A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes.

BACKGROUND: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. METHODS: From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled. We compared the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile at baseline and after 24 weeks of treatment. To compare lipid parameters between the two groups, we used the analysis of covariance (ANCOVA). RESULTS: A total of 184 patients completed follow-up (mean age: 53.1 ± 6.9 years, mean duration of diabetes: 7.1 ± 5.7 years). From baseline to 24 weeks, HDL-cholesterol (HDL-C) levels were increased by 0.5 (95% CI, -0.9 to 2.0) mg/dl with a DPP-4 inhibitor and by 5.1 (95% CI, 3.0 to 7.1) mg/dl with an SGLT2 inhibitor (p = 0.001). LDL-cholesterol (LDL-C) levels were reduced by 8.4 (95% CI, -14.0 to -2.8) mg/dl with a DPP-4 inhibitor, but increased by 1.3 (95% CI, -5.1 to 7.6) mg/dl with an SGLT2 inhibitor (p = 0.046). There was no significant difference in the mean hemoglobin A1c (8.3 ± 1.1 vs. 8.0 ± 0.9%, p = 0.110) and in the change of total cholesterol (TC) (p = 0.836), triglyceride (TG) (p = 0.867), apolipoprotein A (p = 0.726), apolipoprotein B (p = 0.660), and lipoprotein (a) (p = 0.991) between the DPP-4 inhibitor and the SGLT2 inhibitor. CONCLUSIONS: The SGLT2 inhibitor was associated with a significant increase in HDL-C and LDL-C after 24 weeks of SGLT2 inhibitor treatment in patients with type 2 diabetes compared with those with DPP-4 inhibitor treatment in this study. TRIAL REGISTRATION: This study was conducted by retrospective medical record review.

Elevated lipoprotein(a) levels predict cardiovascular disease in type 2 diabetes mellitus: a 10-year prospective cohort study.

BACKGROUND/AIMS: Elevated lipoprotein(a) (Lp[a]) level is known to be a risk factor for cardiovascular disease (CVD). However, the data that has been reported on the association between the Lp(a) level and CVD in type 2 diabetes has been limited and incoherent. The aim of this study was to investigate the relationship between the Lp(a) concentration and new onset CVD in type 2 diabetes. METHODS: From March 2003 to December 2004, patients with type 2 diabetes without a prior history of CVD were consecutively enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. Cox proportional hazards models were used to identify the associations between the Lp(a) and CVD after adjusting for confounding variables. RESULTS: Of the 1,183 patients who were enrolled, 833 participants were evaluated with a median follow-up time of 11.1 years. A total of 202 participants were diagnosed with CVD (24.2%). The median Lp(a) level for 1st and 4th quartile group was 5.4 (3.5 to 7.1) and 55.7 mg/dL (43.1 to 75.3). Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin and angiotensin converting enzyme inhibitors/angiotensin receptor blockers at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with serum Lp(a) level (hazard ratio, 1.92; 95% confidence interval [CI], 1.26 to 2.92; p < 0.001, comparing the 4th vs. 1st quartile of Lp[a]). CONCLUSIONS: Elevated Lp(a) level was an independent predictable risk factor for CVD in type 2 diabetes. Other cardiovascular risk factors should be treated more intensively in type 2 diabetic patients with high Lp(a) levels.

Baseline-Corrected QT (QTc) Interval Is Associated with Prolongation of QTc during Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM). METHODS: Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged. RESULTS: The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders. CONCLUSION: A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.

Clinical Course and Risk Factors of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus in Korea.

BACKGROUND: We investigated clinical course and risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales. RESULTS: Of the 759 patients, 523 patients (68.9%) completed the follow-up evaluation. During the follow-up period, 235 patients (44.9%) developed DR, and 32 patients (13.6%) progressed to severe nonproliferative DR (NPDR) or proliferative DR (PDR). The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c), and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P=0.005). CONCLUSION: This prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.

Diabetic Cardiovascular Autonomic Neuropathy Predicts Recurrent Cardiovascular Diseases in Patients with Type 2 Diabetes.

