Vol 46, No 3 (2018)

Background: Obesity is a  major risk factor for diabetes mellitus and cardiovascular diseases. Nevertheless, some obese patients have normal parameters of blood arterial pressure, carbohydrate, and lipid metabolism ("metabolically healthy obesity", MHO).

Aim: To study adipocytokine levels and to assess the effect of weight loss on cardiometabolic risk factors in patients with metabolically healthy obesity.

Materials and methods: We conducted a comparative analysis of the main metabolic parameters and adipocytokine levels in 44  female patients with MHO (according to the IDF criteria of the metabolic syndrome, 2005: obese patients with no more than one additional cardiometabolic risk factor) and in 33 women with metabolically unhealthy obesity (MUHO). We also assessed changes of these indices in the patients who reduced their body weight by ≥ 5% at 6 months.

Results: At baseline, body mass index (BMI) and the levels of basal insulin, C-reactive protein (CRP), tumor necrosis factor alfa (TNF-α), adiponectin and retinol-binding protein-4 (RBP-4) in the MHO and MUHO groups were comparable. A  significant difference between these groups was observed for the HOMA index (3.0 and 4.4, respectively; p < 0.05), alanine aminotransferase (ALT) (23.49 and 37.39 U/l; p = 0.001), interleukin-6 (0.76 and 1.5 pg/ml; p < 0.05), chemerin (322.4 and 369.2 ng/ml; p < 0.05), and the duration of obesity (18 and 22.6 years; p < 0.05). At 6 months, in those MHO patients, who reduced body weight by ≥ 5% of the initial (66%), there was a significant increase of adiponectin by 4.54 ± 0.83  µg/ml (p < 0.05) and a reduction of waist circumference (WC) by -8.6 ± 1 cm (p > 0.05), НОМА index by -1.13 ± 0.42 (p < 0.05), CRP by -1.7 ± 0.4 mg/l (p < 0.05), RBP-4 by 2.9 ± 1.0  ng/ml (p < 0.05), and сhemerin by -46.6 ± 17.0 ng/ml (p < 0.05). In the MHO group, we found a positive correlation between changes in the adiponectin levels and the degree of reduction in body weight (p < 0.01), changes in RBP-4 and WC (p < 0.05), and changes in the levels of interleukin-6 and high-density lipoprotein (p < 0.05).

Conclusion: Compared to the complicated obesity, MHO is associated with a  shorter disease history, and lower levels of the HOMA index, interleukin-6, and chemerin levels. The body mass decrease in MHO is associated with a decrease in the proinflammatory adipocytokine levels and of the HOMA index that determines the need for treatment of obesity, regardless of its phenotype.

Rationale: International experts emphasize that treatment strategies for patients with acromegaly should be aimed not only at normalization of biochemical parameters, but also at the achievement of better health-related quality of life (HRQL). However, the published data on the quality of life in patients with acromegaly is scarce.

Aim: To assess HRQL in patients with acromegaly with a disease-specific validated questionnaire (AcroQoL) and to identify potential factors that may influence it.

Materials and methods: One hundred fourteen (114) patients aged from 18 to 83 years (median age, 56 years, interquartile range, 46 to 63). All patients were divided into the age groups, as well as into the groups depending on the treatment they had received and on the control of acromegaly.

Results: In the whole group of the patients (n = 114), the levels of insulin-like growth factor I significantly (p = 0.026) correlated with the domain “personal relationships”. When the patients with newly diagnosed acromegaly (n = 34) were compared to those who had been previously treated (n = 80), there were significant differences for “HRQL global” (p = 0.015) and “physical dimension” (p = 0.009). HRQL of the patients with controlled (n = 37) acromegaly did not differ from HRQL of those with uncontrolled disease (n = 43) (p > 0.05). Surgery and radiation treatment had no impact on the patients' HRQL (p > 0.05), whereas the treatment with somatostatin analogues improved only its physical dimension (p = 0.034).

Conclusion: Treatment interventions do not improve quality of life in patients with acromegaly. This can be explained as follows: modern treatment approaches (surgery, radiation) do not lead to immediate noticeable results, whereas treatment-related complications can manifest themselves clearly. As a result, the patient may get an impression that his/ hers quality of life has not improved, despite the fact that the expediency of the specific treatment administered has been absolutely proven.

Background: The use of molecular genetic technologies has made it possible to show that the genetic factor plays a significant role in the development of obesity. In addition, in obese people the supply with vitamins, in particular with folic acid, is largely controlled genetically.

Aim: To study an association of the rs1801133 polymorphism of the MTHFR gene with folic acid deficiency in the residents of the Moscow region depending on their body mass index.

Materials and methods: rs1801133 polymorphisms were identified in 326 subjects (74 male and 252 female) aged from 20 to 65 years, living in the Moscow region. The DNA was isolated from blood by the sorption on silica gel-coated magnetic particles. DNA was isolated with the use of the epMotion 5075 automatic station (Eppendorf, Germany). To identify the polymorphism, a polymerase chain reaction was used, followed by cleavage of the Hinf1 restriction endonuclease products, with analysis of these products by gel electrophoresis. The equipment CFX96 Real Time System (BIO-RAD, USA) was used. Folic acid was measured by ID-Vit^® Folic Acid test system (R-Biopharm, Germany).

