Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial.

OBJECTIVE: This study compared the efficacy and safety of azelnidipine with that of trichlormethiazide in Japanese type 2 diabetic patients with hypertension. METHODS: In a multicenter, open-label trial, 240 patients with adequately controlled diabetes (HbA1c ≤ 7.0%) under lifestyle modification and/or administration of hypoglycemic agents and inadequately controlled hypertension (systolic blood pressure [sBP] ≥ 130 mmHg or diastolic blood pressure [dBP] ≥ 80 mmHg) who were being treated with olmesartan were enrolled. Participants were randomly assigned to an azelnidipine group or a trichlormethiazide group and were followed up for 48 weeks. Main outcome measure was the difference in the change in HbA1c levels from the baseline values at 48 weeks between these two groups. RESULTS: Of the 240 subjects that were enrolled, 209 subjects (azelnidipine group: 103 patients, trichlormethiazide group: 106 patients) completed this trial. At 48 weeks, the following changes were observed in the azelnidipine and trichlormethiazide groups, respectively: HbA1c levels, 0.19 ± 0.52% and 0.19 ± 0.54%; sBP/dBP, -10.7 ± 9.6/-6.6 ± 6.6 mmHg and -7.1 ± 7.7/-3.3 ± 6.1 mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients [6.6%], P = 0.047) were observed during the 48-week follow-up period. CONCLUSIONS: Azelnidipine was more effective for controlling blood pressure than trichlormethiazide in Japanese type 2 diabetes patients, whereas trichlormethiazide was more effective for reducing albuminuria than azelnidipine. Both of these agents, however, similarly exacerbated glycemic control in type 2 diabetic patients with hypertension. TRIAL REGISTRATION: UMIN 000006081.

Second-line treatments for dyslipidemia in patients at risk of cardiovascular disease.

Previous studies have shown that approximately 50% patients at risk of cardiovascular disease do not achieve lipid management goals. Thus, improvements dyslipidemia management are needed. We investigated the clinical choice and efficacy of second-line treatments for dyslipidemia in the Japanese clinical setting. Using a retrospective cohort design, we collected lipid profile data from patients who had been treated with hypolipidemic agents at a stable dosage for at least 12 weeks. These patients had then been administered a second-line treatment for dyslipidemia because they had not achieved the low-density lipoprotein cholesterol (LDL-C) management goals. We included data from 641 patients in our analysis. The top three choices for second-line treatment were adding ezetimibe, switching to strong statins (statin switching), and doubling the original statin dosage (statin doubling). Adding ezetimibe, statin switching, and statin doubling decreased LDL-C levels by 28.2 ± 14.5%, 23.2 ± 24.4%, and 23.5 ± 17.2%, respectively. Among these three strategies, adding ezetimibe decreased LDL-C levels to the maximum extent. In patients with dysglycemia, baseline-adjusted change in hemoglobin A1c (HbA1c) levels decreased slightly in the adding-ezetimibe, statin-switching, and statin-doubling groups, but the differences were not statistically significant among the groups (-0.10 ± 0.62%, -0.22 ± 0.54%, and -0.12 ± 0.52%, p = 0.19). In conclusion, the most common second-line treatment options for dyslipidemia were adding ezetimibe, statin switching, or statin doubling. Adding ezetimibe resulted in the highest reduction in LDL-C levels. These strategies did not increase HbA1c levels when administered with conventional diabetes treatment.

Relationship between coronary artery disease and retinopathy in patients with type 2 diabetes mellitus.

OBJECTIVE: To examine risk factors for coronary artery disease (CAD) and retinopathy in patients with type 2 diabetes mellitus (DM) and assess the relationship between CAD and retinopathy. METHODS: A total of 1,003 outpatients with type 2 DM (578 men and 425 women) were classified into two groups according to the presence (based on ischemic findings on a resting electrocardiogram or a history of angina or myocardial infarction) or absence of CAD and four retinopathy stages based on the International Clinical Classification of Diabetic Retinopathy. RESULTS: Stepwise multiple regression analyses showed that independent risk factors for CAD were age, the triglyceride (TG) level and smoking, while those for retinopathy included age, age of DM diagnosis, the HbA1c level and a female gender. The prevalence of CAD increased in association with the progression of retinopathy (p<0.01). CONCLUSION: Since it is difficult to distinguish macrovascular and microvascular diseases, diabetic vascular disorders require comprehensive approaches to assessment and treatment.

