Hidetaka Hamasaki

Effects of 6-Month Sitagliptin Treatment on Glucose and Lipid Metabolism, Blood Pressure, Body Weight and Renal Function in Type 2 Diabetic Patients: A Chart-Based Analysis

Background Sitagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors which prevent the inactivation of incretins, increasing the endogenous active incretin levels. Incretins stimulate insulin secretion from pancreatic β-cells and inhibit glucagon secretion from pancreatic α-cells, which is favorable for the treatment of diabetes. Sitagliptin is released on December, 2009, in Japan. We retrospectively studied effects of 6-month-treatment with sitagliptin on glucose and lipid metabolism, blood pressure, body weight and renal function in patients with type 2 diabetes by a chart-based analysis. Methods We retrospectively studied 220 type 2 diabetic patients who have taken sitagliptin for 6 months by a chart-based analysis. Subjects studied include patients treated with sitagliptin monotherapy, sitagliptin add-on therapy, and switching from glinide to sitagliptin. We selected patients who have both data before and after 6-month sitagliptin treatment and compared the data before the sitagliptin treatment with the data at 6 month after the sitagliptin treatment started. Body weight, blood pressure, plasma glucose, hemoglobin A1c (HbA1c), serum lipids, and estimated glomerular filtration rate in type 2 diabetic patients were measured almost at the same time points before and after 6-month-treatment with sitagliptin. Results Body weight was significantly reduced after 6-month sitagliptin treatment by 0.8 kg. HbA1c levels were also significantly decreased after the sitagliptin treatment by 0.6%. We found a significant and negative correlation between change in body weight and body mass index at baseline. We also observed a significant and negative correlation between change in HbA1c and HbA1c levels at baseline. The number of patients who showed the absence of urinary glucose was significantly increased after the sitagliptin treatment.

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes.

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association between hypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide (approximately 45%-76%) and thiazolidinediones (approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high HbA1c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

Effects of Dietary Fat Intake on HDL Metabolism

High-density lipoprotein (HDL) is a lipoprotein which has anti-atherogenic property by reversing cholesterol transport from the peripheral tissues to liver. Low HDL-cholesterol (HDL-C) as well as high low-density lipoprotein-cholesterol (LDL-C) is associated with the development of coronary heart diseases (CHD). Various epidemiological studies have suggested that the development of CHD increase in individuals with less than 40 mg/dL of HDL-C. In spite of accumulation of evidences suggesting a significant association between low HDL-C and CHD, effects of dietary factors on HDL metabolism remained largely unknown. We reviewed published articles about effects of dietary fat intake on HDL metabolism. The substitution of fatty acids (FA) for carbohydrates is beneficially associated with HDL metabolism. Monounsaturated FA intake may not affect HDL-C. Trans-FA is significantly associated with reduction of HDL-C, and is also adversely related with total cholesterol/HDL-C. Fish oils consumption, especially docosahexaenoic acid consumption, may be favorably associated with HDL metabolism. Although plant sterols and stanols may not affect HDL-C, policosanol intake is associated with a clinically significant decrease in the LDL/HDL ratio.

Correlations of non-exercise activity thermogenesis to metabolic parameters in Japanese patients with type 2 diabetes

BackgroundNon-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercise and resistance training in daily life.MethodsWe studied 45 subjects (22 women and 23 men) with type 2 diabetes who did not take any hypoglycemic, anti-hypertensive, or cholesterol-lowering agents and asked them about physical activity concerned with NEAT using an original questionnaire modified from a compendium of physical activities. We studied the association of the NEAT score to body weight, waist circumference, blood pressure, glucose and lipid metabolism, and arterial stiffness.ResultsThe NEAT score was negatively correlated with serum insulin levels (r = -0.42, P < 0.05) in all subjects. The NEAT score was also negatively correlated with waist circumference (r = -0.509, P < 0.05) and positively correlated with high-density lipoprotein-cholesterol levels (r = 0.494, P < 0.05) in women, and negatively associated with serum insulin levels (r = -0.732, p < 0.005), systolic (r = -0.482, P < 0.05) and diastolic blood pressure (r = -0.538, P < 0.05) in patients with abdominal obesity. Furthermore, the NEAT score was negatively associated with pulse wave velocity (r = -0.719, P < 0.005) in smokers.ConclusionThe study demonstrated that NEAT is associated with amelioration in insulin sensitivity, waist circumference, high-density lipoprotein-cholesterol, blood pressure and the marker for atherosclerosis in patients with type 2 diabetes.

Daily physical activity and type 2 diabetes: A review

Physical activity improves glycemic control and reduces the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes (T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework that type 2 diabetic patients should be able to perform without considerable physical burden. This review focuses on the association between daily physical activity and T2D. Walking was the most common form of daily physical activity, with numerous studies demonstrating its beneficial effects on reducing the risk of T2D, CVD, and mortality. Walking for at least 30 min per day was shown to reduce the risk of T2D by approximately 50%. Additionally, walking was associated with a reduction in mortality. In contrast, evidence was extremely limited regarding other daily physical activities such as gardening and housework in patients with T2D. Recent studies have suggested daily physical activity, including non-exercise activity thermogenesis, to be favorably associated with metabolic risks and mortality. However, well-designed longitudinal studies are warranted to elucidate its effects on overall health.

Sodium-Glucose Cotransporter 2 Inhibitors: Possible Anti-Atherosclerotic Effects Beyond Glucose Lowering

The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors. Among 10 kinds of SGLT-2 inhibitors, the number of published articles about dapagliflozin was the greatest among SGLT-2 inhibitors. Since SGLT-2 inhibitors have similar chemical structures, we concentrated on the published articles about dapagliflozin. SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure by a relatively large number of studies. The studies investigating effects of dapagliflozin on visceral fat, insulin sensitivity, serum lipids, inflammation and adipocytokines are very limited. An influence of increase in glucagon secretion by SGLT-2 inhibitors on metabolic risk factors remains unknown.

