Effects of sulfonylurea as initial treatment on testosterone of middle‐aged men with type 2 diabetes: A 16‐week,pilot study

Aims/Introduction

To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes.

Materials and Methods

As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study. After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks. Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group.

Results

Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index. Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values. Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline.

Conclusions

It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.     

Insulin combined with Chinese medicine improves glycemic outcome through multiple pathways in patients with type 2 diabetes mellitus

Introduction/Aims

Insufficient insulin secretion or inefficient insulin response are responsible for the clinical outcome of type 2 diabetes mellitus. Administration of insulin alone is prone to cause secondary effects, resulting in an unsatisfactory outcome. Shen-Qi-Formula (SQF), a well-known Chinese medicinal formula, has been used for diabetic treatment for a long time. The present study was designed to investigate whether SQF in combination with insulin improved the clinical outcome of type 2 diabetes mellitus, and what mechanisms were possibly involved in the treatment.

Materials and Methods

A total of 219 patients were included in the study. Of these, 110 patients were treated with insulin monotherapy, and 109 with the combination therapy of SQF and insulin. Before and after 12-week treatment, the fasting blood glucose, postprandial blood glucose, β-cell function, insulin resistance and blood lipids were measured.

Results

The 12 weeks of SQF treatment in combination with insulin significantly decreased the fasting and postprandial blood glucose levels. Insulin secretion was not increased after the treatment, but β-cell function and insulin resistance were obviously improved. Furthermore, 12 weeks of treatment with SQF and insulin improved the levels of glucagon-like peptide-1, oxidative stress, blood lipids, coagulation function and bodyweight.

Conclusion

The results from our study showed that the combination therapy of SQF and insulin significantly improved the clinical outcome of type 2 diabetes mellitus compared with insulin monotherapy. The mechanism of improvement was possibly involved in the multiple pathways.     

Association between sugar‐sweetened beverages and type 2 diabetes: A meta‐analysis

Aims/Introduction

Many studies have been carried out to examine the association between sugar-sweetened beverages and the incident of type 2 diabetes, but results are mixed. The aim of the present study was to estimate the association between sugar-sweetened beverage intake and the risk of type 2 diabetes.

Materials and Methods

PubMed, Springer Link and Elsevier databases were searched up to July 2014. Prospective studies published on the association between sugar-sweetened beverage intake and the risk of type 2 diabetes were included. The pooled relative risks (RRs) and 95% confidence intervals (CIs) for highest versus lowest category of sugar-sweetened beverages were estimated using a random-effects model.

Results

The pooled effect estimate of sugar-sweetened beverage intake was 1.30 (95% confidence interval [CI] 1.21–1.39) for type 2 diabetes; stratified by geographic region of the studies, the pooled effect estimates were 1.34 (95% CI 0.74–2.43), 1.30 (95% CI 1.20–1.40), 1.29 (95% CI 1.09–1.53) in Asia, the USA and Europe,respectively; the pooled effect estimates were 1.26 (95% CI 1.16–1.36) with adjusting body mass index and 1.38 (95% CI 1.23–1.56) without adjusting body mass index.

Conclusions

Our findings suggested that sugar-sweetened beverage intake was associated with an increased risk of type 2 diabetes, and the association was attenuated by adjustment for body mass index. Specifically, the associations were also found to be significantly positive in the USA and Europe.     

Type 1 diabetes patients have lower strength in femoral bone determined by quantitative computed tomography: A cross‐sectional study

Aims/Introduction

Previous studies have reported osteoporosis measured by dual-energy X-ray absorptiometry in younger patients with type 1 diabetes. Limitations of 2-D imaging, however, limit the precision of dual-energy X-ray absorptiometry for the measurement of bone mineral density and bone strength.

Materials and Methods

Three-dimensional quantitative computed tomography was used to calculate volumetric-bone mineral density (vBMD) and strength in femoral bone subfractions. A total of 17 male type 1 diabetes patients and 18 sex-matched healthy controls aged from 18 to 49 years were investigated in the present cross-sectional study. Patients with overt nephropathy were excluded.

