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ABOUT AUTHORS
Amarjeet Singh*, Sudeep bhardwaj, Ashutosh aggarwal
Department of Pharmacology,
Seth G. L. Bihani S. D. College of Technical Education,
Institute of Pharmaceutical Sciences & Drug Research
amarjeetsingh024@gmail.com
ABSTRACT
Objective: The purpose of this study was to examine the risk assessment of developing type 2 diabetes mellitus in patient on antihypertensive medication.
Material & Method: In the present study total 30 patient with essential hypertension of both sex with mean age (48.6±0.8313) were recruited as per the inclusion criteria. Patients were segregated on the behalf of therapy they were using. 22 patients were on Losartan+HCTZ therapy and 8 patients were on Atenolol therapy.
Result: After six month of antihypertensive therapy Atenolol group showing a significant difference in their blood glucose (0.0014) whereas in Losartan+HCTZ group significant difference was not observed (0.1542). Patients of Atenolol group when compared with patient of Losartan+HCTZ group a significant difference was observed in the serum cholesterol level (0.0290).
Conclusion: We found that the use of β-blocker was independently associated with increased risk of type 2 diabetes. So increase in blood glucose in the Atenolol group patient revealed a significant association between use of Atenolol therapy and metabolic dysfunction whereas in Losartan+HCTZ group significant increase in blood glucose was not observed and from these we can conclude therapy with Losartan+HCTZ therapy not associated with metabolic dysfunction.
REFERENCE ID: PHARMATUTOR-ART-2322
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PharmaTutor (ISSN: 2347 - 7881) Volume 3, Issue 2 How to cite this article: A Singh, S bhardwaj, A Aggarwal; Risk Assessment of developing type 2 diabetes mellitus in patient on antihypertensive medication; PharmaTutor; 2015; 3(3); 41-48 |
INTRODUCTION
Hypertension(HTN) or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated[1].
Hypertension is strongly associated with risk factorsthat impair glucose homeostasis and is often presentedas a component of the metabolic syndrome. Indeed, hypertension is related with obesity, insulin resistanceas well as diabetes mellitus[2&3]. As a result, hypertensive patients have a 2.5-fold higher risk of type 2 diabetesmellitus (T2DM) onset compared with normotensive subjects[4]. The various classes of antihypertensive drugshave different effects on blood glucose metabolism. Indeed, antihypertensive agents, such as β-blockers andthiazide diuretics have been associated with negative effectson blood glucose in contrast to other classes, suchas angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACE-I). As a result, thetreatment of hypertensive subjects should be carefullyselectedsoas further deterioration in glucose homeostasis is minimized [5].
The relation between the use of differentclasses of antihypertensive medicationsand the risk of incident type2 diabetes is unclear. Although thiazidediuretic or beta blocker use may increasethe incidence of diabetes, priorstudies have reported conflicting results[6].
Material and method
A prospective study was conducted in the population of Sri Ganganagar District of Rajasthan. This study was carried out after getting approval from the Institutional Ethics Committee of Seth G.L. Bihani S.D. College of Technical Education Institute of Pharmaceutical Sciences & Drug Research and written informed consent was obtained from all subject.
Recruitment of Subjects:
Total 30study subjects were recruited. 22 patient receiving Losartan + HCTZ as combination therapy and 8 patient receiving Atenolol as monotherapy.
Selection criteria for subjects
Inclusion Criteria:
· Age: 30 Years - 59 Years,
· Genders: Both
· An average seated home DBP > 85 mmHg and home SBP < 180 mmHg. Subjects must also have an average seated (> 5 minutes) clinic DBP between 90 mmHg and 110 mmHg and SBP < 180 mmHg
· BMI : normal range < 18.5 >24.9 kg/m2
· Patient diagnosed with essential hypertension
· Drugs: Atenolol (as monotherapy) and Losartan plus Hydrochlorothiazide (as combination therapy)
Exclusion Criteria:
· Secondaryhypertension
· Patients currently treated with three or more antihypertensive drugs, isolated systolic HTN other diseases requiring treatment with BP lowering medications
· Heart rate < 55 beats/min
· Known cardiovascular disease (including history of angina pectoris, heart failure presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease, including stroke and TIA),
· Diabetes mellitus (Type 1 or 2)
· Primary renal disease
· Pregnancy or lactation
· Current treatment with NSAIDS, COX2-inhibitors, oral contraceptives or estrogen.
Follow up of Patients
The subjects were followed up for 6 months for monitoring of blood glucose, lipid profile Total Cholesterol, HDL- Cholesterol, Triglycerides and anthropometric measurement. During the follow up period blood pressure was monitored on monthly basis. The examinations included interviews conducted at the subjects’ homes.
Subjects were asked to fast for at least 12 hours before blood collection. Lipid profile measured two times first starting of study and second end of study. Fasting blood glucose level measured by glucometer on monthly basis. Blood pressure was measured with a mercury sphygmomanometer with subjects in the sitting positionon monthly basis. Data on demographic variables (age, sex, smoking status, use of alcohol and family historyof diabetes) were obtained by interview. Body-mass index(the weight in kilograms divided by the square of the height in meters) was calculated from anthropometric measurement taken at the base-lineand end of study.
