Use Of Α-glucosidase Inhibitors Research Articles

Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study

AimsFrequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV.MethodsWe conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models.ResultsA total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77–0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69–0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01–1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02–1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55–0.75; IRR: 0.86, 95% CI: 0.79–0.93) and glinide (HR: 0.47, 95% CI: 0.31–0.73; IRR: 0.84, 95% CI: 0.73–0.97) may lead to an increased frequency of within-day GV.ConclusionsAn increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

Oral treatment for diabetes using α-glucosidase inhibitors was a risk factor for chronic obstructive pulmonary disease: a cohort study.

Objectives: Currently, diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) have proven to be risk factors for each other. This study aimed to determine the risk relationship between COPD and five common oral medications for DM among patients with DM.Methods: This population-based cohort study was conducted from 2008 to 2013. Patient data were retrieved from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD). After pairing by gender, age, and index date, time-to-event analysis and multiple regression analysis were performed to determine the factors associated with COPD in patients taking oral medication for DM, including age, gender, income, and comorbidities. We identified 1,028 patients who took oral medication for DM and 1,028 controls who did not take oral medication for DM.Results: We observed that the use of α-glucosidase inhibitors was associated with a higher risk of COPD (hazard ratio [HR]: 1.964, 95% confidence interval [CI]: 1.207-2.380). Furthermore, compared with the control group, α-glucosidase inhibitor users had a higher risk of COPD (HR: 2.295, 95% CI: 1.304-4.038), and no significant difference was observed in other oral medications for DM.Conclusions: Based on present results, we could suggest that patients with DM who used α-glucosidase inhibitors are probably a higher risk of COPD. We recommend that in the future, treatment with α-glucosidase inhibitors upregulate the occurrence of COPD might through gastrointestinal side effects and malnutrition.

Relationship between glucose variability evaluated by continuous glucose monitoring and clinical factors, including glucagon-stimulated insulin secretion in patients with type 2 diabetes

AimsTo evaluate the clinical factors affecting daily and day-to-day glucose variability by using continuous glucose monitoring. MethodsWe performed a cross-sectional analysis of patients with type 2 diabetes mellitus (T2DM) who underwent a glucagon stimulation test (GST) with 72 h of continuous glucose monitoring. Daily glucose variability was evaluated by mean amplitude of glycemic excursions [MAGE], percentage coefficient of variation for glucose (%CV), and day-to-day glucose variability (mean of daily differences [MODD]) by using continuous glucose monitoring. Correlations of clinical factors, including insulin secretion ability by the GST with MAGE, %CV, and MODD, were analyzed. ResultsIn 83 T2DM with insulin therapy, age and hemoglobin A1c (HbA1c) correlated with MAGE and %CV, fasting plasma glucose with MAGE and MODD, and increment of C-peptide immunoreactivity (ΔCPR) by GST correlated inversely with MAGE, %CV, and MODD. In 126 T2DM without insulin therapy, age, diastolic blood pressure, and triglycerides correlated with MODD, HbA1c with MAGE and MODD, and ΔCPR inversely correlated with %CV. Use of α-glucosidase inhibitors inversely correlated with %CV, whereas that of sulfonylurea was associated with MAGE and %CV. ConclusionsThese results suggest that ΔCPR correlated with stability of glycemic control, whereas poorly controlled diabetes is associated with increase in glucose variability. α-glucosidase inhibitors may be superior to sulfonylureas in reducing the glucose variability in T2DM.

929-P: Clinical Factors Associated with the Glucagon Stimulation Test and Daily and Day-to-Day Glucose Variability Determined by Continuous Glucose Monitoring in Type 2 Diabetic Patients

Aims: We studied clinical factors in association with the glucagon stimulation test and daily and day-to-day glucose variability as determined by continuous glucose monitoring (CGM). Methods: We performed a cross-sectional analysis of type 2 diabetes (T2DM; insulin-treated, n=83; not insulin-treated, n=126) patients who underwent the glucagon stimulation test and over 72 h of continuous glucose monitoring. Correlations of clinical factors with the mean amplitude of glycemic excursions (MAGE), percentage coefficient of variation for glucose (%CV), and mean of daily differences (MODD) in CGM were analyzed. Results: In T2DM with insulin therapy, age and HbA1c were correlated with MAGE and %CV; FPG was correlated with MAGE and MODD; and the increment of CPR (ΔCPR) was inversely correlated with MAGE, %CV, and MODD. In T2DM without insulin therapy, age, diastolic blood pressure, and triglycerides were correlated with MODD; ΔCPR was inversely correlated with %CV; HbA1c was correlated with MAGE and MODD; the use of α-glucosidase inhibitors was inversely correlated with %CV; and the use of sulfonylurea (SU) was correlated with MAGE and %CV. Conclusions: Insulin secretion is related to glucose variability in insulin-treated T2DM. Poor glycemic control greatly contributes to glucose variability in T2DM. SU administration increases the daily glucose variability in T2DM without insulin therapy. Disclosure M. Ohara: None. H. Nagaike: None. S. Goto: Research Support; Spouse/Partner; DENKA SEIKEN CO., LTD. H. Kushima: None. M. Hiromura: None. T. Yamamoto: None. Y. Mori: None. T. Fukui: None. T. Hirano: None.

