Standard Test Meal Research Articles

Metabolic and Hormonal Changes After Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: a Randomized, Prospective Trial

BackgroundThe mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.MethodsIn this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).ResultsIn both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p < 0.012 vs. LRYGB).ConclusionsBypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.

Impaired gallbladder motility and the effect of metformin therapy in patients with polycystic ovary syndrome

Impaired gallbladder (GB) emptying is a well-documented contributor to gallstone formation. The aim of this study was to evaluate GB motility in patients with polycystic ovary syndrome (PCOS). The study population consisted of 36 PCOS patients and 20 healthy controls. GB volume was calculated using the ellipsoid formula (π/6 × L × D × W) after three-dimensional measurements were made by ultrasound [length (L), width (W) and depth (D)]. Following the determination of fasting GB volume (V0), patients were given a standard liquid meal. GB volume measurement was then repeated after 10, 20, 30, 40, 50, 60, 75 and 90 min. Gallbladder ejection fraction (GBEF) was calculated after each measurement. PCOS patients were re-evaluated after a 12-week course of metformin therapy at a dose of 1000 mg/day. Mean baseline GB volume (V0) was significantly higher in the patient group compared to the control group (27·2 ± 12·5 cm(3) vs 13·3 ± 7·0 cm(3) , P < 0·001). While baseline GBEF values were similar between groups, increases in GBEF were significantly lower in the PCOS group starting from 20 min after consumption of a standard test meal. A 12-week course of metformin therapy resulted in significant improvements in GB volume and GBEF values with a reversal of metabolic and hormonal abnormalities. For the first time in the literature, we managed to demonstrate impaired GB motility in patients with PCOS. Metformin therapy not only improves the metabolic and hormonal imbalances associated with PCOS but also has a positive influence on GB motility.

Estudo do esvaziamento gástrico por cintilografia em pacientes com insuficiência renal crônica

BACKGROUND AND OBJECTIVES: This study had the purpose of studying gastric emptying in patients with chronic renal failure. MATERIAL AND METHOD: Thirty patients with chronic renal failure were studied, 16 in conservative clinical treatment and 14 in hemodialysis for over six months. The control group (CTL) was composed of 18 asymptomatic volunteers. The method of gastric emptying study was scintigraphy. The standardized test meal was an omelet of three chicken eggs prepared with colloidal sulfur marked with 185 MBq of 99 m technetium. Gastric retention curves were studied and T½ of gastric emptying was obtained from them. A T½ value corresponding to the average of T½ values of control group plus twice standard deviation was considered nornmal. Statistical tests used were χ2 and Kruskal-Wallis. RESULTS: There was no statistically significant difference with regard to total gastric retention curves and T½ of gastric emptying, which was similar in three studied groups. Nine patients had high T½ of gastric emptying, above 125 minutes. These patients were equally distributed among both genders and conservative clinical treatment and hemodialysis groups. CONCLUSIONS: We concluded that gastric retention rate and T½ of gastric emptying in patients with chronic renal failure in conservative clinical treatment and hemodialysis does not differ from the healthy patients group. Hemodialysis does not seem to reduce the risk of gastric retention in patients with chronic renal failure

Gastric Emptying Study by Scintigraphy in Patients with Chronic Renal Failure

This study had the purpose of studying gastric emptying in patients with chronic renal failure. Thirty patients with chronic renal failure were studied, 16 in conservative clinical treatment and 14 in hemodialysis for over six months. The control group (CTL) was composed of 18 asymptomatic volunteers. The method of gastric emptying study was scintigraphy. The standardized test meal was an omelet of three chicken eggs prepared with colloidal sulfur marked with 185 MBq of 99m technetium. Gastric retention curves were studied and T½ of gastric emptying was obtained from them. A T½ value corresponding to the average of T½ values of control group plus twice standard deviation was considered nornmal. Statistical tests used were χ(2) and Kruskal-Wallis. There was no statistically significant difference with regard to total gastric retention curves and T½ of gastric emptying, which was similar in three studied groups. Nine patients had high T½ of gastric emptying, above 125 minutes. These patients were equally distributed among both genders and conservative clinical treatment and hemodialysis groups. We concluded that gastric retention rate and T½ of gastric emptying in patients with chronic renal failure in conservative clinical treatment and hemodialysis does not differ from the healthy patients group. Hemodialysis does not seem to reduce the risk of gastric retention in patients with chronic renal failure.

