Chin J Integr Med 2015 Feb;21(2):157-160
• 157 •
CASE REPORT Effect of Yanggyuksanhwa-Tang on Non-Insulin-Dependent Diabetes Mellitus Unresponsive to Oral Hypoglycemic Agents: A Case Report Jiman Kim1 and Seungwon Kwon2 Diabetes mellitus is the fourth leading cause of death worldwide, following cancer, cerebrovascular disease, and heart disease. It is triggered by hyperglycemia and other metabolic disorders. (1,2) Diabetes is a complex endocrine disease that causes chronic vascular complications such as diabetic nephropathy, retinopathy, and polyneuropathy.(3) In diabetes treatment, adequate blood sugar control is of vital importance to prevent the above complications, as confirmed by the Kumamoto Study (4) or a 10-year United Kingdom Prospective Diabetes Study (UKPDS).(5-7) Blood sugar control is generally achieved by administration of oral hypoglycemic agents or insulin as well as by movement therapy. However, there are patients who, for various reasons, are unable to meet dietary or exercise requirements or who remain unresponsive to drug treatment.
agents were introduced (metformin hydrochloride, 1000 mg/day; glibenclamide, 10 mg/day; acarbose, 300 mg/day). Insulin therapy was recommended in place of the ineffective oral agents to control glucose levels and prevent diabetic complications but the patient refused. He presented at our clinic on March 14, 2011, seeking to reduce blood sugar level with herbal medicine. On presentation, his glucose and hemoglobin A1c (HbA1c) levels on an empty stomach were 19.1 mmol/L and 9.6%, respectively, showing inadequate blood sugar control. He did not complain of serious diabetes symptoms and followed exercise and dietary recommendations. Due to a specific workplace environment, he was unable to quit an alcohol drinking habit (he drank twice a week, 180 mL of Korean distilled liquor). He had an aggressive personality and was a non-smoker.
Laboratory Findings We observed a positive effect of Yanggyuksanhwatang (YGST), a herbal extract used in Korean medicine, in lowering blood sugar levels and reducing symptoms in patients with type 2 diabetes who were unresponsive to oral hypoglycemic agents.
Case History Patient Characteristics and Diagnosis A 51-year-old man (weight, 81 kg; height, 176 cm; waist, 91 cm) with uncontrolled diabetes mellitus and early nonproliferative diabetic retinopathy presented at Kyunghee-saeng Korean Medicine Clinic. A medical examination conducted in 2001 revealed impaired glucose tolerance. Lifestyle modification was recommended but the patient failed to introduce any significant changes. In February 2009, he was diagnosed as type 2 diabetes at a university hospital in Seoul and was prescribed an oral hypoglycemic agent to control blood sugar levels. During the early stage, he received only 1 agent but it was no longer effective after 3 years of treatment, even after an increase in dosage. Therefore, additional oral hypoglycemic
Complete blood count results at baseline were as follows: red blood cells, 5.64×10 12/L (normal range, 4.5–5.5×10 12 /L); hemoglobin, 15.6 g/dL (14.0–18.0 g/dL); and hematocrit, 46.8% (42.0%–52.0%). Biochemical test results were as follows: fasting blood glucose (FBS), 19.1 mmol/L (3.3–5.6 mmol/L); creatinine, 99.0 μmol/L (44.2–106.1 μmol/L); total protein, 7.7 g/dL (6.5–8.3 g/dL); albumin, 50.0 g/L (35–53 g/L); Na+, 138 mmol/L (135–148 mmol/L); K+, 4.0 mmol/L (3.5–5.1 mmol/L); Cl–, 105 mmol/L (98–107 mmol/L). HbA1c levels were 9.6%.
