Late-Evening Snack with Branched-Chain Amino Acid-Enriched Nutrients Does Not Always Inhibit Overt Diabetes in Patients with Cirrhosis: A Pilot Study.

Cirrhosis patients often have abnormal glucose metabolism. We investigated the effects of a late-evening snack (LES) with branched-chain amino acid-enriched nutrients (BCAA-EN) on glucose metabolism in cirrhosis patients. LES with BCAA-EN was administered for 1 week in 13 patients with cirrhosis and hypoalbuminemia. Blood glucose (BG) levels were measured every 15 min. The patients were divided into two groups based on BG levels: group 1 (G1, n = 11): nocturnal BG levels <200 mg/dL and group 2 (G2, n = 2): nocturnal BG levels ≥200 mg/dL. G1 had nocturnal BG levels <200 mg/dL, whereas G2 had nocturnal BG levels ≥200 mg/dL. The average BG levels did not significantly change after BCAA-EN administration in G1 (before 91.9 ± 29.0 mg/dL; after 89.0 ± 24.3 mg/dl). However, the average BG levels significantly increased after BCAA-EN administration in G2 (before 153.6 ± 43.3 mg/dL; after 200.9 ± 59.7 mg/dL) (p < 0.01). The glycated albumin level (16.6 ± 0.9% vs. 16.2 ± 2.1%), fasting immunoreactive insulin (F-IRI) level (53.9 ± 34.0 µU/mL vs. 16.5 ± 11.0 µU/mL), and homeostasis model assessment of insulin resistance (HOMA-IR) score (17.85 ± 10.58 vs. 4.02 ± 2.59) were significantly higher in G2 than in G1 (p < 0.05, p < 0.05, and p < 0.01, respectively). The quantitative insulin sensitivity check indices (0.32 ± 0.03 vs. 0.27 ± 0.02) were significantly higher in G1 than in G2 (p < 0.01). One patient in G2 was obese and had type 2 diabetes. The other patient was obese and had a high HOMA-IR score and F-IRI level. A LES with BCAA-EN does not inhibit overt diabetes in most cirrhosis patients. However, close attention should be paid to fluctuations in BG levels in cirrhosis patients who present with obesity and severe insulin resistance.

Identification of clinical risk factors for histological progression of primary biliary cholangitis.

AIM: To identify laboratory predictors of histological progression (HP) of primary biliary cholangitis (PBC). METHODS: Sequential biopsies were carried out on 35 (11.4%) of 308 patients with PBC treated with ursodeoxycholic acid (UDCA). Patients were divided into high γ-glutamyl transpeptidase (GGT) (n = 18) and low GGT (n = 17) groups, based on the median value of GGT at baseline. Patients were then categorized as showing HP (progressive group, PG) or lacking HP (non-progressive group, NPG) according to the Scheuer and Nakanuma classifications, with the latter grading liver fibrosis (fibrosis score) and bile duct loss (BDL score). RESULTS: According to the Scheuer definition, 12 patients had HP and 23 did not. According to the Nakanuma definition, 8 and 27 patients were in the PG and NPG groups, respectively. The fibrosis and BDL scores progressed in 13 and 8 patients, respectively, whereas 22 and 25 patients did not show HP, respectively. Fisher's exact probability test analysis revealed that the rate of HP using the Nakanuma fibrosis score was significantly higher in the high GGT group compared to the low GGT group (P < 0.05). However, no significant correlation was found between the HP of PBC and the biochemical response to UDCA therapy. Both univariate and multivariate logistic regression analyses indicated that the serum GGT level at baseline is an independent risk factor for an increased Nakanuma fibrosis score. CONCLUSIONS: The level of serum GGT at baseline is significantly associated with liver fibrosis progression in PBC, and therefore could help to predict the HP of PBC.

Combining probiotics and an angiotensin-II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non-alcoholic steatohepatitis.

