Both Isocarbohydrate and Hypercarbohydrate Fruit Preloads Curbed Postprandial Glycemic Excursion in Healthy Subjects

This study aimed to investigate the impact of fruit preloads on the acute postprandial glycemic response (PGR) and satiety response of a rice meal in healthy female subjects based on iso-carbohydrate (IC) and hyper-carbohydrate (HC) contents, respectively. The IC test meals including (1) rice preload (R + 35R), (2) orange preload (O + 35R), (3) apple preload (A + 35R) and (4) pear preload (P + 35R), contained 50.0 g available carbohydrates (AC) where the preload contributed 15.0 g and rice provided 35.0 g. The HC meals included (1) orange preload (O + 50R), (2) apple preload (A+50R) and (3) pear preload (P + 50R), each containing 65.0 g AC, where the fruits contributed 15.0 g and rice provided 50.0 g. Drinking water 30 min before the rice meal was taken as reference (W + 50R). All the preload treatments, irrespective of IC or HC meals, resulted in remarkable reduction (p < 0.001) in terms of incremental peak glucose (IPG) and the maximum amplitude of glycemic excursion in 180 min (MAGE0–180), also a significant decrease (p < 0.05) in the area of PGR contributed by per gram of AC (AAC), compared with the W + 50R. Apple elicited the lowest PGR among all test meals, as the A + 35R halved the IPG and slashed the incremental area under the curve in 180 min (iAUC0–180) by 45.7%, while the A + 50R reduced the IPG by 29.7%, compared with the W + 50R. All the preload meals and the reference meal showed comparable self-reported satiety in spite of the difference in AC. In conclusion, pre-meal consumption of three fruits effectively curbed post-meal glycemia even in the case of a 30% extra carbohydrate load.

Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis

Background/objectives Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. Methods We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. Results The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Recurrent Encephalopathy and Severe Anion Gap Metabolic Acidosis in a Patient with Short Bowel: It Is D-Lactic Acidosis

D-lactic acidosis is a rare and potentially underrecognized condition in patients with short bowel syndrome. We present the case of a 61-year-old female with a history of an ileojejunal bypass at age 18 who presented to hospital with acute-onset encephalopathy, ataxia, and severe anion gap metabolic acidosis (AGMA). On initial investigations there were no identifiable etiologies for the AGMA. Further history revealed that she had been experiencing these symptoms on a recurrent basis for the past 40 years. An oral carbohydrate load was given to the patient in hospital which reproduced her symptoms and the AGMA. A serum D-lactate level returned elevated several weeks later. A 2-month follow-up revealed that all her symptoms had ceased with limitation of carbohydrates to 150 g per day. Patients with short bowel syndrome are susceptible to developing D-lactic acidosis due to the large carbohydrate loads that are delivered to the colon, where they are then metabolized. Due to its rarity, it is likely that there is a delay in recognition of this condition. This case report describes a common clinical presentation of this rare condition and describes the pathophysiology, diagnosis, and management of D-lactic acidosis in small bowel syndrome.

Proposal of Meal Tolerance Test (MTT) For Investigating Ability of Insulin Secretion for Small Carbohydrate Load

Authors and collaborators have continued clinical practice and research on diabetes for long, and begun Low Carbohydrate Diet (LCD) at first in Japan. We have proposed super-, standard-, petite-LCD methods with 12%, 26%, 40% of carbohydrate, and developed medical and social LCD movement by Japanese LCD promotion association (JLCDPA). For research protocol, subjects were 10 healthy young medical staff. Two tests were 75gOGTT and meal tolerance test (MTT) of breakfast of super-LCD with 300kcal and 6g of carbohydrate. Blood glucose and immunoreactive insulin (IRI) were measured at 0 min and 30 min. Results of glucose and IRI in median value (0-30min) showed as follows: i) OGTT; 89.5 mg/dL to 130.5 mg/dL, 5.1 μU/mL to 40.6 μU/mL, ii) MTT; 93.5 mg/dL to 84.5 mg/dL, 4.9μU/mL to 10.6 μU/mL (significant increase, p<0.05). The increments of IRI for GTT (carbo-75g) and MTT (carbo-6g) were analyzed. There was a significant correlation between increments of IRI in GTT and MTT (p<0.05). Blood glucose in MTT tended to decrease from 0 min to 30 min. These results suggested that insulin secretion would be sufficient and relatively excessive for 6g of carbohydrate amount.

Comparison of the Acute Glycemic and Insulinemic Response of Fossence™, a Short Chain Fructo-Oligosaccharide, Taken Alone, Added or Substituted into a Carbohydrate Load

