Vol 46, No 3 (2018)


Adipocytokine profile and effectiveness of the weight loss in patients with metabolically healthy obesity

Romantsova T.I., Ostrovskaya E.V., Gerasimov A.N., Novoselova T.E., Novikova O.V., Valiulina D.S.


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.
Almanac of Clinical Medicine. 2018;46(3):212-221
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Assessment of muscle and fat mass in type 2 diabetes mellitus patients by dual-energy X-ray absorptiometry

Misnikova I.V., Kovaleva Y.A., Klimina N.A., Polyakova E.Y.


Background: Obesity is an important health problem, as its prevalence has reached an epidemic level and continues to increase steadily resulting in higher risk of cardiovascular diseases and metabolic disorders. Currently, new methods and criteria are being developed to assess fat and muscle mass, as well as criteria for diagnosing obesity and sarcopenia.

Aim: To assess the quantitative composition of muscle and adipose tissue in type 2 diabetes mellitus patients based on the dual-energy X-ray absorptiometry for the diagnosis of obesity and sarcopenia.

Materials and methods: We examined 42 type 2 diabetic in-patients admitted to the Department of Therapeutic Endocrinology. Dual-energy X-ray absorptiometry was performed in all patients with subsequent assessment of the composition of muscle and fat tissue.

Results: If assessed by the body mass index, all patients had an excess body weight: median, 32.25 [29.75; 35.70]; in men, 31.3 [28.19; 34.63], in women, 32.29 [30.26; 36.54]. 26.2% of the patients (11/42) were overweight, but not obese. Female patients had more severe obesity than male (in total, 33.3% (10/30) of women had 2nd and 3rd degree of obesity, while men 16.7% (2/12)). The assessment by the fat mass index (FMI) showed that 2.4% (1/42) of the patients were normal-weight. Median FMI was 11.91 [10.40; 13.78] (in men, 8.86 [7.46; 12.1], in women, 12.35 [11.55; 15.47]). Overweight was found in 52.4% (22/42) of the patients; in total, 2nd and 3rd degree of obesity was observed in 25% (3/12) of the men and only in 6.6% (2/30) of the women. Median Appendicular Lean Mass Index (ALMI) in the total group was 7.99 [7.32; 9.05], being expectedly higher than in women: 9.19 [8.42; 9.45] and 7.58 [7.24; 8.49], respectively. Median T-score ALMI was 2.32 [1.73; 3.08], Z-score ALMI 2.15 [1.47; 3.54]. In general, there was a decrease in the appendicular muscle mass with age. There was an inverse correlation between the age and T-score ALMI (r = -0.319, р = 0.020), as well as between the age and Z-score ALMI (r = -0.634, p = 0.000). According to the results of T-score ALMI and Z-score ALMI, there were no patients with sarcopenia. However, the calculation of the T- and Z-criteria, corrected for fat mass, has led to a significant decrease of the medians of these parameters and allowed to identify a group of patients meeting the criteria of sarcopenia (97.6%, 41/42).

Conclusion: Based on ALMI, T-ALMI, and Z-ALMI, there were no patients with sarcopenia. After these criteria were corrected for fat mass, the number of such patients increased to 97.6% (41/42) and 85.7% (36/42), respectively. The potential use of the adjusted T-ALMI (FMI) and Z-ALMI (FMI) as criteria for sarcopenia and muscle mass reduction compared to the age-related normal values, as well as the classification of obesity by FMI should be studied in large epidemiological studies in different populations.

Almanac of Clinical Medicine. 2018;46(3):222-232
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Quality of life in patients with acromegaly based on the AcroQoL questionnaire

Dreval A.V., Pokramovich Y.G., Ilovayskaya I.A., Gilyazova A.D.


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.

Almanac of Clinical Medicine. 2018;46(3):233-239
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Nutritional structure and associated factors in type 2 diabetic patients

Starostina E.G.


Background: The actual structure of nutrition and associated factors in the Russian type 2 diabetic patients have not been systematically evaluated.

Aim: To assess type 2 patients' perceptions of the diet recommendations given by their doctors, how do they deflect in the actual nutrition structure depending on demographic, medical and social factors.

