Genetic determinants of impaired awareness of hypoglycemia in type 1 diabetes
PHARMACOGENETICS AND GENOMICS
Authors: Schouwenberg, Bas J.; Coenen, Marieke J.; Paterson, Andrew D.; Tack, Cees J.; Smits, Paul; Kramers, Cornelis; de Galan, Bastiaan E.
Abstract
Objective It is likely that impaired awareness of hypoglycemia (IAH) and severe hypoglycemia are in part determined by genetic factors. The aim of this study was to investigate candidate genes for associations with IAH and severe hypoglycemia in a cohort of patients with type 1 diabetes. Participants and methods Consecutive patients with type 1 diabetes were genotyped for single-nucleotide polymorphisms in or near the genes for the beta 1 and beta 2 adrenergic receptor (ADRB1, ADRB2), SORCS1, and BNC2, and for the insertion/deletion polymorphism in the ACE gene. IAH and severe hypoglycemia were assessed using a validated questionnaire. Results Of 486 patients, 32.5% were classified as having IAH. The Arg16Gly polymorphism of ADRB2 was associated with IAH (odds ratio: 1.49, 95% confidence interval: 1.01-2.20, P= 0.046) Gly16 (GG) versus carriers of the A allele. In a haplotype analysis, the association was the highest in patients with GG at position 16 and heterozygous at position 27 (odds ratio: 2.19, 95% confidence interval: 1.33-3.61, P= 0.03). There were no associations between IAH and other genes, and none of the studied genes was associated with severe hypoglycemia. Conclusion Genotypes at two variants of ADRB2 are associated with IAH. This association is comparable with the risk of classical risk factors for IAH. (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Increased Abundance of Lactobacillales in the Colon of Beta-Adrenergic Receptor Knock Out Mouse Is Associated With Increased Gut Bacterial Production of Short Chain Fatty Acids and Reduced IL17 Expression in Circulating CD4(+) Immune Cells
FRONTIERS IN PHYSIOLOGY
Authors: Bartley, Akeem; Yang, Tao; Arocha, Rebeca; Malphurs, Wendi L.; Larkin, Riley; Magee, Kacy L.; Vickroy, Thomas W.; Zubcevic, Jasenka
Abstract
Emerging evidence suggests an associative link between gut dysbiosis, the autonomic nervous system (ANS) and the immune system in pathophysiology of neurogenic hypertension (HTN). However, the close interplay between these three systems presents us with difficulties in deciphering the cause-effect relationship in disease. The present study utilized beta 1 and 2 adrenergic receptor knock out (AdrB1(tm1Bkk)AdrB2(tm1Bkk)/J KO) mice to isolate the effects of reduced overall sympathetic drive on gut microbiota and systemic immune system. We observed the following: (i) Diminished beta adrenergic signaling mainly reflects in shifts in the Firmicutes phyla, with a significant increase in abundance of largely beneficial Bacilli Lactobacillales in the KO mice; (ii) This was associated with increased colonic production of beneficial short chain fatty acids (SCFAs) butyrate, acetate and propionate, confirming functional microbiota shifts in the KO mice; (iii) Dampened systemic immune responses in the KO mice reflected in reduction on circulating CD4(+).IL17(+) T cells and increase in young neutrophils, both previously associated with shifts in the gut microbiota. Taken together, these observations demonstrate that reduced expression of beta adrenergic receptors may lead to beneficial shifts in the gut microbiota and dampened systemic immune responses. Considering the role of both in hypertension, this suggests that dietary intervention may be a viable option for manipulation of blood pressure via correcting gut dysbiosis.