# Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight
## 1 Introduction  
Several estimates on the current level of diabetes and its projected cases in the next few decades have been made in recent years. According to the World Health Organization's (WHO), there were 422 million cases in 2014 with 8.5% prevalence that rose from 4.7% in 1980 [1]. Similarly, the major risk factor of diabetes has been recognized as obesity which prevalence in 2014 was 600 million; while the number of adults (18 years and older) reported as overweight were more than 1.9 billion [2]. As we are living in an era where more of the world population are suffering from consequences of excess calories than undernutrition, the cost of diabetes and obesity will remain the major social burden to societies in the next few generations. To date, diabetes is already a direct cause of death for millions of people annually but its impact is even more severe in its association with other diseases such as cardiovascular complications, organ failure (e.g., kidney) and disabilities, such as blindness and limb amputations [1].  
There is as yet no drug of cure for diabetes and the current therapeutic approaches are directed on the management of the disease, primarily on glycemic control. The disease itself, also called diabetes mellitus, is manifested when there is persistent hyperglycemia in the blood arising from either insufficient (or not at all) amount of insulin released from the pancreatic \(\beta\)-cells and/or resistance to insulin is developed by vital organs. The most uncomplicated diabetes case is type-1 diabetes (T1D)were pancreatic \(\beta\)-cells are destroyed through an autoimmune-mediated reaction. On the other hand, type-2 diabetes (T2D) is characterized by insulin resistance with major risk factors being age and obesity. The disease is complex and may involve impaired insulin secretion and \(\beta\) cell death along with various metabolic dysregulations.  
Since its discovery in the 1920's, insulin has been taking the center stage in the therapy of both T1D and T2D [3; 4]. Other classes of antidiabetic drugs include the \(\alpha\)-glucosidase inhibitors (e.g., acarbose, miglitol and voglibose) that target carbohydrate digestion in the gut thereby limiting the availability of glucose taken up by the blood; the biguanides (the metformin-like compounds) that suppress glucose release/production in the liver; the thiazoltionedines such as glitzanones which increase the sensitivity of insulin target organs; the insulin secretagogue sulfonylures and the meglitinides; the glucose-dependent insulinotropic polypeptides (GLP-1) analogues; the DDP-4 inhibitors, among others [5]. These drugs have numerous side effects including gastrointestinal complications and loss of efficacy after pronged usage [6; 7]. The high cost and patient compliance have also been other issues in diabetes therapy considering the required long period of treatment and repeated dosage. Hence, the urgency of identifying novel antidiabetic drugs with safer, more efficacious and cheaper profile cannot be overemphasized. Given diabetes being a complex disease, the rational for the search of multifunctional compounds that target multiple mechanisms of the diffused pathology has been advocated [8]. Furthermore, the antidiabetic potential of many natural products especially polyphenols that combine antioxidant, antiinflammatory, enzyme inhibition and various other general and specific insulin signaling modulatory effects have been outlined in recent years [9; 10; 11]. In this review, attention is given to structurally the smallest molecular weight group of compounds of the terpenids classes of natural products, monoterenes. Attempt is also made to scrutinize their antidiabetic activity profile built from their in vitro and in vivo data. As antidiabetic agents, monoterenes now, somehow unexpectedly, appears to be recognized as small molecules punching a lot more than their weight.