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Aim: Patients with type 2 diabetes (T2DM) who require injectable therapy have been conventionally treated with insulin. A glucagon-like peptide 1 receptor agonist was recently recommended as first-line injectable treatment, but few studies have investigated the effects of switching from insulin to dulaglutide. This study investigated the clinical efficacy and parameters affecting responses to dulaglutide as an alternative to insulin in patients with T2DM in a real-world clinical setting.Methods: Ninety-eight patients with T2DM who were switched from insulin to dulaglutide therapy were retrospectively evaluated. Changes in HbA1c concentrations were assessed after 6 months of consistent treatment with dulaglutide. Multiple linear regression analysis was performed to evaluate parameters affecting the response to dulaglutide treatment.Results: After treatment with dulaglutide for 6 months, patients experienced changes in HbA1c of -0.95% (95% confidence interval [CI]: -1.30% to -0.59%, P < 0.001) and in body weight of -1.75 kg (95% CI: -2.42 to -1.08 kg, P < 0.001). Multiple linear regression analysis showed that higher baseline HbA1c was significantly associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms.Conclusion: Switching from insulin to dulaglutide can lead to significant improvement in HbA1c levels and body weight ​reduction in T2DM patients over 6 months. Higher baseline HbA1c is associated with a better clinical response to dulaglutide. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the efficacy and safety of the free up-titration of basal insulin and fixed-ratio combination (FRC) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients inadequately controlled with GLP-1RA. Methods: With the use of a systematic literature review of PubMed, Embase, Web of Science, and the Cochrane Library databases through July 2021, randomized controlled trials that compared the free up-titration or FRC with remaining on GLP-1RA in T2DM patients uncontrolled with GLP-1RA were included. A comparison of adding basal insulin to maintaining GLP-1RA and an indirect comparison between the two strategies were conducted on the change in HbA1c, fasting plasma glucose (FPG), target achievement [HbA1c < 7.0%], and the risk of confirmed hypoglycemia. The Cochrane Collaboration's tool was used to assess the risk of bias. Results: Two free up-titration and two FRC trials involving 1,612 participants, all lasting 26 weeks, were included. Both approaches significantly lowered HbA1c levels (weighted mean difference [WMD] −0.75%, 95% CI −0.97 to −0.53) but increased hypoglycemic risk [risk ratio (RR) 7.59, 95% CI 3.35−17.17] compared to the unchanged GLP-1RA. No significant differences were discovered between the two methods regarding the decrease in HbA1c (WMD 0.08%, 95% CI −1.07% to 1.23%), FPG (WMD −2.29 mg/dl, 95% CI −45.07 to 40.49 mg/dl), target achievement (RR 1.03, 95% CI 0.50−2.14), and hypoglycemic risk (RR 0.32, 95% CI 0.03−3.59). Conclusion: In patients who failed to reach target HbA1c levels despite the GLP-1RA treatment, both strategies of adding basal insulin, free up-titration and FRC, are comparable options are comparable options. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to evaluate the effectiveness of quadruple oral therapy in patients with inadequately controlled type 2 diabetes (T2D) with the use of three types of oral hypoglycemic agents. Methods: Medical records of 318 patients with T2D who were prescribed quadruple therapy in the Asan Medical Center were reviewed. Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline were assessed. The regimens of quadruple oral therapy included the following: (1) thiazolidinedione (TZD) add-on to metformin (MET) + sulfonylurea (SU) + dipeptidyl peptidase 4 inhibitor (DPP4i), (2) sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on to MET + SU + DPP4i, and (3) DPP4i add-on to MET + SU + TZD. Results: The TZD add-on significantly reduced HbA1c levels by 1.1% (from 9.0 ± 1.1 to 7.9 ± 1.1%, P < 0.001) and FPG levels by 41.4 mg/dL (from 188.9 ± 45.9 to 147.4 ± 51.3 mg/dL, P < 0.001). The SGLT2i add-on changed the mean HbA1c level from 8.9 ± 1.0 to 7.8 ± 1.0%, a reduction of 1.1% (P < 0.001) and changed the mean FPG level from 193.4 ± 46.2 to 152.6 ± 37.0 mg/dL, a reduction of 40.8 mg/dL (P < 0.001). Finally, the DPP4i add-on reduced HbA1c levels by 1.3% (from 9.1 ± 1.3 to 7.8 ± 1.4%, P < 0.001) and FPG levels by 39.3 mg/dL (from 190.7 ± 45.3 to 151.4 ± 41.6 mg/dL, P < 0.001). Patients with higher baseline HbA1c levels (≥ 9.0%) showed a better response to quadruple therapy than those with baseline HbA1c levels lower than 9.0% for all three regimens. Conclusion: Quadruple oral hypoglycemic therapy can be a feasible option in patients with T2D. [ABSTRACT FROM AUTHOR]

