Standard Test Meal Research Articles

Low‐dose Pramlintide Reduced Food Intake and Meal Duration in Healthy, Normal‐Weight Subjects

We previously reported that a single preprandial injection (120 microg) of pramlintide, an analog of the beta-cell hormone amylin, reduced ad libitum food intake in obese subjects. To further characterize the meal-related effects of amylin signaling in humans, we studied a lower pramlintide dose (30 microg) in normal-weight subjects. In a randomized, double-blind, placebo-controlled, cross-over study, 15 healthy men (age, 24 +/- 7 years; BMI, 22.2 +/- 1.8 kg/m(2)) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 microg) or placebo, followed immediately by a standardized pre-load meal. After 1 hour, subjects were offered an ad libitum buffet meal, and total caloric intake and meal duration were measured. Compared with placebo, pramlintide reduced total caloric intake (1411 +/- 94 vs. 1190 +/- 117 kcal; Delta, -221 +/- 101 kcal; -14 +/- 9%; p = 0.05) and meal duration (36 +/- 2 vs. 31 +/- 3 minutes; Delta, -5.1 +/- 1.4 minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and fullness higher during the first hour after pramlintide administration. In response to the buffet, hunger and fullness changed to a similar degree after pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer kilocalories. Visual analog scale nausea ratings remained near baseline, without differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin concentrations did not differ with treatment, whereas glucagon-like peptide-1 concentrations after meals were lower in response to pramlintide than to placebo. These observations add support to the concept that amylin agonism may have a role in human appetite control.

Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes

To investigate the acute and chronic effects of nateglinide versus acarbose on plasma asymmetric dimethylarginine (ADMA) levels and lipid profiles in patients with newly-diagnosed type 2 diabetes. A crossover trial of nateglinide and acarbose was conducted on 16 drug-naïve patients with newly-diagnosed type 2 diabetes during a total period of 9 weeks. Plasma glucose, serum insulin, free fatty acids (FFA), lipids and lipoproteins, and plasma ADMA were measured. The efficiencies of a single dose of nateglinide (120 mg) and acarbose (50 mg) for lowering postprandial hyperglycemia were similar. Compared to acarbose, nateglinide significantly increased postprandial insulin release after a standard meal test in patients with type 2 diabetes. Nateglinide acutely decreased postprandial 120 min FFA concentrations and 240 min ADMA levels more significantly than acarbose. The fasting high-density lipoprotein cholesterol level increased and the low-density lipoprotein cholesterol level decreased significantly, but the fasting levels of triglycerides, total cholesterol, and ADMA were unchanged after 4 weeks of treatment with nateglinide. Acarbose did not affect fasting lipid profiles or the ADMA levels after 4 weeks of treatment. These results suggest that the reduction of postprandial FFA and ADMA concentrations induced by nateglinide may be associated with the partial restoration of early-phase insulin secretion and may impart a cardiovascular advantage in comparison with acarbose.

Other

Two insulin regimens were used to explore acute and chronic postprandial changes in glycemia, lipemia, and metabolic markers associated with increased risk of cardiovascular disease.An open-label, randomized, two-period crossover study (12 weeks/period) compared a prandial regimen [premeal insulin lispro + bedtime neutral protamine Hagedorn (NPH)] with a basal regimen (twice-daily NPH). There were 30 patients (12 women and 18 men; mean age=61 years) with type 2 diabetes mellitus (mean duration=16 years) who were randomized after a 2-month lead-in with twice-daily NPH treatment. A standard lunch test meal developed according to each patient's caloric needs was administered at the end of each treatment period.Insulin lispro was associated with significantly lower postprandial glucose (area under the curve0–5 h=43.54 vs. 57.65 mM/h; P<.001), elevated insulin concentrations, and acutely altered lipid fractions that included an early decrease followed by an increase in free fatty acids, lower triglycerides, elevated total cholesterol, elevated low-density lipoprotein cholesterol (LDL), and elevated high-density lipoprotein cholesterol. After 12 weeks of treatment, insulin lispro + bedtime NPH reduced hemoglobin A1c (HbA1c; mean±SE=7.6±0.2 vs. 8.2±0.2%; P<.001) without increasing hypoglycemia or insulin dose as compared with twice-daily NPH. Furthermore, treatment with the prandial insulin regimen resulted in lower total cholesterol, lower LDL cholesterol, and lower oxidized LDL.Improved postprandial glycemic control, as observed in a regimen containing both prandial insulin lispro and NPH as the basal insulin, is associated with significantly lower HbA1c and acute modulation of lipid fractions after a test meal. These biochemical modifications may potentially have a favorable impact on cardiovascular risk in patients with type 2 diabetes mellitus.

