Diabetes mellitus and gastric emptying: questions and issues in clinical practice

It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non‐diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal‐derived glucose. Copyright © 2009 John Wiley & Sons, Ltd.     

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study

BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses postoperative ileus. We present the results of a double blind, placebo controlled, crossover study of ghrelin in gastric emptying in patients with diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.     

Clinical response to gastric electrical stimulation in patients with postsurgical gastroparesis.

BACKGROUND & AIMS: The aim of this study was to report the long-term clinical response to high-frequency gastric electrical stimulation (GES) in 16 patients with postsurgical gastroparesis who failed standard medical therapy. METHODS: Clinical data collected at baseline and after 6 and 12 months of GES included (1) severity and frequency of 6 upper gastrointestinal (GI) symptoms by using a 5-point symptom interview questionnaire and total symptom score, (2) health-related quality of life including physical composite score and mental composite score, (3) 4-hour standardized gastric emptying of a solid meal by scintigraphy, and (4) nutritional status. RESULTS: The severity and frequency of all 6 upper GI symptoms, total symptom score, physical composite score, and mental composite score were significantly improved after 6 months and sustained at 12 months ( P < .05). All patients had delayed gastric emptying at baseline. Gastric emptying was not significantly faster at 12 months, although 3 normalized. At implantation, 7 of 16 patients required nutritional support with a feeding jejunostomy tube; after GES, 4 were able to discontinue jejunal feeding. The mean number of hospitalization days was significantly reduced by a mean 25 days compared with the prior year. One patient had the device removed after 12 months because of infection around the pulse generator. CONCLUSIONS: Long-term GES significantly improved upper GI symptoms, quality of life, the nutritional status, and hospitalization requirements of patients with postsurgical gastroparesis. Although vagal nerve damage or disruption was part of the underlying pathophysiology, GES therapy was still effective and is a potential treatment option for the long-term management of postsurgical gastroparesis. A controlled clinical trial of GES for PSG patients (who are refractory to medical therapy) is indicated given these encouraging results.     

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.     

Relationship between the effects of cisapride on gastric emptying and plasma glucose concentrations in diabetic gastroparesis

BACKGROUND/AIMS: The effect of erythromycin on gastric emptying is attenuated during hyperglycaemia. The aim of this study was to determine in patients with diabetic gastroparesis whether the effect of cisapride on gastric emptying of solids and liquids is influenced by the plasma glucose concentration. METHODS: Nineteen patients with type 1 diabetes mellitus, who had delayed gastric emptying of solids and/or liquids, were studied. On 2 separate days, each patient received cisapride (20 mg) or placebo orally 60 min before scintigraphic measurement of gastric emptying of a mixed solid (ground beef) and liquid (dextrose) meal. The plasma glucose concentrations were measured at -5, 30, 60, 90, and 120 min during each gastric emptying measurement. RESULTS: Cisapride accelerated both solid (retention at 100 min 43 +/- 4 vs. 69 +/- 4%, p < 0.001) and liquid (T50 27 +/- 2 vs. 39 +/- 2 min, p < 0.001) gastric emptying. The mean plasma glucose level was not significantly different after placebo when compared with cisapride (19.5 +/- 1.1 vs. 18.2 +/- 1.0 mmol/l). The change in the 50% emptying time (T50) for liquid, but not solid, emptying was related (r = 0.55, p = 0.01) to the change in the plasma glucose AUC from 0 to 30 min between the placebo and cisapride tests, i.e., the acceleration was greater if the plasma glucose concentration was relatively less during the gastric emptying test performed on cisapride. CONCLUSION: The effect of cisapride on gastric emptying, at least that of liquids, in patients with diabetic gastroparesis appears to be dependent on the plasma glucose concentration.     

