To assess the effects of soybean-derived pinitol on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus.
Randomized, double-blind, placebo-controlled, parallel-group trial.
Pusan Paik Hospital, Pusan, Republic of Korea.
A total of 30 patients with type II diabetes received an oral dose of 600 mg soybean-derived pinitol or placebo twice daily for 13 weeks.
Pinitol significantly decreased mean fasting plasma glucose, insulin, fructosamine, HbA1c, and the homeostatic model assessment insulin resistance index (HOMA-IR, P<0.001). Pinitol significantly decreased total cholesterol, LDL-cholesterol, the LDL/HDL-cholesterol ratio, and systolic and diastolic blood pressure and increased HDL-cholesterol (P<0.05).
These data suggest that soybean-derived pinitol may be beneficial in reducing cardiovascular risk in Korean type II diabetes.
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (HMP 02-PJ1-PG3-22005-0011).
Although cardiovascular complications are the leading cause of premature death among patients with type II diabetes (O'Keefe, 1999), they can be prevented with good control of blood glucose, dyslipidaemia, and blood pressure (UKPDS, 1998; Garber, 2003). D-3-O-methyl-chiro-inositol (D-pinitol) has been reported to exert insulin-like effects. Pinitol extracted from Bougainvillea spectabilis reduced blood glucose in animal models of diabetes (Narayanan et al, 1987; Bates et al, 2000). Insulin reduced urinary D-chiro-inositol losses and increased plasma levels in poorly controlled diabetic patients (Ostlund et al, 1996). Pinitol has been isolated from soybean (Shin et al, 2001). In this study, we studied the effects of soybean-derived pinitol on glycaemic control and cardiovascular risk factors in patients with type II diabetes.
Subjects and methods
In all, 30 subjects with type II diabetes treated with oral hypoglycaemic agents, diet, and exercise participated in the study. The study protocol was approved by the Institutional Review Board of Pusan Paik Hospital (Pusan, Korea). Informed consent was obtained from all subjects prior to their entry into the study.
Pinitol was generous gift from Amicogen, Inc. (Jinju, Korea). Pinitol with 95% purity was prepared from soybean by water extraction, chromatographic separation using activated carbon, crystallization, and drying (Shin et al, 2001). The main contaminants were oligosaccharides and water.
The study was randomized, double-blinded, and placebo controlled. The patients were randomly assigned to receive an oral dose of 600 mg pinitol or placebo composed of lactose twice daily for 13 weeks. They were asked to avoid legumes and citrus fruits, but not otherwise change their usual medications and habitual diet and life style. They were advised to consume dietary energy to maintain IBW (30–35 kcal/kg IBW, 60% carbohydrates, 20% proteins and 20% fat, Korean Dietitian Society, 2000) and to participate in 30 min of moderate exercise every other day. Compliance to diet and exercise program, usual drug intake, and incidence of potential adverse effects, including hypoglycaemic episode, abdominal pain, flatulence, nausea, diarrhoea, and allergic symptoms, were monitored by questionnaires every week.
Anthropometric and biochemical measurements and food intake assessment using the 24-h recall method were performed at baseline and after the treatment period. Waist circumference was measured at the midpoint between the lower rib margin and the iliac crest with plastic tape and body fat content by a bioimpedance analyzer (HBF-300, Omron, Japan). Blood pressure was measured while the patient was sitting and after 5 min of rest, using a mercury sphygmomanometer (Baumanometer, WA Baum Co, Inc., Copiague, NY, USA).
Blood samples were collected after an overnight fast and centrifuged at 3000 × g for 15 min. HbA1C, plasma glucose, fructosamine, TG, total cholesterol, HDL-cholesterol, LDL-cholesterol, GOT, GPT, BUN, and creatinine were measured using commercial assay kits (Sigma Co., St Louis, MO, USA) and insulin by radioimmunoassay (Linco Co., St. Charles, MO, USA). HOMA-IR was calculated to assess insulin resistance (Matthews et al, 1985). The atherogenic indicies were calculated as LDL/HDL-cholesterol and TG/HDL-cholesterol. All the biochemical assays were carried out at Inje university. Intra-assay variabilities for all the biochemical parameters were within 3.4%.
All statistical analyses were performed using the SAS program (version 8.02). Differences between and within the pre- and post-treatment values of the groups were assessed by two-way, repeated-measures analysis of variance (ANOVA). Significance was defined as a P-value <0.05.
Results and discussion
All 30 patients completed the study. Pinitol was found to be well tolerated and no serious adverse events including hypoglycaemic episode were reported. Characteristics of the patients at baseline are given in Table 1. In all, 13 patients among the pinitol group and 11 among the control group were abdominally obese based on Asia Pacific cutoff (International Atherosclerosis Society (IAS), 2003). BMIs of the both groups fell within an overweight range (Kanazawa et al, 2002).
Intakes of energy, major nutrients, and dietary fibre were similar in the control and the pinitol group at baseline and after the treatment period. At 13 weeks, energy and fibre intakes were 1.940±32 kcal and 27.0±0.7 g for the pinitol group, respectively.