Glycemic control after addition of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes showing inadequate response to thrice-a-day treatment with α-glucosidase inhibitors.

OBJECTIVE: We investigated the effect of addition of alogliptin, while continuing the α-glucosidase inhibitor (αGI) administration at the same or reduced dose, or discontinuing the drug, on the glycemic control in type 2 diabetic patients showing inadequate response to αGI treatment. RESEARCH DESIGN AND METHODS: A prospective, randomized, controlled, multicenter interventional study trial. Subjects were randomly assigned to treatment with alogliptin alone (Intake 0 group), or alogliptin in addition to an αGI administered once-/twice-/thrice-daily (Intake 1, 2 and 3 groups). MAIN OUTCOME MEASURES: Changes in glycemic control were measured. RESULTS: The HbA1c and glycoalbumin levels at 1 and 3 months were significantly lower than the values at the baseline in the Intake 1, 2 and 3 groups, but not the Intake 0 group. The body weight at 3 months was significantly lower than that at the baseline in the Intake 3 group. There were no significant differences in the degree of satisfaction or participating volition recorded, before and after the start of the study treatments. CONCLUSIONS: Addition of alogliptin to once-/twice-daily administration of an αGI may be effective for obtaining improved glycemic control, without lowering the treatment satisfaction level, in type 2 diabetic patients.

Sonographic assessment of fatty liver infiltration using the measurement of para- and perirenal fat thickness.

PURPOSE: Usefulness of abdominal ultrasonography for quantitative estimation of fatty liver by measurement of para- and perirenal sonographic fat thickness (UFT) was investigated. METHODS: Study subjects were 286 patients hospitalized for the treatment of diabetes. These subjects underwent blood chemistry studies, abdominal ultrasonography, and CT. On sonography, the thickness of combined para- and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the UFT. Fatty liver infiltration was graded on a scale of grade 0 to 3: 0, none; 1, mild; 2, moderate; and 3, severe. With abdominal CT, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was measured. RESULTS: A positive correlation was found between UFT and FL grade or between UFT and L/S ratio (p < 0.0001). Positive correlations were also found between UFT and glutamic pyruvic transaminase (p < 0.05), or cholinesterase (p < 0.0001). CONCLUSION: Measurement of UFT is a useful method for the quantification of fatty liver as well as for the quantification of visceral fat.

Hepatic fat content-independent association of the serum level of gamma-glutamyltransferase with visceral adiposity, but not subcutaneous adiposity.

We investigated the association between the serum level of gamma-glutamyltransferase (GGT) and parameters of adiposity and lipid profile, including the serum triglyceride (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in Japanese patients with type 2 diabetes mellitus and non-diabetic subjects. A total of 257 Japanese subjects (169 patients with type 2 diabetes and 88 non-diabetic subjects) were enrolled in the study. To assess the hepatic fat content, the ratio of the CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Serum GGT was significantly correlated with the waist circumference, BMI, visceral fat area (VFA), L/S ratio and TG, but not with the subcutaneous fat area (SFA). The serum GGT was still correlated with the VFA and TG, but not with the SFA, after adjustment for the four variables of age, gender, serum HbA1c and the L/S ratio. Our finding that the serum GGT is specifically associated with the VFA, but not with the SFA, suggests that the serum GGT may be useful as a convenient indicator of VFA in the clinical treatment of obesity.

Sonographic evaluation of visceral fat by measuring para- and perirenal fat.

