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Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add‐on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add‐on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. Materials and Methods: In this randomized, double‐blind, double‐dummy, active‐controlled, parallel‐group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. Results: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were −1.34% with GEMI + DAPA, −0.90% with GEMI (difference between GEMI + DAPA vs. GEMI −0.44% [95% confidence interval {CI}: −0.58% to −0.31%], P <.01) and −0.78% with DAPA (difference between GEMI + DAPA vs. DAPA −0.56% [95% CI: −0.69% to −0.42%], P <.01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. Conclusions: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well‐tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the long‐term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). Materials and Methods: Following a 24‐week randomized, double‐blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open‐label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. Results: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose‐to‐creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. Conclusions: Enavogliflozin 0.3 mg monotherapy provides long‐term glycaemic control in T2DM and is safe and well tolerated during a 52‐week treatment period. [ABSTRACT FROM AUTHOR]

Background. We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. Methods. This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group, n = 37) or escalation of the metformin dose (500 mg, MET group, n = 38) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. Results. At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. MET = − 0.64 % ± 0.34 % vs. − 0.36 % ± 0.50 % , p = 0.009 at week 12; − 0.61 % ± 0.35 % vs. − 0.33 % ± 0.70 % , p = 0.045 at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of β-cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups. Conclusions. Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. Materials and Methods: This was a 52‐week, multicentre, randomized, parallel‐group, open‐label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1‐2 mg/day for 12 months as an add‐on to metformin. Baseline and end of study body composition evaluations included dual‐energy X‐ray absorptiometry and abdominal computed tomography scans. Results: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: −2.59 kg BF mass, −1.94% BF%, −17.55 cm2 VAT area, −18.39 cm2 SAT area, −0.46% glycated haemoglobin, −18.25 mg/dl fasting blood glucose, −3.7 kg weight, −2.21 cm waist circumference, −1.37 kg/m2 body mass index, −6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. Conclusion: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well‐tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add‐on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium‐glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. Materials and Methods: Patients with glycated haemoglobin (HbA1c) of 7.0‐10.0%, entered a 2‐week placebo run‐in period, and were randomized to receive once‐daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. Results: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (−0.79%, −0.89%, −0.92% and −0.08%, respectively; p <.001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were −30.5, −31.1, −35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. Conclusions: Once‐daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well‐tolerated treatment for Korean patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of a novel sodium‐glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise. Materials and Methods: This study was a randomized, double‐blind, placebo‐controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%‐10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study. Results: At week 24, the placebo‐adjusted mean change in HbA1c from baseline in the enavogliflozin group was −0.99% (95% confidence interval −1.24%, −0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p <.0001). Placebo‐adjusted mean changes in fasting plasma glucose (−40.1 mg/dl) and body weight (−2.5 kg) at week 24 were statistically significant (p <.0001). In addition, a significant decrease in blood pressure, low‐density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high‐density lipoprotein cholesterol. No significant increase in treatment‐related adverse events was observed for enavogliflozin. Conclusions: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes may be alleviated by mineral water (MW) ingestion. We investigated whether spring water (SW) (a kind of mixed MW) ingestion influences metabolic parameters via alteration of the gut microbiota in high-fat diet (HFD)-fed mice. Method: We divided 32 C57/BL mice into 4 equal groups: normal diet with tap water (Control), high-fat diet with tap water (HFD), normal diet with SW (SW), and high-fat diet with SW (HFD + SW). During this experiment, we checked the body weight (BW) with fasting blood sugar (FBS) every week and all mice were sacrificed in the 17th week to observe serological markers, internal organs, and composition of gut microbiota. Results: The BW of HFD-fed mice was significantly higher than that of mice fed an HFD + SW diet in the early period of the experiment. Fasting blood glucose (FBG) in the HFD group showed a fluctuating pattern compared to the HFD + SW group, and the area under the curve (AUC) value of the oral glucose tolerance test (OGTT) was significantly greater in the HFD group than in the HFD + SW group. Serologic markers were not significantly different between the HFD and HFD + SW groups. Histologically, the most severe fatty changes in the liver were observed in the HFD group. Lastly, the gut levels of Akkermansia muciniphilia were 100-fold higher in the HFD + SW group than in the HFD mice. Conclusion: These findings indicate that SW ingestion, and the associated high levels of A muciniphilia growth in the gut, may improve the early stage of obesity and ameliorate HFD-induced hyperglycemia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to elucidate the association between weight cycling and clinical outcomes such as type 2 diabetes and hypertension with differential effects of baseline age and obesity. Nationwide data from 6,132,569 healthy adults who underwent five or more health screenings between 2002 and 2011 were analyzed and followed until December 2019 for type 2 diabetes and hypertension. Weight cycling was defined as a change in body weight followed by another change in the opposite direction. Through the Cox proportional hazards model, the number and degree of weight cycles were positively associated with increased risk of type 2 diabetes and hypertension. The hazard ratios (HRs) of weight cycling for type 2 diabetes and hypertension were as high as 1.263 (1.213–1.315) and 1.175 (1.144–1.207) at two or more weight cycles of 10% of body weight (BW), respectively. The association was stronger for females, individuals with normal body weight/BMI, and older individuals. Weight cycling was significantly associated with an increased risk of adverse health outcomes and was stronger in individuals with normal BMI and females, indicating that these people should be informed about the potential risk of weight cycling. [ABSTRACT FROM AUTHOR]

