The work style and living condition survey of diabetologists and the expectations for the Japan Diabetes Society: results of questionnaires about the current state and the future prospect of their carrier in 2017.

The Japan Diabetes Society's Committee to Promote Female Diabetologists conducted a questionnaire survey from May to June 2017 to investigate the work style and living situation of diabetologists. The survey targeted 5298 Board Certified Diabetologists (diabetologists), with answers obtained from 1566 diabetologists (male, n = 1003: females, n = 563). Ninety-four percent of the males and 72% of the females worked full time. Twenty-one percent of the male subjects and 7% of the female subjects were heads of clinical departments, and 23% of the male subjects and 13% of the female subjects were diabetes training instructors, showing that there were fewer women than men in both roles. Regarding the allocation of time per day, men spent 10.7 h working, while women spent 8.5 h working. Both men and women slept 6.3 h. Men spent 1.0 h on housework, while women spent 3.3 h on housework. Men spent 0.7 h on childcare and nursing care, while women, spent 2.8 h. Among diabetologists in the childrearing generation, men spent 1.4 h providing childcare and nursing care, while women spent 4.9 h, showing that women spent significantly more time on these tasks than men. To encourage female diabetologists to work more actively, to reduce overworking on the part of male diabetologists, and to enhance the careers of both men and women as diabetologists, we conclude it necessary to improve the workplace environment and for the Japan Diabetes Society to offer support.

Increased cancer mortality among Japanese individuals with hyperinsulinemia.

AIMS: To evaluate the effect of hyperinsulinemia on cancer death, we clarified the association between hyperinsulinemia and cancer mortality among Japanese individuals. METHODS: All the participants (5586 men and 6652 women) lived in Hiroshima City, underwent a 75 g oral glucose tolerance test between 1994 and 2012, and were followed for mortality until August 2013. A systematic review of death certificates was used to confirm the cause of death. RESULTS: During the follow-up period (median, 10.0 years), 587 participants died of cancer. Lung cancer was the most common cause of organ-specific death. We divided the participants into 3 groups according to the tertiles of fasting immunoreactive insulin (FIRI) levels (low, middle, and high groups). The high group had the highest mortality rate (5.5 per 1000 person-years). The hazard ratio (HR) for cancer mortality of the high group after adjustment for possible confounders, such as age, sex, body mass index, smoking status, alcohol intake, and radiation effects (model 1), was significantly higher than that of the low group (HR, 1.55; 95% confidence interval (CI), 1.23-1.95). In model 2 (model 1 plus fasting plasma glucose) and model 3 (model 1 plus HbA1c), the multivariate HRs for cancer mortality were 1.46 (95% CI, 1.15-1.85) and 1.48 (95% CI, 1.17-1.87), respectively.The HR for cancer death at high FIRI levels (per 1 µU/mL) was 1.04 (95% CI, 1.02-1.05) in all participants after adjusting for fasting plasma glucose level and other confounders. In the subgroup analysis, the HRs were 1.03 (95% CI, 0.98-1.09), 1.05 (95% CI, 1.02-1.08), and 1.04 (95% CI, 1.02-1.06) in the normal, prediabetes, and diabetes group, respectively. CONCLUSIONS: Hyperinsulinemia was associated with a high risk of cancer mortality and may be an important link between cancer mortality and diabetes or prediabetes.

Association between a biomarker of glucose spikes, 1,5-anhydroglucitol, and cancer mortality.