Introduction: Ezetimibe/statin combination therapy has been reported to provide additional cardioprotective effects compared to statin monotherapy. The apolipoprotein B/A1 (apoB/A1) ratio is an effective predictor of cardiovascular diseases. The aim of this study was to compare the efficacy and safety of rosuvastatin/ezetimibe combination therapy versus rosuvastatin monotherapy using the apoB/A1 ratio in patients with diabetes and hypercholesterolemia. Methods: In this randomized, multicenter, open-label, parallel-group study, patients were randomly assigned to receive the combination therapy of rosuvastatin 5 mg/ezetimibe 10 mg once daily (n = 68) or monotherapy with rosuvastatin 10 mg once daily (n = 68), for 8 weeks. Results: After the 8-week treatment, percentage change (least-square means ± standard error) in the apoB/A1 ratio in the rosuvastatin/ezetimibe group was significantly decreased compared to the rosuvastatin group (− 46.14 ± 1.58% vs. − 41.30 ± 1.58%, respectively; P = 0.03). In addition, the proportion of patients achieving > 50% reduction in low-density lipoprotein-cholesterol (LDL-C) and in the comprehensive lipid target (LDL-C < 70 mg/dL, non-HDL-cholesterol [non-HDL-C] < 100 mg/dL, and apoB < 80 mg/dL) was significantly different between the two groups (76.5 and 73.5% in the rosuvastatin/ezetimibe group and 47.1 and 45.6% in the rosuvastatin group, respectively; P < 0.001). The reduction in total cholesterol, non-HDL-C, LDL-C, and apoB were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group. Both treatments were well tolerated, and no between-group differences in drug-related adverse events were observed. Conclusion: The apoB/A1 ratio was significantly reduced in patients receiving combination therapy with ezetimibe and rosuvastatin compared to those receiving rosuvastatin monotherapy. Both treatments were well tolerated in patients with type 2 diabetes and hypercholesterolemia. Trial Registration: NCT03446261. [ABSTRACT FROM AUTHOR]

Purpose: For patients with type 2 diabetes (T2DM) who remain above their glycemic target on insulin therapy, a combination of insulin and a glucagon-like peptide 1 receptor agonist has been recommended. However, few studies have been conducted to determine the clinical efficacy and parameters affecting the response to this combination in a real-world setting. This study aimed to investigate the clinical efficacy and parameters affecting the glycemic response to dulaglutide as an add-on to insulin therapy for T2DM in a real-world clinical setting. Patients and methods: A retrospective study was performed in 120 patients with T2DM who had initiated dulaglutide as an add-on to insulin therapy between January 2017 and December 2018. After 6 months of treatment, the change in glycated hemoglobin (HbA1c) was evaluated. Multiple linear regression analysis was used to determine the parameters affecting the therapeutic response to dulaglutide. Results: The mean age of the patients was 55.1 years and 57.5% were male. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.1%, 27.5 kg/m2, and 17.2 years, respectively. The change in HbA1c between baseline and 6 months was −0.97% (95% confidence interval [CI]: −1.28 to −0.66%, P<0.001), the change in body weight was −2.05 kg (95% CI: −2.93 to −1.17 kg, P<0.001), and the change in total daily insulin dose was −11.67 IU (95% CI: −14.55 to −8.78 IU, P<0.001). In multiple linear regression analysis, higher baseline HbA1c was associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms, but these were well-tolerated. Conclusion: Dulaglutide treatment in combination with insulin resulted in a significant improvement in HbA1c and body weight over a 6-month period in a real-world clinical setting. Higher baseline HbA1c was associated with a good clinical response. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the efficacy and clinical factors affecting the glycemic response to dulaglutide in type 2 diabetes (T2D) in a real-world clinical setting. Methods: We conducted a retrospective study of 234 patients at the Asan Medical Center, Republic of Korea, who had T2D and initiated dulaglutide from June 2016 to December 2017. The primary outcome was the change in glycated hemoglobin (HbA1c) concentration between baseline and 6 months after the initiation of therapy. Multivariate regression analysis was used to determine the clinical parameters contributing to a superior glycemic response to dulaglutide. Results: The mean age of the patients was 53, and 50% were male. Their mean baseline HbA1c, body mass index and duration of diabetes were 8.8%, 27.6 kg/m2 and 10.2 years, respectively. The change in HbA1c between baseline and 6 months was − 0.92% (95% CI: − 1.1% to − 0.74%, p < 0.001). The reduction in body weight over the same period was −2.1 kg (95% CI: − 2.9 to − 1.3 kg, p < 0.001). Using multivariate regression analysis, baseline HbA1c was found to be a significant predictor of superior glycemic response to dulaglutide. Conclusion: The use of dulaglutide was associated with a significant reduction in HbA1c and body weight over a 6-month period in a real-world clinical setting. T2D patients with higher baseline HbA1c concentrations were more likely to demonstrate good clinical responses to dulaglutide. [ABSTRACT FROM AUTHOR]