Chronic hyperglycemia but not glucose variability determines HbA1c levels in well-controlled patients with type 2 diabetes

To determine the relationships between HbA1c, characteristics of hyperglycemia and glycemic variability in well-controlled type 2 diabetes (HbA1c < 7.0%), we studied 63 primary-care patients (36 men and 27 women), aged 34–75 years, with type 2 diabetes for 2–32 years using a continuous glucose monitoring system (CGMS) and standardized meal test (MMT). Duration of hyperglycemia (>8.0 mmol/l), standard deviation score (S.D.-score) and mean amplitude of glycemic excursions (MAGE) were analyzed from CGMS data and postprandial glucose during MMT (PPG MMT). Patients were hyperglycemic for 5.7 h/day (median), experienced 4.1 hyperglycemic episodes/day, and 78% exceeded PPG levels of 8.0 mmol/l. HbA1c, though associated with the extent of hyperglycemia ( r = 0.40, p < 0.001), failed to correlate with S.D.-score and MAGE. Multiple regression analysis demonstrated that HbA1c was predicted only by fasting glucose ( R 2 = 0.24, p < 0.001) but neither by PPG MMT, duration of hyperglycemia, S.D.-score nor MAGE. CGMS and meal test provide the tools for complete characterization of glycemia in type 2 diabetes. In well-controlled type 2 diabetes, HbA1c correlates with chronic hyperglycemia but not with glucose variability. Our data suggest that chronic sustained hyperglycemia and glucose fluctuations are two independent components of dysglycemia in diabetes.

食後高血糖と食後高脂血症を同時に観察するテストミールＡについて

It is now well recognized that both Postprandial hyperglycemia and postprandial hyperlipidemia contribute to the development of atherosclerosis. Both an impaired glucose tolerance (IGT) and hyperglycemia after glucose loading have been reported to be risk factors for coronary arterial disease. Postprandial hyperlipidemia, or an increase in remnant lipoproteins in the plasma after a meal has been recognized as atherogenic. It therefore becomes important to establish an international standard test meal for simultaneously assessing both postprandial hyperglycemia and postprandial hyperlipidemia. Test meal A was developed for this purpose by the Working Group for Test Meals under the Committee of Laboratory Testing for Diabetes Mellitus of the Japan Diabetes Society. Test meal A contains total energy of 450 kcal with 51.4% of carbohydrate, 33.3% of fat and 15.3% of protein. Eighteen diabetics, 12 IGTs and 29 subjects with normal glucose tolerance were enrolled for this study. An oral glucose tolerance test was performed one week after loading with the test meal. There was a close correlation between the blood glucose values 120min. after glucose loading and 120min. after test meal loading. A blood glucose value of 200mg/dl 2 hour after glucose loading corresponds to 150mg/dl at the same sampling point after test meal loading, and a blood glucose value of 140mg/dl 2 hour after glucose loading corresponds to 10mg/dl at the same sampling point after the test meal loading. No significant increase in plasma triglyceride was apparent in the hypertriglyceridemic subjects, while the normotriglyceridemic group showed a significant rise in plasma triglyceride after the test meal loading. The results indicate that test meal A can be applied as a pilot model for the simultaneous assessment of both postprandial hyperglycemia and hyperlipidemia in diabetic subjects.