Pinitol treatment significantly reduced plasma glucose, insulin, fructosamine, HbA1c, HOMA-IR (P<0.001), and systolic and diastolic blood pressure (P<0.05, Table 2). Pinitol also decreased total cholesterol and LDL-cholesterol and increased HDL-cholesterol (P<0.05). Pinitol significantly decreased the LDL/HDL-cholesterol ratio (P<0.01) and tended to decrease TG (P=0.485) and TG/HDL-cholesterol ratio (P=0.094). Body weight, BMI, waist circumference, body fat content, GOT, GPT, BUN, and creatinine were not significantly affected by pinitol treatment.
Inositol phosphoglycan is one of the mediators involved in the actions of insulin; it is generated by the hydrolysis of glycophosphatidylinositol lipids upon the binding of insulin to its receptor (Varela-Nieto et al, 1996). Pinitol is converted to D-chiro-inositol in the body, a component of an inositol phosphoglycan (Ostlund et al, 1996). Nestler et al (1999) demonstrated increased insulin action in women with polycystic ovary syndrome treated with 1200 mg/day D-chiro-inositol. Thus, pinitol could mimic the ability of insulin in this study. However, 4 weeks of soybean-derived pinitol treatment (1200 mg/day) did not increase insulin sensitivity in individuals with obesity and mild type II diabetes (Davis et al, 2000). In this study, treatment of soybean-derived pinitol at the same dose for a longer period (13 weeks) appeared to exert an insulin-sensitizing effect resulting in a strong hypoglycaemic response, lipid profile-improving effect, and blood pressure control without altering body weight and waist circumference.
Evidence from prospective clinical trials suggests that achieving near-normal glycaemic control or tight blood pressure control in diabetic patients is associated with sustained decreased rates of cardiovascular diseases (UKPDS, 1998). Among blood lipids, HDL-cholesterol is the best predictor of coronary heat diseases, followed by triglyceride and total cholesterol in people with type II diabetes (American Diabetes Association, 1999). Thus, soybean-derived pinitol could be an effective oral agent in the treatment of type II diabetes and in the prevention of cardiovascular complications.
American Diabetes Association (1999): Management of dyslipidemia in adults with diabetes (Position Statement). Diabetes Care 22 (s01), 56–59.
Bates SH, Jones RB & Bailey CJ (2000): Insulin-like effect of pinitol. Br. J. Pharmacol. 130, 1944–1948.
Davis A, Christinansen M, Horowitz JF, Klein S, Hellerstein MK & Ostlund Jr RE (2000): Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 23, 1000–1005.
Garber AJ (2003): Metformin and vascular protection: a diabetologist's view. Diabetes Metab 29 (Suppl 6), 113–116.
International Atherosclerosis Society (IAS) (2003): Harmonized clinical guidelines on prevention of atherosclerotic vascular disease. Exec. Summ. 8.
Kanazawa M, Yoshiike N, Osaka T, Numba Y, Zimmet P & Inoue S (2002): Criteria and classification of obesity in Japan and Asia-Oceania. Asia Pacific J. Clin. Nutr. 11, S732–S737.
Korean Dietitian Society (2000): Manual of Medical Nutrition Therapy, pp 180–216. Kyunghee Total Printing Co.: Seoul.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF & Turner RC (1985): Homeostasis model assessment: insulin resistance and cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419.
Narayanan CR, Joshi DD, Mujumdar AM & Dhekne VV (1987): Pinitol—a new anti-diabetic compound from the leaves of Bougainvillea spectabilis. Curr. Sci. 56, 139–141.
Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD & Allan G (1999): Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N. Engl. J. Med. 340, 1314–1320.
O'Keefe JH, Miles JM, Harris WH, Moe RM & McCallister BD (1999): Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clin. Proc. 74, 171–180.
Ostlund RE & Sherman WR (1996): United States Patent. Patent Number 5,550,166.
Shin YC, Jeon YJ, Kim JJ & Choi CM (2001): Korea Patent. Application Number 1020010016111.
UK Prospective Diabetes Study (UKPDS) Group (1998): Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. UKPDS 38. BMJ 317, 703–713.
Varela-Nieto I, Leon Y & Caro HN (1996): Cell signalling by inositol phosphoglycans from different species. Comp. Biochem. Physiol. 115, 223–241.
We are grateful to Amicogen, Inc. (Jinju, Korea), for providing the soybean-derived pinitol.
Guarantor: J-I Kim.
Contributors: JCK was involved in study design. J-IK contributed to the practical organization of the trial. M-JK and M-SL were responsible for biochemical analyses. J-JK was responsible for design and statistical analyses. I-JC was responsible for project management. JCK and J-IK wrote the first draft of the paper and all authors contributed to the final draft.
About this article
Cite this article
Kim, J., Kim, J., Kang, M. et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized controlled study. Eur J Clin Nutr 59, 456–458 (2005) doi:10.1038/sj.ejcn.1602081
- pinitol (3-O-methyl-D-chiro-inositol)
- type II diabetes mellitus
- glycated haemoglobin
Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials
Clinical Nutrition (2019)
Single-Dose Pinitol Ingestion Suppresses Post-Prandial Glucose Levels: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial
Natural Product Communications (2019)
Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials
Clinical Nutrition (2019)
The Study of Dried Ginger and Linggan Wuwei Jiangxin Decoction Treatment of Cold Asthma Rats Using GC–MS Based Metabolomics
Frontiers in Pharmacology (2019)