The Effect of Sitagliptin on Carotid Artery Atherosclerosis in Type 2 Diabetes: The PROLOGUE Randomized Controlled Trial.

BACKGROUND: Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM).METHODS AND FINDINGS: We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged 30 y with T2DM (6.2% HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI -0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72% ± 0.05%, p = 0.008; group mean difference -0.159, 95% CI -0.278 to -0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation.CONCLUSIONS: In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment.TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.


New insulin glargine 300 U/mL versus glargine 100 U/mL in Japanese adults with type 1 diabetes using basal and mealtime insulinglucose control and hypoglycaemia in a randomized controlled trial

.on behalf of the Edition JP 1 study group

To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes. The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight. Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups. In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.


Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors.

Carboxy-terminal telopeptide of type I collagen (ICTP) is generated through matrix metalloproteinase (MMP)-dependent type I collagen digestion, and has been widely utilized as a biomarker for bone turnover. The fact that atherosclerotic lesions are rich in both type I collagen and MMP-producing macrophages led to the hypothesis that serum ICTP concentrations may serve as a non-invasive clinical biomarker for atherosclerosis. Therefore, the association of serum ICTP concentrations with the maximum intima-media thickness (IMT) of carotid arteries, a surrogate index of systemic atherosclerosis, or brachial-ankle pulse wave velocity (baPWV) in patients with atherosclerotic risk factors was evaluated. A total of 52 male and 65 female (mean age: 62.8 yrs) patients without renal failure, malignancies or bone diseases known to affect serum ICTP concentrations were recruited. Patients with max IMTs ≥1.1 mm showed significantly higher serum ICTP concentrations compared with patients with max IMTs <1.1 mm (3.33 ± 0.97 vs 2.82 ± 0.65 ng/mL, p<0.05). Serum ICTP concentration was also positively correlated with max IMT (p<0.001) or baPWV values (p<0.05). Multivariate analyses also revealed that serum ICTP concentrations were correlated with max IMT (p<0.001; 95% CI 0.200 to 0.454). These results suggest that serum ICTP concentrations can be used as a non-invasive biomarker for systemic atherosclerosis.


Carbohydrate Counting and Its Consumption

カーボカウントと糖質摂取

Journal of the The Japan Diabetes Society


糖尿病地域医療連携のIT化の試み∼その現状と課題∼

糖尿病地域医療連携のIT化の試み∼その現状と課題∼

NPO法人日本糖尿病情報学会誌

NPO法人日本糖尿病情報学会誌


Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes.

Serum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.


Development of the Diabetes Oral Health Assessment Tool © for Nurses


Non-invasive Measurement of Skin Autofluorescence as a Beneficial Surrogate Marker for Atherosclerosis in Patients with Type 2 Diabetes

Advanced glycation end-products (AGEs) are thought to play a major role in the pathogenesis of diabetic vascular complications. Skin autofluorescence (AF) was recently reported to represent tissue AGEs accumulation with a non-invasive method. The aim of the present study was to evaluate association between AF value and diabetic vascular complications, such as retinopathy, nephropathy and cervical atherosclerosis using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease in patients with type 2 diabetes. A total of 68 patients with type 2 diabetes were enrolled in a cross-sectional manner. AGEs accumulation was measured with AF reader. Clinical parameters were collected at the time of AF and IMT measurement. Max-IMT was correlated with age and AF (r=0.407, p=0.001), but not with HbA1c, GA, and pentosidine. Also, AF was not correlated with HbA1c, GA and pentosidine, but was correlated with age (r=0.560, p<0.001), duration of diabetes (r=0.256, p<0.05). Multivariate regression analysis revealed that AF, but not age, was an independent determinant of max-IMT. In conclusion, AF might be a beneficial surrogate marker for evaluating carotid atherosclerosis in patients with type 2 diabetes non-invasively. J. Med. Invest. 62: 126-129, August, 2015.

The Journal of Medical Investigation : JMI


Acute effect of fast walking on postprandial blood glucose control in type 2 diabetes


インスリン治療による低血糖と日常生活への影響に関するアンケート調査

インスリン治療による低血糖と日常生活への影響に関するアンケート調査

Japanese Journal of Medicine and Pharmaceutical Science


Impact of newly developed, next-generation artificial endocrine pancreas

Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latter's fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.


The Behavior Modification to the Lifestyle by Healthy Condition Visualization which Utilized NFC Communication Pedometer

NFC通信歩数計を活用した健康データの可視化による生活習慣の行動変容

To record individual body weight and physical activity has been shown to be beneficial for maintaining personal health. We, therefore, established a system which connects a personal computer and health appliances to record body weight, daily step, and blood pressure. We applied this system to 226 employees in 3 companies during the period of October, 2011-March, 2013 and evaluated whether this system could improve individual behavioral modification. One hundred sixty seven persons (73.9%) had continuously recorded the measurement of the pedometer for at least one year. We compared the average of the first three months with the average of the next three months. As a result, the number of steps tended to increase to 7,515±4,629 steps from 7,299±3,731steps (p=0.075). As for blood pressure, the systolic phase significantly decreased from 129.2±13.2 mmHg to 127.1±13.5 mmHg (p=0.028), and diastolic phase decreased from 78.6±9.8 mmHg to 76.0±9.9 mmHg (p=0.00016). BMI also significantly decreased from 23.3±2.9 kg/m2 to 23.2±2.8 kg/m2(p=0.029). In conclusion, to record daily step, body weight and blood pressure by using newly established system improved individual behavior towards a healthy condition.