Results

Type 1 diabetes patients had significantly lower cortical vBMD in the femoral neck, and significantly lower total vBMD, cortical thickness and cortical cross-sectional area (cortical CSA) in the intertrochanter. Bone strength estimated by the buckling ratio (an index of cortical instability) of the intertrochanter was significantly higher in type 1 diabetes patients. The following serum bone markers were comparable between the two groups: bone-specific alkaline phosphatase, N-terminal propeptide of type 1 procollagen, osteocalcin, pentosidine and homocysteine. Serum insulin-like growth factor-1 values were significantly lower in the type 1 diabetes patients than in controls. Serum insulin-like growth factor-1values were positively correlated with serum bone formation markers, and the total vBMD of the femoral neck and lumbar spine in type 1 diabetes patients.

Conclusions

The present study is the first investigation by quantitative computed tomography measurement to show cortical instability and lower vBMD in the intertrochanter of young and middle-aged type 1 diabetes patients. Low insulin-like growth factor-1 might be a causative factor for osteoporosis in type 1 diabetes.     

Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: A multinational, 24‐week,randomized, clinical trial

Aims/Introduction

Asian patients represent a large portion of the global population with type 2 diabetes mellitus, but are underrepresented in trials of glucose-lowering therapies. The present randomized, phase III, placebo-controlled, double-blind, 24-week study evaluated the dipeptidyl peptidase-4 inhibitor, linagliptin, as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus.

Materials and Methods

Patients who were treatment naïve or had been treated with one oral antidiabetes drug were randomized to either linagliptin 5 mg daily or a placebo after washout. The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks.

Results

A total of 300 Asian (87% Chinese) patients with type 2 diabetes mellitus were randomized to linagliptin or placebo at a 2:1 ratio. After 24 weeks of treatment, adjusted mean (standard error) glycated hemoglobin decreased by a placebo-corrected −0.50 ± 0.11 (P < 0.0001). In patients with baseline glycated hemoglobin ≥8.5%, the placebo-corrected decrease in glycated hemoglobin was −0.91 ± 0.20% (P < 0.0001). Adverse events occurred in 28.0 and 28.3% of linagliptin and placebo patients, respectively, but few were drug-related (3.0 and 2.0%, respectively). Hypoglycemia was reported by one linagliptin patient and no placebo patients. Treatment with linagliptin was weight neutral.

Conclusions

In Asian patients with inadequately controlled type 2 diabetes mellitus, linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks.     

Effects of a sodium glucose co‐transporter 2 selective inhibitor,ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Aims/Introduction

To assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.

Materials and Methods

We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.

Results

Continuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.

Conclusions

The ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.     

Randomized,placebo‐controlled,double‐blind glycemic control trial of novel sodium‐dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

In the present dose–response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium‐dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus.

Materials and Methods

A total of 361 patients from 39 Japanese centers were randomized to receive either once‐daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks.

Results

All ipragliflozin‐treated groups had clinically significant, dose‐dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo‐treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were −0.61%, −0.97%, −1.29%, and −1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non‐obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose‐dependently decreased among ipragliflozin‐treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups.

Conclusions

Once‐daily administration of ipragliflozin was dose‐dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non‐obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well‐tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868).     

Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta‐analysis

Aims/Introduction

Recently, the use of rosiglitazone has been limited or withdrawn from the market as a result of cardiovascular risk. However, theoretically adding rosiglitazone to insulin could help insulin to decrease the glucose level. The present meta-analysis was designed to investigate the effect and safety of adding rosiglitazone to insulin therapy in type 2 diabetes.

Materials and Methods

We searched published and unpublished databases through to March 2012. Randomized controlled trials (RCTs) comparing rosiglitazone in combination with insulin (RSG + INS) vs insulin alone (INS) in type 2 diabetes with outcomes including glycated hemoglobin levels, insulin dose, lipid parameters, blood pressure, edema and cardiovascular adverse events were selected.

