Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Adrenalectomy Improves Body Weight, Glucose, and Blood Pressure Control in Patients With Mild Autonomous Cortisol Secretion: Results of an Randomized Controlled Trial by the Co-work of Adrenal Research (COAR) Study.

OBJECTIVE: To assess the metabolic effects of adrenalectomy in patients with mild autonomous cortisol secretion (MACS). BACKGROUND: Despite retrospective studies showing the association of adrenalectomy for MACS with beneficial metabolic effects, there have been only 2 randomized prospective studies with some limitations to date. METHODS: A prospective, multicenter study randomized 132 patients with adrenal incidentaloma without any features of Cushing syndrome but with serum cortisol >50 nmol/L after a 1 mg overnight dexamethasone suppression test into an adrenalectomy group (n = 66) or control group (n = 66). The primary outcomes were changes in body weight, glucose, and blood pressure (BP). RESULTS: Among the 118 participants who completed the study with a median follow-up duration of 48 months (range: 3-66), the adrenalectomy group (n = 46) exhibited a significantly higher frequency of improved weight control, glucose control, and BP control (32.6%, 45.7%, and 45.7%, respectively) compared with the control group (n = 46; 6.5%, P = 0.002; 15.2%, P = 0.002; and 23.9%, P = 0.029, respectively) after matching for age and sex. Adrenalectomy [odds ratio (OR) = 10.38, 95% CI = 2.09-51.52, P = 0.004], body mass index (OR = 1.39, 95% CI = 1.08-1.79, P = 0.010), and cortisol after a 1 mg overnight dexamethasone suppression test levels (OR = 92.21, 95% CI = 5.30-1604.07, P = 0.002) were identified as independent factors associated with improved weight control. Adrenalectomy (OR = 5.30, 95% CI = 1.63-17.25, P = 0.006) and diabetes (OR = 8.05, 95% CI = 2.34-27.65, P = 0.001) were independently associated with improved glucose control. Adrenalectomy (OR = 2.27, 95% CI = 0.87-5.94, P = 0.095) and hypertension (OR = 10.77, 95% CI = 3.65-31.81, P < 0.001) demonstrated associations with improved BP control. CONCLUSIONS: adrenalectomy improved weight, glucose, and BP control in patients with MACS.

Adult-Onset Type 1 Diabetes Development Following COVID-19 mRNA Vaccination.

During the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination-induced hyperglycemia and related complications have been reported. However, there have been few reports of type 1 diabetes triggered by COVID-19 vaccines in subjects without diabetes. Here, we report the case of a 56-year-old female patient who developed hyperglycemia after the second dose of COVID-19 mRNA-based vaccination without a prior history of diabetes. She visited our hospital with uncontrolled hyperglycemia despite administration of oral hyperglycemic agents. Her initial glycated hemoglobin level was high (11.0%), and fasting serum C-peptide level was normal. The fasting serum C-peptide level decreased to 0.269 ng/mL 5 days after admission, and the anti-glutamic acid decarboxylase antibody was positive. The patient was discharged in stable condition with insulin treatment. To our knowledge, this is the first case of the development of type 1 diabetes without diabetic ketoacidosis after mRNA-based COVID-19 vaccination, and is the oldest case of type 1 diabetes development under such circumstances.

Pharmacological Prevention of Ectopic Erythrophagocytosis by Cilostazol Mitigates Ferroptosis in NASH.

