Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Angelina Gideon, Roland von Känel, Cathy Degroote et al.

BackgroundThe mineralocorticoid hormone aldosterone plays a key role in blood pressure regulation and the development of cardiovascular disease. However, the biological mechanisms that underly prospective associations with negative health outcomes are not fully understood. We compared the awakening response of biologically active salivary aldosterone (AldAR) between male participants with coronary heart disease (CHD), essential hypertension (EHT), and normotension (NT) and additionally examined prospective associations with biological CHD risk factors.MethodsAt baseline, 60 CHD patients, 40 EHT and 44 NT repeatedly assessed the AldAR over two consecutive days. In 97 participants, prospective CHD risk was assessed by changes from baseline to follow-up 2.95 ± 0.07 (SEM) years later in the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol. Potential confounding variables were controlled.ResultsWhereas NT showed the regular AldAR, EHT had higher overall aldosterone levels (p’s < .010, with confounders: p’s < .065) but a flattened AldAR (p = .89). Moreover, CHD patients showed the regular AldAR but on a lower level as compared to NT (p = .002, with confounders: p = .075). Greater AldAR area under the curve independently predicted greater increases in overall inflammatory (p’s ≤ .032) and lipid CHD risk markers (p’s ≤ .089). Significantly greater increases were found for LDL cholesterol (ß = .24, p = .037; with confounders: p’s ≤ .067), and tChol (ß = .26, p = .032; with confounders: p’s ≤ .064). A trend for an association was found for IL-6 (ß = .22, p = .068; with confounders: p’s ≤ .079).ConclusionsWe found evidence for altered AldAR in CHD and EHT with higher AldAR predicting higher CHD risk, particularly in relation to systemic inflammation and dyslipidemia. Elevated AldAR levels may contribute to the pathogenesis of atherosclerotic cardiovascular disease.

Hidetsugu Taka, Keiji Sugai, Jumpei Shikuma et al.

Recent advances in automated insulin delivery (AID) system have been remarkable. The advanced hybrid closed-loop (AHCL) system made it easier to achieve optimal glycemic targets. According to previous studies, the AHCL system achieves relatively good glycemic control without strict carbohydrate input. These studies suggested that AID systems potentially improve glycemic control among patients with difficulty with self-management. However, few studies have focused on the efficacy of the systems among these patients. We present a case of a 30-year-old woman with type 1 diabetes and intellectual disabilities (full-scale intelligence quotient = 67) due to Shwachman-Diamond syndrome. While using a sensor-augmented pump with the predictive low glucose suspend system, her glycated hemoglobin levels consistently ranged from 9.0% to 10.0%, and she experienced frequent hospitalizations due to diabetic ketoacidosis. Stepping up to a hybrid closed-loop system achieved better glycemic control and prevented hospitalizations due to diabetic ketoacidosis. Finally, the patient achieved optimal glycemic control through the use of the AHCL system. Our case highlights the potential of AID systems in patients with type 1 diabetes and self-management difficulties, including those with intellectual disabilities.

Young Hye Cho, Jung In Choi, Sang Yeoup Lee

Weihong Huang, Siyi Deng, Siyang Liu et al.

BackgroundMetabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results.ResultsOver a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS−/SP+, MetS+/SP−, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP− (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS−/SP− group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality.ConclusionThe coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

Herodes Guzman, Herodes Guzman, Sahr Yazdani et al.