Results

Nine RCTs with durations of 24–26 weeks involving 1,916 patients were included. The RSG + INS group showed significantly decreased glycated hemoglobin levels by 0.89% (P < 0.00001) with an 8.48-U reduction in daily insulin dose (P <0.00001). However, the risks of hypoglycemia and edema were more frequent in the RSG+INS group (P < 0.0001; P = 0.03, respectively). Total cholesterol level was significantly increased in the RSG+INS group (P < 0.00001), but none of the high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol or triglyceride levels were significantly different between groups. There were no significant differences between groups with regard to the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.

Conclusions

Rosiglitazone could help type 2 diabetes patients with poorly controlled glucose with insulin therapy to decrease glucose levels and reduce their daily insulin dose, but at the cost of increased total cholesterol level, hypoglycemia and edema risk. Compared with insulin therapy, adding rosiglitazone to insulin did not increase the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.     

Adherence to self‐care behavior and glycemic effects using structured education

Aims/Introduction

The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ (CM™) vs usual care in a university-based hospital primary care clinic.

Materials and Methods

This was a randomized, pragmatic clinical trial. Patients with type 2 diabetes were randomly assigned to structured education or usual care groups. The primary outcome was the difference in the mean change of glycated hemoglobin (HbA1c) from baseline to 12 months. Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes.

Results

A total of 245 patients were randomly assigned to two groups (CM™ group n = 121; usual care group, n = 116). The absolute reduction of HbA1c was significantly greater in the CM™ group at 3 and 6 months (Δ = −0.59% and Δ = −1.13%, P < 0.01), but the difference was no longer statistically significant at 9 and 12 months (Δ = −0.43% and Δ = −0.49%), based on an intention-to-treat analysis. A per-protocol analysis showed the significant change was maintained at 12 months (Δ = −0.67%). In the intervention group, greater percentages of patients achieved their American Association of Diabetes Educators Self-Care Behaviours™ framework (AADE7) behavioral goals at 3 months, in particular being active, problem-solving, reducing risk and health coping.

Conclusions

In type 2 diabetic patients with suboptimally controlled glucose, there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CM™ education program compared with outcomes achieved in patients receiving usual care.     

Role of elevated serum uric acid levels at the onset of overt nephropathy in the risk for renal function decline in patients with type 2 diabetes

Aims/Introduction

Despite the use of intensive therapies, declining renal function is often observed during the overt nephropathy stage of type 2 diabetes. We aimed at investigating the role of serum uric acid (SUA) levels at the onset of overt nephropathy in the risk of renal function decline in type 2 diabetes patients.

Materials and Methods

The present cohort study included 290 type 2 diabetes patients who were followed from the onset of overt nephropathy. The relationship between SUA and declining renal function was assessed using Cox regression models after adjusting for known risk factors.

Results

Over a median 4.8-year follow-up period, 85 patients (4.9/100 person-years) showed serum creatinine (Cr) doubling with a total cumulative incidence of 71.9% at 20 years of follow up. The highest SUA tertile resulted in significantly a higher incidence (7.7/100 person-years) and cumulative incidence at 20 years (85.7%) than the middle (3.9/100 person-years, 54.2%) and lowest (3.0/100 person-years, 55.5%) tertiles. The univariate Cox hazard model resulted in significant risks for Cr doubling related to female sex, short diabetes duration, smoking and elevated levels of low-density lipoprotein cholesterol (LDL-c), glycated hemoglobin and SUA tertiles. SUA tertiles remained statistically significant in the multivariate model (highest vs lowest hazard ratio 2.68, 95% confidence interval 1.48−5.00, P = 0.0009).

Conclusions

Elevated SUA levels within the normal range (men >6.3 mg/dL, women >5.1) at the onset of overt nephropathy resulted in an increased risk for declining renal function in type 2 diabetes patients.     

