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Novikova Liliya Boreevna, Izhbuldina Gulnara Ildusovna, Bashkirian State Medical University, Post Education Institute Russia, Ufa
E-mail: [email protected]
Prevalence of abnormal glucose metabolism in the acute phase of ischemic stroke in diabetic and nondiabetic patients
Abstract: To study carbohydrate metabolism characteristics in the acute phase of ischemic stroke. The development of ischemic stroke is accompanied by high levels ofblood C-peptide in both diabetic and non-diabetic patients. Pronounced disorders are interrelated with the severity and clinical outcome of the disease.
Keywords: ischemic stroke, diabetes mellitus, arterial hypertension, glucose, insulin, C-peptide, insulin resistance.
Acute cerebral circulatory disturbances characterized by a high rate of mortality and steady disability of the population are one of the most common problems of contemporary medicine.
At present, among causes increasing risks for the development of stroke, its severity and outcome, carbohydrate metabolism disorders rank first. In diabetic patients an additional stroke risk is 18,6-35% [1; 3; 10]. Among patients with acute cerebral circulatory disturbances, the frequency of hyperglycemia is 60%. Meanwhile, in non-diabetic patients it is 12-53% [2]. A number of studies indicated a direct relationship between marked stress hyperglycemia and the disease severity and outcome [4; 8].
Insulin resistance has been shown to be a risk factor for stroke development, to mark the development of intracranial atherosclerosis in stroke patients without diabetes and to be a prognostic adverse factor for ischemic stroke recurrence or the development of ischemic heart disease in patients who experienced stroke [5; 7]. However, insulin is known to be an unstable hormone, which is rapidly metabolized in the liver. This largely hampers the insulin resistance assessment in patients. In view of this, the most appropriate is to determine blood C-peptide — the cleavage product of proinsulin. Over the last decade, there have been reports about C-peptide metabolic activity, its impact on lipid metabolism [6], proinflammatory and proatherogenic effects on the vascular wall [9]. However, lacking evidence on hormonal-metabolic condition of acute stroke patients fosters conducting the present study.
The purpose of the investigation is to study carbohydrate metabolism characteristics in the acute phase of ischemic stroke.
Materials and methods. The study is based on the results obtained from 126 acute stroke patients who were admitted to hospital during the first 12 hours after the appearance of focal neurologic symptoms (the treatment group). Ischemic stroke was diagnosed in accordance with criteria of the International Classification of Dis-
eases (ICD-10) and other health problems. The patients' age ranged from 41 to 82 years (mean 63,8 ±11,4). There were 61 males (48,4%) and 65 females (51,6%). In all patients, cerebrovascular accidents first developed in the presence of Type 1-3 arterial hypertension.
In 64 patients stroke was associated with Type 2 diabetes mel-litus. Among diabetic patients, 17 (26,9%) individuals received insulin therapy, 6 (9,4%) — diet therapy, 41 (64,1%) — oral sugar-reducing drugs.
The evaluation of neurological status severity was done based on the total score of the NIH Stroke Scale.
The comparison group comprised 50 hypertensive (Type 2-3) diabetes-free patients, 24 (48,0%) males and 26 (52,0%) females (mean age 57,1 ±8,4 years) without a history of stroke or myocardial infarction.
Thirty-five healthy volunteers without cardiovascular diseases were entered into the control group. There were 19 (54,3%) males and 16 (45,7%) females with mean age 49,8 ±7,3 years.
In all patients examined, blood for glucose, IRI and C-peptide was determined on an empty stomach. The level of blood glucose was determined using the glucose-oxidant method. The "IMMU-LITE 1000" immunoassay analyzer with commercial sets ("Diagnostic Products Corporation", USA) aided the immunoluminiscent method for determining IRI and C-peptide in blood serum.
Carbohydrate metabolism in stroke patients was studied within the first three days of the disease onset.
Results and Discussion. The study results are presented in Table 1. In stroke patient group without diabetes we have observed a significant increase in glycemia level (by 28,9%, p<0,05) compared with the control group. Meanwhile, there was no significant difference in the blood insulin concentration in healthy subjects and there was a significant decrease in the comparison group (by 36,6%, p < 0,05).
