Pre-diabetes is a condition of potential diabetes mellitus with an increased risk of developing type 2 diabetes [1
]. In other words, it is a state of either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Pre-diabetes is asymptomatic in many occasions, but once it develops into type 2 diabetes, it makes patients suffer from polydipsia, polyuria, polyphasia, unusual weight loss, and extreme fatigue [3
]. Unmanaged chronic diabetes mellitus affects quality of life and induces life-threatening diabetes-associated complications [4
]. Its mortality rate cannot be ignored in Korea, becoming the fourth leading cause of death by 2030 [6
]. According to the Korean National Health and Nutrition Survey (KNHNS) 2001, prevalence rates of diabetes were 1.4 million (8.1%) in Korean men and 1.3 million (7.5%) in Korean women. Nowadays, it is reported that about 308 million people worldwide are having impaired glucose tolerance (IGT) and among them 25% to 75% will develop diabetes [7
]. Since the exact figures of Korean pre-diabetes patients and diabetes progressing rates were not reported [4
], we can deduce from the above numerical statement that a considerable population must be
at the status of potential diabetes. Socioeconomic expenditures are also high, at 193 million won per year for medication [4
]. Therefore, preventing and treating efforts for the non-insulin taking patients in the stage of pre-diabetes and diabetes are urgently needed to lift the burden from both the nation and patients [10
]. Even though novel remedies have been produced unceasingly, most of them seem to be often ineffective for this disease [11
]. Meanwhile, dietary supplements are known to be relatively effective in treating diabetes, with few adverse effects [13
]. Among 400 reported herbal medicines for diabetes [16
], recent studies suggests that bitter oranges and mulberry leaves have antidiabetic effects. PURIAM110, a compound made from orange fruits and mulberry leaves (patent application no. 10-2006-0020040), is expected to prevent the progress to the early stage of diabetes mellitus, safely [17
]. Bitter orange is a dried, immature fruit of Citrus aurantium L
., used from ancient times to remove the stagnation and distension in hypochondriac regions [19
]. Like other herbal components, its mechanism of action seems to be complex though, the fruit has been identified to produce antihyperglycemic activity. Mulberry leaf is a dried leaf of Morus indica L
., which also shows hypoglycemic properties [21
]. It has been prescribed widely to dispel wind-heat and heat in the lung [23
]. Relying on pathophysiologic mechanisms from traditional Korean medicine, diabetes can be caused when there is heat in the lung or a deficiency of energy (Yang qi) and body fluid. Therefore, bitter orange's qi driving activity and mulberry leaf's heat dispelling function in the lung can be applied to play an antidiabetic role.
Despite the advantages of herb-derived supplements, few RCTs have been conducted [8
], and the bitter oranges and mulberry leaves compound is not an exception. Further trials of dietary supplements have to be done to suggest confirmative evidence.
The aim of this study is to evaluate the efficacy and safety of the PURIAM110, a dietary supplement for the treatment of patients with pre-diabetes and diabetes mellitus non-insulin dependent stage [26
]. This paper is the first pilot study with orange fruits and mulberry leaves on Korean adults who are at the status of pre-diabetes and diabetes mellitus not in the insulin requiring stage. The results of this study will give us the clinical of biochemical parameters, such HbA1c, fructosamine, fasting glucose and 2-h OGTT glucose between the placebo and PURIAM110 groups. On the basis of the results, we can suggest the optimal design, precise sample size, and primary outcome for a further large scale RCT.