Efficacy and safety of lixisenatide in Japanese patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin: Subanalysis of GetGoal‐S

Aims/Introduction

This was a subanalysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation (GetGoal-S) study – a 24-week, randomized, placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin.

Materials and Methods

In GetGoal-S, 127 Japanese patients received the once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo. The primary outcome was change in glycated hemoglobin.

Results

At week 24, lixisenatide significantly reduced mean glycated hemoglobin (least squares mean difference vs the placebo −1.1% [12 mmol/mol, P < 0.0001]), and significantly more lixisenatide patients reached glycated hemoglobin targets of <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) vs the placebo. Lixisenatide produced statistically significant reductions in 2-h postprandial plasma glucose (least squares mean difference vs the placebo −8.51 mmol/L, P < 0.0001) and glucose excursion vs the placebo, and significantly reduced fasting plasma glucose (least squares mean difference vs the placebo −0.65 mmol/L, P = 0.0454). Bodyweight decreased with both lixisenatide and the placebo (least squares mean change −1.12 kg for lixisenatide, −1.02 kg for placebo). The overall incidence of adverse events was similar for lixisenatide and the placebo (84.2 and 82.4%, respectively), the most frequent being gastrointestinal disorders (52.6% for lixisenatide vs 29.4% for placebo). The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo (17.1 and 9.8%, respectively), with no cases of severe symptomatic hypoglycemia in either group.

Conclusions

In the Japanese subpopulation of the GetGoal-S study, lixisenatide produced a significant and clinically relevant improvement in glycated hemoglobin, with a pronounced improvement in postprandial plasma glucose, and a good safety and tolerability profile.     

Simple risk score to detect rural Asian Indian (Bangladeshi) adults at high risk for type 2 diabetes

Aims/Introduction

To develop and evaluate a simple, non-invasive, diabetes risk score for detecting individuals at high risk for type 2 diabetes in rural Bangladesh.

Materials and Methods

Data from 2,293 randomly selected individuals aged ≥20 years from a cross-sectional study in a rural community of Bangladesh (2009 Chandra Rural Study) was used for model development. The validity of the model was assessed in another rural cross-sectional study (2009 Thakurgaon Rural Study). The logistic regression model used included age, sex, body mass index, waist-to-hip ratio and hypertension status to predict individuals who were at high risk for type 2 diabetes.

Results

On applying the developed model to both cohorts, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval 0.68–0.72) for the Chandra cohort and 0.71 (95% confidence interval 0.68–0.74) for the Thakurgaon cohort. The risk score of >9 was shown to have the optimal cut-point to detect diabetes. This score had a sensitivity of 62.4 and 75.7%, and specificity of 67.4 and 61.6% in the two cohorts, respectively. This risk score was shown to have improved sensitivity and specificity to detect type 2 diabetes cases compared with the Thai, Indian, Omani, UK, Dutch, Portuguese and Pakistani diabetes risk scores.

Conclusions

This simple, non-invasive risk score can be used to detect individuals at high risk for type 2 diabetes in rural Bangladesh. Subjects with a score of 9 or above (out of 15) should undergo an oral glucose tolerance test for definitive diagnosis of diabetes.     

The relationship between the frequency of self‐monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

Aims/Introduction

We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software.

Materials and Methods

We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients'' hemoglobin A1c (HbA1c) levels was analyzed using the χ²-test and linear regression analysis was carried out to clarify their relationship.

Results

The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group.

Conclusions

A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII.     

High‐normal urinary albumin‐to‐creatinine ratio is independently associated with metabolic syndrome in Chinese patients with type 2 diabetes mellitus: A cross‐sectional community‐based study

Aims/Introduction

Microalbuminuria is positively related to metabolic syndrome (MetS). Our aim was to investigate whether urinary albumin-to-creatinine ratio (UACR) within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes.

