Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease

Chronic kidney disease (CKD) is the most common cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). CKD increases the risk of cardiovascular diseases; therefore, its prevention and treatment are important. The prevention of diabetic kidney disease (DKD) can be achieved through intensive glycemic control and blood pressure management. Additionally, DKD treatment aims to reduce albuminuria and improve kidney function. In patients with T2DM, renin-angiotensin-aldosterone system inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists can delay the progression of DKD. Hence, there is a need for novel treatments that can effectively suppress DKD progression. Finerenone is a first-in-class nonsteroidal mineralocorticoid receptor antagonist with clinically proven efficacy in improving albuminuria, estimated glomerular filtration rate, and risk of cardiovascular events in early and advanced DKD. Therefore, finerenone is a promising treatment option to delay DKD progression. This article reviews the mechanism of renal effects and major clinical outcomes of finerenone in DKD.

Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea

Background/Aims@#We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. @*Methods@#Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. @*Results@#The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. @*Conclusions@#The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.

Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study

BACKGROUND: Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes. METHODS: In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE), which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F₂α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation. RESULTS: Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046), and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026); however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F₂α did not change after treatment in both groups. CONCLUSION: In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.

Is an Oral Glucose Tolerance Test Still Valid for Diagnosing Diabetes Mellitus?

BACKGROUND: We evaluated the diagnostic rate of diabetes using fasting plasma glucose (FPG), 2-hour plasma glucose (2h PG) after 75 g oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels, and we elucidated the pathophysiologic characteristics and risk factors that give rise to diabetes in patients with prediabetes. METHODS: The data of 236 patients who had the OGTT at Konkuk University Hospital were analyzed. Fasting, 30, and 120 minutes blood glucose levels and insulin levels were measured. The diagnostic rate of diabetes was assessed using FPG, 2h PG, and HbA1c levels. The clinical data and insulin resistance and secretion evaluations were compared using indexes according to the fasting glucose level. RESULTS: Among 236 subjects, 97 (41.1%) were diabetics and 102 (43.2%) were prediabetics. The rate of diabetes diagnosis by one of the individual criteria was 56.7%, 53.6%, and 84.5% for FPG, HbA1c, and 2h PG, respectively. When two criteria were used to diagnose diabetes, 72.2% of the diabetic patients were identified by FPG and HbA1c, while 100% were identified by FPG and 2h PG, and 91.7% were identified by 2h PG and HbA1c. The HbA1c cut-off value for 2h PG ≥200 mg/dL was 6.1%, and the FPG cut-off value was 115 mg/dL. In impaired fasting glucose subjects, the HbA1c level, Matsuda index, and insulinogenic index were associated with risk of occurrence of overt diabetes (P<0.01). CONCLUSION: This study suggests that performing additional OGTT for patients with FPG ≥110 mg/dL or HbA1c ≥6.1% is helpful to reclassify their glucose tolerance status and evaluate their potential for progressing to overt diabetes.

Metformin Based Dual-Combination Therapies in Drug Naive Type 2 Diabetic Patients

No abstract available.

The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults

BACKGROUND: The common characteristics of metabolic syndrome (MetS) and Cushing's syndrome suggest that excess cortisol may be involved in the pathogenesis of MetS. Salivary cortisol measurements are simple and can be surrogates for plasma free cortisol, which is the most biologically active form. We evaluated the association between levels of midnight salivary cortisol and MetS in Korean adults. METHODS: A total of 46 subjects, aged 20 to 70 years, who visited the Health Care Center at Konkuk University Hospital from August 2008 to August 2009 were enrolled. We compared the levels of midnight salivary cortisol in subjects with MetS with those in subjects without MetS. We analyzed the associations between midnight salivary cortisol levels and components of MetS. RESULTS: Midnight salivary cortisol levels were higher in the MetS group (70+/-42.4 ng/dL, n=12) than that in the group without MetS (48.1+/-36.8 ng/dL, n=34) (P=0.001). Positive correlations were observed between midnight salivary cortisol levels and waist circumference, fasting blood glucose, and homeostasis model assessment of insulin resistance. The risk for MetS was significantly higher in subjects with midnight salivary cortisol levels > or =100 ng/dL than in those with levels <50 ng/dL (odds ratio, 5.9; 95% confidence interval, 2.35 to 36.4). CONCLUSION: The results showed a positive correlation between midnight salivary cortisol levels and MetS, suggesting that hypercortisolism may be related to MetS.

A Case of Type 2 Diabetes Mellitus Improved after Surgical Treatment of Primary Hyperparathyroidism / 임상당뇨병

Patients with primary hyperparathyroidism often exhibit insulin resistance and glucose intolerance. In previous studies, glucose intolerance was improved by parathyroidectomy in primary hyperparathyroidism. We report a case of type 2 diabetes mellitus that improved after resection of a parathyroid adenoma along with a review of the literature.

Candidate Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes

No abstract available.

Letter: Risk Factors Associated with Left Ventricular Diastolic Dysfunction in Type 2 Diabetic Patients without Hypertension (Korean Diabetes J 2010;34:40-6) / 당뇨병

No abstract available.

