Metabolic Associated Fatty Liver Disease Increases the Risk of Systemic Complications and Mortality. A Meta-Analysis and Systematic Review of 12 620 736 Individuals

ObjectiveThe recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD.MethodsMEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications.ResultsA total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P < .01), stroke (HR, 1.55; CI, 1.37-1.73; P < .01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy.ConclusionMAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.     

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

ObjectiveNonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality.MethodsMEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity.ResultsFifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I² = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I² = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I² = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I² = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results.ConclusionNAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.     

High Prevalence of Nonalcoholic Fatty Liver Disease Among Adolescents and Young Adults With Hypopituitarism due to Growth Hormone Deficiency

ObjectiveTo investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD.MethodsA cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD.ResultsThe adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS.ConclusionOur results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.     

Fatty Liver Through the Ages: Nonalcoholic Steatohepatitis

ObjectiveThe global epidemic of obesity and type 2 diabetes mellitus is the main driver of the growing global prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to review the current literature on NAFLD and nonalcoholic steatohepatitis (NASH) as it impacts children and adults.MethodsWe performed a literature search on fatty liver specifically NAFLD and NASH among children and adults.ResultsThe prevalence of NAFLD in children ranges from 8% to 12%, while the prevalence in adults ranges 25% to 48%. The prevalence of NASH among children with NAFLD is 23%, while it ranges from 13% to 65% in adults. There are similar risk factors for NAFLD among children and adults. However, in children, the diagnostic tests in the studies of NAFLD are limited to the elevation of the alanine aminotransferase level or a liver biopsy. In adults, additional diagnostic modalities, including noninvasive tests, have been used. From the spectrum of NAFLD, patients with NASH are predominantly at risk of progressive liver disease to cirrhosis and liver-related mortality. NAFLD is associated with impairment of health-related quality of life and substantial economic burden.ConclusionThe comprehensive burden (clinical, health-related quality of life, and economic) of NAFLD is high and increasing.     

Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials

ObjectiveType 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus.MethodsMedline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness.ResultsA total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): ?6.02%, confidence interval (CI): ?10.37% to ?1.67%] and SGLT2 inhibitors (MD: ?2.60%, CI: ?4.87% to ?0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: ?0.06, CI: ?0.10 to ?0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein.ConclusionGlucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.     

Thionamide-induced Agranulocytosis: A Retrospective Analysis of 36 Patients With Hyperthyroidism

ObjectiveAgranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism.MethodsThis retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed.ResultsAgranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 10⁹/L and 0.14 (0.02-0.29) × 10⁹/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day.ConclusionsPatients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.     

Desmopressin Suppresses Gonadotropin-Induced Spermatogenesis in Patients With Pituitary Stalk Interruption Syndrome: A Retrospective,Single-Center Cohort Study

ObjectiveTo explore the influence of desmopressin on gonadotropin-induced spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS).MethodsA single-center retrospective cohort study was conducted. All patients with PSIS had both gonadotropin and growth hormone (GH) deficiency. Patients were divided into desmopressin and nondesmopressin groups. The desmopressin and nondesmopressin groups were defined by the presence or absence of central diabetes insipidus, which determined whether the patient received desmopressin or not.ResultsThe average age of gonadotropin therapy was 24.3 and 26.1 in the desmopressin and nondesmopressin groups, respectively. The rate of successful spermatogenesis in the 2 groups was 31.58% and 77.27%, respectively. The period for first sperm appearance was 13.62 ± 5.95 and 13.48 ± 6.69 months, respectively. A multivariable Cox proportional hazards model found that the adjusted hazard ratio for desmopressin was 0.260, indicating a “possible” detrimental effect of desmopressin on spermatogenesis. Central diabetes insipidus would be expected to show a similar detrimental effect. The spermatogenesis rate decreased with increased dosage of desmopressin. In the nondesmopressin group, the rate of spermatogenesis was similar between the GH group and the non-GH subgroup. The GH group had higher sperm count and concentration than the non-GH group.ConclusionA minority of patients with PSIS had mild diabetes insipidus and received desmopressin therapy. The spermatogenesis rate decreased with increasing desmopressin dosage. In addition, GH supplementation did not affect the spermatogenesis rate.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.     

Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors

ObjectivePatients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency.MethodsWe enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed.ResultsAldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism.ConclusionPTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.     

