D‐tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes

Summary Aim : D‐Tagatose (D‐tag), a hexose bulk sweetener, does not affect plasma glucose levels when orally administered to rodents. Additionally, D‐tag attenuates the rise in plasma glucose after mice are administered oral sucrose. The current study was undertaken to investigate the acute glycaemic effects of oral D‐tag alone or in combination with oral glucose in human subjects with and without type 2 diabetes mellitus. Glycaemic responses to D‐tag also were investigated in subjects after oral sucrose to examine whether the glucose‐lowering effects of D‐tag in rodents may result from a direct inhibition of intestinal disaccharidases. Methods : Eight normal and eight subjects with diabetes mellitus were administered 75 g of glucose, 75 g of D‐tag, or 75 g of D‐tag 30 min prior to a 75 g oral glucose tolerance test (OGTT). Five patients with diabetes mellitus were challenged with a 75 g oral sucrose tolerance test (OSTT) with and without oral pre‐treatment with 75 g of D‐tag. Patients with diabetes mellitus also received separate 0, 10, 15, 20 and 30 g of D‐tag 30 min prior to a 75 g OGTT. Results : Oral loading with D‐tag alone led to no changes in glucose or insulin levels in either normal patients or those with diabetes mellitus. Pre‐OGTT treatment with 75 g D‐tag, however, attenuated the rise in glucose levels in patients with diabetes mellitus (p < 0.02 at 60 and 180 min, and p < 0.01 at 120 min). The glucose area under the curve (AUC) was reduced significantly also by pre‐treatment with D‐tag in a dose‐dependent manner in patients with diabetes mellitus (p < 0.05 for 10 g D‐tag, p < 0.001 for 20 g D‐tag, and p = 0.0001 for 30 g D‐tag). In patients with diabetes mellitus 75 g D‐tag similarly attenuated the rise in glucose following an OSTT (p < 0.01 at 30 min, and p < 0.02 at 60 min). Pre‐treatment with 75 g D‐tag also tended to blunt the rise in insulin following an OGTT in normal patients (p = 0.07 for insulin AUC) but not patients with diabetes mellitus (p = 0.66). Following 75 g of oral D‐tag in four normal patients, plasma D‐tag levels rose to a mean peak level of 3.6 mg/dl at 90 min.The administration of 75 g d ‐tag led to diarrhoea, nausea and/or flatulence in 100% of subjects. When D‐tag was administered at lower doses ranging from 10 g to 30 g, only three of 10 patients with diabetes mellitus had gastrointestinal symptoms which were much more mild than those evoked by 75 g D‐tag. Conclusions : These results show that oral D‐tag significantly blunts the rise in plasma glucose seen after oral glucose in patients with diabetes mellitus in a dose‐dependent manner without significantly affecting insulin levels. The minimal elevation of plasma D‐tag levels in normal patients and the adverse gastrointestinal effects seen following larger doses of D‐tag support poor absorption of this hexose and suggest that D‐tag may act by attenuating glucose absorption in the intestine. D‐tag may be a useful therapeutic adjunct in the management of type 2 diabetes mellitus.