The present case study is the first description of an association between CD and metabolic syndrome, with reversion following the prescription of a GFD, together with complete resolution of ferropenic anemia and elevated transaminase levels. The clinical characteristics of the patient (altered lipid and liver function parameters) were consistent with metabolic syndrome, a condition which following its initial description by Reaven in 1988[6
] has received numerous definitions in seeking a central reference parameter (e.g. insulin resistance or abdominal obesity) capable of confirming its existence as a single clinical entity. However, the many definitions and lack of uniformity have led even Reaven to deny the existence of metabolic syndrome as a distinct clinical entity, thereby stressing the importance of treating rather than of defining the condition. The present case shows how adult CD can present as metabolic syndrome according to any of its definitions[7
], despite the fact that CD is presently not included in the differential diagnosis of hyperlipidemia and has not been given importance in the context of metabolic syndrome.
In contrast, the association of CD with endocrine and metabolic alterations has been known for a long time. Type 1 diabetes mellitus classically has been associated with CD, and the possible corrective role of GFD upon the metabolic alterations of the disease has been extensively studied. When both disorders coexist, the introduction of GFD results in fewer hypoglycemic episodes, with no changes in glycosylated haemoglobin values[8
]. A study in type 1 diabetic children diagnosed with CD demonstrated a recovery of normal BMI after following a GFD, together with improvement in glycosylated haemoglobin values as compared with pre-GFD, and with no expected deterioration in glycemic control during puberty[9
]. Furthermore, the beneficial impact of GFD on BMI has been recently demonstrated, since underweight celiac patients gained weight and overweight or obese patients lost weight 2.8 years after starting on a GFD[10
]. A similar effect of GFD upon lipid metabolism therefore should be considered in celiac patients, along with correction of the alterations associated with exposure to gluten in the diet. In fact, diagnosis of CD and its treatment with a GFD has resulted in improvement in the lipoprotein profile, including an increase in HDL and a decrease in the LDL/HDL ratio[11
]. However, contrary results have been also published[12
], although these may be explicable since following a GFD may require a restriction in carbohydrates intake, often leading to increased fat intake[13
]. Depending on the quality of fat this may result in either an increase or decrease of total cholesterol and triglycerides.
Although our case represents a single observation, and larger studies are needed, it does lead us to reflect upon the importance of CD screening. IgA anti-tissue transglutaminase antibodies are considered to be the most useful markers for CD screening, but their diagnostic value in adult patients is limited[14
]. In the case of children it should be noted that the anti-transglutaminase antibody titers correlate with the degree of the duodenal histological lesion, and are very low in children in whom only lymphocytic enteritis is observed. On the other hand, low antibody titres are the most common finding in the adult forms. Thus, it is estimated that their sensitivity which exceeds 90% in the case of childhood CD[15
] is reduced to a mere 15%-30% in screening for CD in adults[16
], for whom a positivity threshold of 2 U/mL is recommended[17
]. This makes it even more necessary to obtain duodenal biopsies and conduct immunohistochemical studies to establish the diagnosis[18
]. This is confirmed by the presence of a risk HLA haplotype and particularly by a good clinical and biochemical response to GFD. A strategy based on the genetic evaluation of suspect cases, followed by obtaining duodenal biopsies in individuals confirmed to have risk HLA haplotypes, makes it possible to diagnose three times as many affected cases as when the evaluation is limited to serological testing only[15
]. Different experts in CD agree that because of the difficulty of establishing a diagnosis through other tests, the response to strict GFD for at least 6 mo represents the most definitive diagnostic criterion, particularly when there is an improvement or normalization of the previously altered laboratory test parameters without any associated concomitant medication[19
]. Experts do not recommend the repetition of duodenal biopsies following gluten reintroduction in the case of adults with sufficient diagnostic criteria and a good response to the prescribed treatment[14
Our patient was overweight, with an increased waist circumference, mixed hyperlipidemia, altered basal blood glucose and elevated transaminase concentrations. The traditional image of celiac patients, characterized by thin and diarrheic individuals, contrasts with the true situation, since up to 30% of all patients are overweight and 50% suffer constipation[4
], as in our case.
The way in which the malabsorption alterations or immune disorders associated to CD can bring about these metabolic changes is not clear. However, the association between transaminase elevation and CD is well known, and is seen in 60% of all patients with classical clinical manifestations of the disease, as well as in 40% of atypical presentations[4
]. In fact, 10% of all blood transaminase studies result in the diagnosis of CD[14
]. In general, as in obesity, hypertransaminasemia in CD is due to non-alcoholic steatohepatitis and reverts following the introduction of GFD. If no reversion is observed, then the presence of primary biliary cirrhosis, sclerotizing cholangitis or autoimmune hepatitis must be excluded, as these are autoimmune conditions that are also associated to CD.
The changes in lipid profile observed in our patient following the introduction of GFD could also be explained by the dietary modifications imposed by GFD itself, a generally healthier and without precooked foods, rather than by the particular absence of gluten. However, the dietary questionnaire revealed no significant changes in diet in this sense. Likewise, the discrete changes in body weight and waist circumference do not, in isolation, seem to explain these important reductions in lipid levels, which in clinical practice are only achieved with drugs. Our patient did not actually reduce her carbohydrate intake, as is normally the case in celiac patients, where increased fat intake is usually observed when gluten-containing flour and cereals are replaced with others lacking gluten. This factor can therefore be taken to have no crucial impact upon correction of the altered basal blood glucose levels and hypertriglyceridemia. Thus, the effects of the absence of gluten upon lipid metabolism remain as the only plausible explanation and, although it must be remembered that ours is an isolated case, the findings do invite us to investigate the metabolic changes induced by gluten in coeliac patients.