Obesity Research & Clinical Practice (2010) 4, e145—e152
SHORT COMMUNICATION
Telmisartan reduced abdominal circumference and body weight with decreasing triglyceride level in patients with type 2 diabetes and metabolic syndrome Tetsuya Kakuma a,∗, Koro Gotoh a,b,c, Takayuki Masaki a, Emi Itateyama d, Nobuyuki Abe e, Hironobu Yoshimatsu a a
Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan b Ogata General Hospital, Oita, Japan c Okamoto Hospital, Oita, Japan d Usuki Cosmos Hospital, Oita, Japan e Naika Abe Clinic, Oita, Japan Received 5 June 2009 ; received in revised form 10 December 2009; accepted 16 December 2009
KEYWORDS Type 2 diabetes; Metabolic syndrome; Telmisartan; Abdominal circumference; Triglycerides
∗
Summary Telmisartan has the dual ability to inhibit angiotensin II type 1 receptors and activate peroxisome proliferator-activated receptor gamma (PPAR), especially as a selective PPAR modulator that does not strongly promote adipogenesis for weight gain. Accordingly, Telmisartan is expected to provide beneficial effects for glucose and lipid metabolism without causing obesity. In the present study, we examined the effects of Telmisartan in patients with type 2 diabetes and metabolic syndrome. Thirty-two patients enrolled in this study were administered 40 mg per day of Telmisartan for 6 months. Telmisartan treatment significantly reduced systolic and diastolic blood pressure accompanied by induction of plasma renin activity (PRA) and reduction of serum aldosterone concentration and significantly decreased waist circumference, body mass index (BMI), and triglycerides (TG). In the 16 patients who did not take sulfonylurea, fasting plasma glucose (FPG) decreased and HbA1c significantly decreased from 3 months to 6 months. The results provide evidence that Telmisartan may improve glucose and lipid metabolism with the reduction in visceral fat mass in patients with type 2 diabetes and metabolic syndrome. © 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +81 97 586 5793; fax: +81 97 549 4480. E-mail address: [email protected] (T. Kakuma).
1871-403X/$ — see front matter © 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2009.12.003
e146
Introduction Several clinical trials have shown that angiotensin II type 1 receptor blockers (ARBs) can reduce the incidence of new-onset type 2 diabetes via the improvement of insulin resistance [1—3] and prevent cardiovascular events through the development of atherosclerosis by normalizing endothelial dysfunction [4,5]. Therefore, ARBs have currently been recognized as useful antihypertensive drugs for the treatment of metabolic syndrome, which is a cluster of mild cardiovascular risk factors, characterized by visceral fat obesity, elevated blood pressure, dyslipidemia, and impaired glucose tolerance. For all ARBs, Telmisartan has demonstrated the ability not only to inhibit angiotensin II type 1 receptor but also to activate peroxisome proliferator-activated receptor gamma (PPAR␥) and to provide beneficial effects for glucose and lipid metabolism [6]. On the other hand, because Telmisartan works as a selective PPAR␥ modulator, its effects on gene expression partially differ from those of full agonists, such as thiazolidinediones, which strongly promote adipogenesis and cause weight gain. Microassay and quantitative PCR analysis showed that stimulation of Telmisartan on the expression of genes involved in adipocytic lipid storage, for example, prostacyclin receptor and glycerol kinase, was much weaker than that of pioglitazone [7]. This finding suggests that Telmisartan-induced PPAR␥ activation is not associated with weight gain. Indeed, we observed that Telmisartan treatment decreased the weight of visceral adipose tissue without affecting food intake in diet-induced obese mice and increased the mRNA expression of uncoupling protein 1 in brown adipose tissue, accompanied by an increase in oxygen consumption [8]. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in diet-induced obese mice all improved with Telmisartan treatment. Furthermore, Telmisartan treatment increased adiponectin mRNA in visceral adipose tissue and reduced the serum level of resistin, which impairs insulin sensitivity. Our results proposed that Telmisartan may prevent the development of obesity and related metabolic disorders by altering the levels of various adipocytokines and increasing energy expenditure. Recent reports indicate that the visceral fat area (VSA), estimated by abdominal computed tomography scan, decreased in patients with metabolic syndrome after Telmisartan treatment, while the subcutaneous fat area (SFA) did not [9], and the percentage of any decrease in body weight from baseline was significantly enhanced in hypertensive patients with glucose intolerance after Telmisartan
T. Kakuma et al. treatment, compared with Candesartan treatment [10]. However, a significant reduction in the actual measurement of body weight and waist circumference has not been reported. In this study, we examined the effects of Telmisartan on metabolic parameters, plasma renin activity (PRA), serum aldosterone concentration, and adipocytokine level in patients with type 2 diabetes and metabolic syndrome. We also performed sub-analysis in the patients who switched to Telmisartan from other ARBs or ACE inhibitor and were not taking sulfonylurea.