Background. Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and gemigliptin therapy. Methods. RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, gemigliptin, or empagliflozin plus gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation. Results. LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, gemigliptin, and empagliflozin plus gemigliptin, respectively. Empagliflozin and gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling. Conclusions. Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and gemigliptin therapy.Methods: RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, gemigliptin, or empagliflozin plus gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation.Results: LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, gemigliptin, and empagliflozin plus gemigliptin, respectively. Empagliflozin and gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling.Conclusions: Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

We designed a postmarketing surveillance study of linagliptin for patients with type 2 diabetes (T2D) in Korea. This prospective, observational, multicentre study investigated the safety and glycaemic effectiveness of linagliptin as monotherapy or combination therapy with other antidiabetic drugs in routine clinical practice. Endpoints were the incidence of adverse drug reactions (ADRs) and the change in HbA1c. Overall, 3119 and 2171 patients were included in the safety and effectiveness analysis sets, respectively. A total of 56 patients (1.8%) experienced ADRs. The most common ADR was gastrointestinal disorders (0.7%), followed by metabolism and nutrition disorders (0.5%). ADRs of special interest, including pancreatic diseases, cardiac diseases and hypoglycaemia, occurred in 12 patients, 11 of whom had hypoglycaemia, while one had a skin lesion. Mean HbA1c change during the study period was −0.8%. Lower body mass index, shorter diabetes duration and higher baseline HbA1c were independently associated with a better effectiveness, while the presence of diabetic complications, dyslipidaemia and the use of sulphonylureas were associated with a poor response. In conclusion, linagliptin showed an excellent safety profile and glycaemic effectiveness in Korean patients with T2D. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We developed a self‐assessable Korean Diabetes Risk score using the data of the Korean Genome and Epidemiology Study. Materials and Methods: A total of 8,740 participants without diabetes at baseline were followed up biannually over a period of 10 years. We included variables that were significantly different between participants who developed diabetes mellitus and those who did not in the development cohort at baseline. We assigned a maximum score of 100 to the selected variable in each gender group. Next, the 10‐year probability of incident diabetes was calculated and validated in the validation cohort. Finally, we compared the predictive power of Korean Diabetes Risk score with models including fasting plasma glucose or glycated hemoglobin and other cohort models of Atherosclerosis Risk in Communities and Korea National Health and Nutrition Examination Survey. Results: During a median follow‐up period of 9.7 years, 22.7% of the participants progressed to diabetes. The Korean Diabetes Risk score included age, living location (urban or rural area), waist circumference, hypertension, family history of diabetes and smoking history. The developed risk score yielded acceptable discrimination for incident diabetes (area under the curve 0.657) and the predictive power was improved when the model included fasting plasma glucose (area under the curve 0.690) or glycated hemoglobin (area under the curve 0.746). In addition, our model predicted incident diabetes more accurately than previous Western or Korean models. Conclusions: This newly developed self‐assessable diabetes risk score is easily applicable to predict the future risk of diabetes even without the necessity for laboratory tests. This score is useful for the Korean diabetes prevention program, because high‐risk individuals can be easily screened. [ABSTRACT FROM AUTHOR]

Objective: Previous randomized trials found that treating periodontitis improved glycemic control in patients with type 2 diabetes (T2D), thus lowering the risks of developing T2D-related microvascular diseases and cardiovascular disease (CVD). Some payers in the U.S. have started covering nonsurgical periodontal treatment for those with chronic conditions, such as diabetes. We sought to identify the cost-effectiveness of expanding periodontal treatment coverage among patients with T2D.Research Design and Methods: A cost-effectiveness analysis was conducted to estimate lifetime costs and health gains using a stochastic microsimulation model of oral health conditions, T2D, T2D-related microvascular diseases, and CVD of the U.S.Population: Model parameters were obtained from the nationally representative National Health and Nutrition Examination Survey (NHANES) (2009-2014) and randomized trials of periodontal treatment among patients with T2D.Results: Expanding periodontal treatment coverage among patients with T2D and periodontitis would be expected to avert tooth loss by 34.1% (95% CI -39.9, -26.5) and microvascular diseases by 20.5% (95% CI -31.2, -9.1), 17.7% (95% CI -32.7, -4.7), and 18.4% (95% CI -34.5, -3.5) for nephropathy, neuropathy, and retinopathy, respectively. Providing periodontal treatment to the target population would be cost saving from a health care perspective at a total net savings of $5,904 (95% CI -6,039, -5,769) with an estimated gain of 0.6 quality-adjusted life years per capita (95% CI 0.5, 0.6).Conclusions: Providing nonsurgical periodontal treatment to patients with T2D and periodontitis would be expected to significantly reduce tooth loss and T2D-related microvascular diseases via improved glycemic control. Encouraging patients with T2D and poor oral health conditions to receive periodontal treatment would improve health outcomes and still be cost saving or cost-effective. [ABSTRACT FROM AUTHOR]