Effect of altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic patients

The purpose of this study was to determine the effects of altering gastric emptying on postprandial plasma glucose concentration after a physiologic meal in patients with type II diabetes mellitus (T II DM). Nine T II DM patients underwent a double-blind, randomized, three-way crossover study, receiving erythromycin 200 mg, morphine 8 mg, or normal saline (placebo) intravenously prior to ingestion of a radiolabeled, dual-isotope, solid–liquid meal. Gastric emptying of solids and liquids and serial plasma glucose, glucagon, and serum insulin concentrations were measured at baseline and for 5 hr after meal ingestion. Erythromycin accelerated and morphine delayed solid- and liquid-phase gastric emptying compared to placebo (P < 0.05). During the first hour, the postprandial plasma glucose concentrations were higher after erythromycin (P < 0.05) and lower after morphine (P < 0.05) compared to placebo. The peak postprandial plasma glucose concentration was higher after erythromycin (P = 0.05) and lower after morphine (P < 0.05) compared to placebo. In conclusion, pharmacologic acceleration of gastric emptying resulted in higher postprandial glucose concentrations, while delaying gastric emptying resulted in lower postprandial glucose concentrations after a physiologic meal in T II DM. These results suggest that administration of opiate analgesics or prokinetic agents to diabetic patients may alter glucose control. Modifying gastric emptying may be helpful in achieving glucose control in T II DM.     

2型糖尿病合并胃轻瘫患者的动态血糖谱

目的 探讨2型糖尿病合并胃轻瘫患者的动态血糖特征.方法 对31例2型糖尿病患者以核素扫描评估胃排空,并以7例正常糖调节者作对照;所有入组对象在平衡饮食状态下用动态血糖监测系统(CGMS)进行72 h血糖监测.结果 31例2型糖尿病患者中胃轻瘫占58.1%.胃轻瘫组和非胃轻瘫组在早餐后2 h平均血糖值[(7.82 4-1.42)mmol/L比(9.35 4±2.28)mmol/L]、早餐后血糖最高值[(10.21±2.17)mmol/L比(12.24±2.82 mmol/L)]和2 h平均血糖曲线下面积[(877.62±272.78)min·mmol·L-1比(1028.40±283.98)min·mmol·L-1],差异具有统计学意义(P<0.05).结论 2型糖尿病胃轻瘫患者胃排空延迟可能有助于降低餐后平均血糖.     

Guar and gastric emptying in non-insulin dependent diabetes

Summary A gamma camera was used to measure gastric emptying in 10 non-insulin dependent diabetics and 10 control subjects during and after a breakfast meal of porridge labelled with^113mIn. In the diabetics there was a more rapid early phase and a more prolonged later phase of gastric emptying compared with controls. Incorporation of 10 g guar with the meal prolonged the later phase of gastric emptying in controls. However, guar did not significantly alter gastric emptying in the diabetics, although postprandial plasma glucose concentrations were reduced. The study demonstrates abnormalities of both the early and later phases of gastric emptying in an unselected group of non-insulin dependent diabetics. Guar reduced plasma glucose concentrations without affecting gastric emptying in these patients.     

Effect of Oral CNSA-001 (sepiapterin,PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized,placebo-controlled,Phase 2 trial

AimsDiabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH₄) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH₄ levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis.MethodsNon-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10 mg/kg BID CNSA-001 or matching placebo for 14 days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up.ResultsGastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28 days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p = 0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28 days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events.ConclusionsCNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted; ClinicalTrials.gov number, NCT03712124.     

Treatment of high-frequency gastric electrical stimulation for gastroparesis

Background and Aims: The aim of this study was to assess the effects of gastric electrical stimulation (GES) on symptoms and gastric emptying in patients with gastroparesis, and the effects of GES on the three subgroups of gastroparesis. Methods: A literature search of clinical trials using high‐frequency GES to treat patients with gastroparesis from January 1995 to January 2011 was performed. Data on the total symptom severity score (TSS), nausea severity score, vomiting severity score, and gastric emptying were extracted and analyzed. The statistic effect index was weighted mean differences. Results: Ten studies (n = 601) were included in this study. In the comparison to baseline, there was significant improvement of symptoms and gastric emptying (P < 0.00001). It was noted that GES significantly improved both TSS (P < 0.00001) and gastric retention at 2 h (P = 0.003) and 4 h (P < 0.0001) in patients with diabetic gastroparesis (DG), while gastric retention at 2 h (P = 0.18) in idiopathic gastroparesis (IG) patients, and gastric retention at 4 h (P = 0.23) in postsurgical gastroparesis (PSG) patients, did not reach significance. Conclusions: Based on this meta‐analysis, the substantial and significant improvement of symptoms and gastric emptying, and the good safety we observed, indicate that high‐frequency GES is an effective and safe method for treating refractory gastroparesis. DG patients seem the most responsive to GES, both subjectively and objectively, while the IG and PSG subgroups are less responsive and need further research.     

