incretins and Diabetes--Gestational

Gestational diabetes mellitus (GDM) is a metabolic disease affecting an increasing number of pregnant women around the world. It is not only associated with numerous perinatal complications but also has long-term consequences impacting maternal health and fetal development. To prevent them, it is important to keep glucose levels under control. As much as 15-30% of GDM patients will require treatment with insulin, metformin, or glyburide. With that in mind, it is crucial to keep searching for novel and improved pharmacotherapies. Nowadays, there are ongoing studies investigating the use of other groups of drugs that have proven successful in the treatment of T2DM. Glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP-4) inhibitor are among the drugs targeting the incretin system and are currently receiving significant attention. The aim of our review is to demonstrate the potential of these medications in treating GDM and preventing its later complications. It seems that both groups may be successful in the GDM management used alone or as an addition to better-known drugs, including metformin and glyburide. However, more clinical trials are needed to confirm their importance in GDM treatment and to demonstrate effective therapeutic strategies.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide 1; Glyburide; Humans; Hypoglycemic Agents; Incretins; Metformin; Pregnancy

Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Diabetic Retinopathy; Epigenesis, Genetic; Female; Fetal Development; Genetic Predisposition to Disease; Glucagon; Glucagon-Like Peptide 1; Homeostasis; Humans; Incretins; Insulin Resistance; Insulin-Secreting Cells; Life Style; Liver; Muscle, Skeletal; Myocardium; Obesity; Prediabetic State; Pregnancy

Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations.. Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion.. Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised β' 0.393 (0.289-0.498), p = 1.3 × 10. These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Insulin; Placenta; Pregnancy

Incretins are crucial stimulators of insulin secretion following food intake. Data on incretin secretion and action during pregnancy are sparse.. The aim of the study was to investigate the incretin response during an oral glucose tolerance test (OGTT) in pregnant women with and without gestational diabetes mellitus (GDM).. We analyzed data from the ongoing observational PREG study (NCT04270578).. The study was conducted at the University Hospital Tübingen.. We examined 167 women (33 with GDM) during gestational week 27 ± 2.2.. Subjects underwent 5-point OGTT with a 75-g glucose load.. We assessed insulin secretion and levels of total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glicentin, and glucagon during OGTT. Linear regression was used to analyze the relation of GLP-1 and glucose with insulin secretion and the association of incretin levels on birth outcome.. Insulin secretion was significantly lower in women with GDM (P < 0.001). Postload GLP-1 and GIP were ~20% higher in women with GDM (all P < 0.05) independent of age, body mass index, and gestational age. GLP-1 increase was associated with insulin secretion only in GDM, but not in normal glucose tolerance. Postprandial GLP-1 levels were negatively associated with birth weight.. The more pronounced GLP-1 increase in women with GDM could be part of a compensatory mechanism counteracting GLP-1 resistance. Higher GLP-1 levels might be protective against fetal overgrowth.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Macrosomia; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Insulin; Pregnancy

The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB.. In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using. RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group.. GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved.

Topics: Adult; Anastomosis, Roux-en-Y; Blood Glucose; Diabetes, Gestational; Female; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperglycemia; Hyperinsulinism; Incretins; Insulin Resistance; Insulin-Secreting Cells; Lipid Metabolism; Lipids; Obesity; Pregnancy

The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin effect during third trimester and 3 to 4months postpartum in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120min after 75g-oral glucose tolerance test (OGTT) (PG120min): 10.1±0.6mmol/l (mean±SEM)) and eight women with normal glucose tolerance (NGT; PG120min: 7.0±0.1mmol/l) were investigated on four occasions: 4h 50g-OGTT and isoglycaemic intravenous glucose infusion during third trimester and 3 to 4months postpartum. In women with GDM, the incretin effect increased significantly postpartum (31±6 vs. 56±6%, p=0.02), whereas the increment in women with NGT was insignificant (35±12 vs. 56±9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD=100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic levels in women with GDM (37±3%), but increased (p=0.030) to normal levels post partum (58±6%). GIGD did not change significantly in NGT women (48±3 vs. 57±6%, p=0.94). Women with GDM exhibit a reduced incretin effect which is fully reversible alongside the restoration of normal glucose homeostasis, whereas the reduction in incretin effect during pregnancy in women with NGT was insignificant. Our results suggest that decreased incretin effect in women with GDM is a fully reversible phenomenon.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Humans; Incretins; Insulin; Postpartum Period; Pregnancy; Pregnancy Trimester, Third