peptide-yy and Diabetes-Mellitus--Type-1

Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes. Areas covered: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials. Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety issue arises from the as yet unknown potential risks in women of child bearing potential in whom DKA is of utmost concern. The sotagliflozin development program has now been extended to trials in Type 2 diabetes, and long term studies will be needed to assess the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucagon-Like Peptide 1; Glycosides; Humans; Hypoglycemic Agents; Peptide YY; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

In patients with type 2 diabetes, but not type 1 diabetes, abnormal secretion of incretins in response to oral nutrients has been described. In healthy youths, we recently reported accentuated glucagon-like peptide 1 (GLP-1) secretion in response to a diet soda sweetened with sucralose and acesulfame-K. In this study, we examined the effect of diet soda on gut hormones in youths with diabetes.. Subjects aged 12-25 years with type 1 diabetes (n = 9) or type 2 diabetes (n = 10), or healthy control participants (n = 25) drank 240 mL cola-flavored caffeine-free diet soda or carbonated water, followed by a 75-g glucose load, in a randomized, cross-over design. Glucose, C-peptide, GLP-1, glucose-dependent insulinotropic peptide (GIP), and peptide Tyr-Tyr (PYY) were measured for 180 min. Glucose and GLP-1 have previously been reported for the healthy control subjects.. GLP-1 area under the curve (AUC) was 43% higher after ingestion of diet soda versus carbonated water in individuals with type 1 diabetes (P = 0.020), similar to control subjects (34% higher, P = 0.029), but was unaffected by diet soda in patients with type 2 diabetes (P = 0.92). Glucose, C-peptide, GIP, and PYY AUC were not statistically different between the two conditions in any group.. Ingestion of diet soda before a glucose load augmented GLP-1 secretion in type 1 diabetic and control subjects but not type 2 diabetic subjects. GIP and PYY secretion were not affected by diet soda. The clinical significance of this increased GLP-1 secretion, and its absence in youths with type 2 diabetes, needs to be determined.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Carbonated Beverages; Child; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose; Humans; Male; Peptide YY; Young Adult

Previous research indicated that coeliac disease (CD) is associated with type 1 diabetes mellitus (T1DM). However, the gut-brain axis peptide hormones secretion has not been evaluated so far in patients with CD prior to treatment initiation or under treatment, irrespective of patients having concomitant T1DM or not. The aim of the study was therefore to evaluate these gut hormones at the preprandial levels of patients with CD before and under treatment.. Of forty-seven CD children, 12 untreated (UCD), 22 treated with gluten-free diet (TCD) and 13 treated CD with coexisting T1DM (DCD), and 18 healthy controls (HC) were enrolled. Preprandial glucagon-like-peptide-1 (GLP-1), glucose-dependent-insulinotropic-polypeptide (GIP), active amylin, acylated ghrelin (AG), leptin, pancreatic polypeptide (PP) and peptide-tyrosine-tyrosine (PYY) were determined with hormone-map-array technology.. We found in patients with CD compared with HC that the concentration of (i) GLP-1 was reduced remarkably in all patients with CD (P = 0.008), (ii) GIP was lower in patients with UCD (P = 0.008), (iii) amylin was remarkably reduced (P < 0.01) in all patients with CD, (iv) AG was significantly decreased in patients with DCD (P < 0.01), while (v) leptin, PP and PYY were not significantly different. GIP, GLP-1 and amylin levels correlated positively with insulin concentrations (P < 0.001, P = 0.004 and P < 0.01, respectively) in all patients. Amylin and GIP levels were strongly associated with triglycerides concentrations (P < 0.001, for both peptides) in children with CD.. Our study revealed a different secretion pattern of gut-brain axis hormones in children with CD compared with HC. The alterations in the axis were more pronounced in children with both CD and T1DM.