健康データの登録の自動化と可視化ができるシステムを利用することで，計測者が健康改善に向けての意識変化や行動変容が起こるかどうか，健康管理を継続することにより健康データに変化が起こるかどうかについて検証することを目的としている．日常の健康管理を行う際に体重や運動の記録が自動で登録・グラフ化できるように，PCとNFC通信歩数計・体組成計・血圧計などの健康機器を連携したシステムを構築した．このシステムを利用し，健康データを日々計測することによってデータの可視化を図り，計測者が健康改善に向けての行動変容が起きるかについて検証を行った．利用期間が1年を経過している企業3社226名の利用者について，2011年10月から2013年3月までに得られたデータで分析を行った．歩数計の計測を2013年3月まで継続し続けたのは167名(73.9%)となった．歩数は「1カ月∼3カ月」の平均と「4カ月∼6カ月」の平均を比べると，7,299±3,731歩から7,515±4,629歩(p＝0.075)へと増加傾向があった．血圧は収縮期が129.2±13.2 mmHgから127.1±13.5 mmHg(p＝0.028)へ有意に減少し，拡張期も78.6±9.8 mmHgから76.0±9.9 mmHg(p＝0.00016)へと有意に減少しており，BMIについても，23.3±2.9 kg/m2から23.2±2.8 kg/m2(p＝0.029)へと有意に減少していた．これらの結果より，システムを利用することで開始当初に健康データが改善し，その後も血圧に関しては継続効果が認められ，健康改善に向けての行動変容が生じたと考えられた．


Establishment of the Local Medical Care System for Diabetes Using by ICT Network in Tokushima

ICTを活用した徳島県糖尿病医療連携システムの構築 (多職種協働で支える高齢化社会 医療と介護の壁を破る)

日本糖尿病情報学会誌 = Journal of the Japan Association of Diabetes Informatics


Short- and long-term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients.

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.


Vitamin D deficiency is significantly associated with retinopathy in young Japanese type 1 diabetic patients.

The aim of this study was to examine the possible association of vitamin D deficiency with diabetic retinopathy in 75 young Japanese type 1 diabetic patients. A multivariate regression analysis, duration of diabetes and vitamin D deficiency were independent determinants of diabetic retinopathy.


Usefulness of artificial endocrine pancreas during resection of insulinoma.

A 71-year-old woman had an episode of syncope due to hypoglycemia of 27 mg/dl. She was diagnosed with insulinoma and scheduled for laparoscopic enucleation along with the use of an artificial endocrine pancreas (STG-22, Nikkiso Co., Ltd., Tokyo, Japan). Anesthesia was maintained with sevoflurane and remifentanil. Her blood glucose level was controlled using the artificial endocrine pancreas, which enabled continuous blood glucose monitoring and computer-operated glucose and insulin infusion to maintain the blood glucose level at a steady state. The target concentration of blood glucose was set at 80-120 mg/dl during surgery. Until removal of the tumor, the blood glucose level was kept at around 80-100 mg/dl. After removal of the tumor, the blood glucose level gradually increased, but it was kept in the normal range by the artificial endocrine pancreas. The artificial endocrine pancreas was useful to monitor and maintain blood glucose levels during and after the removal of insulinoma, without any hyper- or hypoglycemia. J. Med. Invest. 61: 421-425, August, 2014.


Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.

Unexpectedly, fat accumulation in the skeletal muscle and adipose tissue was not associated with organ-specific IR. Instead, liver fat was associated not only with hepatic IR but also with skeletal muscle IR, suggesting a central role of fatty liver in systemic IR and that a network exists between liver and skeletal muscle.

HGP × FPI was significantly correlated with Rd (r = -0.57, P<0.001), %HGP with %FFA (r = 0.38, P<0.01), and Rd with %FFA (r = 0.27, P<0.05). Liver steatosis score was negatively associated with Rd (r = -0.47, P<0.001) as well as with HGP × FPI (r = 0.43, P<0.001). Similarly, intrahepatic lipid was negatively associated with Rd (r = -0.32, P<0.05). IMCL was not associated with Rd (r = -0.16, P = 0.26). Fat mass and its percentage were associated with HGP × FPI (r = 0.50, P<0.001; r = 0.48, P<0.001, respectively) and Rd (r = -0.59, P<0.001; r = -0.52, P<0.001, respectively), but not with %FFA (r = -0.21, P = 0.10; r = -0.001, P = 0.99, respectively).


Effects of Pioglitazone on Macrovascular Events in Patients with Type 2 Diabetes Mellitus at High Risk of Stroke: The PROFIT-J Study.

