Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus

2016 ◽  
Vol 36 (9) ◽  
pp. 1011-1020 ◽  
Author(s):  
Kira B. Harris ◽  
Cassie L. Boland
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus

2019 ◽  
Vol 76 (21) ◽  
pp. 1739-1748
Author(s):  
Justinne Guyton ◽  
Michelle Jeon ◽  
Amie Brooks
Keyword(s):  
Diabetes Mellitus ◽  
Weight Loss ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Alpha Cell ◽  
Cell Dysfunction ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Purpose The role of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the treatment of type 1 diabetes mellitus (T1DM), including efficacy and safety evidence, is reviewed. Summary Currently approved treatment options for glycemic control in T1DM include insulin, which combats insulin deficiency but does not effectively target disease progression or alpha cell dysfunction; and pramlintide, whose use requires multiple daily doses and involves a high likelihood of gastrointestinal side effects. GLP-1 RAs have a unique mechanism of action in T1DM, addressing alpha cell dysfunction and thereby suppressing inappropriate glucagon secretion. GLP-1 RA dosing varies from once weekly to twice daily, and the class is well tolerated in patients with type 2 diabetes. Among the GLP-1 RAs, exenatide and liraglutide have been studied in patients with T1DM, with published evidence consistently demonstrating weight loss, decreases in total daily insulin requirements, and modest improvements in glycemic control. GLP-1 RA therapy appears to be well tolerated in patients with T1DM and is associated with nonsignificant increases in hypoglycemia risk. Conclusion GLP-1 RA therapy represents an important add-on therapy option for achieving decreased insulin doses, weight loss, and modest improvements in HbA1c levels without significantly increasing hypoglycemia risk in patients with T1DM. Patients who have detectable C-peptide and/or are overweight or cannot achieve glycemic goals without hypoglycemia have been found to benefit the most from GLP-1 RA therapy. Further studies are warranted to evaluate these agents’ potential impact on clinical outcomes such as microvascular and macrovascular complications.

scholarly journals Serum Levels of Incretin Hormones – GLP-1 and GIP in Patients with Type 1 Diabetes Mellitus

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 76-83
Author(s):  
Pavel E. Stanchev ◽  
Maria M. Orbetzova ◽  
Dora D. Terzieva ◽  
Delyana Davcheva ◽  
Dimitar A. Iliev ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Serum Levels ◽  
Incretin Hormones ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulinotropic Peptide ◽  
Type 1 Dm

Abstract Background: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. Aim: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. Materials and methods: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests – height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0’), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. Results: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. Conclusion: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.

scholarly journals Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus

2018 ◽  
Vol 243 (6) ◽  
pp. 586-591 ◽  
Author(s):  
Rachel J Fenske ◽  
Michelle E Kimple
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Signaling ◽  
Type 1 Diabetes Mellitus ◽  
Therapeutic Targets ◽  
Alpha Subunit ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Since its discovery and purification by Frederick Banting in 1921, exogenous insulin has remained almost the sole therapy for type 1 diabetes mellitus. While insulin alleviates the primary dysfunction of the disease, many other aspects of the pathophysiology of type 1 diabetes mellitus are unaffected. Research aimed towards the discovery of novel type 1 diabetes mellitus therapeutics targeting different cell signaling pathways is gaining momentum. The focus of these efforts has been almost entirely on the impact of immunomodulatory drugs, particularly those that have already received FDA-approval for other autoimmune diseases. However, these drugs can often have severe side effects, while also putting already immunocompromised individuals at an increased risk for other infections. Potential therapeutic targets in the insulin-producing beta-cell have been largely ignored by the type 1 diabetes mellitus field, save the glucagon-like peptide 1 receptor. While there is preliminary evidence to support the clinical exploration of glucagon-like peptide 1 receptor-based drugs as type 1 diabetes mellitus adjuvant therapeutics, there is a vast space for other putative therapeutic targets to be explored. The alpha subunit of the heterotrimeric Gz protein (Gαz) has been shown to promote beta-cell inflammation, dysfunction, death, and failure to replicate in the context of diabetes in a number of mouse models. Genetic loss of Gαz or inhibition of the Gαz signaling pathway through dietary interventions is protective against the development of insulitis and hyperglycemia. The multifaceted effects of Gαz in regards to beta-cell health in the context of diabetes make it an ideal therapeutic target for further study. It is our belief that a low-risk, effective therapy for type 1 diabetes mellitus will involve a multidimensional approach targeting a number of regulatory systems, not the least of which is the insulin-producing beta-cell. Impact statement The expanding investigation of beta-cell therapeutic targets for the treatment and prevention of type 1 diabetes mellitus is fundamentally relevant and timely. This review summarizes the overall scope of research into novel type 1 diabetes mellitus therapeutics, highlighting weaknesses or caveats in current clinical trials as well as describing potential new targets to pursue. More specifically, signaling proteins that act as modulators of beta-cell function, survival, and replication, as well as immune infiltration may need to be targeted to develop the most efficient pharmaceutical interventions for type 1 diabetes mellitus. One such beta-cell signaling pathway, mediated by the alpha subunit of the heterotrimeric Gz protein (Gαz), is discussed in more detail. The work described here will be critical in moving the field forward as it emphasizes the central role of the beta-cell in type 1 diabetes mellitus disease pathology.

The role of stress and coping in the management of type 1 diabetes mellitus among college students

2013 ◽  
Author(s):  
Jenifer Thomas ◽  
John Moring ◽  
Anne Bowen ◽  
Adara Lindt ◽  
Victoria Emerson
Keyword(s):  
Diabetes Mellitus ◽  
College Students ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Stress And Coping ◽  
And Coping

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

2016 ◽  
Vol 174 (4) ◽  
pp. R127-R138 ◽  
Author(s):  
F S Hough ◽  
D D Pierroz ◽  
C Cooper ◽  
S L Ferrari ◽  
_ _
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Bone Fragility ◽  
Mineral Density ◽  
Good Glycaemic Control ◽  
Marrow Adiposity ◽  
Igf1 Deficiency

Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.

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