CC BY
47
ванная манжета: слишком длинная или слишком узкая манжета; «скользящая фундоплика-ция» вследствие формирования манжеты не из дна желудка, а из тела; миграция манжеты в грудную клетку из-за недостаточной длинны абдоминальной части пищевода; ахалазия пищевода, не выявленная до операции; псев-доахалазия, развившаяся после операции в результате чрезмерного сжатия пищевода [12] Манометрия пищевода может быть полезна при прогнозировании результатов ре-фундопликации у больных с жалобами на дисфагию. Повторная операция у таких пациентов с выявленной неэффективной моторикой пищевода в сочетании с приобретенным
укорочением пищевода только усугубила симптомы дисфагии.
У пациентов с атипичными симптомами ГЭРБ (кашель) в сочетании с неэффективной моторикой пищевода по данным манометрии после фундопликации не произошло устранения атипичных симптомов.
Выводы
Манометрия пищевода является необходимым этапом в обследовании пациентов перед проведением антирефлюксного оперативного лечения, особенное значение она имеет у больных с ведущими симптомами, связанными с дисфагией и атипичными симптомами ГЭРБ.
Сведения об авторах статьи: Гришина Елена Евгеньевна - аспирант кафедры факультетской хирургии с курсом колопроктологии ГБОУ ВПО БГМУ Минздрава России. Адрес: 450000, г. Уфа, Ленина, 3. E-mail: [email protected]
Рахимов Радмир Радимович - ассистент кафедры факультетской хирургии с курсом колопроктологии ГБОУ ВПО БГМУ Минздрава России. Адрес: 450000, г. Уфа, Ленина, 3.
ЛИТЕРАТУРА
1. Ивашкин, В.Т. Современный подход к терапии гастроэзофагеальной рефлюксной болезни во врачебной практике / В.Т. Ивашкин, А.С. Трухманов// Врач. - 2004. - №8. - С. 4-8.
2. Рощина, Т.В. Гастроэзофагеальная рефлюксная болезнь у больных бронхиальной астмой: автореф. дис... канд.мед.наук.-М.,2002.-21с.
3. JonathanF. Finks, Yonglian Wei, John D. Birkmeyer. Surg Endosc - 2006. -№20. - p.1698-1701.
4. B. Dallemagne, S. Perretta - World J Surg (2011) 35: 1428-1435.
5. Granderath F.A, Kamolz T, et al. Wien: Springer-Verlag, 2006. - P.121-138.
6. Velanovich V.J. Gastrointest. Surg 2004. State U et al. Surg. Endosc. 2008.
7. Spence GM, Watson DI, Jamiesion GG et al. - J. Gastrointest Surg (2006) 10:698-705.
8. Chrysos E, Tsiaoussis J, Zoras OJ et al.- J Am Coll Surg (2003)197:8-15.
9. Booth MI, Stratford J, Jons L et al - Br J Surg (2006) 95: 57-63.
10. Черноусов, А.Ф. Повторные антирефлюксные операции / А.Ф. Черноусов, Т.Ф. Хоробрых, Ф.П. Ветшев // Вестник национального медико-хирургического центра им. Н.И. Пирогова. - 2011. - Т.6, №1. - С. 28-35.
