Low prevalence of exocrine pancreatic insufficiency in patients with diabetes mellitus

IntroductionExocrine pancreatic insufficiency (EPI) can occur in patients with diabetes mellitus (DM). Incidence of EPI and its clinical significance remain poorly defined. The aim of our study was to determine whether exocrine pancreatic function is impaired in patients with DM.Patients and methodsOne hundred and fifty consecutive patients, mean age 59.0 (±12.0 years), with DM lasting at least 5 years were included in the study. We included 50 patients with type 1 DM (DM1), 50 insulin-treated patients DM type 2 (DM2-insulin) and 50 non-insulin treated patients with DM type 2 (DM2 no-insulin). Diagnosis of DM was established from health records, lasting 15.0 ± 9.9 years on average. EPI was diagnosed with a fecal elastase-1 concentration (FE1) of less than 200 μg/g (ELISA).ResultsFE1 was reduced in 8 (5.4%) patients: mildly reduced (100–200 μg/g) in 4 patients (2.7%) and markedly reduced (<100 μg/g) in 4 patients (2.7%). Frequency of EPI was 3 in DM1, 5 in DM2(insulin) and none in DM2 (no-insulin) groups.ConclusionsEPI in DM occurred less frequently than in previous studies, probably due to our strict exclusion criteria (age, alcohol intake).     

Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial

BACKGROUND: Recently, high prevalence of exocrine dysfunction in diabetic populations has been reported. Patients with fecal elastase 1 concentration (FEC) <100 microg/g have also been demonstrated to suffer from steatorrhea in about 60% of cases, indicating the need of pancreatic enzyme replacement therapy. Until now, there have only been a few reports on the use of enzyme replacement therapy in diabetic patients with exocrine pancreatic insufficiency. This investigation was designed to evaluate the impact of enzyme-replacement therapy on glucose metabolism and diabetes treatment in a prospective study of insulin-treated patients with diabetes mellitus. METHODS: A total of 546 patients with diabetes mellitus requiring insulin treatment were screened for exocrine dysfunction by FEC measurements. One hundred and fifteen patients (21.1%) had FEC <100 microg/g (normal >200 microg/g). Of these, 95 patients entered the study and 80 patients were randomized to receive either pancreatin (Creon) (39 patients) or placebo (41 patients) in a double-blind manner. Parameters of glucose metabolism, diabetes therapy and clinical symptoms were recorded in standardized protocols for 16 weeks. RESULTS: During the observation phase of 16 weeks, there were no significant differences between both groups concerning HbA(1c), fasting glucose levels, 2-h pp glucose levels, clinical parameters and safety parameters. A reduction in mild and moderate hypoglycemia was observed in the pancreatin group at the end of the study. CONCLUSIONS: Pancreatin therapy can be used safely in patients with diabetes mellitus and exocrine dysfunction. Parameters of glucose metabolism were not improved by enzyme replacement therapy.     

Screening for pancreatic exocrine insufficiency in patients with diabetes mellitus

