Expression of Cyr61 is associated with clinical course in patients with Crohn's disease.

BACKGROUNDS: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn's disease (CD). METHODS: Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients. RESULTS: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20-0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03). CONCLUSIONS: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.

Effects of meal ingestion on intramyocellular ceramide concentrations and fractional de novo synthesis in humans.

We investigated the effects of meal ingestion on intramyofibrillar (IMF) and subsarcolemmal (SS) ceramide metabolism in volunteers ranging from lean to obese. Thirty-eight women and men underwent a steady-state meal ingestion protocol that included a 6.5-h infusion of [U-13C]palmitate and muscle biopsies 1.5 and 6.5 h after starting the tracer infusion. We measured IMF and SS sphingolipid concentrations and the contribution of plasma palmitate to intramyocellular C16:0 ceramide by use of LC-MS-MS. In response to meal ingestion SS C24 ceramide concentrations, but not C14-C20 concentrations, increased significantly. IMF ceramide concentrations did not change. The increases in SS C24 ceramides were negatively related to parameters of insulin resistance. The fractional contribution of plasma palmitate to intramyocellular C16:0 ceramides in both IMF and SS fractions was inversely related to overweight status (ß = -0.432, P = 0.0095 and ß = -0.443, P = 0.0058, respectively). These data indicate that meal ingestion has differing effects on SS ceramide subspecies and suggest that the fractional de novo synthesis of intramyocellular ceramide from plasma palmitate in the postprandial condition is reduced in those who are overweight.

Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease.

BACKGROUNDS: Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn's disease (CD). METHODS: A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. RESULTS: Median age of patients was 22.5 years (range, 15-49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months-54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). CONCLUSION: Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

Improved trends in cardiovascular complications among subjects with type 2 diabetes in Korea: a nationwide study (2006-2013).

BACKGROUND: Representative data on the secular trends in cardiovascular disease (CVD) are limited in Asian populations with diabetes. We aimed to estimate the temporal trends in cardiovascular complications using Korean nationwide whole population-based claims data in subjects with and without diabetes. METHODS: Type 2 diabetes was defined as a current medication history of anti-diabetic drugs and the presence of International Classification of Diseases (ICD)-10 codes (E11-E14) as diagnosis. We compared the 8-year rates of six cardiovascular complications [i.e., ischemic heart disease, acute myocardial infarction (AMI), ischemic stroke, hemorrhagic stroke, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG)] in Korean adults aged 30 years and older using data from four consecutive nationwide databases (2006-2007, 2008-2009, 2010-2011, and 2012-2013) of Korean national health insurance service. RESULTS: A total of 1,645,348, 1,971,559, 2,291,247, and 2,562,612 subjects with type 2 diabetes were found in the year of 2006-2007, 2008-2009, 2010-2011, and 2012-2013, respectively. Age and gender standardized rates of the six predefined cardiovascular complications decreased in Korean adults with type 2 diabetes during the study period. The greatest relative reductions were observed for hospitalization due to AMI (-37.28%), followed by hospitalizations due to ischemic stroke (-36.98%). In the overall population without type 2 diabetes, the greatest relative reductions were observed for hospitalization for hemorrhagic stroke (-29.47%), followed by hospitalization due to ischemic stroke (-28.92%). Relative decreases in all six predefined cardiovascular complications were generally more profound in adults with diabetes than in those without diabetes, which led to significant decrease in the relative risks of all six cardiovascular complications in subjects with diabetes over the past 8 years. However, people with diabetes still had a two- to sixfold higher risk of hospitalization for major CVD events and interventions than people without diabetes. CONCLUSIONS: Our findings suggest a significant reduction in the rate of people affected by CVD within the diabetic population. However, as the number of people with diabetes rises, the absolute burden of CVD will still be high in Korea.

Subjective taste to polyethylene glycol is associated with efficacy of right colon preparation.

