Eating disorders: a role for dipeptidyl peptidase IV in nutritional control.

Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, has been postulated to modulate nutrition control by modification or inactivation of peptide hormones operating in the enteroinsular axis. We hypothesized that changes of DPP IV activity in serum are related to the nutrition status of patients with eating disorders. Serum DPP IV activity was measured in 52 patients (28 with anorexia nervosa and 24 with bulimia nervosa) in four consecutive weekly analyses. Simultaneously, the number of CD26 (DPP IV)-positive peripheral blood lymphocytes was counted. The same analyses were carried out in 28 healthy female volunteers. In week 1 and throughout the observation period, DPP IV activity in the sera of patients with anorexia nervosa and, to a lesser extent, those with bulimia nervosa was elevated in comparison to that of healthy controls (week 1: means = 92.8 U/L for anorexia-nervosa patients and 89.3 U/L for bulimia-nervosa patients versus 74.7 U/L for healthy control subjects, P = 0.014; weeks 1-4: 91.8 U/L for anorexia-nervosa patients and 86.2 U/L for bulimia-nervosa patients versus 77.6 U/L for healthy controls, P < 0.001). We assume that the increase in DPP IV serum activity will increase the turnover of distinct peptide hormones with known effects on nutrition control and susceptibility to degradation by DPP IV. The potential impact of an increase in DPP IV activity in serum on satiety and nutrition control contributes to previously reported implications for immune function.

Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa.

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.

The genotype of human transcription factor AP-2beta is associated with platelet monoamine oxidase B activity.

Platelet monoamine oxidase B (MAO; EC 1.4.3.4.) activity is stable in the individual and is mainly genetically regulated. Levels of MAO-B in platelets have repeatedly been shown to be associated with personality traits. We have recently also demonstrated an association between the genotype of AP-2beta to a variety of personality traits as well as binge-eating disorder. In the present study we have analysed blood samples from 158 males and 64 females with regard to platelet MAO activity and genotype of transcription factor AP-2beta. In both sexes homozygotes for the long allele [CAAA](5) were significantly associated with low platelet MAO activity P<0.0001 (males) and P=0.0158 (females). This study represents a novel approach to increase the understanding about the molecular mechanisms for how the MAOB gene is regulated in blood cells and how this regulation is linked to personality traits.

Dipeptidyl peptidase IV (DPP IV, CD26) in patients with mental eating disorders.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl Peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leukocyte antigen CD26, is considered to participate in T cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 44 patients (anorexia nervosa (AN): n = 21, bulimia (B): n = 23) in four consecutive weekly analyses. The analysis of CD26-positive cells included the characterization of CD26-bright and CD26-dim positive subsets. Additionally, the expression of CD25 (IL-2 Receptor alpha chain) was evaluated to estimate the degree of T cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD26-positive cells were reduced in patients as compared to healthy controls (mean 40.2% (AN) and 41.1% (B) vs. 47.4% (HC), p < 0.01), while the DPP IV activity in serum was elevated (mean 108.4 U/l (AN) and 91.1 U/l (B) vs. 80.3 U/l (HC), p < 0.01). The potential implications of changes in DPP IV expression and serum activity on--and beyond--immune function are discussed.

Decreased platelet monoamine oxidase activity in female bulimia nervosa.

UNLABELLED: The involvement of brain serotonin systems in the pathophysiology of eating disorders has been repeatedly demonstrated in recent studies. Platelet MAO activity is an index of brain serotonin activity and lowered platelet MAO levels have been found in association with impulsive behaviors. In addition, some preliminary reports indicate that platelet MAO could be lowered in eating disorder patients. METHODS: 47 patients with DSM-IV eating disorders were studied, including 30 with bulimia nervosa and 17 with anorexia nervosa binge eating-purging type. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine and compared with a control group of 30 healthy subjects. Impulsive personality features were studied with specific rating scales. RESULTS: Platelet MAO activity was significantly lower (4.4+/-2.4 nmol/h/10(8) platelets) in the bulimic patients than in the control group (6.9+/-2.5) (p<0.001). No significant differences were found between pure bulimics and binge eating-purging anorectics. Platelet MAO was inversely and significantly correlated with scores on impulsivity scales and with borderline personality disorder characteristics. CONCLUSIONS: Platelet MAO activity is lowered in patients with bulimia, which may reflect dysfunction in impulse control mechanisms. Since platelet MAO has a predominant genetic component, there is need for studies on the association of low platelet MAO and higher risk for developing eating disorders.

