Characterization of mutations in hepatitis B virus DNA isolated from Japanese HBsAg-positive blood donors in 2021 and 2022.

Missense mutations in certain small envelope proteins diminish the efficacy of antibodies. Consequently, tracking the incidence and types of vaccine-escape mutations (VEMs) was crucial both before and after the introduction of universal hepatitis B vaccination in Japan in 2016. In this study, we isolated hepatitis B virus (HBV) DNA from 58 of 169 hepatitis B surface antigen (HBsAg)-positive blood samples from Japanese blood donors and determined the nucleotide sequence encoding the small envelope protein. DNA from six (10%) of the samples had VEMs, but no missense mutations, such as G145R, were detected. Complete HBV genome sequences were obtained from 29 of the 58 samples; the viral genotype was A1 in one (3%), A2 in three (10%), B1 in nine (31%), B2 in five (17%), B4 in one (3%), and C2 in 10 (34%) samples. Tenofovir-resistance mutations were detected in two (7%) samples. In addition, several core promoter mutations, such as 1762A>T and 1764G>A, and a precore nonsense mutation, 1986G>A, which are risk factors for HBV-related chronic liver disease, were detected. These findings provide a baseline for future research and highlight the importance of ongoing monitoring of VEMs and drug resistance mutations in HBV DNA from HBsAg-positive blood donors without HBV antibodies.

Changes in prescription patterns and doses of oral antidiabetic drugs in Japanese patients with type 2 diabetes (JDDM70).

We assessed the prescription patterns of oral antidiabetic drugs in Japanese patients with type 2 diabetes between 2002 and 2020 using data from the Computerized Diabetes Care database. Among 172,960 patients treated with oral antidiabetic drugs, both the sulfonylurea prescription rate and dose decreased from 2002 to 2020. Prescriptions of biguanides, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors increased; their dose and dose frequency remained relatively stable. Trends in oral antidiabetic drug prescriptions changed over time, reflecting guideline recommendations and existing evidence.

Cross sectional study on proportion of sulfonylureas among various oral antidiabetic drugs using for Japanese patients with type 2 diabetes, analyzed from NSAID Study-2.

AIM: We aimed to investigate the certainty of using sulfonylureas in Japanese patients with type 2 diabetes mellitus (T2DM) by analyzing data from the 2018 Nationwide Survey on Actual Intervention for T2DM by Japanese Practitioners (NSAID Study). METHODS: Of the 6525 and 1545 participants in the NSAID Study under the care of general practitioners (GP) and diabetes specialists (SP), respectively, we included 5423 (83.1%) and 1058 (68.5%) patients who were treated with only oral antidiabetic drugs (OADs) by GPs and SPs, respectively, in the analysis. RESULTS: Among the seven OAD classes in monotherapy, sulfonylureas were the third and fifth most prescribed OADs by GPs (7.1%) and SPs (6.4%), respectively. Sulfonylurea usage increased with combination therapy. Glimepiride was the most commonly prescribed sulfonylurea. Patients who used sulfonylureas had higher hemoglobin A1c (HbA1c) levels and lower body mass indices (BMIs) than patients who did not use sulfonylureas. CONCLUSION: The results of this study clearly demonstrated that, among the OADs, sulfonylureas were not frequently used in monotherapy, although the opportunity of using sulfonylurea increased with the number of OADs prescribed in combination therapies by both GPs and SPs in Japan. Moreover, low-dose glimepiride was the most-prescribed sulfonylurea for Japanese T2DM patients, especially for those who were lean and had higher HbA1c levels.

Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61).

AIMS/INTRODUCTION: Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients' BMI levels. MATERIALS AND METHODS: OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD-treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI. RESULTS: Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase-4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m2 . DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m2 , use of BGs and sodium-glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m2 , they were the third most prescribed OADs for patients with BMI >35 kg/m2 after BGs and sodium-glucose cotransporter 2 inhibitors . CONCLUSIONS: DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.

Differences in Dental Care Referral for Diabetic Patients Between General Practitioners and Diabetes Specialists in Japan, Analyzed from NSAID-Study 3.

