Remission of diabetic nephropathy in type 2 diabetic Asian population: role of tight glucose and blood pressure control.

BACKGROUND: Asian has higher prevalence of diabetic nephropathy (DN) and end-stage renal disease when compared to Caucasian. No study to date has evaluated whether multifactorial intervention was associated with remission of microalbuminuria in type 2 diabetic Asian population. We evaluated the effect of tightly controlling multiple factors on the remission of DN in type 2 diabetic Chinese with microalbuminuria. MATERIALS AND METHODS: A longitudinal cohort study was collected 587 type 2 diabetic patients with microalbuminuria. Cohort members received intensified treatment to meet the following ADA recommended goals: HbA1c <7%, systolic blood pressure (SBP) <130mmHg, diastolic blood pressure <80 mmHg, low-density lipoprotein cholesterol <100mgdL(-1) , triglyceride < 150mgdL(-1) , high-density lipoprotein cholesterol >40mgdL(-1) for men and >50mgdL(-1) for women. Remission of microalbuminuria was defined as shift of albumin-creatinine ratio from mircoalbuminuria to normoalbuminuria. RESULTS: During the 4·5-year period, 210 (35·8%) patients achieved remission to normoalbuminuria. A significant association was found between the achievement of ADA goals, including HbA1c < 7% [hazard ratio (HR)=1·345; 95% confidence interval (CI), 1·010-1·792; P=0·04] and SBP <130mmHg (HR, 1·516; 95% CI, 1·100-2·089; P=0·01) and remission of microalbuminuria. The intensive SBP control (<120mmHg) was significantly associated with remission of microalbuminuria (HR, 2·076; 95% CI, 1·347-3·198; P<0·001). CONCLUSIONS: The remission of DN could be achieved under multifactorial intervention. Therapeutic focus on remission by tight glycemic and blood pressure control should be considered in Asian population with diabetes and microalbuminuria.

Significant correlation between left ventricular systolic and diastolic dysfunction and decreased glomerular filtration rate.

Cardiac dysfunction portends a poor prognosis in renal failure and vice versa. Functional abnormalities of heart in patients with renal insufficiency were frequently noted. The aim of this study is to assess the relationship between left ventricular systolic and diastolic function and renal function in patients with various degrees of renal function. This cross-sectional study included 167 patients from our Outpatient Department of Internal Medicine. Left ventricular systolic and diastolic functions were assessed by echocardiography. Clinical and echocardiographic parameters were compared and analyzed. The prevalence of left ventricular ejection fraction (LVEF) <50% was 31.7% and the average value of the ratio of peak early transmitral filling wave velocity (E) to early diastolic velocity of lateral mitral annulus (Ea) was 11.4 ± 6.2. After the multivariate analysis, low systolic blood pressure, rapid heart rate, low albumin, and low estimated glomerular filtration rate (eGFR) (odds ratio = 0.957; 95% confidence interval = 0.929-0.986; p = 0.004) levels were associated with LVEF < 50%. Besides, old age, low albumin, low eGFR (ß = -0.172; p = 0.043), and high uric acid levels were associated with high E/Ea. Our findings show a significant correlation between LVEF < 50% and high E/Ea and decreased eGFR.

The dawn phenomenon in type 2 diabetes: its association with glucose excursions and changes after oral glucose-lowering drugs.

BACKGROUND: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). METHODS: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. RESULTS: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [ß coefficient 0.199, 95% confidence interval (CI) 0.074-0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7-28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6-34.6 ± 17.0 mg/dl, p = 0.776). CONCLUSION: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

GLUCOSE CHANGES IN A PATIENT WITH INSULIN AUTOIMMUNE SYNDROME DEMONSTRATED BY CONTINUOUS GLUCOSE MONITORING.