OBJECTIVES: Fecal elastase 1 (E1) is a relatively sensitive and specific indirect test of pancreatic exocrine function. Despite the high functional reserve of the pancreas, it is recognized that a significant proportion of diabetic patients may also have a deficit of the exocrine function. The aim of this study was to screen patients with diabetes mellitus (DM) for pancreatic exocrine insufficiency. METHODS: A total of 80 patients were enrolled in this prospective study, including 42 patients with DM and 38 nondiabetic controls. Exclusion criteria were as follows: age >75 yr; alcohol intake >40 g/day; intake of orlistat or acarbose; and history of diarrhea, pancreatitis, GI surgery, immunodeficiency, or cancer. All patients underwent the same study protocol, which included clinical evaluation, determination of fecal E1, plain x-rays of the abdomen, and abdominal ultrasound. An immunoenzymatic method (ScheBoTech, Wettenburg, Germany) was used for E1 determination. Diagnosis of pancreatic insufficiency was established for a fecal E1 <200 microg/g. RESULTS: The DM and control groups were comparable regarding age (62 +/- 10 yr vs 56 +/- 10 yr), sex (18 men and 24 women vs 15 men and 23 women), and proportion of patients with excess weight (50% vs 42%). Patients had DM diagnosed for 11.5 +/- 8 yr, with structural changes of the pancreas detected on ultrasound in three cases and calcifications in one case. There was no relationship between E1 determination <200 microg/g and the duration or the type of therapy for DM. Fifteen patients (36%) in the DM group had a fecal E1 <200 microg/g, compared with two patients (5%) in the control group (p < 0.05). In the DM group (n = 42), 11 patients with excess weight presented a fecal E1 <200 microg/g, whereas four patients with a BMI <25 presented this result (p < 0.05). CONCLUSIONS: Pancreatic exocrine insufficiency occurs more frequently in diabetic patients than in controls. Diabetic individuals with excess weight (BMI >25) may be at increased risk for underlying exocrine pancreatic insufficiency.     

Pancreatic exocrine insufficiency in diabetes mellitus - prevalence and characteristics

BackgroundThe prevalence of pancreatic exocrine insufficiency (PEI) in diabetes mellitus (DM) varies widely between studies, which may be explained by methodological problems. We aimed to establish the prevalence of PEI in DM using the faecal elastase-1 (FE-1) assay as a screening test, and to further investigate these patients by the mixed ¹³C-triglyceride (¹³C-MTG) breath test.MethodsOne hundred and thirty-three consecutive type 1 or type 2 DM patients without known exocrine pancreatic disorders were recruited. Demographic parameters, stool consistency, stool frequency, routine laboratory tests, and the presence of DM complications were registered. An FE-1 value <200 μg/g was used as the screening cut-off for PEI, and patients with FE-1 values below this level were referred for a ¹³C-MTG breath test.ResultsOne hundred and two patients returned faecal samples. The prevalence of PEI as measured by low FE-1 was 13%. Insulin usage, type 1 DM, and DM duration were associated with low FE-1. Stool habits were unaffected by low FE-1. Twelve out of 13 patients with low FE-1 performed the breath test, which was normal in all cases.ConclusionsThe prevalence of PEI defined by FE-1 was low in our mixed cohort of type 1 and 2 DM patients. Furthermore, there was a discrepancy between FE-1 and the breath test. Hence, the role of FE-1 in evaluating pancreatic exocrine function in DM should be evaluated in larger studies in order to clarify the association between low FE-1 and clinically relevant PEI.     

150例糖尿病患者胰腺外分泌功能检测及相关因素分析

目的探讨糖尿病患者胰腺外分泌功能不全的发生情况及其相关因素。方法选取2009年3月至2010年6月于第四军医大学西京医院内分泌科就诊的糖尿病患者150例,分为1型糖尿病组（T1DM,23例）、2型糖尿病组（T2DM,127例）,对照组为来我院健康体检者及我科医护人员共48人。记录糖尿病患者的年龄、性别、体质指数（BMI）、病程、糖尿病微血管病变发生情况、糖化血红蛋白（HbAle）等指标。收集受试者24h内排出的粪便,应用酶联免疫吸附实验（ELISA）法测定粪便中粪弹性蛋白酶（FE）的含量,对所有受试者的胰腺外分泌功能进行评估。率的比较采用X2检验或Fisher精确概率法。结果1型糖尿病患者、2型糖尿病患者及对照组粪便FE含量差异有统计学意义[分别为（394±237）比（502±194）比（576±170）μg／g,F=6．93,P〈0．01]。以FE〈200μg／g作为胰腺外分泌功能不全的判断标准,结果显示30．4％（7／23）的T1DM患者及7．9％（10／127）的T2DM患者存在胰腺外分泌功能不全,与对照组（0）相比,差异有统计学意义（Fisher检验P〈0．05）。以是否存在胰腺外分泌功能不全对糖尿病患者进行分组分析,结果显示两组间年龄、性别、BMI、病程、胰岛素治疗与否、糖尿病微血管病变发生情况、稳态模型胰岛素分泌指数（HOMA-B）、空腹胰岛素、餐后2h胰岛素及HbAlc等差异均无统计学意义（均P〉0．05）。结论本研究提示与健康对照相比,T1DM和他DM患者胰腺外分泌功能不全的发生率普遍较高。     