Aim: To perform a prospective study to evaluate the effect of cilostazol (CTZ) compared with aspirin (acetylsalicylic acid; ASA) in Korean people with diabetes and subclinical coronary atherosclerosis. Materials and methods: A total of 100 people with diabetes who had mild to moderate coronary atherosclerosis, assessed by coronary computed tomographic angiography (CCTA), were randomly assigned to either 200 mg/d CTZ or 100 mg/d ASA (n = 50 each group). The primary outcome was change in coronary artery stenosis assessed by CCTA after 12 months of treatment. Secondary outcomes included changes in plaque composition, coronary artery calcium score and cardiac markers. Results: The mean age, body mass index and glycated haemoglobin concentration were 61.5 years, 25.0 kg/m2 and 56.8 mmol/mol, respectively, and were well matched between the two groups. Coronary artery stenosis decreased in the CTZ group (from 44.0 ± 2.1% to 40.4 ± 2.5%) but remained unchanged in the ASA group (from 38.9 ± 2.1% to 40.6 ± 2.1%). In the CTZ group, the non‐calcified portion of plaques decreased significantly (from 20.6 ± 3.0 to 17.3 ± 3.0 mm3), whereas it did not change significantly in the ASA group (15.2 ± 2.8 vs 16.6 ± 2.9 mm3). Increases in HDL cholesterol, decreases in triglycerides, liver enzyme and high‐sensitivity C‐reactive protein levels, and reductions in abdominal visceral fat area and insulin resistance were observed only in the CTZ group. Conclusion: CTZ treatment for 12 months decreased coronary artery stenosis and the non‐calcified plaque component. These results suggest that CTZ treatment may be an option for preventing the progression of coronary atherosclerosis in people with diabetes. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to measure the serum neopterin according to glucose metabolism and to evaluate neopterin as a predictor of type 2 diabetes (T2D) in a hospital-based cohort. Methods: A 75-g oral glucose tolerance test (OGTT) was performed by people who visited the outpatient clinic in Seoul National University Bundang Hospital for suspected abnormal glucose tolerance or a strong family history of T2D. Neopterin was measured using an enzyme-link immunosorbent assay with baseline samples from the OGTT. Results: Neopterin was measured in 184 participants. Indices related to glucose metabolism, such as the HOMA-IR, disposition index, etc. were calculated based on the results of the OGTT. The classifications for the 184 participants were: 24 (13%) had NGT, 89 (48.4%) prediabetes, and 60 (38.6%) T2D. Neopterin increased with deterioration of glucose metabolism (0.55 ± 0.25 vs. 0.58 ± 0.27 vs. 0.67 ± 0.27 ng/ml, p = 0.041; NGT, prediabetes, and T2D, respectively). Neopterin also correlated with fasting plasma glucose, 30-min and 120-min glucose of OGTT and HbA1c (r = 0.251, 0.259, 0.184, and 0.270, all p < 0.05). The HOMA-IR and disposition index correlated with neopterin (r = 0.291 and −0.170, respectively, both p < 0.05). When combined with C-peptide level, neopterin was as powerful as HOMA-IR in predicting future T2D. Conclusion: Serum neopterin appears to be related to impaired insulin secretion and insulin resistance in the development of T2D. Further investigation of the relationship between neopterin and glucose metabolism would be helpful to understand the pathophysiology for the development of T2D. [ABSTRACT FROM AUTHOR]

Aim: To compare pancreatic volume and fat amount, and their associations with glucose homeostasis, in a Korean and a white population. Materials and methods: In 43 healthy Korean and 43 healthy white people, matched for age (±3 years) and body mass index (BMI; ±1 kg/m2), we measured pancreatic volume and fat amount in the pancreas and abdomen using computed tomography. Pancreatic β‐cell function and insulin resistance were estimated according to biochemical characteristics and a 75‐g oral glucose tolerance test. Body composition and resting energy expenditure (REE) were examined using bioimpedance and indirect calorimetry, respectively. Results: The mean ±SD age of the participants was 29.9 ± 5.9 years and 30.0 ± 5.2 years, and BMI was 24.0 ±3.7 and 24.1 ±3.2 kg/m2 in the white participants and the Korean participants, respectively. Pancreatic volume in the white participants was greater than that in Korean participants (77.8 ±11.6 vs 68.2 ±12.1 cm3; P < .001). Pancreatic fat content in Korean participants was 22.8% higher than in white participants (P = .051). Insulinogenic index, disposition index, muscle mass and REE were significantly lower in Korean participants. Pancreatic volume was positively associated with indices linked to β‐cell function; fat content in the pancreas was negatively associated with such indices, and positively with insulin resistance after adjusting for relevant variables including REE. Conclusions: A smaller pancreas and higher fat deposition might be crucial determinants of vulnerability to diabetes in Korean people compared with white people with similar BMI and body fat levels. [ABSTRACT FROM AUTHOR]