Timely diagnosis of persistent neonatal hypoglycemia is critical to prevent neurological sequelae, but diagnosis is complicated by the heterogenicity of the causes. We discuss two cases at separate institutions in which clinical management was fundamentally altered by the results of molecular genetic testing. In both patients, critical samples demonstrated hypoketotic hypoglycemia and a partial glycemic response to glucagon stimulation, thereby suggesting hyperinsulinism (HI). However, due to rapid genetic testing, both patients were found to have deoxyguanosine kinase (DGUOK)-related mitochondrial DNA depletion syndrome, an unexpected diagnosis. Patients with this disease typically present with either hepatocerebral disease in the neonatal period or isolated hepatic failure in infancy. The characteristic features involved in the hepatocerebral form of the disease include lactic acidosis, hypoglycemia, cholestasis, progressive liver failure, and increasing neurologic dysfunction. Those with isolated liver involvement experience hepatomegaly, cholestasis, and liver failure. Although liver transplantation is considered, research has demonstrated that for patients with DGUOK-related mitochondrial DNA depletion syndrome and neurologic symptoms, early demise occurs. Our report advocates for the prompt initiation of genetic testing in patients presenting with persistent neonatal hypoglycemia and for the incorporation of mitochondrial DNA depletion syndromes in the differential diagnosis of HI.

Umair Ilyas, Umair Ilyas, Bisma Nazir et al.

In an attempt to find new targets for α-amylase and α-glucosidase for the treatment of type 2 diabetes mellitus, the present study aims in determining the anti-diabetic potential of synthesized dihydropyrimidinone derivatives. The in vitro α-glucosidase and α-amylase inhibitory activity was performed and the molecular docking analysis of the ligand in the active binding site of target protein was determined. The results revealed significant percent inhibition of α-glucosidase by the compound 6-benzyl-4-(4-hydroxyphenyl)-3,4,6,7-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione (compound A). The active compound showed 81.99% inhibition when compared to standard ascorbic acid having percent inhibition 81.18%. The IC50 of active compound (A) showed to be 1.02 µg/ml. The molecular docking analysis revealed that the ligand bound to the active binding site of protein with the lowest binding energy of -7.9 kcal/mol that was also significantly similar to standard having -7.8 kcal/mol binding energy. The molecular dynamic simulation studies also revealed stable binding of ligand in the active binding site of protein with low RMSD of 1.7 Å similar to the protein RMSD 1.6Å In conclusion, the study revealed a potential new target against α-glucosidase to treat type 2 diabetes mellitus.

Han Wu, Cheng Xiao, Yiting Zhao et al.

Background. Mammalian target of rapamycin (mTOR) is crucial for endothelial function. This study is aimed at assessing whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide has a protective effect on endothelial function via the mTOR signaling pathway. Methods. Human umbilical vein endothelial cells (HUVECs) were administered liraglutide (100 nM) for 0, 10, 30, 60, 720, and 1440 minutes, respectively. Then, the expression and phosphorylation levels of mTOR, mTOR-Raptor complex (mTORC1), and mTOR-Rictor complex (mTORC2) were determined by Western blot and immunoprecipitation, while mTORC1 and mTORC2 expression was blocked by siRNA-Raptor and siRNA-Rictor, respectively. Akt phosphorylation was detected by Western blot. HUVECs were then incubated with liraglutide in the absence or presence of Akt inhibitor IV. Nitric oxide (NO) release was assessed by the nitrate reductase method. Phosphorylated endothelial nitric oxide synthase (eNOS), human telomerase reverse transcriptase (hTERT), and apoptosis-related effectors were assessed for protein levels by Western blot. Telomerase activity was evaluated by ELISA. Results. Sustained mTOR phosphorylation, mTORC2 formation, and mTORC2-dependent Akt phosphorylation were induced by liraglutide. In addition, eNOS phosphorylation, NO production, nuclear hTERT accumulation, and nuclear telomerase activity were enhanced by mTORC2-mediated Akt activation. Liraglutide also showed an antiapoptotic effect by upregulating antiapoptotic proteins and downregulating proapoptotic proteins in an mTORC2-Akt activation-dependent manner. Conclusion. Liraglutide significantly improves endothelial function, at least partially via the mTORC2/Akt signaling pathway.

Dongxiao Zhang, Satoshi Yamaguchi, Xinhao Zhang et al.

Agostino Di Ciaula, Grigorios Christidis, Marcin Krawczyk et al.

