Background The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP). Methods In 2013–16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1,702 participants (59.9–77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D. Conclusions T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.
What is already known on this topic? Filipino American adults have a higher risk of developing type 2 diabetes than White adults, other Asian adults, and residents of the Philippines despite their relatively low body weight.What is added by this report? Among Filipino American adults, the prevalence of overweight and obesity increased from the first to the 3rd generation, whereas rates of type 2 diabetes were only significantly higher in the 2nd generation than the 1st generation.What are the implications for public health practice? Overweight and obesity, diet quality, and other lifestyle factors may explain the higher type 2 diabetes rates among 2nd-generation Filipino American adults. Culturally appropriate interventions are needed to reduce lifestyle factors that result in high rates of type 2 diabetes among Filipino immigrants and their descendants.
Background: As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT. Methods: In 2013-2016, 1,746 participants aged 69.2 (standard deviation, 2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body dual X-ray absorptiometry and abdominal magnetic resonance imaging scans. Participants with self-reported T2D and=or medication were classified as T2D, those with fasting glucose >125 and 100-125 mg=dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status. Results: Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG), with significant ethnic differences (P < 0.0001). In fully adjusted models, VAT, VAT=SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (P < 0.001). Across ethnic groups, the VAT=SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT=SAT in Japanese Americans. Conclusions: These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.
Objectives As features of the gut microbiome may promote the development of type 2 diabetes (T2D), we examined the hypothesis that gut microbiome composition differs by glycemic/diabetes status within a subset of the Multiethnic Cohort. We also estimated the association of lipopolysaccharide-binding protein (LBP) as a measure of circulating bacterial endotoxin with T2D. This outer membrane component of gram-negative bacteria may affect glucose metabolism. Methods In 2013–16, cohort members from 5 ethnic groups completed clinic visits, questionnaires, and stool collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and prediabetes (PT2D). We characterized the gut microbiome through 16S rRNA gene sequencing (V1-V3). Plasma LBP was measured by ELISA. Linear regression was applied to estimate associations of gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1756 participants (59.9–77.4 years), 315 (18%) were T2D, 158 (9%) UT2D, 518 (29%) PT2D, and 765 (44%) normoglycemic (NG). The Shannon diversity index was lower (6.30, 6.25, 6.28, 6.18; P = 0.02) and LBP was higher (26.0, 26.6, 28.6, 28.2 µg/mL; P = 0.0009) in T2D than NG participants. Of 10 phyla, Actinobacteria and Firmicutes were inversely associated with T2D status (P = 0.004). Six of 161 genera were significantly related to T2D status after Bonferroni adjustment: the abundance of Clostridium sensu stricto 1, Lachnospira, Lachnospiraceae NC2004, and Peptostreptococcaceae was lower, while Lachnospiraceae uncultured and Escherichia-Shigella were more abundant among T2D than NG participants. In general, those with PT2D and UT2D had values closer to NG than T2D individuals. Conclusions Participants with T2D showed a lower abundance of bacteria capable of fermenting plant polysaccharides and higher levels of gram-negative endotoxin-producing bacteria indicating that a less favorable pattern of gut microbiome community structure may contribute to T2D through endotoxin binding to toll-like receptors via LBP and activation of the NFkB pathway associated with chronic systemic inflammation. Funding Sources NIH grants P01CA169530, U01CA164973, P30CA071789, #UL1TR000130, R01HL140335.
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