Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors.

Fiber fermentation by gut microbiota yields short-chain fatty acids (SCFAs) that are either absorbed by the gut or excreted in feces. Studies are conflicting as to whether SCFAs are beneficial or detrimental to cardiometabolic health, and how gut microbiota associated with SCFAs is unclear. In this study of 441 community-dwelling adults, we examined associations of fecal SCFAs, gut microbiota diversity and composition, gut permeability, and cardiometabolic outcomes, including obesity and hypertension. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. Fecal SCFA concentrations were inversely associated with microbiota diversity, and 70 unique microbial taxa were differentially associated with at least one SCFA (acetate, butyrate or propionate). Higher SCFA concentrations were associated with a measure of gut permeability, markers of metabolic dysregulation, obesity and hypertension. Microbial diversity showed association with these outcomes in the opposite direction. Associations were significant after adjusting for measured confounders. In conclusion, higher SCFA excretion was associated with evidence of gut dysbiosis, gut permeability, excess adiposity, and cardiometabolic risk factors. Studies assessing both fecal and circulating SCFAs are needed to test the hypothesis that the association of higher fecal SCFAs with obesity and cardiometabolic dysregulation is due to less efficient SCFA absorption.

Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut.

OBJECTIVE: Recent studies suggest the beneficial effects of metformin on glucose metabolism may be microbially mediated. We examined the association of type 2 diabetes, metformin, and gut microbiota in community-dwelling Colombian adults. On the basis of previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)-producing and mucin-degrading microbiota. RESEARCH DESIGN AND METHODS: Participants were selected from a larger cohort of 459 participants. The present analyses focus on the 28 participants diagnosed with diabetes-14 taking metformin- and the 84 participants without diabetes who were matched (3-to-1) to participants with diabetes by sex, age, and BMI. We measured demographic information, anthropometry, and blood biochemical parameters and collected fecal samples from which we performed 16S rRNA gene sequencing to analyze the composition and structure of the gut microbiota. RESULTS: We found an association between diabetes and gut microbiota that was modified by metformin use. Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06 and a distinct operational taxonomic unit of Prevotella and a lower abundance of Enterococcus casseliflavus. CONCLUSIONS: Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin's glycemic and anti-inflammatory properties.

Sex-specific associations of low birth weight with adult-onset diabetes and measures of glucose homeostasis: Brazilian Longitudinal Study of Adult Health.

Emerging evidence suggests sex differences in the early origins of adult metabolic disease, but this has been little investigated in developing countries. We investigated sex-specific associations between low birth weight (LBW; <2.5 kg) and adult-onset diabetes in 12,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Diabetes was defined by self-reported information and laboratory measurements. In confounder-adjusted analyses, LBW (vs. 2.5-4 kg) was associated with higher prevalence of diabetes in women (Prevalence Ratio (PR) 1.54, 95% CI: 1.32-1.79), not in men (PR 1.06, 95% CI: 0.91-1.25; Pheterogeneity = 0.003). The association was stronger among participants with maternal diabetes (PR 1.60, 95% CI: 1.35-1.91), than those without (PR 1.15, 95% CI: 0.99-1.32; Pheterogeneity = 0.03). When jointly stratified by sex and maternal diabetes, the association was observed for women with (PR 1.77, 95% CI: 1.37-2.29) and without (PR 1.45, 95% CI: 1.20-1.75) maternal diabetes. In contrast, in men, LBW was associated with diabetes in participants with maternal diabetes (PR 1.45, 95% CI: 1.15-1.83), but not in those without (PR 0.92, 95% CI: 0.74-1.14). These sex-specific findings extended to continuous measures of glucose homeostasis. LBW was associated with higher diabetes prevalence in Brazilian women, and in men with maternal diabetes, suggesting sex-specific intrauterine effects on adult metabolic health.

Gestational weight gain and obesity, adiposity and body size in African-American and Dominican children in the Bronx and Northern Manhattan.