Treatment Outcomes The patient continued the combination of drug, ©The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2014 1. Kyunghee-saeng Haniwon (Korean Medicine Clinic), Seoul, Korea; 2. Department of Cardiovascular and Neurologic Diseases, College of Korean Medicine, KyungHee University, Seoul, Korea Correspondence to Dr. Seungwon Kwon, Tel: 82-02-958-9128, Fax: 82-02-958-9132, E-mail: [email protected] DOI: 10.1007/s11655-014-2071-z
Chin J Integr Med 2015 Feb;21(2):157-160
• 158 •
exercise, and dietary treatment while simultaneously taking YGST 3 times a day from March 14, 2011 until July 20, 2011. The daily dose of YGST consisted of Menthae herba , Saposhnikoviae radix , Gardeniae fructus , Gypsum fibrosum , Anemarrhena rhizome , and Schizonepeta spica (8 g each) and Rehmanniae radix , Lonicerae folium , and Forsythiae fructus (16 g each). A single day's dose of YGST was boiled with 500 mL of distilled water for approximately 2 h until the volume of solution was concentrated to 100–120 mL. The YGST decoction was administered three times daily after meals. During the administration of YGST and after its discontinuation in June, 2011, regular tests were performed to check its effect on blood sugar levels. During a 23-month follow-up, all parameters were within the normal ranges. In February 2013, normal blood sugar levels were maintained and nonproliferative retinopathy was no longer observed on a retinoscopy. The weight and waistline were slightly higher compared with the values observed during the 3-month treatment. The patient continued movement and dietary treatment but did not quit his drinking habit. The results of follow-up measurements are provided in the Tables 1 and 2. Table 1.
Changes in Laboratory Parameters during Administration of YGST
Time
Glucose (mmol/L)
HbA1c (%)
March 14, 2011
19.1
9.6
April 6, 2011
8.0
9.1
June 20, 2011
4.6
5.8
Table 2. Changes in Laboratory Parameters during Follow-up Time August 26, 2011
Glucose (mmol/L)
HbA1c (%)
4.6
5.5
October 17, 2011
5.5
5.1
February 13, 2012
5.1
5.6
September 7, 2012
–
5.9
February 13, 2013
–
5.9
DISCUSSION We showed that the control of blood sugar and HbA1c levels in a patient with type 2 diabetes that had been unresponsive to oral hypoglycemic agents for 2 years could be achieved by a 3-month treatment with YGST. Moreover, we showed that normal blood sugar levels were maintained during a 23-month follow-up.
Our case study has important implications. Vascular and other diabetic complications may be prevented by herbal medicine. According to large, randomized, prospective studies, namely, the Kumamoto Study (4) and UKPDS, (5-7) rigorous blood sugar control from the early stages of type 2 diabetes can help reduce the risk of micro- and macrovascular diabetic complications. Our patient had suffered from diabetes for 2 years and was also diagnosed as nonproliferative diabetic retinopathy due to uncontrolled blood sugar levels. Therefore, it was important to quickly reduce blood sugar levels with drug treatment. Thus, an alternative therapy was needed because the patient refused insulin therapy. We administered YGST for 3 months and observed an improvement in blood sugar levels and retinopathy. Blood sugar control is assessed on the basis of the HbA1c measurement. The threshold level of HbA1c is 7.0% according to the Diabetes Control and Complications Trial (DCCT)(8) and UKPDS(5-7) and 6.5% and lower according to the Kumamoto Study.(4) Moreover, the Kumamoto researchers set the target blood sugar level at no more than 6.66 mmol/L. Considering the above values and our results, we may conclude that YGST can help prevent diabetic complications and relieve diabetes symptoms. Moreover, its positive effect is continuous and not temporary, as confirmed by our follow-up study. The use of YGST not only prevented diabetic complications but also helped in the treatment of diabetes itself. Therefore, the patient could avoid the side effects of insulin therapy. Prior to treatment with herbal medicine, our patient took 3 different oral hypoglycemic agents in line with the general recommendation that if patients remain unresponsive to one agent, another agent with a different mechanism should be added.(9,10) However, according to a Korean study, Practical Evidences of Antidiabetic Monotherapy (PEAM),(11) a treatment with either glimepiride, metformin, or thiazolidinedione alone for 48 weeks also significantly reduced blood sugar levels with only half of the maximum dose. Accordingly, if a single oral hypoglycemic agent is not effective in a patient with type 2 diabetes, the use of a different type of an oral agent is suggested before the first agent reaches its maximum dose. However, if patients remain unresponsive, they must start insulin therapy.