Subjects and methods Patients Outpatients of either sex, aged ≥18 years, with metabolic syndrome were recruited at Oita University hospital and its group hospitals. Metabolic syndrome was diagnosed according to the Japanese definition and criterion for metabolic syndrome [11]. Because elevated blood pressure (office systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg) was obligatory for the present study, the criterion for metabolic syndrome was as follows. In addition to abdominal obesity (waist circumstance ≥85 cm in men or ≥90 cm in women), at least one of the following clinical conditions should be observed: (A) dyslipidemia: triglyceride ≥150 mg/dl and/or HDL-cholesterol
SHORT COMMUNICATION
Telmisartan reduced abdominal circumference and body weight with decreasing triglyceride level in patients with type 2 diabetes and metabolic syndrome Tetsuya Kakuma a,∗, Koro Gotoh a,b,c, Takayuki Masaki a, Emi Itateyama d, Nobuyuki Abe e, Hironobu Yoshimatsu a a
Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan b Ogata General Hospital, Oita, Japan c Okamoto Hospital, Oita, Japan d Usuki Cosmos Hospital, Oita, Japan e Naika Abe Clinic, Oita, Japan Received 5 June 2009 ; received in revised form 10 December 2009; accepted 16 December 2009
KEYWORDS Type 2 diabetes; Metabolic syndrome; Telmisartan; Abdominal circumference; Triglycerides
∗
Summary Telmisartan has the dual ability to inhibit angiotensin II type 1 receptors and activate peroxisome proliferator-activated receptor gamma (PPAR), especially as a selective PPAR modulator that does not strongly promote adipogenesis for weight gain. Accordingly, Telmisartan is expected to provide beneficial effects for glucose and lipid metabolism without causing obesity. In the present study, we examined the effects of Telmisartan in patients with type 2 diabetes and metabolic syndrome. Thirty-two patients enrolled in this study were administered 40 mg per day of Telmisartan for 6 months. Telmisartan treatment significantly reduced systolic and diastolic blood pressure accompanied by induction of plasma renin activity (PRA) and reduction of serum aldosterone concentration and significantly decreased waist circumference, body mass index (BMI), and triglycerides (TG). In the 16 patients who did not take sulfonylurea, fasting plasma glucose (FPG) decreased and HbA1c significantly decreased from 3 months to 6 months. The results provide evidence that Telmisartan may improve glucose and lipid metabolism with the reduction in visceral fat mass in patients with type 2 diabetes and metabolic syndrome. © 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +81 97 586 5793; fax: +81 97 549 4480. E-mail address: [email protected] (T. Kakuma).
1871-403X/$ — see front matter © 2009 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.orcp.2009.12.003
e146
Introduction Several clinical trials have shown that angiotensin II type 1 receptor blockers (ARBs) can reduce the incidence of new-onset type 2 diabetes via the improvement of insulin resistance [1—3] and prevent cardiovascular events through the development of atherosclerosis by normalizing endothelial dysfunction [4,5]. Therefore, ARBs have currently been recognized as useful antihypertensive drugs for the treatment of metabolic syndrome, which is a cluster of mild cardiovascular risk factors, characterized by visceral fat obesity, elevated blood pressure, dyslipidemia, and impaired glucose tolerance. For all ARBs, Telmisartan has demonstrated the ability not only to inhibit angiotensin II type 1 receptor but also to activate peroxisome proliferator-activated receptor gamma (PPAR␥) and to provide beneficial effects for glucose and lipid metabolism [6]. On the other hand, because Telmisartan works as a selective PPAR␥ modulator, its effects on gene expression partially differ from those of full agonists, such as thiazolidinediones, which strongly promote adipogenesis and cause weight gain. Microassay and quantitative PCR analysis showed that stimulation of Telmisartan on the expression of genes involved in adipocytic lipid storage, for example, prostacyclin receptor and glycerol kinase, was much weaker than that of pioglitazone [7]. This finding suggests that Telmisartan-induced PPAR␥ activation is not associated with weight gain. Indeed, we observed that Telmisartan treatment decreased the weight of visceral adipose tissue without affecting food intake in diet-induced obese mice and increased the mRNA expression of uncoupling protein 1 in brown adipose tissue, accompanied by an increase in oxygen consumption [8]. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in diet-induced obese mice all improved with Telmisartan treatment. Furthermore, Telmisartan treatment increased adiponectin mRNA in visceral adipose tissue and reduced the serum level of resistin, which impairs insulin sensitivity. Our results proposed that Telmisartan may prevent the development of obesity and related metabolic disorders by altering the levels of various adipocytokines and increasing energy expenditure. Recent reports indicate that the visceral fat area (VSA), estimated by abdominal computed tomography scan, decreased in patients with metabolic syndrome after Telmisartan treatment, while the subcutaneous fat area (SFA) did not [9], and the percentage of any decrease in body weight from baseline was significantly enhanced in hypertensive patients with glucose intolerance after Telmisartan
T. Kakuma et al. treatment, compared with Candesartan treatment [10]. However, a significant reduction in the actual measurement of body weight and waist circumference has not been reported. In this study, we examined the effects of Telmisartan on metabolic parameters, plasma renin activity (PRA), serum aldosterone concentration, and adipocytokine level in patients with type 2 diabetes and metabolic syndrome. We also performed sub-analysis in the patients who switched to Telmisartan from other ARBs or ACE inhibitor and were not taking sulfonylurea.
Subjects and methods Patients Outpatients of either sex, aged ≥18 years, with metabolic syndrome were recruited at Oita University hospital and its group hospitals. Metabolic syndrome was diagnosed according to the Japanese definition and criterion for metabolic syndrome [11]. Because elevated blood pressure (office systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg) was obligatory for the present study, the criterion for metabolic syndrome was as follows. In addition to abdominal obesity (waist circumstance ≥85 cm in men or ≥90 cm in women), at least one of the following clinical conditions should be observed: (A) dyslipidemia: triglyceride ≥150 mg/dl and/or HDL-cholesterol
