Medical Care |

Medical Care





Original Article
Effect of Pioglitazone HDL Levels of Type-2 Diabetics Pak Armed Forces Med J 2016; 66(2):212-15 EFFECT OF PIOGLITAZONE ON SERUM HIGH DENSITY LIPOPROTEIN (HDL)
Muhammad Zohaib Iqbal, Raheel Iftikhar*, Khurshid Muhammad
Combined Military Hospital Multan Pakistan, *Pakistan Armed Forces Base Samunigli Quetta Pakistan ABSTRACT
Objective: To study effect of Pioglitazone on serum high density lipoprotein levels in patients with type 2
diabetes mellitus.
Study Design: Single blind randomized controlled trial
Place and Duration of Study: Department of medicine, Combined Military Hospital Multan from 1st Feb 2011
to 30th July 2012.
Material and Methods: A total of 276 already diagnosed patients of diabetes mellitus type 2 between age of
30-80 years, presenting to the outpatient department of Combined Military Hospital Multan were selected.
Type 2 diabetic patients were allocated group A or B using random allocation. Base line blood sugar fasting
(BSF), glycosylated hemoglobin (HbA1c), high density lipoprotein (HDL) levels were taken. Group A was
treated with Pioglitazone along with other hypoglycemic agents while group B was treated with only
hypoglycemic agents and multivitamin tablets were added as placebo.After 12 weeks of treatment, serum
HDL levels were measured to analyze effect of pioglitazone on serum HDL levels.
Results: Pioglitazone group showed significant improvement in the serum HDL levels from baseline HDL
46.38 + 6.44mmol/L to 49.80+ 5.86 mmol/L after 12 weeks of therapy, (p = 0.001).
Conclusion: Pioglitazone when used in combination with other oral hypoglycemic agents has a beneficial
effect on the serum HDL levels of the diabetics.
Keywords: Diabetes Mellitus, High density lipoprotein, Pioglitazone.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

(PPAR-γ) which is a nuclear receptor affecting Type 2 Diabetic patients commonly have cellular function by nuclear transcription6. lipid abnormalities1. These changes are Besides the glucose lowering effect of characterized by elevated triglycerides and Pioglitazone, the inhibition of lipolysis and decreased HDL cholesterol2. The pattern of adipocyte differentiation results in changes in lipid abnormalities in diabetics differ in various the lipid metabolism. The effects include a races and the commonest dyslipidemia in type decrease in triglyceride (TG) levels, increased 2 diabetic local population is low HDL3. high density lipoproteins (HDL)7. The lipid Decreased HDL levels may occur in up to 81% effects of this drug have been studied in the of type 2 diabetics in Pakistani population4. west showing baseline serum HDL mean Decreased HDL cholesterol has been identified 50.6 (±11.9) in general diabetic population on as a major independent risk factor for coronary Sulfonylureas and /or Metformin and artery disease5. 54.4 (±13.4)8 for those diabetics taking Pioglitazone. Data regarding the lipid effects of thiazolidinedione Pioglitazone in the Pakistani population is derivative approved for the treatment of type 2 lacking. Considering one of the most common diabetes mellitus. Pioglitazone acts by binding dyslipidemia in type 2 diabetic Pakistani to Peroxisome proliferator activated receptor population is decreased HDL, studies on this drug may prove it to be more beneficial in our Correspondence: Dr Raheel Iftikhar, Medical Specialist
PAF Base Samunigli Quetta, Pakistan
people. The results of this study may benefit the Email: [email protected] patients by better HDL profile and decreased Received: 24 Jul 2013; revised received: 27 Oct 2014; accepted: 10 Dec cardiovascular complications in such patients. Effect of Pioglitazone HDL Levels of Type-2 Diabetics Pak Armed Forces Med J 2016; 66(2):212-15 This study aims at determining the effect of treatment records and follow up proformas Pioglitazone on serum HDL levels of type 2 were checked for compliance and treatments diabetics in a subset of local population. received in the past 3 months. Patients were MATERIAL AND METHODS
allocated group A or B using random allocation based on computer generated table of random These randomized controlled trials were numbers with 138 subjects in each group. carried out in department of medicine, Fasting Blood Glucose levels, glycosylated Combined Military Hospital Multan, from 1st hemoglobin (HbA1C) and baseline serum HDL Feb 2011 to 30th July 2012. Diagnosed Patients of levels were taken after an overnight fast of 10 diabetes mellitus type 2 between age of 30-80 hours. All 276 patients were using various Table-1: Base line Characteristics of study group.