OBJECTIVE: Insulin autoimmune syndrome (IAS) is an unusual cause of hypoglycemia in individuals without underlying diseases. Continuous glucose monitoring (CGM) has rarely been applied for IAS. We present a case of IAS with available 6-day CGM data. METHODS: A 61-year-old Taiwanese man was admitted because of impaired consciousness while driving, caused by a low blood glucose level of 30 mg/dL. He regained consciousness fully after parenteral glucose administration. RESULTS: During the prolonged fasting test, his C-peptide and insulin levels were respectively 11 ng/mL and 169.34 µIU/mL when plasma glucose was 41 mg/dL. Abdominal magnetic resonance imaging did not show any pancreatic abnormality. His 6-day CGM data revealed fasting hypoglycemia, several instances of postprandial hyperglycemia, and low blood glucose levels before lunch and dinner. Additional diagnostic findings included elevated anti-insulin antibody of 78.2%, thyrotoxicosis due to Graves disease, and gastric ulcer. He was discharged home on prednisolone at 5 mg daily, methimazole at 10 mg daily, and esomeprazole at 40 mg daily. Hypoglycemia and impairment of consciousness did not recur throughout the subsequent year-long follow up. CONCLUSION: We proposed a novel approach using CGM coupled with measurements of plasma insulin, C-peptide, and anti-insulin antibodies as the initial investigation for hypoglycemia in non-diabetic subjects. These relatively inexpensive tests may lead to earlier detection of IAS and thus render hospital admission and more costly explorations unnecessary.

Effect of diabetes mellitus on risk of latent TB infection in a high TB incidence area: a community-based study in Taiwan.

OBJECTIVE: To investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas. DESIGN: Community-based comparison study. SETTING: Outpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants. PARTICIPANTS: A total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES: The interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis. RESULTS: Diabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95% CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95% CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95% CI 1.03 to 1.55) and history of TB (aOR=2.08; 95% CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95% CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI. CONCLUSION: There was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.

Metabolic control with insulin pump therapy: preliminary experience.

BACKGROUND: The benefits of insulin pump therapy on the metabolic control of both type 1 and type 2 diabetes have been reported. Such reports have prompted our interest to investigate the long-term metabolic effects of insulin pump therapy at our institution. METHODS: We retrospectively analyzed the management of type 1 and type 2 diabetic patients who began extended insulin pump therapy at Changhua Christian Hospital between November 2004 and October 2007. One-way ANOVA and post hoc analysis were used to compare baseline glycosylated hemoglobin (HbA1C) values with subsequent values. RESULTS: We studied 12 patients who were on continuous subcutaneous insulin infusion (CSII) therapy at the time of data collection. Mean duration of CSII therapy was 2.3 years. A reduction in HbA1C was found after administering CSII, which was sustained after 1, 2 and 3 years of therapy (7.0%, 6.7% and 6.6%, respectively), with statistical significance (p<0.05). No incidence of severe hypoglycemia or diabetic ketoacidosis occurred during the treatment period. CONCLUSION: Our preliminary experience demonstrated the effectiveness of insulin pump therapy for both type 1 and type 2 diabetic patients. The reduction in their HbA1C values was both statistically and clinically significant. This treatment should be considered for patients poorly controlled by subcutaneous insulin injection therapy.

Diabetes mellitus increased all-cause mortality rate among newly-diagnosed tuberculosis patients in an Asian population: A nationwide population-based study.

AIMS: To investigate the effect of diabetes mellitus (DM) on all-cause mortality among patients with newly-diagnosed tuberculosis (TB) in an Asian population. We also identified risk factors for mortality in these patients. METHODS: The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals and 1627 TB mortality cases in the period of 2000-2010. The mortality data were divided into a DM group and a non-DM group. We measured the incidence density of mortality and identified the risk factors of mortality. RESULTS: The all-cause mortality of newly-diagnosed TB patients progressively increased with an average rate of 16.5% during 2000-2010. DM is an independent risk factor for all-cause mortality with HRs 1.17-1.27 by various models. TB patients with ages above 75years had the highest risk of mortality (HR=11.93) compared with those under 45 years. TB patients with heart failure, peripheral vascular disease, ischemic heart disease, cerebral vascular disease, hypertension, chronic kidney disease, pulmonary disease, liver disease, cancer, peptic ulcer disease, gout, and autoimmune disease had higher mortality compared to those without the aforementioned factors. CONCLUSIONS: The one-year all-cause mortality after TB diagnosis was high among TB patients in Taiwan and it tended to increase in the past decade. While treating these newly-diagnosed TB patients, it is crucial to detect the factors predisposing to death, such as old age, male gender, certain kinds of aforementioned factors and diabetes.

Glycemic excursions are positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy.