Isolation and characterization of an α-glucosidase inhibitor from Musa spp. (Baxijiao) flowers.

The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified as vanillic acid (1), ferulic acid (2), β-sitosterol (3), daucosterol (4) and 9-(4′-hydroxyphenyl)-2-methoxyphenalen-1-one (5). The half maximal inhibitory concentration (IC50) values of compounds 1–5 were 2004.58, 1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known α-glucosidase inhibitor (acarbose, IC50 = 999.31 mg/L), compounds 3, 4 and 5 showed a strong α-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are competitive inhibitors. The inhibition constants (Ki) of compounds 3, 4 and 5 were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show that the compounds 3, 4 and 5 are potent α-glucosidase inhibitors.

Increased Risk of Gastrointestinal Malignancy in Patients with Diabetes Mellitus and Correlations with Anti-Diabetes Drugs: A Nationwide Population-based Study in Taiwan

Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs. From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age- and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated. During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61). Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.

Pharmacologic management of the older patient with type 2 diabetes mellitus

Background: Pharmacologic options for the treatment of elderly patients with type 2 diabetes mellitus (T2DM) are the same as in younger adults; however, treatment considerations differ in the elderly due to changes in renal and hepatic function, life expectancy, and various other clinical and practical considerations. Objective: This article discusses geriatric considerations in the pharmacologic management of T2DM and reviews the potential clinical advantages and disadvantages of pharmacologic agents currently available for the treatment of T2DM, including oral and injectable medications. Methods: A search of MEDLINE was conducted for articles published in English between January 1966 and September 2009 using the terms type 2 diabetes mellitus, elderly, geriatric, treatment, insulin, metformin, sulfonylurea, thiazolidinedione, α-glucosidase inhibitor, meglitinide, DPP-4 inhibitor, colesevelam, exenatide, and pramlintide. Meta-analyses, randomized controlled trials of pharmacologic treatment, and evidence-based reviews and/or expert opinions regarding the treatment of T2DM in the elderly were selected for review. Results: In overweight patients, metformin has been associated with reductions in risk for all-cause mortality and stroke compared with insulin and sulfonylureas. Older patients who are frail, anorexic, or underweight and those with congestive heart failure (CHF), renal or hepatic insufficiency, or dehydration may not be appropriate candidates for metformin therapy. The substantial risk of hypoglycemia with insulin secretagogues is increased by 36% in the elderly compared with younger adults; however, this risk is counterbalanced by the extensive clinical experience with these agents in the geriatric population. Thiazolidinediones should generally be avoided in patients with CHF and are absolutely contraindicated in patients with class II–IV heart failure. They have been associated with peripheral edema, as well as with decreases in bone mineral density in women. There is limited information on the use of dipeptidyl peptidase-4 inhibitors in the elderly, although dose adjustment is required in patients with renal compromise. In practice, substantial gastrointestinal adverse effects limit the use of α-glucosidase inhibitors in older patients. Colesevelam is associated with numerous drug interactions and can cause new or worsening constipation. There are limited data on the use of exenatide in the elderly. It may be beneficial in older patients with limited mobility who could benefit from weight loss, whereas it may not be a good option for frail, underweight adults. Use of exenatide is not recommended in patients with a creatinine clearance <30 mL/min. Given the increased monitoring required to avoid hypoglycemic events with pramlintide, this agent should be used with caution in older adults, particularly the frail elderly. Most patients with T2DM eventually require insulin; however, due to the risk of hypoglycemia and related morbidity, careful use of insulin is warranted in the geriatric population. Conclusions: Overall, there is a scarcity of data regarding the use of pharmacologic agents in older adults with T2DM, and clinical guidance is largely based on data obtained from younger populations. The selection of appropriate drug regimens for these patients remains challenging.

Asymptomatic hyperglycaemia and early atherosclerotic changes

Ultrasonographic scanning of carotid arteries allows non-invasive detection of atherosclerotic changes. This technique has been used to investigate changes in the thickness of the intimal plus medial (IM) complex, in patients with type 2 diabetes, type 1 diabetes and those in the pre-diabetic state of impaired glucose tolerance (IGT). IM thickness (IMT) increases with age, but this process was found to be considerably accelerated in patients with type 2 diabetes. In addition, IMT was significantly greater in patients with cerebral lacunar infarctions, and in those with detectable coronary artery stenosis. A study in patients with type 1 diabetes found that IMT correlates with duration of diabetes as well as age. The correlation with duration of diabetes suggests that hyperglycaemia contributes to the progression of atherosclerosis. IMT was also found to be increased in individuals with hyperinsulinaemic IGT, compared with control individuals with normal glucose tolerance. These results suggest that even relatively small increases in postprandial blood glucose levels can lead to increases in IMT and, hence, increased risk of cardiovascular disease. Further analysis revealed a correlation between hyperinsulinaemia (i.e. insulin resistance) and increased IMT. These results provide a clear rationale for the therapeutic use of α-glucosidase inhibitors, such as acarbose, which attenuate postprandial hyperglycaemia-induced hyperinsulinaemia.