Low Fasting Serum Triglyceride Level as a Precocious Marker of Autoimmune Disorders

Silvia Iannello, MD, Antonina Cavaleri, MD, Paolina Milazzo, MD, Santi Cantarella, MD, Francesco Belfiore, MD

Disclosures

Medscape General Medicine. 2003;5(3) 

In This Article

Subjects and Methods

Since it is well known that TG levels in serum vary to a great extent for interindividual variability, the study included numerous control subjects (a total of 337 individuals). This group of control subjects was subdivided into 2 subgroups because there is the need to compare lean patients with lean control subjects and obese patients with obese control subjects, since it is well known that the values of TG and FFA are different in lean and obese subjects. The 2 groups considered were:

(a) A group of lean control subjects (body mass index [BMI] < 27 kg/m2), which includes all the 128 consecutive patients hospitalized during 2000 for minor illnesses without autoimmune diseases; and

(b) A group of obese control subjects (BMI > 27 kg/m2), which includes 209 patients with overweight or frank obesity, but without autoimmune disorder or other illnesses, received during 2000-2002 on ambulatory or day hospital for metabolic evaluation and dietary treatment.

Characteristics of these subjects are presented in Table 1 . Moreover, 11 lean and 41 obese control subjects with diabetes were studied in order to have a suitable control groups for the few patients with autoimmune disorder who were also diabetic. The parameters of the lean and obese control subjects were used for comparisons with the lean and obese patients with autoimmune disorder, respectively.

The study includes diverse groups of patients affected by several autoimmune disorders or diseases and by hyperactive immune response, as described as follows:

(a) Twenty-four female patients affected by chronic autoimmune thyroiditis subdivided into 2 subgroups, one composed of 5 lean subjects (BMI < 27 kg/m2) and the other of 19 overweight or obese subjects (BMI > 27 kg/m2). These patients presented nodularity of thyroid with euthyroid state, slight increase in serum thyroid-stimulating hormone (TSH), and enhanced concentration of antithyroglobulin antibodies, mainly antithyroid peroxidase (anti-TPO or antimicrosomal) antibodies. In some cases, histologic confirmation of diagnosis was obtained by needle biopsy. The characteristics of these subjects are shown in Table 2 .

(b) Thirty patients affected by chronic thyreopathies without autoantibodies, prevailingly patients with diffuse or multinodular nontoxic goiter or with a slight increased concentration of TSH (without thyroid failure) and absence of circulating antimicrosomal or antithyroglobulin antibodies. In several cases, histologic confirmation of diagnosis was obtained by needle biopsy. These patients were subdivided into 2 subgroups, one composed of 9 lean subjects and the other of 21 overweight or obese subjects. The characteristics of these subjects are shown in Table 3 .

(c) Twenty-six patients affected by chronic active B or C hepatitis who complained of fatigue, malaise, myalgias, hypergammaglobulinemia, and positive markers (and in some cases autoantibody positive titer), but who were free from signs of hepatic insufficiency and hypoalbuminemia, portal hypertension, jaundice with hyperbilirubinemia, and cirrhosis. These patients were subdivided into 2 subgroups, one composed of 7 lean subjects and the other of 19 overweight or obese subjects. The characteristics of these subjects are shown in Table 4 .

(d) Seven prevailingly lean patients with lupus-like syndrome (ie, affected by rheumatologic disorders; chronic fatigue; arthralgias with pain, swelling, and stiffness of the fingers; or mixed connective tissue disease with overlapping features, different from the classical rheumatoid arthritis and that did not fulfill the American Rheumatism Association criteria for systemic lupus erythematosus (SLE).[2] The characteristics of these subjects are shown in Table 5 .

(e) One patient affected by SLE that fulfilled the American Rheumatism Association criteria for SLE[2] and 10 patients affected by rheumatoid arthritis, with a chronic polyarthritis involving peripheral joint with symmetric distribution and deformities. These patients presented increased erythrocyte sedimentation rate, normocytic anemia, positivity for serum Waaler-Rose reaction, and increased rheumatoid factor. They were subdivided into 2 subgroups, one composed of 6 lean subjects and the other of 5 overweight or obese subjects. In the patient L.L., who was a dental technician exposed to ceramic silica dust, the disease was associated with lung interstitial disorder.[3] The HLA typing of this patient showed the HLA-A2-A31, HLA-B18-B51, and HLA-DR3-DR11. Some of these haplotypes are associated or correlated with susceptibility to diverse autoimmune diseases, including rheumatoid arthritis.[3] The characteristics of these subjects are shown in Table 6 .