We aimed to investigate the clinical factors affecting the therapeutic effectiveness of the sodium–glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus (T2DM). We reviewed the medical records of 374 T2DM patients aged between 20 and 75 years who were prescribed empagliflozin 10 mg or 25 mg as add-on therapy for more than 90 consecutive days. Changes in hemoglobin A1c (HbA1c) from baseline levels and the reduction in body weights of the study participants were assessed. We found that younger patients (≤ 50 years), patients with the highest levels of HbA1c (>9%) at baseline, patients with an estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73 m2, and patients with a shorter duration of T2DM (< 10 years) were more likely to exhibit a better glycemic response. Multivariate linear regression analysis revealed that a shorter duration of T2DM, higher baseline levels of HbA1c, and higher eGFR were positively associated with HbA1c reduction. Higher BMI and lower HbA1c levels were predictors of a more significant reduction in body weight among patients taking empagliflozin. The glucose-lowering effect of empagliflozin was more evident in T2DM patients with higher baseline HbA1c levels, better renal function, and shorter duration of T2DM. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of fatty liver disease (FLD) on the risk of incident type 2 diabetes in a population with metabolically healthy obesity (MHO).Methods: The study population comprised 34,258 Koreans without type 2 diabetes. Participants were stratified by BMI (cutoff value, 25.0 kg/m(2) ) and metabolic health state (using Wildman criteria). FLD was defined by the fatty liver index (FLI), a predictive algorithm to detect FLD. Subjects were classified into low and high FLI groups based on tertile.Results: At baseline, there were significant differences in FLI between four study groups. During a median follow-up of 36.5 months, 1.7% individuals developed type 2 diabetes. The risk of incident type 2 diabetes varied for the MHO group according to the level of FLI. The risk of type 2 diabetes in the MHO with low FLI was not significantly elevated compared with the metabolically healthy individuals without obesity (MHNO) with low FLI (multivariate-adjusted HR, 1.19 [95% CI 0.66-2.14]). However, the MHO with high FLI had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 1.99 [95% CI 1.36-2.92]).Conclusions: MHO subjects have a substantially higher risk of incident type 2 diabetes than MHNO subjects. The presence of FLD assessed by FLI partially explains this increased risk. [ABSTRACT FROM AUTHOR]

Aims: This study was performed to investigate whether ventilatory dysfunction is a predictor for the development of prediabetes and type 2 diabetes in Koreans. Methods: We analyzed the clinical and laboratory data of 16,195 Korean adults (age 20-79 years) who underwent routine medical checkups with a mean 4.7-years (range 3.0-5.9 years) interval. Spirometry results were categorized into three patterns: normal, obstructive ventilatory dysfunction [OVD; forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) <0.70], and restrictive ventilatory dysfunction (RVD; FVC < 80 % predicted, FEV/FVC ≥ 0.70). Results: Compared with subjects with normal ventilatory function, subjects with RVD had a higher incidence of type 2 diabetes (3.7 vs. 6.3 %; P < 0.001), whereas subjects with OVD did not (3.7 vs. 4.8 %; P = 0.119). On multivariate logistic regression analysis, the odds ratio (OR) of RVD for type 2 diabetes was significantly increased after adjusting for age, sex, and lifestyle factors (1.40; 95 % CI 1.10-1.78). However, further adjustment for body mass index (BMI), waist circumference, and baseline glucose level attenuated the OR to become insignificant (1.12; 95 % CI 0.86-1.47). Among the 9,461 participants who had normal fasting glucose and HbA1c levels at baseline, the OR for progression to prediabetes or diabetes in the RVD group was significantly increased (1.30; 95 % CI 1.12-1.51). The increased OR remained significant after adjusting for BMI, waist circumference, and baseline glucose level (1.26; 95 % CI 1.07-1.47). Conclusions: Our results indicate that restrictive, but not obstructive ventilatory dysfunction, is independently associated with development of prediabetes and precedes the development of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men. Materials and Methods: This 4year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method. Results: During a 4year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00mg/dl) than in the lowest bilirubin quartile category (i.e., ≤0.90mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48–0.99, P for trend=0.041). Conclusions: The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects. [Copyright &y& Elsevier]

