Metabolic effects of combining American ginseng (Panax quinquefolius L.) and viscous fibre in the treatment of type 2 diabetes

The aim of the thesis was to determine whether synergistic or additive metabolic benefits could be derived with the use of two plant-based components with independent physiological activities and whether the use of these two agents would improve diabetes control in the long term. Viscous fibres reduce postprandial glycaemia, insulinaemia and gastrointestinal hormones levels, their effectiveness being dependent on the viscosity of the fibre. Long term studies with viscous fibre have shown reductions in serum cholesterol, and improvements in metabolic control and blood pressure in type 2 diabetes. Konjac mannan fibre (KJM) is a high viscosity, viscous fibre. American ginseng (AG) increases insulin secretion and improves glycaemic control in type 2 diabetes. The suggested active ginseng components are the ginsenosides. As both AG and KJM have been shown to improve diabetes control through independent physiological mechanisms, this thesis explores the possible benefits of using them in combination. To test potential additive effects of KJM and AG, an acute experiment was performed in thirteen subjects with type 2 diabetes where AG and/or KJM were incorporated into a liquid meal replacement as a breakfast, followed 4 hours later by a standard lunch. Contrary to previous findings, neither AG or KJM when given individually, reduced postprandial glucose and insulin levels by the expected amounts; moreover the combination did not result in glucose levels significantly different from control. The study did demonstrate that KJM flattens the postprandial response of glucose-dependent insulinotropic peptide (p<0.04) and glucagon like peptide-1 (p<0.02). In addition KJM reduced the glucose area under the curve to a standard meal following the fibre enriched breakfast. Subsequent experiments showed that, despite high ginsenoside levels, the AG used was ineffective and the liquid replacement meal inhibited the gel formation of the KJM. In preparation for a long-term intervention study, acute experiments were performed to select a physiologically effective AG, and to determine the most effective and palatable method of KJM incorporation. Incorporation of KJM into bread, capsules and margarine reduced the incremental areas under the glucose curve by 3%, 12% and 34% compared with control, with only the margarine being significantly different (p<0.001). Further experiments showed that incorporation of 1g of KJM into margarine and 4g of KJM into bread reduced the glucose AUC to a similar extent. KJM capsules has no acute effect on postprandial glycaemia, regardless of the timing of their administration relative to the meal. Three months of 6g of viscous fibre and 3g of AG administration to 30 subjects with type 2 diabetes resulted in significant percent-change difference from control in HbA1c (-4.1+/-1.4%, p<0.01), total cholesterol (-5.7+/-1.9%, p<0.00), LDL-cholesterol (- 8.2+/-3.1%, p<0.002) and apoliporotein B (-9.0+/-2.3%, p<0.0005). It was estimated the combination of viscous fibre and AG resulted in a 14% risk reduction in coronary heart disease. The studies in this thesis illustrate some of the difficulties of working with "natural" products but also their potentially effective use in the treatment of type 2 diabetes.