INTRODUCTION: Periodontal disease is a common inflammation worldwide and is not only the foremost cause of tooth loss but also a cause of deterioration of glycemic control in patients with diabetes mellitus. In addition, effective glycemic management improves the control of periodontitis infection. The aim of this study was to clarify whether awareness of the need to refer their patients with diabetes to dentists differs between general practitioners and diabetes specialists. This was achieved by secondary analysis of data from the 2018 Nationwide Survey on Actual Intervention for Type 2 Diabetes Mellitus (T2DM) by Japanese Practitioners (NSAID Study). METHODS: Data from 380 general practitioners and 79 diabetes specialists who participated in the NSAID study and responded to the question of whether they referred T2DM patients to the dentist were analyzed in this study. RESULTS: The proportion of general practitioners who referred T2DM patients to dentists was significantly lower than that of diabetes specialists (35.4% vs. 64.1%, respectively). CONCLUSION: This result suggests that the general practitioners who participated in this study were less cognizant of oral hygiene in patients with diabetes than those who specialized in diabetes. It is also necessary to increase the opportunities for education of physicians who provide diabetic care to promote appropriate dental referrals.

Periodontal disease is a common inflammation worldwide and not only causes tooth loss but also the deterioration of glycemic control in patients with diabetes. In addition, effective glycemic management improves the control of periodontitis infection. Physicians who care for diabetes patients need to be aware of the increased risk and need for improved oral hygiene and to refer their patients to dentists. This study aims to clarify whether awareness of the need to refer their patients with diabetes to dentists differs between general practitioners and diabetes specialists. Responses from 380 general practitioners and 79 diabetes specialists are analyzed in this study. The proportion of general practitioners who refer type 2 diabetes patients to dentists is shown to be significantly lower than that of diabetes specialists. It is necessary to increase the opportunities for education of physicians who provide diabetic care to promote appropriate dental referrals.

Mycobacterium bovis BCG-mediated suppression of Th17 response in mouse experimental autoimmune encephalomyelitis.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease mediated by a pro-inflammatory immune response. Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice with a myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in killed Mycobacterium tuberculosis-containing complete Freund's adjuvant (CFA-EAE) is used as a model of MS. Mycobacterium bovis BCG has been reported to ameliorate clinical symptoms of CFA-EAE, although the precise mechanism has not yet been documented. Since CFA-EAE uses adjuvant with mycobacterial antigens, mycobacterial antigen-specific T cells induced by CFA may cross-react with BCG and modulate EAE. METHODS: To exclude the influence of cross-reactivity, a modified murine EAE model (cell wall skeleton (CWS)-EAE) that does not induce mycobacterial antigen-specific T cells was established and used to reevaluate the therapeutic effects of BCG on EAE. RESULTS: Inoculation with BCG 6 d after CWS-EAE induction successfully ameliorated EAE symptoms, suggesting that the therapeutic effects of BCG are independent of the mycobacterial antigen-specific T cells induced by the CFA-EAE protocol. BCG inoculation into the CWS-EAE mice resulted in reduced levels of MOG-specific Th17 in the central nervous system (CNS) with reduced demyelinated lesions of the spinal cord. In the draining lymph nodes of the MOG-immunized sites, BCG inoculation resulted in an increase in MOG-specific Th17 and Th1 cells at an early stage of immune response. CONCLUSION: The results suggest that BCG inoculation suppresses the Th17 response in the CNS of EAE mice via a mechanism that may involve the suppression of egress of encephalitogenic T cells from lymphoid organs.

Nationwide Survey on Actual Interventions for Type 2 Diabetes by Japanese Practitioners (NSAID Study-1): Glycemic, Weight, and Blood Pressure Management.

INTRODUCTION: Considering the increase in the number of patients with diabetes, the quality of diabetes care provided by general practitioners (GP) is critical for preventing complications. We performed a nationwide survey to determine whether the diabetic management provided to patients with type 2 diabetes mellitus (T2DM) by Japanese practitioners is appropriate. METHODS: We randomly selected 463 clinics throughout Japan; 8070 patients with T2DM (6525 and 1545 under the care of GP and specialists [SP], respectively) were enrolled. We obtained information on hemoglobin A1c (HbA1c) levels, age, height, body weight, diabetes type and treatment modality, blood pressure (BP), and hypertension or dyslipidemia from each patient. Additionally, we surveyed the collaborations among physicians. RESULTS: The median HbA1c level of patients treated by GP was lower than that of patients treated by SP (6.8 [6.2-7.3], median [interquartile range] vs. 6.9 [6.5-7.5], p < 0.0001). The percentage of patients receiving insulin therapy was also higher (23.8%) among patients treated by SP than among those treated by GP (8.6%). Patients not receiving insulin therapy showed lower median HbA1c levels than those receiving insulin therapy, irrespective of the care provider. The mean body mass index of patients with HbA1c levels < 6.9% or > 9.0% cared for by SP was lower than that of those cared for by GP. The rate of target BP (< 140/90 mmHg) achievement was 73.2% and 73.3% among patients with T2DM and hypertension cared for by GP and SP, respectively. Furthermore, 88.2% of GP reported that consulting with SP was easy. CONCLUSION: The present study clearly demonstrated that many patients with T2DM are appropriately cared for by general practitioners instead of diabetes specialists in Japan, although the number of diabetes specialists is insufficient to cover all patients with diabetes.

