Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.

BACKGROUND: In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. MATERIALS AND METHODS: This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. RESULTS: Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). CONCLUSION: In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males.

Type 2 diabetes linked FTO gene variant rs8050136 is significantly associated with gravidity in gestational diabetes in a sample of Bangladeshi women: Meta-analysis and case-control study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a growing public health concern that has not been extensively studied. Numerous studies have indicated that a variant (rs8050136) of the fat mass-associated gene, FTO, is associated with both GDM and Type 2 diabetes mellitus(T2DM). We conducted a meta-analysis on the association between the FTO single nucleotide polymorphism (SNP) rs8050136 and T2DM, followed by a case-control study on the association of the said SNP and GDM in a sample of Bangladeshi women. METHOD: A total of 25 studies were selected after exploring various databases and search engines, which were assessed using the Newcastle-Ottawa Scale (NOS). The MetaGenyo web tool was used to conduct this meta-analysis. A case-control study was performed on 218 GDM patients and 284 controls to observe any association between FTO rs8050136 and GDM. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS) method, and statistical analyses were performed using various statistical softwares. RESULTS: In the meta-analysis 26231 cases and 43839 controls were examined. Pooled association analyses revealed a statistically significant relationship between the FTO rs8050136 polymorphism and an elevated risk of T2DM under all genetic models (P<0.05). In the case-control study, synergistic analyses of the SNP and gravida with GDM revealed a significant (P<0.01) association with an increase in odds by 1.6 to 2.4 folds in multigravida and decrease in odds by 2 folds in primigravida. A positive family history of diabetes and the minor allele of this SNP collectively increased the risk of developing GDM by many-fold (1.8 to 2.7 folds). However, after accounting for family history of diabetes and gravidity, analyses showed no significant association with GDM. CONCLUSION: Our meta-analysis revealed a significant association between SNP rs8050136 of FTO with T2DM, and this variant was substantially associated with an increased risk of GDM in a sample of Bangladeshi multigravida women.

Serum homocysteine level in newly diagnosed young patients with abnormal glucose tolerance.

Background: Hyperhomocysteinemia is an emerging risk factor causing early-onset cardiovascular events. The objective of the study was to assess serum homocysteine levels in newly diagnosed young persons (age < 30 years) with abnormal glucose tolerance. Methodology: This cross-sectional study included 40 young participants with newly diagnosed abnormal glucose tolerance (including prediabetes and diabetes mellitus) and an equal number of young persons with normal glucose tolerance (normal glucose tolerance vs prediabetes vs. diabetes mellitus-age (years): 25.0 (22.0, 28.0) vs 25.50 (21.50, 27.0) vs 28.0 (25.0, 29.0), median (interquartile range)). Glycemic status was diagnosed by American Diabetes Association, 2021 criteria. After taking clinical information, fasting blood was collected to measure homocysteine by chemiluminescent immunoassay. Results: Homocysteine level was different across the spectrum of glycemic status (normal glucose tolerance vs. prediabetes vs. diabetes mellitus: 15.57 (13.89-20.71) vs 13.19 (11.40-18.11) vs 12.27 (9.97-14.42) µmol/L; median (interquartile range); p = 0.006). Serum homocysteine was significantly elevated in participants with normal glucose tolerance than diabetes mellitus (p = 0.006) but statistically similar in prediabetes in comparison to both normal glucose tolerance and diabetes mellitus (p = NS for both). Homocysteine level was above the normal level in 47.5% of participants with normal glucose tolerance and in 22.5% with abnormal glucose tolerance (p = 0.019). Conclusions: Patients under 30 years with diabetes mellitus had lower homocysteine levels than those with normal glucose tolerance.

Ovarian volume is more closely related to the different manifestations of polycystic ovary syndrome than follicle number per ovary.