Increased sucrose intake is not associated with a change in glucose or insulin sensitivity in people with type 2 diabetes

Background Debate continues over the role of sucrose and sucrose-containing food in the diet for people with type 2 diabetes. Traditionally, dietary recommendations have suggested sucrose be reduced to a minimum level to improve glycaemic control. More recently the American Diabetes Association evidence-based guidelines have suggested a more liberal approach.Objective To investigate whether a 50 g increase in sucrose given as three slices of cake a day over a period of 24 days (88±7.5 g total sucrose/day) in combination with an increased monounsaturated fat intake (20% E) in line with current American Diabetes Association recommendations has an effect on glycaemic control or insulin sensitivity in people with type 2 diabetes.Design We re-examined results from a larger study that investigated the type of fat in the diet of people with type 2 diabetes. Nine overweight people with type 2 diabetes received a high-sucrose, high-monounsaturated-fat isocaloric diet for 24 days.Results Weight and glycaemic control remained stable throughout the study. There was no significant change in HbA1c over the study period. There was no change in insulin sensitivity, measured by the short insulin tolerance test. There was no change in fasting or postprandial incremental area under the curve in response to an identical standard test meal for glucose or insulin.Conclusions Over the 3-week intervention period, an isocaloric increase in the dietary intakes of sucrose to 13% of total energy per day in people with type 2 diabetes was not associated with a decline in glycaemic control or insulin sensitivity.

Premeal insulin lispro plus bedtime NPH or twice-daily NPH in patients with type 2 diabetes: acute postprandial and chronic effects on glycemic control and cardiovascular risk factors

Objective Two insulin regimens were used to explore acute and chronic postprandial changes in glycemia, lipemia, and metabolic markers associated with increased risk of cardiovascular disease. Methods An open-label, randomized, two-period crossover study (12 weeks/period) compared a prandial regimen [premeal insulin lispro + bedtime neutral protamine Hagedorn (NPH)] with a basal regimen (twice-daily NPH). There were 30 patients (12 women and 18 men; mean age=61 years) with type 2 diabetes mellitus (mean duration=16 years) who were randomized after a 2-month lead-in with twice-daily NPH treatment. A standard lunch test meal developed according to each patient's caloric needs was administered at the end of each treatment period. Results Insulin lispro was associated with significantly lower postprandial glucose (area under the curve 0–5 h=43.54 vs. 57.65 mM/h; P<.001), elevated insulin concentrations, and acutely altered lipid fractions that included an early decrease followed by an increase in free fatty acids, lower triglycerides, elevated total cholesterol, elevated low-density lipoprotein cholesterol (LDL), and elevated high-density lipoprotein cholesterol. After 12 weeks of treatment, insulin lispro + bedtime NPH reduced hemoglobin A 1c (HbA 1c; mean±SE=7.6±0.2 vs. 8.2±0.2%; P<.001) without increasing hypoglycemia or insulin dose as compared with twice-daily NPH. Furthermore, treatment with the prandial insulin regimen resulted in lower total cholesterol, lower LDL cholesterol, and lower oxidized LDL. Conclusion Improved postprandial glycemic control, as observed in a regimen containing both prandial insulin lispro and NPH as the basal insulin, is associated with significantly lower HbA 1c and acute modulation of lipid fractions after a test meal. These biochemical modifications may potentially have a favorable impact on cardiovascular risk in patients with type 2 diabetes mellitus.

Obesity Is Associated With Increased Transient Lower Esophageal Sphincter Relaxation