Pioglitazone group ( n=138)
Control group (n=138)
Age in years (mean ±SD)
BMI (kg/m²) (mean ±SD) Medications n (%) Gender (male/female)n HbA1c % (mean ±SD) BSF (mmol/l) (mean ±SD) Serum HDL (mg/dl(mean ±SD) Table-2: Clinical characteristics of study group at 12 weeks of treatment.
Pioglitazone group n=138
Control group n=138
BMI (kg/m²) (mean ±SD) HbA1c % (mean ±SD) BSF (mmol/l) (mean ±SD) Serum HDL (mg/dl) mean (SD) *statistically significant years of both genders presenting to the hypoglycemic agents namely, metformin, outpatient department for regular follow-up acarbose, sulfonylureas, insulin therapy. Group and glycemic control were included in the A was started on Pioglitazone 15mg once daily study. Total 276 patients were included in the along with other hypoglycemicagents (which study through non-probability convenienced the patient was already taking). Patients were sampling technique. Informed written consent followed up on regular monthly basis and was taken from all enrolled patients and necessary adjustments made in the dosages to permission from hospital ethical committee was control sugar levels. Dose was adjusted (15- sought. Those using statins in past 08 weeks, 45mg once daily) depending on the fasting HbA1c > 10.5%, ketoacidosis, renal failure, blood sugar levels on fortnightly visits congestive cardiac failure, pregnant females, current smokers, non-compliant to treatment, Group B was started on multivitamin Body Mass Index (BMI) > 30 kg/m², acute or tablet as a placebo along with other chronic hepatitis were excluded from the study. hypoglycemic agents namely, metformin, Sample size was calculated using WHO sample acarbose, sulfonylureas, insulin therapy except size calculator for comparing two means, taking pioglitazone. Dose of hypoglycemic agents was confidence interval of 95%, power of the test adjusted according to the fasting blood glucose 80%. Thorough history was taken and clinical levels. After 12 weeks of treatment, again examination performed. Patients previous Effect of Pioglitazone HDL Levels of Type-2 Diabetics Pak Armed Forces Med J 2016; 66(2):212-15 serum HDL levels were taken after an showed significant increase in HDL levels overnight fast of 10 hours. Patients in both the (p=0.001) at 12 weeks of therapy but in group B groups were followed up for 3 months. Samples there was no change in HDL at 12 weeks were also taken for glycosylated hemoglobin to (p= 0.26). assess the blood glucose control over the DISCUSSION
preceding 3 months. Serum HDL levels were determined in the 10 hour fasting serum Diabetic population has shown increased samples taken by laboratory technician. Patients incidence of dyslipidemThis makes these were asked to sit on a chair and roll up their sleeves above elbow. Venous blood samples complications. So understanding the lipid were collected using full aseptic measures and abnormalities that affect your population group samples were transported to Pathology and having tools and measure to correct them laboratory for analysis. Serum HDL level becomes more important. Decreased serum estimation was done by a timed endpoint HDL levels is one of the commonest lipid method using HDLD reagent. DXC 600 abnormality encountered in Pakistani diabetic automated analyzer was used. The results were populatiPioglitazone is a relatively newer verified by pathologist. GLU reagent was used treatment modality in Pakistan and very little to measure serum glucose levels using DXC-600 work had been done on it, particularly in our automated analyzer. All the data had been population. Pioglitazone has shown many entered in computer software Statistical beneficial effects in the treated diabetic Package for Social Sciences (version 17.0). Mean population and better serum HDL profile is one and standard deviation (SD) were calculated for of major