The serum levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in a middle-aged Korean population and investigated associations with age, gender, body mass index (BMI), metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and dietary habits. The median concentrations of 22 OCPs and 34 PCBs in the serum samples were 483 and 216 ng g lipid, respectively. The most abundant compound was p,p'-DDE, followed by PCB 153, β-HCH, PCB 118, and PCB 180. The results of multiple linear regression and other statistical analyses revealed that serum OCP and PCB levels were higher in women and were positively correlated with age. BMI was positively associated with serum OCP and PCB levels, reflecting the influence of food intake and the preserving effect of body fat. MS and T2DM were significantly associated with serum OCP and PCB levels. The intake of animal foods had positive associations with serum OCP and PCB levels, whereas the intake of phytogenic foods showed negative associations, presumably because of contamination levels in food items and food matrices that governs absorption and excretion of OCPs and PCBs in the body. The relationship between dietary habits and serum OCP and PCB levels were different in participants with MS compared to healthy participants, suggesting MS may alter the influence of food intake on serum OCP and PCB levels. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the prevalence of diabetic retinopathy (DR) in patients with diabetic foot ulcer (DFU) and elucidate the association between DR and DFU severities and their shared risk factors. Methods: A retrospective review was conducted on DFU patients who underwent ophthalmic and vascular examinations within 6 months; 100 type 2 diabetic patients with DFU were included. The medical records of 2496 type 2 diabetic patients without DFU served as control data. DR prevalence and severity were assessed in DFU patients. DFU patients were compared with the control group regarding each clinical variable. Additionally, DFU patients were divided into two groups according to DR severity and compared. Results: Out of 100 DFU patients, 90 patients (90%) had DR and 55 (55%) had proliferative DR (PDR). There was no significant association between DR and DFU severities (R = 0.034, p = 0.734). A multivariable analysis comparing type 2 diabetic patients with and without DFUs showed that the presence of DR [OR, 226.12; 95% confidence interval (CI), 58.07–880.49; p < 0.001] and proliferative DR [OR, 306.27; 95% CI, 64.35–1457.80; p < 0.001), higher HbA1c (%, OR, 1.97, 95% CI, 1.46–2.67; p < 0.001), higher serum creatinine (mg/dL, OR, 1.62, 95% CI, 1.06–2.50; p = 0.027), older age (years, OR, 1.12; 95% CI, 1.06–1.17; p < 0.001), higher pulse pressure (mmHg, OR, 1.03; 95% CI, 1.00–1.06; p = 0.025), lower cholesterol (mg/dL, OR, 0.94; 95% CI, 0.92–0.97; p < 0.001), lower BMI (kg/m2, OR, 0.87, 95% CI, 0.75–1.00; p = 0.044) and lower hematocrit (%, OR, 0.80, 95% CI, 0.74–0.87; p < 0.001) were associated with DFUs. In a subgroup analysis of DFU patients, the PDR group had a longer duration of diabetes mellitus, higher serum BUN, and higher serum creatinine than the non-PDR group. In the multivariable analysis, only higher serum creatinine was associated with PDR in DFU patients (OR, 1.37; 95% CI, 1.05–1.78; p = 0.021). Conclusions: Diabetic retinopathy is prevalent in patients with DFU and about half of DFU patients had PDR. No significant association was found in terms of the severity of these two diabetic complications. To prevent blindness, patients with DFU, and especially those with high serum creatinine, should undergo retinal examinations for timely PDR diagnosis and management. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. Methods: Forty-eight 5-week-old male ApoE mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and empagliflozin 3 mg/kg ( n = 12/group). Plaque size and composition in the aortic arch/valve areas and cardiovascular risk variables in the blood and tissues were evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body composition was determined using dual-energy x-ray absorptiometry. Results: After 8 weeks of treatment, the empagliflozin and glimepiride groups exhibited decreased blood glucose levels. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the empagliflozin groups than in the control or glimepiride groups. Insulin resistance and circulating concentrations of TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and urinary microalbumin decreased after empagliflozin treatment, and this significantly correlated with plaque size. Empagliflozin treatment reduced weight and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in plaque and adipose tissue compared with the control or glimepiride group. Empagliflozin treatment increased adiponectin levels. Conclusions/interpretation: Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by empagliflozin. [ABSTRACT FROM AUTHOR]

