Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Adrenal Hemorrhage in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report and Literature Review

Antiphospholipid syndrome (APS) is an autoimmune disorder while adrenal hemorrhage could be its rare complication. Herein, we report the case of a 32-year-old unmarried woman with a history of systemic lupus erythematosus (SLE) who was hospitalized after complaints of upper abdominal pain, limb weakness, and loss of appetite for 2 weeks. Laboratory examination revealed hyponatremia, low plasma cortisol levels, increased adrenocorticotropic hormone levels, and a positive anticardiolipin antibody status. Furthermore, computed tomography (CT) revealed the presence of bilateral adrenal masses. Ultimately, based on dynamic changes in CT images, these masses were diagnosed as adrenal hemorrhage owing to APS. A computer-assisted literature search was conducted to identify cases of primary adrenal insufficiency associated with APS and/or SLE. The clinical features, laboratory examination, treatments, and outcomes of these cases were summarized. Our findings emphasize the importance of screening for adrenal insufficiency in patients with SLE or APS who present with abdominal complaints, asthenia, and hyponatremia. It is also recommended to test for APS all patients with adrenal hemorrhage

Glucokinase activator improves glucose tolerance and induces hepatic lipid accumulation in mice with diet-induced obesity

Background and aims: Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence. Pharmacological research is becoming increasingly focused on personalized treatment strategies. Drug development based on glucokinase (GK) activation is an important strategy for lowering blood glucose. This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice. Materials and methods: Mice were fed with a high-fat diet (HFD) for 16 weeks to induce obesity, followed by a GK activator (GKA, AZD1656) or vehicle treatment by gavage for 4 weeks. The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests. Hepatic lipid accumulation was assessed by hematoxylin and eosin staining, Oil Red O staining, and transmission electron microscopy. The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis, with a mechanistic study in mouse livers in vivo and AML12 cells in vitro. Results: GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation. Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase (PERK)-unfolded protein response (UPR) pathway activations in GKA-treated HFD-fed mice. Inhibition of the ACC activity, which is an important protein in lipogenesis, attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro. Conclusions: GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression, which subsequently activated the hepatic PERK-UPR signaling pathway

Utility of Neck Circumference for Identifying Metabolic Syndrome by Different Definitions in Chinese Subjects over 50 Years Old: A Community-Based Study

Aims. Whether neck circumference (NC) could be used as a valuable tool for identifying metabolic syndrome (MS) by different criteria in Chinese is still unclear. Methods. We conducted a cross-sectional survey from October 2010 to January 2011 in Shipai community, Guangzhou, Guangdong Province, China. A total of 1473 subjects aged over 50 years were investigated. We measured height, weight, NC, waist circumference, blood pressure, blood glucose, and lipids in all subjects. MS was identified by criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Chinese Diabetes Society (CDS), and International Diabetes Federation (IDF). Results. Mean NC was 38.0 ± 2.7 cm in men and 34.2 ± 2.5 cm in women. By using receiver operating characteristic curves, the area under the curve (AUC) of NC for identifying MS (IDF) was 0.823 in men and 0.777 in women, while for identifying MS (CDS), it was 0.788 in men and 0.762 in women. The AUC of NC for diagnosing MS (ATP III) was 0.776 in men and 0.752 in women. The optimal cut points of NC for MS were 38.5 cm by three definitions in men, while those were 34.2 cm, 33.4 cm, and 34.0 cm in women by IDF, ATP III, and CDS definitions, respectively. No significant difference was observed between the AUC of NC and BMI for diagnosing MS by using different criteria (all p>0.05). Conclusions. NC is associated with MS by different definitions in Chinese subjects over 50 years old. It may be a useful tool to identify MS in a community population

A Randomized Trial of Insulin Glargine plus Oral Hypoglycemic Agents versus Continuous Subcutaneous Insulin Infusion to Treat Newly Diagnosed Type 2 Diabetes

Aims. Basal insulin plus oral hypoglycemic agents (OHAs) has not been investigated for early intensive antihyperglycemic treatment in people with newly diagnosed type 2 diabetes. This study is aimed at comparing the short-term (over a period of 12 days) effects of basal insulin glargine plus OHAs and continuous subcutaneous insulin infusion (CSII) on glycemic control and beta-cell function in this setting. Methods. An open-label parallel-group study. Newly diagnosed hospitalized patients with type 2 diabetes and fasting plasma glucose (FPG) ≥11.1 mmol/L or glycated hemoglobin (HbA1c) ≥9% (75 mmol/mol) were randomized to CSII or insulin glargine in combination with metformin and gliclazide. The primary outcome measure was the mean amplitude of glycemic excursions (MAGE), and secondary endpoints included time to reach glycemic control target (FPG < 7 mmol/L and 2-hour postprandial plasma glucose < 10 mmol/L), markers of β-cell function, and hypoglycemia. Results. Subjects in the CSII (n=35) and basal insulin plus OHA (n=33) groups had a similar significant reduction from baseline to end of treatment in glycated albumin (−6.44 ± 3.23% and− 6.42 ± 3.56%, P=0.970). Groups A and B have comparable time to glycemic control (3.6 ± 1.2 days and 4.0 ± 1.4 days), MAGE (3.40 ± 1.40 mmol/L vs. 3.16 ± 1.38 mmol/L; p=0.484), and 24-hour mean blood glucose (7.49 ± 0.96 mmol/L vs. 7.02 ± 1.03 mmol/L). Changes in the C-peptide reactivity index, the secretory unit of islet in transplantation index, and insulin secretion-sensitivity index-2 indicated a greater β-cell function improvement with basal insulin plus OHAs versus CSII. Conclusions. Short-term insulin glargine plus OHAs may be an alternative to CSII for initial intensive therapy in people with newly diagnosed type 2 diabetes

Direct medical costs for patients with type 2 diabetes in 16 tertiary hospitals in urban China: A multicenter prospective cohort study

Abstract Aims/Introduction To investigate the direct medical costs for patients with type 2 diabetes in China and to examine the influencing factors. Materials and Methods In the present multicenter study, 1,070 patients with type 2 diabetes from 16 tertiary hospitals in 14 major cities of China were enrolled. Patient data and direct medical costs were collected during a follow‐up period of 6 months at intervals of 1 month. The log‐transformed direct medical costs were fitted by a generalized estimation equation to indicator variables for demographics, metabolic control, treatments, complications and comorbidities. Results Data of 871 participants were included in the analysis. The mean annual total direct medical costs and outpatient medical costs were $1,990.20 and$1,687.20 respectively. The average costs per inpatient per admission were $2,127.10. The share of out‐of‐pocket for total medical costs, outpatient costs and cost per inpatient per admission were 45.4, 46.3 and 26.0% respectively. Independent determinants of total medical costs were diabetes duration, dyslipidemia and diabetic complications, such as neuropathy and nephropathy, as well as diabetes treatment, such as the use of glucagon‐like peptide‐1 receptor agonists. Costs showed prominent variation across centers. Conclusions Diabetes is imposing a growing economic burden in patients with type 2 diabetes in China. Diabetes‐related complications and comorbidities have a great impact on the medical costs. As different health policies, economic development and regional health inequalities also have an important influence on the direct medical cost, healthcare reform needs to optimize resource allocation in health service delivery systems, and provide more equitable and affordable healthcare