Causes of In-Hospital Death and Pharmaceutical Associations with Age of Death during a 10-Year Period (2011-2020) in Individuals with and without Diabetes at a Japanese Community General Hospital.

Since diabetes and its complications have been thought to exaggerate cardiorenal disease, resulting in a short lifespan, we investigated causes of death and lifespans in individuals with and without diabetes at a Japanese community general hospital during the period from 2011 to 2020. Causes of death and age of death in individuals with and those without diabetes were compared, and associations between medications used and age of death were statistically analyzed. A total of 2326 deaths were recorded during the 10-year period. There was no significant difference between the mean ages of death in individuals with and those without diabetes. Diabetic individuals had higher rates of hepato-pancreatic cancer and cardio-renal failure as causes of death. The prescription rates of antihypertensives, antiplatelets, and statins in diabetic individuals were larger than those in non-diabetic individuals. Furthermore, the use of sulfonyl urea or glinides and insulin was independently and inversely associated with the age of death. In conclusion, individuals with diabetes were treated with comprehensive pharmaceutical interventions and had life spans comparable to those of individuals without diabetes. This study's discovery of an inverse relationship between the use of insulin secretagogues or insulin and the age of death suggests that the prevention of life-threatening hypoglycemia is crucial for individuals with diabetes.


Cross-Sectional and Longitudinal Associations between Skin Autofluorescence and Tubular Injury Defined by Urinary Excretion of Liver-Type Fatty Acid-Binding Protein in People with Type 2 Diabetes.

= 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury.


Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes.

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia.


Vascular Endothelial Function Is Associated with eGFR Slope in Female and Non-Smoking Male Individuals with Cardiovascular Risk Factors: A Pilot Study on the Predictive Value of FMD for Renal Prognosis.

In individuals with cardiovascular risk factors, evaluation of vascular endothelial function enables prediction of renal prognosis in females and non-smoking males.

Journal of Atherosclerosis and Thrombosis


Phase angle and extracellular water-to-total body water ratio estimated by bioelectrical impedance analysis are associated with levels of hemoglobin and hematocrit in patients with diabetes.

PhA and ECW/TBW but not SMI were associated with levels of Hgb and Hct in patients with diabetes. Therefore, aberrant values of PhA and ECW/TBW suggest a risk of anemia in diabetic patients.


Umami taste sensitivity is associated with food intake and oral environment in subjects with diabetes

Dysgeusia is a serious problem in patients with diabetes because it often leads to overeating, which is associated with disease progression. This study aimed to investigate the association between taste sensitivity, eating habits, and the oral environment. In this cross-sectional study of 75 subjects with diabetes, gustatory function was assessed using the whole-mouth method, and lingual taste receptor gene expression was measured by real-time PCR. Food intake was evaluated using a food frequency questionnaire based on food groups. The oral environment was assessed using xerostomia and periodontal comprehensive examination. In total, 45.3%, 28.0%, and 18.7% of subjects showed lower umami taste sensitivity, low sweet taste sensitivity, and low salt taste sensitivity, respectively. Lower umami sensitivity correlated with lower estimated glomerular filtration rate and higher energy-source food intake. Subjects with diabetes with higher plaque control record showed significantly higher T1R3 gene expression than those with lower plaque control record. Reduced umami taste sensitivity is associated with decreased renal function and high energy food intake in diabetes. Subjects with diabetes with higher plaque control record showed significantly higher T1R3 gene expression, suggesting that the oral environment affects taste gene expression. J. Med. Invest. 70 : 241-250, February, 2023.

The Journal of Medical Investigation : JMI


Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus: A randomized, crossover trial.

The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM.

The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001).


Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.

Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.

Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p<0.001), NFS (p<0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012).


Comparison of continuous subcutaneous insulin infusion treatment and multiple daily injection treatment on the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

To evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima-media thickness and brachial-ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile-onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments.


Novel method utilizing bisulfite conversion with dual amplification-refractory mutation system polymerase chain reaction to detect circulating pancreatic β-cell cfDNA.

We developed a novel method for detecting unmethylated insulin DNA in circulation that can be performed using a conventional real-time PCR system. This method would be useful for analyzing dynamic profiles of β-cells in human disease such as type 1 diabetes.


Basal insulin requirement in patients with type 1 diabetes depends on the age and body mass index.


Taste receptor gene expression is associated with decreased eGFR in patients with diabetes.

Dysgeusia is not only associated with zinc deficiency but also with certain drugs or diseases, including diabetes and renal failure. It often lowers the patient's quality of life and hinders access to proper nutrition. The underlying mechanism is unclear and there is a lack of awareness among patients. Here, we focused on lingual taste receptor gene expression in diabetes and elucidated the relationship between taste receptor gene expression and renal function. Forty-seven patients with diabetes and 10 healthy subjects (control group) were enrolled. Lingual foliate papillae were scraped and the derived cDNA was quantified by real-time polymerase chain reaction. Dysgeusia was assessed using SALSAVE?. All statistical analyses were performed using JMP? software 13. The expression of T1R1 and T1R2 was significantly upregulated in type 2 diabetes patients as compared with that in healthy subjects (P<0.01) but did not change in type 1 diabetes patients. T1R3 expression positively correlated and Scnn1 expression negatively correlated with estimated glomerular filtration rate, suggesting that altered taste receptor gene expression could reflect impaired renal function. Thus, alterations in T1R3 and Scnn1 expression in diabetes correlated with renal function. Taste receptor gene expression dysregulation could indicate dysgeusia associated with impaired renal function in patients with diabetes. J. Med. Invest. 69 : 120-126, February, 2022.


循環血中遊離 DNA を用いた膵β細胞傷害の新規検出法の確立

循環血中遊離 DNA を用いた膵β細胞傷害の新規検出法の確立

In people with type1 diabetes(T1D), biomarkers that can sensitively and quantitatively evaluate injury of pancreatic beta cell are required in order to predict the onset of the disease at an early stage and to provide interventions to prevent the progression of the disease. We developed a new method for quantifying pancreatic beta cell-derived insulin DNA in circulation that combines bisulfite conversion and Amplification Refractory Mutation System(ARMS)PCR, which can be performed using a conventional real-time PCR system. We applied this method to T1D patients and healthy adults, both could be detected in about 30% of cases. The results in healthy adults indicate that this method may have sensitivity to detect the turnover of pancreatic beta cells at physiological conditions. In post-onset T1D patients, there were many negatives because the amount of residual pancreatic beta cells was extremely small. However, in some cases with a short duration of the disease, pancreatic beta cell-derived insulin DNA was detected in negative correlation between the duration of the disease, that suggested the residual pancreatic beta cells continue to be slowly destroyed. It was demonstrated that the time course of pathophysiology in T1D could be understood using this method.


TIA様症状を契機に診断されたインスリノーマの1例

TIA様症状を契機に診断されたインスリノーマの1例

We report the case of a67-year-old woman who had symptoms suggestive of a transient ischemic attack(TIA), such as lightheadedness and transient visual changes before meals for 4 months. She experienced altered consciousness before lunch and was taken to the emergency room2weeks ago. She had repeated hypoglycemia with a blood glucose level of 31 mg/dL. Insulin secretion was not suppressed, with an immunoreactive insulin level of 14．0 μU/mL and connecting peptide immunoreactivity of 1．83 ng/mL for occasional blood glucose levels of 49 mg/dL. Dynamic CT revealed a 17‐mm mass enhanced during the arterial phase in the pancreatic uncinate process, suggestive of a pancreatic neuroendocrine tumor. A selective arterial secretagogue(calcium)injection test revealed the localization of insulinoma in the head of the pancreas. Therefore, pancreatoduodenectomy was performed. Hyperglycemia occurred after the surgery, and it was judged that the insulinoma was resected. This case showed TIA-like symptoms without signs of sympathetic overdrive associated with hypoglycemia. Thus, the diagnosis was delayed. Insulinoma may present with symptoms of neuroglycopenia but not autonomic activity due to hypoglycemia. Insulinoma should be distinguished in patients with unknown neurological symptoms since neuroglycopenia caused by insulinoma is diverse.


情報を活かし地域に沿った腎症重症化予防策「行政・医療機関の情報を活用したヒューマンネットワークによる糖尿病重症化」


A low serum IGF-1 is correlated with sarcopenia in subjects with type 1 diabetes mellitus: Findings from a post-hoc analysis of the iDIAMOND study.

A low serum IGF-1 level is correlated with sarcopenia and low skeletal muscle mass in subjects with T1DM.

The z-score of serum IGF-1 was significantly lower in the subjects with T1DM than that in those without diabetes (p < 0.001). Among subjects with T1DM, the z-score of serum IGF-1 was significantly lower in sarcopenic subjects than in non-sarcopenic subjects. The multivariable logistic regression analysis showed that the serum IGF-1 z-score was an independent determinant of sarcopenia and a low skeletal muscle mass index, but not low grip strength nor slow gait speed in subjects with T1DM.


Protocol for a Randomized, Crossover Trial to Decrease Time in Hypoglycemia by Combined Intervention of the Usage of Intermittent-Scanning Continuous Glucose Monitoring Device and the Structured Education Regarding its Usage: Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study).

The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

The Tokai Journal of Experimental and Clinical Medicine


Journal of the The Japan Diabetes Society


High prevalence and clinical impact of dynapenia and sarcopenia in Japanese patients with type 1 and type 2 diabetes: Findings from the Impact of Diabetes Mellitus on Dynapenia study.

Sarcopenia and dynapenia were more frequent in patients with type 1 diabetes and type 2 diabetes than in individuals without diabetes, which might contribute to their impaired quality of life and incidental falls.


Plasma Heparin Cofactor II Activity Is Inversely Associated with Albuminuria and Its Annual Deterioration in Patients with Diabetes.

The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria.


Progression of the advanced technology and therapy for diabetes mellitus

The Journal of the Japanese Society of Internal Medicine


Urinary adiponectin excretion is an early predictive marker of the decline of the renal function in patients with diabetes mellitus.

Since diabetes-associated kidney complication changes from diabetic nephropathy to diabetic kidney disease (DKD), more suitable biomarkers than urinary albumin are required. It has been hypothesized that urinary adiponectin (u-ADPN) is associated with the progression of DKD. We therefore evaluated the effectiveness of u-ADPN in predicting the decline of the renal function in patients with diabetes prior to end-stage renal disease. An ultrasensitive immune complex transfer enzyme immunoassay (ICT-EIA) was used to measure total and high molecular weight (HMW) adiponectin separately. We evaluated the relationships between the creatinine-adjusted urinary total-ADPN and HMW-ADPN, albumin (UACR) and liver-type fatty acid binding protein (L-FABP) at baseline and the 2-year change of the estimated glomerular filtration rate (ΔeGFR). This 2-year prospective observational study included 201 patients with diabetes. These patients were divided into three groups according to their ΔeGFR: ≤-10 mL/min/1.73m, >-10 and ≤0 mL/min/1.73m, and >0 mL/min/1.73m. Jonckheere-Terpstra test showed that lower ΔeGFR was associated with higher u-HMW-ADPN (p = 0.045). In logistic regression analysis, u-HMW-ADPN was associated with ΔeGFR after adjusted age, sex, and basal eGFR. Urinary HMW-ADPN could predict a declining renal function in patients with diabetes.

Journal of Diabetes and its Complications


Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.