Effect of canagliflozin on the overall clinical state including insulin resistance in Japanese patients with type 2 diabetes mellitus.

AIMS: Information on the clinical efficacy of SGLT2 inhibitors in the Japanese population is limited. The aim of this single-arm, single-center, open-label study was to confirm the body weight- and fat mass-lowering effects of canagliflozin (CANA) and the accompanying improvement in insulin resistance in Japanese patients with Type 2 diabetes mellitus (T2DM). METHODS: Thirty-eight patients were enrolled and administered 100 mg CANA once daily for 24 weeks. Blood and anthropometric parameters were examined before and after treatment. In a subset of patients, insulin sensitivity was assessed based on the glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test. RESULTS: CANA treatment significantly decreased hemoglobin A1c, fasting plasma glucose, and plasma liver enzyme levels, and increased plasma adiponectin levels. In addition, a significant reduction in body weight, visceral and subcutaneous fat area, fat and lean mass, and liver steatosis was also observed. The change in plasma adiponectin levels significantly correlated with the changes in both body fat mass and visceral fat area. GIR increased from 3.25 ±â€¯1.53 to 4.11 ±â€¯1.30 mg/kg/min (P < 0.05). CONCLUSIONS: CANA improved insulin resistance and decreased visceral fat mass in Japanese patients with T2DM.

Relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetic patients (JDDM38).

AIMS/INTRODUCTION: We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. MATERIALS AND METHODS: We analyzed the CoDiC(®) database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug-naïve patients who were initiated with metformin, dipeptidyl peptidase-4 inhibitor (DPP-4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. RESULTS: HbA1c was reduced with all drugs, with the largest effect elicited by DPP-4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age-of-onset of <50 years (P = 0.00). BMI increased with SU in the patients stratified by a BMI of <25 (P = 0.00), and decreased with metformin in the patients with a BMI >25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of <8% (P = 0.00). HbA1c during the study period was higher in patients who were added to or swapped with other drug(s), than in patients continued on the original drug (P = 0.00). CONCLUSIONS: The effect on bodyweight and glycemic control differed among metformin, DPP-4i and SU, and the difference was associated with clinical features.

Both glimepiride and high-dose metformin are important for sustained glucose lowering in Japanese type 2 diabetes patients on glimepiride-sitagliptin-metformin therapy: subanalysis of a single-center, open-label, randomized study.

BACKGROUND: In a previous single-center, open-label randomized 3-month study of triple oral antidiabetes drug (OAD) therapy, we investigated factors affecting the glycemic control afforded by sitagliptin, high-dose metformin, and low-dose glimepiride. Patients were prospectively assigned to either Group 1 (50% reduction in metformin) or Group 2 (discontinuation of glimepiride) and compared. The results showed that the glycated hemoglobin (HbA1c) levels of patients in Group 2 deteriorated more than those in Group 1, whereas HbA1c levels were maintained in some patients in both groups. MATERIALS AND METHODS: To determine the factors associated with maintenance of HbA1c under this triple OAD regimen, data from the prospective study were further analyzed. RESULTS: In both Groups 1 and 2, the baseline HbA1c level was higher in patients with HbA1c ≥7.0% after 3 months of treatment than those with an HbA1c level of <7.0%. A generalized linear model revealed that high-dose metformin was associated with a deterioration of HbA1c levels in Group 2. CONCLUSIONS: Together, the findings indicate that glimepiride and high-dose metformin are important for sustained glycemic control in triple OAD therapy with sitagliptin, metformin, and sulfonylurea.

Glimepiride strongly enhances the glucose-lowering effect in triple oral antidiabetes therapy with sitagliptin and metformin for Japanese patients with type 2 diabetes mellitus.