11. Malhi-ChovlaN., et al. Gastrointestinal Endoscopy. - 2002. - Vol.55. - p. 219-223.
12. Luigi Bonavina, David Bona, et. Al. Langenbecks Arch Surg (2007) 392:653-656.
13. Velanovich V, Mahatme A (2004) J Gastrointest Surg 8(3):335-341.
14. State U, Emmermann A, Fibbe C, Layer P, Zorning C. (2008)Surg Endosc 22:21-30.
УДК 616.379-008.64:616.71-007.234-036-001.5
© В.В. Жуковская, К. Эллер-Ваникер, В.В. Вадзяная, А.П. Шепелькевич,
И.В. Журава, Г.Г. Короленко, О.Б. Салко, Э. Кайроли, П. Бек-Пеккоц, Я. Кьодини, 2013
В.В. Жуковская, К. Эллер-Ваникер, В.В. Вадзяная, А.П. Шепелькевич, И.В. Журава, Г.Г. Короленко, О.Б. Салко, Э. Кайроли, П. Бек-Пеккоц, Я. Кьодини ИЗМЕНЕНИЯ МИНЕРАЛЬНОЙ ПЛОТНОСТИ КОСТИ И ПОЗВОНОЧНЫЕ ПЕРЕЛОМЫ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ I ТИПА
Главный поликлинический госпиталь, Миланский университет, Милан, Италия
Цель исследования - Некоторые исследования показали низкую минеральную плотность кости (МПК) и повышенный риск симптоматических переломов у пациентов с сахарным диабетом 1 типа (СД 1 типа). Насколько нам известно, никаких исследований по распространенности асинтоматических морфометрических позвоночных переломов (VFx) у пациентов с СД1 типа не проводилось. В данном исследовании мы оценили МПК и распространённость VFx при СД1 типа. Материал и методы исследования. Мы обследовали 82 пациента с СД 1 типа (26 мужчин и 56 женщин, в возрасте), контрольная группа составила 82 человека (22 женщины и 60 мужчин). МПК поясничного отдела позвоночника и шейки бедренной кости (как 2-критерий, Z-LS и Z-FN, соответственно) и распространенность VFх оценивались двойной рентгеновской абсорбциомет-рией. Результаты - Пациенты с СД1 типа имели более низкий Z-LS и Z-FN, чем в контрольной группе (-0,55 +/- 1,3 против 0,35 +/- 1.0, P < 0,0001 и -0,64 +/- 1,1 против 0,29 +/- 0.9, P < 0,0001, соответственно) и более высокую распространенность VFх (24,4 против 6,1%, P=0,002). Возраст, продолжительность заболевания, возраст выявления СД, гликозилированный гемоглобин, Z-LS, 2-Р'М, преобладание осложнений были одинаковы для пациентов с и без VFх. В логистическом регрессионном анализе, присутствие VFх было связано с наличием СД 1 типа, но не с МПК. В то время как средней тяжести или тяжелые VFх были связаны с низкой МПК поясничного отдела позвоночника у всей группы пациентов СД 1 типа и контрольной группы, не было выявлено никакой связи между средней тяжести или тяжелыми VFх и МПК поясничного отдела
позвоночника в группе пациентов с СД 1 типа. Выводы - Пациенты с СД 1 типа имеют сниженную МПК и увеличенный риск асинтоматических позвоночных переломов, что связано с присутствием СД 1 типа независимо от МПК.
Ключевые слова: минеральная плотность кости, переломы позвонков, сахарный диабет.
V.V. Zhukovskaya, Cristina Eller-Vainicher, V.V. Vadzianava, A.P. Shepelkevich, I.V. Zhurava, G.G. Korolenko, O.B. Salko, Elisa Cairoli, Paolo Beck-Peccoz, Iacopo Chiodini VARIATION IN BONE MINERAL DENSITY AND VERTEBRAL FRACTURES IN PATIENTS WITH TYPE I DIABETES
Objective - Several studies showed low bone mineral density (BMD) and elevated risk of symptomatic fractures in patients with type 1 diabetes (T1D). To our knowledge, there has been no investigation on the prevalence of asymptomatic vertebral fractures (VFx) in T1D. In the current study, we assessed BMD and the prevalence of VFx in T1D. Research design and methods. We evaluated 82 T1D patients (26 males and 56 females) and 82 controls (22 females and 60 males). Spinal and femoral BMD (as Z-score, Z-LS and Z-FN, respectively) and the prevalence of VFx were evaluated by dual X-ray absorptiometry. Results - T1D patients had lower Z-LS and Z-FN than controls (20.55 +/- 1.3 vs. 0.35 +/- 1.0, P < 0.0001, and 20.64 +/- 1.1 vs. 0.29 +/- 0.9, P < 0.0001, respectively) and a higher prevalence of VFx (24.4 vs. 6.1%, P=0.002). Age, diabetes duration, age at diabetes manifestation, glycosylated hemoglobin, Z-LS, Z-FN, and the prevalence of chronic complications were similar for patients with and without VFx. In the logistic regression analysis, the presence of VFx was associated with the presence of T1D but not with lumbar spine BMD. Whereas moderate or severe VFx was associated with low lumbar spine BMD in the whole combined group of T1D patients and controls, there was no association between moderate or severe VFx and lumbar spine BMD in the T1D group. Conclusions - T1D patients have low BMD and elevated prevalence of asymptomatic VFx, which is associated with the presence of T1D independently of BMD.