Aims: In 2011, we demonstrated that an individualized health management system employing advanced medical information technology, designated ubiquitous (u)-healthcare, was helpful in achieving glycemic control without hypoglycemia in patients with diabetes. Following this, we generated a new multidisciplinary u-healthcare system by upgrading our clinical decision support system (CDSS) rule engine and integrating a physical activity-monitoring device and dietary feedback into a comprehensive package. Methods: In a randomized, controlled clinical trial, patients with type 2 diabetes aged over 60 years were assigned randomly to a self-monitored blood glucose (SMBG) group ( N = 50) or u-healthcare group ( N = 50) for 6 months. The primary endpoint was the proportion of patients achieving glycated hemoglobin (HbA) <7 % without hypoglycemia. Changes in body composition and lipid profiles were also investigated. The u-healthcare group was educated to use a specially designed glucometer and an activity monitor that automatically transferred test results to a hospital-based server. An automated CDSS rule engine generated and sent patient-specific messages about glucose, diet, and physical activity to their mobile phones and a Web site. Results: After 6 months of follow-up, the HbA level was significantly decreased in the u-healthcare group [8.0 ± 0.7 % (64.2 ± 8.8 mmol/mol) to 7.3 ± 0.9 % (56.7 ± 9.9 mmol/mol)] compared with the SMBG group [8.1 ± 0.8 % (64.9 ± 9.1 mmol/mol) to 7.9 ± 1.2 % (63.2 ± 12.3 mmol/mol)] ( P < 0.01). The proportion of patients with HbA < 7 % without hypoglycemia was greater in the u-healthcare group (26 %) than in the SMBG group (12 %; P < 0.05). Body fat mass decreased and lipid profiles improved in the u-healthcare group but not in the SMBG group. Conclusion: This u-healthcare service provided effective management for older patients with type 2 diabetes (ClinicalTrial.Gov: NCT01137058). [ABSTRACT FROM AUTHOR]

High levels of plasma free fatty acid are thought to contribute to the loss of pancreatic beta-cells in type 2 diabetes. In particular, saturated fatty acid such as palmitate or stearate can induce apoptosis in cultured beta cells (lipotoxicity). Endoplasmic reticulum stress is a critical mediator of free fatty acid-induced lipotoxicity. Recently, disorders in mitochondrial respiratory metabolism have been linked to lipotoxicity. Since iron is a critical component of respiratory metabolism, this study is initiated to determine whether abnormal iron metabolism is involved in palmitate-induced beta cell death. Immunoblotting analysis showed that treatment of INS-1 beta cells with palmitate reduced the level of transferrin receptor 1 (TfR1), but increased the level of heavy chain ferritin (FTH). In addition, palmitate reduced intracellular labile iron pool. Whereas iron depletion through treatment with iron-chelators deferoxamine or deferasirox augmented palmitate-induced cell death, iron supplementation with ferric chloride, ferrous sulfate, or holo-transferrin significantly protected cells against palmitate-induced death. Furthermore, overexpression of TfR1 reduced palmitate-induced cell death, whereas knockdown of TfR1 augmented cell death. In particular, treatment with deferoxamine increased the level of endoplasmic reticulum (ER) stress markers phospho-PERK, phospho-eIF2α, CHOP and phospho-c-Jun N-terminal kinase. Treatment with chemical chaperone significantly protected cells against deferoxamine-induced apoptosis. Iron supplementation also protected cells against palmitate-induced primary islet death. These data suggest that iron depletion plays an important role in palmitate-induced beta cell death through inducing ER stress. Therefore, attempts to block iron depletion might be able to prevent beta cell loss in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Methods and Findings: LAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls. Conclusions: Treatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background: Obesity precedes the development of type 2 diabetes (T2D). However, the relationship between the magnitude and rate of weight gain to T2D development and complications, especially in non-White populations, has received less attention. Methods and Findings: We determined the association of rate and magnitude of weight gain to age at T2D diagnosis (AgeT2D), HbA1c at T2D diagnosis (HbA1cT2D), microalbuminuria, and diabetic retinopathy after adjusting for sex, BMI at age 20 years, lifestyles, family history of T2D and/or blood pressure and lipids in 2164 Korean subjects aged ≥30 years and newly diagnosed with diabetes. Body weight at age 20 years (Wt20y) was obtained by recall or from participants’ medical, school, or military records. Participants recalled their maximum weight (Wtmax) prior to T2D diagnosis and age at maximum weight (Agemax_wt). The rate of weight gain (Ratemax_wt) was calculated from magnitude of weight gain (ΔWt = Wtmax–Wt20y) divided by ΔTime (Agemax_wt –20 years). The mean Agemax_wt and AgeT2D were 41.5±10.9 years and 50.1±10.5 years, respectively. The Wt20y and Wtmax were 59.9±10.5 kg and 72.9±11.4 kg, respectively. The Ratemax_wt was 0.56±0.50 kg/year. After adjusting for risk factors, greater ΔWt and higher Ratemax_wt were significantly associated with earlier AgeT2D, higher HbA1cT2D after additional adjusting for AgeT2D, and microalbuminuria after further adjusting for HbA1cT2D and lipid profiles. Greater ΔWt and higher Ratemax_wt were also significantly associated with diabetic retinopathy. Conclusions: This finding supports public health recommendations to reduce the risk of T2D and its complications by preventing weight gain from early adulthood. [ABSTRACT FROM AUTHOR]