Association of Body Mass Index With Clinicopathological Features of Papillary Thyroid Carcinoma: A Retrospective Study

ObjectiveWe examined the effect of body mass index (BMI) on clinicopathological features of papillary thyroid carcinoma (PTC).MethodsThe clinical data of 4476 patients with PTC who underwent surgical treatment were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight (BMI < 18.5 kg/m²), normal weight (18.5 ≤ BMI < 24.0 kg/m²), overweight (24 ≤ BMI < 28 kg/m²), and obese (BMI ≥ 28 kg/m²). Spearman correlation analysis was performed to assess the relationship between the BMI and the size of PTC tumor. Multivariate binary logistic regression analysis was performed to estimate the association of overweight and obesity with clinicopathological features of PTC.ResultsThere was a positive correlation between the BMI and PTC tumor size (r = 0.087, P < .001). As compared with normal weight patients with PTC, overweight and obese patients with PTC had a greater risk of bilaterality (odds ratio [OR] = 1.295, OR = 1.669), multifocality (OR = 1.273, OR = 1.617), extrathyroidal extension (OR = 1.560, OR = 2.477), T (3 + 4) stage (OR = 1.482, OR = 2.392), and recurrence risk (intermediate-high risk) (OR = 1.215, OR = 1.718) (P < .05 for all). As compared with normal weight patients with papillary thyroid microcarcinoma (PTMC), overweight and obese patients with PTMC had a greater risk of bilaterality (OR = 1.341, OR = 1.737), multifocality (OR = 1.244, OR = 1.640), extrathyroidal extension (OR = 1.992, OR = 2.080), T (3 + 4) stage (OR = 1898, OR = 2.039), and recurrence risk (intermediate-high risk) (OR = 1.458, OR = 1.536) (P < .05 for all).ConclusionOverweight and obesity were significantly associated with aggressive clinicopathological features of PTC and PTMC. The impact of overweight and obesity should be considered when choosing treatment decisions for PTC and PTMC.     

Validation of Diagnostic Coding for Diabetes Mellitus in Hospitalized Patients

ObjectiveSome studies have shown that there is an undercoding of diabetes mellitus among hospitalized patients, which can have adverse clinical and financial implications for health systems. We aimed to validate the discharge diagnostic coding of diabetes mellitus in hospitalized patients using clinical and laboratory-based diagnostic indicators as the reference.MethodsThis was a retrospective cohort study of 83 690 discharges of 48 615 unique adult patients who were hospitalized in an academic medical center over 4.5 years and had at least 4 blood glucose measurements during admission. A missing diabetes code (MDC) was defined using 2 criteria. MDC₁ was defined as the presence of any of the following: blood glucose ≥200 (x2), A1C ≥6.5%, home antihyperglycemic medication, or preadmission code for diabetes, whereas MDC₂ was defined as preadmission diabetes or at least 2 other criteria in MDC₁. Multivariable logistic regression was used to identify factors associated with MDC compared to the present diabetes code.ResultsMDC₁ and MDC₂ were present in 12 186 (14.6%) and 3542 (4.7%) discharges, respectively. Factors associated with both MDC₁ and MDC₂ were medium-dose steroid use [adjusted odds ratio (aOR) 2.11, 2.01], high-dose steroid use (aOR 4.70, 2.50), intermediate medical care service (aOR 1.65, 1.55), infection (aOR 1.21, 1.34), and hepatic disease (aOR 1.93, 1.92).ConclusionIn this retrospective study, MDC ranged from 5% to 15% and was associated with various clinical factors. Further prospective studies are needed to validate these findings, explore the mechanisms behind these associations, and understand the clinical and financial implications.     