Gestational weight gain (GWG) is potentially modifiable and is associated with infant size and body composition; however, long-term effects on childhood obesity have not been reported among multi-ethnic urban populations. We examined the association between GWG and child anthropometric measures and body composition at 7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ ≥95%ile) and bioelectrical impedance analysis estimates of percentage body fat (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center for Children's Environmental Health prospective birth cohort study from 1998 to 2013. Linear and logistic regression evaluated associations between excessive GWG [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre-pregnancy BMI and covariates. Pre-pregnancy BMI (mean ± standard deviation, all such values) and total GWG were 25.8 ± 6.2 kg m(-2) (45% overweight/obese) and 16.4 ± 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P < 0.001}, WC [ß: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [ß: 2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5, 5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size, adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was associated with child obesity, greater percentage body fat and abdominal adiposity. Strategies to support healthy GWG are warranted to promote healthy growth and prevent childhood obesity.

Leg length and type 2 diabetes: what's the link?

PURPOSE OF REVIEW: Human leg length is determined by a complex interplay of genetics and environmental exposures during development, which may be associated with long-term metabolic disease risk. Here, we review recent literature on the link between relative leg length and type 2 diabetes in more and less economically developed societies, wherein the contextual influences on relative leg length are unique. We also hypothesize mechanisms underlying and mediating this association. RECENT FINDINGS: Evidence from more economically prosperous Western populations and contemporary adult populations in China and Brazil indicates that lower relative leg length is associated with greater risk for impaired glucose homeostasis and type 2 diabetes. In Brazil, this association was stronger among women with early menarche. Although still poorly defined and in need of further research, the potential mechanisms likely involve suboptimal early-life net nutrition that simultaneously leads to retarded growth and impaired glucose regulation. An untested hypothesis is that the association is mediated by differences in skeletal muscle mass. SUMMARY: Epidemiologic evidence from diverse settings points to humans with shorter legs relative to their stature having higher risk for type 2 diabetes. Although research is needed to test mechanistic hypotheses, the greatest potential for improving public health will come through identification of, and intervention upon, the upstream modifiable determinants of inadequate leg growth.

Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil).

INTRODUCTION: Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals. METHODS: We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and -2-hour postload insulin and measures of insulin sensitivity. RESULTS: We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2-3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02)]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p<0.0001] but not with fasting glucose concentrations (p = 0.07). Coffee was additionally associated with 2-hour postload insulin [Never/almost never: 287.2 pmol/L, ≤1 time/day: 280.1 pmol/L, 2-3 times/day: 275.3 pmol/L, >3 times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations (p = .58). CONCLUSION: Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis.

Socioeconomic status is positively associated with measures of adiposity and insulin resistance, but inversely associated with dyslipidaemia in Colombian children.

BACKGROUND: Low socioeconomic status (SES) has been associated with higher risk of cardiometabolic diseases in developed societies, but investigation of SES and cardiometabolic risk in children in less economically developed populations is sparse. We aimed to examine associations among SES and cardiometabolic risk factors in Colombian children. METHODS: We used data from a population-based study of 1282 children aged 6-10 years from Bucaramanga, Colombia. SES was classified according to household wealth, living conditions and access to public utilities. Anthropometric and biochemical parameters were measured at a clinic visit. Cardiometabolic risk factors were analysed continuously using linear regression and as binary outcomes-according to established paediatric cut points-using logistic regression to calculate OR and 95% CIs. RESULTS: Mean age of the children was 8.4 (SD 1.4) and 51.1% of the sample were boys. Odds of overweight/obesity, abdominal obesity and insulin resistance were greater among higher SES. Compared with the lowest SES stratum, children in the highest SES had higher odds of overweight/obesity (OR=3.25, 95% CI 1.89 to 5.57), abdominal obesity (OR=2.74, 95% CI 1.41 to 5.31) and insulin resistance (OR=2.60, 95% CI 1.81 to 3.71). In contrast, children in the highest SES had lower odds of hypertriglyceridaemia (triglycerides ≥90th centile; OR=0.28, 95% CI 0.14 to 0.54) and low (≤10th centile) high-density lipoprotein (HDL) cholesterol (OR=0.35, 95% CI 0.15 to 0.78). CONCLUSIONS: In Colombian children, SES is directly associated with obesity and insulin resistance, but inversely associated with dyslipidaemia (hypertriglyceridaemia and low HDL cholesterol). Our findings highlight the need to analyse cardiometabolic risk factors separately in children and to carefully consider a population's level of economic development when studying their social determinants of cardiometabolic disease.

