Endocrine-disrupting effects of bisphenol-A, thiamethoxam, and fipronil in hormone-naïve transmen compared to cis-women.

BACKGROUND: Current evidence suggests that the etiology of gender dysphoria (GD) is multifactorial: this, however, remains unclear. Endocrine-disrupting chemicals (EDCs) are one of the etiological hypotheses. OBJECTIVES: In this study, we aimed to evaluate the urinary levels of bisphenol A (BPA), thiamethoxam, and fipronil in hormone-naïve transmen compared with case-matched cis-women as well as the relation between sex hormone levels and EDCs. METHODS: Drug-naïve transmen diagnosed with GD and who were referred from the psychiatry outpatient clinic to the outpatient clinic of the Department of Endocrinology, Marmara University Hospital, were included in the study. These individuals were assessed for eligibility; 38 drug-naïve transmen and 22 cis-women were recruited as the control group. After anthropometric evaluation laboratory tests for FSH, LH, total testosterone, and estradiol were carried out, spot urine samples were collected to evaluate the urine metabolic excretion of BPA, thiamethoxam, and fipronil. RESULTS: We found that androgens, total testosterone, androstenedione, and DHEAS levels were significantly higher in transmen than in cis-women. Thiamethoxam was considerably higher in cis-women than in transmen, whereas fipronil and BPA levels were similar in both groups. A negative correlation was found between thiamethoxam and testosterone and between thiamethoxam and BPA levels. CONCLUSION: The available data suggest that the EDCs that we are most exposed to in our lives are not the only factor in GD development. Even transmen who have not taken hormone replacement have high testosterone levels; however, the mechanism has not as yet been elucidated. The challenge is to determine whether this is a factor leading to GD or a condition that develops in common with GD.

SGLT2 inhibitors improve plasma atherogenic biomarkers in patients with type 2 diabetes: a real-world retrospective observational study.

BACKGROUND: There are cost-effective, non-invasive, and predictive tools used to predict the CVD risk in patients with diabetes such as the "atherogenic index of plasma (AIP)" which is defined as the logarithm to the base 10 of the ratio of fasting plasma TG (mg/dL) to HDL-C [log (TG/HDL-C)], triglyceride to high density lipoprotein (TG-to-HDL-C) ratio and the triglyceride glucose (TyG) index which is calculated as Ln (fasting TG [mg/dL] × fasting blood glucose (mg/dL)/2). These tools are indirect markers of atherosclerosis. Dapagliflozin and empagliflozin have exhibited cardiovascular beneficial effects and this study evaluated the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on AIP, TyG index and TG-to-HDL-C ratio in patients with type 2 diabetes. METHODS: This single center, retrospective, observational study involved patients with type 2 diabetic patients who were prescribed SGLT2i in the endocrinology outpatient clinic between January 2017 and June 2019. Demographic and clinical data were collected from patient files. AIP, TyG index and TG-to-HDL-C ratio were calculated obtained at the first visit and the sixth month visit. RESULTS: Overall, 143 patients with T2DM (75 women, 68 men) were recruited in this study. Sixty-six patients were prescribed dapagliflozin (46.2%), and 77 were prescribed empagliflozin (53.8%). SGLT2i treatment did not alter the lipid profile except the serum triglyceride (TG) levels. Serum TG levels were significantly reduced after 6 months of SGLT2i therapy (P=0.045). All patients had significant reductions in AIP at 6-month follow-up (P<0.001), accompanied by a significant reduction in TyG index (P<0.001). Both empagliflozin and dapagliflozin caused significant decrease in AIP (P=0.043 and P<0.001, respectively) and TyG index (P=0.010 and P<0.001, respectively). CONCLUSIONS: Both dapagliflozin and empagliflozin were noted to significantly affect AIP and TyG indexes, which indicate atherosclerotic cardiovascular risk, with or without statin treatment regardless of lipid parameters.

Hyperandrogenism-related metabolic changes in drug-naïve transmen compared to cisgender women: a case-controlled study.

INTRODUCTION: The aetiology of gender dysphoria is still unclear. Although prior studies have shown that trans men have higher androgen levels than cisgender women, they all concluded unselected populations. Our reason for performing this study is to evaluate trans men's hormone profile and metabolic status to compare with cisgender women in a more selected population. This is the first case-controlled study to compare anthropometric, metabolic, and endocrinological parameters of drug-naïve trans men with those of cisgender women. MATERIAL AND METHODS: We designed this study as a single-centre observational cohort study. We included 70 drug naïve trans men, and the control group comprised 34 healthy cisgender women. We measured and compared hormone profiles and metabolic parameters in the 2 groups. RESULTS: Of the 70 trans men individuals, 16 (22.85%) met the Rotterdam criteria and were diagnosed with polycystic ovary syndrome (PCOS); 4 individuals in the control group met the criteria (11.7%). Although we matched body mass index in the groups, total testosterone, free androgen index, androstenedione, 17 hydroxyprogesterone, muscle strength, triglyceride, and homeostatic model assessment of insulin resistance levels were significantly higher in the trans men than in the cisgender women (p < 0.05). Even after were excluded PCOS patients, hyperandrogenaemia was apparent in the trans men. CONCLUSION: Our study showed that trans men have clearly higher androgen levels, which may have been the reason for metabolic changes compared to cisgender women. However, the main reason for hyperandrogenism in drug-naïve trans men is still not known, and more comprehensive studies are needed.

