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9первично заболевших 14,7 % операций в группе трудоспособного возраста и 85,3% - старше трудоспособного. При этом осложнения после операции составляли 1,3 % в первой из указанных групп и 0,8 %-во второй.
Литература
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2. Яблонская Л.Я. Современные тенденции заболеваемости болезнями глаз и пути совершенствования организации
офтальмологической помощи в субъекте Российской Федерации: Дис. канд. мед. наук. -Екатеринбург, 2006.- С. 132.
3. Нарушения зрения и слепота. Информационный бюллетень N282 ВОЗ. Август 2014 г.
4. Либман Е.С., Шахова Е.В., Чумаева Е.А. Глаукома как медико-социальная проблема // Глаукома: Сб. науч. тр.- М., 1998.- Вып. 3.- С. 5-11
5. Кузнецов НС. Актуальные вопросы повреждений и заболеваний глаз / ИС. Кузнецов, Л.В. Зюзина. Ижевск, 1984. - С. 61 - 62.
METABOLIC EFFECTS OF METFORMIN IN PATIENTS WITH TYPE 2
DIABETES AND HYPOTHYROIDISM
Yuzvenko T.
Ukrainian Research and Practical Centre of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues, Health
Ministry of Ukraine, Kyiv
ABSTRACT
Background. Since metformin improves insulin sensitivity, it has been indicated for patients with type 2 diabetes mellitus (DM), which have insulin-resiflant conditions. In contrafl to its well-known effects on carbohydrate me-tabolism, its potential for reducing thyroid Simulating hormone (TSH), blood pressure have been invefligated less frequently.
Aim of the fludy is to characterize the interplay between metformin and circulating thyroid function parameters by evaluating thyroid hormone axes in different categories of patients who were on metformin treatment.
Patients and Methods. This fludy was conducted with 22 type 2 diabet-ic patients with hypothyroidism who were on flable LT4 subflitution (average dose 87.6±11.2 ^g/day) to examine the short- to mid-term (up to 26 weeks) effects of metformin adminiflra-tion. Serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3) were measured at baseline as well as after 3 and 6 months of therapy. The next fludy was performed in a larger cohort of type 2 diabetic patients including 32 euthyroid patients on levothyroxine (LT4) subflitution (group I), 21 patients with subclinical hypothyroidism who did not receive LT4 treatment (group II), and 52 eu-thyroid patients in whom thy-roid disorders had been excluded.
Results. There were no changes of fT4, and fT3 observed throughout the fludy. Overall, a modefl reduction of baseline TSH values (from 2.14±0.54 to 1.82±0.32 mIU/l, p>0.05) was observed after 6 months of metformin treat-ment. A significant decrease of TSH levels after 6 months of metformin treat-ment was observed in group I and group II subjects but not in group III sub-jects. In detail, mean TSH level was significantly reduced after 6 months on metformin in group I, from 2.36±1.16 mIU/l at baseline to 1.42±1.23 (p< 0.001). Mean basal TSH level in patients of group II was 4.51±0.36 mIU/l and significantly decreased to 2.97±0.46 mIU/l after 6 months of metformin (p < 0.001); TSH reduction never reached subnormal levels in individual patients of this group. Serum fT4 levels did not significantly change during metformin treatments in any group.
Conclusions. Metformin adminiflration in diabetic patients with hypo-thyroidism is associated with a significant reduction in the serum levels of TSH, with no change in fT4. A major clinically relevant consequence of our findings is that a reevaluation of thyroid function within 6 months after flart-ing metformin seems necessary in diabetic patients with concomitant hypothy-roidism.
Keywords: type 2 diabetes mellitus, hypothyroidism, metformin.
Background
Metformin is a widely used drug for the treatment of type 2 diabetes mellitus [1-3]. It is commonly regarded as a safe drug in that no clinically rele-vant pharmacologic interactions have been described when it is prescribed to-gether with the mofl commonly used drugs [4]. Since metformin improves in-sulin sensitivity, it has been indicated for patients with type 2 diabetes mellitus (DM), which have insulin-resiflant conditions. In contrafl to its well-known effects on carbohydrate metabolism, its potential for reducing thyroid flimulat-ing hormone (TSH), blood pressure and its effect on leptin levels have been invefligated less frequently [5]. Recently it has been reported that metformin is able to interfere with thyroid hormone profile, as shown by a decrease in the serum levels of thyrotropin (TSH) to subnormal levels in hypothyroid patients in flable levothyroxine (LT4) treatment [6]. However, no data are available for untreated hypothyroid patients or for euthyroid diabetic patients. Both met-formin treatment and hypothyroidism are frequent occurrences in diabetic pa-tients [7].