Small particle size of a solid meal increases gastric emptying and late postprandial glycaemic response in diabetic subjects with gastroparesis

Our goal was to investigate if food of small particle size increases the gastric emptying rate and lessens the fall in postprandial blood glucose in seven subjects with Type 1 diabetes and gastroparesis. Two solid meals of identical composition but of different particle size, with 5MBq (99m)Tc added to the meals, were ingested in randomized order in seven subjects with Type 1 Diabetes Mellitus and gastroparesis and seven healthy subjects. During 180min blood glucose and insulin concentrations were measured and gastric emptying of the ingested meals was registered by a gamma camera. The lag phase in the stomach was significantly shorter, the radioactivity remaining in the stomach after 120min (T(120)) was significant less and the postprandial blood glucose dip was less and of shorter duration after a small particle (SP) meal, compared to a large particle (LP) meal in diabetic subjects. Gastric emptying did not differ significantly between groups after an SP meal. Food of small particle size increases the gastric emptying rate and reduces the postprandial blood glucose dip in both magnitude and duration in Type 1 diabetic subjects with gastroparesis, which is likely to be of importance in achieving good metabolic control.     

Gastric and oesophageal emptying in insulin-dependent diabetes mellitus

Abstract Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 45 randomly selected insulin-dependent diabetics and in 22 control subjects. In the diabetics, the relationships between oesophageal emptying, gastric emptying, age, duration of diabetes mellitus, upper gastrointestinal symptoms, glycaemic control and the complications, autonomic neuropathy, peripheral neuropathy and retinopathy were examined. The lag period before solid food left the stomach was not significantly different in diabetics compared with control subjects, but the percentage retention of solid food at 100 min was greater ( P < 0.001) in the diabetic subjects. Both the early phase (percentage retention at 10 min) and the 50% emptying time for liquid gastric emptying were delayed ( P < 0.001) in the diabetic subjects. Of the diabetics, 58% had delayed gastric emptying of either the solid and/or the liquid meal; oesophageal emptying was delayed in 42%. Upper gastrointestinal symptoms correlated poorly with both gastric and oesophageal emptying. Oesophageal emptying, solid gastric emptying and the liquid 50% emptying time correlated with the severity of autonomic nerve dysfunction ( P < 0.05). The early phase of liquid emptying (retention at 10 min) was significantly slower ( P < 0.05) in patients with mean plasma glucose concentrations of > 15 mmol/l during the gastric emptying test and the lag period for solid emptying correlated with both the glycosylated haemoglobin and mean plasma glucose concentrations.     

Management of Diabetic Gastroparesis

Symptoms suggestive of gastroparesis occur in 5% to 12% of patients with diabetes. Such a complication can affect both prognosis and management of the diabetes; therefore, practicing clinicians are challenged by the complex management of such cases. Gastroparesis is a disorder characterized by a delay in gastric emptying after a meal in the absence of a mechanical gastric outlet obstruction. This article is an evidence-based overview of current management strategies for diabetic gastroparesis. The cardinal symptoms of diabetic gastroparesis are nausea and vomiting. Gastroesophageal scintiscanning at 15-minute intervals for 4 hours after food intake is considered the gold standard for measuring gastric emptying. Retention of more than 10% of the meal after 4 hours is considered an abnormal result, for which a multidisciplinary management approach is required. Treatment should be tailored according to the severity of gastroparesis, and 25% to 68% of symptoms are controlled by prokinetic agents. Commonly prescribed prokinetics include metoclopramide, domperidone, and erythromycin. In addition, gastric electrical stimulation has been shown to improve symptoms, reduce hospitalizations, reduce the need for nutritional support, and improve quality of life in several open-label studies.     

