Case Report

Diabetic Progression in Obese Subjects after Drinking Anti-Obesity Herbal Tea

Takeda K, Yamamoto C, Kishimoto M, Kusu Y and Kaji H*
Division of Physiology and Metabolism, University of Hyogo, Japan

*Corresponding author: Hidesuke Kaji, Division of Physiology and Metabolism, University of Hyogo, 13-71 KitaOhji-cho, Akashi 673-8588, Japan


Published: 29 Jul, 2016
Cite this article as: Takeda K, Yamamoto C, Kishimoto M, Kusu Y, Kaji H. Diabetic Progression in Obese Subjects after Drinking Anti- Obesity Herbal Tea. Ann Clin Case Rep. 2016; 1: 1070.

Abstract

We report here two obese subjects who started the same anti-obesity herbal tea. Diabetes progressed just after drinking the tea probably through the decreased insulin secretion and sensitivity in the case 1 and 2, respectively. Direct deleterious effects of the tea on insulin secretion and action were confirmed by in vitro studies using RIN-5F and HepG2 cells.

Keywords: Herbal tea; obesity; Insulin secretion; Insulin action; Diabetes mellitus; RIN-5F; HepG2

Introduction

Obesity is a health concern leading to various morbidity and mortality including type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Pharmacotherapy or surgical operation is limited to extremely obese subjects, so life style of food intake and exercise should be corrected to protect obesity. Many obese subjects who can imperfectly continue life style correction use alternative medicine. Herbal remedies are generally known to be safe and effective for the anti-obesity [1]. On the other hand, there are many reports of herbal hepatotoxicity [2]. We report here two obese subjects in whom overt diabetes progressed after drinking the same anti-obesity herbal tea. The clinical course suggested that herbal tea gave some influences on the decline of insulin secretion or action. To clarify the causal relation among the herbal tea and the deterioration of insulin secretion or action, in vitro studies were done to examine direct influences of this herbal tea.

Case Report

The case 1 was 80-year-old male with obesity for several years. His weight was 91kg, height 169 cm, BMI 31.9 kg/m2, waist circumference 102 cm, %fat 30 %. The blood pressure was 130/70 mmHg after his home doctor prescribed calcium antagonist. The fasting plasma glucose (FPG) was 119 mg/ dl, HbA1c 6.3%, total-cholesterol 191 mg/dl, triglyceride 135 mg/dl, AST 46 IU/l, ALT 43 IU/l, and γ-GTP 84 IU/l. Ultrasonography indicated fatty liver. He started 3 packs/day of herbal tea (trade name: Chinese court anti-obesity tea) for weight reduction. A pack of this tea powder is dissolved in adequate amount of water. Nine days after the start, the tea was reduced from 3 packs/day to 1 pack/ day because of diarrhea and was continued for 21 days. His weight was reduced to 81 kg within 3 months after the start. On the other hand, his FPG abruptly rose to 549~595 mg/dl, HbA1c to 13.3%, and urine C-peptide reactivity (u-CPR) was 21 μg/day (normal; 24~97 μg/day) one or two months after starting the herbal tea (Table 1). He stopped the herbal tea a month after the start. Thirty seven days after the stop of the herbal tea, he started and continued SU drug (60-20 mg gliclazide) for 3.5 months. Then FPG was 131 mg/dl, HbA1c 7.2 % and u-CPR 327 μg/day. Even after the cessation of SU drug, HbA1c was 6.4 -7 % and u-CPR 99 μg/day.
The case 2 was 57-year-old female with mild obesity. She had acromegaly 14 years ago, when trans-sphenoidal surgery was done and bromocriptine was prescribed for a short period. The serum GH had been normalized to 0.4~0.7 ng/ml and IGF-I 220~240 ng/ml. Her weight was 77.5 kg, height 162 cm, BMI 29.5 kg/m2, and blood pressure 110/62 mmHg. As shown in Table 2, FPG was 118 mg/dl, IRI 8 μU/ml, and homeostasis model assessment-insulin resistance (HOMA-IR) 2.23 (normal: <1.6). She started and continued 2 packs/day of the same herbal tea for 1.5 months. Two or four months after the start, FPG gradually rose to 224 mg/dl, IRI 18 μIU/ml and HOMA-IR 9.96. Diabetes did not progress further but was not completely improved after the cessation of the herbal tea. Thus she started and continued SU drug (1mg glimepiride).
In vitro study
The first experiment was done to examine the influence of this herbal tea on insulin secretion from rat insulin producing pancreatic tumor cell line RIN-5F cultured in RPMI1640 with 10 % fetal calf serum (FCS) under the atmosphere of 5 % CO2 and 95 % air at 37ºC. Rat insulin was measured by ELISA kit (Mercodia). Addition of 600 but not 60 mg/ml herbal tea for 2-h significantly inhibited insulin secretion from cultured RIN-5F (P<0.05 vs. no addition of herbal tea). Addition of 10 or 50 nM glucose for 5 min stimulated insulin secretion whereas 60 or 600 mg/ ml herbal tea attenuated insulin responses to 10 and 50 mM glucose (Figure 1).
The second experiment was done to test the influence of the same herbal tea on insulin action in human hepatoma cell line HepG2 cultured in Dulbecco’s modified Eagle’s medium with 10 % FCS under the atmosphere of 5 % CO2 and 95 % air at 37ºC. Insulin action was monitored by Western blot analysis using phospho-tyrosine antibodies as described previously [3]. Briefly, lysed cells were applied on SDS gel electrophoresis, and electroblotted to nitrocellulose membrane. Blotted membrane was incubated with phospho-tyrosine antibodies and detected by electrochemi-luminescence. Additions of 0, 10, and 100 nM human insulin (Peptide Institute) in cultured HepG2 for 30 min caused dose-dependent increases in tyrosinephosphorylation of several proteins, whereas simultaneous addition of this herbal tea attenuated insulin-induced tyrosine-phosphorylation of several proteins. When the band area and density were measured by densitometry (Image J, NIH), 10 and 100 nM insulin increased in the density of tyrosine-phosphorylated 47 kDa protein to 163 and 174 % relative to control without insulin, respectively. However, the addition of 600 mg/ml herbal tea attenuated the amount of the tyrosine-phosphorylated 47 kDa protein to 98.4 and 61 % of control in response to 10 and 100 nM insulin, respectively (Figure 2).