BACKGROUND: After approval of sitagliptin and >750 mg of metformin in Japan, a triple oral antidiabetes drug (OAD) regimen including sulfonylurea, metformin, and sitagliptin was sometimes described. However, in the real world of clinical practice, the daily dose of sulfonylurea tended to be decreased according to the warning from the Japan Diabetes Society for avoiding hypoglycemia, instead of increasing the dose of metformin for maintaining hemoglobin A1c (HbA1c) levels with this regimen. This study examined the impact of either a small dose of glimepiride or a high dose of metformin on HbA1c in triple OAD therapy with sitagliptin in a 3-month, single-center, open-label, randomized controlled study. SUBJECTS AND METHODS: Fifty-six type 2 diabetes mellitus patients who had been treated with 50 mg of sitagliptin, ≥ 1,000 mg of metformin, and ≤ 1 mg of glimepiride with an HbA1c level of <7.4% during at least 3 months were enrolled in the study. The patients were randomly assigned to two treatment groups who either received a 50% reduced dose of metformin (n = 27) or discontinued glimepiride (n = 29), while sitagliptin administration continued in both groups. Twenty-six patients from the reduced metformin group and 27 patients from the discontinued glimepiride group completed the study. RESULTS: Significantly greater changes were observed in HbA1c and glycated albumin levels in patients who discontinued glimepiride than in patients with a 50% reduced metformin dose, during the 2-3-month period than in the 1-3-month period. CONCLUSIONS: Glimepiride is important for good glycemic control in triple OAD therapy with sitaglitpin and metformin. This regimen may be useful for those patients who do not achieve satisfactory glycemic control with dual combination therapy.

Short duration of diabetes and disuse of sulfonylurea have any association with insulin cessation of the patients with type 2 diabetes in a clinical setting in Japan (JDDM 30).

Insulin therapy is often required to achieve good glycemic control for the patients with type 2 diabetes mellitus (T2DM), while protraction of glycemic control without insulin therapy may be preferable for patients. To determine the characteristics of and therapeutic regimen in outpatients with T2DM who were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan by a case-control study. The present study was performed on 928 patients with T2DM who started insulin therapy in 2007. Data regarding age, sex, body mass index, duration of diabetes, HbA1c, postprandial plasma glucose, plasma fasting C-peptide immunoreactivity and treatment modality were compared between patients who were able to stop insulin therapy and those who continued with insulin. Of the 928 patients, 37 had stopped insulin therapy within 1 year. In the patients who stopped insulin therapy, the duration of diabetes was significantly shorter and the daily insulin dosage at initiation and the prevalence of sulfonylurea pretreatment significantly lower compared with patients who continued on insulin. In conclusion, almost 4% of T2DM patients were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan. Shorter duration of diabetes and disuse of sulfonylureas prior to insulin may associate with stopping insulin therapy as a near-normoglycemic remission in outpatients with T2DM in Japan.

Self-reported rate of eating is significantly associated with body mass index in Japanese patients with type 2 diabetes. Japan Diabetes Clinical Data Management Study Group (JDDM26).

We examined whether the rate of eating was associated with the body mass index and glycemic control status in Japanese patients with type 2 diabetes (50% women, mean±SD age 59.4±7.5 years). Rapid eating was significantly associated with body mass index (p=0.047). The body mass index of those who reported eating quickly was 0.8 kg/m² higher than in individuals who reported eating at medium speed even after adjustment for known confounders. No significant association was observed between the rate of eating and HbA(1c). Our findings suggest an association between self-reported rapid eating and an elevated body mass index in patients with type 2 diabetes.

Present status of insulin therapy for type 2 diabetes treated by general practitioners and diabetes specialists in Japan: Third report of a cross-sectional survey of 15,652 patients.

UNLABELLED: Aims/Introduction: Insulin therapy is often required to achieve good glycemic control in patients with type 2 diabetes mellitus. However, some providers, particularly general practitioners (GPs), are reluctant to prescribe insulin to their patients. The aim of the present study was to clarify any differences in, as well as any problems associated with, insulin therapy in patients with type 2 diabetes being treated by either a GP or a diabetes specialist in Japan. MATERIALS AND METHODS: Of 15,652 patients across 721 clinics and hospitals, 15,350 were diagnosed with type 2 diabetes (14,312 by GPs and 1038 by specialists). Data regarding glycated hemoglobin (HbA1c) levels, age, height, bodyweight and treatment modality were collected for each patient. RESULTS:   Of the patients with type 2 diabetes, 9.1 and 22.9% had been prescribed insulin monotherapy, and 38.8 and 37.0% were also receiving insulin with an oral antidiabetic (OAD) by GPs or specialists, respectively. Diabetes specialists prescribed analog insulin more frequently than did GPs. GPs chose premixed insulin more frequently than did specialists, and this factor correlated with higher HbA1c levels. A younger age and daily insulin dose in groups being treated by both providers were correlated with high HbA1c levels on insulin monotherapy. Neither type of insulin nor OAD was correlated with HbA1c on insulin plus OAD therapy. CONCLUSIONS:   To achieve better glycemic control with insulin therapy, sufficient insulin dose and intensive treatment regimen, in addition to lifestyle interventions, might be necessary. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00198.x, 2012).