Chin J Integr Med 2015 Feb;21(2):157-160
• 159 •
The Canadian guide on diabetes treatment recommends different modalities depending on baseline blood sugar levels. If the HbA1c level is 9% and over, a combined treatment with 2 or more oral hypoglycemic agents or immediate insulin therapy is recommended.(12) In our patient, the HbA1c level was 9.6% despite the administration of 3 oral hypoglycemic agents, and thus insulin therapy was necessary. However, insulin therapy is known to produce side effects. For example, it requires that patients regularly check their blood sugar levels because they may experience hypoglycemia, which in itself can adversely affect the quality of life. Therefore, it is best to avoid insulin therapy whenever possible because although it helps reduce blood sugar levels over a short period, it significantly increases the risk of hypoglycemia. According to UKPDS,(5-7) hypoglycemia is observed in up to 36.5% of diabetic patients (including those with mild hypoglycemia), and 2.3% of these patients require assistance or hospitalization. Moreover, the DCCT study showed that a strict control of blood sugar levels is associated with a 3-fold higher risk of hypoglycemia.(8) Another side effect is weight gain that affects mainly the abdomen area and is related to the daily dose of insulin and blood insulin levels. Moreover, repeated insulin injections in the abdomen produce a scar and may lead to lipohypertrophy or lipoatrophy.(13) In our case, we were able to avoid insulin therapy and the potential side effects by using YGST.
resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. (17) Geniposide, a glycoside of Genipin, also revealed an anti-obesity effect, an insulin resistance-alleviating effect in a recent experimental study. (18) Furthermore, Forsythiae fructus (19) and Mangiferin, an ingredient of Anemarrhena rhizome (20,21) also revealed an antidiabetic effect in the experimental studies.
Our results are similar to those of several other studies. For example, YGST was reported to improve clinical symptoms, such as frequent urination and unusual thirst, in a study involving 5 patients with type 2 diabetes who received the extract for 8 weeks.(14) The mean glucose, blood pressure, and total protein levels significantly improved. However, unlike in our case, no effect was observed on the lowering of HbA1c levels. Furthermore, in an experimental study on rats with alloxan-induced diabetes, (15) the use of YGST was shown to significantly lower blood sugar levels. A similar result was observed in a study on rats with streptozotocin-induced diabetes. (16) Glucose levels were significantly reduced, while serum insulin levels were only slightly elevated.
Acknowledgments
In addition, we think that YGSY can be a prevention plan for diabetic complications, such as diabetic foot ulcer and diabetes-associated cognitive decline. Anemarrhena rhizome has an alleviating effect on diabetes-associated cognitive decline in rats.(22) And, Rehmanniae radix can treat diabetic foot ulcer through the combined therapy of Astragali radix and Rehmanniae radix . (23,24) Therefore, we can expect that YGST has the preventive effects on the diabetic complications as well as clinical effects on blood sugar control. We showed the positive clinical effects of YGST on blood sugar control and symptom relief in a patient with unresponsive type 2 diabetes. However, this is only a case report and our herbal medication has not been certified by the Good Manufacturing Practice. Therefore, to confirm the clinical effect of the extract, a clinical study involving a control group and a standardized medication is needed.
No financial support was received during the present study.
Conflict of Interest The authors declare that they have no conflicts of interest.
REFERENCES 1.
Kim EJ, Min HK, Choi YG, eds. Diabetes. 3rd ed. Seoul: Goryeo-euhak 2005:169-173, 830-832.
2.
Pickup JC, Williams G. Diagnosis and treatment of diabetes mellitus. KMS 2006:1-6, 437-442.
3.
