. M.H. has received honoraria from Janssen Pharmaceutica and Solvay Pharmaceuticals for serving as a member on their advisory boards.Abbreviations: 3-OMG, 3-O-methylglucose; GLP-1, glucagon-like peptide 1; NO, nitric oxide. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Relationships of Upper Gastrointestinal Motor and Sensory Function With Glycemic Control R E V I E W A R T I C L EAcute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may, accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes. R e v i e w s / C o m m e n t a r i e s / P o s i t i o n S t a t e m e n t s 372DIABETES CARE, VOLUME 24, NUMBER 2, FEBRUARY 2001 Glycemic control and the gut reflux episodes are associated with spontaneous relaxation of the lower esophageal sphincter (38,39); in healthy subjects, the number of transient sphincter relaxations is increased during hyperglycemia (8). The effects of acute hyperglycemia on esophageal motility have not been formally evaluated in diabetic patients. Stomach. Initial studies of the effects of acute changes in the blood glucose concentration on gastric emptying were performed in healthy subjects. Stunkard (40) reported in 1957 that intravenous glucose abolished gastric "hunger contractions," whereas Aylett (41) established in 1962 that there is an inverse relationship between the rate of gastric emptying of water and the blood glucose concentration. Acute hyperglycemia, induced by intravenous glucose infusion, was subsequently shown to slow the emptying of nutrient-containing liquid and solid meals (9,10). Conversely, gastric emptying of both solids and liquids is accelerated during insulin-induced hypoglycemia (11). As early as 1937, Ferroir reported that, in diabetic patients, stomach contractions were "slow, lack vigor, and die out quickly," and that treatment with insulin "alleviates secretory and motor abnormalities even without resulting in hypoglycemia" (42). In type 1 diabetic patients, as in healthy subjects, acute hyperglycemia (blood glucose 16-20 mmol/l) slows emptying of both solids (13,14) and nutrient liquids (13) when compared with euglycemia (5-8 mmol/l) (Fig. ...

The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.

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Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

AIM:To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome (IBS) patients and healthy subjects using molecular-based techniques. METHODS:Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization (FISH) and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction. RESULTS:The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria (4.2 ± 1.3 vs 8.3 ± 1.9, P < 0.01) in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower (6 ± 0.6 vs 19 ± 2.5, P < 0.001) in the IBS patients in both fecal and duodenal brush samples than in healthy subjects. CONCLUSION:Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.

OBJECTIVE -Data on the prevalence of abnormal gastric emptying in diabetic patients are still lacking. The relation between gastric emptying and dyspeptic symptoms assessed during gastric emptying measurement has not yet been investigated. The aim was to investigate the prevalence of delayed gastric emptying in a large cohort of unselected diabetic patients and to investigate the relation between gastric emptying and gastrointestinal sensations experienced in the 2 weeks before and during the test meal, prospectively.RESEARCH DESIGN AND METHODS -Gastric emptying was evaluated in 186 patients (106 with type 1 diabetes, mean duration of diabetes 11.6 Ϯ 11.3 years) using 100 mg 13 C-enriched octanoic acid added to a solid meal.RESULTS -Gastric emptying was significantly slower in the diabetic subjects than in the healthy volunteers (T 50 : 99.5 Ϯ 35.4 vs. 76.8 Ϯ 21.4 min, P Ͻ 0.003; Ret 120 min : 30.6 Ϯ 17.2 vs. 20.4 Ϯ 9.7%, P Ͻ 0.006). Delayed gastric emptying was observed in 51 (28%) diabetic subjects. The sensations experienced in the 2 weeks before the test were weakly correlated with the sensation scored during the gastric emptying test. Sensations assessed during the gastric emptying test did predict gastric emptying to some extent (r ϭ 0.46, P Ͻ 0.0001), whereas sensations experienced in the previous 2 weeks did not.CONCLUSIONS -This prospective study shows that delayed gastric emptying can be observed in 28% of unselected patients with diabetes. Upper gastrointestinal sensations scored during the gastric emptying tests do predict the rate of gastric emptying to some extent and sensation experienced during daily life does not. Diabetes Care 26:3116 -3122, 2003T he prevalence of delayed gastric emptying in patients with diabetes has been subject to debate for several decades. Cross-sectional studies using scintigraphic techniques to measure gastric emptying have shown delayed gastric emptying in patients with diabetes varying from 30 to 60% (1-11). However, there are several important limitations to these studies. First, the vast majority of these studies have been performed in small numbers of patients or in selected patients, which may account for the high percentage of patients showing delayed gastric emptying in some of these studies. Second, none of these studies has been performed during relative euglycemic conditions, whereas recent studies have provided evidence that hyperglycemia has a substantial effect on the rate of gastric emptying (12,13). After taking the aforementioned into account, the prevalence of delayed gastric emptying in diabetic patients who are not selected for gastrointestinal symptoms has yet to be determined.Previous studies have reported a weak association between gastric emptying and upper gastrointestinal symptoms experienced by patients in the period preceding the gastric emptying test, with the exception of the study performed by Jones et al. (10). They studied a large cohort of diabetic subjects over a period Ͼ10 years and reported that abdominal bloating and fullness were as...

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