Aim: The present study evaluated the effects of pioglitazone treatment on the incidence of primary cardiovascular events in Japanese subjects with type 2 diabetes mellitus at high risk of stroke. Methods: A prospective, multicenter, randomized, open label, comparative study was conducted among diabetic patients recruited from 50 medical institutions nationwide. A total of 522 patients with hypertension and/or dyslipidemia who had one or more silent cerebral infarcts, advanced carotid atherosclerosis or microalbuminuria at baseline were randomly treated with (n=254) or without pioglitazone (n=268) and observed for a medium of 672 days. The hypertension and dyslipidemia were concurrently treated according to the respective treatment guidelines. The primary outcome was the time to the first occurrence of a composite of all-cause death, nonfatal cerebral infarction and nonfatal myocardial infarction. Results: Treatment with pioglitazone resulted in significant reductions in the levels of HbA1c, diastolic blood pressure and LDL-cholesterol and a significant increase in the levels of HDL-cholesterol. The pioglitazone non-users exhibited a significant reduction in the LDL-cholesterol levels alone. Primary events were registered during the study period in nine patients in the pioglitazone group and 10 patients in the non-pioglitazone group. The difference in the cumulative incidence of the primary outcome was not significant between the two groups(1.8% per year). Conclusions: Pioglitazone therapy produces immediate and effective improvements in glycemic control, diastolic blood pressure and lipid profiles. While this study was too underpowered to determine the effects of pioglitazone on the incidence of cardiovascular events, the results indicated that two years of pioglitazone treatment did not produce any statistically significant reductions in the rate of primary cardiovascular events.

Journal of Atherosclerosis and Thrombosis


Diabetic conditions differentially affect the endothelial function, arterial stiffness and carotid atherosclerosis.

Aim: The levels of fasting and postprandial plasma glucose, HbA1c and other risk factors for atherosclerosis have distinct effects in patients with and those without diabetes mellitus. The aim of this study was to determine the impact of diabetic surrogate markers on the endothelial function, arterial stiffness and carotid atherosclerosis in individuals with and without diabetes. Methods: A total of 320 Japanese subjects(mean age: 61.2±12.1 years) were recruited in this study. Demographic, clinical and laboratory parameters, including 75 g OGTT(155 subjects) results, were examined. The endothelial function was evaluated according to the flow-mediated vasodilation of the brachial artery(%FMD). In addition, arterial stiffness was evaluated according to the brachial-ankle pulse wave velocity(baPWV), and carotid atherosclerotic changes were estimated according to the maximum intima-media thickness(max-IMT) and resistive index of the common carotid artery(CCA-RI). A multiple regression analysis was performed to identify independent determinants of these vascular surrogate markers. Results: None of the glucose-related parameters were associated with the %FMD. In contrast, the presence of T2DM, the HbA1c level and an increased plasma glucose level at 60 minutes during 75 g OGTT were associated with an increased baPWV. The HbA1c level was also correlated with an increased max-IMT. The fasting plasma glucose(FPG) level and the presence of T2DM correlated with an increased CCA-RI. In the subjects with T2DM, the protective effects of high-density lipoprotein cholesterol(HDL-C) on the %FMD and baPWV were abolished. Conclusions: Various glucose metabolism parameters have different effects the degree of arterial stiffness and presence of carotid atherosclerosis, but not the endothelial function, suggesting that pharmacological intervention has the potential to preserve the endothelial function in diabetic individuals. In addition, the presence of T2DM blunts the vascular protective effects of HDL-C on the endothelial function and progression of arterial stiffness.


Carbohydrate Content in Dishes Other than Staple Foods Based on the Food Exchange Lists (7th edition) Allowing for a 50-60 % Energy Intake from Carbohydrates

第7版食品交換表に基づいた炭水化物50~60%での主食以外の炭水化物含有量

Journal of the The Japan Diabetes Society


Comparison of Continuous Glucose Monitoring (CGM) Values before and after Adrenalectomy in a Case of Adrenaline-producing Pheochromocytoma

術前後で持続血糖モニター(CGM)を比較しえたアドレナリン優位褐色細胞腫の1例

A 77-year-old woman was incidentally found to have a left adrenal mass measuring 2.5 cm in January 2012. The urine metanephrine concentration was 3.0 mg/day (normal range, 0.04-0.19 mg/day), and an iodine-131 metaiodobenzylguanidine (MIBG) scan showed uptake in the area of the left adrenal gland, leading to a diagnosis of pheochromocytoma. In addition, the patient had a history of diabetes mellitus for nine years, with gradually worsening blood glucose control since 2010. The patient was subsequently admitted to our hospital for perioperative care. On admission, her fasting blood glucose level was 121 mg/dl and her HbA1c level was 8.5 %. She was treated with basal-bolus insulin therapy during hospitalization and underwent adrenalectomy at the urology department after her glycemic control had improved. The total daily insulin dose was immediately decreased from 50 to 14 units after the adrenalectomy procedure. In addition, the mean glucose level on preoperative continuous glucose monitoring (CGM) had been 141 mg/dl with a standard deviation (SD) of 54. However, after the operation, the mean glucose level increased to 153 mg/dl while the SD decreased to 24; thus, the range of glycemic fluctuation markedly decreased after surgery. Therefore, excess endogenous adrenalin primarily contributed to the glycemic fluctuations observed in this patient with pheochromocytoma.