Key words: mineral density of bones, vertebral fractures, diabetes.
Type 1 diabetes (T1D) has been suggested to be associated with an increased risk of fractures [1]. The exact mechanisms accounting for bone fragility in T1D are not known in detail [2,3). In most but not all studies, bone mineral density (BMD), as measured by dual X-ray ab-sorbtiometry (DXA), appears to be reduced [13]. In particular, in adults, who have reached the peak of bone mass, the findings are somewhat heterogeneous, although most studies point toward a negative effect of T1D on BMD [2,4]. In keeping with this, combined study analysis estimated that T1D increases the risk of clinical fractures by 1- to 2-fold at the spine, 1.5- to 2.5-fold at the hip, and 2-fold at the distal radius [2]. No data are available regarding the risk of asymptomatic morphometric vertebral fracture (VFx) in T1D patients. This is an important lack of knowledge, because it is known that the presence of a morphometric VFx increases the risk of a subsequent spinal or hip fracture, regardless of BMD [5]. In addition, a recent meta-analysis demonstrated an absolute risk of hip fracture in T1D higher than that expected on the basis of BMD variation [1]. This suggests that in T1D the reduction of BMD estimates the fracture risk only partially. In this study, we evaluated the BMD and the prevalence of morphometric VFx in a group of adult T1D patients.
Research design and methods
This cross-sectional case-control study was performed in the following 3 Belarusian Medical hospitals: Republic Clinical Hospital of Medical Rehabilitation (Minsk, Belarus), 1st Minsk City Clinical Hospital (Minsk, Belarus), and 10th Minsk City Clinical Hospital (Minsk, Belarus). From 2007 to 2011, a total of 200 consecutive T1D patients were evaluated. The diagnosis of T1D was based on the American Diabetes Asso-
ciation criteria [6]. Inclusion criteria were as follows: age between 20 and 55 years, duration of disease >2 years, and eugonadal status. The exclusion criteria were as follows: 1) the presence of severe chronic kidney disease, 2) the presence or history of diseases and syndromes associated with low BMD (i.e., noncompensated hypothyroidism, hyperthyroidism, hyperparathyroidism, intestinal malabsorption, inflammatory bowel disease, or history of malignancy), 3) intake of drugs that can influence bone metabolism, 4) the pregnancy and lactation periods, and 5) the presence of acute infectious disease. Ultimately, 82 T1D patients were enrolled.
In the same period, 82 healthy subjects were recruited as controls among 932 subjects referred to our outpatient clinic by health providers of general medicine for the suspicion of hypothyroidism or Hashimoto thyroiditis. The control subjects were enrolled in the study if they had normal thyroid function and negative autoim-munity and if they fulfilled the inclusion criteria (age 20-55 years, eugonadal status) without any exclusion criteria (the presence of diabetes melli-tus; the presence or history of diseases and syndromes associated with low BMD, such as hy-perparathyroidism, intestinal malabsorption, inflammatory bowel disease, or history of malignancy; intake of drugs that can influence bone metabolism; the pregnancy and lactation periods; and the presence of acute infectious disease).
In all patients and controls, height and weight were measured and BMI was calculated. In all subjects, BMD was assessed with DXA (Prodigy Lunar; General Electric Medical Systems) and expressed as SD units (Z-values) in relation to an age-matched reference population at both lumbar spine (Z-LS) and femoral neck (Z-FN). BMD was adjusted for weight and classified
as normal, osteopenic, or osteoporotic on the basis of Z-LS or Z-FN BMD [7]. We decided to use both Z-score and T-score because the sample was composed of premenopausal women and men younger than 50 years.