Discrete effects of glimepiride and metformin on preprandial and postprandial glucose and contributions to the amelioration of chronic hyperglycemia

Glimepiride and metformin have been adopted throughout the world as effective regulators of fasting glucose. Little is known, however, about the effects of these agents on postprandial glucose and insulin secretion, and how these effects contribute to HbA1c reduction. Our group has investigated these effects in type 2 diabetic patients by performing standard meal tests, before and after treatment. At 1 and 2 h after the test meal, glimepiride significantly reduced postprandial glucose excursion by 32.6 and 42.6%, respectively, and significantly increased postprandial IRI by 56.3 and 69.2%, respectively. Metformin reduced PPG and improved FPG at almost identical levels, although the 2 h postprandial glucose excursion during metformin treatment was significantly lower than the initial value by 27.1%. Metformin significantly improved the HOMA-R index from 2.60 to 2.00 (P = 0.0018), and had no effect on insulin secretion in either the fasting or the postprandial state. In correlation analysis, changes in FPG, 1 h PPG, and 2 h PPG were significantly correlated with the reduction of HbA1c in both the glimepiride and metformin groups. In multivariate analysis, amelioration of HbA1c was positively attributed to reduction of the 1 h PPG in the glimepiride group and to reduction of both the 2 h PPG and FPG in the metformin group. In conclusion, glimepiride and metformin had different effects on postprandial glucose, insulin, and the consequent change in HbA1c. Glimepiride improved PPG by early response of insulin secretion, and the 1 h PPG improvement contributed substantially to HbA1c reduction. Metformin had no effect in hindering insulin secretion, and it improved 2-h mealtime blood glucose excursion by reduction of insulin resistance, which achieved HbA1c amelioration with the aid of FPG reduction.

The Effects of Ginger on Gallbladder Motility in Healthy Male Humans

Background/AimsGinger has been used to treat a number of diseases including those affecting the digestive tract. This study was aimed to investigate the effects of ginger on gallbladder volume and gastrointestinal sensation in healthy male subjects.MethodsNineteen healthy male volunteers (age 21.3 ± 3.9 years, body mass index 21.6 ± 1.9 kg/m2) were studied on 2 occasions in a double blind randomized crossover design. After ingesting ginger (1,200 mg) or placebo capsules (starch), abdominal ultrasound was used to measure the gallbladder volume (calculated from gallbladder width, depth and diameter) and ejection fraction following a standard test meal. Gastrointestinal symptoms were also recorded at regular intervals by visual analogue scales.ResultsThere were no differences in gallbladder volume or ejection fraction between ginger and placebo. Abdominal symptoms of bloating, fullness, nausea, discomfort and hunger was not different between the 2 occasions.ConclusionsGinger (1,200 mg) may not affect gallbladder ejection fraction and possible relevant abdominal symptoms in healthy male human subjects.

Application of the lactose13C‐ureide breath test for measurement of equine orocaecal transit time