症例は78歳女性．2012年1月，25 mm大の左副腎腫瘍，尿メタネフリン高値，MIBGシンチからアドレナリン優位型褐色細胞腫と診断され，5月当科を紹介された．罹病期間9年の糖尿病があり内服加療をうけるも2010年頃よりHbA1cは悪化し，初診時8.5 %で，褐色細胞腫の周術期管理および血糖管理目的で当科入院した．入院後速やかにインスリン導入を行い，目標血糖値に達した際の持続血糖モニター(以下CGMと略す)の標準偏差(SD)は54であった．腹腔鏡下腫瘍摘除後は，一日総インスリン量が術前50単位から術後14単位に減少し，術後CGMでSDが24に改善した．また退院時はグリメピリド0.5 mg，シタグリプチン50 mgで管理可能となった．本例は，家族歴がなくやせ型で術後の血糖管理の改善からアドレナリン過剰が術前の病態の中心と考えられた．


Consensus Statement on Continuous Subcutaneous Insulin Infusion and Continuous Glucose Monitoring

日本先進糖尿病治療研究会によるCSⅡおよびCGMに関するステートメント

The use of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in clinical practice is increasing in Japan. Against this background, the Association for the Study of Innovative Diabetes Treatment in Japan (ASINDTJ) arranged a Consensus Statement of opinions for the optimal and safe routine use of CSII and CGM. The Consensus Statement on the routine use of CSII and CGM includes patient selection and indications for clinical outcomes as well as risk management for routine use. The development of patient educational programs conducted by diabetologists in association with certified diabetes educators (CDEs) regarding the use of pumps and/or CGM is a prerequisite for clinical use. In addition, items associated with CSII and CGM, such as insulin dose adjustment, application methods for use in daily life, diet and exercise, risk management of pump difficulties, " sick day" occasions and skin problems, are included in the Consensus Statement. Our consensus opinion and suggestions also emphasize the usefulness of CSII and CGM in adult diabetic patients as well as children with type 1 and type 2 diabetes and pregnant diabetic patients. According to the Consensus Statement, the development of detailed educational guidelines for the use of CSII and CGM is needed.

最近，持続インスリン皮下注入療法(Continuous subcutaneous insulin infusion:以下CSII)と持続血糖モニタリング(Continuous glucose monitoring:以下CGM)が糖尿病の治療機器として普及しつつある．我々はCSIIおよびCGMに関する科学的根拠をもとに，これをコンセンサスステートメントとしてまとめた．CSIIでは適応，臨床効果，リスク管理など，さらに，運用法の実際的な要点，シックデイ，妊娠，食事・運動などに関する注意などについて述べた．CGMに関してもその適応と効果，糖尿病治療への活用法，注意点を述べた．CSIIおよびCGMは1型糖尿病，2型糖尿病の一部や妊娠中の糖尿病症例にも重要な臨床機器であり，このステートメントをもとに内科および小児科領域の患者教育に適応できる具体的なガイドラインの作成が望まれる．


Effectiveness of miglitol combined with various types of insulin therapy for reducing the daily glycemic fluctuation on Japanese type 2 diabetic patients: Evaluation with self-monitoring blood glucose (SMBG)

糖尿病患者に対する血糖平坦化を目指したミグリトールとインスリン併用療法の有用性の検討ー血糖自己測定(SMBG)を用いた評価ー


Usefulness of a novel system for measuring glucose area under the curve while screening for glucose intolerance in outpatients.

The findings suggest that our glucose AUC measurement system using MIET would be useful for screening of glucose intolerance. In the future, this system may prove to be a useful aid as a screen for glucose intolerance before performing an OGTT for diagnosis.

Good correlation between MIET-predicted and reference AUCs obtained using PG levels was confirmed for a wide AUC range. By introducing a threshold level for AUC to separate glucose intolerance with peak glucose ≥180 mg/dL from normal glucose tolerance, the system was demonstrated to provide better screening accuracy compared with conventional methods that use HbA1c and fasting PG levels. The results of a questionnaire-based survey administered to the subjects suggested that this system was readily accepted by the majority as a painless monitoring method.


Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement.

We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice.

Journal of Diabetes Science and Technology


A Case of Hypocalcemia with Severe Vitamin D Deficiency following Treatment for Graves' Disease with Methimazole.

We herein report the case of a 41-year-old Japanese female office worker who developed symptomatic hypocalcemia with severe vitamin D deficiency following treatment for Graves' disease with methimazole. The patient's hypocalcemia was mainly caused by vitamin D deficiency due to unbalanced diets and inadequate exposure to sunlight in addition to the resolution of hyperthyroidism. Vitamin D deficiency is increasing worldwide, and it has been more recently shown to relate to the pathogenesis of Graves' disease. However, vitamin D deficiency as a cause of hypocalcemia has received little attention. Taken together, this case suggests that we should take more care in calcium kinetics and vitamin D status during treatment for Graves' disease with antithyroid drugs.


The New Paradigm 722 Insulin Pump Can Achieve Good Glycemic Control with Carbohydrate Counting Alone : A Case Report of Type 1 Diabetes Mellitus

新たなインスリンポンプParadigm 722によりカーボカウントのみで血糖管理が可能となった1型糖尿病の1例

インスリンポンプParadigm712は，インスリン作用時間(AIT)が8時間の設定のため，十分な食後血糖補正インスリン投与を提案しないが，新しいParadigm 722はAITを2~8時間に設定できる．そこで，Paradigm 722の食後血糖補正インスリン量の妥当性を検証した．症例は1型糖尿病の50歳代女性．入院の上インスリンリスプロでParadigm 722を導入，食事スキップで基礎インスリンを設定し，糖質/インスリン比を各食前(11，15，13)g/Uとしたカーボカウントのもと，AITを3時間，インスリン効果値を60mg/dl/Uと設定した．退院前1週間の食後2時間血糖補正の際，150mg/dlを目標にインスリン効果値を用いた補正による自己算出インスリン量とポンプでの自動算出インスリン量とを比較した．食後高血糖に対する補正インスリンは，14回中7回で自己算出量よりも自動算出量が適切であった．Paradigm 722による食後補正インスリン自動算出法は，自己算出法と同等で，これを用いることで良好な血糖管理が簡便になった．(著者抄録)


Outcomes of 6 years of activities by the Tokushima Medical Associations Steering Committee for Diabetes prevention to prevent type 2 diabetes in the general population of Tokushima Prefecture.