Bowman WC, Rand MJ. Endocrine function of the pancreas. In: Textbook of pharmacology. 2nd ed. London: Blackwell Scientific Publications; 1980:1943-1964.
4.
Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the
Anti-diabetic effect of YGST in this case report is supported by several experimental studies. Genipin, an ingredient of Gardeniae Fructus has an ameliorative effect on age-related insulin
progression of diabetic microvascular complications in Japanese patients with non-insulin dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-117.
• 160 •
5. UK Prospective Diabetes Study (UKPDS) Group.
Chin J Integr Med 2015 Feb;21(2):157-160 rats. Kyung Hee Univ Orient Med J 1992;15:113-133.
Intensive blood-glucose control with sulphonylureas or
16. Kim EJ, Kim YS. Effects of Yanggyuksanhwa-tang on
insulin compared with conventional treatment and risk of
diabetic rats induced by streptozotocin. Kor J Ori Physiol
complications in patients with type 2 diabetes (UKPDS 33).
Pathol 2007;21:474-478.
Lancet 1998;352:837-853.
17. Guan L, Feng H, Gong D, Zhao X, Cai L, Wu Q, et al. Genipin
6. UK Prospective Diabetes Study (UKPDS) Group. Effect
ameliorates age-related insulin resistance through inhibiting
of intensive blood-glucose control with metformin on
hepatic oxidative stress and mitochondrial dysfunction. Exp
complications in overweight patients with type 2 diabetes
Gerontol 2013 Sep 14. doi: 10.1016/j.exger.2013.09.001.
(UKPDS 34). Lancet 1998;352:854-865.
Epub ahead of print.
7. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull
18. Kojima K, Shimada T, Nagareda Y, Watanabe M, Ishizaki
CA, et al. Association of glycaemia with macrovascular and
J, Sai Y, et al. Preventive effect of geniposide on metabolic
microvascular complications of type 2 diabetes (UKPDS 35):
disease status in spontaneously obese type 2 diabetic mice
prospective observational study. BMJ 2000;321:405-412.
and free fatty acid-treated HepG2 cells. Biol Pharm Bull
8. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennil
2011;34:1613-1618.
A, Goldstein DE. Defining the relationship between plasma
19. Kim CJ, Cho SK, Shin MS, Cho H, Ro DS, Park JS, et al.
glucose and HbA(1c): analysis of glucose profiles and
Hypoglycemic activity of medicinal plants. Arch Pharm Res
HbA(1c) in the Diabetes Control and Complications Trial.
1990;13:371-373.
Diabetes Care 2002;25:275-278. 9. Riddle MC. Glycemic management of type 2 diabetes: an emerging strategy with oral agents, insulins, and combinations. Endocrinol Metab Clin North Am 2005;34:77-98. 10. Van Gaal LF, De Leeuw IH. Rationale and options for combination therapy in the treatment of type 2 diabetes. Diabetologia 2003;46(Suppl 1):M44-M50.
20. Miura T, Ichiki H, Hashimoto I, Iwamoto N, Kato M, Kubo M, et al. Antidiabetic activity of a xanthone compound, mangiferin. Phytomedicine 2001;8:85-87. 21. Ichiki H, Miura T, Kubo M, Ishihara E, Komatsu Y, Tanigawa K, et al. New antidiabetic compounds, mangiferin and its glucoside. Biol Pharm Bull 1998;21:1389-1390. 22. Liu YW, Zhu X, Lu Q, Wang JY, Li W, Wei YQ, et al.
11. Yoon KH, Shin JA, Kwon HS, Lee SH, Min KW, Ahn YB,
Total saponins from Rhizoma Anemarrhenae ameliorate
et al. Comparison of the efficacy of glimepiride, metformin,
diabetes-associated cognitive decline in rats: involvement
and rosiglitazone monotherapy in Korean drug-naive type
of amyloid-beta decrease in brain. J Ethnopharmacol
2 diabetic patients: the practical evidence of Antidiabetic
2012;139:194-200.
Monotherapy Study. Diabetes Metab J 2011;35:26-33.
