Comparison of the effects of slowly and rapidly absorbed carbohydrates on postprandial glucose metabolism in type 2 diabetes mellitus patients: a randomized trial.

BACKGROUND: Isomaltulose attenuates postprandial glucose and insulin concentrations compared with sucrose in patients with type 2 diabetes mellitus (T2DM). However, the mechanism by which isomaltulose limits postprandial hyperglycemia has not been clarified. OBJECTIVE: The objective was therefore to assess the effects of bolus administration of isomaltulose on glucose metabolism compared with sucrose in T2DM. DESIGN: In a randomized, double-blind, crossover design, 11 participants with T2DM initially underwent a 3-h euglycemic-hyperinsulinemic (0.8 mU · kg(-1) · min(-1)) clamp that was subsequently combined with 1 g/kg body wt of an oral (13)C-enriched isomaltulose or sucrose load. Hormonal responses and glucose kinetics were analyzed during a 4-h postprandial period. RESULTS: Compared with sucrose, absorption of isomaltulose was prolonged by ∼50 min (P = 0.004). Mean plasma concentrations of insulin, C-peptide, glucagon, and glucose-dependent insulinotropic peptide were ∼10-23% lower (P < 0.05). In contrast, glucagon-like peptide 1 (GLP-1) was ∼64% higher (P < 0.001) after isomaltulose ingestion, which results in an increased insulin-to-glucagon ratio (P < 0.001) compared with sucrose. The cumulative amount of systemic glucose appearance was ∼35% lower after isomaltulose than after sucrose (P = 0.003) because of the reduction in orally derived and endogenously produced glucose and a higher first-pass splanchnic glucose uptake (SGU). Insulin action was enhanced after isomaltulose compared with sucrose (P = 0.013). CONCLUSIONS: Ingestion of slowly absorbed isomaltulose attenuates postprandial hyperglycemia by reducing oral glucose appearance, inhibiting endogenous glucose production (EGP), and increasing SGU compared with ingestion of rapidly absorbed sucrose in patients with T2DM. In addition, GLP-1 secretion contributes to a beneficial shift in the insulin-to-glucagon ratio, suppression of EGP, and enhancement of SGU after isomaltulose consumption. This trial was registered at clinicaltrials.gov as NCT01070238.

Studies on absorption and metabolism of palatinose (isomaltulose) in rats.

We evaluated the absorption and metabolism of palatinose in rats by the carbohydrate load test and the 13C- and H2-breath tests. We compared the results of these tests with those of sucrose, since sucrose is an isomer of palatinose and generally known to be degraded and absorbed from the small intestine. In the carbohydrate load test, blood glucose and plasma insulin levels after oral administration of palatinose rose more gradually and reached a maximum that was lower than that after sucrose administration. In the 13C-breath test, rats were orally administrated [1-13C]sucrose or [1-13C]palatinose and housed in a chamber. The expired air in the chamber was collected, and the level of 13CO2 in the expired air was measured at appropriate intervals for 360 min. The value of time taken to reach the maximum concentration for expired 13CO2 from [1-13Cglucose] ([1-13Cglc]) and [1-13Cfructose] ([1-13Cfru]) palatinose was significantly longer than that from [1-13Cglc] and [1-13Cfru]sucrose, respectively. The value of area under the curve (AUC) for [1-13Cglc]palatinose was larger than that for [1-13Cglc]sucrose, but AUC for [1-13Cfru] showed no difference between palatinose and sucrose. In the H2-breath test, the concentration of H2 in the expired air was measured for 420 min. H2 was hardly detected with both palatinose and sucrose and no significant difference was observed between the two groups. These results suggest that palatinose is utilised in vivo at a rate equal to that of sucrose.

Role of periplasmic trehalase in uptake of trehalose by the thermophilic bacterium Rhodothermus marinus.