The association between daily physical activity and plasma B-type natriuretic peptide in patients with glucose intolerance: a cross-sectional study

Objectives In spite of accumulating evidences suggesting an inverse association between insulin resistance and plasma B-type natriuretic peptide (BNP) levels, the effect of daily physical activity on plasma BNP in individuals with glucose intolerance remains unknown. We investigated the association of physical activity level (PAL) with plasma BNP in patients with impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. Design Cross-sectional study. Setting Outpatients visiting the National Center for Global Health and Medicine Kohnodai Hospital. Participants A total of 60 patients with glucose intolerance who did not take any hypoglycaemic agents, cholesterol-lowering agents and antihypertensive agents were recruited. Patients who were diagnosed as having heart failure and renal impairment, engaged in sports-like exercise and resistance training were excluded. Primary outcome measures PAL was objectively measured by a triaxial accelerometer. The association between PAL and plasma BNP levels was assessed by multiple regression analysis. Results PAL was positively correlated with plasma BNP levels (r=0.296, p=0.021). PAL was still significantly correlated with plasma BNP levels after adjustment for age (β=0.290, p=0.014), and adjustment for age and body mass index (β=0.282, p=0.018). Plasma BNP levels were inversely correlated with serum insulin levels (r=−0.350, p=0.006) and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r=−0.363, p=0.004). Serum insulin levels (mean±SD, 8.1±6.4 μU/mL) and HOMA-IR (2.4±1.9) in the high-BNP group were significantly lower than those (11.2±7.4 μU/mL and 3.7±3.0, respectively) in the low-BNP group. Conclusions Our findings propose the possibility that plasma BNP may be increased by daily physical activity and BNP is associated with insulin resistance.

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes

Aim. To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). Methods. Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). Results. A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (β = −0.124, P = 0.018) and fasting serum triglycerides (β = −0.239, P = 0.035), insulin (β = −0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (β = −0.351, P = 0.044), fasting plasma glucose (β = −0.369, P = 0.025) and insulin (β = −0.362, P = 0.012), and HOMA-IR (β = −0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. Conclusion. Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.)

Hospitalization for Hypoglycemia in Japanese Diabetic Patients: A Retrospective Study Using a National Inpatient Database, 2008–2012

Abstract We aimed to elucidate the epidemiology, patient demographics, and clinical outcomes of hospitalization for hypoglycemia in diabetic patients using a Japanese large-scale database. We conducted a retrospective study using a national inpatient database of acute care hospitals in Japan. Diabetic patients ages ≥15 years with hypoglycemia as a main diagnosis for hospitalization were eligible. We estimated the annual number of hospitalizations in Japan and compared the annual admission rate by age and treatment groups. We also analyzed the association between patient characteristics and in-hospital mortality. Among 22.7 million discharge records from July 2008 and March 2013, a total of 25,071 patients were eligible. The mean age was 73.4 years, and the mean body mass index (BMI) was 22.3 kg/m2. The estimated annual hospitalization for hypoglycemia in Japan was ∼20,000. Annual admission rates for hypoglycemia per 1000 diabetic patients and 1000 diabetic patients receiving insulin or oral hypoglycemic agents were 2.1 and 4.1, respectively. Patients <40 years and >70 years old were at a higher risk of hospitalization. In-hospital mortality was 3.8%, and risk factors associated with poor survival were male sex, older age, lower bed capacity, community hospital, low BMI, coma at admission, and higher Charlson Comorbidity Index. To prevent severe hypoglycemia that leads to death and complications, individualized and careful glycemic control are important, especially in very old or young patients and in those with comorbid conditions or low BMI.

Associations between lower extremity muscle mass and metabolic parameters related to obesity in Japanese obese patients with type 2 diabetes

Background. Age-related loss of muscle mass (sarcopenia) increases the incidence of obesity in the elderly by reducing physical activity. This sarcopenic obesity may become self-perpetuating, increasing the risks for metabolic syndrome, disability, and mortality. We investigated the associations of two sarcopenic indices, the ratio of lower extremity muscle mass to body weight (L/W ratio) and the ratio of lower extremity muscle mass to upper extremity muscle mass (L/U ratio), with metabolic parameters related to obesity in patients with type 2 diabetes and obesity. Methods. Of 148 inpatients with type 2 diabetes treated between October 2013 and April 2014, we recruited 26 with obesity but no physical disability. Daily physical activity was measured by a triaxial accelerometer during a period of hospitalization, and which was also evaluated by our previously reported non-exercise activity thermogenesis questionnaire. We measured body composition by bioelectrical impedance and investigated the correlations of L/W and L/U ratios with body weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area, subcutaneous fat area, serum lipid profile, and daily physical activity. Results. The L/W ratio was significantly and negatively correlated with BMI, WC, WHR, body fat mass, body fat percentage, subcutaneous fat area, and serum free fatty acid concentration, was positively correlated with daily physical activity: the locomotive non-exercise activity thermogenesis score, but was not correlated with visceral fat area. The L/U ratio was significantly and positively correlated with serum high-density lipoprotein cholesterol. Conclusions. High L/W and L/U ratios, indicative of relatively preserved lower extremity muscle mass, were predictive of improved metabolic parameters related to obesity. Preserved muscle fitness in obesity, especially of the lower extremities, may prevent sarcopenic obesity and lower associated risks for metabolic syndrome and early mortality.