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Open access

Guang-Ran Yang, Dongmei Li, and Zidian Xie

Objective

There is a lack of consensus on whether a high BMI increases the risk of diabetic retinopathy (DR). We aimed to investigate the association between BMI, overweight, obesity, and DR using the data of diabetes respondents in the 2015 US Behavioral Risk Factor Surveillance System survey.

Methods

Diabetes respondents aged over 18-year-old with complete information as well as undergone fundus examination in the past 2 years or had been diagnosed with DR were included. Weighted logistic regression analyses were used to identify the association of BMI with DR.

Results

Among the 21,647 diabetes respondents, 4588 respondents had DR with a weighted prevalence of 22.5%. The mean BMI of all diabetes respondents was 31.50 ± 6.95 kg/m2 with 18,498 (86.5%) overweight and 11,353 (54.6%) obese. The mean BMI of the DR group (31.83 ± 7.41 kg/m2) was significantly higher than that of the non-DR group (31.41 ± 6.81 kg/m2, P < 0.05). The proportion of obese respondents in the DR group was higher than the non-DR group (54.3%, P < 0.001). The weighted prevalence of DR was 0.8, 13.8, 29.7, and 55.7% for the emaciation group, the normal weight group, the overweight group, and the obesity group, respectively (P < 0.001). Weighted logistic regression analysis showed that both BMI (adjusted OR = 1.004, 95% CI 1.003–1.004) and obesity (adjusted OR = 1.051, 95% CI 1.048–1.055) were associated with DR after adjusting for the confounding variables. However, overweight was not significantly associated with DR.

Conclusion

The prevalence of DR in the normal weight, overweight, and obesity groups increased gradually. Obesity, rather than overweight, was significantly associated with increased DR prevalence.

Open access

Melinda Kertész, Szilárd Kun, Eszter Sélley, Zsuzsanna Nagy, Tamás Kőszegi, and István Wittmann

Background

Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well.

Methods

In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line.

Results

Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect.

Conclusion

Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

Open access

Elena V Varlamov, Dan Alexandru Niculescu, Swechya Banskota, Simona Andreea Galoiu, Catalina Poiana, and Maria Fleseriu

Purpose

The number of international acromegaly related registries is increasing; however, heterogeneity of acromegaly symptoms and signs across countries is not well described. We compared clinical disease manifestations at diagnosis between two large University referral centers from two continents.

Methods

Retrospective, comparative epidemiological study of acromegaly patients at two centers: (i) C. I. Parhon National Institute of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy Bucharest, Romania (Parhon), and (ii) Pituitary Center, Oregon Health & Science University, Portland, Oregon, United States (OHSU) from approved data repositories was undertaken. Data were extracted from medical charts and questionnaires. Binary logistic regression analysis was undertaken for the most frequently noted symptoms and clinical signs.

Results

The study included 216 patients (87 Parhon, 129 OHSU). Age, sex, and median delay in diagnosis were similar between centers. IGF-1 index was higher in patients at Parhon (3.3 vs 2.1, P < 0.001). The top five symptoms at both centers were enlarged hands/feet, headache, arthralgia, fatigue, and irregular menses in women. A significant difference was noted for multiple signs and symptoms frequency, often > 20 percentage points between centers. Center was a predictor of many signs and symptoms, independent of acromegaly biochemical severity or disease duration.

Conclusion

We show in the first comparative study that differences in medical practice, documentation, and likely cultural differences can influence patients’ symptom(s) reporting and screening patterns in geographically different populations. Pooling data into large multicenter international registry databases may lead to loss of regional characteristics and thus a mixed overall picture of combined cohorts.

Open access

Anna Sjöström, Susanne Rysz, Henrik Sjöström, and Charlotte Höybye

Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients’ medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269–6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.

Open access

Christine Rode Andreasen, Andreas Andersen, Filip Krag Knop, and Tina Vilsbøll

In recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of action, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Open access

Caroline Y Hayashi, Danilo T A Jaune, Cristiano C Oliveira, Bárbara P Coelho, Hélio A Miot, Mariângela E A Marques, José Vicente Tagliarini, Emanuel C Castilho, Carlos S P Soares, Flávia R K Oliveira, Paula Soares, and Gláucia M F S Mazeto

Background

Thyroid nodules diagnosed as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/suspected follicular neoplasm' (FN/SFN), according to Bethesda’s classification, represent a challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy.

Methods

We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility.

Results

In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61–0.93) in 10 of the 12 nuclear parameters evaluated.

Conclusion

CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.

Open access

Laszlo Samson, Ildiko Hircsu, Monika Katko, Miklos Bodor, Annamaria Gazdag, Andrea Anett Gazso, Bela Kovacs, Janos Posta, Eszter Balogh, Peter Mocsary, Harjit Pal Bhattoa, and Endre V Nagy

Objective

To investigate factors affecting conscious iodine intake among pregnant and lactating women in a rural area in Hungary.

