1.
SGLT2i increased the plasma fasting glucagon level in patients with diabetes: A meta-analysis.
Zhu, X, Lin, C, Li, L, Hu, S, Cai, X, Ji, L
European journal of pharmacology. 2021;:174145
Abstract
Increased glucagon level was hypothesized to participate in the ketoacidosis associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) treatment. However, the effect of SGLT2i on glucagon remains controversial. Hence, we conducted this meta-analysis to assess the overall effect of SGLT2i treatment on plasma fasting glucagon level in patients with diabetes. PubMed/MEDLINE, Embase, and Cochrane databases were searched for studies published before August 2020. Clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus with reports of glucagon changes before and after SGLT2i intervention were included. Eligible trials were analyzed by fixed-effect model, random effect model, and meta-regression analysis accordingly. In total, ten trials were included in this meta-analysis. Compared with the non-SGLT2i treatment group, SGLT2i treatment resulted in increased plasma fasting glucagon levels with significance (WMD, 8.35 pg/ml; 95% CI, 2.17-14.54 pg/ml, P<0.01) in patients with diabetes mellitus. Besides, when compared with non-SGLT2i control group, the insulin level decreased (WMD, -2.78 μU/ml; 95% CI, -5.11 to -0.46 μU/ml, P = 0.02) and ketone body level increased (WMD, 0.17 mmol/l; 95% CI, 0.09-0.25 mmol/l, P<0.01) in patients with type 2 diabetes. In conclusion, our result indicated SGLT2i intervention would increase the plasma fasting glucagon level in patients with diabetes mellitus. The increase in plasma fasting glucagon level may be associated with reduced insulin level. The increased glucagon-insulin ratio after the use of SGLT2i may make diabetic patients susceptible to ketosis.
2.
The role of glucagon in weight loss-mediated metabolic improvement: a systematic review and meta-analysis.
Silvestre, MP, Goode, JP, Vlaskovsky, P, McMahon, C, Tay, A, Poppitt, SD
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;(2):233-253
Abstract
Aims This meta-analysis aimed to investigate the role of glucagon suppression in regulating glucose homeostasis following diet or bariatric surgery. Methods A comprehensive search of intervention and observational studies was conducted in Medline, Scopus, Web of Science, PubMed and Embase. Random effects model meta-analysis was performed. Primary outcomes were (i) body weight change, (ii) fasting glucagon, (iii) fasting glucose and (iv) fasting insulin concentrations. Results Twenty articles reporting data from 29 interventions were eligible for analysis. Bariatric surgery caused greater weight loss than diet (bariatric -29.7 kg [CI:-36.8, -22.6]; diet -5.8 kg [CI: -8.4, -3.3]; P < 0.00001), an effect that remained significant after adjusting for study duration (P < 0.05). Mean fasting glucagon decreased in parallel with weight loss (-11.8 ng/L [CI: -15.9, -7.8]; P < 0.00001) with no difference between bariatric and diet intervention. Both fasting glucose, and insulin decreased following weight loss (both P < 0.00001; glucose -1.7 mmol/L [CI: -2.0, -1.3]; insulin -50.6 pmol/L [CI: -66.5, -34.7] with greater decrease in fasting insulin between bariatric versus diet (P = 0.01). Conclusions Synergistic suppression of fasting glucagon and insulin resistance may act together to restore normoglycaemia following weight loss. Whether suppression of plasma glucagon may contribute to increased hunger after weight loss and gradual weight regain is not yet known.
3.
Genetic determinants of circulating GIP and GLP-1 concentrations.
Almgren, P, Lindqvist, A, Krus, U, Hakaste, L, Ottosson-Laakso, E, Asplund, O, Sonestedt, E, Prasad, RB, Laurila, E, Orho-Melander, M, et al
JCI insight. 2017;(21)
Abstract
The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals. We identified 6 genome-wide significant functional loci associated with plasma incretin concentrations in or near the SLC5A1 (encoding SGLT1), GIPR, ABO, GLP2R, F13A1, and HOXD1 genes and studied the effect of these variants on mRNA expression in pancreatic islet and on metabolic phenotypes. Immunohistochemistry showed expression of GIPR, ABO, and HOXD1 in human enteroendocrine cells and expression of ABO in pancreatic islets, supporting a role in hormone secretion. This study thus provides candidate genes and insight into mechanisms by which secretion and breakdown of GIP and GLP-1 are regulated.