Cardiovascular autonomic neuropathy (CAN) is a risk factor for cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. This study evaluated the relationship between CAN and recurrent CVD in type 2 diabetes. A total of 206 patients with type 2 diabetes who had a history of CVD within 3 years of enrollment were consecutively recruited from January 2001 to December 2009 and followed-up until December 2015. Cardiovascular autonomic function tests were performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver and standing. We estimated the recurrence of CVD events during the follow-up period. A total of 159 (77.2%) of the 206 patients enrolled completed the follow up, and 78 (49.1%) patients had recurrent episodes of CVD, with an incidence rate of 75.6 per 1,000 patient-years. The mean age and diabetes duration were 62.5 ± 8.7 and 9.2 ± 6.9 years, respectively. Patients who developed recurrent CVD also exhibited hypertension (P = 0.004), diabetic nephropathy (P = 0.012), higher mean systolic blood pressure (P = 0.006), urinary albumin excretion (P = 0.015), and mean triglyceride level (P = 0.035) than did patients without recurrent CVD. Multivariable Cox hazard regression analysis revealed that definite CAN was significantly associated with an increased risk of recurrent CVD (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.39-6.60; P = 0.005). Definite CAN was an independent predictor for recurrent CVD in patients with type 2 diabetes who had a known prior CVD event.

Lipoprotein(a) predicts the development of diabetic retinopathy in people with type 2 diabetes mellitus.

BACKGROUND: Lipoprotein(a) [Lp(a)] has mainly been considered to be a predictor of the incidence of cardiovascular disease. In addition, previous studies have shown potential linkage between Lp(a) and diabetic microvascular complications. OBJECTIVES: We investigated the incidence and risk factors for the development of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: A total of 787 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists. The main outcome was new onset of DR. RESULTS: The median follow-up time was 11.1 years. Patients in the DR group had a longer duration of diabetes (P < .001), higher baseline HbA1c (P < .001), higher albuminuria level (P = .033), and higher level of Lp(a) (P = .005). After adjusting for sex, age, diabetes duration, presence of hypertension, renal function, LDL cholesterol, mean HbA1c, and medications, the development of DR was significantly associated with the serum Lp(a) level (HR 1.57, 95% confidence interval [1.11-2.24]; P = .012, comparing the 4th vs 1st quartile of Lp(a)). The patient group with the highest quartile range of Lp(a) and mean HbA1c levels ≥7.0% had an HR of 5.09 (95% confidence interval [2.63-9.84]; P < .001) for developing DR compared with patients with lower levels of both factors. CONCLUSIONS: In this prospective cohort study, we demonstrated that the DR was independently associated with the serum Lp(a) level in patients with type 2 diabetes.

Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes.

BACKGROUND: We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes. METHODS: The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis. RESULTS: Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use. CONCLUSION: We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

Cardiovascular Autonomic Dysfunction Predicts Diabetic Foot Ulcers in Patients With Type 2 Diabetes Without Diabetic Polyneuropathy.

We investigated the factors that might influence the development of diabetic foot ulcers (DFUs) in type 2 diabetes patients without diabetic polyneuropathy (DPN).From January 2000 to December 2005, a total of 595 patients who had type 2 diabetes without DPN between the ages of 25 and 75 years, and had no prior history of DFUs were consecutively enrolled in the study. A cardiovascular autonomic function test was performed to diagnose cardiovascular autonomic neuropathy (CAN) using heart rate variability parameters.The median follow-up time was 13.3 years. Among the 449 (75.4%) patients who completed the follow-up evaluation, 22 (4.9%) patients developed new ulcers, and 6 (1.3%) patients underwent the procedure for lower extremity amputations. The patients in the DFUs group had a longer duration of diabetes, higher baseline HbA1c levels, higher rates of nephropathy, and CAN. A Cox hazard regression analysis results revealed that the development of DFUs was significantly associated with the presence of CAN (normal vs definite CAN; HR, 4.45; 95% confidence interval, 1.29-15.33) after adjusting for possible confounding factors.The development of DFUs was independently associated with CAN in patients with type 2 diabetes without DPN. We suggested the importance of CAN as a predictor of DFUs even in the patients without DPN, and the need to pay attention to patients with definite CAN and type 2 diabetes.

