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The mixed meal tolerance test (MMTT) and oral glucose tolerance test (OGTT) are used in the diagnosis of prediabetes and hypoglycaemia. Data suggest that oxidative stress caused by hyperglycaemia during OGTT may have adverse metabolic effects in prediabetic patients. In this study, we aimed to evaluate oxidant and antioxidant levels in OGTT and MMTT.The study included 72 patients who underwent MMTT and OGTT at one-week intervals. Total Oxidant Status (TOS) and total antioxidant status (TAS) levels were analysed in samples taken from patients at zero, first and second hours of MMTT and OGTT and Oxidative Stress Index (OSI) was calculated, and the data were compared.OGTT and MMTT results were compared with each other within the patient group. While significant differences were found between first-hour glucose, TOS and OSI values (p<0.01), no significant differences were observed for zero and second-hour values (p>0.05). There was no significant difference in TAS values (p>0.05). When zero, first, and second-hour results were compared for OGTT and MMTT within the same test, no significant differences were found for the other parameters except for glucose (p<0.01 for both tests). The correlation between glucose and TOS, TAS and OSI values in MMTT and OGTT was not found.Our study concludes that the body experiences more oxidative stress in the first hour following an OGTT than the oxidative stress induced by hyperglycaemia in a mixed-meal diet. Further research is needed to determine whether oxidative stress in the first hour triggers dysmetabolic events in the body. [ABSTRACT FROM AUTHOR]

Context Distinguishing different types of diabetes is important in directing optimized treatment strategies and correlated epidemiological studies. Objective Through detailed analysis of hormone responses to mixed meal tolerance test (MMTT), we aimed to find representing characteristics of post-acute pancreatitis diabetes mellitus (PPDM-A) and post-chronic pancreatitis diabetes mellitus (PPDM-C). Methods Participants with PPDM-A, PPDM-C, type 1 diabetes, type 2 diabetes, and normal controls (NCs) underwent MMTT. Fasting and postprandial responses of serum glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, gastric inhibitory peptide (GIP), glucagon like peptide-1 (GLP-1), and peptide YY (PYY) were detected and compared among different groups. Focused analysis on calculated insulin sensitivity and secretion indices were performed to determine major causes of hyperglycemia in different conditions. Results Participants with PPDM-A were characterized by increased C-peptide, insulin, glucagon, and PP, but decreased ghrelin, GIP, and PYY compared with NCs. Patients with PPDM-C showed secretion insufficiency of C-peptide, insulin, ghrelin, and PYY, and higher postprandial responses of glucagon and PP than NCs. In particular, both fasting and postprandial levels of ghrelin in PPDM-C were significantly lower than other diabetes groups. PYY responses in patients with PPDM-A and PPDM-C were markedly reduced. Additionally, the insulin sensitivity of PPDM-A was decreased, and the insulin secretion for PPDM-C was decreased. Conclusion Along with the continuum from acute to chronic pancreatitis, the pathological mechanism of PPDM changes from insulin resistance to insulin deficiency. Insufficient PYY secretion is a promising diagnostic marker for distinguishing PPDM from type 1 and type 2 diabetes. Absent ghrelin secretion to MMTT may help identify PPDM-C. [ABSTRACT FROM AUTHOR]

Background/aim: Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology. Method: A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms. Result: Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and Cpeptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms. Conclusion: These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology. [ABSTRACT FROM AUTHOR]

Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial. [ABSTRACT FROM AUTHOR]

Postprandial reactive hypoglycemia, or late dumping syndrome, is a common but underrecognized complication from bypass surgery. We report an unusual case of postprandial reactive hypoglycemia in a patient with a severe esophageal stricture from corrosive agent ingestion who underwent ileocolic interposition and an antecolic Billroth‐II gastrojejunostomy. A 22‐year‐old male patient with a one‐year history of corrosive ingestion was referred to the hospital for a surgical correction of severe esophageal stricture. After the patient underwent ileocolic interposition and an antecolic Billroth‐II gastrojejunostomy, he experienced multiple episodes of gastroesophageal refluxsymptoms during nasogastric feeding and had onset of hypoglycemic symptoms. His plasma glucose level was 59 mg/dL. After we had intraoperatively re‐inserted a jejunostomy tube bypassing the ileocolic interposition, and reintroduced enteral nutrition, his hypoglycemic symptoms resolved. We performed a mixed meal tolerance test by nasogastric tube, but the results did not show postprandial hypoglycemia. Although the specific mechanism is unclear, this case suggests gastroesophageal reflux to the ileal interposition may have caused a state of exaggerated hyperinsulinemic response and rebound hypoglycemia. To the best of our knowledge, we are the first to report case of postprandial hypoglycemia after ileocolic interposition, which may have been caused by exaggerated hyperinsulinemic response due to gastroesophageal reflux to the ileal interposition. This syndrome should be considered in the patient who has had ileocolic interposition surgery and has developed postprandial hypoglycemia. [ABSTRACT FROM AUTHOR]