Application of the lactose (13) C-ureide breath test (LUBT) for measurement of equine orocaecal transit time (OCTT) has not been reported previously. The ability to assess OCTT noninvasively, and to investigate its relationship to gastric emptying rate and small intestinal transit, would be of both clinical and research value. 1) Assessment of the LUBT in healthy horses, with comparison of induced versus noninduced test protocols. 2) Application of a new dual stable isotope breath test (lactose (13) C-ureide and (13) C-octanoic acid) for gastrointestinal transit measurement. The LUBT will allow quantification of equine OCTT, and test efficacy will be enhanced by prior administration of lactose (12) C-ureide as shown in vitro. The dual tracer breath test will permit simultaneous measurement of gastric emptying, OCTT and small bowel transit times. Induced and noninduced LUBTs were performed in 3 healthy mature horses in randomised order using a standard test meal and protocol. Combined LUBT and (13) C-octanoic acid breath tests ((13) C-OABT) were performed in 4 individuals on 4 occasions at weekly intervals. Expiratory isotopic recovery was modelled to allow generation of gastric emptying data, small bowel transit times and caecal transit parameters. The induction protocol for the LUBT increased the rate and magnitude of expiratory (13) CO(2) significantly. Mean ± s.d. values for OCTT, caecal lag phase (t(lag) ) and caecal t(1/2) using the induced LUBT were 3.24 ± 0.65 h, 5.62 ± 1.22 h and 6.31 ± 1.21 h, respectively. Dual stable isotope tests resulted in the production of 2 discrete peaks in expiratory (13) CO(2) in 15/16 tests from which gastric t(1/2), OCTT and small bowel transit (SBT) parameters could be calculated. The induced LUBT provides a reliable noninvasive measure of equine OCTT and can be paired with the (13) C-OABT to provide further information about small intestinal motility.

Prevalence of cardiovascular disease risk factor in the Chinese population: the 2007-2008 China National Diabetes and Metabolic Disorders Study

Cardiovascular disease (CVD) is now the most prevalent and debilitating disease affecting the Chinese population. The goal of the present manuscript was to analyse cardiovascular risk factors and the prevalence of non-fatal CVDs from data gathered from the 2007-2008 China National Diabetes and Metabolic Disorders Study. A nationally representative sample of 46 239 adults, 20 years of age or older, was randomly recruited using a multistage stratified design method. Lifestyle factors, diagnosis of CVD, stroke, diabetes, and family history of each subject were collected, and an oral glucose tolerance test or a standard meal test was performed. Various non-fatal CVDs were reported by the subjects. SUDAAN software was used to perform all weighted statistical analyses, with P < 0.05 considered statistically significant. The prevalence of coronary heart disease, stroke, and CVDs was 0.74, 1.07, and 1.78% in males; and 0.51, 0.60, and 1.10% in females, respectively. The presence of CVDs increased with age in both males and females. The prevalence of being overweight or obese, hypertension, dyslipidaemia, or hyperglycaemia was 36.67, 30.09, 67.43, and 26.69% in males; and 29.77, 24.79, 63.98, and 23.62% in females, respectively. In the total sample of 46 239 patients, the prevalence of one subject having 1, 2, 3, or ≥4 of the 5 defined risk factors (i.e. smoking, overweight or obese, hypertension, dyslipidaemia, or hyperglycaemia) was 31.17, 27.38, 17.76, and 10.19%, respectively. Following adjustment for gender and age, the odds ratio of CVDs for those who had 1, 2, 3, or ≥4 risk factors was 2.36, 4.24, 4.88, and 7.22, respectively, when compared with patients with no risk factors. Morbidity attributed to the five defined cardiovascular risk factors was high in the Chinese population, with multiple risk factors present in the same individual. Therefore, reasonable prevention strategies should be designed to attenuate the rapid rise in cardiovascular morbidity.

582 PERSONAL ANXIETY AND RISK DEVELOPMENT OF CARDIOVASCULAR DISEASES AT POPULATION MEN 25-64 YEAR OLD DURING 24 YEARS (WHO “MONICA”)

Background: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism.Aim: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia.Design: A randomized double-blind sequential cross-over study.Subjects and methods: Thirty subjects of both genders (20 M/10 F), mean age 45.5±9.9 years (M±SD), BMI 26.6±2.2 kg/m2, with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight(R)) (10.6 g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1 h after the administration of 5.3 g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated.Results: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47±0.70 and 6.44±0.78 mmol/l (n.s.) and plasma triglycerides were 1.53±0.71 and 1.56±0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37±38 vs. 33±35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14 490±7416 vs. 17 760±7710 pmol/l × 300 min; P<0.02).Conclusions: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

Lipid metabolism in normal pregnancy – a magnetic resonance spectroscopy pilot study

BackgroundGestational diabetes mellitus (GDM) affects 5% of pregnancies and is associated with poor obstetric outcome. The mechanism of insulin resistance in pregnancy is unclear but may be due to increased...

