Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise.

AIMS: To evaluate the efficacy and safety of the selective sodium glucose co-transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise. METHODS: Patients received placebo or dapagliflozin (5 or 10 mg) once daily for 24 weeks. The primary outcome measure was change from baseline in glycated haemoglobin (HbA1c). RESULTS: Patients (N = 261) had modestly elevated baseline HbA1c (mean ≈ 7.5%) and most had mild or moderate renal impairment (estimated glomerular filtration rate range 43-103 ml/min/1.73 m(2)). Greater reductions in mean HbA1c level were observed with dapagliflozin (5 mg, -0.41%; 10 mg, -0.45%) than with placebo (-0.06%) at week 24 and these were greater in patients with higher baseline HbA1c levels. Fasting plasma glucose (FPG) was also significantly reduced with dapagliflozin (5 mg, -8.6 mg/dl; 10 mg, -13.7 mg/dl) compared with placebo (+5.8 mg/dl). Dapagliflozin significantly reduced body weight (5 mg, -2.13 kg; 10 mg, -2.22 kg) compared with placebo (-0.84 kg). Overall, 47.7 and 64.8% of patients with dapagliflozin 5 and 10 mg, respectively, and 51.7% with placebo experienced ≥ 1 adverse event, mostly mild or moderate, and unrelated to study treatment. Two patients on dapagliflozin 10 mg reported hypoglycaemia. Four patients across all groups reported events suggestive of genital infection and four of urinary tract infection. No events of pyelonephritis were reported. CONCLUSION: Dapagliflozin (5 and 10 mg) was well tolerated and effective in reducing HbA1c, FPG and body weight over 24 weeks in Japanese patients with T2DM inadequately controlled by diet and exercise.

Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.

AIMS: To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone. METHODS: This was a 52-week, randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n = 408), uptitrated over 18 weeks according to tolerability and glycaemic response to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin (≥ 1500 mg/day) with a 156-week double-blind extension period. Data over 104 weeks are reported here. RESULTS: In total, 53.1% of patients completed 104 weeks of treatment. After the greater initial decrease (0-18 weeks) in glycated haemoglobin (HbA1c) with glipizide, the 18-104-week HbA1c coefficient of failure (CoF) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year), resulting in significant dapagliflozin versus glipizide differences of -0.46%/year (95% CI -0.60,-0.33; p = 0.0001) for CoF and -0.18%(-2.0 mmol/mol) [95% CI -0.33(-3.6),-0.03(-0.3); p = 0.021] for 104-week HbA1c. Dapagliflozin produced sustained reductions in weight and systolic blood pressure, whereas glipizide increased weight and systolic blood pressure, giving 104-week dapagliflozin versus glipizide differences of -5.1 kg (95% CI: -5.7,-4.4) and -3.9 mmHg (95% CI: -6.1,-1.7), respectively. Over 104 weeks, the hypoglycaemia rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%), whereas patient proportions with events suggestive of genital infection and of urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%, respectively) than with glipizide (2.9 and 9.1%, respectively). CONCLUSIONS: Over 2 years, compared with glipizide, dapagliflozin demonstrated greater glycaemic durability, sustained reductions in weight and systolic blood pressure and a low hypoglycaemia rate; however, genital infections and UTIs occurred more frequently.

Health-related quality of life (EQ-5D) among type 2 diabetes mellitus patients treated with dapagliflozin over 2 years.

AIMS: This study evaluated health status and health-related quality of life (HRQOL) among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing glucose excretion, in a double-blind, randomised clinical trial. METHODS: Subjects with T2DM who had inadequate glycaemic control on metformin alone were enrolled in a 24-week, double-blind, randomised, placebo-controlled study with a 78-week extension period to evaluate the effect of dapagliflozin in combination with metformin. Subjects treated with dapagliflozin 10 mg + metformin (n = 89) were compared with subjects treated with placebo + metformin (n = 91) at baseline and at weeks 24, 50 and 102. EQ-5D change from baseline was derived from a repeated-measures mixed model, adjusting for baseline EQ-5D, treatment group, time point and use of rescue medication. RESULTS: Mean (SD) EQ-5D index was 0.85 (0.16) and 0.82 (0.15) at baseline and 0.85 (0.19) and 0.84 (0.19) at week 102 for dapagliflozin and placebo, respectively. The model indicated no change over 102 weeks in EQ-5D index scores in either treatment group. Mean (SD) EQ-5D visual analogue scale (VAS) was 72.5 (19.5) and 73.7 (15.6) at baseline and 79.8 (13.3) and 78.2 (12.1) at week 102 for dapagliflozin and placebo, respectively. The model indicated similar small improvements in EQ-5D VAS scores in both groups over 102 weeks. CONCLUSION: Patients maintained high HRQOL scores from baseline through week 102 in both treatment groups. Dapagliflozin, a novel SGLT2 inhibitor, did not adversely affect HRQOL over 2 years of treatment.