Circulating FGF23 is not associated with cardiac dysfunction, atherosclerosis, infection or inflammation in hemodialysis patients.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone regulating serum inorganic phosphate (Pi) concentration. FGF23 is also involved in the development of chronic kidney disease (CKD)-mineral and bone disorder. Serum FGF23 concentration begins to increase early in the progression of CKD and can be remarkably high in hemodialysis patients with end-stage renal disease. It has been reported that high FGF23 concentration is a risk factor for cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. FGF23 was also shown to induce cardiac hypertrophy directly acting on cardiomyocytes. However, it is still controversial whether high FGF23 is causing cardiac dysfunction, atherosclerosis, infection or systemic inflammation in CKD patients. In the current study, we investigated whether FGF23 concentration is associated with cardiac dysfunction, atherosclerosis, infection or systemic inflammation in Japanese hemodialysis patients. We recruited 119 hemodialysis patients and examined the association between serum FGF23 concentration and several parameters concerning mineral metabolism, cardiac dysfunction, atherosclerosis, infection, and systemic inflammation. Serum FGF23 concentration was independently associated with serum calcium and Pi concentration (β = 0.276, p < 0.001; β = 0.689, p < 0.001). However, serum FGF23 concentration was not associated with parameters of cardiac dysfunction, atherosclerosis, infection, and systemic inflammation, either. Our results do not support the hypothesis that high FGF23 in dialysis patients is the cause of cardiac dysfunction, atherosclerosis, infection or systemic inflammation.


糖尿病患者の口腔保健行動アセスメントツールを用いた看護支援プログラムの評価

糖尿病患者の口腔保健行動アセスメントツールを用いた看護支援プログラムの評価


Predictive Factors of the Adherence to Real-Time Continuous Glucose Monitoring Sensors: A Prospective Observational Study (PARCS STUDY).

Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

Journal of Diabetes Science and Technology


Modified diabetes oral health assessment tool (M-DiOHAT©) for nurses and their association with efficacy beliefs and outcome expectancies in patients with diabetes

JNI : The Journal of Nursing Investigation


Predictive factors of posttransplant glucose intolerance in Japanese patients with type 1 diabetes after pancreas transplantation.

120 at the initial examination. In conclusion, insulinogenic index and iAUCR from OGTT performed in the early posttransplantation period were predictive factors of future glucose intolerance.


Clinical impact of sarcopenia and dynapenia on diabetes.

Sarcopenia as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. On the other hand, an age-related decline in muscle strength prior to the reduction of muscle mass, is proposed to be "dynapenia". Sarcopenia and dynapenia have recently been recognized as a diabetic complications in type 2 diabetes. We firstly indicated that sarcopenia was frequently observed in 16.6% of patients with type 1 diabetes aged even over 40 years. Additionally, we recently reported that the prevalence rate of dynapenia was higher than sarcopenia in patients with type 2 diabetes. Chronic hyperglycemia accelerates accumulation of advanced glycation end products (AGEs), which causes diabetic vascular complications through oxidative stress and chronic inflammation. We also demonstrated that skin autofluorescence (AF) as a marker of AGEs, was the independent determinant for skeletal muscle mass and strength in patients with type 2 diabetes and muscle strength in type 1 diabetes. Therefore, the early diagnosis of muscle weakness is essential for patients with diabetes and sustained good glycemic control with exercise and dietary intervention might be beneficial to prevent the progression of muscle weakness in these patients.


Circulating osteocalcin as a bone-derived hormone is inversely correlated with body fat in patients with type 1 diabetes.