Hepatic iron overload (HIO) is a hallmark of nonalcoholic fatty liver disease (NAFLD) with a poor prognosis. Recently, the role of hepatic erythrophagocytosis in NAFLD is emerging as a cause of HIO. We undertook various assays using human NAFLD patient pathology samples and an in vivo nonalcoholic steatohepatitis (NASH) mouse model named STAMTM. To make the in vitro conditions comparable to those of the in vivo NASH model, red blood cells (RBCs) and platelets were suspended and subjected to metabolic and inflammatory stresses. An insert-coculture system, in which activated THP-1 cells and RBCs are separated from HepG2 cells by a porous membrane, was also employed. Through various analyses in this study, the effect of cilostazol was examined. The NAFLD activity score, including steatosis, ballooning degeneration, inflammation, and fibrosis, was increased in STAMTM mice. Importantly, hemolysis occurred in the serum of STAMTM mice. Although cilostazol did not improve lipid or glucose profiles, it ameliorated hepatic steatosis and inflammation in STAMTM mice. Platelets (PLTs) played an important role in increasing erythrophagocytosis in the NASH liver. Upregulated erythrophagocytosis drives cells into ferroptosis, resulting in liver cell death. Cilostazol inhibited the augmentation of PLT and RBC accumulation. Cilostazol prevented the PLT-induced increase in ectopic erythrophagocytosis in in vivo and in vitro NASH models. Cilostazol attenuated ferroptosis of hepatocytes and phagocytosis of RBCs by THP-1 cells. Augmentation of hepatic erythrophagocytosis by activated platelets in NASH exacerbates HIO. Cilostazol prevents ectopic erythrophagocytosis, mitigating HIO-mediated ferroptosis in NASH models.

Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80-85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. METHODS: We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients' tissues. RESULTS: We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. CONCLUSIONS: Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

Hedonic Rating of Sucrose Is Sub-Regionally Associated with Striatal Dopamine Transporter in Humans.

BACKGROUND: Eating behavior is determined by both homeostatic and hedonic values. OBJECTIVE: We investigated the association of hedonic value with striatal dopamine transporter (DAT) availability sub-regionally. METHOD: An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo, and the emission data were acquired over 90 min. DAT availability and binding potential (BPND) were measured via the simplified reference tissue method. Subjects were assessed with sensory taste test of sucrose solutions. The "most liked" sucrose concentration (%) was determined as the hedonic rating for sucrose. RESULTS: Twenty healthy males participated in this study. After glucose loading, BPNDs of putamen significantly increased, and those of caudate nucleus showed the increasing trend, while those of ventral striatum were not significantly different. After glucose loading, the "most liked" sucrose concentration (%) was negatively associated with BPNDs of caudate nucleus and showed the trend of positive association with those from ventral striatum. Slopes of regression lines were significantly different according to the sub-regions of striatum. CONCLUSION: We have highlighted that striatal DAT increased after glucose loading in dorsal striatum, not in ventral striatum. These changes of striatal DAT were sub-regionally associated with the hedonic rating of sucrose from each subject.

Hepatic STAMP2 mediates recombinant FGF21-induced improvement of hepatic iron overload in nonalcoholic fatty liver disease.

Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated the mechanism underlying the therapeutic effect of recombinant FGF21 on NAFLD, focusing on the involvement of hepatic STAMP2. In this study, we used human nonalcoholic steatosis patient pathology samples, C57BL/6 mice for a high-fat diet (HFD)-induced in vivo NAFLD model, and used human primary hepatocytes and HepG2 cells for oleic acid (OA)-induced in vitro NAFLD model. We observed that recombinant FGF21 treatment ameliorated hepatic steatosis and insulin resistance through the upregulation of STAMP2 expression. We further observed hepatic iron overload (HIO) and reduced iron exporter, ferroportin expression in the liver samples obtained from human NAFLD patients, and HFD-induced NAFLD mice and in OA-treated HepG2 cells. Importantly, recombinant FGF21 improved HIO through the hepatic STAMP2-mediated upregulation of ferroportin expression. Our data suggest that hepatic STAMP2 may represent a suitable therapeutic intervention target for FGF21-induced improvement of NAFLD accompanying HIO.

Striatal dopamine transporter changes after glucose loading in humans.

AIMS: The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading-induced changes in striatal DAT levels could be associated with food intake in humans. MATERIALS AND METHODS: An intravenous bolus injection of 18 F-FP-CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume-of-interest-based analysis, an atlas involving sub-striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND ) were measured using a simplified reference tissue method with cerebellum as the reference. RESULTS: The glucose-loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo-loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPND s: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. CONCLUSION: Striatal DAT changes after glucose loading, and BMI is associated with glucose-loaded DAT availability, not with placebo-loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Comparison of the effects of gemigliptin and dapagliflozin on glycaemic variability in type 2 diabetes: A randomized, open-label, active-controlled, 12-week study (STABLE II study).

