Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

OBJECTIVES: Mushrooms, known for their nutritious and functional components, are considered healthy and medicinal. This study investigated the prospective association between dietary mushroom consumption and the incidence of type 2 diabetes among Korean adults aged ≥40 years. METHODS: In total, 16,666 participants who were not taking anti-diabetic medication or insulin and had normal fasting blood glucose (FBG; <126 mg/dL) were included. We used the cumulative average dietary consumption of mushrooms as an exposure metric, calculated from food frequency questionnaires at every follow-up, along with covariates collected during a baseline survey. To estimate incidence rate ratios (IRRs) for type 2 diabetes, a modified Poisson regression model with a robust error estimator was applied. RESULTS: In multivariable models, dietary mushroom consumption was inversely associated with type 2 diabetes incidence in both genders (men: IRR, 0.65; 95% confidence interval [CI], 0.47 to 0.90; plinearity=0.043 in the highest quartile (Q4) vs. the lowest quartile (Q1); women: IRR, 0.70; 95% CI, 0.54 to 0.93; plinearity=0.114 in Q4 vs. Q1). The inverse association remained after adjustment for dietary factors instead of dietary quality index, the baseline FBG, and the exclusion of incidence within the first year. Additionally, no significant interaction was found regarding the risk of type 2 diabetes between dietary mushroom consumption and participants’ gender or other factors. CONCLUSIONS Dietary mushroom consumption was inversely linked with the risk of type 2 diabetes incidence in both genders, indicating the beneficial role of mushrooms in preventing the disease.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

OBJECTIVES: Dietary soy, known for its high phytoestrogen content, has been suggested to exhibit a sex-specific association with type 2 diabetes. However, evidence regarding the sex-specific associations of different legume subtypes with type 2 diabetes remains scarce. We aimed to evaluate whether habitual consumption of soy and non-soy legumes (beans and peanuts) was prospectively and sex-specifically associated with the risk of type 2 diabetes incidence, taking into considering significant sex-specific genetic factors beyond legume consumption. METHODS: A total of 16,666 participants (96,945 person-years) were followed and 945 incident cases were observed. Cumulative intake of legume subtypes was calculated using a food frequency questionnaire administered at baseline and during the revisit surveys. RESULTS: Non-soy legumes are inversely associated with type 2 diabetes in both men and women. Dietary soy intake, however, demonstrated a unilaterally interacting sex-specific association with type 2 diabetes risk (pinteraction for sex=0.017). Specifically, there was a significant inverse association with type 2 diabetes risk in women (incidence rate ratio, 0.66; 95% confidence interval, 0.48 to 0.80; ptrend=0.007), but no such association was observed in men. This sex-specific association persisted and even appeared antagonistic in minor allele carriers of 2 novel single nucleotide polymorphisms, rs10196939 (LRRTM4) and rs11750158 (near GFPT2) (pinteraction for sex=0.001 and 0.011, respectively). CONCLUSIONS Habitual consumption of legumes shows protective impacts against type 2 diabetes, although these benefits vary by sex. Non-soy legumes provide health advantages for both men and women, whereas soy consumption seems to be beneficial exclusively for women.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

OBJECTIVES: Dietary soy, known for its high phytoestrogen content, has been suggested to exhibit a sex-specific association with type 2 diabetes. However, evidence regarding the sex-specific associations of different legume subtypes with type 2 diabetes remains scarce. We aimed to evaluate whether habitual consumption of soy and non-soy legumes (beans and peanuts) was prospectively and sex-specifically associated with the risk of type 2 diabetes incidence, taking into considering significant sex-specific genetic factors beyond legume consumption. METHODS: A total of 16,666 participants (96,945 person-years) were followed and 945 incident cases were observed. Cumulative intake of legume subtypes was calculated using a food frequency questionnaire administered at baseline and during the revisit surveys. RESULTS: Non-soy legumes are inversely associated with type 2 diabetes in both men and women. Dietary soy intake, however, demonstrated a unilaterally interacting sex-specific association with type 2 diabetes risk (pinteraction for sex=0.017). Specifically, there was a significant inverse association with type 2 diabetes risk in women (incidence rate ratio, 0.66; 95% confidence interval, 0.48 to 0.80; ptrend=0.007), but no such association was observed in men. This sex-specific association persisted and even appeared antagonistic in minor allele carriers of 2 novel single nucleotide polymorphisms, rs10196939 (LRRTM4) and rs11750158 (near GFPT2) (pinteraction for sex=0.001 and 0.011, respectively). CONCLUSIONS Habitual consumption of legumes shows protective impacts against type 2 diabetes, although these benefits vary by sex. Non-soy legumes provide health advantages for both men and women, whereas soy consumption seems to be beneficial exclusively for women.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.