AIM: Intestinal endotoxin is important for the progression of non-alcoholic steatohepatitis (NASH). Circulating endotoxin levels are elevated in most animal models of diet-induced non-alcoholic fatty liver disease (NAFLD) and NASH. Furthermore, plasma endotoxin levels are significantly higher in NAFLD patients, which is associated with small intestinal bacterial overgrowth and increased intestinal permeability. By improving the gut microbiota environment and restoring gut-barrier functions, probiotics are effective for NASH treatment in animal models. It is also widely known that hepatic fibrosis and suppression of activated hepatic stellate cells (Ac-HSCs) can be attenuated using an angiotensin-II type 1 receptor blocker (ARB). We thus evaluated the effect of combination probiotics and ARB treatment on liver fibrosis using a rat model of NASH. METHODS: Fisher 344 rats were fed a choline-deficient/L-amino acid-defined (CDAA) diet for 8 weeks to generate the NASH model. Animals were divided into ARB, probiotics, and ARB plus probiotics groups. Therapeutic efficacy was assessed by evaluating liver fibrosis, the lipopolysaccharide Toll-like receptor (TLR)4 regulatory cascade, and intestinal barrier function. RESULTS: Both probiotics and ARB inhibited liver fibrosis, with concomitant HSC activation and suppression of liver-specific transforming growth factor-ß and TLR4 expression. Probiotics reduced intestinal permeability by rescuing zonula occludens-1 disruption induced by the CDAA diet. Angiotensin-II type 1 receptor blocker was found to directly suppress Ac-HSCs. CONCLUSIONS: Probiotics and ARB are effective in suppressing liver fibrosis through different mechanisms. Currently both drugs are in clinical use; therefore, the combination of probiotics and ARB is a promising new therapy for NASH.

Proton pump inhibitor therapy does not increase serum endotoxin activity in patients with cirrhosis.

AIM: Proton pump inhibitors (PPIs) are frequently prescribed in patients with cirrhosis, but this therapy entails potential complications. We aimed to investigate the influence of PPI use on intestinal permeability in patients with cirrhosis. METHODS: We recruited 228 patients with cirrhosis and divided them into four groups. Group (Gp)1 comprised patients receiving a PPI with concurrent neomycin (NEO) (PPI-NEO group, n = 14 [6.1%]), Gp2 and Gp3 comprised those receiving either PPI or NEO (PPI group, n = 91 [39.9%]; and NEO group, n = 11 [4.4%]), and Gp4 comprised those receiving neither of these medications (control group; n = 112 [49.1%]). We assessed the intestinal permeability by measuring endotoxin activity (EA) using a luminol chemiluminescence method. RESULTS: Endotoxin activity levels were significantly higher in patients with Child B cirrhosis than in those with Child A cirrhosis, but we found no significant differences in EA levels between patients with Child C cirrhosis and those with either Child A or B cirrhosis. We observed no significant differences in EA levels among groups 1-4. Patients without antibiotic exposure (n = 203), comprising 91 patients on PPI therapy (Gp2) and 112 no-PPI-therapy controls (Gp4), were subdivided according to Child-Pugh (CP) classification. We found no significant differences in EA levels between Gp2 and Gp4 in either CP class. CONCLUSION: Our results suggest that PPI usage does not have a significant impact on serum levels of gut-derived endotoxins, which are already elevated because of the increased intestinal permeability in patients with cirrhosis.

Efficacy and tolerability of interferon-free regimen for patients with genotype-1 HCV infection.

Depression is a major reason for interferon (IFN) therapy cessation. IFN-free direct-acting antiviral (DAA) therapy for depression is not well-documented. Thus, four different IFN-free regimens were assessed in genotype-1 hepatitis C virus (HCV) patients with depression. Overall, 287 HCV genotype-1 patients who received combination therapies with IFN-free DAAs of daclatasvir/asunaprevir (DCV/ASV) (n=84), sofosbuvir/ledipasvir (SOF/LDV) (n=95), ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) (n=74), and elbasvir/grazoprevir (EBR/GZR) (n=34) were included. Treatment-induced depression as a complication of HCV therapy in IFN-free DAA regimens was assessed. The severity of depression was evaluated using the Beck Depression Inventory-II (BDI-II) questionnaire. It was demonstrated that all four DAA regimens achieved similar high efficacy in Japanese patients with HCV genotype-1 infection. Moreover, in seven patients with depression who received the 24-week DCV/ASV treatment regimen, the BDI-II scores significantly increased at week 4 as compared with pretreatment values; furthermore, they decreased below baseline at week 12 despite the rapid decline of serum HCV levels after the initiation of DCV/ASV therapy. The BDI-II scores gradually decreased during therapy in the remaining 77 DCV/ASV-treated patients without depression. The BDI-II scores showed a significant decrease from baseline to the end of treatment with 12-week regimens, including SOF/LDV and EBR/GZR. The 12-week DAA regimen of SOF/LDV and EBR/GZR can be safely used with high efficacy in patients with genotype-1 HCV infection, including those with depression.

Correction to: Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ).

In the original publication, second author's name was incorrectly published as Hiroki Shin. The correct name should read as 'Koki Shin'.

Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ).

INTRODUCTION: To measure the burden of pharmacotherapy on patients with type 2 diabetes mellitus (T2DM), we developed the Diabetes Treatment Burden Questionnaire (DTBQ), a patient-administered questionnaire composed of 18 questions, and evaluated its reproducibility and validity. METHODS: We enrolled 240 patients with T2DM under pharmacotherapy over 20 years of age at seven institutes in Japan. Their physicians filled out report forms on patient backgrounds, and the patients answered both the DTBQ and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). For evaluation of reproducibility, 48 of the enrolled subjects completed a 2nd DTBQ at home after leaving the medical institutes. RESULTS: Statistical analyses were performed for two sets of subjects, the validity analysis set (N = 236) and the reproducibility analysis set (N = 47). Factor analysis found a simple structure in the DTBQ item scores using a three-factor model with varimax rotation; the three subscales were designated as "implementation burden", "flexibility burden", and "blood glucose control burden". All intraclass correlation coefficients for the subscale scores were 0.8 or higher, indicating high reproducibility. Negative correlations were observed between the DTSQ satisfaction score and the DTBQ subscale scores. Moreover, as the dosing frequency of diabetic medicines increased, the DTBQ total score (total burden score) also became higher. Likewise, expected associations were observed between patient backgrounds and DTSQ scores. CONCLUSION: The DTBQ has adequate reproducibility and validity as a measurement scale for treatment burden on T2DM patients. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) 000026382. FUNDING: Eli Lilly Japan.

Association of proton pump inhibitor use with the risk of the development or progression of albuminuria among Japanese patients with diabetes: A prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 16)].

AIMS: We aimed to determine the prospective association between proton pump inhibitor (PPI) use and the subsequent risk of the development or progression of albuminuria or eGFR. METHODS: Longitudinal data of patients with diabetes were obtained from a large Japanese diabetes registry. To assess the independent correlation between PPI use and the development or progression of urine microalbuminuria, the time-varying Cox proportional hazards model was used with adjustment for potential confounders. RESULTS: The mean patient age, body-mass index (BMI), and hemoglobin A1c (HbA1c) levels were 65.7 y, 24.5 kg/m2, and 7.5% (57.9 mmol/mol), respectively. In 1711 patients without albuminuria, we observed 599 cases with development of albuminuria over median follow-up of 4.0 years, and in 1279 patients with microalbuminuria, 290 cases with urinary albuminuria progression over 4.0 years, and 257 eGFR decline cases over 3.8 years. PPI use was not associated with the development of albuminuria (HR = 0.88; 95%CI, 0.77-1.01; p = .058), progression of albuminuria (HR = 1.24; 95%CI, 0.87-1.79; p = .236), nor eGFR decline (HR = 1.05; 95%CI, 0.81-1.34; p = .973) even in a propensity score-adjusted model with time-varyingly updating PPI use information. CONCLUSIONS: In conclusion, PPI use was not associated with the subsequent risk of development or progression of albuminuria, or eGFR decline in patients with diabetes.

Glycogenic Hepatopathy in Type 1 Diabetes Mellitus.

Glycogenic hepatopathy (GH) is a rare complication of poorly controlled type 1 diabetes mellitus (T1DM), and is characterized by elevated liver enzymes, hepatomegaly, and glycogen accumulation. We herein present the case of a 23-year-old man with poorly controlled T1DM who had liver dysfunction. Imaging studies showed severe hepatomegaly and fatty liver. The examination of a liver biopsy specimen revealed fatty droplets, ballooning, inflammation, and mild fibrosis. Subsequent periodic acid-Schiff (PAS) staining after diastase digestion confirmed GH. In this case, the improvement of hyperglycemia, not HbA1c, resulted in the improvement of the patient's liver function. This is the first report on the use of continuous glucose monitoring in patients with GH to show that continuous hyperglycemia may worsen GH.

Predisposing factors for hepatocellular carcinoma recurrence following initial remission after transcatheter arterial chemoembolization.