INTRODUCTION: 1,5-Anhydroglucitol (1,5-AG) is a biomarker of glucose spikes. To evaluate the effect of acute glucose excursions on cancer death, we clarified the association between 1,5-AG and cancer mortality among Japanese individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: We measured 1,5-AG in 6783 (2842 men, 3941 women) individuals with normal fasting and 2-hour plasma glucose who received a 75 g oral glucose tolerance test between 1994 and 2012. They were followed for mortality until August 2013. A systematic review of death certificates was used to confirm the cause of death. We divided the participants into four groups according to the quartile of 1,5-AG level at registration. We used Cox regression to clarify the association between 1,5-AG levels and cancer mortality with multivariate adjustment for possible confounders. RESULTS: During the follow-up period (median, 10.0 years), 140 men and 109 women died of cancer. The HR for cancer mortality of the lowest quartile group was higher than that of the highest quartile group in men (HR, 2.62; 95% CI, 1.60 to 4.41) and in women (HR, 1.47; 95% CI, 0.88 to 2.47). These associations were not attenuated with further adjustment for HbA1c. CONCLUSIONS: 1,5-AG was associated with high risk of cancer mortality in Japanese men after adjustment for HbA1c.

Longitudinal examination of pancreatic ß-cell function in Japanese individuals.

AIMS/INTRODUCTION: We carried out a retrospective, longitudinal analysis of ß-cell function between a diabetes mellitus group, including those that progressed to diabetes mellitus during the follow-up period, and a diabetic type with glycated hemoglobin (HbA1c) <6.5 group, including those that progressed to a diabetic type during the follow-up period. ß-Cell function was assessed using homeostasis model of assessment of ß-cell function. MATERIALS AND METHODS: The relationship between the duration of diabetes mellitus or the diabetic type and pancreatic ß-cell function was compared between the diabetes mellitus group (1,817) and diabetic type with HbA1c <6.5 group (1,843) using results from an oral glucose tolerance test. Linear mixed effects models were used to analyze repeated measurements of oral glucose tolerance tests. RESULTS: The slope of the regression line of ß-cell function for the duration of the diabetes mellitus group was -2.2%/year before the diagnosis. The slope differed after the diagnosis, and the difference was 1.3. The slope of the diabetic type group was -1.2%/year, and no significant difference was observed in the slope before and after the diagnosis. ß-Cell function at the onset was 54.3% in the diabetic type group and 40.6% in the diabetes mellitus group, and the slope of the regression line was significantly higher in the diabetes mellitus group. We divided the diabetes mellitus and diabetic type with HbA1c <6.5 groups into obese and non-obese participants. ß-Cell function declined more with obesity. CONCLUSIONS: Subsequent declines in ß-cell function were faster in the diabetes mellitus group than that in the diabetic type with HbA1c <6.5 group, and increased with obesity.

Evaluation of the new criteria of 2010 for diabetes mellitus: Japan Diabetes Society.

We investigated the characteristics of the new criteria for diabetes mellitus (DM) issued by the Japan Diabetes Society in 2010, which include HbA1C measurement, and differences between 1999 criteria, in order to indicate clinical caution points. If a person with fasting plasma glucose (FPG) ≥126 mg/dl or an oral glucose tolerance test (OGTT) 2-h value ≥200 and HbA1C ≥6.5 % is determined as having DM, the disease can be detected at a rate of ≥70 % in persons <60 years and at no more than 40-50 % in elderly persons. In longitudinal examination, we observed that individuals with DM with FPG ≥126 mg/dl and HbA1C ≥6.5 % obtained the same determination over time at a rate of nearly 90 %. The percentage of persons whose result shifted from normal type to DM was 3- to 4-fold lower than that of persons whose result shifted from normal type to diabetic type. Based on these results, measurement of FPG and HbA1C at the same time may be extremely effective in identifying DM, although we should pay attention to a higher likelihood that mild glucose metabolism disorders will be overlooked.

Association between the Postprandial Glucose Levels and Arterial Stiffness Measured According to the Cardio-ankle Vascular Index in Non-diabetic Subjects.

