Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008–2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.
Background While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. Methods We described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups. Results No COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. Conclusions Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.
Objective: This study investigated the sex-associated difference in the impact of obesity on antibody response to a COVID-19 vaccine.Methods: This study included 2,435 health care workers who received two doses of the BioNTech, Pfizer (BNT162b2) vaccine and participated in a serological survey, during which they were tested for anti-SARS-CoV-2 spike immunoglobin G (IgG) antibodies and asked for information on height, weight, and vaccination history via a questionnaire. Multivariable linear regression analysis was used to estimate the geometric mean titers (GMT) of antibodies for each sex and BMI category. Results:The relationship between BMI and anti-SARS-CoV-2 spike IgG titers markedly differed by sex (p value for interaction = 0.04). Spike IgG antibody titers tended to decrease with increasing BMI in men (p value for trend = 0.03); GMT (95% CI) were 6,093 (4,874-7,618) and 4,655 (3,795-5,708) for BMI < 18.5 and ≥30 kg/m 2 , respectively. In contrast, spike IgG antibody titers did not significantly differ across BMI categories in women (p value for for trend = 0.62); GMT (95% CI) were 6,171 (5,714-6,665) and 5,506 (4,404-6,883) for BMI <18.5 and ≥30, respectively. Conclusions: Higher BMI was associated with lower titers of SARS-CoV-2 spike antibodies in men, but not in women, suggesting the need for careful monitoring of vaccine efficacy in men with obesity, who are at high risk of severe COVID-19 outcomes.
Aims/IntroductionHigher iron storage has been linked to an increased risk of type 2 diabetes, but little is known about the mediator of this association. Here, we prospectively investigated the association between circulating ferritin, a marker of iron storage, and the incidence of type 2 diabetes among Japanese individuals.Materials and MethodsThe participants were 4,754 employees who attended a comprehensive health check‐up in 2008–2009 and donated blood for the study. During 5 years of follow up, diabetes was identified based on plasma glucose, glycated hemoglobin and self‐report. Two controls matched to each case on sex, age and date of check‐up were randomly chosen using density sampling, giving 327 cases and 641 controls with ferritin measurement. Cox proportional hazards regression was used to estimate the hazard ratio while adjusting for a series of potential confounders or mediators.ResultsElevated serum ferritin levels were associated with a significantly increased risk of type 2 diabetes, with the hazard ratio adjusted for known risk factors in the highest vs lowest quartile of 1.42 (95% confidence interval: 1.03–1.96). This association was unchanged after adjustment for C‐reactive protein and adiponectin, but attenuated after adjustment for liver enzyme and insulin resistance (hazard ratio 1.04). The ferritin–diabetes association was confined to non‐obese participants.ConclusionsThese results suggest that elevated iron storage is associated with increased risk of type 2 diabetes in normal weight individuals, and that this association is partly mediated through liver dysfunction and resulting insulin resistance.
OBJECTIVE Prediabetes has been suggested to increase risk for death; however, the definitions of prediabetes that can predict death remain elusive. We prospectively investigated the association of multiple definitions of prediabetes with the risk of death from all causes, cardiovascular disease (CVD), and cancer in Japanese workers. RESEARCH DESIGN AND METHODS The study included 62,785 workers who underwent a health checkup in 2010 or 2011 and were followed up for death from 2012 to March 2019. Prediabetes was defined according to fasting plasma glucose (FPG) or glycated hemoglobin (HbA 1c ) values or a combination of both using the American Diabetes Association (ADA) or World Health Organization (WHO)/International Expert Committee (IEC) criteria. The Cox proportional hazards regression model was used to investigate the associations. RESULTS Over a 7-year follow-up, 229 deaths were documented. Compared with normoglycemia, prediabetes defined according to ADA criteria was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.53; 95% CI 1.12–2.09) and death due to cancer (HR 2.37; 95% CI 1.45–3.89) but not with death due to CVD. The results were materially unchanged when prediabetes was defined according to ADA FPG, ADA HbA 1c , WHO FPG, or combined WHO/IEC criteria. Diabetes was associated with the risk of all-cause, CVD, and cancer deaths. CONCLUSIONS In a cohort of Japanese workers, FPG- and HbA 1c -defined prediabetes, according to ADA or WHO/IEC, were associated with a significantly increased risk of death from all causes and cancer but not CVD.
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