Korean red ginseng (Panax ginseng C.A. Meyer) root fractions: Differential effects on postprandial glycemia in healthy individuals

Variations in ginsenoside profile may predict the postprandial glucose (PPG)-lowering efficacy of ginseng. Previously we reported differential PPG-lowering effects with two Korean red ginseng (KRG) root. FRACTIONS: body and rootlets, of variable ginsenoside profiles. Whether this effect is reproducible with a different KRG source is unclear. We therefore tested two root fractions from a KRG source with elevated ginsenoside levels to assess its effect on PPG. After a 12-h overnight fast, 13 healthy individuals (6M:7F; age=28 ± 10 y; BMI=24.1 ± 3 kg/m2; FBG=4.77 ± 0.04 mmol/L) randomly received either 3g of KRG-body, rootlets or placebo, on three separate visits. Treatments were consumed 60 min prior to a standard test meal with capillary blood samples at -60, 0, 15, 30, 45, 60, 90 and 120 min. The KRGrootlets had>6 fold total ginsensosides than the KRG-body but did not significantly affect PPG. Despite a reduced ginsenoside profile, KRG-body lowered PPG levels at 45, 60, 90 and 120 min during the test (p<0.05), rendering an overall reduction of 27% in incremental area under the glucose curve compared to the control (p<0.05). Comparing the results with a previously studied batch of KRG suggests a potential therapeutic dose range for ginsenosides. This observation should be clinically verified with acute screening and ginsenoside composition analysis.

Analysis of the urinary glucose-[15N, 15N]-ureide content in the study of the lactose-[15N, 15N]-ureide metabolism in healthy humans

Lactose-[(15)N, (15)N]-ureide is used to study the fate of the colonic urea-nitrogen metabolism. During the passage through the gastrointestinal tract, lactose ureide is hydrolysed to glucose ureide, which is absorbed to a limited extent from the small intestine and is excreted urinarily. In the present study, a procedure has been developed to quantify the urinary excretion of glucose-[(15)N, (15)N]-ureide. In addition, urine and faecal samples obtained during a dietary intervention study with the prebiotic lactulose were retrospectively analysed. The glucose ureide and lactose ureide content was measured by GC-MS in 19 healthy volunteers. After consumption of a standard test meal containing 75 mg lactose-[(15)N, (15)N]-ureide, six healthy volunteers performed a fractionated 24 h urine collection to investigate the urinary excretion of glucose-[(15)N, (15)N]-ureide. In 13 volunteers, the effect of lactulose administration on the urinary excretion of glucose-[(15)N, (15)N]-ureide was analysed. The urinary excretion of glucose-[(15)N, (15)N]-ureide reached its maximum level in the 3-6 h urine collection and decreased in the 6-9 h urine. The label was still detectable in the 9-24 h urine collection. The cumulative excretion of (15)N-labelled glucose ureide after 24 h amounted 12.91%. No significant differences in glucose-[(15)N, (15)N]-ureide excretion were found in either of the urine fractions after administration of lactulose, compared with baseline. In none of the urine samples lactose-[(15)N, (15)N]-ureide was detected. In conclusion, the results obtained in the present study indicated that the percentage dose glucose-[(15)N, (15)N]-ureide recovered in urine is rather constant and not influenced by the presence of lactulose.

Inclusion of Solid Swallows and a Test Meal Increase the Diagnostic Yield of High Resolution Manometry (HRM) in Patients With Dysphagia

