Vol 44, No 4 (2016)

Background: Prediction of clinical benefits of somatostatin analogues in patients with neuroendocrine tumors (NET) is very important prior to their administration. Data on immunohistochemical assessment of the expression of somatostatin receptors (SSR) of various types, obtained from large samples of NET with various localization, functional activity and degree of malignancy, are scarce; therefore, the study was aimed at assessment of the latter.

Materials and methods: We performed an immunohistochemical study with antibodies to SSR1, 2A, 3 and 5  types on tissue samples obtained during diagnostic and intra-operative biopsies from 399 NETs: 168 from pancreas, 120 from gastrointestinal tract (stomach, 48, from small intestine, 39, 14 of which being from duodenum; appendix, 6, colon and the rectum, 15 and 12, respectively), 84 from lung, 6 from thymus/mediastinum, and 21 from NET metastases of unknown primary localization.

Results: Very high levels expression of receptors SSR2A preferentially binding to somatostatin analogues, which are currently used in clinical practice, were detected in the small intestine NETs (22/25, 88%), appendix (5/6, 83.3%), colon (10/15, 66.7%), thymus (4/6, 66.7%), atypical carcinoids of the lung (10/15, 66.7%), stomach (27/41, 65.8%) and pancreas (105/165, 63.6%). The lowest expression was found in rectal NETs (5/12, 41.7%) and small and large cell neuroendocrine lung carcinomas (20, 11.1%). Among functioning NETs, the highest level of SSR2A was found in gastrinomas (18/19, 94.7%), glucagonomas (15/16, 93.8%), small intestine carcinoids (31/35, 88.6%), and somatostatinomas (2/3, 66.7%). The lowest expression was detected in ACTH secreting tumors with Cushing's syndrome (11/12, 50%), and in insulinomas (34/69, 49.3%). SSR2A expression in functionally inactive pancreatic NETs was significantly higher than in insulinomas (57/82, 34/69 vs 69.5 and 49.3%, respectively). SSR2A expression was associated with the degree of malignancy and is higher in pancreatic NET Grade 2A (Ki67 to 10%), Grade 2B (Ki67 10–19%) and in neuroendocrine carcinomas Grade  3, compared to Grade  1 (16/50 (32%), 37/61 (60.6%), 8/12 (66.7%) and 20/24 (83.3%), respectively). Overexpression of SSR5, which is the second clinically significant receptor, was observed in NETs of the duodenum (7/10, 70%) and appendix (2/5, 60%), and among functionally active NETs in glucagonomas and gastrinomas (12/15, 80%). SSR3 are less common, than SSR2A and 5, and are found most often in the gastric NETs (6/11, 54.5%), insulinomas (16/37, 43.2%), neuroendocrine carcinomas of pancreas Grade  3 (4/9, 44.7%), and typical lung carcinoids (7/16, 41.2%). SSR1 in all tumors are rare, the maximum level of expression was observed in small intestine carcinoids (9/21, 42.9%).

Conclusion: Depending on their localization and grade  of malignancy, neuroendocrine tumors differ in expression of various SSR types. Therefore, determination of the receptor profile of each tumor is necessary before administration of somatostatin analogues.

Background: New diagnostic criteria for gestational diabetes mellitus (GDM) are being currently implemented into clinical practice. GDM prevalence and pregnancy outcomes in women with GDM diagnosed according to the new criteria have not been studied in Russia.

Aim: To evaluate prevalence of GDM and pregnancy outcomes in women with GDM based on the Russian consensus criteria 2012 ("Gestational diabetes mellitus: diagnosis, treatment and postpartum follow-up") in the population of the Moscow Region.

Materials and methods: The study included 176 pregnant women living in the Moscow Region. We retrospectively analyzed 100  pregnant women (mean age±SD  – 28.3±6 years) who delivered before 2013 with collection of data on blood glucose and gestational age of its measurement, body mass index (BMI) at conception and pregnancy outcomes. The prospective part of the study conducted from January to July  2015 included screening of 820  pregnant women helped to identify 76 cases of GDM (mean age±SD – 30.4±5.5 years); their follow-up included monitoring of glucose levels, gestational term, and pregnancy outcomes.

Results: In the retrospective part of the study, 19  women (19%) were identified with their fasting glucose levels≥5.1  mmol/L (5.39±0.29  mmol/L) at 14.4±9.3  weeks of gestation, that corresponds to diagnosis of GDM with 2012 criteria. The comparison of pregnant women with and without fasting hyperglycemia showed no difference in age and pre-pregnancy BMI values. Women with fasting hyperglycemia had high total rates of adverse pregnancy outcomes than those without (52.6%  vs 24.6%, respectively, p<0.017), as well as higher rates of fetal asphyxia during delivery and clavicle fractures (15.8%  vs 3.7%, p=0.04 and 10.5% vs 0%, p=0.03). In the prospective part of the study, 820  pregnant women were screened for GDM, and it was found in 76 (9.2%) of them. Among those, in 50 (65.8%) the diagnosis of GDM was based on fasting glucose in venous plasma (5.5±0.3 mmol/L) at 11.3±6.1 weeks of gestation. Pregnant patients with fasting hyperglycemia in the retrospective and prospective parts of the study did not differ in their age, pre-pregnancy BMI, fasting glucose levels and terms of assessment; however, in the prospective study, the rate of fasting hyperglycemia was lower than in the retrospective (6% vs 19%). The second phase of the screening performed at 20 to 30 weeks of gestation helped to identify 26  women (34.2%) with GDM: in 15 of them (19.7%) the diagnosis was based on repeatedly high fasting glucose (5.5±0.3 mmol/L) and in 11 (14.5%), on the results of the oral glucose tolerance test. To all pregnant women with GDM, diet and blood glucose self-monitoring were recommended. Pregnancy outcomes were assessed in 64 GDM patients, with their comparison in compliant patients (n=30) vs non-compliant (n=34). Patients with poor compliance had higher rates of preterm delivery (11.4% vs 0%, р=0.05), macrosomia (32.3%  vs 6.6%, р=0.01) and other adverse outcomes (76.5% vs 50%, р=0.03) than those with good compliance.