Plasma pentraxin 3 levels are associated with carotid IMT in type 1 diabetic patients.

AIMS: Pentraxin3 (PTX3), a recently discovered inflammatory mediator, is produced abundantly in various cells in atherosclerotic lesions, and therefore, its plasma level could reflect local inflammation at the site of atherosclerotic lesion. The present study evaluated whether plasma PTX3 levels are associated with subclinical atherosclerosis in young subjects with type 1 diabetes. METHODS: Plasma PTX3 levels, urinary albumin excretion, diabetic retinopathy, and carotid intima-media thickness (IMT) were examined in 78 Japanese type 1 diabetic patients (30 men and 48 women, aged 28.5±5.3 years (±SD), duration of diabetes 19.7±6.5 years). RESULTS: There was statistically significant association between plasma PTX3 levels and Max-IMT (r=0.363, p=0.001). A stepwise multivariate regression analysis including conventional coronary risk factors as independent variables revealed that plasma PTX3 levels (=0.389, p<0.001), duration of diabetes (=0.256, p=0.035), and serum triglyceride levels (=0.371, p<0.001) were independent determinants of Max-IMT. In addition, plasma PTX3 levels was an independent determinant of urinary albumin excretion, an indicator of diabetic nephropathy (=0.258, p=0.018). However, there was no significant association between plasma PTX3 levels and diabetic retinopathy. CONCLUSIONS: Increased levels of plasma PTX3 are associated with accelerated atherosclerotic change and increased albuminuria in young patients with type 1 diabetes.


Regular insulin, rather than rapid-acting insulin, is a suitable choice for premeal bolus insulin in lean patients with type 2 diabetes mellitus.

The aim of the present study was to compare the usefulness of premeal rapid-acting and regular insulin in type 2 diabetes patients. A total of 56 type 2 diabetic patients were investigated during hospitalization. Premeal rapid-acting insulin was applied instead of other medications. Premeal insulin was titrated to adjust premeal and bedtime blood glucose levels to 81-120 mg/dL. Premeal rapid-acting insulin was changed to regular insulin just before a meal at the same dosage if the postmeal blood glucose level was lower than the premeal blood glucose level. A total of 15 patients changed to regular insulin, and 41 patients continued rapid-acting insulin. The blood glucose level was comparable between these two groups. Body mass index was significantly lower in the patients using regular insulin. According to the multivariate logistic regression analysis, low body mass index was an independent variable accounting for the usefulness of regular insulin. Regular insulin, rather than rapid-acting insulin, is a suitable choice for premeal insulin in lean type 2 diabetic patients.


Association of serum YKL-40 levels with urinary albumin excretion rate in young Japanese patients with type 1 diabetes mellitus.

YKL-40 is a marker of inflammation and endothelial dysfunction, both of which play important roles in the progression of diabetic complications. However, little information has been obtained about serum YKL-40 levels in type 1 diabetic patients. We evaluated YKL-40 levels and its association with diabetic micro- and macroandgiopathy in 131 young Japanese type 1 diabetic patients without advanced diabetic complications (aged 24.7±5.9 years) and 97 age- and gender-matched healthy controls. YKL-40 levels were significantly elevated in type 1 diabetic patients than in healthy controls (median (range) 46.4 (20.3-136.7) and 52.3 (21.4-274.1) ng/ml, respectively, p = 0.006). There was a significant positive association between YKL-40 levels and urinary albumin creatinine ratio (UACR) (r = 0.226, p = 0.013). Furthermore, a multivariate regression analysis demonstrated that YKL-40 levels were a determinant of UACR independently of conventional risk factors. In addition, YKL-40 levels were significantly higher in participants with diabetic retinopathy compared to those without it (median (range) 55.5 (23.3-274.1) and 50.3 (21.4-237.4) ng/ml, respectively, p = 0.039). Serum YKL-40 levels were elevated in type 1 diabetic patients and associated with increasing level of albuminuria. YKL-40 could be a predictor to assess the risk of diabetic microangiopathy in the early stage in type 1 diabetic patients.


Basal insulin requirements after progesterone treatment in a type 1 diabetic pregnant woman.

We herein report the case of a 37-year-old type 1 diabetic pregnant woman treated with an insulin pump. Although the patient's glycemic control deteriorated following progesterone treatment for the prevention of preterm delivery and miscarriage, it was improved by adjusting the basal insulin rate on the days of progesterone treatment. Excess progesterone is known to impair both insulin sensitivity and secretion. The present case is the first report to evaluate deterioration of glycemic control induced by progesterone treatment and to determine the dose of insulin required in a type 1 diabetic pregnant woman whose insulin secretion was completely depleted.


Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation.