Changes in weight loss-related quality of life among type 2 diabetes mellitus patients treated with dapagliflozin.

AIMS: This study evaluated change in health-related quality of life (HRQOL) associated with ongoing weight change among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing urinary glucose excretion and is associated with body weight reductions. METHODS: Patients with T2DM who had inadequate glycaemic control on metformin (MET) alone were enrolled in a 24-week, double-blind, randomized, placebo-controlled study with a 78-week extension to evaluate the effect of dapagliflozin + MET on body weight. Patients also completed the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes Weight Questionnaire-9 (SHIELD-WQ-9), a weight change-related HRQOL survey. Difference in proportions of patients treated with dapagliflozin 10 mg + MET (n = 89) or placebo + MET (n = 91) who reported improvement in HRQOL was analysed with Fisher's exact test. RESULTS: Dapagliflozin patients had significantly greater weight loss than placebo patients over 102 weeks (p < 0.05). This corresponded to a numerically greater proportion of dapagliflozin-treated patients reporting ongoing weight loss and associated improvements in most HRQOL domains at three different evaluation points (weeks 24, 50 and 102) than placebo-treated patients. In a post-hoc analysis among patients who reported ongoing weight loss regardless of treatment arm, a significantly greater proportion of patients reporting weight loss versus weight gain reported improvements in physical health, self-esteem and overall HRQOL at weeks 24, 50 and 102. CONCLUSIONS: Dapagliflozin-induced weight loss was associated with improvement in overall HRQOL. Overall, ongoing weight loss was associated with improvements in several HRQOL domains compared with weight gain.

Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin.

AIMS: Dapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long-term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment. METHODS: This randomized, double-blind, placebo-controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.7 years; HbA1c 7.2%; body mass index (BMI) 31.9 kg/m(2) ; body weight 91.5 kg] inadequately controlled on metformin. Patients (N = 182) were randomly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 102, changes from baseline in HbA1c, weight, waist circumference, total body fat mass as measured by dual-energy X-ray absorptiometry (DXA), serum markers of bone turnover, bone mineral density (BMD) as measured by DXA, and adverse events were evaluated. RESULTS: A total of 140 patients (76.9%) completed the study. Over 102 weeks, dapagliflozin-treated patients showed reductions in HbA1c by -0.3%, weight by -4.54 kg, waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia. Compared with placebo, no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks. One fracture occurred in each treatment group. The frequency of urinary tract infection (UTI) and genital infection was similar in both treatment groups. CONCLUSIONS: Over 102 weeks, dapagliflozin improved glycaemic control, and reduced weight and fat mass, without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin.

[Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride]. / Effekt von Dapagliflozin bei Typ-2-Diabetikern mit unzureichender Blutzuckereinstellung unter Glimepirid.

AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10 %] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82 %, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1 %; hypoglycaemic events 4.8 versus 7.1-7.9 %; events suggestive of genital infection 0.7 versus 3.9-6.6 %; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9 %. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.

Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial.

