Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

Wewalka, Marlene; Patti, Mary‐Elizabeth; Barbato, Corinne; Houten, Sander M.; Goldfine, Allison B.

doi:10.1210/jc.2013-3367

Cited by 112 publications

(94 citation statements)

References 39 publications

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“…Furthermore, there is an accelerated time to peak postprandial levels that is observed post–RYGB for both FGF19 and total BAs. These findings are consistent with findings of Wewalka et al, who also noted that improved glycemic control via IMM in T2DM patients did not increase fasting BA levels [36]. Though it is impossible to exclude the confounding effect of greater weight loss after RYGB, the study by Kohli et al, which controlled for weight loss and demonstrated significantly increased levels of BAs in nondiabetic patients undergoing RYGB but not LAGB suggests that weight loss alone does not account for increased levels of BAs [30].…”

Section: Discussionsupporting

confidence: 92%

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

et al. 2015

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Purpose To quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Materials and Methods Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n=15) or RYGB (n=15). Results Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 mo the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB FGF19 increased in the fasted (93±15 to 152±19 pg/ml; P=0.008) and postprandial states (AUC, 10.8 ± 1.9 to 23.4 ± 4.1 pg × hr/ml × 103; P=0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC × 103, 6.63 ± 1.3 to 15.16 ± 2.56 M × h; P=0.003) and decreased after IMM (AUC × 103 8.22 ±1.24 to 5.70 ± 0.70; P=0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r=0.54, P=0.04) and trended negatively with HbA1c (r=−0.44; P=0.09); these associations were not observed after IMM. Conclusion BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

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Section: Discussionsupporting

confidence: 92%

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

et al. 2015

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“…This pattern is not directly linked to obesity and glucose per se [25] . However, increases in taurine-conjugated bile acid in patients with T2DM may be related to lower rates of taurine deconjugation that is catalyzed by some bile salt hydrolases enriched in the human gut microbiota [26] .…”

Section: Bile-acid Metabolismmentioning

confidence: 84%

Intestinal microbiota and type 2 diabetes: From mechanism insights to therapeutic perspective

Han¹,

Lin²

2014

WJG

145

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The incidence of type 2 diabetes (T2DM) is rapidly increasing worldwide. However, the pathogenesis of T2DM has not yet been well explained. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host. Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM.

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“…Thus, it is clear that the metabolic abnormalities associated with obesity, insulin resistance and T2D exist on a spectrum and are not necessarily independent of one another, and may be a function of altered enterohepatic bile acid circulation (Haeusler et al, 2015). Better understanding of the molecular basis for these improvements is an area of intense research (Wewalka et al, 2014). …”

Section: Bile Acids and Obesitymentioning

confidence: 99%

Bile acids and bariatric surgery

Albaugh

Banan

Ajouz

et al. 2017

Molecular Aspects of Medicine

111

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Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40-80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short-and long-term metabolic improvements after bariatric surgery is critically examined.

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Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

Cited by 112 publications

References 39 publications

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

Intestinal microbiota and type 2 diabetes: From mechanism insights to therapeutic perspective

Bile acids and bariatric surgery

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