Hepatocellular carcinoma (HCC) is prone to recurrence following curative treatment. The purpose of the present study was to identify the predisposing factors of HCC recurrence following complete remission achieved by transarterial chemoembolization (TACE). A retrospective cohort study of 70 consecutive patients with HCC who underwent TACE as the initial treatment was conducted. The patients were divided into two groups according to their 1-year disease-free survival (DFS) status; the early recurrence group (ER group; n=32), with HCC recurring within 1 year of initial TACE; and the non-early recurrence group (NER group; n=38), who did not experience recurrence within 1 year. The parameters identified as significantly associated with DFS time on univariate analysis were aspartate aminotransferase (AST), alanine aminotransferase and α-fetoprotein levels, as well as the tumor number (P=0.003, P=0.027, P=0.002 and P=0.005, respectively). Multivariate analysis revealed that AST levels and tumor number were significantly associated with a shorter DFS period (P=0.009 and P=0.038, respectively). The Mantel-Haenszel test revealed a significant trend of decreasing DFS with increasing tumor number. Among the patients with HCC in the ER group, locoregional recurrence occurred more frequently in those who received TACE alone compared with those treated with TACE combined with radiofrequency ablation treatment. In summary, multinodularity of HCC is the most potent predictive factor for the recurrence of HCC within 1 year of initial TACE.

Association between dipstick hematuria and decline in estimated glomerular filtration rate among Japanese patients with type 2 diabetes: A prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 14)].

AIMS: To assess the association between dipstick hematuria and estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. METHODS: Longitudinal data were obtained from 3068 Japanese patients with type 2 diabetes. To assess the independent association between dipstick hematuria and eGFR decline, we used Cox proportional hazard model adjusted for potential confounders. RESULTS: Median follow-up period was 699.7days. Mean age, body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m2, and 7.5% (58.1mmol/mol), respectively. Positive dipstick hematuria was significantly associated with baseline eGFR and severity of albuminuria (p<0.001). The multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick hematuria compared with those without dipstick hematuria was 2.19 [95% confidence interval (CI): 1.22-3.91]; this association remained significant even after the exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39; 95% CI: 1.13-5.04). CONCLUSION: Positive dipstick hematuria was associated with severity of albuminuria and renal function. A significant association was found between dipstick hematuria and increased risk of eGFR decline among patients with type 2 diabetes. Therefore, our results suggest that dipstick hematuria is perhaps indicative of more severe diabetic nephropathy.

Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis.

Human parvovirus (HPV) B19 is linked to a variety of clinical manifestations, such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic anemia. Although a few cases have shown HPVB19 infection as a possible causative agent for hepatitis-associated aplastic anemia (HAAA) in immunocompetent patients, most reported cases of HAAA following transient hepatitis did not have delayed remission. Here we report a rare case of severe aplastic anemia following acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously healthy young male. Clinical laboratory examination assessed marked liver injury and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies. Immunosuppressive therapy was initiated 2 months after the onset of acute hepatitis when liver injury and jaundice were improved. Cyclosporine provided partial remission after 2 months of medication without bone marrow transplantation. Our case suggests that HPVB19 should be considered as a hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.

Clinical significance of the Scheuer histological staging system for primary biliary cholangitis in Japanese patients.

BACKGROUND: Inadequate response to ursodeoxycholic acid (UDCA) is associated with unfavorable outcomes in patients with primary biliary cholangitis (PBC). We aimed to identify surrogate markers for predicting long-term prognosis and biochemical response to UDCA in patients with PBC. PATIENTS AND METHODS: In this single-center, retrospective study, 99 patients with PBC were classified into responders (n=53) and nonresponders (n=46) based on reductions in the γ-glutamyl transpeptidase levels at 1 year after initiating UDCA therapy (Nara criteria). We assessed whether the criteria for patentability by different countries are useful in predicting the prognosis of PBC. The accuracy of Scheuer and Nakanuma staging systems in predicting prognosis and treatment response was compared. RESULTS: Nara definition had comparable utility to the Paris-II definition for selecting patients in whom UDCA monotherapy can be safely continued. Patients at Scheuer stage 1 had a significantly better prognosis than those at Scheuer stages 3 or 4 (P<0.05 and 0.0001, respectively). Patients at Nakanuma stage 4 had decreased survival compared with those at stage 1 (P<0.05). The proportion of responders to nonresponders was significantly higher in stages 1-3 PBC than in stage 4 PBC, according to both staging systems (P<0.05 for both). All patients with Scheuer stage 4 PBC were nonresponders, whereas only 28.6% (2/7) of those with Nakanuma stage 4 PBC were responders. CONCLUSION: The Scheuer staging system had greater utility in predicting long-term prognosis and UDCA response than the Nakanuma staging system.