The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration.

The Journal of Medical Investigation : JMI


Evaluation of the Sugar Content in the Side Dishes Served in Elementary School Lunches

小学校給食の副食に含まれる糖質量の検討

Kuroda et al. proposed a simple method for calculating the carbohydrate content based on a food exchange list (Shokuhin Koukanhyou), with a sugar content of dietary staples of 40 % for rice, 50 % for bread, and 20 % for boiled noodles and a side dish containing 20 g sugar. This study focused on the sugar content in in school lunches, which have a nutrient composition that is different from diabetic meals. The total energy content of school lunches and the sugar content in their side dishes were investigated in 42 school lunches served in elementary school. The average energy intake in the total lunch increased depending on the school grade (670±44 to 752±50 kcal; means±standard deviation). On the other hand, the sugar content of side dishes increased from 29.7±7.5 g in the 1st-2nd grade to 31.2±8.1 g in the 5th-6th grade, thus it could be estimated to be 30 g regardless of the energy intake. Two hundred milliliters of milk containing approximately 10 g of carbohydrate was served in every school lunch, which accounted for the 10 g increase in comparison to hospital lunches. These results indicate that the sugar content in the side dishes of elementary school lunches can be estimated to be 30 g regardless of the energy intake.

「食品交換表に基づく新たなカーボカウント法」(黒田ら，糖尿病2010)に基づいて糖尿病食1食に含まれる糖質量を算出する場合，1食を主食と副食にわけ，副食は一律20 gと概算する．しかし，小児期は必要エネルギー量や栄養素バランスが食品交換表とは異なる．よって本研究では，小児期の副食糖質量を検討することを目的とした．学校給食摂取基準に基づく学校給食42食分を小学校の学年別に検討した．その結果，1食のエネルギーは670±44∼752±50(平均値±標準偏差)kcalと学年が上がるに従い増加したが，副食糖質量は29.7±7.5∼31.2±8.1 gであり，エネルギー量にかかわらず副食糖質量を約30 gに概算できた．学校給食では糖質約10 gの牛乳が毎食提供されるため糖尿病食や病院普通食に比較して副食糖質量が10 g増加すると考えられた．以上より，小学校給食では副食糖質量を30 gとしてカーボカウントを指導できることが明らかとなった．<br>

Journal of the The Japan Diabetes Society


Association of serum copper levels and glycemic control in patients with type 2 diabetes.

It has been suggested that copper ion is involved in the pathogenesis of various diseases. The aim of this study is to examine the association of serum copper levels and glycemic control in patients with type 2 diabetes. We recruited a total of 132 patients with type 2 diabetes, and measured their serum copper levels by atomic absorption spectrometry. Serum copper levels were positively correlated with HbA1c levels (r=0.176, p=0 .044). In addition, after 3-month glycemic control, we evaluated whether the improvement of glycemic control influenced serum copper levels. As hemoglobin A1c (HbA1c) levels were decreased (from 8.7% to 6.8%, p<0.001), copper levels tended to be decreased (from 105.7 g/dL to 101.8 g/dL, p=0.069). In conclusion, it is likely that serum copper levels are associated with glycemic control in patients with type 2 diabetes.


Carbohydrate-to-Insulin Ratio Is Estimated from 300-400 Divided by Total Daily Insulin Dose in Type 1 Diabetes Patients Who Use the Insulin Pump.

Abstract Background: To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Subjects and Methods: Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Results: Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; P<0.01). Conclusions: CIR has diurnal variance and is estimated from the formula CIR=300/TDD at breakfast or CIR=400/TDD at lunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.


Effect of metformin on hepatic glucose production in Japanese patients with type 2 diabetes mellitus.

We investigated the effect of metformin on hepatic glucose production and peripheral glucose uptake in Asian patients with type 2 diabetes mellitus. We recruited ten Japanese patients whose fasting glucose levels remained poorly controlled under meal-time injection of short-acting insulin. Metformin was added to their insulin therapy, and both hepatic glucose production and peripheral glucose uptake were assessed before and one week after metformin treatment, with the use of stable isotope [6,6-²H₂] glucose. Metformin was titrated to a maximum dose of 500 mg. As a result, fasting glucose levels and hepatic glucose production were significantly improved after the metformin treatment (p < 0.01 and 0.02), whereas their peripheral glucose uptake was not significantly changed (p = 0.63). Furthermore, the change of fasting glucose levels was significantly correlated with that of hepatic glucose production, whose coefficient ρ was 0.76 (p = 0.01). On the other hand, there was no significant correlation between the change of fasting glucose levels and that of peripheral glucose uptake (p = 0.43). In conclusion, low dose of metformin significantly reduced hepatic glucose production in Japanese patients with type 2 diabetes mellitus. The efficacy of metformin on correcting fasting hyperglycemia was strongly associated with reduced hepatic glucose production, rather than ameliorated peripheral glucose uptake.


血糖正常化 : カーボカウントを用いたアプローチ (特集 血糖値の把握と正常化を目指して)


Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes.

It is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.