Hypoglycemia due to Focal Nesidioblastosis in a Patient with Type 2 Diabetes Mellitus / 당뇨병

We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.

Letter: Effects of Aerobic Exercise Intensity on Insulin Resistance in Patients with Type 2 Diabetes Mellitus (Korean Diabetes J 33(5):401-411, 2009) / 당뇨병

No abstract available.

The Effect of Rosiglitazone and Metformin Therapy, as an Initial Therapy, in Patients with Type 2 Diabetes Mellitus / 당뇨병

No abstract available.

Clinical Features in 147 Patients with Systemic Contact Dermatitisdue to the Ingestion of Chicken Boiled with Japanease Lacquer Tree / 대한피부과학회지

BACKGROUND: Systemic contact dermatitis (SCD) due to the ingestion of Japanese lacquer tree (Rhus verniciflua) is pretty common in Korea, and it is on a trend of increment. It is thought that the increase in ingestion of chickens boiled with the lacquer tree has been caused by the regard of the lacquer tree as a health food or herbal medicine for gastrointestinal disease. OBJECTIVE: To review the clinical findings and laboratory findings, and to make people aware of the harmful effects of the lacquer tree. METHODS: We retrospectively reviewed the medical records of 147 patients who had SCD due to chicken boiled with lacquer tree, 98 patients in Wonkwang University Hospital over the last 20 years (1998`2007) and 49 patients in Areumdaun Dermatology Clinic over the past 5 months (August~December, 2007). RESULTS: The sex ratio of patients (male to female) was 1.3:1 and the average age was 44.0 years old (range: 11~76). They ate chicken boiled with lacquer tree as a health food (42.9%) and for the treatment of gastrointestinal disease (22.4%). The mean incubation period was 47.7 hours (range: 30 min~16 days). The first symptoms they had were erythematous maculopapules (42.9%), itching without rash (33.7%), and edematous change (16.3%). The skin lesions developed as maculopapules (50.6%), erythroderma (40.9%), and erythema multiforme-like lesion (8.4%), vesicles, wheals, purpura, and pustules. On laboratory findings, some people had leukocytosis (61.2%), increment of Ig E (26.4%), abnormalities of liver function test (ALT: 16.3%, AST: 4.1%). Sixty percent of patients had a history of contact dermititous contracted via chicken boiled with rhus lacquer ingestion (36.7%) or contact with the lacquer tree. Clinical symptoms were developed by 29.5% who ate chicken boiled with lacquer. Mainly they had been treated with corticosteroids, antihistamines. The mean period needed for treatment was 8+/-2.4 days. CONCLUSION: Systemic contact dermatitis due to ingestion of the lacquer tree was developed in either sensitized or non-sensitized persons. It is suggested that SCD is caused by the highly allergic and toxic effects of lacquer. Physicians need to make people aware of the harmful effects of the lacquer tree and educate people not to ingest it.

Effects of lovastatin on free fatty acid oxidation in human skeletal muscle cells / 대한내과학회지

BACKGROUDN: Recent clinical studies have suggested that statins improve insulin resistance and glucose metabolism in the skeletal muscle of diabetic patients. To evaluate a possible component of this action, we measured free fatty acid oxidation in cultured human skeletal muscle cells (HSMC). METHODS: Seven normal controls and 7 type 2 diabetic patients underwent quadriceps muscle biopsy. The HSMCs (n=14) were treated with or without lovastatin (Lova, 20 micrometer) for 2 days, and the free fatty acid (FFA) oxidation was measured. RESULTS: Lova increased the oxidation of the long-chain FA palmitate to 271.2+/-32.7% of the control (p<0.01). Oxidation of the medium chain FA octanoate also increased after treatment of Lova (158.3+/-21.9%, p<0.05). One pathway of regulation of FFA is through AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation. Following Lova treatment, AMPK phosphorylation did not show a significant change while the total protein expression of AMPK was decreased (73.6+/-6.2% of the control, p<0.01). Lova treatment significantly increased ACC phosphorylation (149.5+/-20.6% of the control, p<0.05). CONCLUSION: Lova increased FFA oxidation by increasing the ACC phosphorylation in human skeletal muscle cells. Stimulation of skeletal muscle FFA oxidation may be one mechanism by which statins act to lower intramyocellular triglyceride and improve insulin action on glucose metabolism.

A case of necrotizing fasciitis caused by Klebsiella pneumoniae secondary to chronic otitis media / 대한내과학회지

Necrotizing fasciitis is a relatively uncommon infectious disorder where a bacterial organism penetrates the subcutaneous tissues and superficial fascia, ultimately causing necrosis of vast areas of soft tissue. Although invasive Streptococcus spp., most commonly group-A streptococci, is the most frequent cause of this disorder, in a single organism-infection, necrotizing fasciits caused by Klebseilla pneumoniae is becoming more frequently reported, perhaps due to the recent increase in the frequency of diabetes and liver diseases. Necrotizing fasciitis caused by K. pneumoniae is usually secondary to hematogenous dissemination, most commonly caused by trauma or liver abscess and usually results in multiple organ failure. The progression of the disease is so rapid that the mortality rate is high despite aggressive surgical intervention and extensive use of antibiotics at an early disease stage. Here we report a case of necrotizing fasciitis caused by hematogenously spread K. pneumoniae from incompletely treated chronic otitis media in a patient with alcoholic liver cirrhosis and diabetes.