Aim of the fludy is to characterize the interplay between metformin and circulating thyroid function parameters by evaluating thyroid hormone axes in different categories of patients who were on metformin treatment.
Patients and Methods
This fludy was conducted with 22 type 2 diabetic patients with hypo-thyroidism who were on flable LT4 subflitution (average dose 87.6±11.2 ^g/day) to examine the short- to mid-term (up to 26 weeks) effects of metfor-min adminiflration. Serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3) were measured at baseline as well as after 3 and 6 months of therapy. The next fludy was performed in a larger cohort of type 2 diabetic patients includ-ing 32 euthyroid patients on LT4 subflitution (group I), 21 patients with sub-clinical hypothyroidism who did not receive LT4 treatment (group II), and 52 euthyroid patients in whom thyroid
disorders had been excluded based on clin-ical hiflory, physical examination, measurement of serum fT4, fT3, TSH, and TPO-Antibody, as well as thyroid ultrasonography (group III). All subjects gave their informed consent to the fludy, which was performed in accordance with the Declaration of Helsinki.
Between- and within-group comparisons were performed by an ANOVA general linear model, including repeated-measures analysis (SPSS version 11; SPSS, Evanflon, IL). A p value <0.05 was considered Satirically significant.
Results
There were no changes of fT4, and fT3 observed throughout the fludy. Overall, a modefl reduction of baseline TSH values (from 2.14±0.54 to 1.82±0.32 mIU/l, p>0.05) was observed after 6 months of metformin treat-ment. Clinical characteriflics and mofl relevant data in the three groups of pa-tients are summarized in Table 1.
Table 1
Demographic data, treatment and thyroid function in the three groups of type 2 dia-betic patients
Group I Group II Group III
BMI (kg/m2)
Baseline 32.4±5.2 31.4±4.8 33.1±4.7
After 6 months on metformin 31.9±5.6 30.8±4.7 32.6±4.6
TSH (mIU/l)
Baseline 2.36±1.16 4.51±0.36* 2.73±0.81
After 6 months on metformin 1.42±1.23** 2.97±0.46** 2.54±1.14
fT4 (pg/ml)
Baseline 12.47±2.08 12.52±2.07 12.84±1.92
After 6 months on metformin 12.69±2.11 12.23±1.81 13.07±2.21
Data are means ± SD. Between-group differences: *p < 0.001 for group I vs. group III. Within-group differences: **p < 0.001 for on treatment vs. baseline.
A significant decrease of TSH levels after 6 months of metformin treat-ment was observed in group I and group II subjects but not in group III sub-jects. In detail, mean TSH level was significantly reduced after 6 months on metformin in group I, from 2.36±1.16 mIU/l at baseline to 1.42±1.23 (p< 0.001).
Mean basal TSH level in patients of group II was 4.51±0.36 mIU/l and significantly decreased to 2.97±0.46 mIU/l after 6 months of metformin (p < 0.001); TSH reduction never reached subnormal levels in individual patients of this group. Serum fT4 levels did not significantly change during metformin treatments in any group.
Discussion
The results of this fludy showed that treatment with metformin was as-sociated with a significant reduction in the serum levels of TSH in diabetic pa-tients with primary hypothyroidism; TSH reduction was not associated with reciprocal changes in any other thyroid function parameter; the TSH-lowering effect of metformin developed slowly and was detectable after a few months of treatment; and metformin had no effect on circulating thyroid function parame-ters in euthyroid diabetic patients. This is a clinically relevant observation, es-pecially when considering that hypothyroidism occurs in 10-15% of type 2 di-abetic patients [8] and many of them are presumably also treated with metfor-min.
The mechanisms by which metformin lowers TSH level is ¿till unclear, and the design of the present fludy does not allow drawing causal inferences. However, the present data would exclude biological interferences of metformin with the TSH assay, increased LT4 absorption from the gaflrointeflinal tract, or any influence of changes in body weight associated with metformin treat-ment.
We hypothesize that metformin may enhance the inhibitory modulation of thyroid hormones on central TSH secretion. Another explanatory hypothe-sis could be that metformin ameliorates the thyroid function reserve in those patients with hypothyroidism both treated and untreated. Future fludies
will be needed to fully elucidate the mechanisms of the here-described TSH-lowering effect of metformin. Conclusions
The results of this fludy show that metformin adminiflration in diabetic patients with hypothyroidism is associated with a significant reduction in the serum levels of TSH, with no change in fT4. No effect is detectable in patients with an intact pituitary-thyroid axis. A major clinically relevant consequence of our findings is that a reevaluation of thyroid function within 6 months after Parting metformin seems necessary in diabetic patients with concomitant hy-pothyroidism.
No potential conflicts of interefl relevant to this article were reported.
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