Vitamin D receptor and estrogen receptor gene polymorphisms in men with type 2 diabetes: Effects on Bone Metabolism.

Purpose: There is an increased fracture risk in type 2 diabetes mellitus [DM] patients independent of bone mineral density [BMD], both in men and women. Estrogen receptor [ER]-alpha and vitamin D receptor [VDR] gene polymorphisms may predispose patients to increased osteoporosis and fracture risk. This study aims to analyze the relationship of the ER-alpha gene and VDR gene polymorphisms with indicators of bone turnover and BMD in male type 2 diabetic patients. Methods: Type 2 diabetic men diagnosed with diabetes for at least one year and healthy controls were included in this cross-sectional study. BMD was measured by dual X ray absorptiometry. Gene polymorphisms were evaluated with polymerase chain reaction-restriction length polymorphism. Serum iPTH, calcium, beta-CrossLaps (cTx), osteocalcin, and free testosterone levels were also evaluated. Results: Participants were 141 type 2 diabetic men [55 ± 8 years] and 100 healthy controls [53 ± 7 years]. BMD measurements were not statistically different between the groups. While iPTH [p < 0.05] and serum calcium levels [p = 0.03] were higher in men with type 2 DM; beta-CrossLaps [p = 0.0001], osteocalcin [p = 0.005], and free testosterone [p = 0.04] were lower than controls. The differences in terms of the frequencies of VDR Apa, Taq, Bsm, Fok and ER-alpha polymorphisms were not statistically significant between the groups. No relationship was observed between polymorphisms and BMD in both groups. Conclusions: VDR and ER-alpha gene polymorphisms seem to have no effect on BMD and bone turnover in men with DM.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

OBJECTIVE: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. METHODS: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. RESULTS: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. CONCLUSION: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.

Genetic and Clinical Characterization of Patients with Maturity-Onset of Diabetes of the Young (MODY): Identification of Novel Variations.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is a rare monogenic type of diabetes, and accounts for 2-5% of all diabetes cases. An early age of onset, a family history supporting autosomaldominant inheritance, insulin resistance, and the absence of autoimmunity are the major characteristics of MODY. However, genetic testing is crucial for diagnosis. AIMS: To investigate the 7 MODY-related genes and clinical findings of patients with a preliminary clinical diagnosis of MODY. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In this study, 7 genes (KCNJ11, ABCC8, INS, GCK, HNF4A, HNF1A, and HNF1B) related to MODY were screened via targeted sequencing in 182 cases with a confirmed pre-diagnosis of MODY. The clinical characteristics of the patients were evaluated retrospectively. RESULTS: A total of 182 patients, 48% of whom were women, between the ages of 18-62 were included in the study. In 30 cases (16.4%), 28 different pathogenic variations were found, of which 20 were previously reported and 8 were novel variations segregated by disease within the family. Pathogenic variations were detected in the following genes in order of mutation frequency; GCK, HNF1A, ABCC8, HNF4A, HNF1B and KCNJ11. Interestingly, six of the 30 cases (20%) carried a pathogenic variation in the ABCC8 gene. No mutation was detected in the INS gene. A family history of vertically transmitted diabetes and elevated HbA1C at the time of diagnosis were found in 20 (66%) and 16 (52%) cases, respectively. CONCLUSION: In this series, 28 different pathogenic variations are identified, 8 of which are novel. The rate of pathogenic variation in the ABCC8 gene is unexpectedly high. Two-thirds of cases have a family history of vertically transmitted diabetes.

When do we need to suspect maturity onset diabetes of the young in patients with type 2 diabetes mellitus?

ABSTRACT Objetivo: Maturity onset diabetes of the young (MODY) patients have clinical heterogeneity as shown by many studies. Thus, often it is misdiagnosed to type 1 or type 2 diabetes(T2DM). The aim of this study is to evaluate MODY mutations in adult T2DM patients suspicious in terms of MODY, and to show clinical and laboratory differences between these two situations. Subjects and methods: In this study, we analyzed 72 type 2 diabetic patients and their relatives (35F/37M) who had been suspected for MODY and referred to genetic department for mutation analysis. The gene mutations for MODY have been assessed in the laboratory of Marmara University genetics. Totally 67 (32F/35M; median age 36.1) diabetic patients were analyzed for 7 MODY mutations. Twelve patients who have uncertain mutation (VUS) were excluded from study for further evaluation. MODY(+) (n:30) patients and T2DM patients (n:25) were compared for clinical and laboratory parameters. Results: In MODY(+) subjects, mutations in GCK (MODY 2) (n:12; 40%) were the most common followed by HNF4A (MODY 1) (n:4; 13.3%). Diabetes diagnosis age was younger in MODY(+) group but not statistically significant. Sixty-six percent of MODY(+) subjects had diabetes history at 3-consecutive generations in their family compared with 28% of T2DM patients statistically significant (p:0.006). Gender, BMI, C-peptide, HbA1c, lipid parameters, creatinine, GFR, microalbuminuria, vitamin D and calcium were not statistically different between the groups. Conclusion: According to present study results, MODY mutation positivity is most probable in young autoantibody (-) diabetic patients diagnosed before 30 years of age, who have first degree family history of diabetes.