Invasive Primary Colonic Aspergillosis in the Immunocompetent Host without Classical Risk Factors.

Invasive aspergillosis (IA), generally considered an opportunistic infection in immunocompromised hosts, is associated with high morbidity and mortality. IA commonly occurs in the respiratory tract with isolated reports of aspergillosis infection in the nasal sinuses, central nervous system, skin, liver, and urinary tract. Extra-pulmonary aspergillosis is usually observed in disseminated disease. To date, there are a few studies regarding primary and disseminated gastrointestinal (GI) aspergillosis in immunocompromised hosts. Only a few cases of primary GI aspergillosis in non-immunocompromised hosts have been reported; of these, almost all of them involved the upper GI tract. We describe a very rare case of IA involving the lower GI tract in the patient without classical risk factors that presented as multiple colon perforations and was successfully treated by surgery and antifungal treatment. We also review related literature and discuss the characteristics and risk factors of IA in the immunocompetent hosts without classical risk factors. This case that shows IA should be considered in critically ill patients, and that primary lower GI aspergillosis may also occur in the immunocompetent hosts without classical risk factors.

Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.

Rapid fabrication of designable large-scale aligned graphene nanoribbons by electro-hydrodynamic nanowire lithography.

A new technique, electro-hydrodynamic nanowire (e-NW) lithography , is demonstrated for the rapid, inexpensive, and efficient fabrication of graphene nanorib bons (GNRs) on a large scale while simultaneously controlling the location and alignment of the GNRs. A series of interesting GNR architectures, including parallel lines, grids, ladders, and stars are produced. A sub-10-nm-wide GNR is obtained to fabricate field-effect transistors that show a room-temperature on/off current ratio of ca. 70.

N-doped graphene field-effect transistors with enhanced electron mobility and air-stability.

Although graphene can be easily p-doped by various adsorbates, developing stable n-doped graphene that is very useful for practical device applications is a difficult challenge. We investigated the doping effect of solution-processed (4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)dimethylamine (N-DMBI) on chemical-vapor-deposited (CVD) graphene. Strong n-type doping is confirmed by Raman spectroscopy and the electrical transport characteristics of graphene field-effect transistors. The strong n-type doping effect shifts the Dirac point to around -140 V. Appropriate annealing at a low temperature of 80 ºC enables an enhanced electron mobility of 1150 cm(2) V(-1) s(-1). The work function and its uniformity on a large scale (1.2 mm × 1.2 mm) of the doped surface are evaluated using ultraviolet photoelectron spectroscopy and Kelvin probe mapping. Stable electrical properties are observed in a device aged in air for more than one month.

Severe carbamazepine intoxication unresponsive to albumin-enhanced continuous venovenous hemodiafiltration with low dialysate flow.

Carbamazepine (CBZ) intoxication can be associated with severe toxicity, including neurological and cardio-respiratory abnormalities. Highly protein-bound, CBZ is not removed efficiently through conventional hemodialysis. Charcoal hemoperfusion is the most effective extracorporeal elimination therapy for CBZ intoxication. Recent reports have indicated that continuous venovenous hemodiafiltration (CVVHDF), albumin-enhanced continuous venovenous hemodialysis, high-flux hemodialysis and plasma exchange can be as effective as charcoal hemoperfusion. In contrast to recent reports, which demonstrated the effectiveness of CVVHDF with high dialysate flow in CBZ intoxication, we observed that serum CBZ level was decreased minimally by albumin-enhanced CVVHDF with low dialysate flow. Therefore, albumin-enhanced CVVHDF with high dialysate flow should be considered in severe CBZ intoxication, if hemoperfusion is unavailable because of the lack of facilities or if it cannot be performed.