AIM: Dapagliflozin is a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor under development as a treatment for type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of dapagliflozin monotherapy in Japanese T2DM patients with inadequate glycaemic control. METHODS: Patients (n = 279) were randomized to receive dapagliflozin (1, 2.5, 5 or 10 mg/day) or placebo once daily for 12 weeks. The primary endpoint was change from baseline in haemoglobin A1c (HbA1c) at week 12. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and proportion of patients achieving HbA1c <7.0% at week 12. RESULTS: Significant reductions in HbA1c were seen with all dapagliflozin doses (-0.11 to -0.44%) versus placebo (+0.37%). Reductions were also observed in FPG with dapagliflozin (-0.87 to -1.77 mmol/l [-15.61 to -31.94 mg/dl]) versus placebo (+0.62 mmol/l [+11.17 mg/dl]). No significant difference in the proportion of patients achieving HbA1c levels <7.0% was noted with dapagliflozin versus placebo. Adverse events (AEs) were more frequent with dapagliflozin (40.7-53.8%) versus placebo (38.9%) and were mostly mild/moderate in intensity. Three hypoglycaemic events were reported (1 each with placebo, dapagliflozin 2.5 mg and 10 mg). The frequency of signs and symptoms suggestive of urinary tract or genital infections was 0-3.8 and 0-1.8% respectively with dapagliflozin and 1.9 and 0% with placebo. No AEs of pyelonephritis were observed. CONCLUSIONS: Compared with placebo, dapagliflozin significantly reduced hyperglycaemia over 12 weeks with a low risk of hypoglycaemia in Japanese T2DM patients with inadequate glycaemic control.

Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.

AIMS: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment. METHODS: This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years; HbA1c 6.5-8.5%; BMI ≥ 25 kg/m(2) ; body weight ≤ 120 kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives. RESULTS: One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported. CONCLUSIONS: Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial.

AIMS: Progressive deterioration of glycaemic control in type 2 diabetes mellitus (T2DM) often requires treatment intensification. Dapagliflozin increases urinary glucose excretion by selective inhibition of renal sodium-glucose cotransporter 2 (SGLT2). We assessed the efficacy, safety and tolerability of dapagliflozin added to glimepiride in patients with uncontrolled T2DM. METHODS: This 24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicentre trial (ClinicalTrials.gov NCT00680745) enrolled patients with uncontrolled T2DM [haemoglobin A1c (HbA1c) 7-10%] receiving sulphonylurea monotherapy. Adult patients (n = 597) were randomly assigned to placebo or dapagliflozin (2.5, 5 or 10 mg/day) added to open-label glimepiride 4 mg/day for 24 weeks. Primary endpoint was HbA1c mean change from baseline at 24 weeks. Secondary endpoints included change in body weight and other glycaemic parameters. RESULTS: At 24 weeks, HbA1c adjusted mean changes from baseline for placebo versus dapagliflozin 2.5/5/10 mg groups were -0.13 versus -0.58, -0.63, -0.82%, respectively (all p < 0.0001 vs. placebo by Dunnett's procedure). Corresponding body weight and fasting plasma glucose values were -0.72, -1.18, -1.56, -2.26 kg and -0.11, -0.93, -1.18, -1.58 mmol/l, respectively. In placebo versus dapagliflozin groups, serious adverse events were 4.8 versus 6.0-7.1%; hypoglycaemic events 4.8 versus 7.1-7.9%; events suggestive of genital infection 0.7 versus 3.9-6.6%; and events suggestive of urinary tract infection 6.2 versus 3.9-6.9%. No kidney infections were reported. CONCLUSIONS: Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.

Herring (Clupea harengus) supplemented diet influences risk factors for CVD in overweight subjects.

OBJECTIVE: To assess the effect of a 4-week herring diet compared to a reference diet on biomarkers for cardiovascular disease in obese subjects. DESIGN: Randomized crossover trial. SETTING: Department of Internal Medicine, Sahlgrenska University Hospital. SUBJECTS: Fifteen healthy obese men and women (age 24-70 years) included, 13 completed. INTERVENTION: Subjects were randomly assigned to four weeks of herring diet (150 g baked herring fillets/day 5, days/week) or reference diet (pork and chicken fillets) and switched diets after 2 weeks washout. P-total cholesterol, p-TAG, p-HDL, p-HDL(2), p-HDL(3), p-LDL, p-apolipoprotein A, p-apolipoprotein B, p-Lipoprotein (a), p-fibrinogen, p-C- reactive protein and p-antioxidative capacity were analysed at 0,2,4,6,8 and 10 weeks. RESULTS: P-HDL was significantly higher after the herring diet period compared to after the reference diet period; 1.22 vs 1.13 mmol/l (P=0.036). There was a small, but not statistically significant, decrease in TAG but no effect on other biomarkers. TEAC and FRAP, but not ORAC-values, indicated that plasma antioxidants may have been reduced. CRP tended to be lower after the herring diet compared to after the reference diet. CONCLUSIONS: Consumption of oven-baked herring (150 g/day, 5 days/week) for 4 weeks, compared to consumption of pork and chicken fillets, significantly increased p-HDL. Patients with insulin resistance and obesity, who commonly have low HDL, may therefore benefit from addition of herring to the diet.