Utility of fecal fat concentrations as screening test in pancreatic insufficiency

We explored the utility of fecal fat concentration (gram fecal fat per 100 gram wet stool weight) as a screening test for pancreatic steatorrhea. Data were analyzed on 24 patients with pancreatic insufficiency and steatorrhea, six groups of patients (N-70) with nonpancreatic causes of steatorrhea, and 31 controls without steatorrhea. Patients with pancreatic steatorrhea had significantly (P<0.05) higher mean fecal fat concentrations than all groups except for patients with hepatobiliary disease. Using a fecal fat concentration of >9.5% as a cutoff point in all patients with steatorrhea, the test was 41.7% sensitive and 92.0% specific for the diagnosis of pancreatic insufficiency. For patients with fecal fat excretion >20 g/day, the test increased in sensitivity to 61.5% but specificity dropped to 85.3%. Measurements of fecal fat concentrations are therefore only moderately helpful, and further evidence is required to secure a diagnosis of pancreatic steatorrhea.     

Follow-up of exocrine pancreatic function in type-1 diabetes mellitus

In a previous study, mild to moderate exocrine pancreatic insufficiency, as measured by the secretin-pancreozymin test, was found in 23 (43%) of 53 patients with type-1 diabetes mellitus. Of these 53 patients, 20 (7 of whom initially had an abnormal secretin-pancreozymin test) were available for a follow-up examination 11 years later. Of the 7 patients with abnormal exocrine pancreatic function at the first test, 5 remained abnormal and 2 became normal, whereas of the 13 patients with initially normal pancreatic function the test result remained normal in 11 patients and became abnormal in 2. In these 2 groups the test result did not differ significantly between both tests. However, exocrine pancreatic function had returned to normal or had become abnormal in 2 patients, respectively, at the second test. In the 3 patients with exocrine pancreatic insufficiency at the first and second tests, the lipase level had not fallen below 10% or less than the normal level at which steatorrhea occurs and therapy is required. There was no significant correlation between the duration of the diabetes and the test results for both time points of investigation. The data suggest that mild to moderate exocrine pancreatic insufficiency found in type-1 diabetes is due to an early event in the course of the diabetes and does not progress. Therefore, this finding is of minor clinical importance and expensive pancreatic enzyme substitution will not be required.     

Prevalence of exocrine pancreatic insufficiency in type 2 diabetes mellitus with poor glycemic control

ObjectivesTo evaluate the relationship between exocrine pancreatic insufficiency and the level of glycemic control in diabetes (DM).MethodsPatients with type 2 DM treated in our clinic were prospectively recruited into the study. Pancreatic diabetes was excluded. Cases with HbA1c ≥7% formed Group A (n = 59), and with HbA1c <7% Group B (n = 42). The fecal level of pancreatic elastase (PE-1) was measured and morphological examinations of the pancreas were performed.ResultsThe PE-1 level was significantly lower in Group A than in Group B (385.9 ± 171.1 μg/g, vs. 454.6 ± 147.3 μg/g, p = 0.038). The PE-1 level was not correlated with HbA1c (r = −0.132, p = 0.187), the duration of DM (r = −0.046, p = 0.65), age (r = 0.010, p = 0.921), BMI (r = 0.203, p = 0.059), or pancreatic steatosis (r = 0.117, p = 0.244). The size of the pancreas did not differ significantly between Groups A and B.ConclusionsAn exocrine pancreatic insufficiency demonstrated by fecal PE-1 determination is more frequent in type 2 DM patients with poor glycemic control. The impaired exocrine pancreatic function cannot be explained by an alteration in the size of the pancreas or by pancreatic steatosis.     

