Toshihide Kawai

Plasma 25-Hydroxyvitamin D Is Independently Associated with Hemoglobin Concentration in Male Subjects with Type 2 Diabetes Mellitus

Introduction. It was reported that 25-hydroxyvitamin D level was independently associated with anemia in chronic kidney diseases, but the relation between vitamin D and anemia in diabetes mellitus is not still certain. We analyzed the relation between plasma 25-hydroxyvitamin D level and hemoglobin concentration. Materials and Methods. A cross-sectional study in male patients with type 2 diabetes was performed. Correlation coefficients and standardized partial regression coefficient for the hemoglobin concentration were evaluated. Results. Hemoglobin concentration was positively correlated with body mass index, HbA1c, estimated glomerular filtration rate, cholinesterase, and 25-hydroxyvitamin D level and negatively correlated with age, duration of diabetes mellitus, serum creatinine, and urinary albumin creatinine ratio. Multiple regression analysis revealed the independent relation of 25-hydroxyvitamin D to hemoglobin concentration. Conclusions. Plasma circulating form of vitamin D is significantly associated with hemoglobin concentration in diabetes mellitus independent of the clinical markers for kidney function or nutrition.

Effects of 16-week high-intensity interval training using upper and lower body ergometers on aerobic fitness and morphological changes in healthy men: a preliminary study.

It is unclear whether combined leg and arm high-intensity interval training (HIIT) improves fitness and morphological characteristics equal to those of leg-based HIIT programs. The aim of this study was to compare the effects of HIIT using leg-cycling (LC) and arm-cranking (AC) ergometers with an HIIT program using only LC. Effects on aerobic capacity and skeletal muscle were analyzed. Twelve healthy male subjects were assigned into two groups. One performed LC-HIIT (n=7) and the other LC- and AC-HIIT (n=5) twice weekly for 16 weeks. The training programs consisted of eight to 12 sets of >90% VO2 (the oxygen uptake that can be utilized in one minute) peak for 60 seconds with a 60-second active rest period. VO2 peak, watt peak, and heart rate were measured during an LC incremental exercise test. The cross-sectional area (CSA) of trunk and thigh muscles as well as bone-free lean body mass were measured using magnetic resonance imaging and dual-energy X-ray absorptiometry. The watt peak increased from baseline in both the LC (23%±38%; P<0.05) and the LC–AC groups (11%±9%; P<0.05). The CSA of the quadriceps femoris muscles also increased from baseline in both the LC (11%±4%; P<0.05) and the LC–AC groups (5%±5%; P<0.05). In contrast, increases were observed in the CSA of musculus psoas major (9%±11%) and musculus anterolateral abdominal (7%±4%) only in the LC–AC group. These results suggest that a combined LC- and AC-HIIT program improves aerobic capacity and muscle hypertrophy in both leg and trunk muscles.

Factors Associated with the Decline of Kidney Function Differ among eGFR Strata in Subjects with Type 2 Diabetes Mellitus.

Introduction. There is no report about risk factors for renal deterioration according to the clinical stage, divided by the estimated glomerular filtration rate (eGFR) in type 2 diabetes. Materials and Methods. We evaluated the factors correlated with the annual eGFR decline in 1303 subjects with type 2 diabetes whose eGFR was ≥30 mL/min/1.73 m2. eGFR strata were defined by baseline eGFR value as follows: stratum 1: ≥90, stratum 2: ≥60, <90, and stratum 3: ≥30, <60. Results. The annual eGFR decline was 2.3 ± 5.4 mL/min/1.73 m2 in overall subjects. Multiple linear regression analysis demonstrated that age, male sex, systolic blood pressure, logarithmically transformed albumin excretion rate (AER), eGFR strata, and hemoglobin concentration were significantly correlated with the annual eGFR decline. When stratified by eGFR, the factors that showed a significant correlation were different among eGFR strata. AER was significantly correlated with annual eGFR decline in all eGFR strata. Hemoglobin concentration showed a significant correlation only in the advanced eGFR stratum. Conclusion. The factors correlated with the annual eGFR decline were different among eGFR strata in type 2 diabetes mellitus, and hemoglobin concentration and AER were important factors for renal deterioration, especially in the advanced eGFR stratum.

Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by chronic anovulation, hyperandrogenism, obesity and a predisposition to type 2 diabetes mellitus (T2DM). Since obesity plays an important role in the etiology of PCOS, we sought to determine if variants in the perilipin gene (PLIN), a gene previously implicated in the development of obesity, were also associated with PCOS. We typed six single nucleotide polymorphisms (haplotype tagging and/or previously associated with obesity or related metabolic traits) in PLIN in 305 unrelated non-Hispanic white women (185 with PCOS and 120 without PCOS). None of the variants was associated with PCOS (P<0.05). However, the variant rs1052700*A was associated with increased risk for glucose intolerance (impaired glucose tolerance or T2DM) in both non-PCOS (OR=1.75 [1.02-3.01], P=0.044) and PCOS subjects (OR=1.67 [1.08-2.59], P=0.022). It was also associated with increased LDL (P=0.007) and total cholesterol levels (P=0.042). These results suggest that genetic variation in PLIN may affect glucose and lipid metabolism in women both with and without PCOS.

Plasma antimicrobial peptide LL-37 level is inversely associated with HDL cholesterol level in patients with type 2 diabetes mellitus

Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n = 133, 115 men and 18 women; age 64.7 ± 11.5 years; HbA1c 8.1 ± 1.6%). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2 ± 22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r = −0.450, P < 0.01), triglyceride (r = 0.445, P < 0.01), and high sensitive C-reactive protein (r = 0.316, P < 0.01) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β = −0.411, P < 0.01) and high sensitive C-reactive protein (β = 0.193, P < 0.05). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

Increased grip strength with sodium-glucose cotransporter 2.

In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes trial (EMPA-REG OUTCOME) study, empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, significantly reduced the risk of cardiovascular death and hospitalization for heart failure among patients with type 2 diabetes (T2D) and established cardiovascular disease. Possible mechanisms for these benefits include decreased blood pressure, visceral fat reduction, weight loss, and volume reduction due to a mild diuretic effect. Sarcopenia is a loss of muscle mass, resulting in reduced strength and functional decline, and in association with diabetes is a major public health concern because it leads to frailty and mortality. Subjects with diabetes exhibit a progressive decline in muscle mass and quality, caused by reduced insulin sensitivity, hormone imbalance, decreased mitochondrial function, and reduced muscle regenerative capacity. In turn, reduced physical activity further worsens sarcopenia. There remains a lack of consensus as to how to screen for sarcopenia. A recent large longitudinal study revealed that hand grip strength was inversely associated with all-cause mortality, cardiovascular mortality, and myocardial infarction in the general population. Measurement of maximal hand grip strength could be a simple and inexpensive method for cardiovascular risk stratification among subjects with T2D. We examined the change in maximal hand grip strength before and after SGLT2 inhibitor treatment. The study was performed on 112 Japanese subjects with T2D (92 men, 20 women). In men, mean (± SD) age, baseline body mass index (BMI), and HbA1c was 62.8±10.2 years, 25.6± 4.5 kg/m, and 7.0± 1.3%, respectively. In women, mean (± SD) age, baseline BMI, and HbA1c was 65.2 ±9.0years, 24.5±4.3kg/m, and 7.3±1.5%, respectively. Subjects were treated with ipragliflozin 50mg, luseogliflozin 2.5mg, or dapagliflozin 5 or 10mg daily for at least 4weeks. The mean (± SD) observation period was 10.3±2.9weeks after SGLT2 inhibitor treatment. In both men and women, grip strength increased in both hands after SGLT2 inhibitor treatment (P< 0.01, paired t-test; Fig. 1). These findings were

Relationship between Stage of Diabetic Retinopathy and Pulse Wave Velocity in Japanese Patients with Type 2 Diabetes

Objectives. We investigated the relationship between the stage of diabetic retinopathy and pulse wave velocity (PWV). Methods. This was a cross-sectional study of 689 patients (406 men and 283 women) with type 2 diabetes who were admitted to our hospital from 2004 to 2007. Brachial-ankle pulse wave velocity (baPWV) was measured by an arterial pressure measurement device as PWV/ABI. Diagnosis of diabetic retinopathy was made by ophthalmologists based on the Davis classification: no diabetic retinopathy (NDR), simple retinopathy (SDR), pre-proliferative retinopathy (pre-PDR), and proliferative retinopathy (PDR). Results. There was a significant difference in PWV between patients without diabetic retinopathy (1657.0 ± 417.9 m/s (mean ± SD)) and with diabetic retinopathy (1847.1 ± 423.9 m/s) (P < 0.001). In addition, the stage of diabetic retinopathy was associated with aortic PWV (1657.0 ± 417.9 m/s in NDR (n = 420), 1819.4 ± 430.3 m/s in SDR (n = 152), 1862.1 ± 394.0 m/s in pre-PDR (n = 54), and 1901.1 ± 433.5 m/s in PDR (n = 63) (P < 0.001)). Conclusions. In patients with diabetic retinopathy, even in those with SDR, PWV was higher than that in patients without diabetic retinopathy. Physicians should therefore pay attention to the value of PWV and macroangiopathy regardless of the stage of diabetic retinopathy.