The objective of the present study was to investigate the correlations between serum undercarboxylated osteocalcin (ucOC) or osteocalcin (OC) concentrations and %body fat, serum adiponectin and free-testosterone concentration, muscle strength and dose of exogenous insulin in patients with type 1 diabetes. We recruited 73 Japanese young adult patients with childhood-onset type 1 diabetes. All participants were receiving insulin replacement therapy. The correlations between logarithmic serum ucOC or OC concentrations and each parameter were examined. Serum ucOC and OC concentrations were inversely correlated with %body fat (r = -0.319, P = 0.007; r = -0.321, P = 0.006, respectively). Furthermore, multiple linear regression analyses were performed to determine whether or not serum ucOC or OC concentrations were factors associated with %body fat. Serum ucOC and OC concentrations remained significant factors even after adjusting for gender, HbA1c, body weight-adjusted total daily dose of insulin and duration of diabetes (β = -0.260, P = 0.027; β = -0.254, P = 0.031, respectively). However, serum ucOC and OC concentrations were not correlated with serum adiponectin or free-testosterone concentrations, muscle strength or dose of exogenous insulin. In conclusion, our study demonstrates the inverse correlation between serum ucOC or OC concentrations and body fat in patients with type 1 diabetes.


Development and Validation of the Continuous Subcutaneous Insulin Infusion-related Quality of Life (CSII-QOL) Scale.

The CSII-QOL is the first CSII-related QOL scale for people with T1D. This short, validated, and reliable instrument might potentially be useful in future clinical studies and routine clinical patient care. Further validation is required to confirm these issues because of the small and potentially biased sample. (UMIN-CTR: UMIN000031595).


Association of accumulated advanced glycation end-products with a high prevalence of sarcopenia and dynapenia in patients with type 2 diabetes.

Advanced glycation end-products (AGEs), which are a major cause of diabetic vascular complications, accumulate in various tissues under chronic hyperglycemic conditions, as well as with aging in patients with diabetes. The loss of muscle mass and strength, so-called sarcopenia and dynapenia, has recently been recognized as a diabetic complication. However, the influence of accumulated AGEs on muscle mass and strength remains unclear. The present study aimed to evaluate the association of sarcopenia and dynapenia with accumulated AGEs in patients with type 2 diabetes. We recruited 166 patients with type 2 diabetes aged 30 years (mean age 63.2 ± 12.3 years; body mass index 26.3 ± 4.9 kg/m ; glycated hemoglobin 7.1 ± 1.1%). Skin autofluorescence as a marker of AGEs, limb skeletal muscle mass index, grip strength, knee extension strength and gait speed were assessed. Sarcopenia and dynapenia were observed in 7.2 and 13.9% of participants, respectively. Skin autofluorescence was significantly higher in patients with sarcopenia and dynapenia. Skin autofluorescence was the independent determinant for skeletal muscle mass index, grip strength, knee extension strength, sarcopenia and dynapenia. Accumulated AGEs could contribute to reduced muscle mass and strength, leading to sarcopenia and dynapenia in patients with type 2 diabetes.


移植医療と再生医療の進歩 特集にあたって

Journal of the The Japan Diabetes Society


第32回日本糖尿病・妊娠学会年次学術集会 第1回公開講座ピアサポート報告

第32回日本糖尿病・妊娠学会年次学術集会 第1回公開講座ピアサポート報告


Safety of the batteries and power units used in insulin pumps: A pilot cross-sectional study by the Association for the Study of Innovative Diabetes Treatment in Japan.

As trouble related to the batteries and power units of insulin pumps was frequent, practical guidance should be provided to respective patients regarding the use of reliable batteries, and to be well prepared for unexpected insulin pump failure.


New risk factors of severe hypoglycemia.


糖尿病最新医療の進化と展望 特集にあたって


Accuracy and Time Delay of Glucose Measurements of Continuous Glucose Monitoring and Bedside Artificial Pancreas During Hyperglycemic and Euglycemic Hyperinsulinemic Glucose Clamp Study.

Both CGM and AP failed to follow plasma glucose values during nonphysiologically rapid glucose rising, but indicated accurate values during physiological glucose change.

Journal of Diabetes Science and Technology


Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review.

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.


Advanced glycation end products is a risk for muscle weakness in Japanese patients with type 1 diabetes.