OBJECTIVE: Although a relationship between post-challenge hyperglycemia and arterial stiffness has been reported, the relationship between the postprandial glucose levels and cardio-ankle vascular index (CAVI) in non-diabetic subjects is not clear. This study thus evaluated the association between the postprandial glucose levels after a composite meal and the degree of arterial stiffness measured according to CAVI in non-diabetic subjects. METHODS: The subjects included 1,291 individuals (655 men and 636 women; mean age, 48.6 years; range, 23-85 years) who underwent medical examinations, including blood tests and CAVI assessments, between October 2005 and April 2012. The 1-hour postprandial glucose levels were determined after a 600-kcal traditional Japanese meal. RESULTS: The CAVI values were significantly higher in the subjects with higher 1-hour postprandial glucose levels (≥140 mg/dL in men; ≥158 mg/dL in women). A simple regression analysis indicated that the CAVI values were significantly correlated with the 1-hour postprandial glucose levels in men (r=0.286, p<0.0001) and women (r=0.228, p<0.0001). After adjusting for age, BMI, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, 1-hour postprandial glucose, homeostatis model assessment of insulin resistance, estimated glemerular filtration rate, and high sensitive C-reactive protein, stepwise multiple regression analysis demonstrated that the 1-hour postprandial glucose level was an independent predictor associated with the CAVI in men (p=0.003) and older women 50 years of age or older (p=0.003). CONCLUSION: This study demonstrated that the 1-hour postprandial glucose levels are associated with increased CAVI values in non-diabetic men and older women 50 years of age or older.

The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects.

Few studies addressed the relation of visceral adiposity and high-molecular weight (HMW) adiponectin to arterial stiffness. We investigated the impact of visceral adipose tissue (VAT) and HMW adiponectin on cardio-ankle vascular index (CAVI) in asymptomatic Japanese subjects. We studied 487 consecutive subjects (271 men and 216 women) who underwent general health examination between October 2005 and May 2008. The abdominal, visceral, and subcutaneous adipose tissue areas were determined by low-dose x-ray computed tomography. Serum levels of total and HMW adiponectin were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. Cardio-ankle vascular index was positively correlated with VAT area and negatively correlated with HMW adiponectin levels. We also found the positive association of the number of metabolic syndrome components with CAVI in both sexes. A stepwise multiple regression analysis revealed that age, VAT area, serum HMW adiponectin levels, and homeostasis model assessment of insulin resistance were independent determinants of CAVI. Receiver operating characteristic analyses demonstrated that the predictive value of the VAT area for the extent of CAVI (mild: <25th percentile vs severe: >75th percentile) exceeded that of total or HMW adiponectin levels in both sexes. In conclusion, increased CAVI is associated with both amounts of VAT measured by computed tomography and serum HMW adiponectin levels in asymptomatic Japanese subjects. Receiver operating characteristic analysis indicates that the VAT area is a lot better predictor of arterial stiffness than adiponectin levels.

Is there any association between subcutaneous adipose tissue area and plasma total and high molecular weight adiponectin levels?

This study was conducted for the purpose of clarifying the correlations between the subcutaneous adipose tissue area and plasma total and high-molecular weight (HMW) adiponectin levels. The subjects of this study comprised 359 men and 142 women who underwent general health examinations from October 2005 to December 2006. The abdominal subcutaneous and visceral adipose tissue areas were measured using low-dose x-ray computed tomography. Total and HMW adiponectin levels were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. There were negative correlations between the plasma total and HMW adiponectin levels and visceral and subcutaneous adipose tissue areas using simple correlation analysis. Multiple linear regression analysis clearly indicated that the subcutaneous adipose tissue area was independently correlated with the HMW adiponectin levels in men and closely related in women. Many studies reported that only the visceral adipose tissue area showed a significant correlation with metabolic syndrome. However, these results clearly indicate that it is also important to consider the subcutaneous adipose tissue area in metabolic syndrome.

A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.

Effectiveness of Semmes-Weinstein monofilament examination for diabetic peripheral neuropathy screening.