Alterations in expression and in serum activity of dipeptidyl peptidase IV (DPP IV, CD26) in patients with hyporectic eating disorders.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.

Significance of vomiting for hyperamylasemia and sialadenosis in patients with eating disorders.

The authors investigated the significance of vomiting for hyperamylasemia and sialadenosis in patients with bulimia nervosa. Hyperamylasemia was found in 61% of the bulimics and in 20% of the restrictor anorectics but in no patients with binge-eating syndrome. In more than three fourths of the bulimics there was a close positive correlation between the frequency of vomiting and total serum amylase levels. Both frequency and type of vomiting seem to be relevant to the extent of salivary gland enlargement. The significance of vomiting for the etiopathology of hyperamylasemia and for the diagnosis of eating disorders will be discussed.

[Alpha-amylase isoenzymes in serum and saliva of patients with anorexia and bulimia nervosa]. / alpha-Amylase-Isoenzyme im Serum und Speichel bei Patienten mit Anorexia und Bulimia nervosa.

In the serum and saliva of 45 patients with eating disorders and in 30 normal controls, alpha-amylase activity and isoamylase levels were measured. Of the 45 patients evaluated, 12 had restrictive anorexia nervosa, 13 were bulimic anorectics and 20 had bulimia nervosa. In all these groups, the mean alpha-amylase values in serum and saliva were higher than that of the control group. The proportion of pancreatic (P)- and salivary (S)-alpha-amylase isoenzymes in serum were within the normal range for the patient group with restrictive anorexia nervosa, whereas the bulimic anorexia nervosa and bulimia nervosa patients showed significantly greater increases in S- than P-isoamylase activity. The correlation of the salivary alpha-Amylase isoenzym pattern in serum and saliva pointed to the salivary glands as origin of the elevated salivary isoamylase levels in serum. Hyperamylasemia was found in 10 (25%) of the 45 patients with eating disorders. Three of these patients showed besides an increased S-alpha-amylase activity also pathologically elevated P-alpha-amylase and lipase activity in serum; however there were no abdominal symptoms, laboratory data or ultrasonic signs of pancreatitis. In all patients with eating disorders, the mean concentration and secretion of alpha-amylase in saliva were increased. Swelling of the salivary glands was present in 14 patients. In these cases the percentage of salivary-isoamylase activity in total serum alpha-amylase activity was increased significantly, whereas the alpha-amylase secretion in the resting saliva was decreased.

Hyperamylasemia in bulimia nervosa.

To determine the value of total serum amylase levels and salivary and pancreatic isoenzyme levels as biologic indices of behavioral disturbance in bulimia nervosa, the authors monitored these levels in 40 bulimic patients participating in a placebo-controlled trial of desipramine and in 25 controls. In the patients, the total and salivary amylase levels were significantly elevated and a significant correlation existed between the frequencies of binge eating and vomiting and the level of salivary amylase. However, the ability to discriminate patients from controls on the basis of serum amylase levels was limited. In addition, a significant positive relationship between binge frequency and level of serum amylase was observed in less than one quarter of 22 patients with five or more amylase determinations. Therefore, although hyperamylasemia is associated with bulimia nervosa, we believe that serum amylase determinations have limited utility in the assessment of patients with this syndrome.

Hyperamylasemia and its relationship to binge-purge episodes: development of a clinically relevant laboratory test.

