Adolescent ; Diabetes Mellitus ; drug therapy ; metabolism ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Infant, Newborn ; Male ; Sulfonylurea Compounds ; adverse effects ; therapeutic use

BACKGROUND: Metformin, sulfonylurea, and dietary fiber are known to affect gut microbiota in patients with type 2 diabetes mellitus (T2DM). This open and single-arm pilot trial investigated the effects of the additional use of fiber on glycemic parameters, insulin, incretins, and microbiota in patients with T2DM who had been treated with metformin and sulfonylurea. METHODS: Participants took fiber for 4 weeks and stopped for the next 4 weeks. Glycemic parameters, insulin, incretins during mixed-meal tolerance test (MMTT), lipopolysaccharide (LPS) level, and fecal microbiota were analyzed at weeks 0, 4, and 8. The first tertile of difference in glucose area under the curve during MMTT between weeks 0 and 4 was defined as ‘responders’ and the third as ‘nonresponders,’ respectively. RESULTS: In all 10 participants, the peak incretin levels during MMTT were higher and LPS were lower at week 4 as compared with at baseline. While the insulin sensitivity of the ‘responders’ increased at week 4, that of the ‘nonresponders’ showed opposite results. However, the results were not statistically significant. In all participants, metabolically unfavorable microbiota decreased at week 4 and were restored at week 8. At baseline, metabolically hostile bacteria were more abundant in the ‘nonresponders.’ In ‘responders,’ Roseburia intestinalis increased at week 4. CONCLUSION: While dietary fiber did not induce additional changes in glycemic parameters, it showed a trend of improvement in insulin sensitivity in ‘responders.’ Even if patients are already receiving diabetes treatment, the additional administration of fiber can lead to additional benefits in the treatment of diabetes.
Bacteria ; Diabetes Mellitus, Type 2 ; Dietary Fiber ; Gastrointestinal Microbiome ; Glucose ; Humans ; Incretins ; Insulin ; Insulin Resistance ; Metformin ; Microbiota ; Sulfonylurea Compounds

BACKGROUND: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. METHODS: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-Interact™online, and contraindicated, major, or moderate severity level in Micromedex® were included. SAS version 9.4 was used for data analysis. RESULTS: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. CONCLUSION: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.
Aged* ; Anti-Infective Agents ; Ciprofloxacin ; Cohort Studies ; Cross-Sectional Studies ; Drug Interactions ; Fluconazole ; Gliclazide ; Glipizide ; Glyburide ; Humans ; Hypoglycemia* ; Korea* ; Levofloxacin ; Male ; National Health Programs ; Ofloxacin ; Prescriptions ; Risk Factors ; Statistics as Topic ; Sulfonylurea Compounds

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium (K(ATP)) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the K(ATP) channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.
Diabetes Mellitus* ; Humans ; Insulin ; Live Birth ; Potassium ; Potassium Channels ; Sulfonylurea Compounds ; Treatment Outcome

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients. METHODS: We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with > or =25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks. RESULTS: At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level < or =7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of beta-cells. CONCLUSION: An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.
Blood Glucose ; Body Weight ; C-Peptide ; Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors ; Fasting ; Female ; Hemoglobin A, Glycosylated ; Homeostasis ; Humans ; Hypoglycemia ; Insulin Resistance ; Metformin* ; Sulfonylurea Compounds ; Triglycerides

OBJECTIVETo explore the effect of glimepiride on the glucose uptake as well as glucose transporter (GLUT)-1 and GLUT-3 expression levels of rat mandibular osteoblasts in hyperglycemia.

METHODSPrimary osteoblasts were isolated and cultured. Then, the cells were placed in an osteogenic medium containing two glucose concentrations (5.5 and 16.5 mmol X L(-1)), with or without glimepiride (10 micromol x L(-1)). Glucose uptake was determined by employing 18F-deoxyglucose (18F-FDG) in the cells, and GLUT-1 and GLUT-3 expression levels were evaluated by Western blot analysis.