Abstract Postprandial reactive hypoglycemia, or late dumping syndrome, is a common but underrecognized complication from bypass surgery. We report an unusual case of postprandial reactive hypoglycemia in a patient with a severe esophageal stricture from corrosive agent ingestion who underwent ileocolic interposition and an antecolic Billroth‐II gastrojejunostomy. A 22‐year‐old male patient with a one‐year history of corrosive ingestion was referred to the hospital for a surgical correction of severe esophageal stricture. After the patient underwent ileocolic interposition and an antecolic Billroth‐II gastrojejunostomy, he experienced multiple episodes of gastroesophageal refluxsymptoms during nasogastric feeding and had onset of hypoglycemic symptoms. His plasma glucose level was 59 mg/dL. After we had intraoperatively re‐inserted a jejunostomy tube bypassing the ileocolic interposition, and reintroduced enteral nutrition, his hypoglycemic symptoms resolved. We performed a mixed meal tolerance test by nasogastric tube, but the results did not show postprandial hypoglycemia. Although the specific mechanism is unclear, this case suggests gastroesophageal reflux to the ileal interposition may have caused a state of exaggerated hyperinsulinemic response and rebound hypoglycemia. To the best of our knowledge, we are the first to report case of postprandial hypoglycemia after ileocolic interposition, which may have been caused by exaggerated hyperinsulinemic response due to gastroesophageal reflux to the ileal interposition. This syndrome should be considered in the patient who has had ileocolic interposition surgery and has developed postprandial hypoglycemia.

Objective: The aims were (1) to assess beta‐cell function in GCK diabetes patients over 2‐year period; (2) to evaluate the dynamics of beta‐cell function in HNF1A and KCNJ11 patients after treatment optimization; using mixed meal tolerance test (MMTT) as a gold standard for non‐invasive beta‐cell function assessment. Research Design and Methods: Twenty‐two GCK diabetes patients, 22 healthy subjects, 4 patients with HNF1A and 2 with KCNJ11 were recruited. Firstly, beta‐cell function was compared between GCK patients versus controls; the dynamics of beta‐cell function were assessed in GCK patients with two MMTTs in 2‐year period. Secondly, the change of beta‐cell function was evaluated in HNF1A and KCNJ11 patients after successful treatment optimization in 2‐year period. Results: GCK diabetes patients had lower area under the curve (AUC) of C‐peptide (CP), average CP and peak CP compared to controls. Also, higher levels of fasting, average, peak and AUC of glycemia during MMTT were found in GCK patients compared to healthy controls. No significant changes in either CP or glycemia dynamics were observed in GCK diabetes group comparing 1st and 2nd MMTTs. Patients with HNF1A and KCNJ11 diabetes had significantly improved diabetes control 2 years after the treatment was optimized (HbA1c 7.1% vs. 5.9% [54 mmol/mol vs. 41 mmol/mol], respectively, p = 0.028). Higher peak CP and lower HbA1c were found during 2nd MMTT in patients with targeted treatment compared to the 1st MMTT before the treatment change. Conclusion: In short‐term perspective, GCK diabetes group revealed no deterioration of beta‐cell function. Individualized treatment in monogenic diabetes showed improved beta‐cell function. [ABSTRACT FROM AUTHOR]

Abstract Background Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM). Methods To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m2) received Boost® high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2) ingested either Boost® high Protein 20 g protein or the isocaloric Boost® high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV). Results Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%). Conclusion MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses. Trial registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093

Aim: To gain further insights into the efficacy of SAR425899, a dual glucagon‐like peptide‐1/glucagon receptor agonist, by providing direct comparison with the glucagon‐like peptide‐1 receptor agonist, liraglutide, in terms of key outcomes of glucose metabolism. Research Design and Methods: Seventy overweight to obese subjects with type 2 diabetes (T2D) were randomized to receive once‐daily subcutaneous administrations of SAR425899 (0.12, 0.16 or 0.20 mg), liraglutide (1.80 mg) or placebo for 26 weeks. Mixed meal tolerance tests were conducted at baseline (BSL) and at the end of treatment (EOT). Metabolic indices of insulin action and secretion were assessed via Homeostasis Model Assessment (HOMA2) and oral minimal model (OMM) methods. Results: From BSL to EOT (median [25th, 75th] percentile), HOMA2 quantified a significant improvement in basal insulin action in liraglutide (35% [21%, 74%]), while secretion enhanced both in SAR425899 (125% [63%, 228%]) and liraglutide (73% [43%, 147%]). OMM quantified, both in SAR425899 and liraglutide, a significant improvement in insulin sensitivity (203% [58%, 440%] and 36% [21%, 197%]), basal beta‐cell responsiveness (67% [34%, 112%] and 40% [16%, 59%]), and above‐basal beta‐cell responsiveness (139% [64%, 261%] and 69% [−15%, 120%]). A significant delay in glucose absorption was highlighted in SAR425899 (37% [52%,18%]). Conclusions: SAR425899 and liraglutide improved postprandial glucose control in overweight to obese subjects with T2D. A significantly higher enhancement in beta‐cell function was shown by SAR425899 than liraglutide. [ABSTRACT FROM AUTHOR]

Summary: When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. Introduction: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. Methods: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21–59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. Results: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). Conclusion: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health. [ABSTRACT FROM AUTHOR]

Background: Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM). Methods: To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m2) received Boost®high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2) ingested either Boost®high Protein 20 g protein or the isocaloric Boost®high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV). Results: Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%). Conclusion: MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses. Trial registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this parallel-group, double-blinded (study personnel and participants), randomised clinical trial was to assess the interaction between metformin and exercise training on postprandial glucose in glucose-intolerant individuals. Methods: Glucose-intolerant (2 h OGTT glucose of 7.8–11.0 mmol/l and/or HbA1c of 39–47 mmol/mol [5.7–6.5%] or glucose-lowering-medication naive type 2 diabetes), overweight/obese (BMI 25–42 kg/m2) individuals were randomly allocated to a placebo study group (PLA, n = 15) or a metformin study group (MET, n = 14), and underwent 3 experimental days: BASELINE (before randomisation), MEDICATION (after 3 weeks of metformin [2 g/day] or placebo treatment) and TRAINING (after 12 weeks of exercise training in combination with metformin/placebo treatment). Training consisted of supervised bicycle interval sessions with a mean intensity of 64% of Wattmax for 45 min, 4 times/week. The primary outcome was postprandial glucose (mean glucose concentration) during a mixed meal tolerance test (MMTT), which was assessed on each experimental day. For within-group differences, a group × time interaction was assessed using two-way repeated measures ANOVA. Between-group changes of the outcomes at different timepoints were compared using unpaired two-tailed Student's t tests. Results: Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group (∆PLA: −0.7 [95% CI −1.4, 0.0] mmol/l, p = 0.05 and ∆MET: −0.7 [−1.5, −0.0] mmol/l, p = 0.03), with no between-group difference (p = 0.92). In PLA, the entire reduction was seen from MEDICATION to TRAINING (−0.8 [−1.3, −0.1] mmol/l, p = 0.01). Conversely, in MET, the entire reduction was observed from BASELINE to MEDICATION (−0.9 [−1.6, −0.2] mmol/l, p = 0.01). The reductions in mean glucose concentration during the MMTT from BASELINE to TRAINING were dependent on differential time effects: in the PLA group, a decrease was observed at timepoint (t) = 120 min (p = 0.009), whereas in the MET group, a reduction occurred at t = 30 min (p < 0.001). V̇O2peak increased 15% (4.6 [3.3, 5.9] ml kg−1 min−1, p < 0.0001) from MEDICATION to TRAINING and body weight decreased (−4.0 [−5.2, −2.7] kg, p < 0.0001) from BASELINE to TRAINING, with no between-group differences (p = 0.7 and p = 0.5, respectively). Conclusions/interpretation: Metformin plus exercise training was not superior to exercise training alone in improving postprandial glucose. The differential time effects during the MMTT suggest an interaction between the two modalities. Funding: The Beckett foundation, A.P Møller Foundation, DDA, the Research Foundation of Rigshospitalet and Trygfonden. Trial registration: ClinicalTrials.gov (NCT03316690). [ABSTRACT FROM AUTHOR]

Purpose: Precise evaluation of serum testosterone levels is important in making an accurate diagnosis of androgen deficiency. Recent practice guidelines on male androgen deficiency recommend that testosterone be measured in the morning while fasting. Although there is ample evidence regarding morning measurement of testosterone, studies that evaluated the effect of glucose load or meals were limited by inclusion of hypogonadal or diabetic men, and measurement of testosterone was not performed using mass spectrometry.Methods: Sixty men (23-97 years) without pre-diabetes or diabetes who had normal total testosterone (TT) levels underwent either an oral glucose tolerance test (OGTT) or a mixed meal tolerance test (MMTT) after an overnight fast. Serum samples were collected before and at regular intervals for 2 h (OGTT cohort) or 3 h (MMTT cohort). TT was measured by LC-MS/MS. LH and prolactin were also measured.Results: TT decreased after a glucose load (mean drop at nadir = 100 ng/dL) and after a mixed meal (drop at nadir = 123 ng/dL). Approximately 11% of men undergoing OGTT and 56% undergoing MMTT experienced a transient decrease in TT below 300 ng/dL, the lower normal limit. Testosterone started declining 20 min into the tests, with average maximum decline at 60 min. Most men still had TT lower than baseline at 120 min. This effect was independent of changes in LH or prolactin.Conclusion: A glucose load or a mixed meal transiently, but significantly, lowers TT levels in healthy, non-diabetic eugonadal men. These findings support the recommendations that measurement of serum testosterone to diagnose androgen deficiency should be performed while fasting. [ABSTRACT FROM AUTHOR]

Background The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery. Methods A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUC (ΔAUC) were compared between the two groups. Results One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC0′–180′ of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC0′–180′ for hunger and ΔAUC0′–180′ for desire to eat in the GB group, while negatively correlated with ΔAUC0′–180′ for fullness in the SG group. Discussion Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery.

Background: The aim of the study was to investigate the different B-cell responses after a glucagon stimulation test (GST) versus mixed meal tolerance test (MMTT).Methods: We conducted GST and MMTT in 10 healthy people (aged 25-40 years) and measured C-peptide, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) at different time points after the administration of 1 mg i.v. glucagon for GST or a liquid mixed meal for MMTT.Results: The GST stimulated C-peptide showed a mean increase of 147.1%, whereas the mean increase of MMTT stimulated C-peptide was 99.82% (Δincrease = 47.2%). Maximum C-peptide level reached with the MMTT was greater than that obtained with the GST (C-pept max MMTT = 2.35 nmol/L vs C-pep max GST = 1.9 nmol/L). A positive and linear correlation was found between the GST incremental area under the curve C-peptide and the MMTT incremental area under the curve C-peptide (r = 0.618, P = .05). After GST, there was no increment of GIP and glucagon like peptide-1 levels compared to baseline levels. A positive and linear correlation between GIP and C-peptide levels was observed only for the MMTT (r = 0.922, P = .008) indicating that in the GST, the C-peptide response is independent of the incretin axis response.Conclusions: Although the 2 stimulation tests may elicit a similar response in C-peptide secretion, B-cell response to MMTT depends on a functionally normal incretin axis. These results may have implications when investigating the B-cell response in people with diabetes and for studies in which stimulated C-peptide secretion is used as primary or secondary outcome for response to therapy. [ABSTRACT FROM AUTHOR]

Background: Recent investigations have linked elevated gastrin levels to the improvement of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective treatments for T2DM, but it is not known if this is related to postoperative alterations of gastrin secretion. Methods: Twenty women previously operated with RYGB or SG and 13 female controls were enrolled and evaluated for body mass index, lipids, C-peptide, HbA1c, and anti- H. pylori IgG. Glucose, gastrin, insulin, and glucagon-like peptide 1 (GLP-1) concentrations were measured before and 30, 60, 90, and 120 min after ingestion of a protein-rich mixed meal. Results: Six participants primarily selected were excluded due to usage of proton pump inhibitors, positive H.pylori IgG, or history of T2DM, yielding the following groups: RYGB ( n = 9), SG ( n = 8), and controls ( n = 10). There were no differences in age, body mass index, HbA1c, or C-peptide levels between groups. RYGB had significantly lower area under the curve (AUC) for glucose during the test compared to controls ( p = 0.013). RYGB showed lower serum gastrin levels compared to SG and controls ( p < 0.05 for all). There was a non-significant increased gastrin release in SG compared to controls ( p = 0.091). For SG and controls, there was a negative correlation between glucose and gastrin response ( p = 0.0043). Conclusion: Gastrin secretion is diminished after RYGB. Hypergastrinemia was not present after SG, but a tendency of enhanced gastrin secretion was observed. These findings require further investigation in prospective studies. [ABSTRACT FROM AUTHOR]

Background: Elevated BCAA levels are strongly associated with diabetes, but how diabetes affects BCAA, branched-chain ketoacids (BCKAs), and the broader metabolome after a meal is not well known., Objective: To compare quantitative BCAA and BCKA levels in a multiracial cohort with and without diabetes after a mixed meal tolerance test (MMTT) as well as to explore the kinetics of additional metabolites and their associations with mortality in self-identified African Americans., Methods: We administered an MMTT to 11 participants without obesity or diabetes and 13 participants with diabetes (treated with metformin only) and measured the levels of BCKAs, BCAAs, and 194 other metabolites at 8 time points across 5 h. We used mixed models for repeated measurements to compare between group metabolite differences at each timepoint with adjustment for baseline. We then evaluated the association of top metabolites with different kinetics with all-cause mortality in the Jackson Heart Study (JHS) (N = 2441)., Results: BCAA levels, after adjustment for baseline, were similar at all timepoints between groups, but adjusted BCKA kinetics were different between groups for α-ketoisocaproate (P = 0.022) and α-ketoisovalerate (P = 0.021), most notably diverging at 120 min post-MMTT. An additional 20 metabolites had significantly different kinetics across timepoints between groups, and 9 of these metabolites-including several acylcarnitines-were significantly associated with mortality in JHS, irrespective of diabetes status. The highest quartile of a composite metabolite risk score was associated with higher mortality (HR:1.57; 1.20, 2.05, P = 0.00094) than the lowest quartile., Conclusions: BCKA levels remained elevated after an MMTT among participants with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the interaction of BCAA and diabetes. Metabolites with different kinetics after an MMTT may be markers of dysmetabolism and associated with increased mortality in self-identified African Americans., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetes presenting with ketoacidosis is a heterogeneous disorder. The purpose of this study was to determine whether ketosisprone diabetes (KPDM) in Thai patients were different from type1 diabetes by assessment of the beta-cell response to a standardized mixed meal and pancreatic autoantibodies. Material and Methods: 20 patients who were categorized as ketosis-prone diabetes based on the occurrence of unprovoked DKA after the age of 30 years were compared with 12 type1 diabetic patients. The beta-cell function and pancreatic autoantibodies were followed after resolution of DKA every 6 months for 2 years. Results: Mean ( ± SD) age at presentation was 38.8 ± 11.5 and 26.7 + 10.3 years in KPDM and type1 DM, respectively (p < 0.05). Median (IQR) fasting plasma C-peptide obtained after resolution of DKA within 2 weeks was 0.90 ng/dl (0.20-1.30) in KPDM compared with 0.10 ng/dl (0.10-0.45) in type1 diabetes and median peak stimulated plasma C-peptide was 6.80 ng/dl (0.90-9.80) compared with 0.10 ng/dl (0.10- 0.75). Based on Aβ classification, 4 patients were classified as A + β-, 12 patients were classified as A-β + , and 4 patients were classified as A-β-. No patient was classified as A + β + in this study. At the median time of 31 months follow-up (range from 8-44 months), 11 patients from 12 A-β + KPDM (92 %) could be withdrawn from insulin treatment successfully at median time of 5 months after admission. Conclusions: Thai KPDM patients had variable clinical course which were diff erent from typical type1 DM. The Aβ classification was proven to be useful predictors for consideration of insulin withdrawal after resolution of DKA. [ABSTRACT FROM AUTHOR]