Background: Elevated ferritin concentration has been implicated in the etiology of type 2 diabetes. Accumulating evidence, mostly from studies conducted on western populations, has demonstrated a strong association between the elevated ferritin concentrations and incident type 2 diabetes. In Asian populations, however, the longitudinal studies investigating the association of elevated serum ferritin levels and type 2 diabetes are lacking. In present study, we aimed to determine whether elevated serum ferritin levels are related to the incident type 2 diabetes in healthy Korean men. Methodology/Principal Findings: This 4 year longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 2,029 men without type 2 diabetes who underwent routine health examination in 2007 (baseline) and 2011 (follow-up). Baseline serum ferritin concentrations were measured by chemiluminescent two-site sandwich immunoassay. In multiple-adjusted model, the relative risk (RR) for incident type 2 diabetes was significantly higher in highest compared with the lowest ferritin quartile category, even after adjusting for confounding variables including homeostasis model assessment of insulin resistance (RR = 2.17, 95% confidence interval 1.27–3.72, P for trend = 0.013). Conclusions/Significance: These results demonstrated that elevated level of serum ferritin at baseline was associated with incident type 2 diabetes in an Asian population. [ABSTRACT FROM AUTHOR]

Lipid accumulation in nonadipose tissues is closely related to the development of type 2 diabetes in obese subjects. We examined the potential preventive effect of peroxisome proliferator-activated receptor (PPAR)α and PPAR-γ stimulation on the development of diabetes in obese diabetes-prone OLETF rats. Chronic administration of a PPAR-α agonist (0.5% [wt/wt] fenofibrate) or a PPAR-γ agonist (3 mg · kg[sup -1] · day[sup -1] rosiglitazone) completely prevented the development of glycosuria. Pancreatic islets from untreated OLETF rats underwent sequential hypertrophy and atrophy, which was completely prevented by chronic fenofibrate treatment. In contrast, rosiglitazone treatment did not affect islet hypertrophy at earlier stages but prevented β-cell atrophy at later stages. Fenofibrate treatment decreased body weight and visceral fat, whereas rosiglitazone treatment increased body weight. Despite the opposite effects on adiposity, both drugs were equally effective in improving insulin actions in skeletal muscle. Furthermore, both drugs significantly decreased the triglyceride content in the soleus muscle and pancreatic islets. The present study demonstrates that the PPAR-α agonist fenofibrate prevents the development of diaberes in OLETF rats by reducing adiposity, improving peripheral insulin action, and exerting beneficial effects on pancreatic β-cells. [ABSTRACT FROM AUTHOR]

Aims: Visceral fat accumulation is known to be an independent risk factor for type 2 diabetes. We aimed to determine the optimal cutoff values of visceral fat area (VFA) for predicting incident type 2 diabetes in Koreans.Methods: Our study population consisted of 13,004 individuals initially free of type 2 diabetes the ages between 20 and 69 years, who underwent routine health examinations between January 2012 and December 2012 and returned for follow-up examinations between January 2016 and December 2016. VFA values were derived from bioelectrical impedance analysis (BIA) at baseline.Results: During a median follow-up of 4.02 years, a total of 481 (4.6% for men and 2.3% for women) incident cases of type 2 diabetes were identified. According to the receiver operating characteristic (ROC) curve, the optimal VFA cutoff values for predicting incident type 2 diabetes were 118.8 cm2 in men and 82.6 cm2 in women, respectively. In a multivariable-adjusted model including obesity and glycemic status, the odds ratios (ORs) of VFA over 120 cm2 in men and 80 cm2 in women were 1.72 and 3.56, respectively.Conclusions: Higher VFA at baseline was an independent risk factor for developing type 2 diabetes and the optimal VFA cutoff values were markedly different between men and women. Therefore, sex-specific reference values for visceral fat obesity such that men with a VFA ≥120 cm2 and women with a VFA ≥80 cm2 should be considered to predict incident type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Vaspin, an adipocytokine recently identified in a rat model of type 2 diabetes, has been suggested to have an insulin-sensitizing effect. However, the exact mechanism underlying this action has not been fully elucidated. Furthermore, the specific function of vaspin is largely unknown, especially in vascular cells. We examined whether vaspin affects the insulin-signaling pathway in cultured endothelial cells and is capable of preventing free fatty acid (FFA)-induced apoptosis in endothelial cells through its insulin sensitizing effect, specifically, through its stimulatory effect on PI3-kinase/Akt signaling pathways. Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin. Moreover, pretreatment with vaspin prevented LA-induced apoptosis in insulin-stimulated endothelial cells; this anti-apoptotic effect of vaspin was also eliminated by pretreatment with Wortmannin. The present study indicates that vaspin protects vascular endothelial cells from FFA-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. Our study is the first to demonstrate that vascular cells can be targets of vaspin. Our results further suggest that vaspin could have beneficial effects on the atherosclerosis. [Copyright &y& Elsevier]

Abstract: The aim of this study was to examine the possible association between serum ceruloplasmin, a copper carrying protein, and albuminuria in 456 males with type 2 diabetes. Multivariate regression analysis demonstrated that elevated serum ceruloplasmin was a determinant of albuminuria independently of conventional risk factors. [Copyright &y& Elsevier]