Materials and Methods

A total of 514 participants (206 males and 308 females; mean age 66 years) with UACR less than 3.5 mg/mmol were enrolled from two downtown areas of Shanghai. The participants were stratified into quartiles according to UACR levels. The prevalence of MetS was assessed and compared among the four groups by binary logistic regression.

Results

Compared with participants with UACRs in the first quartile, the other quartiles had a higher prevalence of MetS (65.9%, 74.4% and 81.3%, respectively, P = 0.001) after adjustment for sex and age. After adjusting for potential confounders, participants in the second to the fourth quartile group had a 1.36-, 1.84- and 2.73-fold risk of MetS, respectively, relative to those in the lowest quartile. Furthermore, UACR, whether as quartile groups or as a continuous variable, is an independent predictor of MetS after fully adjusting for other variables.

Conclusions

These results suggest that UACR even within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes mellitus.     

Morphological changes of the peripheral nerves evaluated by high‐resolution ultrasonography are associated with the severity of diabetic neuropathy,but not corneal nerve fiber pathology in patients with type 2 diabetes

Aims/Introduction

To evaluate the morphological changes of the median and posterior tibial nerve using high-resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients.

Materials and Methods

The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high-resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy.

Results

The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P < 0.05 to P < 0.001), and further increased relative to the severity of neuropathy (P < 0.0001). All morphological changes of both nerves were negatively associated with motor and sensory nerve conduction velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000-Hz current perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber pathology occurred before developing the neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor.

Conclusions

The morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology.     

Efficacy of glimepiride/metformin fixed‐dose combination vs metformin uptitration in type 2 diabetic patients inadequately controlled on low‐dose metformin monotherapy: A randomized,open label,parallel group,multicenter study in Korea

Aims/Introduction

To compare the efficacy and safety of early combination therapy with glimepiride/metformin to metformin uptitration in reducing glycated hemoglobin (HbA1c) levels in Korean type 2 diabetic patients inadequately controlled on low-dose metformin monotherapy.

Materials and Methods

In a randomized, open label, parallel group, multicenter study, 209 Korean type 2 diabetic patients (HbA1c 7.0–10.0%, on metformin 500–1,000 mg/day) received glimepiride/metformin fixed-dose combination (G/M FDC) or metformin uptitration treatment (Met UP). The primary end-point was the change in HbA1c from baseline to week 24.

Results

G/M FDC therapy provided significantly greater adjusted mean decreases vs Met UP therapy in HbA1c (−1.2 vs −0.8%, P < 0.0001), and fasting plasma glucose (−35.7 vs −18.6 mg/dL, P < 0.0001). A significantly greater proportion of patients with G/M FDC therapy achieved HbA1c < 7% (74.7 vs 46.6%, P < 0.0001) at the end of the study. More patients experienced hypoglycemia with G/M FDC therapy compared with Met UP therapy (41 vs 5.6%, P < 0.0001), but there was no serious hypoglycemia in any group. A modest increase in mean bodyweight occurred in the patients who were treated with G/M FDC therapy (1.0 kg), whereas a slight decrease was observed in the patients who were treated with Met UP therapy (−0.7 kg).

Conclusion

The present study showed that glimepiride/metformin fixed-dose combination therapy was more effective in glycemic control than metformin uptitration, and was well tolerated in type 2 diabetic patients inadequately controlled by low-dose metformin monotherapy in Korea. This trial was registered with ClinicalTrial.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00612144","term_id":"NCT00612144"}}NCT00612144).     

Association of cholesteryl ester transfer protein genotypes with paraoxonase‐1 activity,lipid profile and oxidative stress in type 2 diabetes mellitus: A study in San Luis,Argentina

Aims/Introduction

Diabetic dyslipidemia is common in type 2 diabetes. The TaqIB polymorphism in cholesteryl ester transfer protein (CETP; B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The aim of the present study was to assess associations of CETP genotypes with lipoprotein profile, oxidant/anti-oxidant status and the plasma activity of paraoxonase-1 (PON-1) in a population of diabetic patients living in San Luis, Argentina.