Personalized nutrition may be more effective in changing lifestyle behaviors compared to population-based guidelines. This single-arm exploratory study evaluated the impact of a 10-week personalized systems nutrition (PSN) program on lifestyle behavior and health outcomes. Healthy men and women (n = 82) completed the trial. Individuals were grouped into seven diet types, for which phenotypic, genotypic and behavioral data were used to generate personalized recommendations. Behavior change guidance was also provided. The intervention reduced the intake of calories (−256.2 kcal; p < 0.0001), carbohydrates (−22.1 g; p < 0.0039), sugar (−13.0 g; p < 0.0001), total fat (−17.3 g; p < 0.0001), saturated fat (−5.9 g; p = 0.0003) and PUFA (−2.5 g; p = 0.0065). Additionally, BMI (−0.6 kg/m2; p < 0.0001), body fat (−1.2%; p = 0.0192) and hip circumference (−5.8 cm; p < 0.0001) were decreased after the intervention. In the subgroup with the lowest phenotypic flexibility, a measure of the body's ability to adapt to environmental stressors, LDL (−0.44 mmol/L; p = 0.002) and total cholesterol (−0.49 mmol/L; p < 0.0001) were reduced after the intervention. This study shows that a PSN program in a workforce improves lifestyle habits and reduces body weight, BMI and other health-related outcomes. Health improvement was most pronounced in the compromised phenotypic flexibility subgroup, which indicates that a PSN program may be effective in targeting behavior change in health-compromised target groups. [ABSTRACT FROM AUTHOR]

Aim: MLR-1023, called Tolimidone when evaluated unsuccessfully by Pfizer for gastric ulcer disease, has been repurposed as a novel oral insulin sensitizer with its effects mediated by selective activation of Lyn kinase. We aimed to evaluate the optimal dose, efficacy and safety of MLR-1023 in patients with type 2 diabetes.Methods: Type 2 diabetes patients (18-75 years) on diet/exercise therapy were randomized and double-blinded to receive MLR-1023 (100-mg or 200-mg, once-daily [qd] or twice-daily [bid]) or matching placebo for 28 days. The primary endpoint was postprandial glucose (PPG) area under the curve (AUC0-3h) in a mixed meal tolerance test (MMTT) at day 29. Secondary endpoints included changes in fasting plasma glucose (FPG), insulin, HbA1c, lipids and body weight and adverse events. ANCOVA model was used for efficacy analysis.Results: The placebo-corrected least-squares mean differences (ΔLSM) in MMTT PPG AUC0-3 h (mmol/L) were -5.96 and -5.6 (both p = 0.03) in the MLR-1023 100-mg qd and 100-mg bid groups, respectively. The placebo-corrected ΔLSM in FPG (mmol/L) was -2.34 (p = 0.003) in the MLR-1023 100-mg qd group. Triglycerides improved with MLR-1023 (ΔLSM, -0.56 mmol/L, p = 0.07 and -0.59 mmol/L, p = 0.05) in the 200mgqd and 200 mg bid groups, respectively. Reductions in fasting insulin, HbA1c and body weight were not statistically significant. Most common adverse events with MLR-1023 treatment were headache (4.2%) and somnolence (2.5%).Conclusions: MLR-1023 100-mg once-daily for 4 weeks was the most effective dose with significant reduction in PPG AUC following a MMTT. MLR-1023 was safe and well-tolerated in patients with type 2 diabetes. Clinical Trials Registration Number: NCT02317796. [ABSTRACT FROM AUTHOR]

Background: The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery., Methods: A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUC (ΔAUC) were compared between the two groups., Results: One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC 0'-180' of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC 0'-180' for hunger and ΔAUC 0'-180' for desire to eat in the GB group, while negatively correlated with ΔAUC 0'-180' for fullness in the SG group., Discussion: Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery., Competing Interests: The authors declare there are no competing interests.

IL-2 facilitates immunity or tolerance depending on its availability. In model systems, it is well established that low dose IL-2 promotes selective expansion of regulatory T cells (Treg), an IL-2 responsive cell type known to control autoimmunity. Moreover, many autoimmune diseases are marked by defects in Treg and/or IL-2/IL-2 receptor signaling. Thus, patients with immune-mediated diseases were treated with IL-2 with the goal of increasing Treg and controlling autoimmunity. In graft versus host disease, HCV-induced vasculitis and type 1 diabetes (T1D), Treg numbers increased with IL-2 therapy. Yet there was no relationship between Treg number and clinical outcome. In fact, in T1D subjects treated with rapamycin and IL-2 therapy there was no measureable clinical benefit. In this review, we compare results from IL-2 treatment of patients with immune-mediated diseases, discuss possible mechanisms of IL-2 treatment and suggest future directions for use of IL-2 therapy in T1D., (Copyright © 2013 Elsevier Inc. All rights reserved.)