Food-related gastrointestinal symptoms in the irritable bowel syndrome.

BACKGROUND/AIMS: Postprandial symptoms are common in patients with irritable bowel syndrome (IBS). However, existing studies have come to different conclusions about the role of food in the pathophysiology of IBS. We explored the prevalence of subjective food-related gastrointestinal (GI) symptoms and its relationship to clinical characteristics and psychological factors in IBS. METHODS: 330 patients with IBS and 80 healthy volunteers completed a food questionnaire developed for this study. The subjects graded their subjective symptoms after 35 different foods and a food score was obtained by adding the item scores. The relationship between subjective food-related GI symptoms and referral status, IBS subgroup (predominant bowel pattern), sex, anxiety, depression and body mass index (BMI) was estimated. RESULTS: In 209 (63%) of the patients the GI symptoms were related to meals. Gas problems and abdominal pain were the most frequently reported symptoms. Foods rich in carbohydrates, as well as fatty food, coffee, alcohol and hot spices were most frequently reported to cause symptoms. The food score was higher in patients than in controls (p < 0.0001). In the IBS group higher scores were observed in patients with anxiety (p = 0.005), and females (p < 0.001), but the results were unrelated to IBS subgroup, referral status or BMI. The BMI did not differ between groups. CONCLUSION: A majority of IBS patients consider their symptoms to be related to meals. Especially foods rich in carbohydrates and fat cause problems. Nevertheless, the majority of IBS patients are normal or overweight. Female sex and anxiety predict a high degree of food-related symptoms in IBS.

Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study.

BACKGROUND: The ketohexose D-tagatose is a new sweetener with a low energy content. This low energy content may be due to either low absorption of the D-tagatose or decreased absorption of other nutrients. OBJECTIVE: The aims of this study were to measure the excretion of D-tagatose from the human small bowel, to calculate the apparent absorption of D-tagatose, and to study the effects of D-tagatose on the small-bowel excretion of other carbohydrates. DESIGN: A controlled diet was served for 2 periods of 2 d during 3 consecutive weeks to 6 ileostomy subjects. In one of the periods, 15 g D-tagatose was added to the diet daily. Duplicate portions of the diet and ileostomy effluents were freeze-dried and analyzed to calculate the apparent net absorption of D-tagatose and carbohydrates. RESULTS: Median D-tagatose excretion was 19% (range: 12-31%), which corresponded to a calculated apparent absorption of 81% (69-88%). Of the total amount of D-tagatose excreted [2.8 g (1.7-4.4 g)], 60% (8-88%) was excreted within 3 h. Between 3 and 5 h, 32% (11-82%) was excreted. Excretion of wet matter increased by 41% (24-52%) with D-tagatose ingestion. Sucrose and D-glucose excretion increased to a small extent, whereas no significant changes were found in the excretion of dry matter, energy, starch, or D-fructose. CONCLUSIONS: The apparent absorption of 15 g D-tagatose/d was 81%. D-Tagatose had only a minor influence on the apparent absorption of other nutrients.

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects.

OBJECTIVE: To study the short-term effect of resistant starch (RS) from retrograded high-amylose corn starch (HACS) on the excretion of bile acids and nutrients from the small bowel in humans. DESIGN: Seven healthy ileostomists were given a controlled, constant diet during three days. On days 2 and 3, 100 g/d of one of two test-products--drum-dried ordinary corn starch and autoclaved retrograded HACS, providing 5 and 39 g RS/d, respectively--was given, in random order. Ileostomy effluents were collected for 24 h per day and analysed for wet weight, dry weight, energy, bile acids and nutrients. SETTINGS: In-patient study at the metabolic ward, Department of Clinical Nutrition, Sahlgrenska University Hospital, Göteborg. RESULTS: Consumption of retrograded HACS caused (1) a 42% lower mean excretion of cholic acid (P = 0.024); (2) a 42% lower mean wet weight concentration of bile acids (P < 0.001); (3) a 70% increased excretion of dry weight (P = 0.001); and (4) a 41% increased excretion of energy (P= 0.036) compared with consumption of drum-dried ordinary corn starch. CONCLUSION: The reduced ileal excretion and concentration of cholic acid would be protective regarding colon cancer risk in addition to the increased fermentation substrate provided by RS and other energy-yielding components.