Obesity has been associated with gastroesophageal reflux disease (GERD) and its complication, but the mechanism is unclear. We evaluated the association between obesity and function of lower esophageal sphincter (LOS) in subjects without GERD. We prospectively recruited consecutive obese (BMI >30) patients referred for weight reduction procedure and age- and sex-matched overweight (BMI 25-30) and normal weight (BMI > or =20 and <25) subjects. Exclusion criteria included esophagitis, reflux symptoms, use of proton pump inhibitor, hiatus hernia >2 cm, and diabetes mellitus with microvascular complication. All participants underwent combined 2-hour postprandial esophageal manometry and pH monitoring after a standard test meal followed by 24-hour ambulatory pH monitoring. Eighty-four subjects (obese, 28; overweight, 28; normal weight, 28) were studied. All 3 groups had comparable mean LOS pressure, LOS length, and peristaltic function. During the postprandial period, both obese and overweight groups had substantial increase in 2-hour rate of transient lower esophageal sphincter relaxation (TLOSR) (normal weight: 2.1 +/- 1.2 vs overweight: 3.8 +/- 1.6 vs obese: 7.3 +/- 2.0, P < .001), proportion of TLOSR with acid reflux (normal weight: 17.6% +/- 22.0% vs overweight 51.8% +/- 22.5% vs obese: 63.5% +/- 21.7%, P < .001), and gastroesophageal pressure gradient (GOPG) (normal weight: 4.5 +/- 1.2 mm Hg vs overweight: 7.1 +/- 1.4 mm Hg vs obese: 10.0 +/- 1.5 mm Hg, P < .001). Using multiple regression model, BMI (r(2): 0.70, B: 0.28, 95% CI: 0.24-0.33, P < .001) and waist circumference (r(2): 0.65, unstandardized regression coefficient [B]: 0.10, 95% CI: 0.08-0.11, P < .001) were significantly correlated with TLOSR. Obesity is associated with increased TLOSR and acid reflux during the postprandial period in subjects without GERD. Abnormal postprandial LOS function may be an early event in the pathogenesis of obesity-related GERD.

GLP-1 and Changes in Glucose Tolerance following Gastric Bypass Surgery in Morbidly Obese Subjects

It has been proposed, that the dramatic amelioration of type 2 diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However, human data supporting this hypothesis is scarce. A 12-month prospective study on the changes in glucose homeostasis, and active GLP-1 in response to a standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1+/-1.0 kg/m(2)) who had different degrees of glucose tolerance: normal glucose tolerance (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10). At 6 weeks after RYGBP, despite the subjects still being markedly obese (BMI 43.5+/-0.9 kg/m(2)), fasting plasma glucose and HbA1c decreased in the 3 study groups (P<0.05). Insulin sensitivity improved, but was still abnormal in a comparable proportion of subjects among groups (P=0.717). When insulin secretion was accounted for the prevailing insulin sensitivity, an increase was found in subjects with diabetes (P<0.05) although it remained lower compared to NGT- and IGT-subjects (P<0.01). At 12 months follow-up, no differences among groups were found in the evaluated glucose homeostasis parameters. Compared to baseline, at 6 weeks the incremental AUC(0-120') of active GLP-1 in response to the STM increased in NGT and IGT (P<0.05) but not in subjects with diabetes (P=0.285). However, the GLP-1 response to a STM was comparable among groups at 12 months follow-up (P=0.887). 1) RYGBP was associated with an improvement but not complete restoration of glucose homeostasis at 6 weeks after surgery. 2) GLP-1 is not a critical factor for the early changes in glucose tolerance.

Validity of 13C octanoic acid breath test for measurement of solid meal gastric emptying time in children

Background/Purpose It is important to establish a physiologic range of gastric emptying (GE) in children. Gastric emptying time measured with 99Tc-labeled solid meal (GE Tc) is the gold standard. Large-scale studies with GE Tc are ideal but not feasible because of radiation exposure. The 13C-labeled octanoic acid breath test (GE 13C) does not involve radiation and is suitable for large studies. The aim of this study was to validate GE 13C with GE Tc and to explore whether GE 13C could be used to establish a physiologic range of GE in children. Method Twenty-five healthy children underwent simultaneous GE Tc and GE 13C using a standardized solid test meal. The time taken for the stomach to empty half its content (T½ 13C) and solid lag phase (lag 13C) for GE 13C were computed from the fractional excretion of 13C in expired air. T½ 13C and lag 13C were compared with corresponding values obtained by GE Tc. Result Correlation coefficient between T½ 13C and T½ Tc was 0.69 ( P < .01; r = 0.92 if 3 outliers were omitted). Correlation coefficient between lag 13C and lag Tc was 0.39 ( P < .05). There was good agreement between the methods by the Bland Altman method. Conclusion There is good agreement between GE 13C and GE Tc. GE 13C can be safely used to establish the reference range of GE in healthy children.