Data from lumbar spine scans were used only if at >3 vertebrae were visualized without interfering artifacts. Fractured vertebrae were excluded from BMD measurement. The coefficient of variation BMD measurements at lumbar spine and femoral neck was <1.5%. X-ray loading in one projection was 0.04 mSv. In both T1D patients and controls, the presence of morpho-metric VFx was assessed with DXA with the software Vertebral Fracture Assessment (VFA) from T4 to L4 vertebrae. This software is a program within the Prodigy Lunar system, including a lateral projection of the spine. The manufacturer refers to this lateral projection as "dual-energy vertebral assessment, DVA." VFx was diagnosed
according to the classification of Genant et al. [8]. Each vertebra was considered as intact (grade 0) or as having approximately mild (20-25% compression), moderate (25-40% compression), or severe (>40% compression) deformity (grades 1, 2 and 3, respectively). The DXA and VFA reviewers were blinded to the presence of diabetes. In all patients with evidence of a VFx on VFA, conventional spinal radiographs in lateral (T4-L4) and anteroposterior projection (L1-L4) were obtained. In all cases, the X-ray evaluation confirmed the VFA results.
In T1D patients the presence of chronic complications was evaluated. Diabetic neuropathy evaluation was based on symptoms, quantitative sensory testing (temperature, vibration, and pressure perception) and quantitative motor testing (patellar and ankle reflexes). All T1D patients underwent funduscopic examination.
Table 1
Clinical characteristics of patients with T1D and control subjects
Parameters T1D patients (n=82) Controls (n=82) P
Age (years) 31.1 +/- 8.6 (20-54) 32.9 +/- 5.8 (21-46) 0.11
Height (cm) 169.1 +/- 8.1 (150-188) 168.1 +/- 7.6 (150-188) 0.4
Weight (kg) 67.4 +/- 11.1 (46-100) 67.9 +/- 14.6 (43-131) 0.82
BMI (kg/m2) 23.5 +/- 3.3 (17.5-35.6) 23.9 +/- 4.8 (16.6-45) 0.54
Male/female ratio 26:56 22:60 0.61
Diabetes duration (years) 12.8 +/- 8.3 (2-36) - -
Age at diabetes diagnosis(years) 18.6 +/- 8.7 (2-39) - -
Daily insulin dose (U/kg) 0.8 +/- 0.3 (0.12-1.54) - -
HbA1c (%) 8.4 +/- 2.3 (4.4-13.6) - -
HbA1c (mmol/mol) 68 +/- 6.9 (25-125) - -
ClCr (mL/min) 101.7 +/- 29.4 (59.1-202.7) 106.4 +/- 33.7 (76.0-246.5) 0.54
Patients with neuropathy 58 (70.7) - -
Patients with retinopathy 35 (42.7) - -
Patients with nephropathy 22 (26.8) - -
T-LS -0.56 +/- 1.3 (-3.1 to 2.6) 0.16 +/- 0.9 (-1.9 to 1.8) 0.001
Z-LS -0.55 +/- 1.3 (-3.3 to 2.8) 0.35 +/- 1.0 (-2.1 to 3.2) <0.001
Subjects with Z-LS less than-1.0 30 (36.6) 9 (11.0) <0.001
T-FN -0.77 +/- 1.3 (-4.1 to 1.8) 0.12 +/- 0.9 (-2.3 to 1.6) <0.001
Z-FN -0.64 +/- 1.1 (-3.8 to 1.9) 0.29 +/- 0.9 (-1.8 to 3.5) <0.001
Subjects with Z-FN less than-1.0 23 (29.5) 6 (7.3) <0.001
Subjects with osteoporosis at any site (T-score -2.5 or less) 9 (14.5) 0 (0) 0.004
Subjects with VFx 20 (24.4) 5 (6.1) 0.002
Subjects with mild VFx 14 (17.1) 4 (4.9) 0.022
Subjects with moderate VFx 4 (4.9) 1 (1.2) 0.37
Subjects with severe VFx 2 (2.4) 0 (0) 0.5
Subjects with VFx and Z-LS -1.0 or
greater 11 (13.4) 3 (3.7) 0.047
Subjects with VFx and Z-LS -2.5 or
greater 16 (19.5) 5 (6.1) 0.018
Diabetic retinopathy was categorized as nonproliferative, preproliferative, or proliferative [9]. Diabetic nephropathy was assessed by measuring microalbumin in 24-h urine samples (normal values <30 mg/day) twice (at enrolment and after 3-6 months) to determine persistent microalbuminuria. Microalbuminuria and macroalbu-minuria were diagnosed on the basis of albumin excretion rate between 30 and 300 mg/day or >300 mg/ day, respectively [9]. For each patient, the diabetes complication score was calculated on
the basis of the presence of 0, 1, 2 or 3 complications among neuropathy, retinopathy, and nephropathy (score of 0, 1, 2 or 3, respectively).