Trehalose uptake at 65 degrees C in Rhodothermus marinus was characterized. The profile of trehalose uptake as a function of concentration showed two distinct types of saturation kinetics, and the analysis of the data was complicated by the activity of a periplasmic trehalase. The kinetic parameters of this enzyme determined in whole cells were as follows: Km = 156 +/- 11 microM and Vmax = 21.2 +/- 0.4 nmol/min/mg of total protein. Therefore, trehalose could be acted upon by this periplasmic activity, yielding glucose that subsequently entered the cell via the glucose uptake system, which was also characterized. To distinguish the several contributions in this intricate system, a mathematical model was developed that took into account the experimental kinetic parameters for trehalase, trehalose transport, glucose transport, competition data with trehalose, glucose, and palatinose, and measurements of glucose diffusion out of the periplasm. It was concluded that R. marinus has distinct transport systems for trehalose and glucose; moreover, the experimental data fit perfectly with a model considering a high-affinity, low-capacity transport system for trehalose (Km = 0.11 +/- 0.03 microM and Vmax = 0.39 +/- 0.02 nmol/min/mg of protein) and a glucose transporter with moderate affinity and capacity (Km = 46 +/- 3 microM and Vmax = 48 +/- 1 nmol/min/mg of protein). The contribution of the trehalose transporter is important only in trehalose-poor environments (trehalose concentrations up to 6 microM); at higher concentrations trehalose is assimilated primarily via trehalase and the glucose transport system. Trehalose uptake was constitutive, but the activity decreased 60% in response to osmotic stress. The nature of the trehalose transporter and the physiological relevance of these findings are discussed.

Control of oxidative stress and metabolic homeostasis by the suppression of postprandial hyperglycemia.

Repeated mental stress may lead to chronic alterations in cortisol and catecholamine concentrations and to insulin resistance. Furthermore, chronically elevated cortisol concentrations may favour the development of abdominal obesity and of the metabolic syndrome. Oxidative stress impairs glucose uptake in muscle and fat and correlates with BMI. Obese subjects with type 2 diabetes, especially soon after the onset of diabetes, usually exhibit postprandial hyperglycemia with delayed hyperinsulinemia. It is recognized that insulin resistance causes postprandial hyperglycemia; however, it is also possible that impairment of early insulin secretion in response to an oral glucose load is the reason why postprandial hyperglycemia occurs. Since even modest increases in postprandial glucose values can be a risk factor for cardiovascular disease. Therefore, the effects of palatinose based functional food which reduces postprandial hyperglycemia and hyperinsulinemia were investigated in rats. This novel food definitely reduced visceral fat accumulation and improved insulin sensitivity. Therefore, it is suggested that functional food which suppresses postprandial glucose level is beneficial for both stress and metabolic controls.

Isomaltulose (Palatinose): a review of biological and toxicological studies.

Isomaltulose is a natural occurring disaccharide composed of alpha-1,6-linked glucose and fructose. Commercial isomaltulose is produced from sucrose by enzymatic rearrangement and has been used as a sugar in Japan since 1985. It is particularly suitable as a non-cariogenic sucrose replacement and is favorable in products for diabetics and prediabetic dispositions. In vivo studies with rats and pigs indicate that isomaltulose is completely hydrolyzed and absorbed in the small intestine. This is supported by in vitro studies showing that intestinal disaccharidases from various species (including man) can hydrolyze isomaltulose. The rate of hydrolysis, however, is very slow compared with sucrose and maltose. Thus, blood glucose and insulin levels in humans after oral administration rise slower and reach lower maxima than after sucrose administration. After absorption, fructose and glucose are metabolized as typical for these monosaccharides. From intravenous studies it can be assumed that any systemic isomaltulose would be hydrolyzed as well, or excreted in urine. In several subchronic toxicity studies, the administration of large doses (up to 7.0 and 8.1 g/kg body weight/day in male and female rats, respectively) of isomaltulose, did not result in adverse effects. Isomaltulose induced neither embryotoxic or teratogenic effects in rat foetuses, nor maternal toxicity at levels up to 7 g/kg body weight/day. Isomaltulose was non-mutagenic in the Ames test. As hydrolysis in the small intestine is complete, even high levels of isomaltulose are well tolerated in animals and humans. In studies with healthy as well as diabetic subjects high doses up to 50 g were tolerated without signs of intestinal discomfort. On the basis of the data reviewed it is concluded that the use of isomaltulose as an alternative sugar is as safe as the use of other digestible sugars consisting of glucose and fructose.