Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.

Although proteinuria is highly prevalent in obese individuals, the association between proteinuria and low body weight is equivocal. In this study we determine whether low body weight is more strongly associated with proteinuria compared with normal weight. The association between body mass index (BMI) and proteinuria was examined in a cross-sectional study of 62,582 asymptomatic individuals aged 20-70 years without known kidney diseases recruited, based on the results of medical checkups in 1999. We also examined the incidence of recurrent or nonrecurrent proteinuria in an 8-year longitudinal analysis of 12,493 individuals without proteinuria at baseline. The prevalence of proteinuria showed a J-shaped relationship with BMI. Multivariate regression analysis showed that BMI of 27.0 kg/m(2) and above or 18.9 kg/m(2) and less was significantly associated with proteinuria relative to BMI 21.0-22.9 kg/m(2), even after adjusting for relevant cardiometabolic risk factors. In the longitudinal study, similar J-shaped relationships between the incident rates of proteinuria and baseline BMI groups were observed at post-baseline checkups. Baseline BMI 27.0 kg/m(2) and above was associated with significantly greater risk for recurrent and nonrecurrent proteinuria, whereas BMI 18.9 kg/m(2) and less was only associated with nonrecurrent proteinuria. Thus, obesity and low body weight may be associated with different types of proteinuria independent of cardiometabolic risk factors.

Background:In the past few decades, the incidence of cardiometabolic diseases and disorders of the liver, kidney, pancreas, heart, and lung, have been increasing in Western and Asian countries, including Japan. Numerous factors, including abnormal body weight (obesity, overweight, or underweight), infrequent exercise, and other unfavorable lifestyle factors (e.g., smoking and heavy alcohol drinking) have been proposed as risk factors for the development and the progression of diseases, such as type 2 diabetes, hypertension, and dyslipidemia, which ultimately lead to impaired organ function and possibly death. However, the mechanisms that link these risk factors with diseases are still poorly understood, and the potential treatments, including pharmacotherapy and diet, have not been fully evaluated. Methods: In 2011, we established a new collaborative research program, the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS). This multidisciplinary observational epidemiological research study was designed to cover several high-profile diseases and some traditional fields of internal medicine, as well as apparently unrelated fields and particular lifestyle factors, such as unhealthy eating behaviors. In a series of studies, apparently healthy subjects who underwent a regular medical checkup were retrospectively identified based on the results of their medical checkups. In this way, the incidence, prevalence, causality, and clinical relevance of specific conditions and diseases have been investigated in cross-sectional analyses of 100,000 -200,000 adults, and in longitudinal studies of several thousand subjects who underwent medical checkups multiple times. Discussion: This article describes the background, rationale, purpose, and methods of the SCDOIS. Using data obtained from annual medical checkups, our goals are to 1) establish criteria or identify clinical features that would enable clinicians to detect the presence of abnormal conditions associated with cardiometabolic diseases and/or organ impairment much earlier in the disease course; and 2) determine the potential mechanisms and therapies for these conditions.

ObjectivesLow 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.DesignA cross-sectional observational study with multivariate analysis.SettingSubjects were recruited in a healthcare centre in Saitama, an eastern district of Japan, near Tokyo.ParticipantsA 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 measuresSerum amylase, cardiometabolic risk factors, NAFLD determined by ultrasound, MetS determined by Adult Treatment Panel-III criteria and diabetes were assessed.ResultsThe 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).ConclusionsOur 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.

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