Table 1 - Carbohydrate metabolism indicators in stroke patients
Parameters Control (n = 35) IS without DM (n = 62) IS with DM (n = 64) AH without IS (n = 50)
Glucose (mmol/l) 4,12 ± 0,31 5,31 ± 0,68 a 6,74 ± 1,77 a b 4,51 ± 0,26
Insulin (mKME/ml) 12,7 ± 1,19 9,38 ± 4,34 b 14,4 ± 5,29 14,8 ± 0,97
C-peptide (nmol/l) 0,49 ± 0,04 0,90 ± 0,31 a b 1,19 ± 0,29 a b 0,27 ± 0,03 a
C-peptide/insulin 0,035 ± 0,004 0,107 ± 0,039 a b 0,091 ± 0,038 a b 0,021 ± 0,003 a
Note: a — a difference between indicators in the control group, b
In patient group IS with DM the blood glucose concentration did not differ significantly from that of the diabetes-free group and exceeded significantly indicators in healthy subjects (by 63,4%, p <0,05) and in patients with arterial hypertension (by 49,4%, p<0,05). It is noteworthy that there were much higher average insulin levels (by 49,2%) than in IS without DM group. However, these differences were statistically insignificant.
— in the group AH without IS is statistically significant at p < 0.05
In both stroke patient groups there was a significant increase in the blood C-peptide concentration formed along with insulin in enzymatic proinsulin splitting as compared with the control: in IS without DM — by 83,7% (p<0,01), in IS with DM — by 142,9% (p<0,001). In hypertensive patients without vascular accidents there was a decrease in C-peptide level by 44,7% (p<0,01). Our findings are consistent with those reported by Li Y. and colleagues [2014]
Prevalence of abnormal glucose metabolism in the acute phase of ischemic stroke in diabetic and nondiabetic patients
about a significant association of high C-peptide levels with stroke development in diabetes-free patients. It should be noted that despite available literature data on an association of increased C-peptide levels with risks for developing cardiovascular complications in diabetic patients, the number of studies dedicated to analysis of a relationship between C-peptide levels and a stroke risk in diabetes-free patients is not sufficient.
The results of assessment of the C-peptide/insulin ratio indicate that proinsulin secretion in acute ischemic stroke is abruptly activated (table 1). In patients with IS without DM the current parameters were at 3,06 times higher than in healthy subjects (p < 0,001), in patients with IS not associated with DM — at 2,60 times higher (p < 0,001). Conversely, in hypertensives the value of C-peptide/insulin ratio was by 40,0% (p < 0,01) lower than the control levels.
A significant decline in C-peptide levels in the presence of normal blood insulin and glucose levels in the comparison group patients suggests that in arterial hypertension, dysfunction of proinsulin conversion into insulin occurs with preserved sensitivity of tissues to insulin first of all. At the same time, with the development of acute stroke in hypertensives, there occurs a sharp increase in both insulin secretion underlined by high C-peptide levels and its
Among diabetic patients, values of the C-peptide/insulin ratio with severe stroke exceeded those in patients with both mild (by 51,9%, p < 0,05) and moderate-to-severe stroke (by 44,4, p < 0,05). The correlation analysis results have shown the presence of a positive relationship between the value of the C-peptide/insulin ratio and assessment of NIHSS neurologic deficit rating (r = 0,311; p = 0,040). It should be noted that in this patient group with mild stroke, blood glucose and insulin levels were significantly higher than in patients without DM with the same severity of stroke (by 25,6% and 81,5%, p < 0,05, respectively).
Analysis of a clinical outcome of ischemic stroke on day 21 demonstrated that in IS patient group without DM health status improved in 43 (69,4%) patients, in the remaining 19 (30,6%) subjects there were no changes. There was no evidence of lethal outcomes. Among patients with mild stroke, clinical improvement
utilization since these patients have hypoinsulinemia in the presence of relative hyperglycemia.
To answer the question whether stroke severity is due to detected carbohydrate metabolism disorders, we have studied hormonal-metabolic profiles depending on neurologic deficit ratings. Among IS patients without DM, neurologic deficit was mild (< 5 NIHSS grades) in 25 (40,3%) patients, moderate (from 6 to 14 grades) — in 23 (37,1%) patients, severe (more than 14 grades) — in 14 (22,6%) patients. Among examined patients with stroke developed in the presence of DM, mild, moderate and severe ratings of neurologic deficit were observed in 24 (37,5%), 20 (31,3%) and 20 (31,3%) patients, respectively.
As shown in Table 2, in both acute ischemic stroke patient groups, mean blood glucose, insulin and C-peptide levels were not related to the disease severity. At the same time, the C-peptide/in-sulin ratio indicators have a strong tendency to an increase with elevated neurologic deficit ratings. In diabetes-free patients with severe stroke its value was significantly higher than in those with a mild form of the disease (by 35,6%, p < 0,05). The correlation analysis results have shown the presence of a positive relationship between the C-peptide/insulin ratio and assessment of neurologic deficit rating using the NIH Stroke Scale (r = 0,304; p = 0,021).
was achieved in 23 (92,0%) cases, with moderate stroke — in 15 (65,2%), with severe stroke — in 5 (35,7%) cases. In IS patient group with DM, 38 (59,4%) subjects achieved health improvement. No health changes were observed in 26 (40%) cases. There was no evidence of lethal outcomes.
Comparative results of the hormonal-metabolic profiles assessment depending on the disease outcome indicate significantly higher values of the C-peptide/insulin ratio in patients without changes in their health status (table 3). So, in IS group without DM these differences were 39,6% (p < 0,05), in IS group with DM — 52,0% (p < 0,05). We should emphasize a positive correlation between values of stroke clinical outcome using the Rivemead mobility index and values of the C-peptide/insulin ratio in stroke patients both not associated with DM (r = -0,533; p = 0,0001), and developed in the presence of Type 2 DM (r = -0,390; p = 0,009).
Table 3. - Carbohydrate metabolism indicators depending on ischemic stroke clinical outcome
Parameters IS without DM IS with DM
Improvement (n = 43) Without improvement (n = 19) Improvement (n = 38) Without improvement (n = 26)
Glucose (mmol/l) 5,36 ± 0,62 5,22 ± 0,48 7,34 ± 1,29 5,88 ± 0,86
Insulin (mkME/ml) 10,11 ± 3,36 8,05 ± 3,12 16,31 ± 3,34 11,72 ± 2,48
C-peptide (nmol/l) 0,89 ± 0,27 0,91 ± 0,29 1,13 ± 0,34 1,28 ± 0,37
C-peptide/ insulin 0,096 ± 0,021 0,134 ± 0,014 0,075 ± 0,021 0,114 ± 0,016 a
Note: a — a difference between values in patients of the same group with favorable outcome significantly (p < 0,05)
Table 2. - Carbohydrate metabolism indicators depending on ischemic stroke severity
Parameters Neurologic deficit rating (using the NIH Stroke Scale)
IS without DM IS with DM
Mild (n = 25) Moderate (n = 23) Severe (n = 14) Mild (n = 24) Moderate (n = 20) Severe (n = 20)
Glucose (mmol/l) 5,54 ± 0,43 5,29 ± 0,39 5,00 ± 0,54 6,96 ± 0,78 c 7,38 ± 1,03 c 5,84 ± 0,93
Insulin (mkME/ml) 8,86 ± 3,17 10,27 ± 3,84 8,43 ± 1,92 16,08 ± 3,42 c 16,22 ± 3,81 10,87 ± 1,54
C-peptide (mmol/l) 0,78 ± 0,16 1,05 ± 0,27 0,91 ± 0,28 1,16 ± 0,23 1,20 ± 0,29 1,21 ± 0,26
C-peptide/insulin 0,087 ± 0,010 0,106 ± 0,015 0,118 ± 0,017 a 0,077 ± 0,016 0,081 ± 0,019 0,117 ± 0,014 a b
Note: a — a difference between values in patients of the same group with mild stroke; b — between values in patients of the same group with moderate-to-severe stroke; c — between values in patients with IS without DM with similar stroke course is statistically significant at p< 0.05.
Conclusion. Thus the results of this study suggest that acute ischemic stroke is characterized by high levels of blood C-peptide regardless the presence or absence of diabetes mellitus. Pronounced hormonal-metabolic disorders are interrelated with severity and clinical
outcome of the disease.
References:
1. Dedov I. I., Shestakova M. V. Diabetes Mellitus and Arterial Hypertension. M: MIA, 2006; 344.
2. Badiger Sh., Akkasaligar P. T., Narone U. Hyperglycemia and Stroke. Int. J. Stroke Res. 2013; 1: 1-6.
3. Beckman J. A., Creager M. A., Libby P. Diabetes and Atherosclerosis. Epidemiology, pathophysiology and management. J. Am. Med. Assoc. 2002; 287: 2570-2581.