benefits derived from this therapy. all the quantitative variables i.e. age, BMI, Patients with Diabetes Mellitus frequently glycosylated hemoglobin, fasting blood sugar encounter dyslipidemia or deranged lipid and serum HDL levels. Frequency and profile therefore, a drug which not only percentage was used to express qualitative improves glycemic control but has added variables. Stratification was done to control benefits becomes important and drug of choice. effect modifiers like age, gender and BMI. This drug has a relatively safe side effect profile Comparison between groups was done therefore most of the patients tolerated the independent samples t test, difference between before and after treatment values were analysed This aspect of dyslipidemia has been using paired t test. A p value < 0.05 was studied very less in our population but is considered significant. gaining large attention in the world. The results of the study clearly show that there is statistically significant improvement in serum The age of the study population ranged HDL profile in patients treated with from 30 to 80 years. Mean age of the patients in Pioglitazone. In this study, patients in both the group A was 54.43 ± 9.66 years and mean age in groups belonged to either gender or the age group B was 53.62 ± 9.57. In group A, the mean group included 30-80 years. Statistically Serum HDL levels at presentation was 46.38 significant results were seen as improvement in ±6.45 mg/dl, in group B it was 45.93 ± 6.43 serum HDL levels of the group treated with Pioglitazone. Test of significance revealed p- characteristics of study group are described in value of<0.05(0.0001). Since most common dyslipidemia is deranged HDL levels, this drug In group A, mean serum HDL, 3 months can be more beneficial in our population. after treatment was 49.80 ± 5.86 mg/dl and the Pioglitazone is currently approved as a mean in group B was 45.73 ± 5.97 mg/dl, with third line therapy. But in patients who show significant difference(p=0.001).There were no marked lipid abnormalities this may be used significant differences of BMI, BSF, Hba1c levels earli Also for those patients in which HDL between group A and group B. Group A remains low despite treatment, Pioglitazone Effect of Pioglitazone HDL Levels of Type-2 Diabetics Pak Armed Forces Med J 2016; 66(2):212-15 may offer an effective alternative to standard conflict of interest. treatment for better metabolic profile. Similar REFERENCES
results were seen in a Japanese study though 1. Wasim A, Shamail Z, Ashraf M. Comparison of Dyslipidemias in there is much difference in the ethnic buildup, controlled and uncontrolled type 2 diabetics. Ann King Edward Med lifestyles and diet of the two population Coll 2004;10:158-60 2. Nesto RW. Correlation between cardiovascular disease and diabetes group Tamio T, et all conducted a mellitus: current concepts. Am J Med 2004;116 (Suppl. 5A):11S–22S randomized controlled trial involving 92 3. Samar F, Muhammad Z K. Comparison of patterns of lipid profile in type 2 diabetics and non diabetics. Ann King Edward Med Coll patients and compared the effects of 4. Abdul B, Muhammad Zafar I H, Rubina H, Muhammad Y A, Qamar Pioglitazone therapy with Glibenclamide in M. Frequency of chronic complications of type II Diabetes. J Coll terms of serum lipid profi This study Physicians Surg Pak Feb 2004;14:79-83 5. Cardenas GA, Lavie CJ, Milani RV. Importance and management of indicated a statistically significant improvement low levels of high density lipoproteins cholesterol in older adults. Part in serum HDL profile. From baseline HDL II screening and treatment. Geriatrics Aging.2004;7(3):40-4 6. Nathan DM, Buse JB, Davidson MB, Hiene RJ, Holman RR. mean 50.6(±11.9 mg/dl) improved to 54.4 Management of hyperglycemia in type 2 diabetes: a consensus (±13.4mg/dl). The change from baseline was algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the study of Diabetes. Diabetologia 2006;49:1711-21 7. Semple RK, Chatterjee VK, O' Rahilly S. PPAR gamma and human In a review of the clinical data, Kelley14 metabolic disease J Clin Invest 2006;116:581-9. 