Abstract: Loss of beta cells is a pathogenic cause for the development of type 2 diabetes. High glucose/free fatty acid (HG/FFA)-induced glucolipotoxicity was thought to play a role in the beta cell loss. Thus, application of small molecules capable of preventing HG/FFA-induced glucolipotoxicty to beta cells could be an avenue for a therapeutic intervention for the development of type 2 diabetes. We screened a representative library supplied from Korean Chemical Bank for prevention of high glucose/palmitate (HG/PA)-induced viability reduction of INS-1 beta cells and were able to identify a new small molecule (DW1182v) with a function to protect HG/PA-induced glucolipotoxicity. The protective effect was specific to HG/PA-induced beta cell death since DW1182v did not protect streptozotocin- or cytokine-induced INS-1 cell death. The protective effect by DW1182v was likely due to the reduction of death-promoting endoplasmic reticulum (ER) stress responses such as phospho-C-Jun N-terminal kinase (JNK) and C/EBP homologous protein (CHOP). Treatment of obese diabetic db/db mice with DW1182v preserved islet integrity and thus increased insulin secretion and lowered blood glucose after glucose infusion. These results suggest that a small molecule protecting HG/PA-induced glucolipotoxicity to beta cells can be a new therapeutic candidate to prevent the development of type 2 diabetes. [Copyright &y& Elsevier]

Summary Objective Vaspin is visceral adipose-tissue-derived adipokine, which has an insulin-sensitizing effect in obese type 2 diabetic rodent models. As adipokines may serve as a link between visceral adiposity and atherosclerosis, we investigated whether plasma vaspin concentrations were associated with the metabolic syndrome and coronary atherosclerosis. Design and Methods We measured fasting plasma vaspin levels in 81 subjects with the metabolic syndrome and 241 age- and sex-matched control subjects without the metabolic syndrome using the enzyme-linked immunosorbent assay. Multi-detector row cardiac computed tomography was performed to evaluate coronary atherosclerosis. We analysed sex-specific plasma vaspin concentrations according to the presence of the metabolic syndrome and the severity of coronary atherosclerosis. Results Plasma vaspin concentrations were significantly higher in men with the metabolic syndrome compared with those without the metabolic syndrome [median 0·60 (inter-quartile range 0·40-0·99) ng/ml vs 0·40 (0·26-0·66) ng/ml, P = 0·002]. There was a positive correlation between plasma vaspin concentrations and body mass index, waist circumference, and per cent body fat in men. However, these relationships were not found in women. Plasma vaspin concentrations were associated with the presence and severity of coronary artery stenosis such as higher Agatstone calcium score, number of diseased vessels and characteristics of coronary artery plaque only in women. Conclusions Higher plasma vaspin concentrations are significantly associated with metabolic syndrome in men. In women, vaspin concentrations are associated with coronary atherosclerosis. Further studies regarding the role of vaspin in the pathogenesis of obesity and atherosclerosis are required. [ABSTRACT FROM AUTHOR]

Background: Recent genome-wide association studies in East Asians have identified polymorphisms in KCNQ1 as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in KCNQ1 are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM. Methods: Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h. Results: rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01-1.36, p = 0.039; OR 1.24, 95% CI 1.07-1.45, p = 0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance. Conclusions: The single nucleotide polymorphisms in KCNQ1 showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in KCNQ1 confer a risk for GDM by altering pancreatic β-cell function. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We aimed to investigate the association of iron and polyunsaturated fatty acid (PUFA) intake with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes. This cross-sectional study included 147 individuals with type 2 diabetes. Dietary intake was assessed using three-day food records. DPN was diagnosed on the basis of a Michigan Neuropathy Screening Instrument—Physical Examination score ≥2.5. Adjusted for total energy intake, iron intake was significantly higher in individuals with DPN than in those without DPN (10.9 ± 4.0 mg vs. 9.9 ± 3.6 mg, p = 0.041). In addition, the iron/PUFA ratio was significantly higher in individuals with DPN (1.4 ± 0.8 vs. 1.1 ± 0.4, p = 0.005). Logistic regression analyses showed that iron intake (odds ratio (OR): 1.152; 95% confidence interval (CI): 1.012, 1.311) and iron/PUFA ratio (OR: 2.283; 95% CI: 1.066, 4.887) were associated with DPN after adjustment for total energy intake, sex, age, body mass index, systolic blood pressure, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, low-density lipoprotein cholesterol, and smoking. In conclusion, high dietary iron intake and an elevated iron/PUFA ratio were associated with the presence of DPN. The present study suggests the importance of the dietary pattern of iron and PUFA intake in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the prediction of type 2 diabetes through abnormal liver function test conducted in Korea. It was concluded that increased activity of liver enzymes like alanine aminotransferase (ALT) is associated with a double increase in the risk of type 2 diabetes independently of conventional factors. It mentions that a marker that could be used to identify individuals at high risk of type 2 diabetes in Asian populations is the measurement of ALT activity.

