Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

Maturity-onset diabetes of the young (MODY) is the most common monogenetic form of diabetes with an autosomal dominant inheritance pattern. MODY is caused by mutations in genes important for the development and function of pancreatic beta cells, resulting in impaired insulin secretion capacity. To date, 14 different types have been described. While glucokinase (GCK)-MODY (formerly MODY-2) generally requires no drug therapy, other forms of MODY, such as hepatocyte nuclear factor-1-alpha (HNF1A)-MODY (formerly MODY-3) and HNF4A (formerly MODY-1), usually respond very well to sulfonylurea therapy. However, these MODY forms are characterised by a progressive course, meaning that insulin therapy is often required as the disease progresses. Both sulfonylurea therapy and insulin therapy are associated with an increased risk of hypoglycaemia and frequent weight gain. Newer blood glucose-lowering therapies, such as SGLT2 inhibitors (SGLT2i), DPP-4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP-1RA), have a much lower risk of hypoglycaemia and usually have a favourable effect on body weight. This review aims to provide an overview of the treatment of MODY patients with SGLT2i, DPP4i and GLP-1RA on the basis of previously published clinical studies, case series and case reports.

Diabetes mellitus (DM) is one of the fastest growing diseases in terms of incidence worldwide and seriously affects cognitive function. The incidence rate of cognitive dysfunction is up to 13% in diabetes patients aged 65-74 and reaches 24% in those aged >75 years. The mechanisms and treatments of cognitive dysfunction associated with diabetes mellitus are complicated and varied. According to previous studies, hyperglycaemia mainly contributes to cognitive dysfunction through mechanisms involving inflammation, autophagy, the microbial-gut-brain axis, brain-derived neurotrophic factors and insulin resistance. Antidiabetic drugs such as metformin, liraglutide and empagliflozin and other drugs such as fingolimod and melatonin can alleviate cognitive dysfunction caused by diabetes. Self-management, indirect fasting and repetitive transverse magnetic stimulation can also ameliorate cognitive impairment. In this review, we discuss the mechanisms linking diabetes mellitus with cognitive dysfunction and propose a potential treatment for cognitive dysfunction related to diabetes mellitus.

Aim: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity.

Methods: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before.

Results: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population.

Conclusions: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

Ocular motor mononeuropathies affect cranial nerves III, IV and VI and are more frequent in diabetes mellitus, with oculomotor nerve involvement being predominant. The aim of this narrative brief review was to discuss the clinical manifestations, diagnosis and management of ocular motor nerve palsies in subjects with diabetes. Clinical manifestations often include ptosis, diplopia, and periorbital pain. A characteristic of third nerve palsy is pupillary sparing. Differential diagnosis may be challenging due to overlapping symptoms with nerve palsies of other aetiologies. Treatment includes optimised glycaemic control and management of vascular risk factors. Neuroprotective agents, mainly alpha-lipoic acid and botulinum toxin A have been occasionally used, as well. Spontaneous recovery is also seen in many cases.

Objective: To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology).

Methods: This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients.

Results: Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001).

Conclusion: The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.

Introduction: In recent years, a growing number of clinical and biological studies have shown that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing Parkinson's disease (PD). Prolonged exposure to hyperglycemia results in abnormal glucose metabolism, which in turn causes pathological changes similar to PD, leading to selective loss of dopaminergic neurons in the compact part of the substantia nigra. Dihydromyricetin (DHM) is a naturally occurring flavonoid with various biological activities including antioxidant and hepatoprotective properties. In this study, the effect of DHM on high glucose-induced dopaminergic neuronal damage was investigated.

Methods: The potential modulatory effects of DHM on high glucose-induced dopaminergic neuronal damage and its mechanism were studied.

Results: DHM ameliorated high glucose-induced dopaminergic neuronal damage and autophagy injury. Inhibition of autophagy by 3-methyladenine abrogated the beneficial effects of DHM on high glucose-induced dopaminergic neuronal damage. In addition, DHM increased levels of p-AMP-activated protein kinase (AMPK) and phosphorylated UNC51-like kinase 1. The AMPK inhibitor compound C eliminated DHM-induced autophagy and subsequently inhibited the ameliorative effects of DHM on high glucose-induced dopaminergic neuronal damage.

Discussion: DHM ameliorates high glucose-induced dopaminergic neuronal damage by activating the AMPK-autophagy pathway.

Aims: Hypothyroidism is a common side effect of radiotherapy for nasopharyngeal carcinoma. However, the impact of thyroid hormone replacement therapy on patients with radiation-induced subclinical hypothyroidism has not been extensively explored. This study aimed to analyze the efficacy of thyroid hormone replacement therapy in nasopharyngeal carcinoma patients with subclinical hypothyroidism.

Methods: Patients diagnosed with nasopharyngeal carcinoma who developed subclinical hypothyroidism after definitive radiotherapy between September 2019 and December 2020 were selected for inclusion in this study. Prior to thyroid hormone replacement therapy and after maintaining euthyroidism for 6-12 months through thyroid hormone replacement therapy, assessments using the SF36 Brief Health Status Scale and the Hypothyroidism-related Symptom Questionnaire were conducted via trained questionnaires. Lipid profiles were assessed at baseline and after 6-12 months of thyroid hormone replacement therapy. Statistical analyses were performed using matched samples T-test or Mann-Whitney U test.