8. Goldberg RB, Kendall DM, Deeg MA, Buse JB, Zagar AJ, Pinaire JA, (2007) found that Pioglitazone has a modest Tan MH, Khan MA, et al. The GLAI Study Investigators: A comparison improvement in the serum HDL levels in the of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care Diabetic population. In another landmark 2005;28:1547-54. PROACTIVE trial (Prospective pioglitazone 9. Tamio T, Nobuhiro Y, Kohji S, Yasushi S. Effects of Pioglitazone Hydrochloride on Japanese Patients with Type 2 Diabetes Mellitus. J Clinical Trial In macrovascular Events) , Wilcox AtherosclerThromb, 2007; 14:86-93. R et al ,shared similar results and showed 10. Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect of metformin and rosiglitazone combination therapy in patients with type improvement in HDL levels but found an 2 diabetes mellitus. A randomized controlled trial. JAMA 2000;283:1695-702. association with heart failure. None of our 11. Uwaifo GI, Ratner RE. Differential effects of oral hypoglycemic agents patients reported or presented with heart on glucose control and cardiovascular risk. Am J Cardiol. 2007;99:51-67. failure during the treatmen 12. Rosanoff A, Seelig MS. "Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals". J Am CollNutr 2004; Dormandy et al16, (2005) studied this drug 23 (5): 501–5. with cardiovascular event as endpoints and 13. Ahmed I, Furlong K, Flood J, Treat VP, Goldstein BJ. Dual PPAR α/γ agonists: promises and pitfalls in type 2 diabetes. Am J Ther. found it to not only improve serum HDL levels but also decrease cardiovascular mortality. AS, Bank AJ. The cardiovascular effects of the thiazolidinediones: a review of the clinical data. J Diabetes Complications. 2007;21:326-34. CONCLUSION
15. Wilcox R, Bousser MG, Betteridge DJ. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results Pioglitazone is one of the better treatment from PROactive (PROspective Pioglitazone Clinical Trial In options available for the treatment of diabetes. MacrovascularEvents ). Stroke. 2007;38:865-73. 16. Dormandy JA, Charbonnel B, Eckland DJA. Secondary prevention of This drug improves the serum HDL levels in macrovascular events in patients with type 2 diabetes in the PROactive these patients and thus offers a decrease in Study (PROspectivepioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279-89. diabetic complications and an improved 17. DeFronzo, Ralph N Eng J Med 2011; 364: 1104-1115. 18. Abbink EJ, de Graaf J, de Haan JH, Heerschap A, Stalenhoef AF, Tack CONFLICT OF INTEREST
CJ. Effects of pioglitazone in familial combined hyperlipidaemia. J Intern Med 2006;259:107-16. The authors of this study reported no 19. Uwaifo GI, Ratner RE. Differential effects of oral hypoglycemic agents onglucose control and cardiovascular risk. Am J Cardiol. 2007;99:51-61.


Bats in buildings

Bat Conservation Trust Bats and Buildings Specialist Support Series Bats use buildings increasingly for roosting, as natural roosting places in tree holes and caves become more scarce or disturbed. All buildings, in particular the walls, eaves and roofs, are potential roost sites. Anyone working regularly in these areas, such as surveyors, architects,

Copyright 2008 by the American Psychological Association 2008, Vol. 53, No. 3, 357–369 DOI: 10.1037/a0012973 Advanced Regression Methods for Single-Case Designs: Studying Propranolol in the Treatment for Agitation Associated With Traumatic Daniel F. Brossart Texas A&M University Wayne State University Richard I. Parker, James McNamara, and Timothy R. Elliott Texas A&M University