23. Lau KM, Lai KK, Liu CL, Tam JC, To MH, Kwok HF, et
12. Canadian Diabetes Association 2003 Clinical Practice
al. Synergistic interaction between Astragali Radix and
Guidelines for the Prevention and Management of Diabetes
Rehmanniae Radix in a Chinese herbal formula to promote
in Canada. Can J Diabetes 2003;27 (Suppl 2):S58-S65. 13. Park SM. Types, effects and side effects of insulin.
diabetic wound healing. J Ethnopharmacol 2012;141:250-256. 24. Or PM, Lam FF, Kwan YW, Cho CH, Lau CP, Yu H, et
Korean Association of Diabetes Mellitus. Diabetes Mellitus
al. Effects of Radix Astragali and Radix Rehmanniae , the
2006;10-11.
components of an anti-diabetic foot ulcer herbal formula,
14. Jung SI, Kim JW. Clinical study about the diabetes mellitus
on metabolism of model CYP1A2, CYP2C9, CYP2D6,
patients. Administration of Yangkyuksanwha-tang. Kor J Ori
CYP2E1 and CYP3A4 probe substrates in pooled human
Physiol Pathol 2002;16:1308-1313.
liver microsomes and specific CYP isoforms. Phytomedicine
15. C h o i B I , K o B H , S o n g I B . E f f e c t s o f S o y a n g i n yanggueksanwhatang, indongduenjigolpitan and Sookjiwhanggosamtang on the alloxan-iInduced diabetic
2012;19:535-544. (Received July 12, 2013) Edited by WANG Wei-xia
• 157 •
CASE REPORT Effect of Yanggyuksanhwa-Tang on Non-Insulin-Dependent Diabetes Mellitus Unresponsive to Oral Hypoglycemic Agents: A Case Report Jiman Kim1 and Seungwon Kwon2 Diabetes mellitus is the fourth leading cause of death worldwide, following cancer, cerebrovascular disease, and heart disease. It is triggered by hyperglycemia and other metabolic disorders. (1,2) Diabetes is a complex endocrine disease that causes chronic vascular complications such as diabetic nephropathy, retinopathy, and polyneuropathy.(3) In diabetes treatment, adequate blood sugar control is of vital importance to prevent the above complications, as confirmed by the Kumamoto Study (4) or a 10-year United Kingdom Prospective Diabetes Study (UKPDS).(5-7) Blood sugar control is generally achieved by administration of oral hypoglycemic agents or insulin as well as by movement therapy. However, there are patients who, for various reasons, are unable to meet dietary or exercise requirements or who remain unresponsive to drug treatment.
agents were introduced (metformin hydrochloride, 1000 mg/day; glibenclamide, 10 mg/day; acarbose, 300 mg/day). Insulin therapy was recommended in place of the ineffective oral agents to control glucose levels and prevent diabetic complications but the patient refused. He presented at our clinic on March 14, 2011, seeking to reduce blood sugar level with herbal medicine. On presentation, his glucose and hemoglobin A1c (HbA1c) levels on an empty stomach were 19.1 mmol/L and 9.6%, respectively, showing inadequate blood sugar control. He did not complain of serious diabetes symptoms and followed exercise and dietary recommendations. Due to a specific workplace environment, he was unable to quit an alcohol drinking habit (he drank twice a week, 180 mL of Korean distilled liquor). He had an aggressive personality and was a non-smoker.
Laboratory Findings We observed a positive effect of Yanggyuksanhwatang (YGST), a herbal extract used in Korean medicine, in lowering blood sugar levels and reducing symptoms in patients with type 2 diabetes who were unresponsive to oral hypoglycemic agents.