Venous blood samples were taken from all T1D patients in the morning before the insulin injection after a 10-h fast, centrifuged, and stored at 2708C until analysis. Glycosylated hemoglobin (HbA1c, normal value 4.0-6.0%) and serum creatinine were measured by high-performance liquid chromatography with autoanalyzer D10 (Bio-Rad) and with analyzer HITACHI 911
(Roche Diagnostics, Germany), respectively. Creatinine clearance (ClCr) was calculated with the formula of Cockcroft-Gault: ClCr (mL/ min)=[140 - age (years) x weight (kg)/ 72 x 11.3 x serum creatinine (mmol/L)] for males and ClCr (mL/min)=0.85 x [140 - age (years) x weight (kg)/72 x 11.3 x serum creatinine (mmol/L)] for females [9].
Statistical analysis was performed with the SPSS version 18.0 statistical package (IBM Corporation, Armonk, NY). The distribution of variables was tested with the Kolmogorov-Smirnov test. The results are expressed as mean +/- SD or median as appropriate. The comparison of continuous variables between patients and controls was performed with the Student t test or MannWhitney U test as appropriate. General linear modeling was performed to compare the continuous variables between patients and controls after adjusting for age. The categorical variables were compared by x2 test or Fisher exact test. The associations between variables were tested by either Pearson or Spearman correlation, as appropriate. Multivariate logistic or linear regression analysis assessed the association between the presence of morphometric VFx (categorical dependent variable) and the following independent variables: age, sex, BMI, lumbar spine BMD, score of diabetes complications (expressed as a continuous variable), and physical activity. These variables were chosen because they are factors known to influence the skeletal metabolism. P < 0.05 was considered significant.
Results
The general characteristics of T1D patients and controls are reported in Table 1. Age, an-thropometric parameters (height, weight, and BMI), sex distribution, and renal function were comparable between patients and controls. Patients with T1D had significantly lower Z-LS and Z-FN and higher prevalence of low BMD (Z-score less than -1.0). General linear modeling confirmed these results after adjusting for age. Moreover, T1D patients showed significantly higher prevalence of morphometric VFx than controls did. About the 25% of T1D patients (n=20) had at least 1 VFx. Among these, 14 patients had only mild VFx, whereas the remaining 4 and 2 patients had moderate or severe VFx, respectively; the difference from controls was statistically significant for mild VFx but not for moderate or severe VFx (Table 1). Even after excluding patients with mild fractures, these differences were substantially confirmed (T1D vs. controls, subjects with VFx 8.5 vs. 1.2%, P=0.064, respectively).
When analyzing male and female subjects separately, the results were the same as for the whole T1D group both for T1D males (T1D males vs. controls, Z-LS 21.0 6 1.1 vs. 0.4 6 0.67, P, 0.001, and Z-FN 21.0 6 1.1 vs. 0.35 6 0.6, P, 0.001; subjects with VFx 23.1 vs. 4.5%, P=0.078, respectively) and T1D females (T1D female patients vs. controls, Z-LS 20.34 6 1.3 vs. 0.32 6 1.1, P=0.003, and Z-FN 20.45 6 1.2 vs. 0.27 6 1.0, P=0.01; subjects with VFx 25 vs. 6.7%, P=0.009, respectively).
