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

Aim: D-Tagatose (D-tag), a hexose bulk sweetener, does not affect plasma gl ucose levels when orally administered to rodents. Additionally, D-tag atten uates 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 als o were investigated in subjects after oral sucrose to examine whether the g lucose-lowering effects of D-tag in rodents may result from a direct inhibi tion of intestinal disaccharidases. Methods: Eight normal and eight subjects with diabetes mellitus were admini stered 75 g of glucose, 75 g of D-tag, or 75 g of D-tag 30 min prior to a 7 5 g oral glucose tolerance test (OGTT). Five patients with diabetes mellitu s were challenged with a 75 g oral sucrose tolerance test (OSTT) with and w ithout oral pre-treatment with 75 g of D-tag. Patients with diabetes mellit us 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 insu lin levels in either normal patients or those with diabetes mellitus. Pre-O GTT treatment with 75 g D-tag, however, attenuated the rise in glucose leve ls 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 signif icantly also by pre-treatment with D-tag in a dose-dependent manner in pati ents 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 < 0.0 1 at 30 min, and p < 0.02 at 60 min). Pre-treatment with 75 g D-tag also te nded 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 r ose 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 ri se in plasma glucose seen after oral glucose in patients with diabetes mell itus in a dose-dependent manner without significantly affecting insulin lev els. The minimal elevation of plasma D-tag levels in normal patients and th e adverse gastrointestinal effects seen following larger doses of D-tag sup port poor absorption of this hexose and suggest that D-tag may act by atten uating glucose absorption in the intestine. D-tag may be a useful therapeut ic adjunct in the management of type 2 diabetes mellitus.