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Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.
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The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed.
Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in non-diabetic subjects.
This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.
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We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.
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We evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data.
We collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hospitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic model assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels <1.70 ng/mL, respectively.
A total of 75.1% and 22.6% of participants had insulin resistance and β-cell dysfunction, respectively. The proportion of participants with insulin resistance but no β-cell dysfunction increased, and the proportion of participants with β-cell dysfunction but no insulin resistance decreased as body mass index (BMI) increased. People diagnosed with diabetes before 40 years of age had significantly higher HOMA-IR and BMI than those diagnosed over 65 years of age (HOMA-IR, 5.0 vs. 3.0; BMI, 28.7 kg/m2 vs. 25.1 kg/m2). However, the β-cell function indices were lower in people diagnosed before 40 years of age than in those diagnosed after 65 years of age (homeostatic model assessment of β-cell function, 39.3 vs. 64.9; insulinogenic index, 10.3 vs. 18.7; disposition index, 0.15 vs. 0.25).
We observed that the main pathogenic mechanism of type 2 diabetes is insulin resistance in participants with newly diagnosed type 2 diabetes. In addition, young adults with diabetes are more likely to have higher insulin resistance with obesity and have higher insulin secretory defect with severe hyperglycemia in the early period of diabetes than older populations.
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The aim of this study was to explore the differences in the clinical characteristics and diagnostic rates of diabetes mellitus (DM) according to various criteria in different age groups and to evaluate the efficacy of each criterion for screening older patients.
We studied 515 patients and measured the fasting plasma glucose level (FPG), 2-hour plasma glucose level after the 75 g oral glucose tolerance test (2-hour postload glucose [2-h PG]), and glycosylated hemoglobin (HbA1c) for re-evaluation of hyperglycemia without a history of diabetes. Patients with newly diagnosed DM were grouped by age as younger (<65 years) or older (≥65 years).
Older patients had significantly lower HbA1c, FPG, and 2-h PG levels and a higher homeostatic level of pancreatic β-cell function compared with younger patients (
In the older patients, the 2-h PG level was the most accurate diagnostic criterion. When we consider the costs and convenience, a combination of the FPG and HbA1c criteria may be recommended as a screening test for DM in older people.
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The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.
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The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.
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The Korean Diabetes Association (KDA) recently updated the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus (T2DM). In combination therapy of oral hypoglycemic agents (OHAs), general recommendations were not changed from those of the 2015 KDA guidelines. The Committee on Clinical Practice Guidelines of the KDA has extensively reviewed and discussed the results of meta-analyses and systematic reviews of effectiveness and safety of OHAs and many clinical trials on Korean patients with T2DM for the update of guidelines. All OHAs were effective when added to metformin or metformin and sulfonylurea, although the effects of each agent on body weight and hypoglycemia were different. Therefore, selection of a second agent as a metformin add-on therapy or third agent as a metformin and sulfonylurea add-on therapy should be based on the patient's clinical characteristics and the efficacy, side effects, mechanism of action, risk of hypoglycemia, effect on body weight, patient preference, and combined comorbidity. In this review, we address the results of meta-analyses and systematic reviews, comparing the effectiveness and safety among OHAs. It will help to choose the appropriate drug for an individual patient with T2DM.
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In order to improve the quality of life and to prevent chronic complications related to diabetes mellitus, intensive lifestyle modification and proper medication are needed from the early stage of diagnosis of type 2 diabetes mellitus (T2DM). When using the first medication for diabetic patients, the appropriate treatment should be selected considering the clinical characteristics of the patient, efficacy of the drug, side effects, and cost. In general, the use of metformin as the first treatment for oral hypoglycemic monotherapy is recommended because of its excellent blood glucose-lowering effect, relatively low side effects, long-term proven safety, low risk of hypoglycemia, and low weight gain. If metformin is difficult to use as a first-line treatment, other appropriate medications should be selected in view of the clinical situation. If the goal of achieving glycemic control is not achieved by monotherapy, a combination therapy with different mechanisms of action should be initiated promptly.
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In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.
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Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects
Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated.
In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels ≥100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (
The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6±874.8 to 1,451.0±770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6±801.0 to 1,341.4±855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (
The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients.
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