To examine the effects of telmisartan on peroxisome proliferator–activated receptor γ activation, we compared the effects of telmisartan with those of candesartan on adipocytokines and glucose and lipid metabolism in vivo and in vitro. In vivo, 56 patients with both type 2 diabetes and hypertension were enrolled and randomized to receive either telmisartan (40 mg) or candesartan (8 mg) for 3 months. Serum adiponectin, HbA1c levels, lipid profiles and blood pressure were recorded at the beginning and 3 months later. In vitro, differentiated 3T3-L1 adipocytes were treated with telmisartan, candesartan, pioglitazone or vehicle for 24 h, and then adiponectin mRNA and protein levels were measured. The results showed that most of the metabolic parameters, including the lipid profiles, did not change significantly during the study in either group. However, the changes in serum adiponectin and plasma glucose over 3 months were significantly greater in the telmisartan group than in the candesartan group. In vitro, although the protein level of adiponectin was not significantly elevated, the mRNA expression of adiponectin was elevated 1.5-fold by telmisartan in 3T3-L1 adipocytes. Our findings suggest that telmisartan may have beneficial effects in type 2 diabetes beyond its antihypertensive effect.

We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding. All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite. Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

We previously showed that a non-calorie-restricted, moderately low-carbohydrate diet (mLCD) is more effective than caloric restriction for glycemic and lipid profile control in patients with type 2 diabetes. To determine whether mLCD intervention is sustainable, effective, and safe over a long period, we performed a 36-month observational study. We sequentially enrolled 200 patients with type 2 diabetes and taught them how to follow the mLCD. We compared the following parameters pre- and post-dietary intervention in an outpatient setting: glycated hemoglobin (HbA1c), body weight, lipid profile (total cholesterol, low and high-density lipoprotein cholesterol, triglycerides), systolic and diastolic blood pressure, liver enzymes (aspartate aminotransferase, alanine aminotransferase), and renal function (urea nitrogen, creatinine, estimated glomerular filtration rate). Data from 157 participants were analyzed (43 were lost to follow-up). The following parameters decreased over the period of study: HbA1c (from 8.0 ± 1.5% to 7.5 ± 1.3%, p < 0.0001) and alanine aminotransferase (from 29.9 ± 23.6 to 26.2 ± 18.4 IL/L, p = 0.009). Parameters that increased were high-density lipoprotein cholesterol (from 58.9 ± 15.9 to 61.2 ± 17.4 mg/dL, p = 0.001) and urea nitrogen (from 15.9 ± 5.2 to 17.0 ± 5.4 mg/dL, p = 0.003). Over 36 months, the mLCD intervention showed sustained effectiveness (without safety concerns) in improving HbA1c, lipid profile, and liver enzymes in Japanese patients with type 2 diabetes.

Objective: In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation. Results: By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities.

For prevention of the aggravation of diabetic nephropathy, a treatment method that combines self-care with medical guidance is becoming increasingly important, leading to the development of programs for lifestyle modification for the patients. To assess the effectiveness of such programs, we have conducted a feasibility study of a patient self-care support program with medical collaboration by registered pharmacists in community pharmacies involving patients with diabetic nephropathy who are under treatment at medical institutions, including our hospital. This study evaluated the two primary measurements, which are A) the actual execution rate versus planned programs, and B) the patient satisfaction rate. In addition, the achievement rate of behavioral objectives, satisfaction rate of diabetes treatment, degree of concerns (Diabetes Treatment Satisfaction Questionnaire; DTSQ, Problem Areas in Diabetes; PAID) and other physiological indicators have been evaluated. With the approval of the IRB at Kitasato University, sixteen out of 18 patients have continued to participate in the support program, and the study has shown high patient satisfaction with pharmacist coaching support. Patients have gained interest in managing their lifestyles, thereby increasing self-efficacy. Also, information shared between the pharmacists and the physicians has clarified patients' issues and concerns pertaining to their lifestyles, which were effectively utilized in the coaching program. Through meetings with pharmacists, patients have been reassured of the expertise of the pharmacist and thus gained mutual trust, which leads to the patient's behavioral change. We believe that the collaboration of patients, pharmacists and physicians has resulted in effective team-based patient care.