Introduction Standard manometry studies diagnose oesophageal dysmotility in patients presenting with dysphagia on the basis of a small number of small volume water swallows. The association of symptoms with abnormal pressure events strongly support the clinical relevance of manometry findings; however, patients report symptoms infrequently with 5–10 ml water swallows. Solid swallows and normal eating behaviour have not entered clinical practice because of the difficulty interpreting the complex pressure events and a lack of control values. The aim of this study was to assess the prevalence of symptomatic oesophageal dysfunction following individual liquid and solid bolus swallows and a standardised test meal in patients presenting with dysphagia and asymptomatic volunteers Methods 30 consecutive patients referred for investigation of endoscopy negative dysphagia and 23 healthy volunteers underwent HRM (Manoscan 360°, SSI) with 10 × 5 ml water and 5 × 1 cc bread swallows in the upright seated position. A test meal (cheese and onion pie: 500 Kcal, 34 g fat) was provided if patients consented and for 10 healthy volunteers Results Water and bread swallows were successful in 29/30 patients (12 M:18 F, age 16–86) and all healthy volunteers (11 M:12 F, age 20–56). 10 patients and 10 volunteers completed the test meal. No healthy subject had clinically significant dysmotility or complained of symptoms. 2/29 (7%) patients experienced their typical symptoms with water, 13/29 (45%) with bread (p = 0.023), 8/10 (80%) with the meal and 16/29 (55%) when results of bread and meal were combined (p = 0.008 compared to water swallows). A change in HRM diagnosis was made in 8/29 (28%) patients on the basis of solid compared to water swallows, of whom 5 (17%) complained of typical symptoms. When a meal was provided, there was a change in HRM findings in 7/10 patients compared to 5 ml water, of whom 4 complained of typical symptoms. When results were combined 10/29 (35%) showed a change in diagnosis and 5 had typical symptoms. Pathology that would have been missed with water swallows alone included: hypertensive contractility (2), spasm (2), variant achalasia (1) and increased resistance to flow at the gastro-oesophageal junction (3). The clinical relevance of 5/8 (62.5%) of these was confirmed with typical symptoms coincident with abnormal pressure events. Two patients with asymptomatic hypotensive dysmotility with water showed normalisation with solid swallows Conclusion The diagnostic yield and ability to associate symptoms with oesophageal dysfunction is increased with inclusion of solid swallows and a test meal compared to water swallows alone in patients with endoscopy-negative dysphagia

High resolution manometry during a standardised test meal and free drinking

IntroductionPublished reference values for oesophageal High Resolution Manometry (HRM) are available only for 5 ml water swallows in the supine position; however this is not representative of normal behaviour and...

A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes

To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of LY2189265 (LY), a novel, long-acting glucagen-like peptide-1 analogue, administered once weekly to subjects with type 2 diabetes. This was a placebo-controlled, parallel-group, subject- and investigator-blind study of LY in subjects (N = 43) with type 2 diabetes mellitus controlled with diet and exercise alone or with a single oral antidiabetic medication. Subjects taking metformin or thiazolidinediones continued on their therapy. Subjects receiving sulfonylurea, acarbose, repaglinide or nateglinide were switched to metformin prior to enrollment. Subjects received five once-weekly doses of 0.05, 0.3, 1, 3, 5 or 8 mg. Effects on glucose, insulin and C-peptide concentrations were determined during fasting and following standard test meals. The pharmacokinetics of LY and its effects on HBA1c, glucagon, body weight, gastric emptying and safety parameters were assessed. Once-weekly administration of LY significantly reduced (p < 0.01) fasting plasma glucose, 2-h post-test meal postprandial glucose and area under the curve (AUC) of glucose after test meals at doses ≥1 mg. These effects were seen after the first dose and were sustained through the weekly dosing cycle. Most doses produced statistically significant increases in insulin and C-peptide AUC when normalized for glucose AUC. Statistically significant reductions in HBA1c were observed for all dose groups except 0.3 mg. The most commonly reported adverse effects (AEs) were nausea (35 events), headache (20 events), vomiting (18 events) and diarrhoea (8 events). LY showed improvement in fasting and postprandial glycaemic parameters when administered once weekly in subjects with type 2 diabetes. The pharmacokinetics and safety profiles also support further investigation of this novel agent.

