglycaemia reflects the inadequancy of current mathods of insulin delievery which lead ot inappropriately high insulin concentration, particularly some persons after eating more foods at night onset of blindness and also a major risk factor heart disease and stroke (Heller, 2003).

TYPES OF DIABETE MELLITUS TYPE 1 DIABETES MELLITUS (IDDM): Type I diabetes affect children of all ages, both sexes and all athenic groups. type 1 diabetes usually occurs by mechanisms. It is most common metabolic condition in children and adolescents (Bui, 2004). Type1diabetes is characterized by immune mediated destruction of pancreatic b -cells resulting in insulin deficiency. This results in a common biochemical end point of hyperglycaemia and risk of ketoacidosis, but the clinical presentaion varies, widely depending on the rate and degree of b -cells failure (Lambert & Bingley. 2005). Type II diabetes mellitus (NIDDM): Type II diabetes is a complex metabolic disorder associated with, b -cells dysfunction and with varying degree of insulin resistance primary pathogenic factors leading insulin resistance leading to type 2 diabetes and decreased insulin, secretion which arise from abnormalities with in liver, skeletal muscle and pancreatic b -cells (charles & clark, 1996).

GESTATIONAL DIABETUS MELLITUS : Women who develop glucose intolerance in late pregnancy and womens who with previously undiagnosed diabetes.

SECONDARY DIABETUS MELLITUS: Secondary diabetes is due to disease of the pancreatic and endocrime system, genetic disorders, or exposure to chemical agents. Type – I diabetes formerly known as insluin dependent diabetes mellitus (IDDM), is characterized by the destruction of the pancreatic beta cells that produces inslulin Type – I diabetes formerly known as insulin dependent diabetes(IDDM),is characterized by the destruction of pancreatic beta cells that produces insulin.Type-1 diabetes occures most often in children and young adults but it can occures at any age.(Anderson et al 2007). Type-11 diabetes is not straight uprward. A pancreas that does not produce enough insulin. Liver that release too much glucose,muscle cells that do not readily take in glucose.(Carren 2008) Many genetic factors are involved in the development of diabetes.Because of new genetic methodology researchers are closers to identifying all of the cadidate gene for both non –insulin dependent and insulin dependent diabetes(Bernhard,1995). Woman who had gestation diabetes are more likely to develop Type-11diabetes themselves.Pergnant women with diabetes are another disadvantaged group.They need much more intensive antenatal care and close monitoring of blood sugar,blood pressure and weight.(jawed2006) Over weight children the progression of child obesity into adulthood is associated with early develop of complications, including IgpG2 diabetes and cardiovascular disease.Type diabetes is the most common clinical form of diabetes accountingforabout 90% of all cases,it is currently undergoing world wide epidemic. Type 11diabetes mellitus is caused by body’s infective use of insulin, it is often results from excess body weight and physical inactivity(WHO 2007).

PREVALACES& IINCIDENCE : Diabetes mellitus increases with aging, in 200 the prevalance of diabetes,it was estimated to be 0.19% people<20 years old and 8.6% in people>20 years old.There is considered geographic variation in the incidence of both type-1 and type-11 diabetes mellitus.Scavandinvian has the highest incidence of type-1 diabetes mellitus e.g in Finland, the incidence is 35/100,000 per year the pacific rim has a much lower rate in japan and china the incidence is 1 to 3/100,00 per year of type-1 diabetes mellitus, Northern Europe and the United States share an intermediate rate (8to17/100,000 per year).The prevalence of type 11 diabeties mellitus is highest in certain pacific island, intermediate in countries such as India and the United States, and relatively low in Russia and China.This variability is likely due to genetic, beharioral and enviromental factors(Power 2005).Diabettes mellitus prevalance also arises among different ethic population within a given countries it is common inall ethnic groups its prevalance increased with age and more than 5% of individuals of more than 65 years of age have diabetes mellitus (David Owerback 1988).The World wide prevalence of diabetes mellitus has risen dramatically over past two decades.The prevalence of type11 diabettes mellitus is expected, type 11 diabetes mellitus is more prevalent among Hispanies Native Americas,African,American,and Asians, pacific Islanders than in non- Hispanic whites,the incidence is essentially equal in woman and men in all populations. Type 11 diabetes is becoming increasingly common because people are living longer,and the prevalence of diabetes increases with age it is also seen more frequently now than before in young people, in association with the rising prevalenceof childhood obesity although type11 diabetes still countries with the estimated nubers of cases of diabetes in 2000and 2030.