Case History Patient Characteristics and Diagnosis A 51-year-old man (weight, 81 kg; height, 176 cm; waist, 91 cm) with uncontrolled diabetes mellitus and early nonproliferative diabetic retinopathy presented at Kyunghee-saeng Korean Medicine Clinic. A medical examination conducted in 2001 revealed impaired glucose tolerance. Lifestyle modification was recommended but the patient failed to introduce any significant changes. In February 2009, he was diagnosed as type 2 diabetes at a university hospital in Seoul and was prescribed an oral hypoglycemic agent to control blood sugar levels. During the early stage, he received only 1 agent but it was no longer effective after 3 years of treatment, even after an increase in dosage. Therefore, additional oral hypoglycemic
Complete blood count results at baseline were as follows: red blood cells, 5.64×10 12/L (normal range, 4.5–5.5×10 12 /L); hemoglobin, 15.6 g/dL (14.0–18.0 g/dL); and hematocrit, 46.8% (42.0%–52.0%). Biochemical test results were as follows: fasting blood glucose (FBS), 19.1 mmol/L (3.3–5.6 mmol/L); creatinine, 99.0 μmol/L (44.2–106.1 μmol/L); total protein, 7.7 g/dL (6.5–8.3 g/dL); albumin, 50.0 g/L (35–53 g/L); Na+, 138 mmol/L (135–148 mmol/L); K+, 4.0 mmol/L (3.5–5.1 mmol/L); Cl–, 105 mmol/L (98–107 mmol/L). HbA1c levels were 9.6%.
Treatment Outcomes The patient continued the combination of drug, ©The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2014 1. Kyunghee-saeng Haniwon (Korean Medicine Clinic), Seoul, Korea; 2. Department of Cardiovascular and Neurologic Diseases, College of Korean Medicine, KyungHee University, Seoul, Korea Correspondence to Dr. Seungwon Kwon, Tel: 82-02-958-9128, Fax: 82-02-958-9132, E-mail: [email protected] DOI: 10.1007/s11655-014-2071-z
Chin J Integr Med 2015 Feb;21(2):157-160
• 158 •
exercise, and dietary treatment while simultaneously taking YGST 3 times a day from March 14, 2011 until July 20, 2011. The daily dose of YGST consisted of Menthae herba , Saposhnikoviae radix , Gardeniae fructus , Gypsum fibrosum , Anemarrhena rhizome , and Schizonepeta spica (8 g each) and Rehmanniae radix , Lonicerae folium , and Forsythiae fructus (16 g each). A single day's dose of YGST was boiled with 500 mL of distilled water for approximately 2 h until the volume of solution was concentrated to 100–120 mL. The YGST decoction was administered three times daily after meals. During the administration of YGST and after its discontinuation in June, 2011, regular tests were performed to check its effect on blood sugar levels. During a 23-month follow-up, all parameters were within the normal ranges. In February 2013, normal blood sugar levels were maintained and nonproliferative retinopathy was no longer observed on a retinoscopy. The weight and waistline were slightly higher compared with the values observed during the 3-month treatment. The patient continued movement and dietary treatment but did not quit his drinking habit. The results of follow-up measurements are provided in the Tables 1 and 2. Table 1.
Changes in Laboratory Parameters during Administration of YGST
Time
Glucose (mmol/L)
HbA1c (%)
March 14, 2011
19.1
9.6
April 6, 2011
8.0
9.1
June 20, 2011
4.6
5.8
Table 2. Changes in Laboratory Parameters during Follow-up Time August 26, 2011
Glucose (mmol/L)
HbA1c (%)
4.6
5.5
October 17, 2011
5.5
5.1
February 13, 2012
5.1
5.6
September 7, 2012
–
5.9
February 13, 2013
–
5.9
DISCUSSION We showed that the control of blood sugar and HbA1c levels in a patient with type 2 diabetes that had been unresponsive to oral hypoglycemic agents for 2 years could be achieved by a 3-month treatment with YGST. Moreover, we showed that normal blood sugar levels were maintained during a 23-month follow-up.