RESULTSGlucose at 16.5 mmol x L(-1) significantly inhibited 18F-FDG uptake and downregulated GLUT-3 protein expression in osteoblasts. Hyperglycemia increased GLUT-1 protein expression. Glimepiride significantly increased glucose uptake and upregulated GLUT-1 and GLUT-3.

CONCLUSIONGlimepiride enhance the glucose transporter in rat osteoblasts at two different glucose concentrations.

Animals ; Fluorodeoxyglucose F18 ; Glucose ; Glucose Transporter Type 1 ; Hyperglycemia ; Mandible ; Osteoblasts ; Rats ; Sulfonylurea Compounds

BACKGROUNDDiabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients. Hyperglycemia markedly increases the risk of cardiovascular disease. Endothelial dysfunction is common in type 2 diabetes mellitus (DM) and is an early indicator of diabetic vascular disease. Therefore, it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium. The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.

METHODSForty male Sprague-Dawley rats (age, 8 weeks; weight, 180-200 g) were included in this study and fed with a normal chow diet for 1 week. Rats (n = 10) served as the normal control group (NC group) were fed with a normal chow for another 2 weeks and received an injection of saline. The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups (n = 10 rats per group) as follow: type 2 DM group (DM group), DM + gliquidone group (GLI group) and DM + metformin group (MET group). Five weeks later, all rats were fasted overnight and taken tail blood samples for biochemical determinations. Then rats in the NC and DM groups were administrated with normal saline, while rats in the MET and GLI groups were administrated with metformin (100 mg/kg) or gliquidone (10 mg/kg), respectively. All medicines were given via intragastric administration for 8 weeks. After 16 weeks, plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were measured. The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H&E staining.

RESULTSMetformin treatment prevented weight gain ((315.80 ± 52.16) g vs. (318.70 ± 68.48) g, P = 0.773), improved plasma TG, HDL-C and LDL-C levels (P = 0.006, 0.003, 0.001, respectively, all P < 0.05). However, gliquidone showed no significant effects on plasma TG and TC levels (P = 0.819, 0.053, respectively). LDL-C and HDL-C in the GLI group changed ((0.46 ± 0.10) mmol/L vs. (0.36 ± 0.14) mmol/L, P = 0.007; (0.99 ± 0.27) mmol/L vs. (1.11 ± 0.18) mmol/L, P = 0.049). Both metformin and gliquidone treatment lowered blood glucose levels (P = 0.001, 0.004, respectively, P < 0.05). Under light microscopy, no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group. In the DM group, the aortic wall structure was unclear, the intima was thickened with irregular intima, and membrane elastic fibers collapsed. The aortic intima in the MET and GLI groups was smoother compared with the DM group, but the endothelial structure of the MET group was closer to that of the NC group.

CONCLUSIONSBoth metformin and gliquidone have anti-atherosclerotic effects. But the endothelial structure of the MET group was closer to that of the NC group. Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C, whereas gliquidone therapy did not lose weight and decrease serum level of TG. These data may have important implications for the treatment of patients with type 2 DM.

Animals ; Aorta ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Angiopathies ; prevention & control ; Hypoglycemic Agents ; therapeutic use ; Male ; Metformin ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonylurea Compounds ; therapeutic use

BACKGROUND: Vildagliptin is believed to improve glucose variability by restoring the physiologic pattern of insulin secretion and improving beta and alpha cells' sensitivity to glucose but with less increase in insulin secretion compared to sulfonylureas resulting in similar glucose levels but with less risk of hypoglycemia.
OBJECTIVE: To compare the effect of vildagliptin and glimepiride on glucose variability among Type 2 diabetic patients not controlled on metformin alone.
METHODS: This investigation is a prospective, interventional, open-labeled, active control, parallel assignment, efficacy study that included patients with inadequate glycemic control on monotherapy with metformin, randomly assigned either to vildagliptin or glimeparide. For one month, one group took vildagliptin 50mg/tablet one tablet twice a day while the other group took glimepiride 1 mg/tablet one tablet once a day. Subjects were asked to monitor their capillary blood glucose at seven points throughout the day for 35 days.
RESULTS: A total of 18 patients were recruited for the study and randomly assigned to either of the two treatment arms. However, only 16 patients completed the study. The vildagliptin and glimepiride groups had comparable blood sugars at baseline and at the end of the study although the glimepiride group showed a steeper decline in the blood sugar levels. Subjects in both groups showed a downward trend in the blood glucose values from day one to the 35th day with comparable mean glucose values between treatments and across combinations of day and treatment. Likewise, mean postprandial incremental area under the curve (AUCpp)and mean amplitude of glycemic excursions (MAGE) were comparable across treatments and across combinations of day and treatment, although the Glimepiride group showed relatively higher MAGE values.
CONCLUSION: Vildaglipitin and glimepiride both improved glycemia of patients with uncontrolled blood sugar on monotherapy with metformin as both groups showed downward glucose trend, although vildagliptin showed relatively less abrupt glucose lowering effect suggesting lesser risk of hypoglycemia. Mean postprandial glucose excursions of the two groups were also comparable but the vildagliptin arm had lower MAGE and may suggest an improvement in both ?- and ?-cell function.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Adamantane ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Glucose ; Hypoglycemia ; Insulins ; Metformin ; Nitriles ; Prospective Studies ; Pyrrolidines ; Sulfonylurea Compounds

Various fetal and maternal conditions are known to be associated with oligohydramnios. In general, oligohydramnios developed early in pregnancy is less common but frequently has a poor prognosis. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists during pregnancy has been associated with oligohydramnios as well as growth restriction, pulmonary hypoplasia with respiratory distress, acute renal failure, cranial malformation and fetal death. Although many researchers report a use of oral hypoglycemic agents such as glyburide or metformin in gestational diabetes mellitus, but potential adverse effects of glimepiride, which is relatively recently developed, is not well known owing to the lack of clinical data, especially early in pregnancy. A 41-year-old woman with chronic hypertension and type 2 diabetes mellitus was treated with drugs including metformin, glimepiride and angiotensin receptor antagonist until approximately 20 weeks' gestations, when severe oligohydramnios was noted. After the hospitalization for bed rest, fetal surveillance, and discontinuation of the agents, amniotic fluid reaccumulated, and the infant was delivered at term. We report this case with a brief review of literatures.
Acute Kidney Injury ; Amniotic Fluid ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Antihypertensive Agents ; Bed Rest ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diabetes, Gestational ; Female ; Fetal Death ; Glyburide ; Hospitalization ; Humans ; Hypertension ; Hypoglycemic Agents ; Infant ; Metformin ; Oligohydramnios ; Pregnancy ; Prognosis ; Sulfonylurea Compounds

Insulin resistance is frequently associated with chronic liver disease, and the interaction between hepatitis C virus (HCV) infection and insulin resistance is a major public health issue, bound to increase in the near term. Because of their potential synergism on liver disease severity, a better understanding of the clinical consequences of the relationship between HCV infection and insulin resistance is needed. This translates into accelerated liver disease progression, reduced response to anti-viral agents and, in susceptible individuals, increased risk of developing type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Little is known regarding the effect of anti-diabetic agents on HCV infection, and a possible association between use of exogenous insulin or a sulfonylurea agents and the development of hepatocellular carcinoma has recently been reported. Thus, modified lifestyle and pharmacological modalities are urgently warranted in chronic hepatitis C with metabolic alterations.
Antiviral Agents/therapeutic use ; Diabetes Mellitus, Type 2/complications/drug therapy/metabolism ; Genotype ; Hepatitis C, Chronic/*drug therapy/etiology/metabolism ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; *Insulin Resistance ; Liver Cirrhosis/etiology ; Liver Neoplasms/etiology ; Sulfonylurea Compounds/therapeutic use