OBJECTIVE: Polycystic ovary (PCO), a diagnostic component of polycystic ovary syndrome (PCOS), requires either an ovarian volume (OV) criterion or a follicle number per ovary (FNPO) criterion. This study investigated the association of OV and FNPO criteria with various manifestations of PCOS. METHODS: This cross-sectional study was conducted at a university hospital among 100 patients newly diagnosed with PCOS (according to the revised Rotterdam criteria). Fasting blood samples were collected to measure glucose, total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), lipid, insulin, and hemoglobin A1c levels. An oral glucose tolerance test was performed. Transabdominal or transvaginal ultrasound of the ovaries was done, depending on patients' marital status. All investigations were conducted in the follicular phase of the menstrual cycle. OV >10 mL and/or FNPO ≥12 indicated PCO. A homeostasis model assessment of insulin resistance (IR) value ≥2.6 indicated IR, and metabolic syndrome (MS) was defined according to the international harmonization criteria. RESULTS: Seventy-six participants fulfilled the OV criterion, 70 fulfilled the FNPO criterion, and 89 overall had PCO. Both maximum OV and mean OV had a significant correlation with TT levels (r=0.239, p=0.017 and r=0.280, p=0.005, respectively) and the LH/FSH ratio (r=0.212, p=0.034 and r=0.200, p=0.047, respectively). Mean OV also had a significant correlation with fasting insulin levels (r=0.210, p=0.036). Multivariate binary logistic regression analysis showed that IR (odds ratio [OR], 9.429; 95% confidence interval [CI], 1.701 to 52.271; p=0.010) and MS (OR, 7.952; 95% CI, 1.821 to 34.731; p=0.006) had significant predictive associations with OV alone, even after adjustment for age and body mass index. CONCLUSION: OV may be more closely related to the androgenic and metabolic characteristics of PCOS than FNPO.

Turner Syndrome With Isochromosome Structural Abnormalities: A Case Report.

Turner syndrome (TS) is the most common cause of short stature and delayed puberty in females. Approximately half of the patients have the classic form with a genotype of 45,XO, one-fourth of patients have different mosaic forms, and the remaining one-fourth have structural abnormalities on the X chromosome. Among the structural abnormalities, the most common is isochromosome Xq. Females with structural variants of TS can present with delayed menarche, amenorrhea, and infertility rather than classic manifestations of TS. This study describes two rare variants of TS. One was a structural abnormality on the X chromosome, 46X,iso(Xq), and the other involves a mosaic variety of TS, including isochromosome X in the form of 45,XO/46X,iso(Xq). Both patients presented with short stature and secondary amenorrhea without classic manifestations of TS. In TS with or without mosaicism, the frequency of isochromosomes is reported to be about 15% to 18%. Owing to the absence of classical manifestations of TS, diagnosis may be delayed or missed. Therefore, females of short stature with secondary amenorrhea should be evaluated for rare variants of TS by chromosomal analysis.

Intestinal alkaline phosphatase deficiency increases the risk of diabetes.

INTRODUCTION: Our previous case-control study demonstrated that a high level of intestinal alkaline phosphatase (IAP), an endotoxin-detoxifying anti-inflammatory enzyme secreted by villus-associated enterocytes and excreted with stool, plays a protective role against type 2 diabetes mellitus (T2DM) irrespective of obesity. In the current study, we investigated the long-term effect of IAP deficiency (IAPD) on the pathogenesis of T2DM. RESEARCH DESIGN AND METHODS: A healthy cohort of participants without diabetes (30-60 years old), comprising 188 without IAPD (IAP level: ≥65 U/g stool) and 386 with IAPD (IAP level: <65 U/g stool), were followed up for 5 years. We measured stool IAP (STAP) and fasting plasma glucose, and calculated the risk ratio (RR) using log-binomial regression model. RESULTS: T2DM incidence rates were 8.0%, 11.7%, 25.6%, and 33.3% in participants with 'persistent no IAPD' (IAP level: always ≥65 U/g stool), 'remittent IAPD' (IAP level: increased from <65 U/g stool to ≥65 U/g stool), 'persistent IAPD' (IAP level: always <65 U/g stool), and 'incident IAPD' (IAP level: decreased from ≥65 U/g stool to <65 U/g stool), respectively. Compared with 'persistent no IAPD' the risk of developing T2DM with 'incident IAPD' was 270% higher (RR: 3.69 (95% CI 1.76 to 7.71), χ2 p<0.001). With 'persistent IAPD' the risk was 230% higher (RR: 3.27 (95% CI 1.64 to 6.50), p<0.001). 'Remittent IAPD' showed insignificant risk (RR: 2.24 (95% CI 0.99 to 5.11), p=0.0541). Sensitivity analyses of persistent IAP levels revealed that, compared with participants of the highest persistent IAP pentile (always >115 U/g stool), the rate of increase of fasting glycemia was double and the risk of developing T2DM was 1280% higher (RR: 13.80 (95% CI 1.87 to 101.3), p=0.0099) in participants of the lowest persistent IAP pentile (always <15 U/g stool). A diabetes pathogenesis model is presented. CONCLUSIONS: IAPD increases the risk of developing T2DM, and regular STAP tests would predict individual vulnerability to T2DM. Oral IAP supplementation might prevent T2DM.

