J. Teichmann

High prevalence of exocrine pancreatic insufficiency in diabetes mellitus: A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients

Background: There have been numerous reports on pancreatic exocrine dysfunction in diabetes mellitus using either direct or indirect function tests. The measurement of fecal elastase 1 concentrations (FEC) has been used as a screening tool for exocrine pancreatic disease in different patient groups indicating a high prevalence of exocrine dysfunction in diabetic populations. In this study we had the opportunity to study more than 1,000 diabetic patients to confirm recent observations in smaller populations. Methods: FEC were measured by ELISA in 323 patients with type 1 and 697 type 2 diabetes mellitus. Subjects with a history of alcohol abuse, gastrointestinal surgery, cancer or inflammatory diseases were not included. Diabetes history and clinical data were recorded using a standard case report form. Findings: 1,021 patients (334 female, 687 male; mean age 50 years; mean diabetes duration 11 years; mean age at onset of diabetes 39 years) were studied. FEC was normal (>200 µg/g) in 59.3% and severely reduced (<100 µg/g) in 22.9%. There were significant differences between type 1 and type 2 patients as well as between insulin-treated and non-insulin-treated patients. Furthermore, there were weak associations between FEC and diabetes duration, age at onset of diabetes and body mass index, respectively. Interpretation: We could confirm that both type 1 and type 2 diabetic patients show pathological exocrine function in high prevalence. Exocrine insufficiency seems to be correlated to early onset of endocrine failure, long-lasting diabetes mellitus and low body mass index levels.

Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis

Abstract Recent studies have shown that systemic lupus erythematosus (SLE) is associated with a loss of trabecular bone. However, these changes have not been not described in patients with SLE at the time of diagnosis. To investigate the markers of bone metabolism 20 female patients with a recently manifested clinical picture of SLE were selected. All patients included in this study met the ARA criteria (for classification) of SLE. For comparison, 35 female patients with SLE, which had previously manifested itself and which had been treated with glucocorticoids, were included in a second group. A control group (III) consisting of 20 healthy individuals of the same age was formed to compare the results obtained. Test parameters comprised both serum levels of osteocalcin (OC) as the marker for bone formation and crosslinks excretion (CE) in urine as a specific marker for bone resorption. The bone density (BMD) was examined by dual energy X-ray absorption (DEXA) of the vertebral column (L2–L4), femoral neck, Wards triangle and trochanter. The patients under study received either no medication or nonsteroidal antirheumatic drugs. The BMD of the vertebral column was significantly lower than expected in SLE-afflicted subjects of group II when compared with the age-matched normal female controls. The reduction of BMD in female patients with SLE was related to the significantly increased excretion of urinary pyridinoline, to hypoparathyroidism, and to the decrease in serum OC. Bone loss in women with fresh manifestation of SLE (I) increases to a degree similar to that of patients in group II. Lowered BMD predicts an increased risk for bone fractures. Therefore, female premenopausal SLE patients should be monitored for osteoporosis.

High Prevalence of Steatorrhea in 101 Diabetic Patients Likely to Suffer from Exocrine Pancreatic Insufficiency According to Low Fecal Elastase 1 Concentrations: A Prospective Multicenter Study

Impaired exocrine pancreatic secretion has been frequently observed in diabetic patients by different methods, including direct function tests. However, the clinical importance remained unclear. In the present study, the fecal fat excretion in patients with type 1 or type 2 diabetes mellitus and exocrine dysfunction according to fecal elastase 1 concentrations <100 μg/g was investigated. Subjects with a history of gastrointestinal cancer, gastrointestinal surgery, alcohol abuse, or inflammatory diseases were excluded. In 101 patients the mean (±SD) fat excretion was 9.19 ± 5.39 g. Only 41 patients (40.6%) had normal fat excretion <7 g/day. In 40 patients (39.6%), it was higher than 10 g/day, indicating relevant steatorrhea. The fat excretion did not correlate with diabetes type, duration, or clinical symptoms. This finding is of some clinical importance and might influence pathophysiological concepts and the management of diabetic patients.

Relationship between disease activity and serum levels of vitamin D metabolites and parathyroid hormone in ankylosing spondylitis.