Insulin Dosing and Glycemic Outcomes Among Steroid-treated Hospitalized Patients

ObjectiveTo determine the optimal insulin-to-steroid dose ratio for the attainment of glycemic control in hospitalized patients.MethodsWe retrospectively studied data collected from the electronic health records within an academic medical center from 18 599 patient-days where patients were treated concurrently with insulin and steroids. Multivariate logistic regression analyses, which included demographic and clinical variables, were performed to assess the relationships between the exposures of total and basal insulin-to-steroid ratios and the outcomes of glycemic control (all blood glucose readings on the following patient-day were >70 and ≤180 mg/dL) and hypoglycemia within 3 subgroups of steroid dosing: low (≤10-mg prednisone equivalent dose [PED]), medium (from >10-mg to ≤40-mg PED), and high (>40-mg PED).ResultsIncreased insulin-to-steroid ratio was associated with increased odds of both glycemic control and hypoglycemia. The optimal total insulin-to-steroid ratio for attaining glycemic control was 0.294 U/kg/10-mg PED in the low-dose subgroup, 0.257 U/kg/10-mg PED in the medium-dose subgroup, and 0.085 U/kg/10-mg PED in the high-dose subgroup. The optimal basal insulin-to-steroid ratio was 0.215 U/kg/10-mg PED in the low-dose subgroup, 0.126 U/kg/10-mg PED in the medium-dose subgroup, and 0.036 U/kg/10-mg PED in the high-dose subgroup.ConclusionIncreasing insulin-to-steroid ratios are positively associated with glycemic control and hypoglycemia. Our study suggests that approximately 0.3 U/kg/10-mg PED is an optimal dose for low- and medium-dose steroids, whereas approximately 0.1 U/kg/10-mg PED is an optimal dose for high-dose steroids. Further prospective studies are needed to identify insulin regimens that will optimize glycemic control in steroid-treated patients while minimizing the risk of hypoglycemia.     

Evaluating the Impact of Inadequate Meal Consumption on Insulin-Related Hypoglycemia in Hospitalized Patients

ObjectiveMeal intake is sometimes reduced in hospitalized patients. Meal-time insulin administration can cause hypoglycemia when a meal is not consumed. Inpatient providers may avoid ordering meal-time insulin due to hypoglycemia concerns, which can result in hyperglycemia. The frequency of reduced meal intake in hospitalized patients remains inadequately determined. This quality improvement project evaluates the percentage of meals consumed by hospitalized patients with insulin orders and the resulting risk of postmeal hypoglycemia (blood glucose [BG] <70 mg/dL, <3.9 mmol/L).MethodsThis was a retrospective quality improvement project evaluating patients with any subcutaneous insulin orders hospitalized at a regional academic medical center between 2015 and 2017. BG, laboratory values, point of care, insulin administration, diet orders, and percentage of meal consumed documented by registered nurses were abstracted from electronic health records.ResultsMeal consumption ≥50% was observed for 85% of meals with insulin orders, and bedside registered nurses were accurate at estimating this percentage. Age ≥65 years was a risk factor for reduced meal consumption (21% of meals 0%-49% consumed, P < .05 vs age < 65 years [12%]). Receiving meal-time insulin and then consuming only 0% to 49% of a meal (defined here as a mismatch) was not rare (6% of meals) and increased postmeal hypoglycemia risk. However, the attributable risk of postmeal hypoglycemia due to this mismatch was low (4 events per 1000) in patients with premeal BG between 70 and 180 mg/dL.ConclusionThis project demonstrates that hospitalized patients treated with subcutaneous insulin have a low attributable risk of postmeal hypoglycemia related to inadequate meal intake.     

Correlation of Hemoglobin A1C and Outcomes in Patients Hospitalized With COVID-19

ObjectiveDiabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19). We conducted this study to determine if there is a correlation between hemoglobin A1C (HbA1C) level and poor outcomes in hospitalized patients with diabetes and COVID-19.MethodsThis is a retrospective, single-center, observational study of patients with diabetes (defined by an HbA1C level of ≥6.5% or known medical history of diabetes) who had a confirmed case of COVID-19 and required hospitalization. All patients were admitted to our institution between March 3, 2020, and May 5, 2020. HbA1C results for each patient were divided into quartiles: 5.1% to 6.7% (32-50 mmol/mol), 6.8% to 7.5% (51-58 mmol/mol), 7.6% to 8.9% (60-74 mmol/mol), and >9% (>75 mmol/mol). The primary outcome was in-hospital mortality. Secondary outcomes included admission to an intensive care unit, invasive mechanical ventilation, acute kidney injury, acute thrombosis, and length of hospital stay.ResultsA total of 506 patients were included. The number of deaths within quartiles 1 through 4 were 30 (25%), 37 (27%), 34 (27%), and 24 (19%), respectively. There was no statistical difference in the primary or secondary outcomes among the quartiles, except that acute kidney injury was less frequent in quartile 4.ConclusionThere was no significant association between HbA1C level and adverse clinical outcomes in patients with diabetes who are hospitalized with COVID-19. HbA1C levels should not be used for risk stratification in these patients.     