Low faecal elastase 1 concentrations in type 2 diabetes mellitus

BACKGROUND: Previous studies have suggested an association between impaired pancreatic exocrine function and diabetes, but the evidence is weak because the invasive nature of the tests used to define exocrine function has led to small studies on selected patients. The availability of faecal elastase 1 as a non-invasive test has aided the detection of impaired exocrine function in population studies. We describe the association between levels of faecal elastase 1 and Type 2 diabetes. METHODS: 544 Type 2 diabetic patients (age: 63 +/- 8 years) were randomly selected from local diabetes registers in Cambridgeshire, UK and individually matched for age, sex and practice to 544 controls in whom diabetes was excluded by HbA1c measurement. RESULTS: Faecal elastase 1 concentrations were significantly lower in cases than controls (median: cases 308 microg/g; controls 418 microg/g; P < 0.01). Low levels of faecal elastase 1 (< 100 microg/g) were found in 11.9% of cases and 3.7% of controls (age-sex-adjusted odds ratio; 95% CI: 3.6; 2.2-6.2). After adjustment for potential confounding factors, the OR was 4.5 (2.6-8.3). Among patients with diabetes, poor glycaemic control (HbA1c > or = 7%) was associated with a higher risk of low elastase 1 level (OR 5.6; 1.5-37). No significant association was found with diabetes duration, peripheral neuropathy, alcohol intake, or prior gastrointestinal diseases. CONCLUSIONS: Faecal elastase 1 concentrations are lower in Type 2 diabetic patients than in non-diabetic controls, suggesting the co-existence of diabetes and impaired pancreatic exocrine function. Among the diabetic patients, the risk of having low elastase 1 levels was associated with glycaemic control.     

A case of fulminant type 1 diabetes mellitus with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion

Non-specific aggression to endocrine alpha and beta cells as well as exocrine pancreas has been suggested in fulminant type 1 diabetes (FT1DM), while its effect on glucagon secretion and exocrine function is unknown. Here, we report a FT1DM case with exocrine pancreatic insufficiency and enhanced glucagon response to meal ingestion.     

胰弹力蛋白酶1在胰腺外分泌功能测定中的作用

粪胰弹力蛋白酶1(PE1)ELISA法可用于诊断胰腺外分泌功能不足,这一方法可间接反映胰腺外分泌功能,特异、敏感,操作简便,对患者无损伤,且不受非胰腺疾病和酶替代疗法的影响。     

Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency

Background/Aim—The suggestion that estimation offaecal elastase 1 is a valuable new tubeless pancreatic function testwas evaluated by comparing it with faecal chymotrypsin estimation inpatients categorised according to grades of exocrine pancreatic insufficiency (EPI) based on the gold standard tests, thesecretin-pancreozymin test (SPT) and faecal fat analysis.
Methods—In 64 patients in whom EPI was suspected,the following tests were performed: SPT, faecal fat analysis, faecalchymotrypsin estimation, faecal elastase 1 estimation. EPI was gradedaccording to the results of the SPT and faecal fat analysis as absent,mild, moderate, or severe. The upper limit of normal for faecalelastase 1 was taken as 200 µg/g, and for faecal chymotrypsin 3 U/gstool. Levels between 3 and 6 U/g stool for faecal chymotrypsin areusually considered to be suspicious for EPI. In this study, both 3 and 6 U/g stool were evaluated as the upper limit of normal.
Results—Exocrine pancreatic function was normal in34 patients, of whom 94, 91, and 79% had normal faecal elastase 1 andfaecal chymotrypsin levels (<3 U/g and <6 U/g) respectively. Thirtypatients had EPI, of whom 53, 37, and 57% had abnormal faecal enzymelevels (differences not significant). When EPI was graded as mild,moderate, or severe, 63% of patients had mild to moderate EPI, and37% had severe EPI. In the latter group, between 73 and 91% ofpatients had abnormal faecal enzymes. In the group with mild tomoderate EPI, abnormal test results were obtained for both faecalenzymes in less than 50% of the patients (differences notsignificant). Some 40% of the patients had pancreatic calcifications.There were no significant differences for either faecal enzyme between the two groups with and without pancreatic calcifications. In 62% ofthe patients who underwent an endoscopic retrogradecholangiopancreatography (ERCP), abnormal duct changes were found.Again, there were no significant differences for either faecal enzymebetween the two groups with abnormal and normal ERCP.
Conclusion—Estimation of faecal elastase 1 is notdistinctly superior to the traditional faecal chymotrypsin estimation.The former is particularly helpful only in detecting severe EPI, but not the mild to moderate form, which poses the more frequent and difficult clinical problem and does not correlate significantly withthe severe morphological changes seen in chronic pancreatitis.