AIM: A prospective observational trial with preparations using polyethylene glycol (PEG) to compare patient compliance and adverse events according to individual subjective taste. METHODS: A total of 299 outpatients (mean ± standard deviation [SD] 56.5 ± 13.8 years, 172 males) were recruited for our study. We assessed the efficacy of bowel preparation, subjective taste to their regimens, compliance and adverse events during the preparation. RESULTS: We achieved adequate preparation in 267 (89.3%). A total of 124 patients (41.5%) had 'unacceptable taste' to their regimens. The patients with acceptable taste had better compliance than the patients with unacceptable taste (p = .009). The patients with unacceptable taste had more frequent adverse events such as nausea, vomiting and abdominal bloating than the patients with acceptable taste (all p < .001, Table 2). Patients with unacceptable taste (16.1%) had more frequent inadequate preparation in overall colon than patients with acceptable taste (6.9%, p = .011). There was a significant difference in the efficacy of preparation of right colon between the two groups (p = .004). CONCLUSION: Subjective taste to PEG is associated with efficacy of right colon preparation. In addition, subjective taste to PEG is associated with compliance and adverse events.

Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes.

BACKGROUND/AIMS: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. METHODS: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. RESULTS: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the ß-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the ß-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05). CONCLUSION: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.

Risedronate increases osteoblastic differentiation and function through connexin43.

Bisphosphonates are potent antiresorptive drugs which have antifracture efficacy by reducing bone turnover rate and increasing bone mineral density. In addition to inhibiting osteoclast function, bisphosphonates have been reported to also promote survival of osteocyte and osteoblast via an anti-apoptotic effect, mediated by opening of hemi-gap junction channels formed by connexin43 (Cx43). In this study, we investigated the effect of risedronate, one amino-bisphosphonate, on osteoblast differentiation and Cx43 expression using the mesenchymal cell line C2C12. Risedronate dose-dependently increased the activity of osterix (OSE)-luciferase containing Runx2 response element with highest activity at 50µM. The activity of osteocalcin (OC)- and bone sialoprotein (BSP)-luciferase reporters, markers of osteoblast differentiation, were also increased by risedronate. When risedronate and BMP2 were used in combination, alkaline phosphatase (ALP) activity increased to a larger extent than when BMP2 was used alone. Risedronate as well as the pro-osteogenic transcription factors, Runx2, Osterix or Dlx5, increased transcriptional activity of the Cx43 promoter in a dose-dependent manner. In the presence of Runx2 or Dlx5, risedronate had an additive effect on Cx43 promoter activity. Accordingly, risedronate increased protein expression of Cx43, Runx2, Osterix, and Dlx5. These results suggest that risedronate promotes osteoblastic differentiation and positively regulates Cx43 gene transcription.

Ceramide concentrations in liver, plasma, and very low-density lipoproteins of humans with severe obesity.

We investigated the relationships between ceramide species concentrations in liver, plasma and very low-density lipoproteins (VLDL) particles of humans with obesity as well as the relationships between hepatic fat content and hepatic ceramide concentrations and proportional distribution. Twenty-five obese (body mass index >35 kg/m2 ) adults participated in this study. Plasma, VLDL and hepatocellular ceramide concentrations were measured by liquid chromatography/tandem mass spectrometry. The proportionate distribution of measured ceramide species differed between liver, whole plasma and the VLDL fraction. We found significant, positive correlations between the proportion of C14:0, C18:0, C20:0 and C24:1 ceramide in the liver and whole plasma (γ = 0.491, p = 0.013; γ = 0.573, p = 0.003; γ = 0.479, p = 0.015; γ = 0.716, p = 0.00006; respectively). In contrast, only the proportional contribution of C24:1 ceramide correlated positively between VLDL and liver (γ = 0.425, p = 0.013). The percent hepatic fat correlated positively with the proportion of C18:1, C18:0 and C20:0 hepatic ceramides (γ = 0.415, p = 0.039; γ = 0.426, p = 0.034; γ = 0.612, p = 0.001; respectively), but not with total hepatic ceramide concentration. The proportions of whole plasma ceramide subspecies, especially C14:0, C18:0, C20:0 and C24:1chain length, are reflective of those of hepatic ceramide subspecies in obese humans; these appear to be markers of hepatic ceramide species composition.