DPP-4阻害薬ビルダグリプチンの臨床評価

DPP-4阻害薬ビルダグリプチンの臨床評価


Pancreas after Kidney Transplant from Donor with Elevated Agonal HbA1c : A Case Report

死戦期HbA1c高値ドナーからの腎移植後膵移植の1例


Computational assessment of insulin secretion and insulin sensitivity from 2 horal glucose torerance tests for clinical use for type 2 diabetes

In type 2 diabetes mellitus, glucose homeostasis is tightly maintained through insulin secretion and insulin sensitivity. Therefore, finding an accurate method to assess insulin secretion and sensitivity using clinically available data would enhance the quality of diabetic medical care. In an effort to find such a method, we developed a computational approach to derive indices of these factors using a 2-h oral glucose tolerance test (OGTT). To evaluate our method, clinical data from subjects who received an OGTT and a glucose clamp test were examined. Our insulin secretion index was significantly correlated with an analogous index obtained from a hyperglycemic clamp test (r = 0.90, n = 46, p < 0.001). Our insulin sensitivity index sensitivity was also significantly correlated with an analogous index obtained from a hyperinsulinemic-euglycemic clamp test (r = 0.56, n = 79, p < 0.001). These results suggest that our method can potentially provide an accurate and convenient tool toward improving the management of diabetes in clinical practice by assessing insulin secretion and insulin sensitivity.


Beneficial effects of foot care nursing for people with daibetes mellitus:an uncontrolled before and after intervention study

The aim of this study was to assess the effectiveness of a preventative foot care nursing programme for diabetic patients. Foot complications are common in diabetic patients and prevention of such complications requires foot care. However, there is little information on the effectiveness of foot care nursing on the incidence and recurrence of diabetic foot. We developed a diabetic foot care programme based on the International Working Group on the Diabetic Foot. We studied 88 patients who attended our foot care programme for 2 years, and collected data from April 2005 to March 2009. Patients were divided into four groups according to the risk classification, and received foot care. We evaluated the incidence of foot ulceration or recurrence and non-ulcerated foot condition. Characteristics of the patients were analysed using the paired t-test and McNemar's test, and changes in severity of tinea pedis and grade of callus were analysed using Wilcoxon's signed rank sum test. The programme reduced the severity score of tinea pedis (P < 0·001) and improved callus grade (P < 0·001). All these were evaluated by Wilcoxon's signed rank sum test. None of the patients of risk-group-3 (history of foot ulceration) showed recurrence of callus-related foot ulcers. Six high-risk patients developed foot ulceration during the programme because of minor injury, but the ulcers healed without development of gangrene. A nurse-based foot care programme is effective in preventing diabetic foot in diabetic patients.


Impaired suppression of endogenous glucose production in lean Japanese patients with type 2 diabetes mellitus.


Basal Insulin Requirement Is ~30% of the Total Daily Insulin Dose in Type 1 Diabetic Patients, Who Use the Insulin Pump.

OBJECTIVE To investigate the basal insulin requirement in total daily insulin dose in Japanese type 1 diabetic patients, who use the insulin pump. RESEARCH DESIGN AND METHODS The basal insulin requirement in 35 type 1 diabetic patients without detectable C-peptide using the insulin pump (Paradigm 712) was investigated during 2-3 weeks of hospitalization. The patients were served diabetic diets of 25-30 kcal/kg ideal body weight. Each meal omission was done to confirm stable blood glucose levels within 30 mg/dL variance until the next meal. Target blood glucose level was set at 100 mg/dL before each meal and 150 mg/dL at 2 h after each meal. RESULTS Total daily insulin dose was 31.6 ± 8.5 units, and total basal insulin requirement was 8.7 ± 2.9 units, which was 27.7 ± 6.9% of the total daily dose. CONCLUSIONS Basal insulin requirement is ∼30% of the total daily dose in Japanese type 1 diabetic patients, who use the insulin pump.


Aldose reductase C-106T gene polymorphisnm is associated with diabetic retinopathy in Japanese patients with type 2 diabetes

It is likely that the C allele of the polymorphism at position -106 in the promoter of aldose reductase gene, which codes a rate-limiting enzyme of the polyol pathway, is a susceptibility allele for diabetic retinopathy in Japanese type 2 diabetic patients.


YKL-40, a new biomarker of endothelial dysfunction, is independently associated with albuminuria in type 2 diabetic patients.

The aim of this study was to examine the possible association between YKL-40, a new biomarker of endothelial dysfunction, and albuminuria in 180 type 2 diabetic patients. Multivariate logistic regression analyses demonstrated that serum YKL-40 level was a determinant of albuminuria independently of conventional risk factors.


Relationship between carotid intima-media thickness and the presence and extent of coronary stenosis in type 2 diabetic patients with carotid atherosclerosis but without history of coronary artery disease.

Our data suggest that max-IMT might be closely associated with the extent of coronary stenosis in type 2 diabetic patients without history of CAD but with carotid atherosclerosis.

Max-IMT in the ≥ 50% stenosis group by multi-slice computed tomography coronary angiography estimation was significantly greater than the 0-25 and 25-50% stenosis group (2.68 ± 0.77 vs. 1.61 ± 0.49 mm, P < 0.0005, and 2.14 ± 0.81 mm, P < 0.05, respectively), and max-IMT in the 25-50% stenosis group was significantly greater than the 0-25% stenosis group (P < 0.05) after adjustment for age, sex, duration of type 2 diabetes, hypertension, and dyslipidemia. In the analysis for trend through the categories of max-IMT, as max-IMT increased, the percentage of ≥ 50% stenosis increased and the percentage of 0-25% stenosis decreased.