Our case study has important implications. Vascular and other diabetic complications may be prevented by herbal medicine. According to large, randomized, prospective studies, namely, the Kumamoto Study (4) and UKPDS, (5-7) rigorous blood sugar control from the early stages of type 2 diabetes can help reduce the risk of micro- and macrovascular diabetic complications. Our patient had suffered from diabetes for 2 years and was also diagnosed as nonproliferative diabetic retinopathy due to uncontrolled blood sugar levels. Therefore, it was important to quickly reduce blood sugar levels with drug treatment. Thus, an alternative therapy was needed because the patient refused insulin therapy. We administered YGST for 3 months and observed an improvement in blood sugar levels and retinopathy. Blood sugar control is assessed on the basis of the HbA1c measurement. The threshold level of HbA1c is 7.0% according to the Diabetes Control and Complications Trial (DCCT)(8) and UKPDS(5-7) and 6.5% and lower according to the Kumamoto Study.(4) Moreover, the Kumamoto researchers set the target blood sugar level at no more than 6.66 mmol/L. Considering the above values and our results, we may conclude that YGST can help prevent diabetic complications and relieve diabetes symptoms. Moreover, its positive effect is continuous and not temporary, as confirmed by our follow-up study. The use of YGST not only prevented diabetic complications but also helped in the treatment of diabetes itself. Therefore, the patient could avoid the side effects of insulin therapy. Prior to treatment with herbal medicine, our patient took 3 different oral hypoglycemic agents in line with the general recommendation that if patients remain unresponsive to one agent, another agent with a different mechanism should be added.(9,10) However, according to a Korean study, Practical Evidences of Antidiabetic Monotherapy (PEAM),(11) a treatment with either glimepiride, metformin, or thiazolidinedione alone for 48 weeks also significantly reduced blood sugar levels with only half of the maximum dose. Accordingly, if a single oral hypoglycemic agent is not effective in a patient with type 2 diabetes, the use of a different type of an oral agent is suggested before the first agent reaches its maximum dose. However, if patients remain unresponsive, they must start insulin therapy.
Chin J Integr Med 2015 Feb;21(2):157-160
• 159 •
The Canadian guide on diabetes treatment recommends different modalities depending on baseline blood sugar levels. If the HbA1c level is 9% and over, a combined treatment with 2 or more oral hypoglycemic agents or immediate insulin therapy is recommended.(12) In our patient, the HbA1c level was 9.6% despite the administration of 3 oral hypoglycemic agents, and thus insulin therapy was necessary. However, insulin therapy is known to produce side effects. For example, it requires that patients regularly check their blood sugar levels because they may experience hypoglycemia, which in itself can adversely affect the quality of life. Therefore, it is best to avoid insulin therapy whenever possible because although it helps reduce blood sugar levels over a short period, it significantly increases the risk of hypoglycemia. According to UKPDS,(5-7) hypoglycemia is observed in up to 36.5% of diabetic patients (including those with mild hypoglycemia), and 2.3% of these patients require assistance or hospitalization. Moreover, the DCCT study showed that a strict control of blood sugar levels is associated with a 3-fold higher risk of hypoglycemia.(8) Another side effect is weight gain that affects mainly the abdomen area and is related to the daily dose of insulin and blood insulin levels. Moreover, repeated insulin injections in the abdomen produce a scar and may lead to lipohypertrophy or lipoatrophy.(13) In our case, we were able to avoid insulin therapy and the potential side effects by using YGST.
resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. (17) Geniposide, a glycoside of Genipin, also revealed an anti-obesity effect, an insulin resistance-alleviating effect in a recent experimental study. (18) Furthermore, Forsythiae fructus (19) and Mangiferin, an ingredient of Anemarrhena rhizome (20,21) also revealed an antidiabetic effect in the experimental studies.
Our results are similar to those of several other studies. For example, YGST was reported to improve clinical symptoms, such as frequent urination and unusual thirst, in a study involving 5 patients with type 2 diabetes who received the extract for 8 weeks.(14) The mean glucose, blood pressure, and total protein levels significantly improved. However, unlike in our case, no effect was observed on the lowering of HbA1c levels. Furthermore, in an experimental study on rats with alloxan-induced diabetes, (15) the use of YGST was shown to significantly lower blood sugar levels. A similar result was observed in a study on rats with streptozotocin-induced diabetes. (16) Glucose levels were significantly reduced, while serum insulin levels were only slightly elevated.