Abstract: Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication of ankylosing spondylitis (AS) and various factors may contribute to the development of osteoporosis in AS. It is known that inflammatory activity in rheumatic disease (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) seems to be another possible candidate for mediatory function in regulating both the inflammatory process and bone turnover. The aim of this study was to evaluate the relation between disease activity, bone turnover and calciotropic hormones. In 70 patients with established AS and an age- and sex-matched control group, the relation between disease activity (erythrocyte sedimentation rate, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index), and serum levels of vitamin D metabolites, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and urinary pyridinium crosslinks were determined. Serum levels of 1,25(OH)2D3 (p<0.01) and PTH (p<0.01) were negatively correlated with disease activity, the excretion of urinary pyridinium crosslinks showed a positive correlation with disease activity (p<0.01), and 1,25(OH)2D3 and PTH were positively correlated with bAP (p<0.01). These results indicate that high disease activity in AS is associated with an alteration in vitamin D metabolism and increased bone resorption. Furthermore, the decreased levels of 1,25(OH)2D3 may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest further research is necessary to determine whether low levels of 1,25(OH)2D3 as an endogenous immune modulator suppressing activated T cells and cell proliferation may accelerate the inflammation process in AS.

Ankylosing spondylitis and bone mineral density—what is the ideal tool for measurement?

Ankylosing spondylitis (AS) is characterised by chronic inflammation and partial ossification, yet vertebral fractures due to osteoporosis, although common, are frequently unrecognised. The aim of this study was to (1) show the frequency of changes in the progress of osteopenia/osteoporosis in AS depending on duration and stage of the disease and (2) assess the ranking of two different methods of bone density measurement in this clinical pattern. We measured bone density in 84 male and female patients with both dual X-ray absorptiometry (DXA) and single energy quantitative computed tomography (SE-QCT). In the initial and advanced stages of the disease, a high decrease in axial bone density could be verified (DXA: osteopenia in 5% and osteoporosis in 9.2%; SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3%). Peripheral bone density decrease as in osteopenia could be proven in 17.6% by DXA measurement. With SE-QCT, a decrease in vertebral trabecular bone density could already be observed in the initial stage and continued steadily during the course of the disease; cortical bone displayed the same trend up to stages of ankylosis. With DXA, valid conclusions are more likely to be expected in less marked ankylosing stages of AS. In stages of advanced ankyloses in the vertebral region (substantial syndesmophytes), priority should be given to SE-QCT, due to the selective measurement of trabecular and cortical bone. The DXA method often yields values that are too high, and the replacement of vertebral trabecular bone by fatty bone marrow is not usually recorded as standard. There may already be an increased risk of bone fracture in AS in osteopenia on DXA along with an osteoporosis already established on SE-QCT.

Vitamin D3 in Patients with Various Grades of Chronic Pancreatitis, According to Morphological and Functional Criteria of the Pancreas

There are still too few conclusive reports about conspicuous vitamin D deficiency in patients with chronic pancreatitis, or any connection of the deficiency to the severity of the disease. Between October 1999 and September 2000, we investigated 42 patients at an average age of 53 years, suffering from chronic pancreatits, as well as 20 healthy male controls at an average age of 49 years. Serum levels of D3 vitamins, 1,25-(OH)2-vitamin D3 and 25-(OH)-vitamin D3, as well as the concentration of fecal elastase 1 were determined in patients and controls. Furthermore, the severity of chronic pancreatitis in patients was determined via endoscopic retrograde cholangiopancreatography (ERCP) into 3 grades, based on the Cambridge classification. Elastase 1 in feces revealed sensitivities of 14%, 87%, and 95% for Cambridge-grades I, II, and III, respectively, and correlated significantly with this classification of severity of chronic pancreatitis (P < 0.01). In patients with Cambridge-grade II and III 1,25-(OH)2-D3 was markedly decreased (26.7 ± 7.7 pg/ml and 27.6 ± 9.0 pg/ml) compared to those with Cambridge-grade I (38.0 ± 10.5 pg/ml; between I and II P = 0.027, between I and III P = 0.033). 25-(OH)-D-3 did not differ significantly within the various Cambridge-grade groups (P = 0.07). Nevertheless, vitamin D3 and fecal elastase 1 in patients correlated significantly (P < 0.01) and, compared to controls, both were extremely low (means in patients: fecal elastase 1 140.7 ± 75.7 μ g/g, 1,25-(OH)2-D3 29.9 ± 9.5 pg/ml, 25-(OH)-D3 26.7 ± 9.7 nmol/liter; controls: fecal elastase 1 694.9 ± 138.6 μ g/g, 1,25-(OH)2-D3 67.5 ± 4.3 pg/ml, 25-(OH)-D3 69.5 ± 13.5 nmol/liter). The amounts of both D3 vitamins in patients were significantly lower when the content of fecal elastase 1 was under 200 μ g/g compared to the others [for 1,25-(OH)2-D3P < 0.01, for 25-(OH)-D3P < 0.05]. Therefore, ERCP and fecal elastase 1 verify the severity grade of a chronic pancreatitis, and thus show a vitamin D3 deficiency, depending on the progress of the disease. There seems to be a connection between inflammatory pancreas destruction (Cambridge classification), exocrine insufficiency (fecal elastase 1), and perhaps even the characteristics of sterol-binding of pancreatic elastase 1, which seems to be relevant for vitamin D supply.