Keywords:faecal elastase 1; faecal chymotrypsin; secretin-pancreozymin test; faecal fat analysis; exocrine pancreaticinsufficiency; diagnosis

     

1型糖尿病患者的临床特点和多种胰岛自身抗体检出情况

目的分析1型糖尿病（T1DM）患者多种胰岛自身抗体的检出情况和不同类型T1DM的临床特征。方法选取2010年11月至2011年11月在中日友好医院住院的67例T1DM患者,分析其临床特征及胰岛细胞抗体（ICA）、胰岛素抗体（IAA）、谷氨酸脱羧酶抗体（GADA）[酶联免疫吸附试验（ELISA）法和免疫沉淀法（RIP）检测]、蛋白酪氨酸磷酸酶抗体（IA2A）和锌转运蛋白8抗体（ZnT8A）等6种胰岛自身抗体情况。结果本组T1DM共67例,其中经典型T1DM53例,成人迟发性自身免疫糖尿病（LADA）12例和暴发性1型糖尿病（FT1D）2例。起病年龄2～77岁,体质指数（BMI）（22±4）kg／m2,糖化血红蛋白（HbAlc）9．7％±2．4％,空腹C肽（0．3±O．4）μ／L。GADA（ELISA）阳性51例（76．1％）,GADA（RIP）阳性35例（52．2％）,IA2A阳性19例（28．3％）,ZnT8A阳性16例（23．9％）,IAA阳性16例（23．9％）,ICA阳性10例（14．3％）。前4种抗体检测方法至少1种阳性者共56例（83．6％）。51例ELISA法GADA阳性包括了35例RIP检测GADA阳性中的33例、19例IA2A阳性中15例及16例ZnT8A阳性中的14例。经典1型糖尿病在发病初至半年内需要胰岛素治疗,而LADA平均在发病3．9年后需要胰岛素治疗。2例FT1D患者起病急,发病时血糖分别为41．1和23．1mmol／L,HbAlc分别为7．8％和6．5％,空腹及餐后血C肽均小于0．03μg／L或不能测出。结论ELISA检0n．0GADA对1型糖尿病的诊断有较高敏感性,联合多种抗体检测对T1DM诊断作用有限。FT1D起病急骤,代谢紊乱更为严重。     

Titrimetric measurements of fecal trypsin and chymotrypsin in cystic fibrosis with pancreatic exocrine insufficiency

Summary A modification of a previously reported method for the quantitative determination of fecal trypsin and chymotrypsin using specific synthetic substrates and automatic titration has simplified the technic and greatly increased the sensitivity of measurements. Pancreatic exocrine function was objectively evaluated by measuring 24-hr. fecal fat excretion in subjects with cystic fibrosis, with and without malabsorption, and in normal controls.The author gratefully acknowledges the very helpful suggestions of Dr. J. Lowden, the assistance provided by Dr. W. S. Hartroft, and, especially, the permission of Dr. D. Crozier to investigate a large group of subjects from the Cystic Fibrosis Clinic. The Banting Foundation, Toronto, Canada, generously provided funds for purchase of the required tools.