DNA methylation of angiotensin II receptor gene in nonalcoholic steatohepatitis-related liver fibrosis.

AIM: To clarify whether Agtr1a methylation is involved in the development of nonalcoholic steatohepatitis (NASH)-related liver fibrosis in adult rats. METHODS: A choline-deficient amino acid (CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis. Agtr1a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid (CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR. Hepatic stellate cells (HSCs) were isolated by collagenase digestion of the liver, followed by centrifugation of the crude cell suspension through a density gradient. Agtr1a methylation and its gene expression were also analyzed during the activation of HSCs. RESULTS: The mean levels of Agtr1a methylation in the livers of CDAA-fed rats (11.5% and 18.6% at 8 and 12 wk, respectively) tended to be higher (P = 0.06 and 0.09, respectively) than those in the livers of CSAA-fed rats (2.1% and 5.3% at 8 and 12 wk, respectively). Agtr1a was not methylated at all in quiescent HSCs, but was clearly methylated in activated HSCs (13.8%, P < 0.01). Interestingly, although Agtr1a was hypermethylated, the Agtr1a mRNA level increased up to 2.2-fold (P < 0.05) in activated HSCs compared with that in quiescent HSCs, suggesting that Agtr1a methylation did not silence its expression but instead had the potential to upregulate its expression. These findings indicate that Agtr1a methylation and its upregulation of gene expression are associated with the development of NASH-related liver fibrosis. CONCLUSION: This is the first study to show that DNA methylation is potentially involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis.

Efficacy of alogliptin in preventing non-alcoholic fatty liver disease progression in patients with type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes. The study was a single arm, multi-centre, non-randomised study of NAFLD patients with type 2 diabetes. NAFLD was diagnosed according to ultrasonographic findings. All the patients received 25 mg/day of alogliptin for 12 months. The efficacy of alogliptin in preventing NAFLD progression was assessed using overall NAFIC scores [non-alcoholic steatohepatitis (NASH), ferritin, insulin and type IV collagen 7S] and individual component scores according to baseline haemoglobin A1c (HbA1c) levels. Of the 39 patients enrolled in the study, 16 patients (40.3%) had NAFIC scores >2 points, indicating the presence of NASH. NAFIC scores markedly decreased following 12 months of alogliptin administration, but remained >2 points in 10 patients, indicating that NASH may have persisted in these patients. The relative risks for persistent NASH were 4.92 (95% confidence interval, 0.61-40.0) in the highest HbA1c tertile group compared with those in the lowest group. However, no statistically significant linear trend was observed across all HbA1c categories (P=0.145). DPP4-I may have efficacy against NAFLD progression in patients with type 2 diabetes with relatively lower HbA1c levels. DPP4-I may represent a potential new therapeutic strategy for the prevention of disease progression in NAFLD patients with type 2 diabetes.

Diabetes treatment-related quality of life is associated with levels of self-care activities in insulin injection among Japanese patients with type 2 diabetes: Diabetes Distress and Care Registry at Tenri (DDCRT 8).

AIMS: We investigated the association between diabetes treatment-related quality of life (QOL) and levels of self-care activities in insulin injection among Japanese patients with type 2 diabetes. METHODS: Data from 1394 patients with type 2 diabetes on insulin therapy were obtained from a diabetes registry in Japan. We used the Diabetes Therapy-Related QOL (DTR-QOL) questionnaire and relative risk regression analysis to assess the independent association of high levels of self-care activities in insulin injection and DTR-QOL scores while adjusting for possible confounders. RESULTS: The mean age, BMI and HbA1c level were 65.8 years, 24.8 kg/m(2) and 62 mmol/mol (7.8 %), respectively. The frequency of insulin injection omission was associated with DTR-QOL scores. In the multivariable-adjusted model, the relative risks for high levels of self-care activities in insulin injection was 1.15 (95 % confidence interval, 1.05-1.26) in the highest quintile compared with those in the lowest quintile of DTR-QOL scores. Subgroup analysis confirmed this association in patients <65 years. CONCLUSIONS: DTR-QOL was associated with self-reported levels of self-care activities in insulin injection, particularly among Japanese patients <65 years with type 2 diabetes. DTR-QOL might be a useful tool to identify patients who consequently omit insulin. For patients with low DTR-QOL score, healthcare providers should discuss their treatment-related problems to prevent insulin injection omission.