Combination Therapy with a Dipeptidyl Peptidase-4 Inhibitor, Sulfonylurea, and Metformin Markedly Improves HbA1c Levels in Japanese Patients with Type 2 Diabetes Mellitus.

Combination therapy with a dipeptidyl peptidase (DPP)-4 inhibitor and metformin or sulfonylurea results in substantial and additive glucose-lowering effects in patients with type 2 diabetes mellitus (T2DM). However, it is not known whether triple combination therapy with a DPP-4 inhibitor, metformin, and sulfonylurea has greater additive effects or synergic effects. In the present report, we investigated the effect of addition of sitagliptin, the first-in-class DPP-4 inhibitor, to ongoing metformin and sulfonylurea therapy in three female Japanese patients with T2DM who refused insulin therapy. Combined treatment with all three drugs resulted in marked improvements in HbA1c. In the first patient, HbA1c levels decreased from 11.1% to 6.1% after the addition of sitagliptin to metformin 1000 mg, glibenclamide, and miglitol, even though the dose of glibenclamide was decreased. HbA1c levels decreased similarly in the second patient, who was being treated with metformin and glibenclamide, from 7.9% to 6.0% after addition of sitagliptin and an increase in metformin to 2250 mg; this patient ceased glibenclamide because of hypoglycemia and instead was started on low-dose glimepiride. In the third patient, HbA1c levels decreased from 8.6% to 7.1% after addition of glimepiride to ongoing sitagliptin and metformin therapy. All three patients had refused insulin therapy, despite the fact that ongoing combination therapy had failed to achieve satisfactory glycemic control. Based on these results, it is likely that the addition of sitagliptin to metformin and at least a small dose of sulfonylurea may be effective in reducing HbA1c levels without weight gain. This triple combination therapy may prove useful in at least some patients who need initiation of insulin therapy.

Present status of sulfonylurea treatment for type 2 diabetes in Japan: second report of a cross-sectional survey of 15,652 patients.

Sulfonylureas are commonly used for the treatment of patients with type 2 diabetes mellitus (T2DM). However, some clinical concerns regarding their use have grown over the past decade. Thus, results of a previous Japan-wide cross-sectional survey of patients with type 2 diabetes mellitus (T2DM) were analyzed to determine the present status and problems associated with the use of sulfonylureas in the treatment of T2DM by general practitioners (GPs) and diabetes specialists. Of 15,652 patients across 721 clinics and hospitals from the previous survey, 15,350 were diagnosed as T2DM (14,312 by GPs and 1,038 by specialists). For each patient, data were collected for HbA1c levels, age, height, body weight, and treatment modality. Of T2DM patients being treated by GPs, 35.4% and 60.0% received sulfonylureas in entire oral drugs or as monotherapy, respectively, compared with 29.2% and 61.2% of patients, respectively, treated by specialists. Of the patients treated with sulfonylurea monotherapy, 1335 patients (35.2%) achieved HbA1c <6.5%, whereas HbA1c was >or=8.0% in 531 patients (14.0%). Patients with HbA1c levels >or=8.0% had a higher body mass index, used glibenclamide more frequently, and used higher doses of sulfonylureas than patients in whom HbA1c levels were <6.5%. In conclusion, the present study shows that sulfonylureas are central in the treatment of T2DM in Japan. However, careful consideration of suitable patients, agents, and doses is necessary to achieve appropriate glycemic control.

Nicotine suppresses energy storage through activation of sympathetic outflow to brown adipose tissue via corticotropin-releasing factor type 1 receptor.

