Mikio Yamauchi

Current Status of Antihypertensive Prescription and Associated Blood Pressure Control in Japan

The importance of tight blood pressure (BP) control has been established. We performed cross-sectional studies on the current status of BP control and the prescription and efficacy of antihypertensive drugs in hypertensive patients in Japan. The data were also evaluated in subgroups with or without diabetes mellitus (DM) and in winter and summer. Analyses were performed on the collected data of 12,437 treated hypertensive patients in winter and 5,972 in summer 2002. In winter, 50.3% of patients received calcium channel blockers (CCBs), 15.3% received angiotensin converting enzyme inhibitors (ACEIs) and 11.0% received angiotensin receptor blockers (ARBs). In the patients receiving monotherapy, 69% of patients received a CCB, 13% an ACEI and 11.0% an ARB. A total of 2,918 patients received combination therapy, and CCBs were the most frequently (89.6%) prescribed component of such therapy. Prescriptions of β-blockers (BBs) decreased and those of CCBs and diuretics (D) increased with age (p<0.001). The rate of patients with adequately controlled BP less than 140/90 mmHg was 40.3% in the CCB group, 37.6% in the D group, and 36.9% in the BB group (p<0.001). In patients receiving combination therapy, those with CCB+D had the best rate of BP control (40.7%). The rate of patients with adequately controlled BP was lower in winter than in summer at both a target BP of 140/90 mmHg (36.2% vs. 43.8%, p<0.001) and a target BP of 130/85 mmHg in patients younger than 60 years old (15.5% vs. 18.6%, p<0.02). In diabetic patients, the target BP (130/80 mmHg) was achieved in only 11.3%, which was lower (p<0.05) than the rate in non-diabetic patients (13.1%). In conclusion, the present cross-sectional study showed that CCBs were the most frequently prescribed agent for the treatment of hypertension in Japan. The rate of adequate BP control was less than 50% and was even worse in patients with DM and in winter. Our results indicate that physicians should treat hypertension more intensively to achieve the target BP.

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.

How does deep breathing affect office blood pressure and pulse rate

Little is known about the relation between deep breathing (DB) and blood pressure (BP). We studied the relationship between DB and BP in a large Japanese population. The subjects were recruited from randomly selected clinics and hospitals that were members of a medical association, and divided into two groups. In one group, BP was measured before and after taking 6 DB over a period of 30 s, and in the other group BP was measured before and after a 30-s rest in a sitting position without DB. Before these measurements, all patients rested 10 min or more in the waiting room and another 2 min or more in the doctors office. Analyses were performed on data collected from 21,563 subjects. In both groups, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were significantly reduced after DB or a 30-s rest compared with the baseline measurements (p<0.001). SBP reductions were greater in the DB group than in the 30-s rest group (normotensives: -6.4±8.3 vs. -3.0±7.4 mmHg, p<0.001; untreated hypertensives: -9.6±10.2 vs. -5.9±9.1 mmHg, p<0.001; treated hypertensives: -8.3±9.6 vs. -4.4±8.3 mmHg, p<0.001). Greater BP reductions were found in patients with a higher baseline BP in both the DB and 30-s rest groups. In conclusion, the present study showed a baseline BP-dependent BP reduction by DB, suggesting that BP measurement should be done without DB in the office because DB lowers BP.

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.

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.

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.

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.