Latent associations of low serum amylase with decreased plasma insulin levels and insulin resistance in asymptomatic middle-aged adults.

BACKGROUND: Low serum amylase is likely to be associated with obesity and metabolic abnormalities, which are often accompanied by impaired insulin action. However, it is unclear whether low serum amylase is associated with impaired insulin action in clinical settings. Therefore, we investigated the associations of low serum amylase with plasma insulin levels, and obesity-related parameters, including leptin. RESEARCH DESIGN AND METHODS: We measured serum amylase, plasma insulin, obesity-related parameters such as leptin, cardiometabolic risk factors, and anthropometric parameters in a cross-sectional study of 54 asymptomatic subjects (mean age 48.6 ± 7.6 years) who were not being treated for diabetes. RESULTS: Body mass index (BMI) and plasma glucose at 120 min after a 75-g oral glucose tolerance test (OGTT) were significantly higher in subjects with low serum amylase (< 60 IU/l, n = 21) than in those with normal-to-high serum amylase (n = 33) (P = 0.04 and P = 0.004, respectively). In univariate correlation analysis, serum amylase was significantly correlated with BMI alone (r = -0.39, P = 0.004). By contrast, multivariate logistic analysis showed that each 1-SD increase in quantitative insulin sensitivity check index, and each 1-SD decrease in plasma insulin OGTT at 0 and 60 min, homeostasis model assessment of insulin resistance (HOMA)-R, and HOMA-ß were significantly associated with low serum amylase, particularly after adjusting for BMI. When subjects were divided into three groups according to HOMA-R, serum amylase levels were significantly lower in subjects with HOMA-R > 2.5 (n = 23) compared with subjects with HOMA-R 1.6-2.5 (n = 10) (61.1 ± 13.6 U/ml versus 76.9 ± 20.5 U/ml, Bonferroni test, P = 0.02), but not compared with subjects with HOMA-R<1.6 (n = 21; 62.7 ± 17.6 U/ml). Similar trends were observed when subjects were divided according to plasma leptin and fasting plasma insulin levels. CONCLUSIONS: These results suggest that after adjusting for BMI, low serum amylase is associated with decreased basal insulin levels and insulin secretion, as well as high insulin resistance. The nature of these associations remains to be elucidated in further studies.

Low serum amylase in association with metabolic syndrome and diabetes: A community-based study.

BACKGROUND: Low serum amylase levels may reflect impaired exocrine-endocrine relationship in the pancreas. However, few clinical studies have addressed this issue. Therefore, in this epidemiological study, we investigated whether low serum amylase was associated with the pathogenesis of impaired insulin action: metabolic syndrome (MetS) and diabetes. RESEARCH DESIGN AND METHODS: Serum amylase, cardiometabolic risk factors, MetS (Adult Treatment Panel III criteria), and diabetes were examined in 2,425 asymptomatic subjects aged 30-80 years who underwent medical checkups recently (April 2009-March 2010) and 5 years ago. RESULTS: Clinical variables, except for age and estimated glomerular filtration rate (eGFR), shifted favorably with increasing serum amylase levels. Plasma glucose levels at 1- and 2-hr during OGTT increased significantly with decreasing serum amylase levels. Multiple logistic analyses showed that, compared with highest quartile of serum amylase, lowest quartile was associated with increased risk for MetS and diabetes after adjustment for confounding factors [odds ratio (95% CI), 2.07 (1.39-3.07) and 2.76 (1.49-5.11), respectively]. In subjects who underwent checkups 5 years ago (n = 571), lower amylase at the previous checkup were associated with larger numbers of metabolic abnormalities at the recent checkup. The fluctuation over time in serum amylase levels in subjects with low serum amylase at the previous checkup was slight and was unaffected by kidney dysfunction. CONCLUSIONS: Our results indicate that low serum amylase is associated with increased risk of metabolic abnormalities, MetS and diabetes. These results suggest a pancreatic exocrine-endocrine relationship in certain clinical conditions.

Relationship between a Urine Protein-to-creatinine Ratio of 150 mg/gram Creatinine and Dipstick Grade in the Health Checkup: Substantial Number of False-negative Results for Chronic Kidney Disease.

OBJECTIVE: Proteinuria is a marker for cardiovascular diseases and all-cause mortality. In the Specific Health Checkups in Japan, when subjects show trace proteinuria (grade±) on dipstick assay, further examination is recommended to them. Although 150 mg/gCr is a threshold for diagnosing chronic kidney disease (CKD), little data on the relationship between dipstick grade± and the protein-creatinine ratio have been reported. METHODS: A cross-sectional study using urine specimens obtained in a single institute, JCHO Saitama Northern Medical Center, was performed from October 2014 to March 2016. The level of proteinuria was measured in fresh morning urine samples from 819 volunteer participants of the Specific Health Checkups by two methods: Eiken Uropaper III to detect and qualitatively grade proteinuria, and total protein concentration by the pyrogallol red method. RESULTS: Sensitivity, specificity, and the positive likelihood ratio to detect proteinuria of 30 mg/dL by 1+ were 90.3%, 97.8%, and 41.9, whereas 150 mg/gCr by ± were 45.3%, 81.4%, and 2.4, respectively. Therefore, screening for 150 mg/gCr by dipstick grade± had a false-negative rate of 54.7% and false-negative rate was significantly higher in women (8.0%) than in men (1.7%) (p < 0.0001). CONCLUSIONS: Although the dipstick assay is useful to detect clinically significant proteinuria, substantial numbers of false-negative results occur in checkups for identifying subjects with a risk of CKD.

[Chronological analysis of individually linked data for patients with intractable disease receiving public financial aid for treatment].

PURPOSE: Nationwide surveys of intractable disease patients receiving public financial aid for treatment were performed by Research Committee for Epidemiology of Intractable Disease (Ministry of Health and Welfare, Japan) 4 times in the past, in 1984, 1988, 1992 and 1997. The purpose of the present study was to clarify the features of continuance with intractable disease patients receiving public financial aid for treatment. METHODS: Individual information collected by each nationwide survey was linked using the disease, the residence, the sex, and the birth date. The proportion of intractable disease patients according to receipt duration, kind of medical insurance, sex and age was calculated with reference to the disease and an estimation of the receipt persistence rate was calculated for every year. Moreover, in consideration of variation in the data, average receipt persistence rates over years were also calculated. RESULTS: According to observation on individual patient's follow up, the proportion for which financial aid was discontinued within four years was 25%, while 70% continued receiving aid for at least four years and some 55% for eight or nine years. The proportion of those who continue receiving support long-term is high about the so-called autoimmune diseases, such as systemic lupus erythematosus, Behçet's disease, and the aortic syndrome. In contrast, with diseases having a poor prognosis, such as fulminant hepatitis, amyloidosis, and amyotrophic lateral sclerosis, periods of continuance are short. The proportion needing long-term continuation is higher in women than in men, especially with diseases which have long been eligible for support. However, with diseases for which receipt was started recently, there is a tendency for persistence to be higher in men than in women. CONCLUSION: With reform of insurance systems, including the medical system for intractable diseases, it is predicted that receipt continuation will change with alteration of social factors, and it is necessary to monitor receipt continuation carefully from now on.

[Characteristics of patients with intractable diseases receiving public financial aid for treatment--results of a nationwide survey, 1997].

OBJECTIVES: In order to clarify the characteristics of medical institutions visited by patients with selected intractable diseases, we analyzed data from the fourth nationwide survey in 1997. METHODS: We asked 47 prefectural governments to provide data concerning every patient receiving financial aid for treatment of 39 selected intractable diseases from April 1997 to March 1998. Out of 399,719 whose information was reported by prefectural governments, we analysed data of 370,232 patients whose medical institutions were reported. We performed detailed analysis on the relation between patients' residences and locations of medical institution which the patients visited, and on the characteristics of medical institutions. These analyses were respectively compared by sex and age, the beginning year of the financial aid, whether the patients were inpatients or outpatients, type of insurance, and clinical division where the patient was treated. RESULTS: 1. Analysis showed that 7.4% of all patients were treated in medical institutions outside the prefectures where they lived. Patients who lived in the neighboring prefectures of huge cities like Tokyo, tended to be treated in the medical institutions there. 2. We found that 23.5% of patients were treated in university hospitals, and 11.9% were seen in clinics. 3. There was a difference between patients with SMON and patients with myastenia gravis, pemphigus, epidermolysis bullosa or primary pulmonary hypertension. Of the two groups, the former preferred to visit clinics and be treated in medical institutions located in the same cities, towns, and villages where they lived. On the contrary, patients with the latter 4 diseases tended to visit large hospitals and be treated in those outside their prefectures. 4. Elderly patients over 70 years old tended to be treated in clinics or hospitals located in their neighborhoods. 5. Compared with past surveys, the percentage of patients treated in university hospitals had decreased, and that of patients treated in clinics had increased year by year. No change was found in the proportion of patients treated in medical institutions outside their prefectures. CONCLUSIONS: By the present analysis of a nationwide survey taken in fiscal year 1997, we were able to clarify the characteristics of medical institutions visited by patients with selected intractable diseases. This kind of analysis should be continued to obtain important information on the epidemiology of intractable diseases.