13C-MIXED TRIGLYCERIDE BREATH TEST (13C-MTG) DEMONSTRATES SUPERIORITY OF ENTERIC COATED MONOLITHIC ENZYME PREPARATION OVER PLACEBO

Background: Currently, no non-invasive pancreatic function tests are broadly available apart from fecal elastase-1 (El-1) which has limited sensitivity and specificity. We applied the 13C-MTG for measurement of the effects of a monolithic enteric coated enzyme preparation (i.e. single unit, no microgranules) on lipid digestion and absorption. Due to dissociation between gastric emptying of meal nutrients and enzyme supplements, these older preparations are assumed to be virtually ineffective and potential effects can only be shown by sensitive methods. Methods: 20 patients with documented chronic pancreatitis (19 males, 1 female, age: 52±2 yrs, BMI: 23.1±0.7 kg/m2, El-1: 42.1±8.2 μg/g, mean-SEM) were included in 3 study centres. On two study days which were 3-14 days apart and each preceeded by at least 3 days without intake of enzyme supplements, patients received a monolithic enteric-coated pancreatin preparation (40,000 U of lipase) or placebo together with a standardised test meal containing 250 mg of 13C-mixed triglycerides according to a randomised, double blind, cross-over study design. Differences between cumulative 13C-exhalation were evaluated as markers of lipid digestion during treatment with verum and placebo. Results: (mean±SEM, statistics: ANOVA): One patient had to be excluded because of major protocol violations; 6 patients were excluded from the per protocol analysis because of normal intestinal lipolysis during placebo treatment despite decreased El-1. In the remaining 13 patients, mean cumulative 13C-exhalation over 6 and 8 hours was markedly higher following treatment with verum compared to placebo (6 h: 11±2 vs. 5±1% of dose, p = 0.035; 8 h: 18±3 vs. 9±1% of dose, p = 0.015). Conclusions: In contrast to current belief, single administration of a monolithic enteric-coated pancreatin preparation containing 40,000 U of lipase significantly improves lipid digestion and absorption compared to placebo in patients with severe pancreatic exocrine insufficiency. Sensitivity of the 13C-MTG allows detection of these effects and, thus, this non-invasive test may expand our diagnostic armamentarium in pancreatic exocrine insufficiency.

A single-center, randomized, double-blind, three-way crossover study examining postchallenge glucose responses to human insulin 70/30 and insulin lispro fixed mixtures 75/25 and 50/50 in patients with type 2 diabetes mellitus

Objective: The aim of this study was to test the ability of human insulin 70130, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50150 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus (DM). Methods: This single-center, randomized, double-blind, 3-way crossover study was conducted at the Diabetes and Glandular Disease Research Center, San Antonio, Texas. We measured serum glucose responses after a standardized breakfast test meal (500 kcal; 50% carbohydrate, 34% fat, 16% protein) in patients with type 2 DM receiving a single preprandial dose of human insulin 70/30, insulin lispro 75/25, or insulin lispro 50/50 by SC injection. All patients previously used insulin for at least 1 month prior to the study. The glucose responses were compared with those of healthy, untreated subjects administered the identical meal. Results: A total of 33 patients were enrolled (23 with type 2 DM and 10 healthy controls). The baseline characteristics of the patients were as follows: sex ratio (M:F), 17:6; mean (SD) age, 61.3 (10.0) years; mean (SD) body weight, 98.5 (13.2) kg; mean (SD) body mass index, 33.0 (3.8) kg/m 2; mean (SD) glycosylated hemoglobin, 8.1% (1.6%); mean (SD) fasting serum glucose (FSG), 158.7 (27.6) mgldL; and 56.5% white, 8.7% black, and 34.8% Hispanic. The mean (SD) doses (U/d) of the fixed-mixture preparations were similar: human insulin 70/30, 44.1 (18.2); insulin lispro 75/25, 44.1 (18.2); and insulin lispro 50/50, 43.8 (17.8). FSG levels obtained before the test meal were not significantly different between treatments. Compared with those in healthy subjects, incremental glucose AUC values for the 4 hours after the meal (AUCglucose 0–4) for patients with type 2 DM were 6.4-fold higher with human insulin 70/30, 4.6-fold higher with insulin lispro 75/25, and 3.0-fold higher with insulin lispro 50/50. Each insulin regimen produced AUC glucose 0–4 and 2-hour PPG values significantly different from all other regimens (all, P < 0.05). Mean (SD) 2-hour PPG values (mg/dL) were lower with mixtures containing insulin lispro than with human insulin 70/30 and decreased as the proportion of insulin lispro within the fixed mixtures increased: human insulin 70/30, 212.6 (47.0); insulin lispro 75/25, 198.0 (67.5); and insulin lispro 50/50, 158.8 (52.3). Conclusions: In this small study in patients with type 2 DM and healthy controls, preprandial administration of a fixed mixture containing rapid-acting or regular insulin and intermediate-acting components was associated with attenuation of the rise in PPG in patients with type 2 DM administered a test meal. Mixtures containing insulin lispro were associated with greater decreases in PPG concentrations compared with human insulin 70/30. Furthermore, greater amounts of rapid-acting insulin contained within the mixture were associated with better PPG control.

Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide are incretin hormones, secreted in response to meal ingestion. The incretin hormones stimulate insulin secretion and are essential for the maintenance of normal plasma glucose concentrations. Both incretin hormones are metabolized quickly by the enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired incretin effect. Therefore, the aim of the present study was to investigate plasma DPP-IV activity in the fasting and the postprandial state in type-2 diabetic patients and control subjects. The study included two protocols. Protocol one involved 40 fasting type-2 diabetic patients (28 men); age 61 +/- 1.4 (mean +/- s.e.m.) years; body mass index (BMI) 31 +/- 0.6 kg/m(2); HbAlc 7.2 +/- 0.2%; and 20 matched control subjects (14 men) were studied. Protocol two involved eight type-2 diabetic patients (six men); age 63 +/- 1.2 years; BMI 33 +/- 0.5 kg/m(2); HbAlc 7.5 +/- 0.4%; eight matched control subjects were included. In protocol one, fasting values of DPP-IV activity were evaluated and in protocol two, postprandial DPP-IV activity during a standard meal test (566 kcal) was estimated. Mean fasting plasma DPP-IV activity (expressed as degradation of GLP-1) was significantly higher in this patient group compared with the control subjects (67.5 +/- 1.9 vs 56.8 +/- 2.2 fmol GLP-1/h (mean +/- s.e.m.); P=0.001). In the type-2 diabetic patients, DPP-IV activity was positively correlated to FPG and HbAlc and negatively to the duration of diabetes and age of the patients. No postprandial changes were seen in plasma DPP-IV activity in any of the groups. Plasma DPP-IVactivity increases in the fasting state and is positively correlated to FPG and HbAlc levels, but plasma DPP-IV activity is not altered following meal ingestion and acute changes in plasma glucose.

Relationship between HbA1c and indices of glucose tolerance derived from a standardized meal test in newly diagnosed treatment naive subjects with Type 2 diabetes