Results
In the present study total 30 patient with essential hypertension of both sex with mean age (48.6±0.8313) were recruited as per the inclusion criteria. The base line clinical characteristics like smoker, liquor, BMI, systolic BP, diastolic BP, Blood glucose, Lipid profile are shown in the table 1. From the above recruited total 30 hypertensive patient, 13 were found alcoholic and 2 smoker. Patients were segregated on the behalf of therapy they were using. 22 patients were on Losartan + Hydrochlorothiazide therapy and 8 patients were on Atenolol therapy.
Comparison of Base line Clinical characteristics with clinical characteristics after six month of Losartan+HCTZ therapy are shown in table 2. Table 3 & table 4 are showing Clinical characteristics of male and female respectively for Losartan+HCTZ therapy.
Comparison of Base line Clinical characteristics with clinical characteristics after six month of Atenolol therapy are shown in table 5. Table 6 & 7 showing clinical characteristics of male & female respectively for Atenolol therapy.
Monitoring of blood glucose, BMI, Blood pressure
Patients were followed up for the six month for monitoring of blood glucose, Blood pressure, BMI. When BMI of recruited patient compared after six month of therapy no significant difference was observed in both Atenolol and Losartan+HCTZ group respectively (0.9754) & (0.8961). After six month of antihypertensive therapy Atenolol group showing a significant difference in their blood glucose (0.0014) whereas in L+H group significant difference was not observed (0.1542). Table 8 & 9 are showing a comparison of BMI, Blood glucose, systolic BP, diastolic BP, lipid profile between Atenolol group and Losartan+HCTZ group after six month of therapy.
Monitoring of Lipid profile
Patients were followed up for the six month for monitoring of lipid profile. Patients of Atenolol group when compared with patient of Losartan+HCTZ group a significant difference was observed in the serum cholesterol level (0.0290). When TG, HDL, LDL, VLDL compared no significant difference was observed between Atenolol group and Losartan+HCTZ group shown in table 9.
Table No.1 Clinical characteristics of total patient at baseline
|
Characteristics |
Total |
Male |
Female |
p value |
|
Number of subjects |
30 |
25 |
5 |
|
|
Age (year) |
48.6±0.8313 |
48.04±0.8935 |
51.4±1.939 |
0.1344ns |
|
Sex (% of male) |
83.33 |
|
|
|
|
Smoker % |
6.66 |
8 |
0 |
0.0001 |
|
Liquor % |
43.33 |
52 |
0 |
0.0001 |
|
BMI (kg/m2) |
22.29±0.3098 |
22.378±0.3505 |
21.892±0.6644 |
0.5680ns |
|
Blood pressure |
||||
|
Systolic BP mmHG |
130.53±1.020 |
130.24±1.074 |
132±3.16 |
0.5297ns |
|
Diastolic BP mmHG |
88.26±0.7907 |
88.16±0.9322 |
88.8±1.02 |
0.7687ns |
|
Blood examination |
|
|||
|
Glucose (mg/dl) |
93.03±0.9878 |
92.44±1.124 |
96±1.378 |
0.1838ns |
|
Total Cholesterol (mg/dl) |
172.89±2.481 |
173.41±2.56 |
170.312±8.305 |
0.6491ns |
|
HDL Cholesterol (mg/dl) |
47.057±1.457 |
92.275±3.412 |
98.008±6.284 |
0.8667ns |
|
Triglycerides (mg/dl) |
93.231±3.016 |
47.17±1.577 |
46.496±4.209 |
0.4884ns |
|
LDL |
107.23±1.441 |
18.44±0.6815 |
19.596±1.257 |
0.3588ns |
|
VLDL |
18.63±0.6025 |
107.83±1.459 |
104.22±4.874 |
0.4853ns |
· Mean±SEM
· ns non significant
· *** significant
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Table No. 2 Clinical characteristics of Losartan+HCTZ group at base line & end of study
|
Characteristics |
At base line |
end of study |
P value |
|
Number of subject |
22 |
22 |
|
|
BMI (kg/m2 ) |
22.18±0.4050 |
22.36±0.3397 |
0.8961ns |
|
Blood Pressure |
|||
|
Systolic BP |
129.81±1.22 |
127.81±0.9662 |
0.2061ns |
|
Diastolic BP |