I.O. Tsaryk, N.V. Pashkovska

This article provides up-to-date information about diabetic kidney disease (DKD), given its phenotypes. The literature data on the epidemiology, factors and mechanisms for the development of phenotypes of this complication in diabetes mellitus (DM), as well as the possibility of its diagnosis and treatment are presented. Variants of DKD course depending on the type of diabetes are described, based on our own researches. The analysis data are presented for 1,576 patients with type 1 and type 2 diabetes mellitus and latent autoimmune diabetes in adults, the distribution of patients according to the stages of CKD and phenotypes of DKD is described. According to laboratory and instrumental studies, non-albuminuric renal dysfunction is the dominant phenotype among patients with diabetes (60 % — with type 1 diabetes mellitus, 43 % — with type 2 diabetes mellitus, 53 % — with latent autoimmune diabetes in adults). The differences found depending on the type of DM are probably related to the difference in the mechanisms of kidney damage in various types of DM. Since type 2 DM is usually diagnosed long after manifestation, all pathogenetic links in the occurrence of DKD, including the phenomenon of glucose toxicity, endothelial dysfunction, oxidative stress, etc., lead to greater changes than in patients with type 1 DM, which is diagnosed immediately after the onset of the disease. Also, the frequency of the albuminuric form of DKD in type 2 DM is apparently related to the aggravating effects of hypertension, dyslipidemia, and insulin resistance, which cause the progression of DKD. A decrease in the prevalence of albuminuria phenotype is associated with both the improvement of the nephroprotective effect of hypoglycemic drugs, which allows us to stop the development of proteinuria and contributes to the regression of existing kidney damage, and with an increase in the number of patients having a decline in glomerular filtration rate without proteinuria. These data may be the result of earlier diagnosis of the underlying disease and its complications.

Antonio Mancini, Angela Maria Rita Favuzzi, Carmine Bruno et al.

Yanara Sampaio, Lara Benigno Porto, Thais Cabral Gomes Lauand et al.

ABSTRACT Objective: To describe the clinical characteristics, management, and fetal outcomes of patients diagnosed with gestational diabetes mellitus (GDM) or overt diabetes (OD) during pregnancy who followed up at a public healthcare referral center in Brazil. Materials and methods: A retrospective cohort study based on the medical records of women diagnosed with dysglycemia during pregnancy between January 2015 and July 2017 was conducted. Results: Out of 224 pregnant women evaluated, 70% were overweight/obese. GDM was observed in 78.6% of pregnant women, while 21.4% presented with OD. Approximately 59% of patients could be diagnosed with GDM or OD by fasting plasma glucose (FPG) alterations alone. Exclusive diet therapy was used in 50.9% of patients. The need for insulin therapy was higher in OD patients (60.4%) than in GDM patients (38.1%) (p = 0.006). Women who needed insulin (n = 96) had a mean initial dose of 0.33 IU/kg (±0.27) and a final value of 0.39 IU/kg (±0.34). The cesarean rate was 74.3%. The fetal outcomes evaluated were macrosomia (2.15%), large for gestational age (LGA) fetus (15.83%), intensive care unit (ICU) need (4.32%), Apgar score ≤7 (6.47%), hypoglycemia (14.39%) and jaundice (16.55%). Conclusions: Patients with GDM and OD presented with several similar clinical features. Approximately half of the patients presented with adequate glycemic control only with diet management. Patients with OD presented a higher need for insulin therapy. Although overweight and obesity were frequent within both groups, they could possibly explain many of our findings.

Leweihua Lin, Huibiao Quan, Kaining Chen et al.

Maturity-onset diabetes mellitus of the young (MODY) is a monogenic diabetes characterized by autosomal dominant inheritance. Its atypical clinical features make diagnosis difficult and it can be misdiagnosed as type 1 or type 2 diabetes. Fourteen subtypes of MODY have been diagnosed so far, of which MODY12 is caused by mutation of the ABCC8 (ATP Binding Cassette Subfamily C Member 8) gene, which is rarely reported in China. This paper reports a Chinese family of MODY12 caused by a rare missense mutation on the ABCC8 gene, which has not been reported to be associated with MODY in China or in other countries, with the aim of increasing clinicians' awareness and attention to the disease.