Small intestinal malabsorption and colonic fermentation of resistant starch and resistant peptides to short-chain fatty acids.

Some starch and protein, as well as fiber, remains unabsorbed in the small intestine and is degraded by anaerobic bacteria to short-chain fatty acids, hydrogen, methane, and carbon dioxide in the large intestine. The production of butyrate from starch has received the most attention, because butyrate seems to possess several important functions in the large bowel, including antineoplastic properties. In 16.6% fecal homogenates, starch polysaccharides, whether digestible or resistant to in vitro hydrolysis by amylase, pectin, and glucose, were all completely degraded to equal amounts of short-chain fatty acids (mean 60 wt/wt%; range 49-67 wt/wt%). However, starch that was resistant to hydrolysis by amylase was much more slowly fermented with the production of proportionally less butyrate and propionate than digestible starch (butyrate, 15 and 33%, respectively; propionate, 3 and 20%, respectively). The daily intake of 35 g resistant starch (100 g amylomaize starch) by 7 ileostomy subjects increased ileal dry-matter effluent by 38 +/- 2 g/day, due exclusively to increased excretion of carbohydrates of nonfiber origin (starch-polysaccharides and oligo- and monosaccharides) from 14 +/- 1 to 51 +/- 2 g/day, with no change in excreted nonstarch polysaccharides, nitrogen, and ileal volume. The ileal excreted resistant starch increased the formation of total short-chain fatty acids by 50% in fecal homogenates incubated with ileal dry matter from the amylomaize starch period, with comparatively little effect on the ratio of produced butyrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Digestion and absorption of sorbitol, maltitol and isomalt from the small bowel. A study in ileostomy subjects.

OBJECTIVE: To quantify small bowel digestion and absorption of sorbitol, isomalt and maltitol in ileostomy patients and estimate the metabolizable energy. SUBJECTS: Study A: Nine ileostomy patients, under a constant controlled diet, ate during three consecutive days 2 milk chocolate bars per day, containing 2 x 15 g of polyol, each day with another polyol in random order. The first bar was taken 30 min after breakfast, and the second bar, 7 h after breakfast. Effluents were recovered during the whole study. Study B: 5, 10 or 20 g of sorbitol or isomalt were consumed each day in a drink during two 3-day periods by two ileostomy subjects. The recovery in the ileal effluent was measured over 24 h. RESULTS: Study A: Carbohydrate recovery in ileostomy effluent was 26.8 +/- 2.8% (mean+SEM) for sorbitol, 24.8 + 5.7% for maltitol (2/3 as sorbitol) and 40.0 +/- 0.7% for isomalt (1/3 being sorbitol and mannitol). Ileal excretion, compared with a day without polyol, was compared in 4 subjects. The total volume excreted, as well as dry matter increased after polyol consumption. When taking this extra loss into account, the metabolizable energy value of the polyols for 2 x 15 g intake were: sorbitol, 12 kJ/g (2.8 kcal/g); maltitol, 13 kJ/g (3.1 kcal/g); isomalt, 9 kJ/g (2.1 kcal/g). Study B: The level of digestion and absorption of both sugar alcohols was dose dependent. CONCLUSIONS: These results indicate that sorbitol, maltitol and isomalt are rather extensively absorbed, but the digestibility of the other nutrients is also reduced, due to the osmotic load caused by the polyols in the small intestine. There are evidences of a dose dependency of the energy value of the polyols.

Sugar-beet fibre increases cholesterol and reduces bile acid excretion from the small bowel.