Topics: Adolescent; Case-Control Studies; Celiac Disease; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diet, Gluten-Free; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Incretins; Islet Amyloid Polypeptide; Leptin; Male; Pancreatic Polypeptide; Peptide YY

Gastric emptying was measured in female non-obese diabetic (NOD) mice with a duration of diabetes of 28-35 days. As controls, age- and sex-matched BLAB/cJ mice were used. Gastric emptying of diabetic mice was significantly slower than that of controls. The faeces weight and water content were significantly higher in diabetic mice than controls. The endocrine cells known to correlate with gastric emptying, namely secretin, serotonin, peptide YY (PYY) and enteroglucagon cells, were identified by immunocytochemistry and quantified by computer image analysis. The densities of duodenal secretin, serotonin and colonic PYY cells in NOD mice were significantly higher than that of control mice. Changes in these three endocrine cell types may play a role in delayed gastric emptying and in the manifestation of diarrhoea in this animal model of human diabetes type 1.

Topics: Animals; Colon; Diabetes Mellitus, Type 1; Diarrhea; Duodenum; Endocrine Glands; Feces; Female; Gastric Emptying; Mice; Mice, Inbred NOD; Peptide YY; Reference Values; Secretin; Serotonin; Water

Changes in the numbers of PYY- and enteroglucagon-immunoreactive cells in colon of animal models of human diabetes have been reported. As these peptides co-localize in the same cells it is possible that the observed changes are a result of changes in co-localization.. Animal models of human type 1 and type 2 diabetes, namely the non-obese diabetic (NOD) mouse and the obese (ob/ob) mouse, were studied. As controls for the NOD mice, BALB/cJ mice were used and for ob/ob mice, homozygous lean (+/+) mice were used. Tissue samples from colon were double-immunostained for PYY and enteroglucagon according to the indirect immunofluorescence method.. Co-localization of enteroglucagon and PYY was found in colonic endocrine cells in all groups investigated. Compared with controls, pre-diabetic NOD mice showed a decreased proportion of enteroglucagon/PYY co-localization. There was no difference in diabetic NOD mice or diabetic ob/ob mice when compared with controls.. Whereas the number of cells containing solely enteroglucagon and solely PYY increases in pre-diabetic NOD mice, production of enteroglucagon in PYY-immunoreactive cells decreases. Although the numbers of PYY and enteroglucagon cells have been reported to be changed in both diabetic NOD mice and in obese mice, the balance between co-expressing and mono-expressing cells seems to be preserved.

Topics: Animals; Colon; Diabetes Mellitus, Type 1; Enteroendocrine Cells; Female; Glucagon-Like Peptides; Homozygote; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, Obese; Peptide YY; Prediabetic State; Reference Values

In patients with chronic pancreatitis (CP) the relation among exocrine pancreatic secretion, gastrointestinal hormone release, and motility is disturbed. We studied digestive and interdigestive antroduodenal motility and postprandial gut hormone release in 26 patients with CP. Fifteen of these patients had pancreatic insufficiency (PI) established by urinary para-aminobenzoic acid test and fecal fat excretion. Antroduodenal motility was recorded after ingestion of a mixed liquid meal. The effect of pancreatic enzyme supplementation was studied in 8 of the 15 CP patients with PI. The duration of the postprandial antroduodenal motor pattern was significantly (P < 0.01) prolonged in CP patients (324 +/- 20 min) compared with controls (215 +/- 19 min). Antral motility indexes in the first hour after meal ingestion were significantly reduced in CP patients. The interdigestive migrating motor complex cycle length was significantly (P < 0.01) shorter in CP patients (90 +/- 8 min) compared with controls (129 +/- 8 min). These abnormalities were more pronounced in CP patients with exocrine PI. After supplementation of pancreatic enzymes, these alterations in motility reverted toward normal. Digestive and interdigestive antroduodenal motility are abnormal in patients with CP but significantly different from controls only in those with exocrine PI. These abnormalities in antroduodenal motility in CP are related to maldigestion.

Topics: Adult; Aged; Cholecystokinin; Chronic Disease; Diabetes Mellitus, Type 1; Digestion; Duodenum; Eating; Enzymes; Female; Gastrointestinal Motility; Humans; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; Peptide YY