Results: According to the results of folic acid measurements in blood, a deficiency of this vitamin was found in 24.2% of the studied residents of the Moscow region. Analysis of the genotyping results did not show any association of the rs1801133 MTHFR gene polymorphism with the serum levels of folic acid. However, in the subjects with overweight and obesity, there was a statistically significant association between the T allele of the rs1801133 of the MTHFR gene polymorphism and a low level of folic acid (odds ratio 2.5, 95% confidence interval 1.09–5.74, p = 0.03).

Conclusion: The rs1801133 polymorphism of the MTHFR gene significantly contributes to the development of folic acid deficiency in overweight and obese individuals.

Rationale: Biochemical diagnostics of neuroendocrine tumors (NETs) is based on the analysis of universal and specific markers, according to the tumor type and clinical manifestations of the disease. Measurement of gastrin levels in the serum of NETs patients is important in the diagnosis of the functioning pancreatic, gastric and duodenal NETs.

Aim: To perform a comparative analysis of the results of gastrin measurement as a biochemical marker of NETs using different test-systems.

Materials and methods: Serum gastrin was measured in the serum of 30 NET patients and 18 normal controls by immunochemiluminescent (Immulite 2000 Gastrin, “Siemens”) and ELISA (Gastrin-17 ELISA, “Biohit”) assays.

Results: The analysis of the results of gastrin measurement by immunochemiluminescent and ELISA methods showed significant variability of its levels, reaching 2016 and 1988 pmol/l, respectively. Comparable analytical sensitivity of the two test systems was confirmed by similar increases (over 30- to 40-fold) of the median levels of the hormone in the serum of patients with gastric NETs, compared to healthy controls. The analysis of diagnostic efficacy accounting for their respective cut-offs demonstrated higher sensitivity (95.4%) of the Immulite 2000 Gastrin test-system, which measures total gastrin, than that of the ELISA method (80.0%), specific to gastrin-17.

Conclusion: The analysis shows high efficacy of immonochemiluminescent method of measurement of total gastrin as a biochemical marker of NETs.

Multiple endocrine neoplasia syndrome type 1 (MEN1, Wermer's syndrome) is a group of heterogeneous inherited diseases, with its pathogenesis related to hyperplasia or neoplasms of several endocrine glands. This syndrome is characterized by autosomal dominant mode of inheritance, high penetrance and similar prevalence among males and females. Prevalence of MEN1 is estimated to be 1:100,000 of the population. An interesting feature of the presented clinical case is a relapse and transformation of pituitary tumor from a prolactin-secreting into the mixed one, with distinct compartments of ACTH- and prolactin-secreting, in a female patient with a family MEN1 syndrome, with involvement of the pancreas, parathyroid and pituitary glands. Her brother had a synchronous manifestation of the same types of tumors, except corticotropinoma. The presented clinical case highlights the necessity of a comprehensive and life-long follow-up of MEN1 patients for a timely detection of neoplasms and appropriate treatment.

Preeclampsia is an obstetric complication that is becoming a major cause of maternal and perinatal morbidity and mortality. The rate of preeclampsia in diabetes mellitus is 3 to 5-fold higher than in the population. Heparin is used for prevention of preeclampsia due to its experimentally shown important role in the trophoblast invasion and differentiation, as well as its influence on the production of proangiogenic factors. The paper gives a clinical case report that broadens our understanding on the preeclampsia pathophysiology and possibilities of its prevention. A 30-year old patient with no past history of serious physical illnesses had her two previous pregnancies with severe preeclampsia of early onset (arterial hypertension, massive proteinuria, thrombocytopenia, renal and hepatic insufficiency). Both babies were born extremely preterm (24 to 25 weeks of gestation) and died. Her hereditary background included type 2 diabetes in her maternal grandmother. At early terms of both pregnancies she had her fasting venous plasma glucose of 3.8 to 4.6 mmol/L (normal, < 5.1 mmol/L). Oral glucose tolerance test which had to be performed at 24 to 28 weeks of gestation, according to the protocol, was not performed. While planning for the third pregnancy, her body mass index was 29 kg/m², with normal values of the blood pressure and renal function, no proteinuria and no evidence of the anti-phospholipid syndrome. In the 1^st trimester, she had her fasting venous plasma glucose of 4.4 mmol/L. From the early term of her pregnancy, the patient was administered low molecular weight heparin; from the week 15, she was started with antihypertensive medications due to gestational arterial hypertension. Manifest diabetes was diagnosed at week 24 to 25 based on the results of the oral glucose tolerance test (4.96–10.42–11.46 mmol/L). With diet treatment, she had her postprandial glycaemia of up to 8.9 mmol/L, causing the initiation of basal-bolus insulin therapy from week 25  of gestation (0.4 U/kg), with achievement of good glucose control. At week 16, she had her sFlt1/PlGF level of 44 (high risk of preeclampsia). Molecular genetic assessment identified a HNF4A gene mutation, associated with MODY1. From week 34, she had moderate preeclampsia and fetal growth delay. An elective cesarean section was performed at week 38, with a healthy boy of 2300 g and 48 cm. After delivery, her diabetes was controlled by diet. The baby had an identical mutation. Thus, one cannot exclude a genetically determined link between complications of previous pregnancies and manifest diabetes diagnosed during the current pregnancy. Diagnosis of MODY1 in a pregnant patient would require the earliest initiation insulin treatment to prevent fetal macrosomia and neonatal hypoglycemia, as well as to prevent preeclampsia. The reason of successful outcome of this pregnancy could be related to heparin administration at the early terms of pregnancy that allowed for appropriate implantation and placenta formation, as well as for timely good glucose control.