Effect of Administration Time of Exenatide on Satiety Responses, Blood Glucose, and Adverse Events in Healthy Volunteers

The objective was to investigate whether varying administration time of exenatide affects the magnitude of satiety responses, blood glucose, and adverse events in healthy volunteers. In this randomized, single-blind, placebo-controlled, 4-period crossover, single-dose study, the authors measured satiety responses, blood glucose, and adverse events in 20 participants receiving exenatide (10 µg) at either -60 minutes, -30 minutes, or -15 minutes or placebo at -30 minutes relative to a standardized test meal. Compared with placebo, exenatide reduced caloric intake (P = .0059), food intake (P = .0032), and glucose concentrations at 60 (P < .001) and 120 minutes after meals (P = .015). Nausea (63% vs 20%), reduced appetite (43% vs 10%), and vomiting (18% vs 0%) occurred more frequently in exenatide-treated subjects compared with placebo (P < .05). Significant differences were noted in caloric intake (P = .0149) and food intake (P = .0205) based on the administration time of exenatide, with doses given further from meals producing reduced feeding responses. No such difference was found in postprandial glucose concentrations or adverse events based on timing of exenatide administration. Single-dose exenatide administered further from mealtime had an increased magnitude on satiety responses in healthy volunteers. Postprandial glucose concentrations and the frequency of adverse events did not differ by the administration time of exenatide.

Comparative pharmacodynamic and pharmacokinetic characteristics of subcutaneous insulin glulisine and insulin aspart prior to a standard meal in obese subjects with type 2 diabetes

Aims: A multinational, randomized, double-blind, two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus, subcutaneously administered insulin glulisine (glulisine) and insulin aspart (aspart) in insulin-naÏve, obese subjects with type 2 diabetes.Methods: Thirty subjects [9/21 females/males; mean ± SD age: 60.7 ± 7.7 years; body mass index (BMI): 33.5 ± 3.3 kg/m2; duration of diabetes: 6.8 ± 4.6 years; HbA1c: 7.1 ± 0.8%] were included in the analysis. They fasted overnight and then received a 0.2 U/kg subcutaneous dose of glulisine or aspart 2 min before starting a standardized test meal, 7 days apart, according to a randomization schedule. Blood samples were taken every 15 min, starting 20 min before the meal and ending 6 h postprandially.Results: The area under the absolute glucose concentration–time curve between 0 and 1 h after insulin injection and maximal glucose concentration was significantly lower with glulisine than with aspart (p = 0.0455 and 0.0337, respectively). However, for the total study period, plasma glucose concentration was similar for glulisine and aspart. Peak insulin concentration was significantly higher for glulisine than for insulin aspart (p < 0.0001). Hypoglycaemic events (≤ 70 mg/dl with or without symptoms) occurred in 13 and 16 subjects treated with glulisine and aspart, respectively, but there were no cases of severe hypoglycaemia requiring intervention.Conclusions: Glulisine was associated with lower glucose levels during the first hour after a standard meal; the remaining glucose profiles were otherwise equivalent, with higher insulin levels observed throughout the study period.

Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass: Unraveling the Role of Gut Hormonal and Pancreatic Endocrine Dysfunction

Profound hypoglycemia occurs rarely as a late complication after Roux-en-Y gastric bypass (RYGB). We investigated the role of glucagon-like-peptide-1 (GLP-1) in four subjects who developed recurrent neuro-glycopenia 2 to 3 y after RYGB. A standardized test meal (STM) was administered to all four subjects. A 2 h hyperglycemic clamp with GLP-1 infusion during the second hour was performed in one subject, before, during a 4 wk trial of octreotide (Oc), and after 85% distal pancreatectomy. After cessation of both glucose and GLP-1 infusion at the end of the 2 h clamp, blood glucose levels were monitored for 30 min. Responses were compared with a control group (five subjects 12 mo status post-RYGB without hypoglycemic symptoms). During STM, both GLP-1 and insulin levels were elevated 3- to 4-fold in all subjects, and plasma glucose-dependent insulinotropic peptide (GIP) levels were elevated 2-fold. Insulin responses to hyperglycemia ± GLP-1 infusion in one subject were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 40 mg/dL. During Oc, the GLP-1 and insulin responses to STM were reduced (>50%). During the clamp, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1. Glucagon levels during hyperglycemia alone were suppressed and further suppressed after the addition of GLP-1. With the substantial drop in glucose during the 30 min follow-up, glucagon levels failed to rise. Due to persistent symptoms, one subject underwent 85% distal pancreatectomy; postoperatively, the subject remained asymptomatic (blood glucose: 119-220 mg/dL), but a repeat STM showed persistence of elevated levels of GLP-1. Histologically enlarged islets, and β-cell clusters scattered throughout the acinar parenchyma were seen, as well as β-cells present within pancreatic duct epithelium. An increase in pancreatic and duodenal homeobox-1 protein (PDX-1) expression was observed in the subject compared with control pancreatic tissue. A persistent exaggerated hypersecretion of GLP-1, which has been shown to be insulinotropic, insulinomimetic, and glucagonostatic, is the likely cause of post-RYGB hypoglycemia. The hypertrophy and ectopic location of β-cells is likely due to overexpression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1.

