Yeterli kan şeker regülâsyonu sağlanamayan tip 1 diabetes mellituslu hastalarda insülin ile roziglitazon kombinasyon tedavisinin kan şeker regülâsyonu, inflamasyon parametreleri, serbest yağ asitleri ve serum adipositokin düzeyleri üzerine etkinliğinin incelenmesi
Loading...
Date
2009
Authors
Güçlü, Metin
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Yeterli glisemik kontrol sağlanamayan tip 1 diyabetik hastaların bir kısmında insulin direncinin de olabileceği ve bu durumun tedaviye istenen yanıtların alınmasını engelleyebileceği düşünülmektedir. Çalışmamızın amacı; yoğun insülin tedavisine rağmen yeterli kan şeker regülâsyonu sağlanamamış hastalarda, roziglitazon ile insülin kombinasyonun, kan şeker regülâsyonu, metabolik parametreler, serbest yağ asitleri, günlük toplam insülin ihtiyacı, inflamasyon göstergeleri ve adipositokin düzeyleri üzerine olan etkilerinin 18 hafta süreyle prospektif olarak incelenmesidir. Araştırmamıza 18- 65 yaş arasında, beden kitle indeksi (BKİ) >27 kg/m2 ve/veya >40 Ü/gün yoğun insulin tedavisi alırken glikozile hemoglobin (A1c) >%6,5 olan, kalp yetmezliği, kronik karaciğer ve böbrek hastalığı olmayan, uygun yaşam tarzı değişiklikleri ve etkin tıbbi beslenme tedavisi uygulamayı kabul eden, 61 tip 1 diyabetik hasta alındı. Hastalar yaş, hastalık süresi, vücut ağırlığı (VA), BKİ ve başlangıç A1c düzeyleri açısından benzer olacak şekilde, açık etiketli olarak, yoğun insülin tedavisine 4 mg/gün roziglitazon eklenen hastalar grup 1 (n=30) ve tek başına yoğun insülin tedavisine devam eden hastalar grup 2 (n=31) olarak randomize edildiler. Akut metabolik komplikasyon dışında, sabit doz insülin tedavisini sürdürmeleri istenen hastalar, 18 haftada toplam 4 vizitte, fizik muayene, glisemik kontrol, tedavi değişiklikleri, gelişebilecek komplikasyonlar ve istenmeyen ilaç etkileri açısından yakın takibe alındılar. Her bir grupta araştırmayı tamamlayan 28 hastada VA ve BKİ açısından istatistiksel olarak anlamlı artış olmasına ragmen, bel çevresi (BÇ) ve bel kaça oranı (BKO) açısından anlamlı bir değişim izlenmedi. Birinci gruptaki hastalarda ortalama 2,58±3,10 (p<0,05), ikinci grupta 1,47±1,53 (p<0,001) kilo artışı oldu. Sistolik kan basıncı (SKB), diyastolik kan basıncı (DKB) ve nabız dakika sayısı açısından sadece grup 2'de SKB değişiklikleri istatistiksel olarak anlamlıydı. İlk grupta açlık kan şekeri (AKŞ) ölçümleri ortalama 30 mg/dl, A1c %0,11 azalırken (p>0,05), ikinci grupta AKŞ ortalama 45mg/dl (p=0,006), A1c %0,29 (p=0,05) azaldı Renal fonksiyonlar, albumin kreatinin oranı, apartat amino transferaz (AST) ve alanin amino tarnsferaz (ALT) düzeylerinde anlamlı sayılabilecek bir değişiklik bulunamadı. İki grupta da total kolesterol (T Kol), LDL Kol ve serbest yağ asitleri (SYA) düzeyleri azalırken, HDL Kol düzeyleri artmış, trigliserid (TG) düzeyleri grup 1'de hafif azalmış, grup 2 'de hafif artmış olarak bulundu. Bu değişimler sadece ikinci grupta bulunan hastalarda HDL K değişimi açısından istatistiksel olarak anlamlı (p=0,038) iken diğer parametrelerde anlamlı fark yoktu. Sadece Grup 1'de Hgb ve fibrinojen düzeyi istatistiksel olarak anlamlı düşüş gösterirken PLT sayısı ise artmış olarak bulundu. Eritrosit sedimentasyon hızı (ESH) ve highly sensitive-C reaktif protein (hs-CRP) düzeyleri hem grup içinde hem de gruplar arasında anlamlı değişim göstermedi. Her iki grupta da rezistin ve leptin düzeylerinde anlamlı derecede azalma, adiponektin düzeylerinde ise anlamlı olmayan bir artış ortaya çıktı. Vizitlerden 7 gün önce 8 nokta ve 3 gün önce 3 öğün açlıkta alınan kan şekeri ölçümleri ve bu dönemde uygulanan insülin dozlarında gerek grup içinde gerekse de gruplar arasında istatistiksel olarak anlamlı değişim izlenmedi. İlk grupta iki hastada majör hipoglisemik atak, ikinci grupta iki hastada ise diyabetik ketoasidoz gelişti. İlk grupta hasta başına ortalama 5,35, ikinci grupta ise 4,61 minör hipoglisemik olay yaşandı (p=0,437). Sonuç olarak; değerlendirme parametrelerimizden sadece fibrinojen ve adiponektin düzeyleri açısından gruplar arasında roziglitazon lehine anlamlı etki farkı görülmüş, ancak hastaların vücut ağırlığı artmış, insülin duyarlılığında anlamlı bir değişiklik izlenmemiş ve hipoglisemi sıklığı azalmamıştır. Roziglitazonun olumlu etkilerinin tip 1 diyabetik hastalarda görülmemesi bu ilaçların ancak endojen hiperinsülinizm varlığında etkin olabileceğini düşündürmektedir.