Gabriella Garruti, Ana F. Pina, M. Paula Machedo et al.

Leonardo Tovar Rojas

Conclusiones • Confirmamos la afirmación de Mc Girr y Hutchison de que hay una forma de cretinismo esporádico con absorción alta de yodo radioactivo por el tiroides. • Se corrobora lo dicho por Lawson Wilkins, George Clayton y Morgan Berthrong, en el sentido de la buena respuesta a  la terapéutica con hormona tiroidea en pacientes afectos de cretinismo esporádico. En los casos con bocio, este llegó a desaparecer por completo. • Pienso que en cretinismo esporádico con absorción alta de yodo radioactivo por el tiroides hay carencia de tirosina para combinar el yodo elemento que la glándula ha captado de la sangre. Por lo tanto, el yodo elemento el cual es muy activo, se combinará con sustancias proteicas que no son tirosina y formará por lo tanto compuestos orgánicos de yodo que no llegan a completar el ciclo metabólico que conduce a la producción de tiroxina. • Esta combinación de yodo elemento con una proteína que no es tirosina sería, a mi juicio, la responsable de que en algunos casos el radioyodo proteico en sangre presenta cifras altas y, sin embargo el organismo sufre las consecuencias de la carencia de hormona tiroidea. • En el cretinismo esporádico la captación alta de yodo radioactivo por el tiroides, puede hacerse disminuir a niveles normales o subnormales por medio de la terapéutica con hormona tiroidea según lo que se deduce del estudio de mis casos. • He observado que la disminución de la captación de radio-yodo por el tiroides es tanto mayor cuanto más elevada sea la administración de extractos tiroideos. • A mi parecer, y según mis casos, en el cretinismo esporadico con captación alta de yodo radioactivo por el tiroides, el radioyodo proteico en sangre está en la mayor parte de los casos más acorde con el cuadro clínico de estos enfermos, que el estudio topográfico y las cifras globales de absorción del isótopó. 

Elena Dozio, Elena Passeri, Rosanna Cardani et al.

ContextMyotonic dystrophies (DM) are dominantly inherited muscle disorders characterized by myotonia, muscle weakness, and wasting. The reasons for sarcopenia in DMs are uncleared and multiple factors are involved. Irisin, a positive hormone regulator of muscle growth and bone, may play a role.ObjectivesTo investigate (1) circulating irisin in a series of DM1 and DM2 male patients compared with healthy controls and (2) the relationships between irisin and anthropometric, metabolic and hormonal parameters.Design and study participantsThis is a cross-sectional study. Fasting blood samples for glucometabolic, gonadic, bone markers, and irisin were collected from 28 ambulatory DM1, 10 DM2, and 23 age-matched healthy male subjects. Body composition and bone mineralization [bone mineral density (BMD)] were measured by DEXA. Echocardiographic assessment and visceral adiposity, namely, liver and epicardial fat, were investigated by ultrasound. Irisin released from cultured myotubes derived from 3 DM1, 3 DM2, and 3 healthy donors was assayed.ResultsPlasma irisin levels were definitely lower in both DM1 and DM2 patients than in controls with no difference between DM1 and DM2. Irisin released from DM1 and DM2 myotubes was similar to that released from myotubes of the non-DM donors, though diabetic DM2 myotubes released more irisin than DM1 myotubes. There was no correlation between irisin and muscle strength or lean mass in both DM1 and DM2 patients. In DM1 patients, plasma irisin levels correlated negatively with oxygen consumption and positively with insulin resistance, while in DM2 patients plasma irisin levels positively correlated with fat mass at arms and legs levels. No correlation with visceral fat, left ventricular mass, and gonadal hormones could be detected. In both DM1 and DM2 patients, legs BMD parameters positively correlated with plasma irisin levels.ConclusionPlasma irisin is reduced in both DM1 and DM2 male patients likely reflecting muscle mass reduction. Moreover, insulin resistance may contribute to modulation of plasma irisin in DM1 patients. The irisin-mediated cross talk muscle–adipose tissue–bone may be active also in the male myotonic dystrophies’ model.