Effect of metoclopramide in diabetic gastroparesis

The aims of our study were to: determine the effect of metoclopramide parenterally and orally on delayed gastric emptying of a radionuclide test meal in symptomatic patients with diabetic gastroparesis not explained by ulceration or other mechanical problems; and evaluate in a double-blind crossover fashion the efficacy of metoclopramide in relieving the symptoms of diabetic gastroparesis. Thirteen patients with subjective evidence of gastric stasis had delayed gastric emptying of an isotope-labeled semisolid meal which was significantly accelerated (p less than 0.05) after 10 mg of metoclopramide parenterally. Patients then received metoclopramide 10 mg and placebo before meals and prior to retiring for 3 weeks in a randomized double-blind crossover design. During metoclopramide therapy nausea, vomiting, anorexia, fullness, and bloating were significantly (p less than 0.05) ameliorated compared to placebo with an overall mean symptom reduction of 52.6%. Gastric emptying studies after completion of the trial is seven patients, subjectively improved and receiving open-labeled metoclopramide, showed significantly less gastric retention. Individual improvements in gastric emptying after parenteral or oral metoclopramide, however, could not be correlated with symptom change during the treatment trial. We conclude that metoclopramide is an important therapeutic adjunct in the management of diabetic gastroparesis and its therapeutic effects are mediated through its prokinetic properties as well as centrally mediated antiemetic actions.     

Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy

Aims Diabetic gastroparesis is a common condition occurring in some 30–50% of patients with long-term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients. Methods Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires. Results Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half-emptying time of solids was 128 ± 116 min and of liquids 42 ± 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 ± 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population. Conclusions Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.     

Gastric emptying of solid and liquid meals in healthy controls compared with long-term type-1 diabetes mellitus under optimal glucose control.

BACKGROUND: Neuropathy of the enteric nervous system and hyperglycaemia are regarded as the main causes of diabetic gastroparesis. PATIENTS AND METHODS: In ten patients with Type-1 diabetes mellitus and sensomotoric neuropathy gastric emptying half times were compared with ten healthy controls by employing the 13C-octanoic acid and the 13C-sodiumacetate breath test, resp., following the intake of equally composed and isocaloric liquid and solid meals. Plasma glucose concentrations were controlled by permanent intravenous administration of insulin. RESULTS: In diabetes mellitus gastric emptying half times after the intake of the liquid meal (p < 0.05) but not after ingestion of the solid meal were slightly prolonged. Gastric emptying half times in patients and controls were not different when liquid and solid meals were compared. CONCLUSIONS: Acute hyperglycaemia appears to be more important than the neuropathy of the enteric nervous system in the pathophysiology of diabetic gastroparesis. The rate of gastric emptying is obviously not dependent on the phase of a meal, but rather on the composition and the caloric content.     

A longitudinal study on patients with diabetes and symptoms of gastroparesis – associations with impaired quality of life and increased depressive and anxiety symptoms

Aims

To examine patient reported outcomes (PRO) in patients previously assessed for diabetic gastroparesis, and to investigate how symptoms of gastroparesis evolve over time. In addition, to further evaluate outcomes in those with versus without diabetic gastroparesis at baseline.

Delay in gastric emptying in patients with chronic renal failure

Background: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. Methods: Thirty‐nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6?h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6?h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. Results: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P?=?0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0–63.3)% versus 0 (0–2.1)%, P?P?P?=?0.93), but 4 women with CRF had delayed gastric emptying (P?=?0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0–55.0)% versus 47.5 (5.0–65.0)%, P?=?0.51, F: 16.6 (0–63.3)% versus 13.3 (0–59.2)%, P?=?0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. Conclusions: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.     

Effects of lipase inhibition on gastric emptying of,and on the glycaemic,insulin and cardiovascular responses to,a high-fat/carbohydrate meal in type 2 diabetes

Aims/hypotheses We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients.Methods Eight type 2 diabetic patients, who were aged 62 years (median range: 49–68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq ^99mTc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device.Results Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean ± SEM], 61±8 min vs 98±5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not.Conclusions/interpretation Inhibition of fat digestion by orlistat may—as a result of more rapid gastric emptying—exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.Conflict of Interest: None of the authors have a conflict of interest in relation to this study.     

The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM

Summary In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At −30 min the patients self-injected their usual morning insulin and at −15 min they injected the study drug (either placebo or 30, 60 or 90 μg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with ^99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with ¹¹¹In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal. [Diabetologia (1998) 41: 577–583] Received: 22 September 1997 and in revised form: 14 January 1998