Materials and Methods

For oxidative stress status parameters, thiobarbituric acid-reactive substances (TBARS) and nitric oxide (NO) levels, and catalase and PON-1 activity were assessed in 40 patients with type 2 diabetes mellitus and 30 healthy participants. CETP polymorphism was analyzed by polymerase chain reaction-based methods.

Results

Type 2 diabetes mellitus had significantly higher concentrations of oxidative stress parameters: TBARS (P < 0.0001) and catalase activity (P < 0.0001). PON-1 activity and NO levels were significantly lower in diabetics (P = 0.0002 and P = 0.0008, respectively). The CETP genotypes distribution among study groups was not significantly different. The B2 carriers of the TaqIB CETP polymorphism are associated with higher high-density lipoprotein cholesterol levels and PON-1 activity in control and type 2 diabetes mellitus patients. Linear regression analysis showed that there was a significant and positive correlation between the changes of PON-1 activity and high-density lipoprotein cholesterol levels in non-B1B1 (B2 carriers) in controls (r = 0.83, P < 0.0001) and diabetic patients (r = 0.39, P = 0.0003).

Conclusions

The results of the current study show that type 2 diabetes mellitus is characterized by intense oxidative stress, and that the alterations observed in the lipoprotein profile and PON-1 activity might be related to the higher CETP activity in diabetic patients as a consequence of insulin resistance.     

Detection of CAPN10 copy number variation in Thai patients with type 2 diabetes by denaturing high performance liquid chromatography and real‐time quantitative polymerase chain reaction

Aims/Introduction

A combination of multiple genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Copy number variations (CNVs) are associated with complex human diseases. However, CNVs can cause genotype deviation from the Hardy–Weinberg equilibrium (HWE). A genetic case–control association study in 216 Thai diabetic patients and 192 non-diabetic controls found that, after excluding genotyping errors, genotype distribution of calpain 10 (CAPN10) SNP44 (rs2975760) deviated from HWE. Here, we aimed to detect CNV within the CAPN10 SNP44 region.

Materials and Methods

CNV within the CAPN10 SNP44 region was detected using denaturing high-performance liquid chromatography, and the results confirmed by real-time quantitative polymerase chain reaction with SYBR Green I.

Results

Both methods successfully identified CNV in the CAPN10 SNP44 region, obtaining concordant results. Correction of genotype calling based on the status of identified CNVs showed that the CAPN10 SNP44 genotype is in good agreement with HWE (P > 0.05). However, no association between CNV genotypes and risk of type 2 diabetes was observed.

Conclusions

Identified CNVs for CAPN10 SNP44 genotypes lead to deviation from HWE. Furthermore, both denaturing high-performance liquid chromatography and real-time quantitative polymerase chain reaction are useful for detecting CNVs.     

Comparison of three α‐glucosidase inhibitors for glycemic control and bodyweight reduction in Japanese patients with obese type 2 diabetes

Aims/Introduction

α‐Glucosidase inhibitors (αGIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three αGIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes.

Materials and Methods

Japanese patients (n = 81) with obese type 2 diabetes (body mass index [BMI] ≥25 kg/m²) were enrolled in this multicenter, open‐label study. The participants were randomized into the miglitol (n = 18), acarbose (n = 22), voglibose (n = 19) or control (n = 22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low‐density lipoprotein and high‐density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4 weeks for 12 weeks.

Results

In the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12 weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12 weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12 weeks in the miglitol (r = 0.759, P < 0.001) and voglibose groups (r = 0.667, P = 0.002). Serum lipid and adipocytokine levels were not altered in any groups.

Conclusions

αGIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type 2 diabetes. This study was registered with UMIN (no. UMIN000006465).     

Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post‐hoc analysis of a cross‐sectional study

Aims/Introduction

A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes.

Materials and Methods

The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production.

Results

Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome.

Conclusions

The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome.