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The association between non-alcoholic fatty liver disease (NAFLD) and diabetic kidney disease assessed using either albuminuria or proteinuria remains controversial. This study aimed to investigate the association between hepatic steatosis or fibrosis and albuminuria or proteinuria in Korean patients with type 2 diabetes mellitus (T2D). We enrolled 1108 patients with T2D and categorized as 3 groups; non-proteinuria (NP), isolated non-albumin proteinuria (iNAP), and albuminuria. Urinary albumin and protein levels were assessed as urinary albumin-to-creatinine ratio (uACR) and urinary protein-to-creatinine ratio (uPCR), respectively. Hepatic steatosis and fibrotic burden were assessed using the NAFLD liver fat score, Fibrosis-4 calculator (FIB-4) index, and NAFLD fibrosis score (NFS). The prevalence of significant steatosis was similar among groups (NP: 74.6% vs iNAP: 70.3% vs albuminuria: 79.9%, P = .085). The prevalence of significant fibrosis was significantly higher in the iNAP (18.7%) and albuminuria (16.5%) groups than in the NP group (9.5%, P = .001). Both uPCR and uACR showed a correlation with NFS (uPCR: r = 0.123, P

Rationale: Transverse myelitis (TM) is a spinal cord inflammatory myelopathy that causes motor/sensory loss and urinary retention below the level of the affected spinal cord. Although a few case reports have described the control of neuropathic pain in patients with TM via spinal cord stimulation, no documented case regarding the control of severe allodynia following TM via intrathecal pump has been described. Patient concerns: A 37-year-old woman was referred to a pain clinic for severe intractable pain below the T5 level followed by Sjögren's syndrome-induced TM. Diagnoses: A neurological examination revealed paresthesia and allodynia below the T5 level. The sensory evaluation was limited by extreme pain and jerking movements. The muscle strength of both lower limbs was grade 3. Interventions: Intrathecal pump was inserted into the left lower abdomen. Catheter tip was placed at the midline of the T8 level. Outcomes: The numeric rating scale (NRS) for pain score decreased from 10 to 5. Functional Independence Measure score increased from 67 before implantation to 92 at the time of discharge, while the patient's Barthel score increased from 31 to 46. Lessons: Neuropathic pain due to Sjögren's syndrome-related TM could be controlled effectively using the intrathecal morphine pump.

This study investigated the effects of the presence of type 2 diabetes mellitus (T2D) and/or chronic liver disease (CLD) on the incidence and prognosis of dementia during a 10-year period in Korea using a nationwide population-based dataset from the Korea National Health Insurance Service. To assess the impact of T2D and CLD on the incidence of dementia, we included subjects aged ≥60 years without dementia, T2D, and CLD from 2003 to 2005. We created another cohort for evaluating the all-cause mortality in subjects with dementia between 2003 and 2005. The participants were categorized into 4 groups: control (neither CLD nor T2D), CLD-only, T2D-only, and T2D-and-CLD groups, and they were followed up until 2013. The incidence of dementia was higher in the T2D-only group than in the control and CLD-only groups (2.78 vs. 2.04 and 2.00 per 1000 person-years). After adjustment for age, gender, and comorbid conditions, both T2D and CLD increased the risk of any type of dementia; however, the impact of CLD alone was much lower [hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.06–1.08] than that of T2D alone (HR 1.27, 95% CI: 1.27–1.28). The risk of dementia did not significantly change in patients with the co-occurrence of T2D and CLD compared to those with T2D alone. The all-cause mortality rate was the lowest in the control group (2.59 per 1000 person-years) and the highest in the T2D-and-CLD group (3.77 per 1000 person-years). Presence of T2D or CLD alone was associated with higher mortality (HR 1.46 and HR 1.21, respectively) compared with in the absence of both the diseases. Furthermore, the presence of both the diseases further significantly increased the mortality rate compared to the presence of each disease alone (HR 1.67, 95% CI: 1.65–1.69). In conclusion, this study found that the incidence of dementia was much higher in patients with T2D. CLD was associated with a modest increase in risk of dementia; however, there was no additive effect with T2D. In the population with dementia, however, the presence of CLD was associated with high mortality in patients with or without T2D.

Supplemental Digital Content is available in the text, Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes. Genetic variations of rs3765467 in GLP-1 receptor were explored in 246 patients with type 2 diabetes who received DPP-4 inhibitors treatment for 24 weeks in addition to previous medication. Patients with glycated hemoglobin (HbA1c) > 7% and who were naive to any DPP-4 inhibitors were enrolled. Responders were defined as those who showed a > 10% reduction in HbA1c after DPP-4 inhibitor treatment. DPP-4 inhibitors improved glycemic parameters and lipid profiles. Compared to the major genotype (GG), a larger proportion of patients with the minor allele genotype (GA/AA) were responders (P = 0.018), and also showing greater HbA1c reductions (1.3 ± 1.1 vs 0.9 ± 1.2%; P = 0.022). This genetic effect remained significant even after adjustment for other confounding factors (OR = 2.00, 95% CI = 1.03–3.89). Polymorphism in the GLP-1 receptor may influence DPP-4 inhibitor response. Further studies in larger population will help determine the association between genetic variation and interindividual differences in DPP-4 inhibitor therapy.

Supplemental Digital Content is available in the text, Hyperglycemia is associated with increased mortality and morbidity in patients with type 2 diabetes mellitus (T2DM) who are undergoing dialysis. Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been widely used in end-stage renal disease (ESRD) patients with T2DM, there are few studies on their efficacy in this population. We studied the effect of 3 different DPP-4 inhibitors on metabolic parameters in ESRD patients with T2DM. Two hundred ESRD patients with T2DM who were treated with DPP-4 inhibitors (sitagliptin, vildagliptin, or linagliptin) were enrolled and analyzed retrospectively. The changes in glycated hemoglobin (HbA1c), fasting plasma glucose, and lipid profiles were assessed before and after 3 months of treatment with DPP-4 inhibitors. Subgroup analysis was done for each hemodialysis (HD) and peritoneal dialysis (PD) group. There was no significant difference in the decrease in the HbA1c level among sitagliptin, vildagliptin, and linagliptin treatment groups (−0.74 ± 1.57, −0.39 ± 1.45, and −0.08 ± 1.40, respectively, P = 0.076). The changes in fasting blood glucose and lipid profiles were also not significantly different. In HD patients (n = 115), there was no difference in the HbA1c level among the 3 groups. In contrast, in PD patients (n = 85), HbA1c was reduced more after 3 months of treatment with sitagliptin compared with vildagliptin and linagliptin (−1.58 ± 0.95, −0.46 ± 0.98, −0.04 ± 1.22, respectively, P = 0.001). There was no significant difference in the glucose-lowering effect between the different DPP-4 inhibitors tested in ESRD patients. In PD patients, sitagliptin tends to lower the HbA1c level more than the other inhibitors. The glucose-lowering efficacy of the 3 DPP-4 inhibitors was comparable.

Supplemental Digital Content is available in the text, Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus. This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code. More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48–6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02–10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51–13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46–56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51–13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer. Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with

To verify that the Korean Diabetes Score (KDS), a self-assessment, predicts the risk of diabetes in various comprehensive risk models, and to investigate factors that enhance its predictive ability in a large cohort. We analyzed 8735 adults without diabetes in the Korean Genome and Epidemiology Study, an ongoing large community-based 10-year cohort study. Incident diabetes was defined as fasting blood glucose ≥126 mg/dL or postload 2-hour glucose ≥200 mg/dL by 75 g oral glucose tolerance test conducted biennually, or currently taking medication for diabetes. Hazard ratios (HRs) using Cox regression were calculated for relative risk of developing diabetes as associated with the KDS, and performance of risk models was assessed by area under the receiver-operating characteristic curve (AUC). Of 8735 participants, 1497 (17.1%) developed diabetes over 10 years. The prevalence of incident diabetes was 10.3% in people with a KDS

Renal hyperfiltration is closely linked to cardiometabolic disorders, and it may increase the mortality risk of the general population. Despite the well-established association between cardiometabolic diseases and sarcopenia, the relationship between renal hyperfiltration and sarcopenia has not yet been assessed. This population-based, cross-sectional study used a nationally representative sample of 13,800 adults from the 2008 to 2011 Korea National Health and Nutrition Examination Survey. Renal hyperfiltration was defined as the age- and sex-specific glomerular filtration rate above the 90th percentile in subjects with normal kidney function (>60 mL/min/1.73 m2). Appendicular skeletal muscle (ASM), measured by dual-energy x-ray absorptiometry, was used to assess pre-sarcopenia, which the international consensus defines as both ASM per se and ASM that was adjusted for the body mass index and the height. A total of 1402 (10.2%) participants were classified as having renal hyperfiltration. The prevalence of pre-sarcopenia ranged from 11.6% to 33.0%, by definition. Individuals with pre-sarcopenia had higher risks of renal hyperfiltration compared to those without pre-sarcopenia (10.9% vs 17.4%, P

Recently, several renal tubular damage markers have gained considerable attention because of their clinical implications as sensitive and specific biomarkers for early stage diabetic kidney disease. However, little is known about the demographic and glucometabolic factors affecting levels of urinary N-acetyl-β-d-glucosaminidase (NAG), a marker of proximal tubular damage, in type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the clinical relevance of urinary NAG with regard to demographic and glucometabolic parameters, as well as nephropathic parameters, by comparing the glomerulopathic marker of albuminuria. In this retrospective cross-sectional study, we enrolled a total of 592 patients with either prediabetes (N = 29) or T2DM (N = 563). Glucometabolic parameters (glucose, hemoglobin A1c, glycated albumin [GA], insulin, C-peptide, homeostasis model assessment [HOMA] of insulin resistance, HOMA-β, postprandial C-peptide-to-glucose ratio [PCGR], and urinary glucose-to-creatinine ratio) and nephropathic parameters (urinary NAG, albumin-to-creatinine ratio [ACR], and estimated glomerular filtration rate) were measured. The levels of urinary NAG showed moderate positive correlation with the levels of urinary ACR in T2DM (r = 0.46). In correlation analysis, urinary NAG was more strongly correlated with body mass index (BMI) (r = −0.22; P

Supplemental Digital Content is available in the text, Low-density lipoprotein cholesterol (LDL-C) is frequently estimated using the empirical Friedewald equation. We compared the accuracy of the novel equation named as the 180-cell method (180-c), which estimates LDL-C using a stratification approach, to those of 9 previously suggested formulas, including the Friedewald equation. We compared the accuracy of 10 equations by calculating intraclass correlation coefficient (ICC) and weighted kappa index in relation to direct LDL-C measurement values. Two independent populations used in the validation were the Severance Hospital LDL-C (SHL) registry (n = 164,358) and the Korea National Health and Nutrition Examination Survey (KNHANES) 2009 to 2010 (n = 3,854), each representing the hospital patient population and the general Korean population, respectively. The 180-c and DeLong equations showed the highest ICCs, indicating the best agreement with direct LDL-C measurement. The 180-c and Chen equations showed the highest kappa indices. For the hypertriglyceridemic subpopulation from SHL, the 180-c equation showed the best agreement with direct LDL-C measurement in terms of ICC. We compared the novel 180-c method for LDL-C estimation with 9 previous formulas in a non-US population as the first external validation. The 180-c equation, with Chen equation, appeared to be more accurate than the Friedewald equation. Although the DeLong equation showed better performance in the hypertriglyceridemic subpopulation, the 180-c equation performed appropriately in Asian population.

Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases. We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≤25 GT repeats) and long (L, >25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy. Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95% confidence interval, 1.088 − 2.285; P = 0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele. In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.

Supplemental digital content is available in the text, Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are strongly associated with obesity, insulin resistance, and type 2 diabetes. We recently developed and validated a self-assessment score in the Korean population to identify people at high risk for diabetes. The objective of this study was to evaluate whether the self-assessment risk score for diabetes can also be used to screen for the presence of NAFLD or NASH. The study population included 15,676 subjects (8313 men and 7363 women) over 20 years old who visited the National Health Insurance Service Ilsan Hospital in Korea between 2008 and 2010. Anthropometric, clinical, and laboratory data were analyzed during regular health checkups. Fatty liver disease was diagnosed using ultrasound, discrimination capability was assessed based on the area under the receiver operating characteristic curve (AUC), and evaluation measures, including sensitivity and specificity, were calculated. Multiple logistic analyses were also performed. We calculated a self-assessed risk score for diabetes (range: 0–11), and a cutoff of ≥5 identified 60% (50%) of men (women) at high risk for NAFLD, reflecting a sensitivity of 79% (85%), a specificity of 60% (66%), a positive predictive value (PPV) of 68% (51%), and a negative predictive value (NPV) of 73% (91%), with an AUC of 0.75 (0.82) for men (women). A cutoff point of ≥6 identified 43% (31%) of men (women) at high risk for NASH, reflecting a sensitivity of 80% (86%), a specificity of 64% (75%), a PPV of 30% (28%), and a NPV of 94% (98%), with an AUC of 0.77 (0.86) for men (women). The odds ratios that a 1-point increase in the diabetes risk scores would be associated with an increased risk for NAFLD and NASH were 1.20 [95% confidence interval (CI): 1.16–1.25] and 1.57 (95% CI: 1.49–1.65), respectively, in men, and 1.28 (95% CI: 1.21–1.34) and 1.89 (95% CI: 1.73–2.07), respectively, in women. The present study indicates that our self-assessment risk score for diabetes could be an effective primary screening tool for the presence of NAFLD or NASH.