BACKGROUND: The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). METHODS: Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100. RESULTS: Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (ß = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P < 0.05 for all models). CONCLUSIONS: In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D.

Association between serum uric acid level and components of the metabolic syndrome.

BACKGROUND: Serum uric acid (UA) level has been suggested to be associated with factors that contribute to the metabolic syndrome. However, the association between metabolic syndrome and UA has not been elucidated. We sought to determine the association between serum UA level and the number of components that contribute to the metabolic syndrome, and which component was associated most with higher serum UA level. METHODS: A consecutive sample was taken of the health examinations of all hospital staff who were assessed between January 2004 and December 2004 in a medical center. A total of 3,065 subjects aged 18 to 81 years (635 males, 2,430 females) participated. Blood tests and all physical variables were examined using standard methods. Subjects were divided into 5 groups according to their possession of 0, 1, 2, 3 or > or = 4 components of the metabolic syndrome. The differences in all variables between groups were analyzed by ANOVA. The relationship between serum UA level and the number of metabolic components was determined by linear regression analysis. The contribution to elevated UA of possessing different risk factors was determined by a multivariate linear regression model. RESULTS: Mean serum UA level increased as the number of metabolic factors increased. Serum UA level was higher in subjects with abnormal triglyceride (TG), waist circumference, high-density lipoprotein cholesterol (HDL-C) level and blood pressure (BP),with mean increases in UA level of 22.8, 21.4, 14.4 and 9.4 micromol/L, respectively (p < or = 0.001), compared to subjects with normal levels. After controlling for body mass index, abnormal TG, HDL-C and BP continued to account, in order of influence, for elevated UA. CONCLUSION: Serum UA level was elevated significantly as the number of metabolic components increased. Abnormal TG had the most influence on serum UA. A prospective study is warranted to determine if the prevention or treatment of hyperuricemia affects the development of metabolic syndrome.

Characteristics predicting dyslipidemia in drug-naïve type 2 diabetes patients.

BACKGROUND: Plasma lipid concentrations are related to a variety of attributes in obese subjects, but these relationships have not been extensively examined in type 2 diabetes patients. METHODS: A cross-sectional survey was conducted on type 2 diabetes patients who had never been treated with antihypertensives, lipid-lowering agents, and oral antidiabetic drugs other than sulfonylureas. Statistical analysis was performed to search for the correlation between lipid profiles and various parameters. RESULTS: Among diabetic men, the plasma triglyceride (TG) level was positively correlated with the waist-to-hip ratio (WHR) and alcohol consumption, whereas high-density lipoprotein cholesterol (HDL-C) was negatively correlated with age and body mass index (BMI). Obese persons and alcohol drinkers were more likely to need pharmacologic treatment for dyslipidemia. Among diabetic women, the plasma TG level was positively correlated with WHR and the duration of diabetes since diagnosis, while HDL-C was negatively correlated with WHR and BMI. The necessity of treatment for dyslipidemia increased with the duration of diabetes. CONCLUSION: We recommend a more intensive monitoring of lipid levels in drug-naive diabetic patients who possess the characteristics of alcohol consumption or older age (men), long duration of diabetes (women), and higher BMI or WHR (both genders).

High diabetes mellitus prevalence with increasing trend among newly-diagnosed tuberculosis patients in an Asian population: A nationwide population-based study.

AIMS: Our aims were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated factors in an Asian population. METHODS: The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals in the period of 2000-2010. The data were divided into a DM group and a non-DM group. We measured the prevalence and the associated comorbidities of DM. RESULTS: During 2000-2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55-64 years had the highest association of DM (OR=3.53) compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were more likely to associate with DM (ORs=1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. CONCLUSIONS: The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.

Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes.

AIM: The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). METHODS: Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. RESULTS: A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (ß coefficient 0.345, p=0.036) or acarbose (ß coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). CONCLUSIONS: Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Synchronous parathyroid and papillary thyroid carcinoma.