To determine the relationship between HbA1c and other indices of glycaemic status derived during a standardized meal tolerance test (MTT) in newly diagnosed treatment-naive subjects with Type 2 diabetes (T2DM). T2DM subjects (n = 262) consumed a standard MTT in the morning after a 10-h overnight fast. Frequent samples for plasma glucose (PG) were collected over the 4-h test period. The relationship between HbA1c and other glycaemic indices derived from the MTT were explored. The postprandial glucose exposure was calculated as the area under the incremental plasma glucose curve above the fasting level for the test period (AUC1). Excess hyperglycaemia was calculated as the AUC0-4 h above the arbitrary PG concentrations of 6.0 mmol/l (AUC2) and 5.5 mmol/l (AUC3), respectively [upper limit of fasting normoglycaemia according to World Health Organization (WHO) and American Diabetes Association (ADA), respectively]. Fasting hyperglycaemia was also estimated, being the difference between each of the above and the postprandial excursion. The participants were divided into three subgroups according to HbA1c (Group 1, <or= 7.0%; Group 2, 7.1-9.0%; Group 3, > 9.0%) and the relative contribution calculated of the postprandial glucose and fasting hyperglycaemia to the excess hyperglycaemia above the designated international thresholds for fasting plasma glucose. HbA1c was more strongly correlated with the fasting plasma glucose (r = 0.85, P < 0.001) than the overall postprandial glucose exposure (r = 0.539, P = 0.003). The contribution of fasting hyperglycaemia to excess hyperglycaemia using the WHO criteria for normal fasting plasma glucose for the three groups (Groups 1, 2 and 3) was 50.4%, 54.3% and 69.8%, respectively, and 57.8%, 58.8% and 71.4% using the ADA criteria. The contribution of fasting hyperglycaemia to excess hyperglycaemia increases as glycaemic control deteriorates, becoming dominant with an HbA1c in excess of 7.0%. These findings indicate which therapeutic approach needs to be adopted based on the HbA1c of the person with T2DM.

Postprandial lipid metabolism

Atherogenic effects of postprandial lipoproteins are supported by many studies comparing patients with advanced clinical signs or early markers of cardiovascular disease with subjects without vascular disease. Postprandial lipoprotein abnormalities are more frequent in individuals with type 2 diabetes and other states of insulin resistance, which could be a major factor accounting for the higher rate of cardiovascular diseases observed in these conditions. In patients with type 2 diabetes multiple abnormalities of lipoproteins of both endogenous and exogenous origin are observed also in the presence of good blood glucose control and normal fasting triglyceridaemia, and a direct role of insulin resistance in the development of postprandial dyslipidaemia has been demonstrated. Clinical and experimental studies have demonstrated that a high fat consumption is associated with impaired insulin sensitivity and may worsen postprandial hypertriglyceridemia in individuals with type 2 diabetes and/or hyperlipidaemia. In addition to the amount of fat also the physical structure of the food in which fat is present is able to influence postprandial lipaemia. Data on the effects of dietary fatty acid (FA) modifications in humans are scarce. These studies have provided some evidence that dietary polyunsaturated FA, particularly those of the n-3 class, induce an attenuated postprandial lipaemic response as compared to saturated FA (SFA) and monounsaturated FA (MUFA); however, the data are often conflicting and their interpretation is, generally, controversial. Very little is known in patients with type 2 diabetes, in whom both insulin sensitivity and postprandial lipaemia are particularly relevant. In a medium term (3 weeks) study in type 2 diabetic patients, a MUFA rich diet did not modify insulin sensitivity as compared to the SFA rich diet. The MUFA diet induced a higher early peak of chylomicrons and a significantly lower postprandial response o f small VLDL after a standard test meal, rich in saturated fat. In conclusion, postprandial lipoprotein abnormalities are a frequent feature of type 2 diabetes and of other conditions clustering with insulin resistance. The total amount of fat, more than the specific type of fatty acid, seems to influence postprandial lipoproteins. Data are needed on long term interventions as well as on the interactions between dietary fat and other food components or physical structure. Keywords: postprandial lipoproteins; metabolism of dietary fat

Twelve-week Monotherapy with the DPP-4 Inhibitor Vildagliptin Improves Glycemic Control in Subjects with Type 2 Diabetes

Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n=70) VS. placebo (bid, n=28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 +/- 0.2 % (p=0.0012) for the whole cohort (baseline 8.0 %) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 +/- 0.4 (p=0.0043) and 1.9 +/- 0.5 mmol/l (p <0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 +/- 0.02 (p=0.0258) and + 0.10 +/- 0.03 nmol/l (p=0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %). monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in beta-cell function were also observed. Subjects with higher baseline HbA1c levels showed greater response.