Jeffrey Nadelson, Sanjaya K. Satapathy, Satheesh Nair

Introduction. Aim of this study is to determine if HbA1c levels are a reliable predictor of glycemic control in patients with decompensated cirrhosis. Methods. 200 unique patients referred for liver transplantation at University of Tennessee/Methodist University Transplant Institute with a HbA1c result were included. Three glucose levels prior to the “measured” A1c (MA1c) were input into an HbA1c calculator from the American Diabetes Association website to determine the “calculated” A1c (CA1c). The differences between MA1c and CA1c levels were computed. Patients were divided into three groups: group A, difference of <0.5; group B, 0.51–1.5; and group C, >1.5. Results. 97 (49%) patients had hemoglobin A1c of less than 5%. Discordance between calculated and measured HbA1c of >0.5% was seen in 47% (n=94). Higher level of discordance of greater than >1.5 was in 12% of patients (n=24). Hemoglobin was an independent predictor for higher discordance (odds ratio 0.77 95%, CI 0.60–0.99, and p value 0.04). HbA1c was an independent predictor of occurrence of HCC (OR 2.69 955, CI 1.38–5.43, and p value 0.008). Conclusion. HbA1c is not a reliable predictor of glycemic control in patients with decompensated cirrhosis, especially in those with severe anemia.

Tandi E. Matsha, Carmen Pheiffer, Tinashe Mutize et al.

The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p≤0.033) and in screen-detected diabetes compared to known diabetes on treatment (p=0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p>0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β=0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.

Claudio Casella, Pierluigi Rossini, Carlo Cappelli et al.

Background. A proper localisation of pathological parathyroid glands is essential for a minimally invasive approach in the surgical treatment of primary hyperparathyroidism (PHP). The recent introduction of portable mini gamma-cameras (pMGCs) enabled intraoperative scintigraphic scanning. The aim of our study is to evaluate the efficacy of this new method and compare it with the preoperative localisation surveys. Methods. 20 patients were studied; they were evaluated preoperatively by neck ultrasound and Tc-sestaMIBI-scintigraphy and intraoperatively with the pMGC IP Guardian 2. The results obtained from the three evaluations were compared. Results. The pMGC presented a sensitivity of 95%, a specificity of 98.89%, and a diagnostic accuracy of 98.18%, which were higher than those of preoperative ultrasound (sensitivity 55%; specificity 95%; diagnostic accuracy 87%) and scintigraphy with Tc-sestaMIBI (sensitivity 73.68%; specificity 96.05%; diagnostic accuracy 91.58%). Conclusions. The pMGC can be used effectively as an intraoperative method to find the correct location of the pathological parathyroid glands. The pMGC is more reliable than the currently used preoperative and intraoperative localisation techniques.

Irene Catambing, Michael Villa

Objectives. To determine the skin and subcutaneous thickness of adult diabetic Filipinos using ultrasonography. Methodology. We studied 293 Filipino diabetic adults who had ultrasonographic measurements of their skin thickness (ST) and subcutaneous thickness (SCT) at common insulin injection sites.   Results. The mean ST ranges from 1.76 mm to 2.75mm. The mean SCT ranges from 6.91 mm to 19.1 mm. The anterior thigh area has the thinnest mean ST and SCT. On the other hand, the buttocks have the thickest mean ST and area of abdomen has the thickest mean SCT.   On multiple regression analysis, the predictors for skin thickness are injection site, age, BMI, gender and insulin use, however the overall influence of all these factors on skin thickness is variable at best.   Conclusion.  Skin thickness among Filipinos varies marginally depending on injection site being thickest at the buttocks and thinnest at the thighs. On the other hand, there is greater variability in SCT depending on the injection site, being thickest at the abdominal area and thinnest at the anterior thigh.