68 Ga-FAPI PET/CT Imaging of the Pancreas in a Patient With Fulminant Type 1 Diabetes.

ABSTRACT: Fulminant type 1 diabetes is a recently recognized diabetes subtype characterized by extremely rapid destruction of the pancreatic beta cells, leading to an absolute deficiency in insulin secretion. Fulminant type 1 diabetes is clinically characterized by the drastic onset of hyperglycemia and ketoacidosis within a few days, as well as near-normal glycated hemoglobin (HbA 1c ) levels despite remarkable hyperglycemia at initial presentation. A 41-year-old woman diagnosed with fulminant type 1 diabetes underwent 68 Ga-FAPI PET/CT, which showed intense FAPI uptake throughout the pancreas, especially in the pancreatic tail. Contrast-enhanced abdominal CT failed to reveal any pancreatic abnormalities. This case indicated that 68 Ga-FAPI PET/CT might be useful for evaluating patients with fulminant type 1 diabetes.

Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes.

Aims: To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes. Methods: We evaluated 332 patients with type 2 diabetes in a cross-sectional study. Result: The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 µg/mL; Q2 [7.7-15.0 mg/g], 17.5 µg/mL; Q3 [15.1-61.4 mg/g], 18.6 µg/mL; Q4 [≥61.5 mg/g], 22.3 µg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (ß = 0.285, p <0.001). Conclusion: Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.

Parkin-mediated mitophagy is negatively regulated by FOXO3A, which inhibits Plk3-mediated mitochondrial ROS generation in STZ diabetic stress-treated pancreatic ß cells.

Diabetes mellitus (DM) is one of the most researched metabolic diseases worldwide. It leads to extensive complications such as cardiovascular disease, nephropathy, retinopathy, and peripheral and central nervous system through an inability to produce or respond to insulin. Although oxidative stress-mediated mitophagy has been reported to play an important role in the pathogenesis of DM, specific studies are still lacking as well as remain highly controversial. Here, we found that Parkin-mediated mitophagy in pancreatic ß cells under streptozotocin (STZ)-diabetic stress was induced by Polo-like kinase 3 (Plk3) and inhibited by the transcription factor Forkhead Box O3A (FOXO3A). STZ stress induces mitochondrial recruitment of Parkin through Plk3-mediated mitochondrial reactive oxygen species (ROS) generation, which causes pancreatic cell damage. Conversely, FOXO3A acts as negative feedback to prevent diabetic stress by inhibiting Plk3. Meanwhile, antioxidants including N-acetylcysteine (NAC) and natural COA water scientifically block these mitochondrial ROS and mitochondrial recruitment of Parkin by inhibiting Plk3. Through a 3D organoid ex vivo model, we confirmed that not only ROS inhibitors but also mitophagy inhibitory factors such as 3-MA or Parkin deletion can compensate for pancreatic cell growth and insulin secretion under STZ diabetic stress. These findings suggest that the Plk3-mtROS-PINK1-Parkin axis is a novel mitophagy process that inhibits pancreatic ß-cell growth and insulin secretion and FOXO3A and antioxidants may provide new alternatives for effective diabetes treatment strategies in the future.

Natural COA water inhibits mitochondrial ROS-mediated apoptosis through Plk3 downregulation under STZ diabetic stress in pancreatic ß-cell lines.