Acknowledgments
In addition, we think that YGSY can be a prevention plan for diabetic complications, such as diabetic foot ulcer and diabetes-associated cognitive decline. Anemarrhena rhizome has an alleviating effect on diabetes-associated cognitive decline in rats.(22) And, Rehmanniae radix can treat diabetic foot ulcer through the combined therapy of Astragali radix and Rehmanniae radix . (23,24) Therefore, we can expect that YGST has the preventive effects on the diabetic complications as well as clinical effects on blood sugar control. We showed the positive clinical effects of YGST on blood sugar control and symptom relief in a patient with unresponsive type 2 diabetes. However, this is only a case report and our herbal medication has not been certified by the Good Manufacturing Practice. Therefore, to confirm the clinical effect of the extract, a clinical study involving a control group and a standardized medication is needed.
No financial support was received during the present study.
Conflict of Interest The authors declare that they have no conflicts of interest.
REFERENCES 1.
Kim EJ, Min HK, Choi YG, eds. Diabetes. 3rd ed. Seoul: Goryeo-euhak 2005:169-173, 830-832.
2.
Pickup JC, Williams G. Diagnosis and treatment of diabetes mellitus. KMS 2006:1-6, 437-442.
3.
Bowman WC, Rand MJ. Endocrine function of the pancreas. In: Textbook of pharmacology. 2nd ed. London: Blackwell Scientific Publications; 1980:1943-1964.
4.
Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the
Anti-diabetic effect of YGST in this case report is supported by several experimental studies. Genipin, an ingredient of Gardeniae Fructus has an ameliorative effect on age-related insulin
progression of diabetic microvascular complications in Japanese patients with non-insulin dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-117.
• 160 •
5. UK Prospective Diabetes Study (UKPDS) Group.
Chin J Integr Med 2015 Feb;21(2):157-160 rats. Kyung Hee Univ Orient Med J 1992;15:113-133.
Intensive blood-glucose control with sulphonylureas or
16. Kim EJ, Kim YS. Effects of Yanggyuksanhwa-tang on
insulin compared with conventional treatment and risk of
diabetic rats induced by streptozotocin. Kor J Ori Physiol
complications in patients with type 2 diabetes (UKPDS 33).
Pathol 2007;21:474-478.
Lancet 1998;352:837-853.
17. Guan L, Feng H, Gong D, Zhao X, Cai L, Wu Q, et al. Genipin
6. UK Prospective Diabetes Study (UKPDS) Group. Effect
ameliorates age-related insulin resistance through inhibiting
of intensive blood-glucose control with metformin on
hepatic oxidative stress and mitochondrial dysfunction. Exp
complications in overweight patients with type 2 diabetes
Gerontol 2013 Sep 14. doi: 10.1016/j.exger.2013.09.001.
(UKPDS 34). Lancet 1998;352:854-865.
Epub ahead of print.
7. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull
18. Kojima K, Shimada T, Nagareda Y, Watanabe M, Ishizaki
CA, et al. Association of glycaemia with macrovascular and
J, Sai Y, et al. Preventive effect of geniposide on metabolic
microvascular complications of type 2 diabetes (UKPDS 35):
disease status in spontaneously obese type 2 diabetic mice
prospective observational study. BMJ 2000;321:405-412.
and free fatty acid-treated HepG2 cells. Biol Pharm Bull
8. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennil
2011;34:1613-1618.
A, Goldstein DE. Defining the relationship between plasma
19. Kim CJ, Cho SK, Shin MS, Cho H, Ro DS, Park JS, et al.
glucose and HbA(1c): analysis of glucose profiles and
Hypoglycemic activity of medicinal plants. Arch Pharm Res
HbA(1c) in the Diabetes Control and Complications Trial.
1990;13:371-373.
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