CDKAL1 gene rs7756992 A/G and rs7754840 G/C polymorphisms are associated with gestational diabetes mellitus in a sample of Bangladeshi population: implication for future T2DM prophylaxis.

BACKGROUND: Association of single nucleotide polymorphisms (SNP) rs7756992 A/G and rs7754840 G/C of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene with the susceptibility of gestational diabetes mellitus (GDM) has been studied in a group of Bangladeshi women. METHODS: In this case-control study, 212 GDM patients and 256 control subjects were genotyped for rs7756992 and rs7754840 by PCR-RFLP and TaqMan™ allelic discrimination assay method respectively. Genotyping results were confirmed by DNA sequencing and replicated TaqMan™ assay. The odds ratios and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and GDM. RESULTS: The genotype frequencies of rs7756992-AA/AG/GG in the GDM group and the control group were 37%/48%, 53%/45%, 10%/7% and those of rs7754840-CC/CG/GG were 51%/55%, 40.1%/39.8%, 9%/5% respectively. Under dominant and log additive models rs7756992 was revealed significantly associated with GDM after being adjusted for family history of diabetes (FHD) and gravidity. Conversely, rs7754840 was significantly associated (P = 0.047) with GDM only under the recessive model after the same adjustment. The risk allele frequency of both SNPs was higher in the GDM group but significantly (P = 0.029) increased prevalence was observed in the rs7756992 G allele. When positive FHD and risk alleles of these SNPs were synergistically present in any pregnant woman, the chance of developing GDM was augmented by many folds. The codominant model revealed 2.5 and 2.1 folds increase in odds by AG (rs7756992) and GC (rs7754840) genotypes and 3.7 and 4.5 folds by GG (rs7756992) and CC (rs7754840) genotypes respectively. A significant 2.7 folds (P = 0.038) increase in odds of GDM resulted from the interaction of rs7756992 and family history of diabetes under the dominant model. The cumulative effect of multigravidity and risk alleles of these SNPs increased the odds of GDM more than 1.5 folds in different genotypes. CONCLUSION: This study not only revealed a significant association between rs7756992 and rs7754840 with GDM but also provided the possibility as potential markers for foretelling about GDM and type 2 diabetes mellitus in Bangladeshi women.

A Hospital-Based Study of Iodine Nutrition Status of Breastfeeding Mothers in Bangladesh.

Adequacy of iodine nutrition status in breastfeeding mothers is vital in preventing iodine deficiency disorder (IDD) in neonates and children. The aim of the study was to assess urinary iodine status in breastfeeding mothers attending Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital in Bangladesh. In this cross-sectional study carried out from January 2014 to January 2015, urinary iodine (UI; µgm/L) level of 266 mothers (age 26.6 ± 4.7 years (mean ± SD), exclusively breastfeeding: 132 and nonexclusively breastfeeding: 134), recruited on consecutive basis from BSMMU outdoor and indoor, were measured in spot urine following the wet digestion method. Median UI in the participants was 298.6 (interquartile range, IQR 206.6-454.9) µgm/L and only 6.4% lactating mother had low UI (i.e. <100 µgm/L). There was no difference of median UI in relation to exclusive or nonexclusive breast feeding, presence of goiter, parity, and age of breastfed baby (p=ns for all). But median UI was higher in older subjects (≥30 years vs. <30 years: 364.4 (228.4-529.9) vs. 283.7 (205.4-434.0); median (IQR) p=0.040)), with good socioeconomic condition (good vs. average or less: 328.2 (243.8-510.0) vs. 274.4 (200.0-433.3); median (IQR); p=0.020), and in those who are aware regarding the importance of iodine (aware vs. unaware: 316.6 (225.2-506.3) vs. 270.1 (196.0-407.2); median (IQR); p=0.018). The proportion of participants with UI < 100 µgm/L was similar in all the groups. Logistic regressions to predict deficient UI status revealed none of the variables to be an independent predictor. This study indicates that deficient iodine nutrition status in Bangladeshi breastfeeding mothers is not frequent at present.