Peripheral arterial disease (PAD) is one of major risk factors for cardiovascular morbidity and mortality in diabetic patients. The incidence of PAD is 3-4 fold higher in patients with diabetes than non-diabetic subjects. Moreover, the characteristics of PAD are much extensive but frequently asymptomatic in diabetic subjects compared to normal subjects. The ankle-brachial index (ABI) has been used to screen PAD but, more effective screening tool is needed to detect asymptomatic PAD in diabetic patients, especially with medial sclerosis. We investigated the usefulness of color Doppler ultrasonography and carotid intima-media thickness (C-IMT) for diagnosis of PAD in diabetic subjects with normal ABI. We enrolled 256 patients (mean age 62±9 yr, Male 62%) with type 2 diabetes from 2003 to 2006. All patients were performed ABI, color Doppler ultrasonography and C-IMT. We had checked past and current medical history and clinical symptoms of subjects at the time of procedure. The degree of stenosis in PAD was defined according to Jager's criteria. Among 256 patients, ABI values were normal (>0.9) in 232 (91%) and abnormal(≤0.9) in 24 (9%). Among the 232 patient with normal ABI, 22 (18%) had Grade III (50%-99% stenosis) lesions and 32 (14%) had Grade IV (100% stenosis) lesions by color Doppler ultrasonography. Most subjects with diagnosis of PAD are asymptomatic (78%). Most lesions were infra-popliteal (58%) and multi-segmental involvement reached up to 25%. In multivariate logistic regression, high C-IMT (≥ 1.0mm) was independent predictor for PAD (RR 3.4, 95% C.I. 1.5-7.5, p<0.05) after adjusting confounding factors (age, sex, smoking history, leg symptom, duration of diabetes) Our data suggest that color Doppler ultrasonography could be an important non-invasive tool for early diagnosis of asymptomatic PAD in diabetic patients, especially with high C-IMT (≥l.0mm) even though in patients with normal ABI. [ABSTRACT FROM AUTHOR]

Metformin is one of the most commonly prescribed drugs in the management of Type 2 diabetes mellitus (T2DM). In the fear of potential lactic acidosis, metformin is contraindicated in the patients with creatinine clearance (Ccr) < 60 ml/min (serum creatinine ≥ 1.5 mg/dL in men, ≥ 1.4 mg/dL in women). In this study, we intended to derive an equation predicting Ccr from clinical parameters and its relation with acidosis in the Korean T2DM patients. Total 311 (151 men and 160 women, 58.2 ± 10.6 yrs) were enrolled in this study. Ccr was measured by 24hr urine collection and compared with Cockcroft-Gault (CG) equation and Modification of Diet in Renal Disease (MDRD) equation. New equation predicting Ccr was derived using muscle mass measured by bioimpedence analyzer. The Ccr measured by 24hr-urine collection was 70.3 ± 19.5 mL/min/1.72m² and correlated with Ccr estimated by CG or MDRD equation (r = 0.894, P < 0.001 and r = 0.635, P < 0.001, respectively). The regression equation for Ccr using muscle mass was; estimated Ccr = (1.8 x muscle mass - 0.18 x age) ÷ serum creatinine, which showed a good correlation with measured Ccr (r = 0.902, P < 0.001). Serum creatinine corresponding to Ccr 60 mL/min/1.72m² is 1.15mg/dL in men and 0.95 mg/dL in women. Serum anion gap was not associated with the dose of metformin nor Ccr. We hereby showed that the Ccr could be easily predicted using muscle mass and serum creatinine in Type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Aims: Diabetic peripheral neuropathy (DPN) is a major risk factor for sarcopenia or frailty in older patients with diabetes. In this study, we investigated the association between DPN and muscle strength in type 2 diabetes.Methods: DPN was assessed using the Michigan Neuropathy Screening Instrument Questionnaire (MNSI-Q) and Physical Examination (MNSI-PE) in 230 subjects with type 2 diabetes. Handgrip strength (HGS) was measured using an electronic grip strength dynamometer.Results: The prevalence of DPN was 26.4% in men and 34.7% in women. HGS was significantly lower in men with DPN compared with men without DPN (27.0 ± 9.4 vs. 29.7 ± 8.4 kg, p = 0.036). This effect was not seen in women. In men, multivariate regression analysis showed that HGS was negatively associated with the MNSI-Q (β = -1.200, p = 0.003) and MNSI-PE scores (β = -0.937, p = 0.046) and resulted in an abnormal 10-gram monofilament test score (β = -10.895, p < 0.001). However, HGS was not significantly associated with neuropathy in women.Conclusions: Muscle strength was lower in men with DPN than in those without DPN. Assessment of muscle function may have clinical implications in the prevention of sarcopenia and frailty in men with DPN. [ABSTRACT FROM AUTHOR]