Table 1

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Table 1
Body weight and biochemical markers before and after drinking anti-obesity herbal tea in the case 1.

Figure 1

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Figure 1
(a) Insulin secretion from cultured RIN-5F incubated with 0, 60, 600 mg/ml herbal tea for 2-h. Each bar is mean + SD. *; P<0.05 vs. no herbal tea. (b) Insulin secretion from RIN-5F for 5 min in response to 0, 10, 50 nM glucose with 0, 60, 600 mg/ml herbal tea. Each bar represents mean + SD. Insulin secretion in the absence of glucose is defined as 100% in 0, 60, and 600 mg/ml herbal tea.

Table 2

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Table 2
Body weight and biochemical markers before and after drinking anti-obesity herbal tea in the case 2.

Figure 2

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Figure 2
Tyrosine phosphorylation in response to insulin and herbal tea. (a) HepG2 cells were incubated for 30 min with 0, 10, and 100 nM insulin in the absence or the presence of 600 mg/ml herbal tea. Method of Western blot was described in In vitro study. Representative result in 3 independent experiments is shown. (b) Densitometric analysis of tyrosine-phosphorylated 47 kD protein in the experiment shown in (a). Each point represents the density of insulin-induced tyrosine-phosphorylation of 47 kD protein relative to control without insulin in the absence and the presence of herbal tea.

Discussion

In the clinical course of the case 1, FPG and HbA1c were within normal range but rose to 595 mg/dl and 13.3 %, respectively, just after the start to drink the herbal tea. His body weight reduction was 6.5 kg and simultaneous measurement of u-CPR was low, suggesting that the hyperglycemia is caused by the decreased insulin secretion. There was no particular cause except for the herbal tea to explain these changes. The case revealed fatty liver and showed mild elevation of liver enzyme, but no progression of liver dysfunction was found after the start. To elucidate whether the tea deteriorates insulin secretion directly, the in vitro study was done and the results suggested that the tea directly caused a decrease in insulin secretion from RIN-5F.
In the clinical course of the case 2, FPG was within normal range and rose to 225 mg/dl with HbA1c 8.5 % just after the start to drink the herbal tea. Plasma IRI and HOMA-IR is concomitantly increased, suggesting that the hyperglycemia is caused by decreased insulin sensitivity. This patient had acromegaly, but GH and IGF-I had been normalized. Thus it is unlikely that excess GH secretion is a factor of insulin resistance. The possibility of the tea to deteriorate insulin sensitivity was examined by in vitro studies. The results suggested that the tea directly caused attenuation of insulin action.
It is unknown which contents of this tea are attributable to these deleterious effects. The tea contained several herb mixture such as hawthorn, fruit of the matrimony vine, licorice, Chinese citron, litchi, pu-erh tea etc. Among them hawthorn was reported to have anti-diabetic effects in mice [4]. Oligonol derived from lychee fruit attenuates gluco-lipotoxicity-mediated renal disorders in type 2 diabetic db/db mice [5]. Pu-erh tea decreases blood sugar by inhibiting α-glucosidase in mice [6] and inhibits advanced glycation end product formation and ameliorates progression of experimental diabetic nephropathy [7]. In addition to these herbs, D-sorbitol and β-cyclo dextrin were also included in this tea. Thus we cannot exclude the possibility that these contents or other undescribed substances may affect insulin secretion and action.
It has been reported that herbal tea such as Xiaoke tea [8], olive leaf extract [9], decaffeinated green tea [10] are beneficial for diabetic humans and that MonCam (a preparation containing a standardized green tea extract complexed with phospholipids) plus a hypocaloric diet is beneficial for obese humans [11]. Moreover, herbal tea such as the flower tea coreopsis tinctoria [12], persimmon leaf [13], green tea fermented with Aquilariae Lignum [14,15], green rooibos (Aspalathus linearis) extract [16] are beneficial for diabetic mouse or rat models. Although there was a report showing that herbal tea such as costus spicatus tea failed to improve diabetic progression in diabetic model mice [17], there has been no report that herbal plants including this tea contents has deleterious effects on insulin secretion and action.
In conclusion, some kinds of herbal tea might have deleterious effects on insulin secretion and action. Thus anti-obesity herbal tea should be carefully permitted to use in obese subjects to avoid diabetic progression.

Acknowledgment

This study is supported in part by JSPS KAKENHI Grant Number JP 16K00860.

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