Relative leg length is associated with type 2 diabetes differently according to pubertal timing: the Brazilian longitudinal study of adult health.

OBJECTIVES: Studies from developed societies have shown that individuals with short legs relative to height have higher risk of type 2 diabetes. This has been much less explored in less developed populations where influences on relative leg length and diabetes may differ. The Brazilian Longitudinal Study of Adult Health (in Portuguese, ELSA-Brasil) allows us to test, in a cohort born (1934-1975) and raised when undernutrition was common, whether short legs relative to height is positively associated with diabetes, independent of early-life factors, including birth weight, age at menarche, and young-adult BMI. METHODS: We used baseline, cross-sectional data from 15,105 participants aged 35-74 years participating in ELSA-Brasil. We created age-and-sex-specific Z scores for leg length index (leg length/height × 100) according to an external reference. Diabetes was defined by self-reported physician diagnosis, medication use, fasting and 2-h post-75-g-load glucose, and A1C. RESULTS: A one-unit decrement in leg-length-index Z score was associated with 12% (8-17%) higher prevalence of diabetes in Brazilian adults, after adjustment through Poisson regression for confounders, including race, maternal education, and birth weight. This association persisted after further adjustment for menarche age, BMI (at age 20), buttocks circumference, and waist circumference. It was stronger among women with early menarche (P interaction = 0.02). Leg length index was also inversely associated with fasting glucose, fasting insulin, 2-h glucose, and A1C (P < 0.05). CONCLUSIONS: In contemporary Brazilian adults, short legs relative to height is positively associated with diabetes independent of measures of intrauterine growth, pubertal timing, and young-adult adiposity. This association is stronger in women with early menarche.

Earlier age at menarche is associated with higher diabetes risk and cardiometabolic disease risk factors in Brazilian adults: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVES: Early menarche has been linked to higher risk of type 2 diabetes in Western and Asian societies, yet whether age at menarche is associated with diabetes in Latin America, where puberty and diabetes may have different life courses, is unknown. We tested the hypothesis that earlier menarche is associated with higher diabetes risk in Brazilian adults. METHODS: We used data from 8,075 women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had complete information on age at menarche, diabetes status, and covariates. Diabetes was defined based on self-reported physician diagnosis, medication use, and laboratory variables (fasting glucose, 2-hour glucose, and glycated hemoglobin). Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Menarche onset < 11 years [vs. 13-14 years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI: 1.14-1.57) after adjusting for sociodemographic factors, maternal education, maternal and paternal diabetes, and birth weight. This persisted after further control for BMI at age 20 years and relative leg length. Additionally, among those not taking diabetes medications, earlier menarche [<11 years vs. 13-14 years (referent)] was associated with higher % glycated hemoglobin (p < 0.001), alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at baseline exam (p < 0.001). CONCLUSION: These findings support the hypothesis that earlier menarche is associated with greater risk for adult diabetes and cardiometabolic disease in the Brazilian context.

Adiposity indices in the prediction of insulin resistance in prepubertal Colombian children.

OBJECTIVE: To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children. DESIGN: We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models. SETTING: Bucaramanga, Colombia. SUBJECTS: Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study. RESULTS: A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01). CONCLUSIONS: ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

Information channels associated with awareness of human papillomavirus infections and vaccination among Latino immigrants from safety net clinics.

We report on information channels associated with awareness about human papillomavirus (HPV) among immigrant Central and South American Latinos. We conducted a survey of 1,334 Latino ≥ 21 years attending safety-net clinics in 2007-2008. Logistic regression analyses evaluated associations with HPV awareness. Forty-eight percent were aware of HPV infection and 40% were aware of the vaccine. Spanish television (38%) and providers (23%) were the primary HPV information sources. Infection awareness was associated with internet use (OR 1.47; 95% CI 1.10-1.96) and self-efficacy to find health information (OR 1.19; 95% CI 1.08-1.30). Vaccine awareness was associated with media use for health information (OR 1.27; 95% CI 1.09-1.49) and internet use (OR 1.59; 95% CI 1.18-2.13). Although Spanish television has reached this low HPV awareness group, there may be missed opportunities for education by providers. Television and the internet may also be effective channels for future interventions.