Basal-Supported Oral Therapy with Sitagliptin Counteracts Rebound Hyperglycemia Caused by GLP-1 Tachyphylaxis.

Introduction. Treatment with a glucagon-like peptide 1 (GLP-1) analog fails in some patients due to rebound hyperglycemia caused by tachyphylaxis (GLP-1 tachyphylaxis). We investigated the efficacy of basal-supported oral therapy (BOT) with insulin glargine and sitagliptin for counteracting GLP-1 tachyphylaxis. Materials and Methods. The subjects were 12 men and 3 women aged 59.9 ± 10.0 years who had been treated with GLP-1 analogs. All of them had developed rebound hyperglycemia caused by GLP-1 tachyphylaxis. Their GLP-1 analog-based therapy was switched to BOT with insulin glargine plus sitagliptin and other medications. The primary outcomes were whether switching of therapy was associated with a change of hemoglobin A1c (HbA1c) and whether weight gain occurred. Results. Baseline HbA1c was 8.0 ± 0.9%. It decreased to 7.3 ± 0.9% at 3 months after switching (P < 0.01) and to 7.2 ± 0.9% at 4 months (P < 0.05). Weight gain was 1.1 kg after 1 month (P < 0.01) and 2.3 kg after 5 months (P < 0.01). Conclusion. Switching to BOT with insulin glargine and sitagliptin improved glycemic control. The significant decrease of HbA1c demonstrated that this combination can counteract deterioration of glycemic control due to rebound hyperglycemia secondary to GLP-1 tachyphylaxis. However, weight gain remains a problem.

Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by β-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan. Thus, this study aimed to clarify the difference in the clinical characteristics of GADA-ELISA-positive and GADA-ELISA-negative patients originally diagnosed as SPIDDM by GADA-RIA test. As a result, 42 of 63 original GADA-RIA-positive SPIDDM patients (66.7%) were found to be GADA-ELISA-positive, whereas the remaining 21 patients (33.3%) were found to be GADA-ELISA-negative. In patients with shorter disease duration, GADA-ELISA-positive patients showed significantly lower serum C-peptide levels than GADA-ELISA-negative patients. Meanwhile, in patients with longer disease duration, serum C-peptide levels were comparably decreased in GADA-ELISA-positive and GADA-ELISA-negative patients. A significant inverse correlation between serum C-peptide level and disease duration was observed in GADA-ELISA-negative patients, but not in GADA-ELISA-positive patients, suggesting that insulin secretory capacity may be gradually impaired over time also in GADA-ELISA-negative SPIDDM patients. In conclusion, physicians should be aware that GADA-ELISA-positive SPIDDM may be strongly associated with a future insulin-dependent state. Meanwhile, physicians should be careful in treating GADA-ELISA-negative SPIDDM patients diagnosed as type 2 DM, and cautiously follow the clinical course, in accordance with SPIDDM.

Factors affecting consultation length in a Japanese diabetes practice

AIMS Sufficient consultation time is important for establishing good doctor-patient relationship. We examined the factors that affect consultation length in Japanese diabetes practice. METHODS This was a cross-sectional study performed at a diabetes clinic in central Tokyo, Japan. Regular diabetes consultations of 1197 patients with 22 physicians were analyzed. Consultation time and clinical characteristics were obtained from the electronic records. A negative binomial model, which included patient and physician characteristics, was constructed to examine the association of the variables with consultation length. RESULTS Of the 1197 patients (mean age, 66; women, 25%; type 1 diabetes, 10%), the mean consultation time was 10.1min. In the multivariate model, longer consultation time was recorded in patients with type 1 diabetes, higher glycated hemoglobin (HbA1c), use of insulin injections, and use of hypnotics/anxiolytics. The consultation time was longer in patients with HbA1c of ⩾7.0 to <8.0% (⩾53 to <64mmol/mol), ⩾8.0 to <9.0% (⩾64 to <75mmol/mol) and ⩾9.0% (⩾75mmol/mol), compared to those with HbA1c of <7.0% (<53mmol/mol) with the ratios of 1.03 (95% confidence interval (CI)=0.96-1.10), 1.16 (95% CI=1.07-1.26) and 1.17 (95% CI=1.06-1.29), respectively. Body mass index was also associated with long consultation. Older and female physicians provided longer consultation. CONCLUSIONS Clinical consultation length in diabetes practice was associated with certain patient and physician characteristics. The findings can be used for making diabetes consultation more efficacious, which could eventually lead to the provision of the most appropriate consultation time for individual patients.