Diabetes mellitus refers to a group of metabolic disorders characterized by a rise in blood sugar, due to defects in secretion or function of insulin. The prevalence of type II diabetes in Iran is about 8.9%, which rises 1% every year, and the age of onset in Iran is 15 years below the global average. All synthetic hypoglycemic drugs have adverse effects, including drop in blood sugar, weight gain caused by sulfonylureas, gastrointestinal symptoms (nausea, cramps and diarrhea), lactic acidosis, vitamin B12 deficiency caused by metformin and flatulence and hepatic necrosis caused by alpha-glycosidase inhibitors. Several medicinal plants have blood sugar lowering effects and their efficacy has been demonstrated in clinical trials. Indeed, in management of the blood sugar levels of diabetic patients, several measurements are taken and an attention to medicinal plants is of importance, because they can be used as an efficient adjuvant treatment for lowering blood sugar and play a role in reducing the adverse effects and raising patient compliance.
Fenugreek seed has shown antidiabetic and cholesterol lowering effects in animal and human models. These effects have been attributed to the saponins in fenugreek and its high content of fiber, and are most probably irrelevant to its main alkaloid trigonelline. Its anti-hyperglycemic effects are related to a delay in gastric evacuation due to its fiber content and to unknown constituents that inhibit carbohydrate digesting enzymes. In vivo, administration of fenugreek might raise insulin levels in the plasma. In vitro, its main free amino acid, 4-hydroxyisoleucine stimulates insulin secretion in the pancreas. Its cholesterol lowering effect has been attributed to hepatic cholesterol conversion to biliary salts due to their loss via stool and complex formation with the fibers in fenugreek and its saponins. Treatment with fenugreek selectively reduces LDL and VLDL; also, in diabetic mice induced with alloxan and patients with type II diabetes, HDL rises following treatment with fenugreek. No report exists regarding toxic effects of fenugreek use. Therefore, its regular use might be advantageous in management of diabetes and prevention of atherosclerosis and coronary heart disease.(1)
In 2005, a product made from dialyzed aqueous extract of fenugreek seed (FSE) was studied by Vijayakumar et. al. The results of this study showed that in vivo, the hypoglycemic effect of FSE, at least partly, is due to activation of an insulin signaling pathway in adipocytes and hepatic cells.(2)
In a survey of the effect of extended use (multiple doses) of FSE on blood sugar level and body weight and its short time effect (single dose) on serum insulin and hepatic enzymes in experimental diabetes in mice, it was demonstrated that the mechanism of action of FSE is extrapancreatic and that the FSE product corrects the metabolic changes of diabetes with insulin-like properties and has good potential for clinical use.(2)
The hypoglycemic effects of fenugreek seed has been demonstrated in laboratory animals and human. In patients with diabetes, fenugreek lowers the levels of fasting blood sugar and blood sugar after meal. Nonetheless, it is not evident that improvement in glucose tolerance is due to the effect of fenugreek on glucose absorption or its metabolism. Therefore, a metabolic study with a cross-sectional design was carried out and for 15 days a diet of with or without 25 g fenugreek was randomly prescribed for 10 patients with non-insulin dependent diabetes. Avascular Glucose Tolerance Test (GTT) at the end of the study showed that the fenugreek present in daily diet significantly decreased the area under the curve for plasma glucose (half-life) and increased the rate of metabolic clearance. Moreover, fenugreek increased the number of insulin receptors in red blood cells. These results demonstrate that fenugreek can improve the peripheral uptake of glucose, which helps improve glucose tolerance. Therefore, fenugreek might exert its hypoglycemic effect through affecting insulin receptors, also at the level of the gastrointestinal system.(4)
To evaluate the efficacy and safety of Total Fenugreek Saponins in combination with sulfonylureas for treatment of patients with type II diabetes, who were not entirely managed by Sulfonylureas alone, 69 patients were divided into treatment (46 patients) and control (23 patients) groups and received for 12 weeks either TFGs or placebo three times a day, 6 tablets each time. Simultaneously, the patients continued using their main anti-hyperglycemic medications. The indicators of effect on the patient’s symptoms in Traditional Chinese Medicine, Fasting Blood Sugar (FBS), 2 hours Postprandial Blood Glucose (2h PBG), Glycated hemoglobin (HbA1c), Clinical Symptomatic Quantitative Score (CSQS), Body Mass Index (BMI), also hepatic and renal function was studied and compared before and after the intervention. In the treatment group, in comparison with the control group, the effect on the symptoms of the disease in Traditional Chinese Medicine was evidently better (p<0.01) and significant statistical reduction was seen in cases of FBG, 2h PBG, CSQS and HbA1c in the treatment group in comparison with the control group (p<0.01 or p<0.05), while no significant difference was observed between the two groups regarding BMI and hepatic and renal function. The researchers came to the conclusion that a combination therapy including Total Fenugreek Saponins and Sulfonylureas can lower the amount of blood glucose and improve clinical symptoms in type II diabetes, and this treatment is relatively safe.(5) To evaluate the effect of fenugreek seed in glycemic control and insulin resistance (as determined by HOMA model) in mild to moderate cases of type II diabetes, in a placebo-controlled, double-blind trial, 23 patients with recently diagnosed type II diabetes (FBS lower than 200 mg/dl) were randomly divided into two groups. The first group (12 patients) received 1 g per day hydro-alcoholic extract of fenugreek seed and the second group (13 patients) received conventional care (diet control and exercise) and placebo capsule for 2 months. At the beginning of the study, both groups were identical in terms of anthropometric and clinical parameters. The results of Oral Glucose Tolerance Test, blood lipid, fasting C-peptide, Glycated hemoglobin (HbA1c) and insulin resistance model HOMA were identical as well. At the end of two months, in group 1 compared to group 2, FBS (148.3 ± 44.1 to 119.9 ± 25 vs. 137.5 ± 41.1 to 113.0 ± 36.0) and 2h PBG (210.6 ± 79.0 to 181.1 ± 69 vs. 219.9 ± 41.0 to 241.6 ± 43) were not different. However, the area under the curve for blood sugar (2375 ± 574 vs. 27597 ± 274) and insulin (2493 ± 2536 vs. 5631 ± 2428) was significantly lower (p<0.001). Insulin resistance in HOMA model manifested a reduction in beta cell secretions in group 1 in comparison to group 2 (86.3 ± 32 vs. 70.1 ± 52) and increase in percentage of sensitivity to insulin (112.9 ± 67 vs. 92.2 ± 57) (p<0.05). In group 1, compared to group 2, the levels of serum triglyceride lowered and HDL rose (p<0.05). The researchers came to the conclusion that adjuvant treatment with fenugreek seeds results in improvement in glycemic control and reduction in insulin tolerance in patients with mild type II diabetes; it also has desirable effects on high triglyceride.(6)