Materials and methods: 297  out- and in-patients with type 2 diabetes mellitus were consecutively recruited into this cross-sectional study (mean age ± standart deviation, 61.0 ± 10.1 years, with duration of diabetes from 1 to 35  years). 21% of the patients were treated with the diet only, 53%, with oral hypoglycemic agents (OHA), 26%, with insulin or insulin + OHA. In addition to their comprehensive clinical and laboratory assessment, the patients filled in the following questionnaires: 1) to assess their obstacles and barriers with diabetes treatment; 2) to assess the diet recommendations and factors that might influence their choice of foods; 3) to assess the nutritional structure. The data is given as mean ± standard deviation.

Results: Diet was chosen as the most challenging aspect of diabetes treatment by 53% of patients, whereas insulin therapy was found to be most challenging by 12% of them, blood glucose self-monitoring by 10% and OHA treatment by 4%. The patient's diet is influenced most of all by recommendations given by their doctors (66%), with tastes and nutritional habits of the patients ranking second (48%), their well-being ranking 3rd (43%), and food costs ranking 4th (40%) with a small difference with the 3rd. The analysis of patients' understanding of the diet components and evaluation of their actual nutritional structure showed their non-concordance with current evidenced-based approaches to medical nutrition. The patient's nutrition is dominated by exclusion of fast-absorbable carbohydrates and total carbohydrate restriction, as well as by an excessive intake of vegetable oils and unfounded restraint from fried and spicy foods. Total daily caloric intake was reduced only by 37% of the patients. The patients undervalue the necessity of increased fiber intake. The group of very highly consumed foods (≥ 75% of the patients) included vegetable oils (84.0%), soft drinks (82.9%) and dairy products (78.9%). The group of highly consumed foods (50–74% of the patients) included soups (72.6%), meat, fish and poultry (70.5%), grains and cereals (total, 69.9%), vegetables, greenery and beans (68.9%), potatoes (58.9%), and fruits and berries (52.2%). The group of moderately consumed foods (25–49% of the patients) included bread and bakery products (44.5%) and eggs (27.9%), whereas the least consumed (< 25% of the patients) were “diabetic foods” (19.4%), pasta (17.1%), fat sauces and cream (21.4%), butter and lard (15.7%), nuts (14.5%), oils preserves and smoked foods (5.7%), and sweets (4.7%). The most unhealthy diet was typical for male patients, those of relatively young age, with short diabetes duration, with obesity and with lower educational level.

Conclusion: Diet is seen by type 2 diabetic patients as the most burdening treatment element. Nutritional structure of type 2 diabetic patients, including those who have participated in the patient education programs, in many ways is not consistent with the current principles of rational medical nutrition and is determined first of all by recommendations of their doctors that are not always optimal. The use of the questionnaire to assess nutritional structure and regularity allows to evaluate the diet style of a given patient and, based on it, to elaborate corrective measures and individual dietetic recommendations.

Almanac of Clinical Medicine. 2018;46(3):240-253
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Evaluation of an association of the rs1801133 MTHFR gene polymorphism with folic acid deficiency in obese patients

Pogozheva A.V., Sorokina E.Y., Aristarkhova T.V.


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.

Almanac of Clinical Medicine. 2018;46(3):254-257
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Polymorphism of the adiponutrin gene (PNPLA3) in the indigenous inhabitants of the Republic of Sakha (Yakutia) with type 2 diabetes mellitus

Kurtanov K.A., Sydykova L.A., Pavlova N.I., Filippova N.P., Dodokhov V.V., Apsolikhova G.A., Solov'eva N.A., D'yakonova A.T., Neustroeva L.M., Varlamova M.A., Borisova N.V.


Rationale: The association of rs738409 I148M polymorphism with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease has been confirmed for several ethnic and territorial groups. Up to now, no such studies have been performed in the populations of Yakutia.

Aim: To study allele frequency distribution and to identify associations of the PNPLA3 gene polymorphism (rs738409 C>G) with T2DM in the Yakuts.

Materials and methods: DNA samples from 106 T2DM patients were used in the study; the control group included samples from 72 healthy volunteers. All study participants were ethnic Yakuts and were living in the territory of the Republic of Sakha (Yakutia), Russian Federation. rs738409 polymorphism of the PNPLA3 gene was studied by polymerase chain reaction and by restriction fragment length polymorphism.

Results: There were no significant difference in the distribution of the allele frequencies and genotypes of the polymorphous variant of the PNPLA3 gene (rs738409) between the T2DM patients and the healthy control. Both groups showed prevailing allele G (р = 0.01) and homozygous genotype GG (96%).

Conclusion: High frequency of the allele G (74.1%) with predominance of GG genotype (58.5%) was found in type 2 diabetic patients.