28 The alteration of multi‐channel Electrogastrography and autonomic nervous system function in patients with gastroesophageal reflux disease with test meal

The aims of this study were to utilize multi‐channel electrogastrography (MEGG) and power spectra analysis of Heart Rate Variability (HRV) to investigate the effects of test meal on MEGG and autonomic nervous system (ANS) function in patients with gastroesophageal reflux disease (GERD).Methods: Sixteen patients with the diagnosis of GERD were enrolled in this study (11 M, 5 F, mean age: 47 yrs) and 16 healthy subjects (HS) matched for age and gender were recruited as control (11 M, 5 F, mean age: 47 yrs). MEGG was recorded simultaneously with the electrocardiogram (ECG) recording for 30 min in the fasting state and 60 min after a standard test meal (450 Kcal). MEGG parameters included dominant frequency (DF), dominant power (DP), the normal percentage of 2–4 cpm gastric slow waves (%N) and the percentage of slow wave coupling (%SWC). ANS parameters included sympathovagal balance LF/HF Ratio, mainly sympathetic activity LF and vagal activity HF.Results: (1) Compared with fasting state, test meal significantly increased the DF but decreased the %N and %SWC in both GERD patients and HS in the 1st 30 min and 2nd 30 min fed state (P &lt; 0.05). DP was not significantly altered by test meal in both groups in fed state. However, there is no significant difference between 1st 30 min and 2nd 30 min fed state for DF, %N and %SWC. 2) Compared with fasting state, test meal significantly increased the LF/HF ratio and LF but decreased the HF in both groups in the 1st 30 min after meal (P &lt; 0.05), however, the increase of LF/HF ratio and LF but decrease of HF were still present in HS whereas absent in patients with GERD in the 2nd 30 min fed state. There is no significant difference between 1st 30 min and 2nd 30 min fed state for those ANS parameters. (3) There was no significant difference between GERD patients and HS in any of those MEGG and ANS parameters neither in fasting state nor in fed state. (4) There was no significant correlation between MEGG parameters and ANS parameters neither in fasting state nor in fed state in both groups.Conclusions: Both patients with GERD and HS may have similar response to test meal in MEGG test. GERD patients could not maintain the response to test meal longer in ANS test suggests that GERD patients may have impaired ANS regulation to test meal.

Glucagon-Like Peptide-1, Peptide YY, Hunger, and Satiety after Gastric Bypass Surgery in Morbidly Obese Subjects

The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood. The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety. This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 +/- 6.1 kg/m(2)] before and 6 wk after RYGBP. Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 +/- 7.8 kg/m(2)), the area under the curve(0-120') of GLP-1 and of PYY in response to the standardized test meal were significantly elevated (P < 0.05 and P < 0.01, respectively). These hormonal responses were significantly larger (P < 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery. The 2.9 +/- 1.2- and 1.6 +/- 1.9-fold increase, respectively, in the area under the curve(0-120') of GLP-1 and PYY were accompanied by a significant decrease in fasting (P < 0.05) and postprandial hunger (P = 0.05) and a significant increase in satiety (P < 0.05) after meal intake. Nevertheless, a significant correlation between changes in the hormonal and eating behavior parameters was not found. Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquid-meal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP.

Glucagon-Like Peptide-2: Update of the Recent Clinical Trials

Although long-term parenteral nutrition is lifesaving in patients with intestinal failure, it is expensive and associated with serious complications such as catheter sepsis, venous occlusions, and liver failure and severely impairs the quality of life in the short bowel patients. Therefore, treatments that increase the absolute intestinal absorption, thereby eliminating or minimizing the need for parenteral support, are needed. In this respect, glucagon-like peptide 2 (GLP-2) has received attention. In this review, the nature of the short bowel syndrome is described, and the antisecretory, transit-modulating, but also intestinotrophic effects of GLP-2 are presented. As illustrated in 2 pilot studies, one using native GLP-2 and the other a degradation-resistant analogue, teduglutide, these new agents may prove important in optimizing remnant intestinal function, thereby eliminating the need for parenteral support and improving quality of life in short bowel patients with intestinal failure.

Improved Prandial Glucose Control With Lower Risk of Hypoglycemia With Nateglinide Than With Glibenclamide in Patients With Maturity-Onset Diabetes of the Young Type 3

To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas. We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug. Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test. A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.