(f) Sixty-six patients with hyperactive immune response disclosed by anamnestic allergy or atopic dermatitis/asthma. These patients were subdivided into 2 subgroups, one composed of 23 lean subjects and the other of 43 overweight or obese subjects. The characteristics of these patients are shown in Table 7 .

(g) A group of patients with various autoimmune disorders was also investigated, as detailed below. One female patient was affected by scleroderma with features of CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia). This patient presented with diffuse cutaneous thickening of proximal and distal extremities without digital ulcers, anemia, hypergammaglobulinemia, and antinuclear antibodies. She was treated with iloprost (a prostacyclin analogue).

One female patient was affected by APECED or type I polyglandular autoimmune syndrome (an autosomal recessive disorder), which had appeared in childhood and was characterized by hypoevolute soma and genitalia, adrenal hypofunction, vitiligo, genital candidiasis and dental/nail dystrophy.

Four female patients were affected by urticaria or urticarial vasculitis (induced by a variety of factors), who showed systemic involvement, prevailingly characterized by recurrent urticarial painful lesions, dyspnea and cough, angioedema of the tongue and soft palate, malaise, arthralgias, and abdominal pain.

One male patient had Reiter syndrome, characterized by fatigue, malaise, conjunctivitis, mucocutaneous lesions (mainly oral ulcers), spondyloarthropathy, and urethritis complicated by chlamydial infection.

One aged female patient was affected by Sjogren syndrome, characterized by fatigue, malaise, xerostomia, dry eyes, arthralgias, renal failure, increased rheumatoid factor titer, and elevated erythrocyte sedimentation rate. The patient was also affected by severe insulin-dependent diabetes.

Three patients were affected by ulcerative proctocolitis and 2 by Crohn's disease, in whom the syndromes were accompanied by arthritic disorder.

One adult female patient was affected by chronic multiple sclerosis with vertigo, visual blurring, diplopia, spasticity with ataxia, and severe disability.

One aged female patient was affected by severe Guillain-Barré syndrome, characterized by rapidly evolving flaccid quadriplegia and lumbosacral pain, developed 15 days after an acute febrile respiratory disease. The recovery was poor despite high-dose intravenous immunoglobulin therapy for 5 days associated with methylprednisolone treatment. She was obese, hypertensive, diabetic (treated with insulin), and also affected by chronic autoimmune thyroiditis (confirmed by needle-biopsy).

Most of the patients affected by autoimmune diseases were female subjects, as was expected. The control subjects and the patients followed their habitual diet (about 2000-2200 Kcal) with a balanced content of carbohydrates (55% to 60%), fats (15% to 25%, prevailingly olive oil) and proteins (15% to 25%). Dietary regimens were comparable between control subjects and patients. None of the patients evaluated (apart from the diabetic patient with Sjogren syndrome) showed clinical or laboratory evidences of liver or kidney insufficiency, nor had history of glucocorticoid or levothyroxine treatment, nor alcohol abuse or oral contraceptive therapy. None was treated with cytotoxics, or with drugs influencing the nutritional state, or with lipid or blood pressure lowering agents, or with other drugs capable of affecting TG or FFA levels.

Serum TG level was measured in the morning, after 12 hours of fasting. In 18 lean and 11 obese control subjects as well as in 22 lean and 18 obese patients without autoimmune disease, fasting serum FFA level was also measured in the morning, after 12 hours of fasting (Tables 1-7). Since it is known that TG level serum vary to a great extent for intraindividual variability, in many patients TG assays were repeated after 2-3 months.

The assay method used for serum TG quantitative determination was the standard enzymatic-colorimetric method, in that TGs were hydrolyzed to glycerol and FFA through the action of lipase, and the reaction was coupled with 3 enzymatic phases catalyzed by glycerol kinase, glycerol oxidase, and peroxidase. The assay included a reagent blank, and the measurement of absorbance was made at Hg 520 nm, at 37° C. The sample material was processed without storage

The method "NEFA C" (by Wako Chemicals GmbH, Neuss, D) was used for serum FFA determination. This is a colorimetric-enzymatic analysis kit by the use of acyl-CoA synthetase, acyl-CoA oxidase, and peroxidase. The assay included a reagent blank, and the measurement of absorbance was made at Hg 550 nm, at 37° C. Serum was separated immediately, and the samples (keep frozen) were processed as soon as possible.

Data were statistically analyzed by means of the student's t test for unpaired data. Considering that data might not show a normal distribution, statistical tests were also calculated after LOG-transformation of data. A value of P < .05 was considered as statistically significant. Data were expressed as mean ± standard error of the mean.

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