Results: The median follow-up period was 14.5 months. The median score of hypothyroid symptoms was 5.5 out of 19 points, with the most common symptoms being chills (65.0%), fatigue (50.0%), weight gain (45.0%), and limb numbness (40.0%). Thyroid hormone replacement therapy did not significantly improve the quality of life, hypothyroidism-related symptoms, or blood lipid profile in patients. However, there was an observed downward trend in serum cholesterol levels following treatment (P=0.052).

Conclusion: Thyroid hormone replacement therapy did not have a significant impact on alleviating hypothyroid symptoms, improving quality of life, or enhancing lipid profiles in patients with radiation-induced subclinical hypothyroidism. Nevertheless, a potential decrease in serum cholesterol levels was noted after thyroid hormone replacement therapy.

Diabetes mellitus is a leading cause of disability with adverse effects on the quality of life. It also affects occupational health by impacting several work-related parameters. This review discusses the relationship between diabetes and absenteeism, presenteeism, work impairment and unemployment. The association between work and diabetic complications such as neuropathic pain, diabetic foot, psychological issues and hypoglycemia due to treatment is also examined. Evidence points to a relationship between diabetes and absenteeism, reduced work productivity, and, thus, overall work impairment. A stronger negative impact on work performance is mediated by painful diabetic neuropathy and diabetic foot. In addition, psychological distress has been positively correlated with total workdays lost and frequency of absence. Depression in the diabetic population has also been linked with increased absenteeism, presenteeism, and work disability. Moreover, hypoglycaemia induced by antidiabetic medication may affect work attendance and performance. Finally, diabetes has been associated with inequality in the work environment, lower job satisfaction and higher unemployment rates, mainly because of its complications.

Introduction: Passive heat treatment has been suggested to improve glycemic control in individuals with type 2 diabetes mellitus (T2DM). Previous studies have focused predominantly on hot water immersion and traditional sauna bathing, as opposed to the more novel method of infrared-based sauna bathing. Here, the impact of a single infrared sauna session on post-prandial glycemic control was assessed in older individuals with T2DM.

Methods: In this randomized controlled crossover trial, 12 participants with T2DM (male/female: 10/2, age: 69±7 y, BMI: 27.5±2.9 kg/m²) rested in an infrared sauna twice: once in a heated (60°C) and once in a thermoneutral (21°C) condition for 40 min, immediately followed by a 2-h oral glucose tolerance test (OGTT). Venous blood samples were obtained to assess plasma glucose and insulin concentrations and to determine the whole-body composite insulin sensitivity index.

Results: Body core and leg skin temperature were higher following the heated condition compared to the thermoneutral condition (38.0±0.3 vs. 36.6±0.2°C and 39.4±0.8 vs. 31.3±0.8°C, respectively; P<0.001 for both). The incremental area under the curve (iAUC) of plasma glucose concentrations during the OGTT was higher after the heated condition compared to the thermoneutral condition (17.7±3.1 vs. 14.8±2.8 mmol/L/120 min; P<0.001). No differences were observed in plasma insulin concentrations (heated: 380±194 vs. thermoneutral: 376±210 pmol/L/120 min; P=0.93) or whole-body composite insulin sensitivity indexes (4.5±2.8 vs. 4.5±2.1; P=0.67).

Conclusions: A single infrared sauna session does not improve postprandial blood glucose handling in individuals with T2DM. Future studies should assess the effect of more prolonged application of infrared sauna bathing on daily glycemic control.

Introduction: The diagnosis of adrenal insufficiency (AI) related to traumatic brain injury (TBI) remains a challenge. We investigated the basal and low-dose adrenocorticotropic hormone (ACTH)-stimulated serum cortisol and salivary cortisol (SaC) levels and the diagnostic utility of SaC levels during 28 days following TBI.

Materials and methods: Blood samples were collected for basal levels [sequentially from day 1 (D1) to D7 and on D28)] and for peak serum cortisol and SaC responses to the low-dose ACTH stimulation test (on D1, D7, and D28). After the patient enrollment period was completed, patients were retrospectively categorized as AI or AS (adrenal sufficiency) for each day separately, based on a basal serum cortisol cut-off level of 11 µg/dL, and data analysis was performed between the groups.

Results: Thirty-seven patients and 40 healthy controls were included. Median basal serum cortisol levels were higher in patients on D1 but were similar on other days. Median basal SaC levels were higher in patients on D1 and D2 but were similar on other days. Median peak serum cortisol and SaC levels were similar on D1 but were lower in patients on D7 and D28. Median basal SaC levels were higher in the AS group than in the AI group on all days.

Discussion and conclusions: When evaluating AI during the course of TBI, the cut-off for basal SaC levels is 0.5-0.6 µg/dL throughout the first week, except for 1.38 µg/dL on D2. SaC levels may serve as a surrogate marker for accurately reflecting circulating glucocorticoid activity.