Accumulation of advanced glycation end products (AGEs) is thought to contribute to muscle weakness in a diabetic animal model. Skin autofluorescence (AF) is a proposed marker for accumulation of AGEs in the skin. We aimed to investigate the relationship between AGEs accumulation, sarcopenia, and muscle function of Japanese patients with type 1 diabetes. Thirty-six patients with type 1 diabetes participated in this cross-sectional study. Sarcopenia parameters (skeletal muscle mass index (SMI) and knee extension strength) were compared with subcutaneous AGEs accumulation using skin AF. The prevalence of sarcopenia and impaired knee extension strength was 16.6% (male: 0.0%, female: 22.2%) and 47.2% (male: 22.2%, female: 55.6%), respectively. Knee extension strength was negatively correlated with skin AF (r²= 0.14, p < 0.05), but not with SMI. In conclusion, the AGEs accumulation might be one of the reasons of impaired lower limb muscle function in Japanese patients with type 1 diabetes. This article is protected by copyright. All rights reserved.


A Pirot study comparing the CGM-assessed glycemic profiles of patients with type 1 diabetes on insulin degludec and insulin glargine


Sequential cleavage of insulin receptor by calpain 2 and -secretase impairs insulin signalling.

Sequential cleavage of IR by calpain 2 and -secretase may contribute to insulin signalling in cells and its inhibition may be partly responsible for the glucose-lowering effects of metformin. Thus, IR cleavage may offer a new mechanism for the aetiology of insulin resistance.


Suppression of the Hypothalamic-pituitary-adrenal Axis by Maximum Androgen Blockade in a Patient with Prostate Cancer.

A 78-year-old Japanese man showed suppression of the hypothalamic-pituitary-adrenal axis during maximum androgen blockade (MAB) therapy including chlormadinone acetate (CMA) for prostate cancer. After stopping the MAB therapy, both the basal ACTH level and the response to CRH recovered. While no reports have indicated that CMA suppresses the hypothalamic-pituitary-adrenal axis in patients with prostate cancer, CMA has been shown to inhibit this axis in animals. These observations suggest that we must monitor the hypothalamic-pituitary-adrenal axis in patients treated with CMA, especially under stressful conditions.


Skin Autofluorescence is Associated with Early-stage Atherosclerosis in Patients with Type 1 Diabetes.

Skin AF was significantly associated with the presence and/or severity of diabetic complications and was an independent risk factor for carotid atherosclerosis.

Skin AF values were significantly higher in type 1 diabetic patients than in healthy controls (2.07±0.50 (mean±SD) and 1.90±0.26, respectively, p=0.024). Skin AF was associated with carotid IMT (r=0.446, p<0.001) and baPWV (r=0.450, p<0.001), but not with ABI (r=-0.019, p=0.8488). Notably, skin AF was an independent risk factor for IMT thickening. Similarly, skin AF was associated with log (UACR) (r=0.194, p=0.049) and was an independent risk factor for UACR. Furthermore, skin AF values were significantly higher in patients with diabetic retinopathy than in those without (2.21±0.08 and 1.97±0.06, respectively, p=0.020).

Journal of Atherosclerosis and Thrombosis


A Review of Insulin-Dosing Formulas for Continuous Subcutaneous Insulin Infusion (CSII) for Adults with Type 1 Diabetes.

Dosing guidelines for patients with type 1 diabetes using continuous subcutaneous insulin infusion (CSII), which are historically based on clinical experience and retrospective studies of patients consuming an American diet, recommend that basal insulin should represent approximately 50 % of the total daily dose (TDD). Recent prospective studies in the USA and Japan conclude that the more appropriate proportion is closer to 30-40 % of TDD. In addition, currently used formulas for calculating the carbohydrate-to-insulin ratio (CIR) and correction factor (CF) may lead to underdosing of bolus insulin by as much as 12.8-50 % for a hypothetical patient. The discrepancies between traditional formulas and data from newer studies can be accounted for by the more rigorous design of the newer studies (e.g., prospective design, controlled diets, meal omission, and frequent glucose monitoring). International differences in diet composition may also be important to consider when developing dosing recommendations for CSII.