American Association of Clinical Endocrinology Consensus Statement: Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity/Adiposity-Based Chronic Disease and Assessing Bias and Stigmatization as Determinants of Disease Severity

ObjectiveTo focus on the intersection of perception, diagnosis, stigma, and weight bias in the management of obesity and obtain consensus on actionable steps to improve care provided for persons with obesity.MethodsThe American Association of Clinical Endocrinology (AACE) convened a consensus conference of interdisciplinary health care professionals to discuss the interplay between the diagnosis of obesity using adiposity-based chronic disease (ABCD) nomenclature and staging, weight stigma, and internalized weight bias (IWB) with development of actionable guidance to aid clinicians in mitigating IWB and stigma in that context.ResultsThe following affirmed and emergent concepts were proposed: (1) obesity is ABCD, and these terms can be used in differing ways to communicate; (2) classification categories of obesity should have improved nomenclature across the spectrum of body mass index (BMI) using ethnic-specific BMI ranges and waist circumference (WC); (3) staging the clinical severity of obesity based on the presence and severity of ABCD complications may reduce weight-centric contribution to weight stigma and IWB; (4) weight stigma and internalized bias are both drivers and complications of ABCD and can impair quality of life, predispose to psychological disorders, and compromise the effectiveness of therapeutic interventions; (5) the presence and of stigmatization and IWB should be assessed in all patients and be incorporated into the staging of ABCD severity; and (6) optimal care will necessitate increased awareness and the development of educational and interventional tools for health care professionals that address IWB and stigma.ConclusionsThe consensus panel has proposed an approach for integrating bias and stigmatization, psychological health, and social determinants of health in a staging system for ABCD severity as an aid to patient management. To effectively address stigma and IWB within a chronic care model for patients with obesity, there is a need for health care systems that are prepared to provide evidence-based, person-centered treatments; patients who understand that obesity is a chronic disease and are empowered to seek care and participate in behavioral therapy; and societies that promote policies and infrastructure for bias-free compassionate care, access to evidence-based interventions, and disease prevention.     

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study

ObjectiveAlthough the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up.MethodsIn this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons.ResultsThis study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease.ConclusionApplying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.     

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses

ObjectiveAn elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR).MethodsThis study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. Multivariable logistic and Cox proportional hazard regression analyses were performed, respectively. VTDR was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or clinically significant macular edema.ResultsA total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, higher corrected serum calcium (odds ratio: 1.31 per 0.1 mmol/L, 95% confidence interval: 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium were independently associated with VTDR. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range: 7.4-10.9 years). Higher corrected serum calcium (hazard ratio: 1.38 per 0.1 mmol/L, 95% confidence interval: 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher glycated hemoglobin were identified as independent risk factors for VTDR.ConclusionsA higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.     

Association Between a Low-Carbohydrate Diet,Glycemic Control,and Quality of Life in Australian Adults Living With Type 1 Diabetes: A Pilot Study

ObjectiveTo examine if there is an association between a low-carbohydrate diet (LCD), glycemic control, and quality of life (QoL) in Australian adults with type 1 diabetes.MethodsThis single-group, pre-post, mixed methods (quantitative and qualitative) study was conducted in an outpatient tertiary hospital. Eligible participants were those aged ≥18 years, with type 1 diabetes for ≥1 year, and using multiple daily insulin injections. Participants followed a 12-week individualized LCD (<100 g/d). Daily glucose levels were monitored using a continuous glucose monitor. Glycated hemoglobin (HbA1c) and QoL were measured preintervention and postintervention. A post-hoc exploratory regression analysis determined whether changes in carbohydrate intake was associated with changes in HbA1c and QoL. Qualitative data collected postintervention explored participants’ perceptions relating to a LCD, glycemic control, and QoL.ResultsParticipants (n = 22) completed the 12-week LCD intervention. An LCD provided a statistically, significant improvement in HbA1c 0.83% (95% CI 0.32%-1.33%), P = .003 but did not impact QoL: estimated change 1.14 units (95% CI: ?5.34 to 7.61); P = .72. The post-hoc exploratory regression analysis showed that participants with poorer baseline glycemic control were more likely to respond to an LCD resulting in significant reductions in HbA1c. Participant perceptions relating to the study variables were mixed.ConclusionsAn LCD (<100 g/d) is a potentially effective and safe strategy to improve glycemic control without negatively effecting QoL in Australian adults with type 1 diabetes.