Diabetes from pancreatic ß cell death and insulin resistance is a serious metabolic disease in the world. Although the overproduction of mitochondrial reactive oxygen species (ROS) plays an important role in the pathogenesis of diabetes, its specific molecular mechanism remains unclear. Here, we show that the natural Charisma of Aqua (COA) water plays a role in Streptozotocin (STZ) diabetic stress-induced cell death inhibition. STZ induces mitochondrial ROS by increasing Polo-like kinase 3 (Plk3), a major mitotic regulator, in both Beta TC-6 and Beta TC-tet mouse islet cells and leads to apoptosis. Overexpression of Plk3 regulates an increase in mitochondrial ROS as well as cell death, also these events were inhibited by Plk3 gene knockdown in STZ diabetic stimulated-Beta TC-6 cells. Interestingly, we found that natural COA water blocks mitochondrial ROS generation through the reduction of Plk3 and prevents apoptosis in STZ-treated beta cells. Furthermore, using the 3D organoid (ex vivo) system, we confirmed that the insulin secretion of the supernatant medium under STZ treated pancreatic ß-cells is protected by the natural COA water. These findings demonstrate that the natural water COA has a beneficial role in maintaining ß cell function through the inhibition of mitochondrial ROS-mediated cell death, and it might be introduced as a potential insulin stabilizer.

Plasma galectin-3 concentration and estimated glomerular filtration rate in patients with type 2 diabetes with and without albuminuria.

This study aimed to investigate the association between galectin-3 concentration and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria. In this cross-sectional study, we examined 334 patients with T2DM. The eGFR was calculated using a creatinine-based formula (eGFRcrea) and a combined creatinine-cystatin C equation (eGFRcrea-cyst). The participants were categorized into two groups based on the urinary albumin-to-creatinine ratio (UACR): patients without albuminuria (UACR < 30 mg/g) and those with albuminuria (UACR ≥ 30 mg/g). Greater concentrations of plasma galectin-3 were associated with lower eGFRcrea-cyst and eGFRcrea levels in patients with and without albuminuria. Plasma galectin-3 concentrations were negatively correlated with eGFRcrea-cyst in patients with normoalbuminuria and albuminuria (γ = - 0.405, P < 0.001; γ = - 0.525, P < 0.001, respectively). Galectin-3 concentrations were significantly associated with eGFRcrea-cyst after adjusting for sex, age, and other confounding factors, including UACR as a categorical or continuous variable in multiple regression analyses (ß = - 0.294, 95% CI - 70.804 to - 41.768, P < 0.001; ß = - 0.265, 95% CI - 65.192 to - 36.550, P < 0.001, respectively). Likewise, when eGFRcrea-cyst was treated in place of eGFRcrea, this result was replicated in the correlation and regression analyses. Galectin-3 concentration was negatively associated with eGFR in patients with T2DM, independent of albuminuria status.

Primary bile acid activates Egr­1 expression through the MAPK signaling pathway in gastric cancer.

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI­N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr­1) and the oncogenes including c­Jun, c­Myc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI): 1.2­16.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI: 1.3­75.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr­1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria.

AIM: To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. METHODS: We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). RESULTS: In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (ß = -0.309, p < 0.001 and ß = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. CONCLUSION: GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.

Relationship Between Fibroblast Growth Factor 19 and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to evaluate whether fibroblast growth factor 19 (FGF19) is associated with the risk of diabetic retinopathy in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 357 patients with T2DM were investigated in this cross-sectional study. Logistic regression analysis was performed to assess the association between FGF19 level and diabetic retinopathy. RESULTS: Serum FGF19 level was significantly lower in patients with diabetic retinopathy in those without diabetic retinopathy. The multivariable analysis revealed a significant association between serum FGF19 level and diabetic retinopathy (odds ratio for every 1 standard deviation increase in logarithmic value = 0.69, 95% confidence interval 0.51-0.94, p = 0.019). CONCLUSION: Serum FGF19 level was negatively associated with diabetic retinopathy in patients with T2DM.

Pathways Linking Health Literacy to Self-Management in People with Type 2 Diabetes.