OBJECTIVE: To evaluate the effectiveness of the Semmes-Weinstein monofilament examination (SWME) for diabetic peripheral neuropathy (DPN) screening at an outpatient clinic. METHODS: Eighty-two type 2 diabetic outpatients were questioned about 13 subjective symptoms and tested for deep reflexes. They were examined using two types of quantitative sensory testing: SWME (using 4.31/2 g and 5.07/10 g monofilaments) and vibration testing (using the C-64 quantitative tuning fork). The patients were diagnosed with DPN when two of the following three criteria from both legs were met: (1) the presence of either pain, numbness, or paraesthesia; (2) a diminished or absent ankle reflex; or (3) a scale below 4 for their vibration perception thresholds (VPT). RESULTS: The most common subjective symptoms were muscle cramps and numbness in the extremities. SWME 4.31/2 g at the great toe or the plantar aspect of the fifth metatarsal was the most useful diagnostic test for DPN, providing 60.0% sensitivity and 73.8% specificity. SWME 4.31/2 g was correlated with lower limb VPT (P=.029) and three subjective symptoms including fainting. SWME 5.07/10 g was correlated with lower limb VPT (P=.011), the ankle reflex (P=.013), the knee reflex (P=.031), and two subjective symptoms. However, the sensitivity to diagnose DPN was low (30.0%). CONCLUSIONS: The abnormalities indicated by SWME correlated well with those identified by lower limb VPT. Moreover, SWME 4.31/2 g correlated with fainting, suggesting that it could detect abnormalities in the small fibers. Considering the minimal time for this examination, SWME 4.31/2 g is a useful examination in an outpatient setting along with lower limb VPT and ankle reflex testing.

Westernization of lifestyle markedly increases carotid intima-media wall thickness (IMT) in Japanese people.

To illustrate the impact of westernization of lifestyle on the development of pre-clinical atherosclerosis in Japanese people, we compared risk factors for atherosclerosis such as serum lipids, blood pressure, BMI, insulin resistance, and smoking habits between non-diabetic native Japanese and non-diabetic Japanese Americans. Two hundred and twenty two non-diabetic Japanese Americans living in Hawaii and 271 non-diabetic Japanese living in Hiroshima, Japan were studied. Carotid intima-media wall thickness (IMT) was measured in all subjects by one physician. For all measurements the same ultrasound instrumentation was used. Although no significant differences were seen in serum total cholesterol (TC), triglycerides, or LDL-cholesterol (LDL-C) levels between the two groups in the 1998 study, previous to 1998 these three parameters were significantly higher in Japanese Americans than native Japanese in our study which has spanned the past 20 years. IMT was significantly greater in Japanese Americans than native Japanese (1.20+/-0.03 mm vs. 0.98+/-0.03 mm, (mean+/-S.E.) respectively; P<0.0001). Moreover Japanese Americans reach an IMT of 1.1 mm at age 50, whereas the native Japanese reach this value at age 70. These observations indicate more rapid atherosclerosis progression in Japanese Americans. Based on our IMT measurements, the status and the estimated progression of atherosclerosis in Japanese Americans is increased. Since IMT is a validated endpoint for assessment of atherosclerotic disease risk, it can be concluded that Japanese Americans are at increased risk for cardiovascular disease.

A successful pregnancy and delivery case of Graves' disease with myeloperoxidase antineutrophil cytoplasmic antibody induced by propylthiouracil.

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

Influence of the extent of westernization of lifestyle on the progression of preclinical atherosclerosis in Japanese subjects.

To clarify the influence of a westernized lifestyle on the risk factors for atherosclerosis and preclinical atherosclerosis in Japanese subjects, we surveyed a Japanese population and Japanese immigrants in the United States. Based on the extent of westernization of their lifestyle, the subjects were classified as Japanese (J), first generation Japanese-Americans (JA-I), and second or later generation Japanese-Americans (JA-II). The consumption of animal fat and simple carbohydrates increased in the order of J, JA-I, and JA-II, while the subjects with strenuous physical activity decreased in the same order. The waist-hip ratio, fasting insulin level, serum cholesterol and triglyceride levels, and prevalence of hypertension increased in the same order as the dietary changes. The carotid intima-media wall thickness and the plaque size, which are indices of preclinical atherosclerosis, also increased in the order of J, JA-I, and JA-II. These data indicate that a westernized lifestyle aggravates the risk factors for atherosclerosis and influences the progression of preclinical atherosclerosis, in correspondence with the extent of westernization.

Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing Graves' disease and immune thrombocytopenic purpura.

Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.