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Objective: Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association.Research Design and Methods: This study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D.Results: During a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78-0.89) after adjustment for age, sex, BMI, race, center, Townsend deprivation index, lifestyle factors, history of disease, and other supplement use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker (P-interaction = 0.02). A genetic risk score for T2D did not modify this association (P-interaction = 0.99).Conclusions: Our findings indicate that glucosamine use is associated with a lower risk of incident T2D. [ABSTRACT FROM AUTHOR]

Little is known about the genetic influence on BMI trajectory throughout adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI-associated variants among 9,971 women and 6,405 men of European ancestry. Serial measures of BMI were assessed from 18 (women) or 21 (men) years to 85 years of age. We also examined BMI change in early (from 18 or 21 to 45 years of age), middle (from 45 to 65 years of age), and late adulthood (from 65 to 80 years of age). GRS was positively associated with BMI across all ages, with stronger associations in women than in men. The associations increased from early to middle adulthood, peaked at 45 years of age in men and at 60 years of age in women (0.91 and 1.35 kg/m2 per 10-allele increment, respectively) and subsequently declined in late adulthood. For women, each 10-allele increment in the GRS was associated with an average BMI gain of 0.54 kg/m2 in early adulthood, whereas no statistically significant association was found for BMI change in middle or late adulthood or for BMI change in any life period in men. Our findings indicate that genetic predisposition exerts a persistent effect on adiposity throughout adult life and increases early adulthood weight gain in women. [ABSTRACT FROM AUTHOR]

Objective: Fibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.Research Design and Methods: We genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.Results: We observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.Conclusions: Our data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake-decreasing allele of the FGF21 variant to improve body composition and abdominal obesity. [ABSTRACT FROM AUTHOR]

Background: Chromosome 9p21 variants are among the most robust genetic markers for coronary artery disease (CAD), and previous studies have suggested that genetic effects of this locus might be modified by dietary factors. Intake of sugar-sweetened beverages (SSBs), which are the main dietary source of added sugar, has been shown to interact with genetic factors in affecting CAD risk factors such as obesity. Objective: We aimed to test whether SSB intake modified the association between chromosome 9p21 variants and CAD risk in Hispanics living in Costa Rica. Design: The current study included 1560 incident cases of nonfatal myocardial infarction (MI) and 1751 population-based controls. Three independent single nucleotide polymorphisms (SNPs) at the chromosome 9p21 locus were genotyped. SSB intake was assessed with the use of a food-frequency questionnaire and was defined as the frequency of intake of daily servings of sweetened beverages and fruit juice. Results: We showed a significant interaction between SSB intake and one of the 3 variants (i.e., rs4977574) on MI risk. The per-risk allele OR (95% CI) of rs4977574 for MI was 1.44 (1.19, 1.74) in participants with higher SSB consumption (>2 servings/d), 1.21 (1.00, 1.47) in those with average consumption (1-2 servings/d), and 0.97 (0.81, 1.16) in subjects with lower consumption (<1 serving/d; P-interaction = 0.005). A genetic risk score derived from the sum of risk alleles of the 3 SNPs also showed a significant interaction with SSB intake on MI risk (P-interaction = 0.03). Conclusion: Our data suggest that unhealthy dietary habits such as higher intake of SSBs could exacerbate the effects of chromosome 9p21 variants on CAD. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein A5 gene (AP0A5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies. Objective: We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial. Design: The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycéride from baseline to 2 y of follow-up. Results: After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk alíele (G alíele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G alíele had a greater increase in HDL cholesterol than did participants without this alíele (P = 0.038). Conclusion: Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk alíele. The Pounds Lost Trial was registered at clinicaltrials.gov as NCT00072995. [ABSTRACT FROM AUTHOR]