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


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


Long-Term Pancreatic Beta Cell Exposure to High Levels of Glucose but Not Palmitate Induces DNA Methylation within the Insulin Gene Promoter and Represses Transcriptional Activity.

Recent studies have implicated epigenetics in the pathophysiology of diabetes. Furthermore, DNA methylation, which irreversibly deactivates gene transcription, of the insulin promoter, particularly the cAMP response element, is increased in diabetes patients. However, the underlying mechanism remains unclear. We aimed to investigate insulin promoter DNA methylation in an over-nutrition state. INS-1 cells, the rat pancreatic beta cell line, were cultured under normal-culture-glucose (11.2 mmol/l) or experimental-high-glucose (22.4 mmol/l) conditions for 14 days, with or without 0.4 mmol/l palmitate. DNA methylation of the rat insulin 1 gene (Ins1) promoter was investigated using bisulfite sequencing and pyrosequencing analysis. Experimental-high-glucose conditions significantly suppressed insulin mRNA and increased DNA methylation at all five CpG sites within the Ins1 promoter, including the cAMP response element, in a time-dependent and glucose concentration-dependent manner. DNA methylation under experimental-high-glucose conditions was unique to the Ins1 promoter; however, palmitate did not affect DNA methylation. Artificial methylation of Ins1 promoter significantly suppressed promoter-driven luciferase activity, and a DNA methylation inhibitor significantly improved insulin mRNA suppression by experimental-high-glucose conditions. Experimental-high-glucose conditions significantly increased DNA methyltransferase activity and decreased ten-eleven-translocation methylcytosine dioxygenase activity. Oxidative stress and endoplasmic reticulum stress did not affect DNA methylation of the Ins1 promoter. High glucose but not palmitate increased ectopic triacylglycerol accumulation parallel to DNA methylation. Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation. Finally, DNA methylation of the Ins1 promoter increased in isolated islets from Zucker diabetic fatty rats. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells. It provides new insights into the irreversible pathophysiology of diabetes.


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.


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.

Journal of Atherosclerosis and Thrombosis


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


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．

Journal of the The Japan Diabetes Society


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


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)


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.


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


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.


Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes.

DNA methylation is a mechanism by which cells control gene expression, and cell-specific genes often exhibit unique patterns of DNA methylation. We previously reported that the mouse insulin-2 gene (Ins2) promoter has three potential methylation (CpG) sites, all of which are unmethylated in insulin-producing cells but methylated in other tissues. In this study we examined Ins2 exon 2 and found a similar tissue-specific methylation pattern. These methylation patterns can differentiate between DNA from insulin-producing beta cells and other tissues. We hypothesized that damaged beta cells release their DNA into circulation at the onset of type 1 diabetes mellitus (T1DM) and sought to develop a quantitative methylation-specific polymerase chain reaction (qMSP) assay for circulating beta cell DNA to monitor the loss of beta cells. Methylation-specific primers were designed to interrogate two or more CpG in the same assay. The cloned mouse Ins2 gene was methylated in vitro and used for development of the qMSP assay. We found the qMSP method to be sensitive and specific to differentiate between insulin-producing cells and other tissues with a detection limit of 10 copies in the presence of non-specific genomic DNA background. We also compared different methods for data analysis and found that the Relative Expression Ratio method is the most robust method since it incorporates both a reference value to normalize day-to-day variability as well as PCR reaction efficiencies to normalize between the methylation-specific and bisulfite-specific components of the calculations. The assay was applied in the streptozotocin-treated diabetic mouse model and detected a significant increase in circulating beta cell DNA before the rise in blood glucose level. These results demonstrate that this qMSP assay can be used for monitoring circulating DNA from insulin-producing cells, which will provide the basis for development of assays to detect beta cell destruction in early T1DM.