AIMS: The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients. MATERIALS AND METHODS: In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. RESULTS: Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups. CONCLUSIONS: Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve.

Development of a risk scoring system for patients with papillary thyroid cancer.

As the importance of personalized therapeutics in aggressive papillary thyroid cancer (PTC) increases, accurate risk stratification is required. To develop a novel prognostic scoring system for patients with PTC (n = 455), we used mRNA expression and clinical data from The Cancer Genome Atlas. We performed variable selection using Network-Regularized high-dimensional Cox-regression with gene network from pathway databases. The risk score was calculated using a linear combination of regression coefficients and mRNA expressions. The risk score and clinical variables were assessed by several survival analyses. The risk score showed high discriminatory power for the prediction of event-free survival as well as the presence of metastasis. In multivariate analysis, the risk score and presence of metastasis were significant risk factors among the clinical variables that were examined together. In the current study, we developed a risk scoring system that will help to identify suitable therapeutic options for PTC.

BRAF-positive multifocal and unifocal papillary thyroid cancer show different messenger RNA expressions.

OBJECTIVE: Thyroid cancer is the most common malignant endocrine tumour, and its incidence has continuously increased worldwide over the past three decades. We focused on the association of multifocal papillary thyroid carcinoma (PTC) with messenger RNA (mRNA) expression to characterize how molecular and histopathologic features relate to multifocality. DESIGN: A retrospective cohort study. PATIENTS: The primary and processed data were downloaded from The Cancer Genome Atlas. A total of 490 patients were included in this study. METHODS: The statistical significance of differences in sex, age, histology, LN metastasis and recurrence were analysed using chi-squared test. To identify differentially expressed genes between BRAF (+) multifocal and unifocal PTCs and between BRAF (-) multifocal and unifocal PTCs, we used the Significance Analysis of Microarray. Over-representation analysis is conducted using CPDB. RESULTS: A total of 237 patients had BRAF (+) PTCs, whereas 253 had BRAF (-) PTCs. There were 110 patients with multifocal PTCs and 127 with unifocal PTCs in the BRAF (+) group and 116 patients with multifocal PTCs and 137 with unifocal PTCs in the BRAF (-) group. In BRAF (+) group, multifocal PTCs had increased expression of 158 mRNAs as compared to that in unifocal PTCs. Ten mRNAs were involved in Wnt-related pathways, and seven mRNAs were included in pluripotency-related pathways. CONCLUSION: Multifocal PTCs have higher expression of mRNAs in Wnt- and pluripotency-related pathways when BRAF mutation is present. This might be the mechanism that accounts for the difference between multifocal and unifocal PTCs.

Change of skeletal muscle mass in patients with pheochromocytoma.

The effects of catecholamine excess due to pheochromocytoma on body composition, including skeletal muscle mass, are unknown. Here, we investigated the effects of catecholamine metabolites on body composition in subjects with pheochromocytoma. After body compositions using bioelectrical impedance analysis, urinary metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two groups. After adjustments for confounders, UM (ß = - 0.171, P = 0.006) and UNM (ß = - 0.249, P < 0.001) levels were correlated inversely with skeletal muscle mass index (SMI), but not FM or percentage FM (pFM), in all subjects. Patients with pheochromocytoma had lower ASM by 7.7% (P = 0.022) and SMI by 6.6% (P = 0.001) than patients with NFAI. Conversely, FM and pFM were not statistically different between the two groups. The odds ratio for low skeletal muscle mass in the presence of pheochromocytoma was 10.33 (95% confidence interval, 2.65-40.22). Our results indicate that patients with pheochromocytoma have a reduced skeletal muscle mass and suggest that catecholamine excess has adverse effects on skeletal muscle metabolism.

New diagnostic criteria for subclinical hypercortisolism using postsurgical hypocortisolism: the Co-work of Adrenal Research study.

OBJECTIVE: There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic-pituitary-adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications. DESIGN: Prospective and cross-sectional, observational, multicentre study in Korea. METHODS: After exclusion of overt Cushing's syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test. RESULTS: Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone-sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98-566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84-6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality. CONCLUSIONS: Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.