88.09±1.017 |
86.72±0.8275 |
0.3043ns |
|
Blood examination |
|||
|
Blood glucose(mg/dl) |
91.36±1.137 |
89.40±0.7227 |
0.1542ns |
|
Total cholesterol(mg/dl) |
169.66±2.75 |
169.27±2.75 |
0.9213ns |
|
Triglyceride(mg/dl) |
90.39±3.56 |
91.05±3.59 |
0.8962ns |
|
HDL cholesterol(mg/dl) |
45.98±1.704 |
46.25±1.603 |
0.9087ns |
|
VLDL |
18.065±0.7113 |
17.44±1.027 |
0.9039ns |
|
LDL |
101.44±4.27 |
104.88±1.639 |
0.7269ns |
· mean±SEM
· *** significant value
· ns non significant
Table No. 3 Clinical characteristics of Losartan+HCTZ Male at base line & end of study
|
Characteristics |
Male (base line) |
Male (end of study) |
p value |
|
Number of subject |
19 |
19 |
|
|
BMI(kg/m2) |
22.44±0.4427 |
22.36±0.3397 |
0.9792ns |
|
Blood pressure |
|||
|
Systolic BP |
129.78±1.25 |
127.47±0.8765 |
0.1387ns |
|
Diastolic BP |
88.21±1.176 |
86.63±0.8793 |
0.2895ns |
|
Blood examination |
|||
|
Blood glucose (mg/dl) |
90.63±1.19 |
89±0.6882 |
0.2431ns |
|
Total cholesterol (mg/dl) |
171.59±2.926 |
171.20±2.914 |
0.9247ns |
|
Triglyceride (mg/dl) |
90.28±4.055 |
91.14±4.068 |
0.8825ns |
|
HDL Cholesterol (mg/dl) |
46.62±1.92 |
46.83±1.82 |
0.9368ns |
|
VLDL |
18.04±0.8094 |
18.20±0.8118 |
0.8901ns |
|
LDL |
106.97±1.653 |
106.17±1.648 |
0.7331ns |
· mean±SEM
· *** significant value
· ns non significant
Table No. 4 Clinical characteristics of Losartan+HCTZ Female at base line & end of study
|
Characteristics |
Female (base line) |
Female(end of study) |
p value |
|
Number of subject |
3 |
3 |
|
|
BMI(kg/m2) |
21.31±0.8313 |
21.72±0.7554 |
0.7336ns |
|
Blood Pressure |
|
|
|
|
Systolic BP mmHG |
130±5.033 |
130±5.033 |
> 0.9999ns |
|
Diastolic BP mmHG |
87.33±0.6667 |
87.33±2.906 |
> 0.9999ns |
|
Blood examination |
|
|
|
|
Blood glucose (mg/dl) |
96±2.51 |
92±3.05 |
0.3694ns |
|
Total cholesterol (mg/dl) |
157.42±3.025 |
157.07±3.78 |
0.9459ns |
|
Triglyceride (mg/dl) |
91.06±6.35 |
90.51±7.15 |
0.9574ns |
|
HDL cholesterol (mg/dl) |
41.93±1.434 |
42.56±0.6533 |
0.7069ns |
|
VLDL |
18.20±1.268 |
18.09±1.431 |
0.9569ns |
|
LDL |
97.28±3.102 |
96.406±3.011 |
0.8492ns |
· mean±SEM
· *** significant value
· ns non significan
Table No. 5 Clinical characteristics of Atenolol group at base line & end of study
|
Characteristics |
At base line |
end of study |
P value |
|
Number of subject |
8 |
8 |
|
|
BMI(kg/m2) |
22.30±0.4010 |
22.28±0.4951 |
0.9754ns |
|
Blood Pressure |
|||
|
Systolic BP mmHG |
132.5±1.76 |
130.5±1.296 |
0.3761 |
|
Diastolic BP mmHG |
88.75±1.065 |
89.5±1.35 |
> 0.9999 |
|
Blood examination |
|||
|
Blood glucose(mg/dl) |
99.375±0.7545 |
99.87±1.469 |
0.0014*** |
|
Total cholesterol(mg/dl) |
181.79±4.19 |
181.35±4.27 |
0.9425ns |
|
Triglyceride(mg/dl) |
101.04±4.968 |
100.58±4.791 |
0.9478ns |
|
HDL cholesterol(mg/dl) |
50.02±2.708 |
50.16±2.41 |
0.9679ns |
|
VLDL |
20.20±2.809 |
20.11±0.9584 |
0.9482ns |
|
LDL |
111.58±2.55 |
111.07±2.55 |
0.8930ns |
· mean±SEM
· *** significant value
· ns non significant
Table No.6 Clinical characteristics of Atenolol Male at base line & end of study
|
Characteristics |
Male (base line) |
Male (end of study) |
P value |
|
|
Number of subjects |
6 |
6 |
|
|
|
BMI(kg/m2) |
22.155±0.4584 |
22.55±0.5198 |
0.5797ns |
|
|
Blood pressure |
||||
|
Systolic BP |
131.66±2.15 |
130.33±1.74 |
0.6410ns |
|
|
Diastolic BP |
88±1.26 |
88.66±1.606 |
0.7510ns |
|
|
Blood examination |
||||
|
Blood glucose (mg/dl) |
98.16±0.7032 |
103.5±1.45 |
0.0080*** |
|
|
Total Cholesterol (mg/dl) |
179.18±4.975 |
178.54±5.043 |
0.9296ns |
|
|
Triglyceride (mg/dl) |
98.57±5.917 |
98.06±5.68 |
0.9513ns |
|
|
HDL Cholesterol (mg/dl) |
48.91±2.55 | |||
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