Concomitant thyroid disease is not unusual among patients with primary hyperparathyroidism. However, the simultaneous occurrence of parathyroid and thyroid carcinoma is extremely rare. We report a 38-year-old man with primary hyperparathyroidism who presented with osteitis fibrosa cystica complicated with pathologic femoral neck fracture. Preoperative investigation for exclusion of multiple endocrine neoplasia did not find evidence of medullary thyroid carcinoma or pheochromocytoma, but imaging studies revealed the presence of nodules in the right lobe and a parathyroid lesion over the left inferior pole of the thyroid gland. Total thyroidectomy, left parathyroidectomy, and bipolar hemiarthroplasty of the left hip were then performed simultaneously. The resected specimens were pathologically identified as papillary thyroid carcinoma and parathyroid carcinoma, respectively. After the operation, 131I ablation therapy was administered at a dose of 120 mCi. Additional doses of 30 mCi were given yearly as serum thyroglobulin level became elevated. Serum calcium level remained normal during yearly follow-up. Although parathyroid carcinoma is an uncommon cause of parathyroid hormone-dependent hypercalcemia, it should nonetheless be given due consideration because its surgical approach differs from that of parathyroid adenoma. As the coexistence of parathyroid and non-medullary thyroid carcinoma has previously been reported, the possibility of both malignancies must also be considered in the setting of primary hyperparathyroidism with thyroid nodules. If confirmed with preoperative parathyroid scintigraphic and other laboratory studies, an optimal outcome may be achieved with complete resection of both tumors at the time of initial operation, followed by adjunctive therapy.

A workable model for the management of hyperglycemia in non-critically ill patients in an Asian population.

OBJECTIVE: The clinical efficacy of applying a western model for managing hyperglycemia in hospitalized patients in Asia has not been studied. METHODS: For this observational case-control study, we divided six medical wards into two groups, an intervention group and a control group. The intervention group, consisting three medical wards on the same floor, received care under a computer-assisted consulting model in which special care was automatically indicated for patients who had two successive high glucose measurements in 1 day. The control group, consisting of another three medical wards distributed on different floors, received regular care. Outcome measures were baseline and post-intervention patient-day weighted mean glucose, percentage of patient-day weighted glucose ≥180 mg/dL, proportion of glucose level 100-180 mg/dL, and prevalence of inpatient hyperglycemia (>180 mg/dL) and hypoglycemia (individual measurement <70 mg/dL and patient-day with any measurement <70 mg/dL). RESULTS: At baseline, the patient-day weighted mean glucose level was 181.6 mg/dL. All parameters were comparable between the intervention and control groups with the exception of prevalence of hypoglycemia, which was found to be higher in the intervention group. After intervention, patient-day weighted mean glucose levels for intervention and control groups were 169.9 mg/dL and 176.7 mg/dL, respectively (p < 0.001). The intervention group had a reduction in hypoglycemia and the control group an increase. CONCLUSION: This computer-assisted consulting model was found to be potentially very workable for the management of inpatient hyperglycemia in hospitals with high patient volumes in Asia.

The Association Between Body Mass Index and All-Cause Mortality in Patients With Type 2 Diabetes Mellitus: A 5.5-Year Prospective Analysis.

Abundances of study in different population have noted that obese cardiovascular disease (CVD) patients have a better prognosis than leaner patients, which refer to the phenomenon of obesity paradox. However, data on the association between body mass index (BMI) and mortality among Asian patients are limited, especially in patients with type 2 diabetes mellitus (T2DM). We investigate the association between BMI and all-cause mortality in Taiwanese patients with T2DM to define the optimal body weight for health.We conducted a longitudinal cohort study of 2161 T2DM patients with a mean follow-up period of 66.7 ±â€Š7.5 months. Using Cox regression models, BMI was related to the risk of all-cause mortality after adjusting all confounding factors.A U-shaped association between BMI and all-cause mortality was observed among all participants. Those with BMIs <22.5 kg/m had a significantly elevated all-cause mortality as compared with those with BMIs 22.5 to 25.0 kg/m, (BMIs 17.5-20.0 kg/m: hazard ratio 1.989, P < 0.001; BMIs 20.0-22.5 kg/m: hazard ratio 1.286, P = 0.02), as did those with BMIs >30.0 kg/m (BMIs 30.0-32.5 kg/m: hazard ratio 1.670, P < 0.001; BMIs 32.5-35.0 kg/m: hazard ratio, 2.632, P < 0.001). This U-shaped association remained when we examined the data by sex, age, smoking, and kidney function.Our study found a U-shaped relationship between all-cause mortality and BMI in Asian patients with T2DM, irrespective of age, sex, smoking, and kidney function. BMI <30 kg/m should be regarded as a potentially important target in the weight management of T2DM.