Selective inhibition of glycogen synthase kinase-3 (GSK3) has been targeted as a novel therapeutic strategy for diabetes mellitus. We investigated the anti-diabetic efficacy and molecular mechanisms of KICG1338 (2-(4-fluoro-phenyl)-3 H -imidazo[4,5-b]pyridine-7-carboxylic acid(4-methyl-pyridin-3-yl)-amide), a GSK3β inhibitor, in three animal models: Otsuka Long-Evans Tokushima Fatty (OLETF) rats, leptin receptors-deficient db / db mice, and diet-induced obese (DIO) mice. Biochemical parameters including glucose tolerance tests and gene expressions associated with glucose metabolism were investigated. Glucose excursion decreased significantly by KICG1338-treated OLETF rats, accompanied by increase in insulin receptor substrate-1 and glucose transporter (GLUT)-4 expressions in muscle and decreased GLUT-2 expression in liver. Glucose-lowering effects were similarly observed in KICG1338-treated db / db and DIO mice. KICG1338 treatment increased adiponectin levels and decreased TNF-α levels. KICG1338 therapy also led to greater β-cell preservation and less hepatic fat infiltration with decreased expressions of genes involved in inflammation and endoplasmic reticulum stress. These data demonstrate anti-diabetic efficacy of KICG1338, a novel GSK3β inhibitor. [ABSTRACT FROM AUTHOR]

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n = 172) or sulfonylurea dose-increasing by 50% ( n = 172) treatment groups. The primary endpoint was a change in HbA 1c after 24 weeks. The secondary endpoints were patients achieving HbA 1c ≤ 7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA 1c at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA 1c levels decreased by −1.19% (−13.09 mmol/mol) with vildagliptin add-on and −0.46% (−5.06 mmol/mol) with sulfonylurea (P < 0.001). Significantly more vildagliptin add-on patients achieved HbA 1c ≤ 7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P < 0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea ( P < 0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137 ). [ABSTRACT FROM AUTHOR]

Aims The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. Methods We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3–6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7–6.4%, 39–46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. Results Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥165 mg/dL and a 30-min C-peptide <5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98–26.16) of developing diabetes than other prediabetic subjects. Conclusions In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated incretin secretion and dipeptidyl peptidase (DPP)-IV activity in Korean type 2 diabetic patients compared with non-diabetic subjects. Type 2 diabetic patients showed intact GLP-1 and total GIP levels similar to those in non-diabetic subjects. Serum DPP-IV activity was significantly higher in type 2 diabetic patients (p =0.022). [ABSTRACT FROM AUTHOR]

Abstract: Objective: Insulin resistance may provide a crucial link between type 2 diabetes and cardiovascular disease. However, it is still unclear whether insulin resistance itself or hyperinsulinemia is independently associated with subclinical atherosclerosis. We hypothesized that insulin resistance, but not hyperinsulinemia, would be associated with carotid atherosclerosis in patients with type 2 diabetes. Methods: We examined 2471 patients with type 2 diabetes, consecutively enrolled in Huh Diabetes Center. Insulin sensitivity was directly assessed by a rate constant for plasma glucose disappearance (Kitt) using short insulin tolerance test. Fasting insulin levels were used as a marker of hyperinsulinemia. Both carotid arteries were examined by B-mode ultrasound. Carotid atherosclerosis was defined by having a clearly isolated focal plaque or mean carotid intima-media thickness (IMT) ≥1.1mm. Results: In multiple regression models, insulin sensitivity index (Kitt) but not hyperinsulinemia was significantly associated with carotid IMT adjusting for known risk factors such as age, sex, BMI, smoking, systolic pressure, HDL and LDL cholesterol. One standard deviation decrease in Kitt was associated with 0.046mm increase in carotid IMT (p =0.015). Furthermore, odds ratio for carotid atherosclerosis was 1.43 (95% CI: 1.10, 1.86) in type 2 diabetic patients with insulin resistance (lowest quartile of insulin sensitivity) adjusting for known risk factors. The results were consistent in all subgroups stratified by sex, age, smoking and hypertension. Conclusion: Insulin resistance measured by short insulin tolerance test, but not hyperinsulinemia, is independently associated with carotid atherosclerosis in patients with type 2 diabetes. [Copyright &y& Elsevier]