Rank Country

2000 Individuals country with diabetes (milloins)

Country

2030 Individuals with diabtes (Million)

India

31.7

India

79.47

China

20.8

China

42.3

USA

17.7

USA

30.3

Indonesia

8.4

Indonesia

21.3

Japan

6.8

Pakistan

13.9

Pakistan

5.2

Brazil

11.3

Russian federation

4.6

Bangladesh

11.1

Brazil

4.6

Japan

8.9

Italy

4.3

Philippines

7.8

Bangladesh

3.2

Egypt

6.7

(Wareham& FOROUHI 2OO6)

DRUG TREATMENT OF DIABETIES MELLITUS : Biguanides lower blood glucose, they increase glucose uptake and utilize in skeletal muscle there by reducing insulin resistance, and reduce hepatic glucose production (gluconeogenesis).Lower blood glucose, addionally reduces low denisity and very low denisity lipoproteins (LDL and VLDL) respectively. Metformin has a half life of about 3 hours and is excreted unchanged in the urine.Clinically metformin used in type 2 diabetic who are obese and who fail treatment with diet alone.Adverse effects are produced dose related gastrointestinal disturbances e.g anorexia,diarrhoea,nausea,lactic acidosis rare but potentially fatal toxic effect.(Dale,2003). Improving insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism Rosigilitazone and Piogiltazone are currently approved.Thiazolidinediones. Thiazolidinediones do not cause hypoglycemia when used alone,although they are usually taken in combination with sulfonylurease. In some incouraging studies, thaiazolidiniones have produced very favorable effects on the heart, including reducing blood pressure and improving triglycerides and cholestrol levels including increasing HDL level,the good cholestrol. They may also block a molecule called 11 Best HSK that may play a significant role in metabolic syndrome,as well as diabetes type11. One study also sugessted that Rosiglitazone may even improve beta cells functions and so help prevent progression of diabetes.Anemia, weight gain, increased risk of fluid buildup, may worson heart failure.Troglitazone,was withdrawn after a few reports of heart failure.Liver failure abd death.Current Thiazoldinediones don not appear to pose the same effects on the liver although there have been a few reports of liver injury. In patients with dietry failur the choice of a sulfonylurea agent or insulin therapy has been controversial and empric in favour of insulin therapy are the studies, who reported marked improvement post receptor diagnostic after intensive short term therapy in untreated type 2 diabetes mellitus (Scarlett et al,1984) Sulfonylureas further classified into two groups or generations based on their potency,duration,drug interaction,side effects profiles. Sulfonylureas enhance insulin action in cells in culture and stimulate the synthesis of glucose transporters (Jacobes et al 1998).A sulfonylurea drug should normally be the insulin secretagogue of choice, NICE (National Institute for Clinical Excellence) also recommends that a generic ,drug should be perscribed (Scsade et al1998).

RESEARCH DESIGN AND MATERIAL AND METHODS: This study was conducted in the deprtment of Pharmacololgy and Therapeutics,Basic Medical Science Institute,Jinnah,Postgraduate Medical Centre,karachi under kind supervision od DRr:GhulamRsool Mashori,Associate Professoer and Head OF Department Of Pharmacology and Therapeutics in colloboration with Medical Outpatient Department Unit111 and Filter Clinic, Medical Department, JPMC,Karachi. Seventy NIDDM (type-II)diabetic patients were initially enrolled in the study from the filter clinic/ out patient department Medical Unit III ,and diabetic clinic.Out of this 60 diabetic patients were associated in whole period of study, remaining 10 patients were dropped due to poor comlpiance or change in residential place.All the patients were divided in two main groups,groupI and in group II these patients were selected in this study according of inclusion and exclusion criteria.

INCLUSION CRITERIA :

Newly diagnose patients of non Insulin Dependent Diabtes Mellitus.

Diagnsed patients of diabetes also including having no any history medication.

Having either sex of age between 30 to 60 years.

Diagnosed patients who were Non Insulin Depedent Diabetes Mellitus who were treated with Pioglitazone.

Diagnosed patients who were Non Imsulin Depedent Mellitus, who were treated with drug Glibenclamide.

EXCLUSION CRIRERIA :

Patients suffering from blood pressure.

Patients suffering from liver disease.

Patients suffering from cardiac disease.

Pregnancies and lactating women.

Patient suffering from renal disorders.

Patients having serious complications.

MATERIAL:

Lacets.

Lancet Hlder(Abbots easy touch TM2 lot 03 Asee).

Glucometer(Medisense) optilim one touch(Abbotts).

Blood glucose nest trpis (IVD for Invitro diagnostic use (Abbott Labortries,Medisense UK Ltd,Abigngdon,Ox14ITR,Masde in UK). Stored between minimum 30?, (4°-30° C) and Maximum 40°C (39°-86°F).