Comparing T1D patients with and without VFx, no differences were found in age, BMI, sex distribution, diabetes duration, age at T1D mani-fe station, HbA1c, renal function, and physical activity.
T1D patients with VFx tended, however, to have a lower BMD at both lumbar spine and femoral neck and higher prevalences of neuropathy and retinopathy and higher complication score relative to patients without VFx. The same trend toward lower BMD at both sites was seen also in controls with VFx relative to those without. Comparing T1D patients with and without VFx divided by sex, we found substantially the same results.
Analyzing diabetic patients together with controls, we found that the presence of mild, moderate, or severe VFx was associated with the presence of T1D but not with spine BMD after adjusting for age, sex, and BMI (Table 2). Separately analyzing T1D patients, we found that the presence of mild, moderate, or severe VFx tended to be associated with low spine BMD after adjusting for age, sex, BMI, complication score, and physical activity (Table 2).
Table 2
Odds ratios for the presence of VFx after adjustment
for lumbar spine BMD and other risk factors
Parameters Vertebral fractures
Odds ratio 95% CI P
T1D patients and controls
BMI (1 kg/m2 decrease) i .05 0.90-i.20 0.43
Age (1-year increase) i.04 0.98-i.i0 0.i9
Sex (female) i.50 0.52-4.i0 0.47
Z-LS (Z-score 1-SD decrease) i.40 0.90-2.00 0.i3
Presence of T1D 4.20 i.40-i2.70 0.0i
T1D patients
BMI (1 kg/m2 decrease) i .08 0.70-i.69 0.7i
Age (1-year increase) i.03 0.92-i.i5 0.62
Sex (female) 7.63 0.49-i i8.58 0.i5
Z-LS (Z-score 1-SD decrease) 3.40 0.80-i5.40 0.096
Complication score (1-unit increase) i.70 0.60-5.03 0.3i
Physical activity (1 h/day decrease) i.0i 0.99-i.03 0.25
Controls
BMI (1 kg/m2 decrease) i .05 0.82-i.37 0.68
Age (1-year decrease) i .05 0.90-i.25 0.52
Sex (female) i .46 0.i5-i4.70 0.75
Z-LS (Z-score 1-SD decrease) i.60 0.50-3.i0 0.62
Conclusions
To our knowledge, this is the first study evaluating the prevalence of morphometric VFx in patients with T1D. We found that BMD was decreased and the prevalence of morphometric VFx was increased in T1D patients.
It is well known that T1D patients frequently show low bone mass, the pathogenesis of which is still not clear [2,3]. In this study, we confirmed that adults with T1D had significantly lower BMD and higher prevalence of low BMD (Z-score BMD less than 21.0) both at the lumbar spine and at the femoral neck relative to controls, as already suggested by previous studies [1,4].
In addition to low bone mass, T1D has been suggested to be characterized by elevated risk of clinical fractures [1,2,10]; this also is consistent with our results, because in this study about 25% of T1D patients had VFx. On the other side, it has been recently suggested that fractures in T1D might be not entirely explained by reduced BMD [1], as happens in several forms of secondary osteoporosis [11]. This is in keeping with the results of the logistic regression analysis (Table 2), which confirms the association of T1D with the presence of VFx regardless of BMD. When limiting the analysis to the moderate or severe fractures, BMD but not T1D was found to be associated with VFx. These apparently discordant findings may have arisen because the reduction of BMD remains crucial and overcomes the role of T1D when only more severe VFx is considered. It is not possible, however, to exclude the possibility that the number of patients with moderate or severe VFx (n=5) was insufficient to evaluate the effect of T1D reliably in this subset of patients.
Notwithstanding these limits, these finding are of clinical importance, because the prevalence of VFx predicts future fractures regardless of BMD [5] and because the recognition of VFx by imaging of the spine may change the patient diagnostic classification, estimation of fracture risk,
and threshold for pharmacological intervention.
