Globally, T2DM has an enormous impact on the health care costs and economy, as such it is highly desirable that this disease be prevented at an early stage. A prediabetes condition does not necessarily develop into diabetes if controlled well. Progression to diabetes can be prevented by lifestyle interventions and pharmacotherapeutic modes. There are several effective pharmacological regimens with encouraging results [17–19] however these regimens are either not usually economically accessible or not well tolerated by all [20]. Hence a need to focus on indigenous, inexpensive food-based regimens.
Traditional plant medicines are used throughout the world as alternative therapies to control diabetes. Although numerous herbs are reported to possess some degree of anti-diabetic activity [21], a significant amount of research, as well as traditional usage suggest that Fenugreek may be among the best in terms of efficacy and safety [7]. Though many studies evaluated the hypoglycemic and hypolipidemic effects of Fenugreek in animal and human models with type 1 and type 2 diabetes, no study is reported in prediabetes till date. Further this is a first study conducted employing a commercially debitterized Fenugreek powder in the prevention of diabetes in subjects with IFG/IGT. The rate of progression to diabetes during the intervention in controls and Fenugreek group is determined in the present study.
Progression to diabetes
It was observed that the conversion rate from IFG and IGT to diabetes by the end of 3 years reduced significantly in Fenugreek group when compared to controls (Fig. 2). At 3 years, glucose levels have normalized in 18.52 % of controls and 34.62 % of Fenugreek subjects. In a 11-year follow up study it was stated that many people with prediabetes (a quarter or more) may revert to normal glucose tolerance on long term, and after a protracted follow-up, only about 50 % of people with IGT or IFG will develop diabetes [22]. In our study the conversion rate from IFG and IGT to diabetes in controls was similar to the study quoted above. Therefore this indicates that progression to diabetes from prediabetes stage is subsided by the consumption of Fenugreek as the conventional conversion rate of diabetes is lowered from 55 to 23 % at the end of 3 years due to Fenugreek.
Anthropometric parameters
It was observed that body weight, BMI, SBP and DBP were unaltered in both control and Fenugreek groups. Simiarly the patient’s weight, BMI and other clinical parameters measured were found to be almost stationary when the dose-dependent effects of Fenugreek in diabetes with dyslipidemia were studied [23].
Biochemical parameters
Hypoglycemic effects
During the study period FPG (p < 0.05) and PPPG (p < 0.01) reduced significantly at the end of 3 years in Fenugreek group.
The hypoglycemic effect of Fenugreek seed powder discussed in our study is well supported by few studies [9, 11, 24, 25] which showed hypoglycemic effect in both type 1 and type 2 diabetes subjects. In vivo study by Kumar RV et al. [26] depicted a significant reduction (p < 0.001) in the postprandial blood glucose levels in the diabetic rats on treatment with Fenugreek formulation AF40.
Hypolipidemic effects
In this study, serum cholesterol and TG levels were almost similar by the end of study period within control and Fenugreek groups, which is in contrast to the studies which reported that cholesterol and TG levels were lower in Fenugreek treated animals over untreated diabetic animals (p < 0.05) [27, 28]. The small changes in serum cholesterol and TG levels could be due to the fact that the mean data for these variables are already in the normal range.
Within controls and Fenugreek group there were no significant changes in HDLc throughout the study period. Analogous to these results few studies also reported that Fenugreek did not alter HDLc levels [23, 29]. The LDLc reduced at the end of 3 years (p < 0.05) in Fenugreek group. Fenugreek seeds contain a gel-like soluble fiber which combines with bile acid and lowers triglyceride and LDL cholesterol levels [30].
Insulinotropic effects
In controls, serum insulin levels remained same during the study period whereas in Fenugreek group, at the end of 3 years, serum insulin had increased significantly (p < 0.01) in Fenugreek group. Various studies [31, 32] suggested that Fenugreek seeds act as insulin secretor, as they reported increased insulin secretion in animal studies. Yadav et al. [33] also suggested that Fenugreek seeds, more precisely the water extract, act as an insulin secretor but they did not monitor insulin levels.
As serum insulin levels have increased in Fenugreek subjects, insulin resistance was assessed by HOMA. Insulin resistance (HOMA IR) was not different in control group during the intervention period but within Fenugreek group HOMA IR increased significantly at the end of 3 years (p < 0.05). This is in contrary with the study which reported that the action of Fenugreek is mediated by improving insulin sensitivity and decreasing insulin resistance apart from the known mechanisms of reduced glucose absorption [11]. The data obtained on insulin resistance in our study are not in agreement with the study where anti-diabetic properties of 4-hydroxy isoleucine, the active compound in Fenugreek were seen for its insulinotropic action and for extrapancreatic insulin-sensitizing effects [34]. The studies reported above were done in type 2 diabetes subjects and it cannot be assumed that Fenugreek actually increases insulin resistance in prediabetes, because the serum insulin levels in our study subjects were within the normal range. In addition, the HOMA-IR level in the Fenugreek group at the end of 3 years was within the normal insulin resistance category (<3). Regression analysis outcome of diabetes in Fenugreek group was positively associated with serum insulin (p < 0.01) and negatively associated with HOMA IR (p < 0.001). Fenugreek may exert its therapeutic effect through its alkaloids content by modulation of insulin secretion. The amino acid 2S,3R,4S, 4-hydroxyisoleucine, purified from Fenugreek seeds, showed insulinotropic effects which increased peripheral glucose uptake in vitro [35].
Strengths, limitations and avenues of the study for future research
This is a prospective, randomized controlled study conducted in men and women, having different life-styles and socio-cultural backgrounds but satisfying the inclusion and exclusion criteria mentioned. Though the sample size had diversified demographics, their anthropometric, clinical and biochemical parameters were similar at baseline. This study could target large populations more cost effectively. So far there was no systematic long term study in prediabetes and as such this is a conventional intervention, carried out for the first time in a different group of population (prediabetes). No study until now has reported the incidence conversion rate to diabetes with the interventional Fenugreek powder in prediabetes. The strength of this intervention lies on the complexity of data analysis which illuminates the statistical correlation between independent risk factors towards the onset or progression to diabetes.
Our estimate of the effect of the intervention can be considered conservative for two reasons. First, data was analyzed according to the intention-to-prevent principle, even though some subjects in the intervention group did not follow the recommendations about Fenugreek consumption. Second, for ethical reasons, all subjects assigned to the control group also received general health advice and counseling on dietary patterns at base line and at annual follow-up visits and may have benefited from this advice.
Participants who dropped out before the end of the 1 year intervention period were not included in the analysis because if their last observation had been carried forward, the differences between the two groups would have been artificially maintained over the follow-up period. Carrying the last observation forward assumes that assigning a no-change status is a conservative analysis, which is not the case, because weight change over time is nonlinear.
Despite of supplying debitterized processed Fenugreek powder to the study group, few subjects have skipped their doses due to its unacceptable palatability. Because of this reason they were advised to consume it along with some flavoring agents. This perhaps, could alter the plasma glucose levels and was found to be one of the limitations of the study. Though there were many reasons for subject dropouts, one of the reasons was their unwillingness towards the consumption of Fenugreek on long term basis due to its undesirable taste. In addition, subjects did not receive any incentives during the study due to which there was a lost to follow-up and the dropout rate in study group was recorded as 13.5 %.
An alternative prediabetic intervention study can be carried out with the supplementation of tulsi with Fenugreek, which can be used to mask the bitter taste of Fenugreek. In addition, the role of Fenugreek in different population groups should also be carried out.