Effect of gemigliptin on glycaemic variability in patients with type 2 diabetes (STABLE study).

The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase-4 (DPP-4) inhibition in patients with type 2 diabetes. This multicentre, randomized, active-controlled, open-label exploratory study included 69 patients with HbA1c > 7.5%. Subjects were randomized to receive gemigliptin 50 mg (n = 24), sitagliptin 100 mg (n = 23) or glimepiride 2 mg (n = 22) for 12 weeks. After 12 weeks, the change in mean amplitude of glycaemic excursion (MAGE) compared with baseline was significantly lower in the DPP-4 inhibitor groups compared with that in patients who received glimepiride. Furthermore, the standard deviation (SD) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride. The DPP-4 inhibition was significantly correlated with changes in MAGE and SD of glucose. In conclusion, gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes, and the DPP-4 inhibition was associated with a reduction in glycaemic variability.

Hepatic STAMP2 alleviates high fat diet-induced hepatic steatosis and insulin resistance.

BACKGROUND & AIMS: Most studies on the role of STAMP2 in metabolism have used adipose tissue. Little knowledge exists concerning the role of STAMP2 in the liver, which is a metabolically central target. We hypothesized that STAMP2 is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. METHODS: We examined our hypothesis using human NAFLD patient pathology samples and a high-fat diet (HFD)-induced NAFLD mouse model. The molecular mechanism underlying hepatic STAMP2-mediated lipid imbalance was explored using an oleic acid (OA)-induced NAFLD in vitro model. RESULTS: Noticeably, the expression level of STAMP2 protein was reduced in the livers obtained from NAFLD patients and HFD-induced NAFLD mice. In vivo knockdown of hepatic STAMP2 by siRNA accelerated hepatic steatosis and insulin resistance in mice fed a HFD. Conversely, the delivery of adenoviral STAMP2 (Ad-STAMP2) improved hepatic steatosis in HFD-induced NAFLD mice. The expression of lipogenic or adipogenic factors was increased in both in vitro and in vivo NAFLD models but was reversed by Ad-STAMP2. Adenoviral overexpression of STAMP2 improved insulin resistance in the HFD-induced NAFLD mice. In vivo and in vitro assays demonstrated that STAMP2 modulates insulin sensitivity and glucose metabolism and that STAMP2 counteracts OA-induced insulin resistance by modulating insulin receptor substrate-1 stability. CONCLUSIONS: The present study revealed that hepatic STAMP2 plays a pivotal role in preventing HFD-induced NAFLD and that STAMP2 overexpression improves hepatic steatosis and insulin resistance in NAFLD. Our findings indicate that STAMP2 may represent a suitable target for interventions targeting NAFLD.

Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

Glucocorticoid-Induced Hyperglycemia: A Neglected Problem.

Glucocorticoids provide a potent therapeutic response and are widely used to treat a variety of diseases, including coronavirus disease 2019 (COVID-19) infection. However, the issue of glucocorticoid-induced hyperglycemia (GIH), which is observed in over one-third of patients treated with glucocorticoids, is often neglected. To improve the clinical course and prognosis of diseases that necessitate glucocorticoid therapy, proper management of GIH is essential. The key pathophysiology of GIH includes systemic insulin resistance, which exacerbates hepatic steatosis and visceral obesity, as well as proteolysis and lipolysis of muscle and adipose tissue, coupled with ß-cell dysfunction. For patients on glucocorticoid therapy, risk stratification should be conducted through a detailed baseline evaluation, and frequent glucose monitoring is recommended to detect the onset of GIH, particularly in high-risk individuals. Patients with confirmed GIH who require treatment should follow an insulin-centered regimen that varies depending on whether they are inpatients or outpatients, as well as the type and dosage of glucocorticoid used. The ideal strategy to maintain normoglycemia while preventing hypoglycemia is to combine basal-bolus insulin and correction doses with a continuous glucose monitoring system. This review focuses on the current understanding and latest evidence concerning GIH, incorporating insights gained from the COVID-19 pandemic.

Intensity of statin therapy and primary prevention of cardiovascular in Korean patients with dyslipidemia.