[Nationwide survey of intractable disease patients. Analyses of patients receiving public financial aid for treatment in fiscal year 1997].

OBJECTIVE: In order to clarify epidemiologic features of selected intractable diseases, an investigation of the fourth nationwide survey, in 1998, was performed. METHODS: We asked 47 prefectural governments to provide data concerning every patient receiving financial aid for treatment of 39 selected intractable diseases from April 1997 to March 1998. The items for each patient required were the beginning year of the financial aid, the disease code, sex, date of birth, residence, type of insurance, whether an in-patient or outpatient, medical institution and the clinical division where the patient was treated. We performed a detailed analysis regarding the age distribution, the prefecture, in-patient or outpatient, the clinical division, the insurance, and the disease, for both males and females. RESULTS: 1. The total number of patients who received financial aid for treatment was 399, 719 with a sex ratio of 0.66 (males 158, 766, or female 240, 953), 60.7% being between 45 and 74 years of age. Of 214, 173 patients whose status could be confirmed regarding outpatient or inpatient. 14.7% were the latter. Of 129, 685 cases, 56, 471 (43.6%) were treated in departments of internal medicine. Of 396, 187 patients, 65, 841 (16.6%) were covered by the health and medical services law for the aged. The greatest number of patients resided in Tokyo, and the least was in Yamanashi Prefecture. 2. With regard to specific intractable diseases, the largest number of patients receiving aid for treatment were suffering from ulcerative colitis at 52, 261, while the least number was for primary pulmonary hypertension at 96. The numbers for each group had increased within the 13 years from 1984 to 1997, except for SMON. As the patients' age increased, the percentage of those receiving treatment also increased and the numbers of aged individuals were especially elevated. 3. The proportion of in-patients for the Creutzfelde-Jakob disease was 76.4 percent, which was remarkably higher than for other diseases. CONCLUSION: By the present analysis of the nationwide survey in fiscal year 1997, we could clarify changes in epidemiologic features of patients receiving financial aid for treatment. This kind of analysis should be continued to obtain important information on the epidemiology of intractable diseases.

Independent association between low serum amylase and non-alcoholic fatty liver disease in asymptomatic adults: a cross-sectional observational study.

OBJECTIVES: Low serum amylase (LSA) was reported to be associated with obesity, metabolic syndrome (MetS) and diabetes. However, it is unknown as to whether LSA is associated with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of MetS and insulin resistance. Therefore, we performed a clinical epidemiological study to investigate this potential association. DESIGN: A cross-sectional observational study with multivariate analysis. SETTING: Subjects were recruited in a healthcare centre in Saitama, an eastern district of Japan, near Tokyo. PARTICIPANTS: A total of 1475 asymptomatic adults aged 30-79 years who underwent detailed medical check-ups and who regularly consumed small amounts of alcohol (<20 g/day). OUTCOME MEASURES: Serum amylase, cardiometabolic risk factors, NAFLD determined by ultrasound, MetS determined by Adult Treatment Panel-III criteria and diabetes were assessed. RESULTS: The prevalence of NAFLD increased significantly from 22.5% to 42.4% (all grades) and from 9.2% to 24.0% (moderate or severe grade) from the highest to the lowest quartile of serum amylase. Multiple logistic regression analysis showed that, compared with the highest quartile of serum amylase, the lowest quartile of serum amylase was significantly associated with any-grade NAFLD and with moderate-to-severe NAFLD, even after adjusting for MetS or diabetes. The association between LSA and any-grade NAFLD disappeared after further adjustment for body mass index or waist circumference, whereas the association between LSA and moderate or severe NAFLD remained statistically significant (ORs (95%CI), 2.01 (1.07 to 3.78) and 2.06 (1.09 to 3.87), respectively, both p=0.01). CONCLUSIONS: Our results suggest that LSA may be associated with moderate or severe NAFLD in asymptomatic adults independent of MetS, diabetes and obesity. These results warrant confirmation in further studies.

Prediabetes and impaired lung function in asymptomatic adults.

Diabetes and metabolic syndrome are associated with impaired lung function. However, it is unknown whether this is also true in prediabetes. In a cross-sectional study of 1237 asymptomatic adults, we found that diabetes and prediabetes were both significantly associated with low vital capacity, even after adjustment for relevant confounding factors.