Serum amyloid A--an indicator of inflammation in ankylosing spondylitis.

Abstract Biological markers of inflammation are useful for the diagnosis and monitoring of inflammatory rheumatic diseases. The present study tested, whether serum amyloid A (SAA) could be used as a marker of inflammatory disease activity in ankylosing spondylitis (AS). In 72 patients with AS, the two valuable surrogate markers of disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and an established clinical activity score (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI) were correlated to the serum levels of SAA. It was found that SAA correlates well with ESR, CRP, and BASDAI. Because of its strong correlation, SAA seems to be an additional very useful disease activity marker. When used in diagnosis, and especially in monitoring of inflammation, further studies are required. Another interesting point of view is the described role of plasma SAA as a precursor of Amyloid A (AA) protein in secondary amyloidosis, a known complication in AS. In all probability, high circulating SAA levels are a predisposing indicator of disease activity.

Ultrasonography of the glenohumeral joints – a helpful instrument in differentiation in elderly onset rheumatoid arthritis and polymyalgia rheumatica

Abstract In a prospective study, the glenohumeral joints of 51 patients (aged 60 or above) were examined, using ultrasonography. Twenty-two patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast, 29 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA, rheumatoid factor negative) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 40.9% (9/22) of the patients with PMR and 65.5% (19/29) of the patients with EORA. A discrete symmetrical biceps tendon sheath effusion was found in only three patients and unilateral in six patients with PMR. In contrast, 12 patients with EORA presented a massive effusion of the biceps tendon sheath, in some cases combined with a bilateral subdeltoid bursitis, and an intraarticular (i.a.) effusion/synovitis. To summarize our results: an i.a. effusion/synovitis, subdeltoid bursitis and biceps tendon sheath effusion were more frequent in patients with EORA, with a predominate symmetry and signs for massive inflammation. The typical ultrasonographic result in patients with PMR was a unilateral inflammation of the glenohumeral joint with predominate discrete biceps tendon sheath effusion and, in comparison with the EORA group, with signs of a low grade inflammation. We conclude that the results of our prospective study might be helpful in the differentiation of PMR and a rheumatoid factor negative subgroup of EORA at the first time of manifestation where clinical overlaps can be observed. However, ultrasonography of the glenohumeral joints might be a good and helpful instrument of differentiation in both diseases.

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART).

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Wards triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART.

Elderly onset rheumatoid arthritis and polymyalgia rheumatica : ultrasonographic study of the glenohumeral joints

Abstract The glenohumeral joints of 32 patients (aged 60 or above) were examined using ultrasonography. Thirteen patients were suffering from characteristic polymyalgia rheumatica (PMR) symptoms. In contrast 19 other patients initially had similar complaints, but were diagnosed as having elderly onset rheumatoid arthritis (EORA) upon development of typical symptoms. Ultrasound examination revealed glenohumeral joint inflammation in 61% (8 out of 13) of the patients with PMR and 63.2% (12 out of 19) of the patients with EORA. These findings suggest that a subgroup of patients with PMR and EORA suffers from shoulder joint inflammation and this synovitis/bursitis/intraarticular effusion might play an important role in the understanding of their symptoms. We conclude that overlapping forms of PMR and a predominate rheumatoid factor negative subgroup of EORA might exist and should be further characterized.