Glycosylated hemoglobin level and number of oral antidiabetic drugs predict whether or not glycemic target is achieved in insulin-requiring type 2 diabetes.

AIMS: Factors predicting success (glycosylated hemoglobin (A1C)<7%) with insulin therapy in patients with insulin-requiring type 2 diabetes need to be identified. METHODS: A retrospective, multi-center, observational study was conducted for outpatients with oral antidiabetic drug (OAD)-treated type 2 diabetes whose A1C levels remained above 7%. Patients were begun on basal insulin between January 2005 and December 2006. Biochemical variables and demographic data were collected before and after 52 weeks of insulin therapy. RESULTS: A total of 565 patients (age, 60.4±11.9 years; A1C levels, 10.11 ±1.81%; duration of diabetes, 11.5±6.8 years) were studied. By study end, 63 patients (11.2%) had achieved the glycemic goal (A1C<7%). The glycemic goal attainment rate was only 9.1% in patients with A1C>8.8% and who were taking >2 OADs at baseline. The highest rate (32.7%) of successful glycemic control was observed in the group of patients with A1C ≤ 8.8% and who used ≤ 2 OADs at baseline. CONCLUSIONS: Insulin-naïve diabetic patients with A1C>8.8%, especially those who are taking >2 OADs, have small chance to achieve good glycemic control with adding only basal insulin therapy.

Post-meal ß-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose.

BACKGROUND: This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. METHODS: Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-ß, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). RESULTS: At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p < 0.001), and from 8.2 ± 0.8% to 7.5 ± 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 ± 24.2 to 74.9 ± 41.9 (p < 0.05), and in the acarbose group, from 62.5 ± 31.4 to 91.7 ± 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA1c and DI120 independently predicted reduction of HbA1c as well as final HbA1c after combination therapy. CONCLUSIONS: In patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA1c reduction and improvement of ß-cell function. Subjects with greater baseline ß-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose. TRIAL REGISTRATION: This study was registered in the ClinicalTrials.gov with registration number of NCT00417729.

Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.

BACKGROUND: Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM. OBJECTIVE: This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin. METHODS: T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. ß-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded. RESULTS: A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. ß-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). CONCLUSIONS: In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.

The beneficial effect of α-glucosidase inhibitor on glucose variability compared with sulfonylurea in Taiwanese type 2 diabetic patients inadequately controlled with metformin: preliminary data.

AIMS: Although sulfonylurea added to metformin is the first oral drug combination regimen for patients with type 2 diabetes recommended by the American Diabetes Association/European Association for the Study of Diabetes consensus statement, it does not allow for individualizing and optimizing therapy with respect to sustaining glycemic control and the reduction of glucose variability. We therefore sought to investigate acarbose as an alternative to glibenclamide in combination with metformin and compare the effects on metabolic control and glucose variability. METHODS: Type 2 diabetic patients 30-70 years of age with glycosylated hemoglobin 7.0%-11.0% while treated with one or two oral antidiabetic drugs were successively enrolled. After 8 weeks of run-in with metformin 500 mg thrice daily, either acarbose 50 mg or glibenclamide 2.5 mg three times daily was randomly added on and force titrated to acarbose 100 mg or glibenclamide 5.0 mg three times daily for the subsequent 16 weeks. Demographic data, biochemical data and continuous glucose monitoring system data were recorded upon randomization and at the end of the study. Various parameters that measure glucose variability were derived from the continuous glucose monitoring system data. RESULTS: Of the 51 type 2 diabetes patients enrolled, data from 40 subjects, 20 in each group, were analyzed after excluding those unqualified information. Both drug combinations improved glycemic control. Glucose variability, expressed as mean amplitude of glycemic excursion or continuous overall net glycemic action and mean of daily differences, decreased significantly (all P<.05) after the addition of acarbose but not glibenclamide. The acarbose-metformin combination has the additional benefits of weight reduction and shorter durations of hyperglycemia compared with metformin monotherapy. CONCLUSIONS: This study suggests that both intraday and interday glucose variability are more effectively reduced by the acarbose-metformin combination than by the glibenclamide-metformin combination, while both combinations reduce the overall glucose level equally.