Yumi Miyashita

Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography

BackgroundAlthough oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D).MethodsAn index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, Glutathione peroxidase-1 (GPx-1), Catalase, Mn-SOD, Cu/Zn-SOD, as well as SNPs of NADPH oxidase as ROS-promoting elements, genes related to onset of T2D (CAPN10, ADRB3, PPAR gamma, FATP4). Age, blood pressure, BMI, HbA1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis.ResultsCACS with Pro/Leu genotype of the GPx-1 gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, p = 0.006). In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; OR = 3.61, CI = 0.97–13.42; p = 0.045) when tested for deviation from Hardy-Weinbergs equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with GPx-1 genotypes and age.ConclusionThe presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant GPx-1.

Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

BackgroundThe large clinical trials proved that Basal-Bolus (BB) insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy.MethodsIn PROBE (Prospective, Randomized, Open, Blinded-Endpoint) design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range) age: 64.5(56.8~71.0)years) with secondary failure of sulfonylurea (SU) were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group) or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group), and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT) of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups.ResultsAfter 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3) → 7.4(6.9~8.7)%, p < 0.01, vs BB;8.9(7.7~10.0) → 6.9(6.2~7.3)%, p < 0.01), with no significant difference between the groups in percentage change in HbA1c (30 Mix; -14.7(-32.5~-7.5)% vs BB -17.8(-30.1~-11.1)%, p = 0.32). There was a significant decrease in daily glycemic profile at all points except dinner time in both groups compared to baseline. There was a significant increase in the amount of insulin used in the 30 Mix group after treatment compared to baseline (30 Mix;0.30(0.17~0.44) → 0.39(0.31~0.42) IU/kg, p = 0.01). There was no significant difference in IMT, BMI, QOL or adiponectin levels in either group compared to baseline.ConclusionBoth BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure.Trial registrationCurrent Controlled Trials number, NCT00348231

Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study

ObjectiveThe study examined changes in and relationship between body mass index (BMI), leptin and adiponectin levels over a 3-year period in a pediatric population-based cohort.Study designA 3-year prospective cohort study of 268 boys and 251 girls aged 9–10 in Ina, Saitama, Japan.ResultsMedian body mass index (BMI) significantly increased from baseline (age 9–10) to follow up (age 12–13) in boys from 17.1 to 18.3 kg/m2 (P < 0.001) and in girls from 16.5 to 18.5 kg/m2 (P < 0.001), respectively. Adiponectin values significantly decreased from baseline to follow up in boys (13.5 to 8.9 μg/ml, respectively) (P < 0.001) and in girls (12.4 to 9.5 μg/ml, respectively) (P < 0.001). Leptin values at follow up significantly decreased from baseline in boys (4.9 to 2.3 ng/dl, respectively) (P < 0.001) and also in girls (5.3 to 5.1 ng/dl, respectively) (P = 0.049).A relatively strong correlation was seen in BMI (Spearmans correlation coefficient, r = 0.864, P < 0.001 in boys; r = 0.873, P < 0.001 in girls), adiponectin (r = 0.705, P < 0.001 in boys; r = 0.695, P < 0.001 in girls), and leptin (r = 0.449, P < 0.001 in boys; r = 0.610, P < 0.001 in girls) before and after the three-year period.The ratio of follow up to baseline BMI was negatively correlated with that for adiponectin (r = -0.224, P < 0.001 in boys; r = -0.165, P = 0.001 in girls) and positively correlated with that for leptin (r = 0.518, P < 0.001 in boys; r = 0.609, P < 0.001 in girls).ConclusionThis study demonstrated that baseline adiponectin, leptin and BMI values measured at ages 9–10 correlated with those measured three years later. However, adiponectin values decreased and leptin values increased in those subjects whose BMI increased during over this period.

Daily Glucose Profiles in Japanese People with Normal Glucose Tolerance as Assessed by Continuous Glucose Monitoring

BACKGROUND Little information is available regarding glucose fluctuations in postprandial states and during the oral glucose tolerance test (OGTT) in Japanese people with normal glucose tolerance (NGT). METHODS Glucose profiles of 27 Japanese people were measured for 4 days by using continuous glucose monitoring. A 75-g OGTT was conducted on the second day, and 24 subjects diagnosed with NGT by a 75-g OGTT were enrolled. The subjects were monitored for their postprandial glucose profile in their ordinary daily life on the third day. RESULTS The results of our study have shown that the median time (interquartile range) to maximum glucose levels in OGTT was 38 (25-49) min after glucose load and that the median time to maximum glucose levels after breakfast, lunch, and dinner was 40 (31-75), 50 (30-70), and 45 (36-50) min, respectively. The median increase in glucose during OGTT was 45 (35-66) mg/dL, and that after breakfast, lunch and dinner was 21 (12-32), 37 (27-48), and 44 (25-63) mg/dL, respectively. Those with a higher insulinogenic index reached their maximum glucose levels in a shorter time (r = -0.46, P = 0.025) and had smaller glucose increments during OGTT (r = -0.49, P = 0.014). CONCLUSIONS This study is the first report to document the glucose profile of Asian people with NGT.

Analysis of 24-Hour Glycemic Excursions in Patients with Type 1 Diabetes by Using Continuous Glucose Monitoring

BACKGROUND Little information is available regarding postprandial glycemic excursions and hypoglycemia in Japanese patients with type 1 diabetes (T1D). METHODS Four male and eight female patients who were on intensive therapy with rapid-acting insulin plus basal insulin underwent retrospective continuous glucose monitoring (CGM). Clinical characteristics (median) of the patients were as follows: age, 40.5 years; body mass index, 22.2 kg/m(2); urinary C-peptide, 0.75 microg/day; hemoglobin A1c (HbA1c) after 2 months of CGM, 6.5%; and total insulin dose, 40.0 units. RESULTS The largest glycemic excursions were observed after breakfast. The time intervals from the start of each meal to the highest postprandial glucose levels peaked at 65-100 min. Hypoglycemia (blood glucose <70 mg/dL) was observed for more than 100 min per 24-h period. HbA1c and 24-h mean glucose levels were significantly correlated (r = 0.727, P = 0.007). The 12 participants were divided into two groups by HbA1c level after 2 months: those whose HbA1c exceeded the median of HbA1c (HbA1c > 6.5%) (n = 6) and those whose HbA1c fell below the median (HbA1c <6.5%) (n = 6). The premeal glucose levels/the highest postprandial glucose levels after breakfast were insignificantly higher in the HbA1c >6.5% group (183/247 mg/dL, respectively) than in the HbA1c <6.5% group (117/221 mg/dL, respectively). The duration of hypoglycemia lasted longer in the HbA1c <6.5% group, with these episodes often occurring during the nighttime. CONCLUSIONS These findings suggest that preventing nighttime hypoglycemia and correcting glucose spikes after breakfast are required in patients with T1D receiving intensive therapy to stabilize and improve glycemic control.