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)


Two Cases of Type 1A Diabetes Associated with Diabetic Ketoacidosis and Thyrotoxicosis without Severe Hyperglycemia

著明な高血糖を呈さず甲状腺中毒症を契機に糖尿病ケトアシドーシスを発症した1A型糖尿病の2症例

A 33-year-old woman who had suffered from thirst, polyposia, polyuria and body weight loss was admitted with diabetic ketoacidosis (DKA). Her plasma glucose level was mildly elevated (243 mg/dl), but the urinary ketone reaction was strongly positive. A 29-year-old woman who had suffered from slight fever, nausea and body weight loss was also admitted with DKA. Her plasma glucose level was moderately elevated (281 mg/dl), but the urinary ketone reaction was strongly positive. There seemed to be few symptoms, however thyrotoxicosis was suspected because of the low level of serum cholesterol and creatinine despite the dehydration. After the admission, painless thyroiditis and Basedow's disease were diagnosed based on the disease course, respectively. Thyrotoxicosis appeared to make a great contribution to ketone synthesis.
 It is well known that autoimmune type 1 diabetes is closely associated with autoimmune thyroid disorder. In the case of DKA in type 1A diabetic patients with moderately elevated plasma glucose level and lower levels of serum cholesterol or creatinine as in these two cases, we should take concomitant thyrotoxicosis into consideration.

症例(1)は33歳，女性．口渇，多飲・多尿，体重減少を主訴に当院を受診し，DKAの診断にて緊急入院となったが，血糖値は243 mg/dlと著明な高血糖は認めなかった．症例(2)は29歳，女性．1A型糖尿病にて通院加療しており，第1子を出産後4ヶ月で微熱，嘔吐が出現し，経口摂取不能となったため当院を受診し，DKAの診断にて緊急入院となったが，血糖値は281 mg/dlと著明な高血糖は認めなかった．両症例とも甲状腺腫大や眼球突出など自己免疫性甲状腺疾患を疑わせる他覚所見は認めなかったが，低脂血症や脱水にもかかわらず血清クレアチニンが低値であることより甲状腺中毒症を疑った．実際に，症例(1)は無痛性甲状腺炎，症例(2)はバセドウ病による甲状腺中毒症を併発しており，DKAの発症に大きく寄与していたと考えられた．1A型糖尿病には，自己免疫性甲状腺疾患の合併率が高いことが知られている．高血糖が顕著ではないDKAの場合，甲状腺中毒症の合併を念頭に置く必要があると考えられた．


Subclinical hypothyroidism is independently associated with albuminuria in people with type 2 diabetes.

We examined a possible association between subclinical hypothyroidism and albuminuria in 159 people with type 2 diabetes. Patients with subclinical hypothyroidism had significantly higher levels of urinary albumin-to-creatinine ratio (UACR) than those with euthyroidism. Multivariate logistic regression analyses demonstrated that serum TSH level was an independent risk factor of albuminuria.


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


Successful pregnancy after simultaneous pancreas-kidney transplantation from a brain-dead donor: The first case report in Japan.

Simultaneous pancreas-kidney transplantation is a revolutionary medical procedure to cure diabetes mellitus and its complications in one step. For women with type 1 diabetes mellitus and end-stage renal disease, this procedure not only treats their disease but may also allow them to have children. Worldwide, 77 pregnancies from 43 pancreas-kidney recipients have been reported. Here, we present the first case report of successful pregnancy after simultaneous pancreas-kidney transplantation from a brain-dead donor in Japan. She conceived spontaneously 32 months after transplantation. Her pregnancy course was favorable except for mild rejection of the grafted pancreas and development of gestational diabetes. She delivered a 2882-g healthy infant in October 2010. Pregnancy after simultaneous pancreas-kidney transplantation is discussed.

The Journal of Obstetrics and Gynaecology Research


血管径が頸動脈洞のプラーク形成に与える影響について

血管径が頸動脈洞のプラーク形成に与える影響について


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.


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.


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