Nicotine is known to stimulate energy expenditure, although the precise mechanism is unclear. To clarify the involvement of corticotropin-releasing factor (CRF) in the mechanism by which nicotine increases energy expenditure, the effect of intraperitoneal injection of nicotine (0.1 or 0.5mg/kg) on the release of noradrenaline (NA), a stimulator of thermogenesis, in brown adipose tissue (BAT) important for energy expenditure was examined in rats. We also examined the effects of CRF receptor subtype antagonists on the nicotine-induced change in BAT NA release. Nicotine significantly increased BAT NA release at a dose of 0.5mg/kg, and the increase was completely blocked by antalarmin, a CRF type 1 receptor antagonist, but not by antisauvagine-30, a CRF type 2 receptor antagonist. These results suggest that nicotine increases energy expenditure by activating BAT function, and that CRF type 1 receptors are involved in the mechanism by which nicotine affects energy balance.

The status of glycemic control by general practitioners and specialists for diabetes in Japan: a cross-sectional survey of 15,652 patients with diabetes mellitus.

To determine the status of diabetes care by general practitioners and diabetes specialists in Japan, we conducted a nation-wide cross-sectional survey. We asked 8112 clinics and hospitals randomly, from throughout Japan, to participate in this study and 721 facilities agreed. A total of 15,652 patients aged from 15 to 97 with type 1 and type 2 diabetes were enrolled. Of these, 14,560 (93.0%) and 1092 (7.0%) patients were cared for by general practitioners and diabetes specialists, respectively. HbA1c levels were measured by a latex agglutination method, and age, height, body weight, type of diabetes and treatment modality were obtained from each patient. Mean HbA1c level for all patients treated by general practitioners was significantly lower than for those treated by the diabetes specialists (6.8+/-1.2% vs. 7.0+/-1.2%, p=0.0002). Mean HbA1c level for patients without insulin therapy was lower than for those treated with insulin, irrespective of caring physician. The proportion of patients treated with insulin therapy by diabetes specialists was higher (17.7%) than that by general practitioners (6.5%). This study showed that average HbA1c levels in Japanese patients treated by either general practitioners or specialists was acceptable, regardless of study limitations or bias.

Association between body mass index and core components of metabolic syndrome in 1486 patients with type 1 diabetes mellitus in Japan (JDDM 13).

There is no recent study on the prevalence of overweight and obesity in patients with type 1 diabetes mellitus (T1DM) in Japan. Being overweight has a significant effect on the metabolic condition and glycemic control of such patients. In the present cross-sectional study, we investigated the effects of body mass index (BMI) on lipid profile, blood pressure, and glycemic control in patients with T1DM. In total, 1486 patients with T1DM (including 401 patients with early onset T1DM who were <20 years of age at diagnosis) were included. Patients were divided into four groups according to their BMI, and glycosylated hemoglobin (HbA1c), daily insulin dose per kg body weight, lipid profile, and blood pressure were compared between groups. We found that 15.7% of all patients were overweight (BMI >or= 25.0 kg/m(2)) and 2.0% were obese (BMI >or= 30.0 kg/m(2)), compared with 17.5% and 2.0%, respectively, in the early onset T1DM subgroup. Significant changes in lipid profiles and blood pressure were found with increasing BMI in both the entire population and the early onset T1DM subgroup. In the entire study population HbA1c and the body weight-adjusted daily insulin dose were significantly higher in patients with a BMI >or= 23 kg/m(2) compared with those with a BMI<23 kg/m(2); however, this was not the case in the early onset T1DM subgroup. This difference may be due to the relatively small number of patients in that subgroup. In conclusion, the prevalence of overweight and obesity in patients with T1DM was less than that in the normal Japanese population. For patients with T1DM, being overweight was associated with higher blood pressure and dyslipidemia. Furthermore, we cannot exclude an association between being overweight and the need for higher daily doses of insulin.

Six-month multicentric, open-label, randomized trial of twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart in Japanese type 2 diabetic patients (JDDM 11).

To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy, we conducted a 6-month multicentric, open-label, randomized trial in Japanese insulin-naive patients with type 2 diabetes mellitus. A total of 160 adult patients at 19 centers were randomized into two groups: those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin (multiple daily injections). At 6 months, mean HbA(1c) decreased by approximately 2.5% in both groups. Reduction of HbA(1c) on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise (-5.0%) than in patients who were previously taking oral antidiabetic agents (-1.0%). No incidence of major hypoglycemia was observed in either regimen. These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months. Furthermore, early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control. This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus, especially for insulin-naive patients over 6 months, although it should be changed to another regimen when expected efficacy is not obtained.