BMC Endocrine Disorders

Diabetes registry enables practitioners to measure the characteristics and patterns of diabetes across their patient population. They also provide insight into practice patterns which can be very effective in improving care and preventing complications. The aim of this study was to assess the patterns, control levels and complications at the baseline of the patients attending clinic at the large tertiary care hospital in Karachi, Pakistan with the help of the registry. This can be used as a reference to monitor the control and also for a comparison between peer groups. This was a cross sectional study with the data obtained from diabetes registry collected with the help of pre-designed questionnaire. HbA1c was used as a central diabetes measure and other related factors and complications were assessed with it. Only 16.6% of the participants had optimal HbA1c ≤ 7.0%. 52.9% of the patients were classified as having poor control defined by HbA1c of >8%. Three fourth of the study population were obese according to Asian specific BMI cutoffs and majority had type 2 diabetes with duration of diabetes ranging from less than one to about 35 years, mean(SD) duration being 7.6 years (7.1). Overall only 4% of the patients were on combine target of HbA1c, LDL and BP. Results of multivariable logistic regression showed that the odds of having optimal glycemic control increased by 3% with every one year increase in age. In addition, having longer duration of diabetes was associated with 56% lower odds of having good glycemic control. Moreover, having higher triglyceride levels was associated with 1% lower odds of having good glycemic control. This highlights the large burden of sub optimally controlled people with diabetes in Pakistani population, a low income country with huge diabetes prevalence and ineffective primary health care system creating enormous health and economic burden.

Omega-3 polyunsaturated fatty acids (PUFAs) produce lipid mediators with both anti-inflammatory and pro-resolution properties, including resolvins. The purpose of this study was to detect serum resolvin E1 (RVE1) levels in Hashimoto’s thyroiditis (HT) patients and healthy controls (HCs) and to evaluate the relationship of RVE1 with thyroid autoimmunity. A total of 57 participants were recruited, including 30 untreated HT patients and 27 age- and sex‐matched HCs. The levels of RVE1 in serum were measured via enzyme-linked immunosorbent assay (ELISA). An electrochemiluminescence immunoassay was used for the measurement of thyroid-stimulating hormone (TSH), total T4 (TT4), TT3, free T4 (FT4), FT3, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) levels. Hemogram tests and routine biochemical analyses were performed on each sample. The serum level of RVE1 of HT patients (24.09, 15.76–34.38 pg/mL) was significantly lower than that of healthy controls (28.51, 20.76–51.23 pg/mL) (P = 0.027). RVE1 levels showed a downward trend with increasing TgAb levels (P for trend = 0.001). Multivariable ordinal logistic regression analysis showed that RVE1 levels were negatively correlated with increasing TgAb levels in both the unadjusted (OR = 0.9446, 95 % CI = 0.9111–0.9782, P = 0.002) and adjusted models (OR = 0.9380, 95 % CI = 0.8967–0.9811, P = 0.005). Decreased RVE1 levels might be a sign that HT is associated with inflammatory resolution dysfunction. RVE1 may serve as a protective factor against increased TgAb levels.

The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.

The complication of Diabetes is one of the important health issues among the older adult population in any region. The higher risks of diabetes prevalence among older adult people in the countries was due to social-cultural changes such as increasing urbanization, dietary changes, without physical activity, and unhealthy lifestyle behavior. The present study examines the prevalence and associated risk factors of diabetes among older adults in the state of West Bengal. The first wave of the Longitudinal Ageing Study in India 2017-18 was used to achieve the study objectives. Descriptive statistics with multinomial logistic regression models were used to carry out crude and adjusted odds ratios with 95% confidence intervals and examine the associated risk factors of diabetes prevalence among older adults. The findings of the study indicate that the overall prevalence of diabetes among the study participants was found to be 12.4% which was significantly higher in urban areas (19%) compare to rural areas (6%). The socio-economic and bio-demographic factors like educational status, richest background family, marital status, obesity, and family history of diabetes were significantly associated with higher risks of diabetes prevalence among the older adult population in West Bengal. The risks of diabetes in the richest adult people were significantly higher than in the poorest adult people (OR = 2.78; 95% CI: 1.974–3.917). The higher risks of diabetes mellitus among the richest wealthy people are because of lifestyle behavior, smoking, and tobacco consumption respectively. The study needs to policy and awareness program to reduce economic inequality and prevention of diabetes care and treatment-seeking behavior, especially for the older adult population in West Bengal.