Conclusion: The prevalence of GDM in a district of the Moscow Region in the prospective study was 9.2%. The retrospective analysis showed an overestimated rate of fasting hyperglycemia (19%). In the majority of GDM patients, the diagnosis was based on an increased fasting glucose level in venous plasma (85.5%). Treatment of GDM patients helps to reduce adverse pregnancy outcomes.

Background: А  specific questionnaire is necessary to perform quantitative assessment of compliance to medical nutrition therapy in patients with type 2 diabetes mellitus (DM).

Aim: Тo develop a questionnaire to assess how type 2 diabetic patients adhere with the principles of medical nutrition therapy and to identify factors associated with good dietary compliance.

Materials and methods: We proposed a questionnaire "Dietary adherence test" (DAT) and validated it in 300 inand out-patients with type 2 DM. DAT was validated against the diabetes-related behavior score, diabetes-related knowledge score, and HbA1c level; the internal consistency coefficient (Cronbach's alfa) was also calculated.

Results: Cronbach's alfa for primary raw and standardized data were 0.7444 and 0.7413, respectively, thus meeting the required range of 0.7–0.8. The score on DAT item 1 (the title item) and total score (the sum of scores of item 2 to 10) correlated with the diabetes-related behavior score (r=0.21, р=0.0006 and r=0.34, р<0.0001, respectively). Patients with poor dietary compliance (average DAT score≤2) had a significantly lower score on the subscale "Nutrition" of the diabetes knowledge test, than those with good dietary compliance (average DAT score≥2) (44.9±15.6 vs 60.2±16.2, р<0.0001). Patients who perceived their diet as the most burdensome element of life with diabetes, had lower total DAT score (24.1±4.6) than those who did not see their diet as a problem (25.9±5.1, р=0.001). There was a  significant difference in average DAT score between patients on insulin therapy and patients on oral treatment (2.8±0.6 vs 2.9±0.6, respectively, р=0.019). Patients with poor and good dietary adherence, according to DAT, differed in their duration of diabetes, social status and diabetes-related behavior score. There was a  weak correlation between the DAT score and duration of diabetes (r=0.16, р=0.009), and weak inverse correlation between the DAT score and total serum cholesterol levels (r=-0.16, р=0.01).

Conclusion: The diagnostic characteristics of the proposed questionnaire meet the criteria of face, content and external validity and internal consistency, or reliability. This self-report questionnaire allows to assess the type 2 DM patient's awareness and adherence to medical nutritional therapy, at no additional time expenses of the doctor. No associations between dietary adherence and main parameters of treatment efficacy in type 2 DM were found.

Background: The metabolic syndrome is seen as a  cluster of high cardiovascular risk factors. New hormone-like substances, such as adipokines leptin and apelin, produced by fat tissue, are important for the pathophysiology of the metabolic syndrome.

Aim: To evaluate levels of plasma apelin and serum leptin in patients with metabolic syndrome.

Materials and methods: We examined 122 male patients with metabolic syndrome and 30 healthy males aged from 25 to 60 years. All patients were assessed accordingly to confirm the diagnosis of the metabolic syndrome, with additional measurements of serum leptin and plasma apelin.

Results: Serum leptin levels were 10-fold higher and plasma apelin levels 3-fold higher in patients with metabolic syndrome (n=122), compared to the controls (n=30): 25.43 vs. 3.99 ng/mL (p<0.05) and 1.13 vs. 0.66 ng/mL (p<0.05), respectively. Serum leptin levels correlated with all parameters of the excess body weight, such as body mass (r=0.79, р<0.05), body mass index (r=0.93, р<0.05), waist circumference (r=0.61, р<0.05), hip circumference (r=0.57, р<0.05), and waist-to-hip ratio (WHR; r=0.4, р<0.05). Plasma apelin levels correlated with the waist circumference (r=0.27, р<0.05) and WHR (r=0.29, р<0.05). There was a significant increase of serum leptin dependent on the bodyweight category: 19.8 ng/mL in patients with obesity Grade I  (n=49) and 28.7  ng/mL in those with obesity Grade II (n=46) (р<0.05). There was a  non-significant trend towards an increase in plasma apelin depending on bodyweight. As far as abdominal obesity is concerned, in patients with WHR<1 (n=35), plasma apelin level was 0.36  ng/mL, whereas in those with WHR of ≥1 (n=87), it was 3-fold higher (1.09 ng/mL, р<0.05); the increase in serum leptin levels was non-significant. There was no association between plasma apelin and serum leptin in patients with metabolic syndrome (r=0.1, р>0.05).

Conclusion: The adipokine levels in men with metabolic syndrome are higher than in normal men. Serum leptin level is a  sensitive parameter indicating accumulation of the fat tissue, irrespective of its localization. Plasma apelin is less sensitive, but it does reflect fat accumulation of the central (abdominal) type.