Hyperamylasemia and parotid hypertrophy are conditions found in bulimic patients. The authors studied serum amylase levels in 56 underweight anorectics, 24 weight-recovered anorectics, 23 normal-weight bulimics, and 31 volunteer women. Normal-weight bulimic patients had significantly higher admission serum amylase values (mean +/- SE = 73.4 +/- 8.0 IU/L) than controls (40.8 +/- 2.4 IU/L). Additionally, the serum amylase test distinguished between restrictor anorectics (N = 31, 44.7 +/- 4.7 IU/L) and bulimic anorectics (N = 25, 68.8 +/- 8.6 IU/L, p less than .05) with a high degree of specificity and a fair degree of sensitivity. A subsample (N = 7) of bulimics showed twofold to fourfold increases in serum amylase values after a controlled period of binge eating and vomiting, whereas normal volunteers showed no change in serum amylase values (p less than .001) after ingesting a large meal. Serum amylase values declined significantly within 6 to 15 days of admission. However, after passes off the unit, serum amylase values returned to admission values, presumably as a result of binge-vomit episodes. The authors observe that modest increases of serum amylase values appear to be a consequence of binge-vomit behavior and suggest that serial serum amylase determination may be useful in monitoring the degree of patient abstinence in therapeutic programs.

Pancreatic abnormalities in patients with eating disorders.

In patients with eating disorders, we evaluated pancreatic abnormalities using serum elastase 1 measurement by RIA and the 50 g oral glucose tolerance test (50 g OGTT). Twenty-one patients had anorexia nervosa (AN) with bulimia and vomiting (AN-B group), 30 had AN without bulimia or vomiting (AN-R group), and 25 had bulimia with normal body weight (B group). The serum elastase 1 level was determined on admission and repeated after body weight gain in 43 anorectic patients. The 50 g OGTT was performed within 2 weeks after admission. The serum elastase 1 level in the AN-B group (363 +/- 47 ng/dl, M +/- SE), and in the AN-R group (352 +/- 37) were significantly higher than that in the B group (242 +/- 18) or in the healthy female controls (191 +/- 10; n = 13). A significant decrease of serum elastase 1 was observed before and after body weight gain; however, there was no significant correlation between the serum elastase 1 level and insulin response to the 50 g OGTT. Elevation of the serum elastase 1 level in AN suggests pancreatic abnormalities other than those related to endocrinological events.

Hyperamylasemia in patients with eating disorders.

Hyperamylasemia, which has been reported in patients with the eating disorders anorexia nervosa and bulimia, generally has been thought to result from pancreatitis. To evaluate the mechanisms of hyperamylasemia, we measured amylase, lipase, and isoamylase activity in 17 consecutive patients admitted to the eating disorder unit. Six patients had elevated amylase activity, and 5 of these 6 had isolated increases in salivary isoamylase activity. Six other patients had normal serum total amylase activity but modest elevations in the salivary isoamylase fraction. No patient developed clinical evidence of pancreatitis during hospitalization. Thus, the hyperamylasemia in patients with anorexia and bulimia often is caused by increased salivary-type amylase activity. The appropriate diagnostic test for hyperamylasemia in patients with anorexia or bulimia is the simple measurement of serum lipase or pancreatic isoamylase activity. If these levels are found to be normal, further tests to exclude pancreatitis are unnecessary.

Serum salivary isoamylase levels in patients with anorexia nervosa, bulimia or bulimia nervosa.

Salivary isoamylase levels were studied in a sample of 35 women with bulimia, anorexia nervosa, or bulimia nervosa. Salivary isoamylase elevation was related to the presence of sham eating, evidenced by elevated isoamylase values in patients with bulimia nervosa or bulimia, and depressed isoamylase values in patients with anorexia nervosa. Salivary isoamylase levels may provide insight and have bearing on the functional interrelationship between appetite regulation and ingestive behavior in patients with eating disorders, as abnormalities may occur during both the cephalic as well as the oral phase of eating.