The most frequently used methods of assessing Graves’ orbithopathy (GO) include: Clinical Activity Score (CAS), ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI). There exists another, slightly forgotten, imaging method: single-photon emission computed tomography (SPECT) with the use of diethylenetriaminepentaacetic acid tagged with 99mTc (99mTc-DTPA). These days it is possible to conduct a SPECT examination fused with a CT scan (SPECT/CT), which increases the diagnostic value of the investigation. The aim of this paper is to evaluate the usefulness of 99mTc-DTPA SPECT/CT in diagnosing Graves orbitopathy, as compared with other methods. Twenty-three patients with suspected active (infiltrative-edematous) Graves’ orbithopathy were included in the study. Each patient underwent a CAS, an MRI, and a SPECT/CT. The obtained results were analysed statistically, with the assumed statistical significance of p < 0.05. The SPECT/CT and MRI were found to have the highest sensitivity: 0.93 each. The SPECT/CT had the highest specificity: 0.89. MRI and CAS had lower values: 0.78 and 0.56, respectively. The occurrence of an active form of GO had no impact on the exacerbation of exophthalmos or the thickness of the oculomotor muscles. The 99mTc-DTPA SPECT/CT method provides a very good tool for assessing the active form of GO and can, alongside the MRI scan, be used as a referential diagnostic procedure in GO.

Gestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy. The primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism. A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P < 0.01) group. In GDM-I, there was a significant decrease in the levels of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3). Moreover, glucose uptake was significantly decreased in GDM-I, although in GDM-D, there was only a decrease in the levels of GLUT1. ATP levels decreased in GDM-I (P < 0.05) and apoptosis occurred in both the GDM-D and GDM-I groups. Compared to the normal controls, the levels of phosphate AKT and phosphate AMPK over total AKT and AMPK were reduced in the GDM-I group. In summary, endothelial dysfunction occurred in pregnancies with GDM even though the plasma glucose levels were controlled, and this dysfunction might be related to the degree of glucose tolerance. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signaling pathway.

Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear. After the hypothyroidism rat model induced by propylthiouracil, we gave rats 25 mg/kg DMF by gavage. The body weight during model building and administration was recorded. The levels of T4 and T3 in serum were detected by an automatic biochemical analyzer. Morris water maze test was used to detect the effect of DMF on cognitive learning ability. The effect of DMF on Nissl bodies in the brain tissue was evaluated by Nissl staining. The mRNA and protein levels of BDNF in brain tissue were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. The degrees of p-AKT/AKT and p-CREB/CREB in brain tissue were detected by Western blot. After DMF treatment, the body weight of hypothyroid rats recovered, and the levels of T3 and T4 in the serum were ameliorated. DMF also reduced the escape latency and distance traveled, and increased the swim speed. The number of Nissl bodies and expression of BDNF, p-AKT/AKT, and p-CREB/CREB in the brain tissue were increased after DMF treatment. DMF improved the cognitive dysfunction of hypothyroid rats by increasing the level of BDNF in the brain tissue of hypothyroid rats.

We assessed the value of positron emission tomography/computed tomography (PET/CT) with [13N]N-ammonia ([13N]N-NH3) and [11C]C-methionine ([11C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET. Nine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [18F]F-FDG PET were enrolled in this study. All of the patients underwent [13N]N-NH3 and [11C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made. In general, [11C]C-MET had a higher uptake in pituitary adenomas (PAs) than that in pituitary tissues, while [13N]N-NH3 had a higher uptake in pituitary tissue than in pituitary adenomas. Increased [11C]C-MET uptake was observed in all nine PAs and three pituitary tissues, while all pituitary tissues and only one pituitary adenoma showed increased [13N]N-NH3 uptake. Four patients had concordant imaging and surgical findings indicative of biochemical remission without hypopituitarism after treatment. Radiotherapy was adopted in two patients, medication in another two, and follow-up observation in one case. Combined [11C]C-MET and [13N]N-NH3 PET/CT is effective in the differentiation of PAs from pituitary tissue in recurrent functional PAs with negative MRI or [18F]F-FDG PET. These results provide a valuable reference for further disease management.

Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.