Health literacy is considered to be an emerging determinant of health behaviors and outcomes. The underlying mechanisms linking health literacy to diabetes self-management are currently unclear. This study assessed a mediation model consisting of a direct pathway between health literacy and self-management, and indirect pathways via social isolation only, self-efficacy only, and social isolation and self-efficacy serially in people with type 2 diabetes. A cross-sectional design was employed, and a total of 524 participants were recruited from outpatient clinics of multi-institutions from June 2020 to February 2021. The mediation model was analyzed using the PROCESS macro on SPSS with bootstrap bias-corrected 95% confidence intervals (CIs) with 10,000 bootstrapping iterations. Health literacy positively affected self-management. The estimated indirect effect of health literacy on self-management via social isolation was significant, at 0.018 (95% CI = 0.004-0.036). The indirect effect via self-efficacy was estimated at 0.214 (95% CI = 0.165-0.266). The indirect effect via social isolation and self-efficacy serially was 0.013 (95% CI = 0.006-0.023). The findings of this study suggest that clinical practice can be improved through more comprehensive diabetes self-management interventions that promote all of the components of health literacy, social contacts/networks, and self-efficacy in particular.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study.

BACKGROUND: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). METHODS: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. RESULTS: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. CONCLUSION: This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Plasma C-peptide level is inversely associated with family history of type 2 diabetes in Korean type 2 diabetic patients.

Type 2 diabetes is characterized by progressive ß-cell dysfunction. Family history of type 2 diabetes has been known to be associated with an increased risk for the development of the disease. However, few studies have evaluated the effects of family history of diabetes on residual ß-cell function in type 2 diabetic patients. We investigated associations among family histories, clinical characteristics and plasma C-peptide levels in type 2 diabetic patients. A total of 1,350 patients with type 2 diabetes were recruited. The patients with a family history of type 2 diabetes had younger age at onset of diabetes, longer diabetes duration, higher LDL-cholesterol, and lower fasting C-peptide levels than the patients without family history. When divided according to the tertiles of diabetes duration, patients with a family history of type 2 diabetes had more decreased concentrations of fasting C-peptide as duration of diabetes increased, but patients without a family history did not. Multiple regression models were used to determine the association between fasting plasma C-peptide levels and a family history of type 2 diabetes mellitus. With adjustments for age and sex, glycated hemoglobin (HbA(1C)), fasting plasma glucose, free fatty acids, body mass index and diabetes mellitus (DM) duration, there was a significant association (P < 0.01). Our results showed that a family history of diabetes was significantly associated with the progressive decline of fasting plasma C-peptide levels in Korean type 2 diabetes mellitus.

[Hypertriglyceridemia-induced pancreatitis treated with insulin in a nondiabetic patient].

Heparin and/or insulin stimulate lipoprotein lipase and are known to decrease serum triglyceride level. However, their efficacy in hypertriglyceridemia-induced acute pancreatitis in nondiabetic patients is not well documented. We report a case of hypertriglyceridemia-induced pancreatitis in 43-year-old nondiabetic woman in whom treatment with insulin was accompanied by reduction in serum triglyceride level and the resolution of pancreatitis. She presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. Her medical history was unremarkable. There was no history of alcohol consumption, and biliary imaging was not remarkable. Subsequent laboratory investigation revealed marked hypertriglyceridemia (1,951 mg/dL), impaired fasting glucose, and normal HbAlc level. The Ransons score and APATCH II score were 1 and 4. Abdominal CT showed diffuse enlargement of pancreas, peripancreatic fat infiltration, and multiple fluid collections around the pancreas. We treated the patient with the infusion of 5% dextrose and 1.5 unit/hr regular insulin to reduce serum triglyceride level. The level of serum triglyceride was decreased to 305 mg/dL on day 5. During the remainder of hospitalization, her clinical symptoms and laboratory values gradually improved.