In our sample, no potential risk factors for VFx other than BMD (among age, sex, BMI, physical activity, and complications) were found to be significantly associated with the presence of VFx in the logistic regression analysis (Table 2). Because T1D patients with VFx tended to have higher complication score and higher prevalence of diabetes complications, in particular retinopa-thy and neuropathy, the presence of chronic diabetes complications might be an adjunctive tool in addition to BMD in evaluating risk factors for fractures in T1D. The statistical significance for complication score was not reached, possibly because of the large SD and the relatively small number of patients with VFx. The link between the presence of the chronic complications and the presence of osteoporosis in T1D is debated [1218]. Recently, the presence of the chronic diabetes complications has been shown to be associated with low BMD in T1D [4]. In contrast, Vestergaard et al. [10] showed that the complications of diabetes other than diabetic kidney disease add little to the overall risk of fracture.
Some data suggest that the nonenzymatic glycosylation of type 1 collagen, with subsequent formation of advanced glycation end products, has a negative impact on mechanical properties of cancellous and cortical bone. The alteration of the organic matrix in bone by advanced glycation end products could be relevant to increased bone fragility with aging and in such disease as diabetes [19,20]. This is a suitable explanation for poor bone quality in T1D. In this study, the lack of association between BMD and VFx in T1D patients may suggest the loss of bone quality as a cause for the increased VFx prevalence in T1D patients.
In conclusion, this study confirms that BMD is reduced in T1D. Moreover, it shows that the prevalence of morphometric VFx is increased in T1D and not associated only with the reduction of BMD.
Contacts
Zhukouskaya Volha - Endocrinology and Diabetology Unit, Department of Clinical Science and Community Health, University of Milan, IRCCS Ca Granda Foundation Policlinico Maggiore of Milan. Pad. Granelli, Francesco Sforza street, 35, Milan 20122, Italy. E-mail: [email protected]
REFERENCES
1. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetesda meta-analysis. Oste-oporos Int 2007;18: 427-444
2. Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 2007; 22:1317-1328
3. McCabe LR. Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 2007;102:1343-1357
4. Eller-Vainicher C, Zhukouskaya VV, Tolkachev YV, et al. Low bone mineral density and its predictors in type 1 diabetic patients evaluated by the classic statistics and artificial neural network analysis. Diabetes Care 2011;34:2186- 2191
5. Crans GG, Genant HK, Krege JH. Prognostic utility of a semiquantitative spinal deformity index. Bone 2005;37:175-179
6. American Diabetes Association. Standards of medical care in diabetesd2007. Di- abetes Care 2007;30(Suppl. 1):S4-S41
7. Leib ES, Lewiecki EM, Binkley N, Hamdy RC; International Society for Clinical Densitometry. Official positions of the International Society for Clinical Densitometry. South Med J 2004;97:107-110
8. Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993;8:1137-1148
9. Donnelly R, Horton E (Eds.). Vascular Complications Of Diabetes: Current Issues in Pathogenesis and Treatment. 2nd ed. Hoboken, NJ, Wiley-Blackwell, 2005.