Effects of glimepiride and glibenclamide on carotid atherosclerosis in type 2 diabetic patients.

We performed a 3-year observation study of type 2 diabetic patients treated with glibenclamide or glimepiride and found that the annual progression of the maximum carotid intima-media thickness was significantly attenuated in the subjects treated with glimepiride (n=20) as compared with those treated with glibenclamide (n=20) (-0.044±0.171mm/year vs. 0.077±0.203mm/year, p=0.0474).


Effect of alogliptin, pioglitazone and glargine on pancreatic β-cells in diabetic db/db mice.

Male db/db mice were treated with a chow including pio, alo, or both of them from 8 to 16 weeks of age. Insulin glargine (gla) was daily injected subcutaneously during the same period.

Combination therapy with pio and alo almost completely normalized β-cell functions in vivo, which was comparable with gla treatment.

Biochemical and Biophysical Research Communications


Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients.

TC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.

A stepwise multivariate regression analysis demonstrated that HDL-C (β = -0.110, p<0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.


Efficacy of occasional self-monitoring of postprandial blood glucose levels in type 2 diabetic patients without insulin therapy.


Five percent weight loss is a significant 1-year predictor and an optimal 5-year cut-off for reducing the number of obesity-related cardiovascular disease risk components: the Japan Obesity and Metabolic Syndrome Study.

This study aimed to identify the amount of weight loss needed in patients with obesity to improve metabolic syndrome (MetS), a risk factor for cardiovascular disease (CVD), over a long period of time. A total of 576 patients with obesity were enrolled in this study. Effects of continuous physician-supervised weight loss on the cumulative MetS components excluding abdominal circumference (defined as obesity-related CVD risk score) were investigated during a 5-year follow-up period. The extent of weight loss required to reduce the obesity-related CVD risk components was assessed using receiver operating characteristic (ROC) curve analyses. Of the 576 participants, 266 completed 5-year follow-up, with 39.1% and 24.1% of them achieving ≥5.0% and ≥7.5% weight loss at the 5-year follow-up, respectively. The area under the ROC curve for reducing the obesity-related CVD risk components was 0.719 [0.662-0.777] at 1 year and 0.694 [0.613-0.775] at 5 years. The optimal cut-off value for weight loss was 5.0% (0.66 sensitivity and 0.69 specificity) and the value with 0.80 specificity was 7.5% (0.45 sensitivity) at 5 years. Greater reductions in weight were associated with greater improvements in the obesity-related CVD risk score at all follow-up periods (-trend <0.001). Obesity-related CVD risk score was significantly improved by 5.0-7.5% and ≥7.5% weight loss at 1 year ( = 0.029 and < 0.001, respectively) and ≥7.5% weight loss at 5 years ( = 0.034). A weight loss of ≥5.0% at 1 year and ≥7.5% at 5 years could reduce the number of obesity-related CVD risk components in patients with obesity.


クリニカルカンファレンスから(第23回) 徳島大学病院の症例 高度肥満による続発性無月経に対し腹腔鏡下スリーブ状胃切除術を施行し妊娠・出産に至った一例


IA-2抗体の高感度検出法(ICT-EIA法)の開発と長期罹患若年性1型糖尿病患者における3種膵島関連自己抗体(GADA,IA-2A,IAA)の検出について

Development of highly sensitive enzyme immunoassay (ICT-EIA) for IA-2 autoantibody and application for detection of three islet-specific autoantibodies ( GADA, IA-2A and IAA) in type I diabetes mellitus Tomoharu Kawano, Satoshi Numata, Yuki Fujimoto, Akio Kuroda, Tetsuyuki Yasuda,Kazuyuki Miyashita, Fumie Sakamoto, Naoto Katakami, Taka-aki Matsuoka, Munehide Matsuhisa and Seiichi Hashida Summary Detection of pancreatic islet-related autoantibodies( insulin antibody [IAA]; glutamic acid decarboxylase antibody [GADA]; and islet antigen-2 antibody [IA-2A], is essential for the diagnosis and prediction of the onset of type I diabetes mellitus. Depending on the disease duration, the detection rate of each autoantibody is different, and using only one kind of autoantibody detection risks overlooking a positive result. The detection precision of type I diabetes mellitus would thus be improved by measuring all three kinds of autoantibodies. We developed a highly sensitive enzyme immunoassay( ICT-EIA) for IA-2 autoantibody. ICT-EIAs for IAA and GADA have already been developed. Using three ICT-EIAs, we attempted to measure autoantibodies in sera from patients with type I diabetes mellitus. Patients comprised 25 males and 51 females( mean age, 33.3±5.7 years; disease duration, 23.9±6.7 years) with type I diabetes mellitus who had been undergoing treatment with insulin for between 11 and 40 years. Among these patients, urinary C-peptide-positive results were seen in three patients. IAA, GADA and IA-2A in sera were measured by ICT-EIA. The newly developed ICT-EIA for IA-2 antibodies was approximately 100-times more sensitive than the conventional ELISA. The positive ratio was 77.6%, representing a high rate of detection. In addition, even in patients with a disease duration >30 years, the positive rate was 64.3%. ICT-EIA was thus suggested to be useful in combination assays for pancreatic islet-related autoantibodies (IAA, GADA and IA-2A).

Research bulletin of Tokushima Bunri University