Retraction: Development of osteoporosis and the imbalance of RANKL/OPG in ankylosing spondylitis / 대한내과학회지

No abstract available.

A Case of Osteitis Condensans Ilii in a Nulliparous Woman / 대한류마티스학회지

Osteitis condensans ilii (OCI) is a benign joint condition, which is most often seen in young multiparous women. It is essentially diagnosed by radiological findings which reveal a bilateral and symmetrical sclerosis of iliac sides of sacroiliac joints or narrowing. A 30-year-old woman presented with a ten-year history of low back pain and buttock pain. She was a nulliparous woman and had no history of pregnancy. Her low back pain was mild and developed intermittently. Physical examinations and laboratory studies were unremarkable. Plain X-ray showed bilateral sclerosis of the iliac bones adjacent sacroiliac joints. Computed tomography confirmed the sclerotic changes in both iliac bones without a bony change in sacrum. There is no joint space narrowing or bony erosion in the sacroiliac joints. On the basis of the imaging studies, she was diagnosed as OCI and treated symptomatically with non-steroidal anti-inflammatory drugs. After the symptomatic treatment, her symptom was improved.

Development of osteoporosis and the imbalance of RANKL/OPG in ankylosing spondylitis / 대한내과학회지

BACKGROUND: To determine the bone mineral density (BMD), serum soluble receptor activator of the nuclear factors kappa B ligand (sRANKL) and the osteoprotegerin (OPG) levels in patients with ankylosing spondylitis (AS), and to determine their relationship with disease activity indexes. METHODS: The disease activity was evaluated by the Bath Ankylosing Spondylitis Disease Activity Score Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Bath Ankylosing Spondylitis Patient Global Score (BAS-G). The BMD was measured by dual energy X-ray absorptiometry. Serum levels of sRANKL and OPG were measured by the sandwich enzyme-linked immunosorbent assay. RESULTS: Osteoporosis and osteopenia of the femoral neck were found in 33% and 41%, respectively. BMD of femoral neck showed a negative correlation with disease activities. The serum levels of sRANKL were higher in patients with AS than in controls, and the ratio of sRANKL to OPG was also elevated in AS, but had no correlation with disease activity. The sRANKL/OPG ratio tended to be higher in patients with lower BMD. CONCLUSIONS: BMD was reduced in 79% of AS patients and reflected disease status. The sRANKL/OPG ratio was upregulated in patients with AS and it appears to be related to BMD and radiological changes. These results suggest that the imbalance between RANKL and OPG might be involved in the pathogenesis and clinical courses of AS.

The Association between CRP and the Metabolic Syndrome in Korean Adults / 대한내분비학회지

BACKGROUND: Metabolic syndrome (MS) is characterized by insulin resistance accompanied by one or more of the following: obesity, hypertension, impaired glucose tolerance, low HDL cholesterol levels, and/or hypertriglyceridemia. However, the precise underlying pathogenic mechanism of MS is not known. Several recent reports have suggested a positive association between components of MS and markers of the acute-phase response, including C-reactive protein (CRP). These results imply that MS is accompanied by an ongoing inflammatory process. The purpose of our study was to evaluate the association between circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with components of metabolic syndrome in Korean adults. METHODS: A total of 1,461 subjects aged between 20 and 81 years, who visited the Health Management Center at Korea university between November 2000 and February 2001 were studied. We investigated the correlation between CRP levels and components of MS. The components of MS were categorized, and age-sex adjusted mean values of CRP calculated for the categorized components. The BMI was categorized into 5 classes, and the CRP levels examined according to their BMI class. In addition, subjects with a different number of the MS components were grouped as follows: group 1 for 0 components, group 2 for 1 components, group 3 for 2 components and group 4 for > or = 3 components, and the CRP levels calculated for each group. RESULTS: There were significant positive correlations of CRP levels with age, BMI, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBS), uric acid, insulin,and homeostasis model assessment IR (HOMAIR). A significant inverse correlation was observed between CRP levels and serum HDL. From the multivariate analysis, age and BMI were significantly correlated with CRP levels. The means of the CRP for the categorized components of MS were significantly higher in the BMI categories: > or =25 for female/27 for male, TG > or =200 mg/dL, fasting plasma glucose > or =126 mg/dL and blood pressure > or =140/90 mmHg, and the CRP levels by BMI class were: 1.19 (BMI 30.0) mg/L. Furthermore, the increase in the CRP levels in relation to the numbers of MS were 1.46 (group 1), 1.70 (group 2), 1.95 (group 3) and 2.11 mg/L (group 4) with statistical significance. CONCLUSION: The above data showed associations between the CRP levels and the different components of MS. This might suggest that MS in Koreans could be accompanied by a systemic inflammation response