Repeatability of Indices of Insulin Sensitivity and Secretion from Standard Liquid Meal Tests in Subjects with Type 2 Diabetes Mellitus or Normal or Impaired Fasting Glucose

The objective of this investigation was to evaluate the test-retest repeatability of insulin sensitivity and secretion indices derived from liquid meal tolerance tests (MTTs) in subjects with normal fasting glucose (NFG) (n = 20), impaired fasting glucose (IFG) (n = 20), or type 2 diabetes mellitus (n = 38). The Matsuda Index of insulin sensitivity and a Disposition Index (the product of the Matsuda Index and the ratio of the total areas under the curves for glucose and insulin from 0 to 120 min) were assessed in two standard liquid MTTs, separated by approximately 1 week. Mean ±SD Matsuda Index values were 14.2±7.6, 8.8 ± 4.7, and 6.3±4.0, and Disposition Index values were 1,009.6 ±355.5, 671.4± 249.0, and 201.8 ±101.3 for NFG, IFG, and diabetes, respectively (all P < 0.05 except Matsuda Index for IFG vs. diabetes, P = 0.241). Differences between tests in subjects with NFG, IFG, and diabetes, respectively, were -0.2 ± 3.6 (coefficient of variation for the method error, 17.9%), 0.2±3.2 (26.1%), and 0.1±3.0 (34.1%) for the Matsuda Index and 16.5±225.8 (16.1%), 13.3±221.6 (23.1%), and 15.2±79.4 (28.1%) for the Disposition Index. The Matsuda and Disposition indices derived from liquid MTTs appropriately ranked categories of fasting glucose tolerance and have repeatability profiles suggesting potential usefulness in population studies and moderately sized clinical trials requiring repeated measurements.

Real‐time visualization of altered gastric motility by magnetic resonance imaging in patients with Parkinson's disease

Gastrointestinal motility is frequently affected in Parkinson's disease (PD) and has even been reported in early stages of PD. We hypothesized that gastric motility can be assessed in vivo by real-time magnetic resonance imaging (MRI), an established, noninvasive method. After an overnight fast and a standardized test meal, 10 patients with PD (six drug naïve, four treated) and 10 healthy volunteers underwent real-time MRI scanning of the stomach. Gastric motility was quantified by calculating the gastric motility indices (GMI) from transversal oblique und sagittal oblique MRI scans. There was a trend toward a decreased gastric motility in patients with PD compared with healthy controls (Mann-Whitney test, P 0.059). This difference in peristalsis was due to a significant reduction in the amplitude of peristaltic contractions (P 0.029) and not to a decelerated velocity of the peristaltic waves (P 0.97). Real-time MRI allows direct visualization of gastric motility in PD. In this pilot study, a relatively high interindividual variability impaired accurate separation of our PD sample from healthy controls. The trend toward decreased gastric motility is in accordance with previous studies that investigated gastric motility in patients with PD using other methods. Our study provides first demonstration of a possible underlying mechanism for disturbed gastric motility in PD (reduced amplitude of contractions versus altered velocity of peristaltic waves). Further studies in drug-naïve PD patients are required to determine the discriminatory power and validity of this technique in PD.