Objectives To explore the physiological response to ingestion of FossenceTM, a short chain fructo-oligosaccharide, when taken alone or when added or substituted into a carbohydrate load. Methods In a randomized, controlled, cross-over design, 25 healthy subjects completed three phases (phase 1: 13M:12F; 41 ± 14y; 24.4 ± 2.2 kg/m²; phase 2: 13M:12F; 40 ± 14y; 24.5 ± 2.4 kg/m²; phase 3: 13M:12F; 41 ± 14y; 24.3 ± 2.6 kg/m²; Mean ± SD). On separate days, each subject received in Phase 1: 10 g FossenceTM(10FOS), 10 g Dextrose (10Dex) or a water control (Control); Phase 2: 50 g Dextrose alone (50Dex), Dextrose with 15 g FossenceTM(50Dex + 15FOS), 35 g Dextrose alone (35Dex) or Dextrose with 15 g FossenceTM(35Dex + 15FOS); and Phase 3 received: 50 g available carbohydrate (avCHO) from white bread alone (50WB) or with 15 g FossenceTM(50WB + 15FOS), 35 g avCHO from white bread alone (35WB) or with 15 g FossenceTM(35WB + 15FOS). Blood samples were collected at fasting and over 2 hours after the start of the test meal and analyzed for glucose and insulin levels. The primary endpoint was differences in glucose IAUC. (ClinicalTrials.gov: NCT03755232). Results Phase 1: The glucose IAUC was significantly lower after 10FOS and Control compared to 10Dex (P &lt; 0.0001). Similarly, the insulin IAUC was significantly lower after Control and 10FOS compared to 10Dex (P &lt; 0.0001). Phase 2: The glucose IAUC was significantly lower after 35Dex and 35Dex + 15FOS compared to 50Dex (P &lt; 0.0001). Insulin IAUC was significantly lower after 35Dex compared to 50Dex and 50Dex + 15FOS, the IAUC of 35Dex + 15FOS was significantly lower than 50Dex (P &lt; 0.0003). Phase 3: The glucose IAUC was significantly lower after 35WB and 35WB + 15FOS compared to 50WB and 50WB + 15FOS (P &lt; 0.00001). Insulin IAUC was significantly lower after 35WB and 35WB + 15FOS compared to 50WB and 50WB + 15FOS (P &lt; 0.00001). Conclusions These studies demonstrate that FossenceTM, when consumed alone, does not increase postprandial glucose and insulin levels, indicating it is resistant to breakdown. When added to a carbohydrate load, no increase in postprandial glucose or insulin levels is observed while substitution of 30% of glycemic carbohydrate by FossenceTMsignificantly decreased postprandial glucose and insulin levels. FossenceTM, being sweet to taste, may be advised to individuals on restricted sugar intake. Funding Sources Tata Chemicals Ltd, India.

Efficacy of Isomaltulose Compared to Sucrose in Modulating Endothelial Function in Overweight Adults

Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low-glycemic index isomaltulose (Palatinose™) with that of sucrose in modulating EF, as assessed by flow-mediated dilation (FMD). In this double-blinded cross-over study, 80 overweight mildly hypertensive subjects were randomized to receive 50 g of either isomaltulose or sucrose. On two non-consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0–T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltulose compared to sucrose (ΔFMD = −0.003% and −0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltulose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p = 0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r-range = −0.20 to −0.23, p < 0.1). Sub-analysis suggested a lower FMD in insulin-resistant (IR) compared to insulin-sensitive subjects. Isomaltulose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltulose to preserve the endothelial function postprandially and consequently play a favorable role in cardiovascular health.

Metabolic consequences of perioperative oral carbohydrates in breast cancer patients — an explorative study

Background The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Trial of registration ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

Influence of pre-operative oral carbohydrate loading vs. standard fasting on tumor proliferation and clinical outcome in breast cancer patients ─ a randomized trial

Background Conflicting results have been reported on the influence of carbohydrates in breast cancer. Objective To determine the influence of pre-operative per-oral carbohydrate load on proliferation in breast tumors. Design Randomized controlled trial. Setting University hospital with primary and secondary care functions in South-West Norway. Patients Sixty-one patients with operable breast cancer from a population-based cohort. Intervention Per-oral carbohydrate load (preOp™) 18 and 2–4 h before surgery (n = 26) or standard pre-operative fasting with free consumption of tap water (n = 35). Measurements The primary outcome was post-operative tumor proliferation measured by the mitotic activity index (MAI). The secondary outcomes were changes in the levels of serum insulin, insulin-c-peptide, glucose, IGF-1, and IGFBP3; patients’ well-being, and clinical outcome over a median follow-up of 88 months (range 33–97 months). Results In the estrogen receptor (ER) positive subgroup (n = 50), high proliferation (MAI ≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p = 0.038). The CH group was more frequently progesterone receptor (PR) negative (p = 0.014). The CH group had a significant increase in insulin (+ 24.31 mIE/L, 95% CI 15.34 mIE/L to 33.27 mIE/L) and insulin c-peptide (+ 1.39 nM, 95% CI 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (− 0.26 nM; 95% CI − 0.46 nM to − 0.051 nM) compared to the fasting group. CH-intervention ER-positive patients had poorer relapse-free survival (73%) than the fasting group (100%; p = 0.012; HR = 9.3, 95% CI, 1.1 to 77.7). In the ER-positive patients, only tumor size (p = 0.021; HR = 6.07, 95% CI 1.31 to 28.03) and the CH/fasting subgrouping (p = 0.040; HR = 9.30, 95% CI 1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with relapse-free survival of 100% in the fasting group vs. 33% in the CH group (p = 0.015; HR = inf). The CH group reported less pain on days 5 and 6 than the control group (p < 0.001) but otherwise exhibited no factors related to well-being. Limitation Only applicable to T2 tumors in patients with ER-positive breast cancer. Conclusions Pre-operative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2 patients. Trial registration CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.