PURPOSE: To evaluate a new method of determining visceral fat amount by measuring para- and perirenal fat on abdominal sonography. METHODS: Fifty-seven patients hospitalized for treatment of their diabetes were examined via waist circumference, abdominal sonography, and CT. On sonography, the thickness of combined para- and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the ultrasound fat thickness (UFT). The visceral fat area was measured on abdominal CT scans at the umbilicus level. Visceral fat deposition was considered elevated above 100 cm2. RESULTS: UFT correlated significantly with VFA and waist circumference (p < 0.0001). A VFA of 100 cm2 was equivalent to a UFT of 10 mm. Waist circumference values of 85 cm in males and 90 cm in females were equivalent to UFT measurements of 11 and 10 mm, respectively. CONCLUSION: A UFT of > or =10 mm reflects increased visceral fat deposition.

Development and progression of retinopathy after inpatient management of diabetes.

OBJECTIVE: To examine factors that affect the development of retinopathy after short-term inpatient management of diabetes. PATIENTS AND METHODS: The subjects were 143 patients with type 2 diabetes who were admitted for inpatient management of diabetes, and did not have retinopathy of the right eye at admission, and had an HbA1c level of > or =8.0%. We studied the characteristics of patients who developed retinopathy within one year after discharge. RESULTS: Between the admission date and one year after discharge, twenty-six patients developed retinopathy and the retinopathy subsequently regressed in 5 patients. The 26 patients who developed retinopathy had a significantly longer duration of diabetes (p<0.005), had a higher fasting blood glucose level at admission (p=0.06), and received insulin therapy during the admission at a higher rate (p=0.06) than the 117 patients without retinopathy. The magnitude of the reduction in HbA1c level at 3 months after discharge was smaller in the 13 patients who developed retinopathy within 3 months after discharge than in the 130 patients who did not. Among the 26 patients who developed retinopathy, the HbA1c level at one year after discharge of the 5 patients whose retinopathy regressed was lower than that of the 21 patients whose retinopathy did not regress (p=0.06). CONCLUSIONS: A long duration of diabetes, high fasting blood glucose level at admission, and treatment with insulin were associated with the development of retinopathy. Patients with these characteristics should undergo frequent fundus examinations after correction of hyperglycemia. The retinopathy was likely to improve if patients maintained strict glycemic control after discharge.

Use of telemedicine in periodic screening of diabetic retinopathy.

Telemedicine was used for taking ocular fundus images of diabetic patients, which were subsequently sent by electronic mail to experienced ophthalmologists at a university hospital. The ophthalmologists provided reports on the patients to the internists. The objective of the study was to evaluate the effectiveness of this telemedicine system. A total of 279 diabetic patients were admitted to the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, for blood sugar control or for education on lifestyle between April, 1999, and October, 2000. The subjects did not have eye disease nor diabetic retinopathy when evaluated by an ophthalmologist (at either Yokohama City University Hospital or other facility) within 3 months before enrollment in the study. After dilation of the pupil, fundus images were taken of each eye from four angles using a nonmydriatic fundus camera. The images were transmitted by electronic mail to the Division of Ophthalmology of Tokyo University Branch Hospital along with other patient information. The ophthalmologists there evaluated the images on the screen according to Fukuda's classification of diabetic retinopathy. They sent ophthalmologic reports to the internists at the Third Department of Internal Medicine of Yokohama City University Hospital, School of Medicine, and recommended whether the patient should be seen by his/her regular ophthalmologist earlier than the next scheduled visit. Fundus images were obtained at the time of admission, at 1, 3, and 6 months after discharge, and at every 6 months thereafter. Out of the images of 1170 eyes obtained at various time points from the 279 patients, 1076 (92.0%) were successfully evaluated by the ophthalmologists at the University of Tokyo, while 60 (5.1%) could not be evaluated and there was a communication problem for the images of 34 eyes. The ophthalmologists determined that 5 eyes of 3 patients required further evaluation by the patient's regular ophthalmologist based on the images transferred by telemedicine. No patient dropped out during the study period.