Weight Machine Model No 1101 Lot No.312. TANTIATA.

DRUGS Tab:Daonil 5 mg (Aventis Pharma) Drug category:Sulphonylurea. Generic Name: Glibenclamide. MFGLIC:No.000007 RegistrationNO.000220 MFG Date:0-06 EXP Date:7-10 Lot NO:B230 Tab:piozer (Hilton Pharm) PvtLTd. Tab:Poizer 15mg Drug category:Thaiazolinedione. Generic Name:Pioglitazone Hydrochloride. MFG LIC: O.000136 Registration No.03270 MFG Date:3-06 EXP Date:3-o9 Lot No:6287 Tab: Poizer (Hilton Pharma)pvt ltd. PARAMETERS: Fasting Blood Sugar (FBS). Random Blood Sugar (RBS). Weight.

Key words:Diabetes mellitus,Non-insulin diabetes mellitus,Insulin depedent diabetes mellitus, Daonil,poizer,Insulin.

RESULTS:

Table 1 Weight and Blood Sugar level observed on baseline day 0 In group1 and group11

  Group 1

Group 11

  Pioglitazone n=27

Glibenclamide n=33

Weight

63.37 + 2.25 ¯

62.7 + 15.56 ¯

Fasting Blood Sugar

172.7 + 13.32 ¯

188.42 + 12.o5 ¯

Random Blood Sugar

285.11 + 15 .532 ¯

284.18 + 17.07 ¯

All Values are expressed in Means± SEM. FIGURE-1 weight and blood sugar levels observed on baseline (day-o)

In table No shpwing the weight (KG’S) and blood sugar (msg/dl0 levels which is observed on baseline (day-0) in both groups 9group: 1 & group11) Group: 1 Weight in (Kg’s) mean + SEM) IS 63.37±2.25 Fasting blood sugar 172.7±13.32,and Random blood sugar 285.11±15.32

Group:11 Weight (KG’s0 (mean +SEM)62.7±1.56 Fasting blood sugar (mg/dl0 188.42±12.05, Random blood sugar is 284.18±17.03. Figure 2: showing the weight and blood sugar levels observed in base line (day-0) in group: 1 and group 11 weight in 9kg’s) its mean values are 63.37,62.7, Fasting blood sugar in (mg/dl) is 172.71, 188.42 Random blood sugar (mg/dl) is 285.11 &284.18. TABLE: 2 Peroidic Observation In All Parameters Group1

Goup1(Pioglitazon) n=27   P-value

  Day-0

Day-45

Day-90

Day-0to45

Day-45-90

Weight

63.37 ±2.25

63.63 ±2.26

63.63 ±2.23

>0.05 (NS)

>0.05 (NS)

Fasting blood sugar

172.7 ±13.32

165.04 ±8.98

153.37 ±7.59

>0.05 (NS)

0.05 (NS)

Randomblood sugar

285.11 ±15.32

279.78 ±13.63

255.56 ±12.65

>0.05 (NS)

>0.05 (NS)

All values are expressed in Mean±SEM .(NS) Non significant.

TABLE NO:2

Showing the periodic observations in all parameters in group 1 (piogiltazone) (n+27) weight P.value (day 0 to day 45)>0.05 (NS). Fasting blood sugar >0.05 (NS) Random blood sugar >0.05 (NS) P.values day 90 weight >0.05 (N.S), FBS>0.05 (N.S) 7RBS >0.05(N.S) NON SIGNIFICANT FIGURE:2 Showing the periodic observation in all parameters in group 1 on day0 day 45& day-90.Mean values in weight (Kg) is 63.37,63.26,63.63, fbs (mg/dl) 172.7,165.04,153.37,RBS(mg/dl) 285.11,279.78,255.56. TABLE NO3 Peroidic Observation in All Parameters Group11

  Group 11 (Glibenclamide) N=33

P-value

  Day-0

Day-45

Day-90

Day-0 to 45

Day-45 to 90

Weight

62.7 ±1.56

65.64 ±2.10

64.55 ±1.92

>0.05(NS)

0.05(NS0

Fasting blood sugar

188.42 ±12.05

168.45 ±10.99

140.06 ±5.68

>0.05(NS)

>0.05(S)

Random blood sugar

284.18 ±17.03

220.12 ±13.39

170.94 ±5.80

<0.005 (MS)

0.002(MS0

(s) significant, (MS) moderate significant All values are expressed in Mean±SEM.