Low Vital Capacity and Electrocardiographic ST-T Abnormalities in Asymptomatic Adults.

Studies have shown that low forced vital capacity (LFVC) is associated with atherosclerosis. However, it is unclear whether LFVC is associated with resting electrocardiographic ST-T abnormalities, a common finding that is prognostic for cardiovascular events. Therefore, pulmonary functions, ST-T abnormalities defined with Minnesota Code, and cardiometabolic risk factors were examined in a cross-sectional study of 1,653 asymptomatic adults without past history of coronary heart diseases. The prevalence of diabetes, metabolic syndrome, and ST-T abnormalities significantly increased with decreasing percent of predicted forced vital capacity (%PFVC). ST-T abnormalities were observed in 73 subjects (4.4% in total). Multiple logistic regression analysis showed that, compared with the highest quartile of %PFVC (≥99.7%), the lowest quartile of %PFVC (≤84.2%) was persistently associated with ST-T abnormalities even after further adjustment for diabetes or metabolic syndrome (odds ratio (95%CI): 2.44 (1.16-5.14) and 2.42 (1.15-5.10), resp.). Similar trends were observed when subjects were divided into quartiles according to percent of predicted forced expiratory volume in 1 second (FEV(1)), but not the ratio of FEV(1)/FVC. In conclusion, LFVC may be associated with ST-T abnormalities independent of metabolic abnormalities in asymptomatic adults, suggesting a plausible link between impaired pulmonary defects and cardiovascular diseases.

Evaluation of a method for issuing warnings pre-epidemics and epidemics in Japan by infectious diseases surveillance.

BACKGROUND: Simple methods have been developed to warn of pre-epidemics and epidemics in small areas using data of infectious diseases surveillance. Epidemic warnings are made if the index of cases per week per sentinel medical institution is greater than a defined value. A pre-epidemic warning means that an epidemic warning will be given in the following four weeks. While the methods are used routinely for surveillance in Japan, they remain to be validated. METHODS: Infectious diseases surveillance data of influenza-like illness and 12 pediatric diseases in the fiscal year between 1999 and 2001 were used in the analysis. We examined the frequency of warnings, temporal changes in the index before and after the onset of a warning, and the sensitivity, specificity, and positive predictive value of pre-epidemic warnings. RESULTS: For the majority of the diseases investigated, the proportion of weeks in which a warning was issued ranged between 0% and 10%. In several diseases including influenza-like illness, we observed a rapid increase and gradual decrease in the index before and after a warning. The sensitivity, specificity, and positive predictive value of a pre-epidemic warning were 90.4%, 93.7% and 23.9% for influenza-like illness, and ranged between 25.1-54.2%, 86.1-99.2%, and 2.5-20.8% for the pediatric diseases (chickenpox, rubella, measles, and mumps), respectively. CONCLUSIONS: The study showed that the methods used for determining whether or not to issue an epidemic warning were satisfactory in some diseases, including influenza-like illness, and may need to be improved in several other diseases.

Annual incidence rate of infectious diseases estimated from sentinel surveillance data in Japan.

BACKGROUND: The estimation of incidence rates of infectious diseases based on the sentinel surveillance data is rather rare. We attempted to estimate these in 2000 in Japan by the surveillance data, and to evaluate their biases. METHODS: We used the incidences of influenza-like illness and 12 pediatric diseases in each of the sentinel medical institutions in Japan based on surveillance data in 2000. The incidence in all medical institutions was estimated under the assumption that the sentinel medical institutions were randomly selected. The possible bias of this estimate was evaluated in comparison with the hypothetical true incidence obtained as the total incidence in all medical institutions estimated by a regression model using the numbers of all disease outpatients per day from the National Survey of Medical Care Institutions of Japan. RESULTS: The estimated annual incidence rate was 75.6 (95% confidence interval: 72.3-78.7) per 1,000 population in influenza-like illness, and ranged from 1.1 (95% confidence interval: 1.0-1.2) to 285.2 (95% confidence interval: 270.2-300.3) per 1,000 population aged 0-19 years among 12 pediatric diseases. The ratio of the estimated incidence to the hypothetical true one was 1.06-1.26 among influenza-like illness and the 12 pediatric diseases. CONCLUSIONS: The incidence rates of influenza-like illness and pediatric diseases in 2000 in Japan were estimated from sentinel surveillance data. The rates obtained provide some useful but not always accurate information. Thus, further research is necessary.