The effect of addition of sugar-beet fibre to the diet on sterol excretion from the small intestine was studied in nine ileostomy subjects. A constant low-fibre diet was given in two 3 d periods with and without 32 g sugar-beet fibre/d in random order. Care was taken to minimize bacterial alteration of the ileostomy contents. The addition of sugar-beet fibre increased net cholesterol excretion by 52 (SE 9)% (P < 0.01), from 294 (SE 99) to 451 (SE 124) mg/d, and decreased bile acid excretion by 26 (SE 15)% (P < 0.01), from 764 (SE 118) to 567 (SE 96) mg/d. The increased cholesterol and decreased bile acid excretion found with sugar-beet fibre addition is different from the pattern associated with fibre sources such as pectin and oat fibre. The interaction between dietary fibre and sterol metabolism may be mediated, therefore, by different mechanisms depending on the fibre source.

Structural features of resistant starch at the end of the human small intestine.

Structural features of in vivo resistant starch were assessed using the ileal contents of four humans. Two of the latter were collected by ileostomy after ingestion of bean flakes or potato flakes and the other two were collected by an intubation technique after ingestion of retrograded high-amylose maize starch or complexed high-amylose maize starch. The degree of polymerizations (DP), solubility and crystallinity were assessed. For all samples, starch fractions which escaped digestion in the small intestine were composed of three populations of alpha-glucans with proportions differing according to the substrate. Small quantities of oligosaccharides made up the first population, illustrating a limitation of absorption in the small intestine. The second population, the main resistant fraction, was comprised of retrograded amylose of mean DPn of about 35 glucose units with a melting temperature at 150 degrees C and exhibiting a B-type pattern. Finally high molecular weight semi-crystalline alpha-glucans were attributed to fragments of starch. This study showed that some potentially digestible starch could reach the colon and crystalline fractions constituted only part of the starch that escaped digestion in the human small intestine.

Nutrients excreted in ileostomy effluents after consumption of mixed diets with beans or potatoes. I. Minerals, protein, fat and energy.

The small intestinal excretion of protein, fat, energy, magnesium, calcium, iron and zinc from two isocaloric diets including either instant bean flakes (174 g/d) or potato flakes (102 g/d) was studied in seven ileostomy subjects. Out of the variable part of the diet all starch and dietary fibre, and about half of the energy was provided from bean flakes or potato flakes, respectively. The small variation in ileostomy excretion between two consecutive days, after one adaptation day, suggests that ileostomy studies can be performed with reasonable precision in 2 days. During the 2-day potato period average daily excretions of gross energy and protein were 236 kcal (988 kJ; 11 per cent of intake) and 13 g (12 per cent), respectively. The excretions were significantly (P less than 0.001) higher during the bean period, 378 kcal (1582 kJ; 16 per cent) and 17 g (15 per cent). Fat intake and excretion were not different. After making allowance for dietary fibre, the apparent nutrient energy digestibilities were over 90 per cent, with only 43 kcal (180 kJ; 2 per cent) difference between the two periods. Apparent absorption of magnesium was lower during the bean period, 7 per cent compared to 25 per cent (P less than 0.02). The study has thus shown that only slightly less apparent small intestinal absorption occurs from a diet with bean flakes compared to potato flakes, so the nutritional consequences of beans on other nutrients seem to be small.

Nutrients excreted in ileostomy effluents after consumption of mixed diets with beans or potatoes. II. Starch, dietary fibre and sugars.

The extent of carbohydrate digestion and absorption from two diets including either instant bean flakes (174 g/d) or potato flakes (102 g/d) was measured in seven ileostomy subjects during a 2-day period. Test foods contributed 40 per cent of the total dietary starch intake (160 g/d), the remainder coming from rice and white bread. Overall, 4 per cent and 0.7 per cent of the dietary starch consumed remained unabsorbed during the bean and potato periods, respectively. Between 9.0 and 10.9 per cent of dietary bean starch and less than 1.7 per cent of potato starch were not absorbed. Dietary fibre and resistant starch were completely recovered in ileostomy effluents. In separate meal tests with 40 g starch, beans gave lower blood glucose (P less than 0.05) and serum insulin (P less than 0.01) responses than potatoes. Dietary starch malabsorption from leguminous foods is less than previously estimated and does not explain the attenuated glycaemic and insulinaemic responses.