Serum high-sensitivity C-reactive protein levels are associated with high risk of development, not progression, of diabetic nephropathy among Japanese type 2 diabetic patients: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT7]).

OBJECTIVE: To assess the prospective association between baseline serum hs-CRP concentration and the subsequent risk of development or progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: Longitudinal data were obtained from 2,518 patients with type 2 diabetes registered in a Japanese diabetes registry. To assess the independent correlations between serum baseline hs-CRP and either the development or progression of diabetic nephropathy 1 year later, the Cox proportional hazards model was used and adjusted for potential confounders. RESULTS: The mean patient age, BMI, and HbA1c level were 66.1 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Baseline serum hs-CRP levels were significantly associated with the urinary albumin-to-creatinine ratio at baseline (P < 0.001). Multivariable adjusted hazard ratio for the development from normoalbuminuria to microalbuminuria was 1.31 (95% CI 0.80-2.17; P = 0.286), 1.55 (1.16-2.08; P = 0.003), and 1.57 (1.22-2.03; P = 0.001), respectively, for the second, third, and fourth quartiles of serum hs-CRP levels, showing a statistically significant linear trend across categories (P < 0.001). We did not observe a significant association between hs-CRP levels and the subsequent risk of diabetic nephropathy progression (P for trend = 0.575). CONCLUSIONS: Serum hs-CRP levels, independent of possible confounders, were associated with a subsequent risk of developing, not progressing, diabetic nephropathy in type 2 diabetic patients. Serum hs-CRP may be useful for predicting the future risk of developing diabetic nephropathy.

Switching from insulin to liraglutide improved glycemic control and the quality of life scores in a case of type 2 diabetes and active Crohn's disease.

A 44-year-old man with type 2 diabetes of five years' duration was admitted for the management of poor glycemic control despite the administration of insulin therapy. On admission, he received vigorous treatment for a 28-year history of Crohn's disease and a 14-year history of a psychiatric disorder. His glycosylated hemoglobin A1c (HbA1c) level was 11.3%, his fasting blood glucose level was 567 mg/dL and his C-peptide level was 1.0 ng/mL. His quality of life (QOL) was severely impaired as a result of frequent episodes of hyperglycemia and hypoglycemia. Treatment with liraglutide was commenced in place of insulin, which improved the patient's glycemic control to an HbA1c level of 5.5% and markedly increased his QOL score with no hypoglycemia.

Elevated levels of hs-CRP are associated with high prevalence of depression in japanese patients with type 2 diabetes: the Diabetes Distress and Care Registry at Tenri (DDCRT 6).

OBJECTIVE: Because of the absence of data on the direct association between inflammation and depression in patients with diabetes, we examined the association between hs-CRP levels and the high prevalence of depression in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional data were obtained from 3,573 patients with type 2 diabetes recruited from a Japanese diabetes registry. A multiple logistic regression analysis adjusted for potential confounders was used to assess independent associations between hs-CRP levels and major depression, as defined by the Patient Health Questionnaire-9. RESULTS: Mean age, BMI, and HbA1c levels were 66.0 years, 24.6 kg/m(2), and 7.4% (57.8 mmol/mol), respectively, and 122 patients (3.4%) suffered from major depression. In the age- and sex-adjusted model, the odds ratio (OR) for major depression was 1.86 (95% CI 1.01-3.42; P = 0.045) in the highest CRP quintile compared with that in the 3rd CRP quintile; however, this association disappeared after adjustment for other possible confounders (OR 1.58 [95% CI 0.85-2.94]; P = 0.148). Among patients with a BMI of ≥25 kg/m(2), a significant association was observed between the highest hs-CRP quintile and major depression (multivariable-adjusted OR 2.69 [95% CI 1.09-7.08]; P = 0.032). CONCLUSIONS: We observed a significant positive association between high hs-CRP levels and depression in patients with diabetes who had a high BMI.