Table No3: Showing the periodic observation in all parameter in goup:11, Group:11 containing drug (Glibenclamide),no of patients (n=33).It’s P-value on day 0 to day 45 on weight >0.05(NS),FBS>0.05(N.S) RBS<0.005 (MS) <0.01- AND DAY 45 TO DAY 90 WEIGHT >0.05 (NS) FBS (0.05) RBS <0.002(M.S0 moderately significant.

Figure 3:Shwing the periodic observations in all parameters in Group 11 weight 62.7,65.64,64.55,FBS (MG/DL) 188.42,168.45 140.06,RBS(mg/dl) 284.18 220.12, 170.94 (on day-0-day 45 to 90).

DISCUSSION: In Denmark Beck-Nielsenet al,skillman TG (1981) published studies demonstation that glyburide increased he number of receptors on the monocytes of patients with type 11 diabetes mellitus. Some patients were treated with diet and in cobination of second generation sulfonyureas agents Wie. The numbers of insulin receptors all patients were measured before and after the treatment.Intrvenous glucose test shows the persistent impairent of insulin secretion afterthe starting of drug therapy.However those patient who were on drug Pioglitazone some results were obtained of insulin secretion in the impairment in early drug drug therapy.Clinical observations have suggested that the second generation sulfonylureas may exert their effects by potentiating insulin released by other primary stimulators Insulin secreting drug. According to the study of WilliamC Dukworth et al(1972), aftr the chronic treatment with sulfonylureas it is well documented that plasma insulin levels were decreased in response to oral glucose load. This apparently occures even though glucose tolerance is improved over pre-treatment, levels,present study clearly support that study. The result og group 11 correlates with the research conducted by Bonnie &Kimmel (2005) produces the same results as FBS reduces from baseline, and at the end of study,with an overall 23.44%,reduction,while with the results showed at the end of study peroid p-value were (p<0,001). Similarly Michael Alvarsson et al (2003) conducted a similar type of study and the found and overall changes of change of 22.11% in Fbs and 40.88% in Rbs at the end of trial p-value were (p<0.001). However a study conducted by (Stone &Brown in (2003) didnot match to our results in the parameter of FBS and observer a reduction of 26.22%. CONCLUSION: In the light of study discussion it is obiovus the glibenclamide was more effective,tolerable and safer than pioglitzone in a short duration.Diabetes Mellitus is chronic prolong disease for whole life.Poor community can afford it easily,on base of marketing of this drug in pakistan diabetes patients easily go and purchase economically,in fact ,mostly people buy it from pharmacy without dr’s perscription,because pharmacist and patient both of know about this disease.Just like dispirin as analgesic,it is famous anti-diabetic drug in our states as compared of other anti-diabetic drugs.

REFERNCES:

Anderson J,Kendall,Perryman.S etal,”Diet and Diabettes” Diabetes 2006,16(3):17-19-

Bui H- Type 1 diabetes in childhood-Medicine 2006,3 ,1-3

Bernhard –Diabetes-type 11 diabetes mellitus Diabetes care 1995,19(100:12-17-

Clark CM-Oral therapyin type11 diabetes-pharmacological properties and clinical use of current use of currently available agents-Diabetes spectrum 1998,11(4):211-221.

Carren M.Types of Diabetes mellitus-Diabettes 2006 10 (3),07-

David Owerback NJ-Prevalence in diabetes population-Diabetes 1988,02(6):31-32

Dale MM,-Treatment of Diabetes mellitus –pharmacology 20035th edition:287-391.

Heller SR –Hypoglycemic in diabetes Ketoacidosis and hypoglycemic-Medicine 2006:34(03):102-110.

Jawad F Untraveling the mystry of Diabetes’Diabetes 2006;15(3):13-15.

Jacobes D-Insulin-Diabetes 1998;6(3);1160126.

Lambert and Bingliy-basic facts-medicine 2006,34(6):3-7.

Natters M-Ketoacdosis and hyperglycemia-Medicine 2006;34(3):104-106.

Power AC-Epidemiology of type11 diabetes Basic facts of diabetes –Diabetes 2005;1(1)7-9

Scarlet Oral therapy in type 11 diabetes sulfonylureas 1984;16(10);3-9.

Schade DS et al A placebo controlled randomized study of glimepiride in patients of Diabetes mellitus- Diabetes 19998, 38(7);636-641.

Warchman and Forouhi-Epidimology of Diabetes- Diabetes basic facts- Medicine 2006 ;34(2);57-60

Wheeler Gd- Aaccident dicovery led to the noble prize for canadian reseachers,2005,01-02.

WHO Report-Health-Diabetes Mellitus-Defiition and types of Diabetes 2007;1:1-4.