Almanac of Clinical Medicine. 2018;46(3):258-263
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Analytical aspects of gastrin measurement in neuroendocrine tumors

Lyubimova N.V., Churikova T.K., Timofeev Y.S., Kharitidy T.Y., Kushlinskii N.E.


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.

Almanac of Clinical Medicine. 2018;46(3):264-269
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Relapse of the pituitary adenoma with a change of its hormonal activity in a female patient with multiple endocrine neoplasia syndrome type 1

Rozhinskaya L.Y., Khandaeva P.M., Lutsenko A.S., Lapshina A.M., Grigor'ev A.Y., Arapova S.D., Belaya Z.E., Mel'nichenko G.A.


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.

Almanac of Clinical Medicine. 2018;46(3):270-275
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Late initiation of treatment for congenital adrenal cortical hyperplasia and gender change in an adult patient

Lutsenko A.S., Rozhinskaya L.Y., Kareva M.A., Belaya Z.E., Maganeva I.S.


Despite the implementation of screening programs for early diagnosis of congenital disorders, both in the Russian Federation, as well as worldwide, there are still cases of late diagnosis of congenital adrenal cortical hyperplasia (CAH), where after long-standing virilization clinicians often face the need of gender assignment, considering not only the medical indications, but also the patient's self-identification. In this article, we present a rare clinical case of patient with hypertonic type of CAH diagnosed in adulthood. At birth, the patient had ambiguous genitalia; the diagnosis of CAH was made, and the patient was assigned to female gender. However, due to some social factors, the patient was not followed up and received no treatment. The lack of treatment resulted in progression of the virilization, disturbance of the patient's gender self-identification (the female patient considered himself male), final short stature and arterial hypertension. The patient attended endocrinology clinic for the first time at the age of 19. The diagnosis of hypertensive type of CAH was based on clinical manifestation of the virile syndrome combined with hyporeninemic arterial hypertension, as well as the results of multisteroid blood analysis with identification of steroid cortisol precursors and the results of the genetic testing for CYP11B1 gene mutation. Administration of glucocorticoid replacement therapy after the late diagnosis of hypertonic type of CAH did not resolve all of the patient's concerns. The disorder of the gender self-identification in a female patient resulted in the change of the passport gender to the male one, with surgical correction in accordance to the chosen gender and replacement androgen therapy. Persistent arterial hypertension required additional anti-hypertensive treatment. This clinical case highlights that psychosocial, ethnic factors and religious factors should be taken into consideration, as well as the multidisciplinary involvement of endocrinologists, psychiatrists, andrologists and gynecologists is necessary for the management of such patients.

Almanac of Clinical Medicine. 2018;46(3):276-281
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Severe preeclampsia and gene mutation HNF4A (MODY1): а case report

Gur'eva V.M., Yablokova M.E., Burumkulova F.F., Zubkova N.A., Tyul'pakov A.N.


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 1st 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.

Almanac of Clinical Medicine. 2018;46(3):282-288
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Diffusion-weighted magnetic resonance imaging in the diagnosis of pancreatic insulinoma: a clinical case

Yukina M.Y., Nuralieva N.F., Troshina E.A., Vorontsov A.V., Vladimirova V.P., Soldatova T.V., Kuznetsov N.S., Latkina N.V., Izmaylova N.S.


The topical diagnosis of insulinoma continues to be an actual problem of modern medicine due to low detection rate of the tumor (about 75%) and inconsistent data on its localization when using various methods of visualization (more than in 50% of cases), as well as the lack of a single diagnostic algorithm. In the clinical practice, many different imaging assessments are conducted, including those with the administration of contrast agents and associated with radiation load, as well as invasive studies, associated with risk of various complications, high costs and duration of the examination. Thus, the search for highly sensitive and safe methods of topical diagnosis of the insulin-producing pancreatic tumor seems relevant. In the presented clinical case, the diagnosis of insulinoma is verified by diffusion-weighted magnetic resonance imaging (DW-MRI). It is an accurate and non-invasive method that does not involve exposure to ionizing radiation and does not require any administration of contrast agents. This technology, based on microstructural pathological changes, allows to identify small tumors and to make a differential diagnosis of benign and malignant neoplasms. However, at present the experience of DW-MRI use for the diagnosis of an insulin-producing neuroendocrine tumor is limited. Evaluation of its effectiveness in a large patient cohort would be necessary to assess the prospects for its introduction into clinical practice.

Almanac of Clinical Medicine. 2018;46(3):289-295
pages 289-295 views

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