Methods

Pregnant women were studied and followed during lactation. Urinary and breast milk iodine concentration (UIC and MIC) were measured by inductively coupled plasma mass spectrometry. Potential interfering factors, including age, educational status and smoking were assessed.

Results

During pregnancy and lactation, mild iodine deficiency was observed; median UIC were 66 and 49 µg/L, respectively. Educational status was found to be a strong determinant of both iodine nutrition and smoking status during pregnancy (P < 0.01 and P < 0.001) and lactation (P < 0.001 and P < 0.01). While smoking and non-smoking lactating mothers had similar concentrations of urinary iodine (median UIC: 47 and 51 µg/L, P = 0.95), the breast milk of smoking mothers contained less iodine (median MIC: 150 and 203 µg/L, P = 0.03).

Conclusions

Both low iodine intake and smoking contribute to the higher risk of iodine deficiency in women with lower educational status. In smokers, MIC is often low in spite of normal UIC, presumably due to the iodine transport blocking effect of the cigarette smoke towards breast milk; normal UIC may be misinterpreted as sufficient iodine supply towards the child. Antenatal health promotion strategies should focus on young women with lower educational status, even in regions where sufficient iodine intake has been achieved in non-pregnant adults.

Open access

Nandini Shankara Narayana, Lam P Ly, Veena Jayadev, Carolyn Fennell, Sasha Savkovic, Ann J Conway, and David J Handelsman

Objective

To define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice.

Design and methods

A prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for pathological hypogonadism or masculinization of female-to-male transgender (transmen) subject to individual dosing titration to achieve a stable replacement regimen.

Results

From 2006 to 2019, 6899 injections were given to 325 consecutive patients. After excluding the 6-week loading dose, 6300 injections were given to 297 patients who had at least three and a median of 14 injections. The optimal injection interval (mean of last three injection intervals) had a median of 12.0 weeks (interquartile range 10.4–12.7 weeks). The interval was significantly influenced by age and body size (body surface area, BSA) but not by diagnosis or trough serum LH, FSH, and SHBG. Longer (≥14 weeks; 68/297, 23%), but not shorter (≤10 weeks; 22/297, 7.4%), intervals were weakly correlated with age but not diagnosis or other covariables. Low blood hemoglobin increased with trough serum testosterone to reach plateau once testosterone was about 10 nmol/L or higher.

Conclusion

Optimal intervals between TU injection after individual titration resulted in the approved 12-week interval in 70% of patients with only minor influence for clinical application of BSA and not of trough serum LH, FSH, and SHBG. Individually optimized inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.

Open access

Ping Gu, Yuege Lin, Qi Wan, Dongming Su, and Qun Shu

Background

Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation. However, the underlying mechanism of β-cell adaptation during gestation or gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physiological hormone in gestation and delivery, and it also contributes to the maintenance of β-cell function. The aim of this study was to investigate the role of oxytocin in β-cell adaptation during pregnancy.

Methods

The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigated. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells.

Results

The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A 3-week oxytocin treatment promoted the proliferation of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion and induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose-stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells.

Conclusions

These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and the lack of oxytocin could be associated with the risk of GDM.

Open access

Sakina H Bharmal, Wandia Kimita, Juyeon Ko, and Maxim S Petrov

Objective

Early identification of individuals at high risk for metabolic derangements after an attack of acute pancreatitis (AP) is critical with a view to tertiary preventing of this disease. The aim was to investigate whether fasting pancreatic and gut hormones at baseline were predictive of future risk of new-onset prediabetes after acute pancreatitis (NOPAP) in individuals with non-necrotising AP.

Methods

This was a prospective longitudinal cohort study that included 69 consecutive non-diabetic participants with AP, of whom 55% (n = 38) had normoglycaemia both at baseline and during follow-up, 25% (n = 17) had prediabetes both at baseline and during follow-up, and 20% (n = 14) were normoglycaemic at baseline but developed NOPAP during follow-up. The associations between the study groups and circulating fasting levels of pancreatic and gut hormones (insulin, glucagon, C-peptide, amylin, glucose-dependent insulinotropic peptide, glucagon-like peptide-1, pancreatic polypeptide, and peptide YY) were studied using multinomial regression in both unadjusted and adjusted analyses.

Results

Elevated plasma insulin and glucagon at baseline were significantly associated with NOPAP (adjusted odds ratio 1.99, 95% CI 1.01 to 3.92 and adjusted odds ratio 3.44, 95% CI 1.06 to 11.19, respectively). The same hormones had no significant association with antecedent prediabetes in AP. The other studied hormones were not significantly associated with the study groups.

Conclusions

Normoglycaemic AP individuals with elevated fasting levels of insulin and glucagon at baseline constitute a high-risk group for future NOPAP.