4. Clark M. E., Payton J. E., Pittiglio LI. Acute Ischemic Stroke and Hyperglycemia. Critical Care Nursing Quarterly 2014; 37: 182-187.
5. Li Y., Meng L., Li Y., Sato Y. Associations of serum C-peptide level with body fat distribution and ever stroke in nondiabetic subjects. J. Stroke Cerebrovasc. Dis. 2014; 23: 163-169.
6. Mavrakanas T., Frachebois C., Soualah A., Aloui F., Julier I., Bastide D. C-peptide and chronic complications in patients with type-2 diabetes and the metabolic syndrome. Presse Medicale 2009; 38: 1399-1403.
7. Rundek T., Gardener H., Xu Q Goldberg RB, Wright CB, Boden-Albala B, Disla N, Paik MC, Elkind MS, Sacco RL. Insulin resistance and risk of ischemic stroke among nondiabetic individuals from the northern Manhattan study. Arch. Neurol. 2010; 67: 1195-1200.
8. Urabe T., Watada H., Okuma Y., Tanaka R., Ueno Y., Miyamoto N., Tanaka Y., Hattori N., Kawamori R. Prevalence of abnormal glucose metabolism and insulin resistance among subtypes of ischemic stroke in Japanese patients. Stroke 2009; 40: 1289-1295.
9. Vasic D, Marx N, Sukhova G, Bach H, Durst R, Grub M, Hausauer A, Hombach V, Rottbauer W, Walcher D. C-peptide promotes lesion development in a mouse model of arteriosclerosis. J. Cell. Mol. Med. 2012; 16: 927-935.
10. Zhang X. D., Chen Y. R., Ge L. Features of stroke in Chinese diabetes patients: a hospital-based study. J. Intern. Med. Res. 2007; 35: 540-546.
Akilov Habibullah Ataullaevich, Vice-rector of the Tashkent Institute of postgraduate training of doctor Primov Farhod Sharifzhanovich, Senior fellow researcher at the Tashkent Institute of postgraduate training of doctor E-mail: [email protected]
Long-term results of the splenectomy with heterotopic transplantation of splenic tissue in children with injuries of the spleen
Abstract: The main causes of postoperative complications in the late postoperative period in patients operated for injuries of the spleen has been the changes of coagulation hemostasis and rheological properties of blood and immune status. Keywords: splenectomy, heterotopic, splenic tissue.
Actuality: In spite of existing a great amount of methods of treatment after splenectomy (SE), opened possibility of transplant surgery has been promoted medicine and surgery, in general, in a new level of quality.
In certain surgical situations to preserve the spleen is not possible and the only way to maintain the function of the spleen after its removal is autologous transplantation of the spleen tissue [1; 2; 3].
Autotransplantation allows to stabilize the antimicrobial resistance of the organism by stimulating humoral immunity and correction content in the blood the level of taftsin, which leads to normalizing the function of mononuclear phagocyte system [2; 4].
Materials and methods: In the period from 3 months to 3 years after surgery was ambulatory examined 7 patients after conservative surgery (CS), 16 - after SE+HAT (heterotopic au-totrasplantation), 38 after SE. In total, long-term results were analyzed in 61 patients with injuries of the spleen in Republican Research Centre of Emergency Medicine were operated in the period from 2005 to 2015. A survey of patients was carried out in an outpatient setting.
Results and discussion: The study was revealed that late postoperative period in patients operated causing by trauma of spleen the complications directly correlated with the type of the operation.
As can be seen from the table in groups of patients, whom was carried out removal of an organ, a high incidences of various complications in the long period after SE as manifestations of the post-splenectomy syndrome can be established. Compare to the above provided information in the group of patients who was carried out CS clinical manifestations was significantly less as well as occurs in more lightly level than in the group SE group.
In this context, the frequency of clinical manifestations after SE can be seen as manifestations of the late postoperative postsple-nectomy syndrome.
Taking into account the greatest risk of hemostatic disorders and manifestations of immunodeficiency, special attention was paid to the study of relevant indicators.
The results of the study of the coagulation hemostasis obtained in patients after surgery on the spleen in the long term period of time comparing to the control group has been presented in Table 1.