10. Vestergaard P, Rejnmark L, Mosekilde L. Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcif Tissue Int 2009;84:45-55
11. Morelli V, Eller-Vainicher C, Salcuni AS, et al. Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: a multicenter longitudinal study. J Bone Miner Res 2011;26:1816-1821
12. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 2000;15:721-739
13. Rozadilla A, Nolla JM, Montaña E, et al. Bone mineral density in patients with type 1 diabetes mellitus. Joint Bone Spine 2000;67:215-218
14. Clausen P, Feldt-Rasmussen B, Jacobsen P, et al. Microalbuminuria as an early indicator of osteopenia in male insulindependent diabetic patients. Diabet Med 1997;14:1038-1043
15. Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 1999;22:827-831
16. Miazgowski T, Pynka S, Noworyta-Zietara M, Krzyzanowska-Swiniarska B, Pikul R. Bone mineral density and hip structural analysis in type 1 diabetic men. Eur J Endocrinol 2007;156:123-127
17. Alexopoulou O, Jamart J, Devogelaer JP, Brichard S, de Nayer P, Buysschaert M. Bone density and markers of bone remodelin g in type 1 male diabetic patients. Diabetes Metab 2006;32:453-458
18. Hamilton EJ, Rakic V, Davis WA, et al. Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes. Diabet Med 2009;26:45-52
19. Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 2010;21:195-214
20. Hamada Y, Kitazawa S, Kitazawa R, Fujii H, Kasuga M, Fukagawa M. Histo- morphometric analysis of diabetic osteopenia in strepto-zotocin-induced diabetic mice: a possible role of oxidative stress. Bone 2007;40:1408-1414
21. Lewiecki EM, Laster AJ. Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab 2006; 91:4215-4222
УДК 616.62-006.6-036-07:575.174.015.3
© В.Н. Павлов, А.А. Измайлов, Т.В. Викторова, С.М. Измайлова, Л.М. Кутлияров, М.Ф. Урманцев, В.З. Галимзянов, И.И. Муратов, 2013
В.Н. Павлов, А.А. Измайлов, Т.В. Викторова, С.М. Измайлова, Л.М. Кутлияров, М.Ф. Урманцев, В.З. Галимзянов, И.И. Муратов ВЫБОР ОБЪЕМА ЛИМФОДИССЕКЦИИ У БОЛЬНЫХ МЫШЕЧНО-ИНВАЗИВНЫМ РАКОМ МОЧЕВОГО ПУЗЫРЯ
ГБОУ ВПО «Башкирский государственный медицинский университет» Минздрава России, г. Уфа
Проанализированы результаты лечения 292 пациентов с мышечно-инвазивным раком мочевого пузыря за период с 2006 по 2012 гг. Проведен молекулярно-генетический анализ полиморфных локусов генов цитохромов P450: CYP1A1 (A2455G), CYP1A2 (T-2464delT), глутатион S-трансферазы: GSTM1 (del), GSTP1 (A313G); Проведен анализ полиморфных локусов этих генов у пациентов с инвазивным раком мочевого пузыря с лимфогенными метастазами и без них. Выявлены генотипы, ассоциированные с риском лимфогенного метастазирования.
Ключевые слова: рак, мочевой пузырь, онкомаркеры, полиморфизм.
V.N. Pavlov, A.A. Izmaylov, T.V. Viktorova, S.M. Izmaylova, L.M. Kutliyarov, M.F. Urmantsev, V.Z. Galimzyanov, I.I. Muratov
CHOOSING THE SIZE OF LYMPH NODE DISSECTION IN PATIENTS OF MUSCLE-INVASIVE BLADDER CANCER
Treatment results (2006-2012) of patients with invasive (N=292) urinary bladder carcinoma were analyzed. Molecular genetic analysis of cytochrome gene P450 polymorphous locus was carried out: CYP1A1 (A2455G), CYP1A2 (T-2464delT), Glutathione S-transferase: GSTM1 (del), GSTP1 (A313G); Furthermore, analysis of these genes polymorphous locus in patients with invasive urine bladder carcinoma with and without lymphogenic metastases was carried out. Genotypes associated with lymphogenic metastasis risk were identified.
Key words: cancer, urinary bladder, oncomarkers, polymorphism.
В последние годы в России возрастает количество больных раком мочевого пузыря (РМП). Так, в 2010 г. впервые выявлен 12721 случай заболевания РМП. Общий прирост заболеваемости РМП с 2000 по 2010 гг. составил 22,57% [1,5]. Радикальная цистэктомия с тазовой лимфаденэктомией является «золотым стандартом» лечения инвазивного рака мочевого пузыря (ИРМП) [8,10]. Общепризнано, что наличие лимфогенного метастази-
рования значительно ухудшает прогноз заболевания, а существующие методы оценки риска лимфогенного метастазирования не имеют достаточной достоверности [11]. Метастатическое поражение лимфоузлов увеличивает риск местного рецидива и прогрессии заболевания [4]. В настоящее время в связи с развитием молекулярной генетики проводится активное изучение дополнительных маркеров прогноза заболевания, объединенных терми-