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ±â€…6.6 months. The mean age of all participants at baseline was 59.2 ±â€…8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ±â€…mg/dL, the mean duration of taking statins was 337.4 ±â€…52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.

Radioactive iodine ablation does not prevent recurrences in patients with papillary thyroid microcarcinoma.

OBJECTIVE: Although papillary thyroid microcarcinoma (PTMC) has a favourable long-term prognosis, disease recurrence after initial treatment remains a problem and controversy exists regarding the role of radioactive iodine (RAI) ablation in PTMC. We performed this study to evaluate the effect of RAI ablation on disease recurrence in patients with PTMC. PATIENTS AND METHODS: Between 1994 and 2004, 2579 patients underwent thyroid surgery for thyroid cancer at Samsung Medical Center. Among these patients, 704 patients with PTMC presumed disease-free after initial treatment were followed up for disease recurrence (median, 64 months; range, 1-185 months). Patients with PTMC with microscopic extrathyroidal extension, cervical lymph node metastases or multifocality were considered to be in the intermediate-risk group for recurrence. RESULTS: Disease recurrence was found in six patients at a median of 29 months (range, 10-70 months) after initial treatment; all six patients with recurrent tumours had received RAI treatment after total thyroidectomy. Disease-related mortality was not observed, even after recurrence. Based on a Cox regression model considering the standardized inverse probability of treatment weight (IPTW) within each propensity score stratum of patients with a similar likelihood of having received RAI ablation, the likelihood ratio for recurrence did not differ between the RAI ablation group and no RAI group (P = 0·17). When we performed a subgroup analysis considering only patients with PTMC at intermediate-risk for recurrence, RAI ablation again did not have a significant effect on recurrence (P = 0·79). CONCLUSIONS: Radioactive iodine ablation after total thyroidectomy in low- and intermediate-risk patients with PTMC did not prevent recurrent tumours. Future randomized, controlled, multicenter prospective trials involving a larger sample of patients followed-up for a longer duration are warranted to confirm our findings.

Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer.

OBJECTIVE: Epidemiological studies have demonstrated that excess weight increases the risk of thyroid cancer. However, the associations between excess weight and prognostic factors for thyroid cancer are uncertain. We evaluated the relationships between body mass index (BMI) and clinico-pathological features and outcomes of papillary thyroid cancer (PTC). PATIENTS AND METHODS: Retrospective analysis of 2057 patients with PTC was performed. Patients were grouped according to BMI (underweight, normal weight, overweight and obesity)-based World Health Organization standardized categories. Logistic regression models were used to assess the relationships between BMI and clinico-pathological features of PTC. A Cox proportional hazards model was used to examine the association between BMI and disease recurrence. RESULTS: A 5-kg/m(2) increase in BMI was associated with PTC tumours larger than 1 cm [odds ratio (OR) 1.31, P < 0.001], with microscopic extrathyroidal invasion (OR 1.23, P = 0.006), and with advanced tumour-node-metastasis (TNM) stage (OR, 1.30, P = 0.003), which is independent of confounding variables such as gender, age, serum TSH, total cholesterol and fasting glucose level. The multivariate-adjusted OR [95% confidence intervals (CI)] in the overweight (25.0-29.9 kg/m(2)) and obese (BMI ≥ 30) groups for tumours larger than 1 cm were 1.41 (1.10-1.81) and 2.17 (1.23-3.82), respectively, compared to the normal weight group (BMI 18.5-24.9). The multivariate-adjusted OR (95% CI) for microscopic extrathyroidal extension in the obesity group was 1.88 (1.06-3.32), and the OR for advanced TNM stage in the overweight group was 1.35 (1.02-1.79) compared to the normal weight group. During follow-up (median, 84 month; range, 1-185), 43 patients (2.1%) experienced recurrence. There were no significant differences in recurrence of PTCs among BMI groups. CONCLUSIONS: Higher BMI was strongly associated with larger tumour size, extrathyroidal invasion and advanced TNM stage of PTCs. However, there was no difference in recurrence rate among BMI groups. This study suggests that excess weight is associated with aggressive features of PTCs. Further studies with long-term follow-up are needed to confirm this finding.