Factors associated with advanced hepatic fibrosis in patients with various internal diseases: A multicenter community-based survey.

BACKGROUND AND AIMS: Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases. PATIENTS AND METHODS: We performed a community-based survey in which 1012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups. Independent factors for the high Fib-4 group were analyzed using logistic regression and decision tree analysis. RESULTS: A high prevalence of high Fib-4 index was observed in patients with cardiovascular diseases; 37.1% of patients with hypertension belonged to the high Fib-4 group. Independent factors associated with the high Fib-4 group were BMI (OR 0.95, 95%CI 0.918-0.989, P < 0.01), male sex (OR 1.35, 95%CI 1.03-1.78, P < 0.05), and hypertension (OR 1.41, 95%CI 1.03-1.92, P < 0.05). In patients with hypertension, a decision tree algorithm revealed three profiles for Fib-4 index: 1) creatinine level < 0.76 mg/dL (high Fib-4; 30.0%), 2) creatinine level ≥ 0.76 mg/dL without sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment (high Fib-4; 48.2%), and 3) creatinine level ≥ 0.76 mg/dL with SGLT2i treatment (high Fib-4; 23.5%). CONCLUSIONS: A high prevalence of advanced hepatic fibrosis was observed in patients with hypertension. Hypertension was an independent risk factor, and creatinine level and SGLT2i were divergence variables for advanced hepatic fibrosis. Thus, hypertension with chronic kidney injury may exacerbate hepatic fibrosis, while SGLT2i treatment may ameliorate hepatic fibrosis.

Adding of Sitagliptin on Insulin Therapy Effectively and Safely Reduces a Hemoglobin A1c Level and Glucose Fluctuation in Japanese Patients with Type 2 Diabetes.

Aims. Efficacy and safety of DPP-4 inhibitor, sitagliptin, add-on therapy to insulin were investigated in Japanese patients with type 2 diabetes. Subjects and Methods. Two hundred and sixteen patients (126 men, 65 ± 12 years old, BMI 24.9 ± 4.5, means ± S.D.) who had been treated by insulin alone or insulin combined with other oral hypoglycemic agents (OHAs) were recruited, and sitagliptin was added for 3 months. Results. HbA1c was significantly decreased after 3 months of add-on therapy as a whole (8.56 ± 1.50% to 7.88 ± 1.25%, P < 0.0001). Body weight did not change and insulin dosage was significantly (P < 0.0001) decreased for 3 months. Furthermore, day-to-day glucose variability was significantly reduced (18.3 ± 9.1 to 16.1 ± 8.1%, P < 0.05). In stepwise multiple regression analysis on ΔHbA1c as an outcome variable, the higher baseline HbA1c value and a preserved CPR were selected as significant predictive variables. Fifteen patients complained of mild hypoglycemia without any assistance during 3 months of sitagliptin add-on, while no severe hypoglycemic episode was reported. Conclusions. Add-on of sitagliptin to ongoing insulin therapy effectively reduced either HbA1c level or glucose fluctuation and could be a practical and well-tolerated alternative to treat Japanese patients with type 2 diabetes who had been inadequately controlled by insulin with or without other OHAs.

The reliability and validity of the Japanese version of the Diabetes Family Behavior Checklist (DFBC) for assessing the relationship between type 2 diabetes mellitus patients and their families with respect to adherence to treatment regimen.

AIMS: An appropriate questionnaire for assessing family support of self-management behavior of Japanese Type 2 diabetes patients has yet to be developed. We produced a Japanese version of the Diabetes Family Behavior Checklist (DFBC) and tested its reliability and validity. METHODS: The study enrolled Japanese patients with Type 2 diabetes mellitus who were living with their families: 158 patients in the Insulin Group and 169 in the Oral Hypoglycemic Agents Group. The external validity of the DFBC was tested with questionnaires of self-managed dietary and exercise behaviors, the Appraisal of Diabetes Scale (ADS), and HbA1c. RESULTS: The DFBC comprised two components: "Negative" and "Positive" feedbacks. Cronbach's alpha in the subcategories was ≥0.93, and the test-retest showed an intraclass correlation coefficient of 0.89. "Positive" and "Negative" scores correlated with self-managed dietary and/or exercise behaviors, the ADS scores in the both Groups. For patients having HbA1c levels of ≤6.8% there was a correlation between their "Positive" and "Negative" scores and the scores of their families in both Groups. CONCLUSION: The DFBC showed evidence of validity and reliability and may be a useful tool for quick assessment of self-managed treatment behavior of Japanese Type 2 diabetes patients and support received from their family.

Classification and characteristics of interferon-related diabetes mellitus in Japan.

AIM: The aim of this study was to assess the classification and clinical characteristics of interferon (IFN)-related diabetes. METHODS: Cases with IFN-related diabetes in Japan were retrieved through web search engines for medical literature until July in 2009, and unreported data were obtained from the authors by letter or e-mail. RESULTS: We collected 143 cases with IFN-related diabetes consisting of 104 type 1 diabetes including 4 own cases, and 39 non-autoimmune type 2-like diabetes. We found a marked increase in IFN-related type 1 diabetes for these 3 years. In contrast, no increase was observed in IFN-related type 2-like diabetes in the literature. Polyethylene glycol (PEG)-IFN and ribavirin had been more frequently used in patients with type 1 diabetes than in patients with type 2-like diabetes. The age of diabetes onset was comparable between type 1 and type 2-like diabetes, while the ratio of male patients was higher and the latency before diabetes was shorter in type 2-like diabetes. Patients with IFN-related type 1 diabetes had HLA types susceptible to Japanese type 1 diabetic patients, and a high positive rate of GAD antibodies. CONCLUSION: Potent combination therapy with PEG-IFN and ribavirin is likely associated with the increase in IFN-related type 1 diabetes. The combined measurement of GAD antibody and HLA-typing could be an effective strategy to predict the onset of type 1 diabetes associated with IFN therapy.

Excessive maternal transmission of diabetes in Japanese families with young-onset type 2 diabetes and insulin secretion defect according to clinical features.

The aim of the study is to identify the clinical characteristics of Japanese patients with young-onset type 2 diabetes (YT2D). Family history of diabetes and clinical data were collected for 30 unrelated males (from 11 to 20 years old at age of onset) and 20 females (from 10 to 20 years old at age of onset) with YT2D diagnosed at ≤ 20 years of age. Fasting C-peptide levels were measured in all, and glucagon stimulation tests were performed twice in six of them over several years. Moreover, 858 people with type 2 diabetes (T2D) diagnosed at >20 years of age were randomly recruited in order to compare the transmission pattern of them. Among the study subjects, 68% reported at least one parent with diabetes. Diabetes was more frequent among mothers than fathers of probands (P = 0.020), although this tendency was not observed in T2D diagnosed at >20 years of age. Fasting C-peptide levels of patients with diabetes duration of ≥ 10 years were significantly lower than for patients with diabetes duration of <10 years (0.61 ± 0.26 vs. 0.84 ± 0.43 nmol/l, P = 0.036). The fasting C-peptide levels among male patients with a family history of diabetes were also significantly lower than those without a family history (0.56 ± 0.25 vs. 0.83 ± 0.37 nmol/l, P = 0.034), while all female subjects had a family history of diabetes. Glucagon stimulation tests showed the following data; 0 min: 0.56 ± 0.31 vs. 0.39 ± 0.22 nmol/l, 3 min: 1.41 ± 0.77 vs. 0.87 ± 0.47 nmol/l, 6 min: 1.37 ± 0.80 vs. 0.79 ± 0.35 nmol/l, 10 min: 1.06 ± 0.60 vs. 0.81 ± 0.49 nmol/l, and 30 min: 0.58 ± 0.30 vs. 0.50 ± 0.19 nmol/l, respectively. These results demonstrated that YT2D among Japanese people occurring in excess with maternal transmission is associated with ß-cell dysfunction at the onset of diabetes and as the disease advances.

Clinical and genetic features of childhood-onset Type 2 diabetes in Japan.

We aimed to define the detailed clinical features of Japanese childhood-onset Type 2 diabetes mellitus (T2DM) patients who were followed-up, and to determine whether discernable characteristics were dissimilar or not from those of adult- and childhood-onset T2DM in other countries. Subjects were 22 patients (10 males and 12 females) under treatment without HNF-1alpha or mitochondrial gene mutations, and who were apparently diagnosed as diabetic when less than 15 years of age. Body mass indexes at onset in boys and girls were 25.8 +/- 6.3 and 24.7 +/- 3.6, respectively, with mean ages 13.3 +/- 1.7 and 12.8 +/- 2.0 years, respectively. Most patients had a short diabetic duration that required insulin treatment. One or both parents of 18 of the 22 T2DM subjects were diabetic and 7 subjects had a history of diabetes in their family across three generations. We demonstrated that a relatively large number of Japanese childhood-onset T2DM cases have a strong genetic factor, and are not necessarily related to excessive obesity. Furthermore, most required insulin therapy in the initial stages because of insufficient pancreatic beta-cell reserves. This suggests that malfunction of pancreatic beta-cells triggers hyperglycemia resulting in the requirement for insulin in Japanese some childhood-onset T2DM patients.

Association of troglitazone-induced liver injury with mutation of the cytochrome P450 2C19 gene.

An anti-diabetic agent, troglitazone, was withdrawn from the market because of its association with liver injury. However, the mechanism of the injury has not been elucidated. We examined, retrospectively, the frequency of the polymorphisms of the cytochrome P450 (CYP) 2C19 and 2D6 genes in eight patients with type 2 diabetes who had troglitazone-induced liver injury and 31 subjects who tolerated troglitazone well. Polymorphisms of CYP 2C19 and 2D6 genes were analyzed by polymerase chain reaction using peripheral white blood cells. The incidence of mutations was compared with known population data for the Japanese. Homozygous or compound heterozygous mutations in CYP 2C19 alleles were found in four of the eight (50.0%) patients with troglitazone-induced liver injury. This rate was significantly higher than that in patients without liver injury (four of 31, 12.9%). The frequency of P450 2D6 mutations was the same in both groups. In conclusion, troglitazone-induced liver injury occurred more frequently in subjects with the CYP 2C19 mutations in Japanese patients.