Investigation of The Effects of Rosiglitazone and Insulin Combination Therapy on Glycemic Control, Inflammation Parameters, Free Fatty Acids and Serum Adipocytokine Levels in Type 1 Diabetic Patients in Whom Adequate Glycemic Regulation could not be Achieved It is suggested that in some patients with type 1 diabetes in whom adequate glycemic regulation could not be achieved insulin resistance may be present and this stiuation may prevent adequate response to the treatment The aim of our study is to prospectively investigate for 18 weeks, the effect of rosiglitazone and insulin combination therapy on glycemic regulation, metabolic parameters, free fatty acids (FFA), total daily insulin (TDI) requirement inflammation markers and serum adipocytokine levels in type 1 diabetic patients with inadequate glycemic regulation in spite of intensive insulin treatment, . Sixty-one type 1 diabetic patients who agree to do suitable life style changes and effective medical nutrition treatment and ages between 18–65 years, body mass indexes (BMI) > 27kg/m2 and/or daily insulin requirement>40U per day, glycosilated hemoglobin (A1c) >6,5%, with no history or findings of heart failure, liver and kidney disease were included to our study. The patients were randomized as open label into two groups, as having similar patients characteristics concerning age, duration of the disease, body weight (BW), BMI and initial A1c levels, as group 1 (n=30) 4 mg/day rosiglitazone combined with intensive insulin treatment (IIT) and group 2 (n=31) continuing IIT alone. In total of 4 visits during 18 week, the patients continued to their stable insulin doses, unless new acute metabolic complications develop, and all patients were followed for glycemic control, treatment changes, development of complications and adverse drug reactions. In both groups 28 patients completed the study and although there were statistically significant increases in BW and BMI there was no significant difference in waist circumfrences (WC) and waist to hip ratio (WHR) in both groups. Mean weight gain was 2,58±3,10 (p<0.05) in the first group and 1,47±1,53 (p<0,001) in the second.group. From the point of heart rate, sistolic (SBP) and diastolic blood pressure (DBP) there were significant SBP changes only in group 2. While mean fasting blood glucose (FBG) decreased by 30 mg/dl and A1c by %0,11 in group 1 (both p value >0,05), FBG decreased by 45 mg/dl (p=0,006), A1c by % 0,29 (p=0,05) in group 2. There were no statistically significant changes in kidney functions, albumin creatinin ratio in spot urine, aspartate amino transferase (AST) and alanine amino transferase (ALT). Total cholesterol (T Chol), LDL C and FFA levels found to be decreased and HDL C levels as increased in both groups while triglyceride (TG) levels were slightly decreased in group 1, slightly increased in group 2. These changes were statistically significant only for HDL levels in group 2 (p=0,038) but not for other parameters. Hemoglobin and fibrinojen levels were found to be decreased and platelet count increased statistically significantly only in group 2. Levels of erytrocyte sedimantation rate (ESR) and highly sensitive C reactive protein (hs-CRP) were not showed any significant changes in and between both groups. Resistin and leptin levels decreased significantly and adiponectin levels increased insignificantly in both groups. There were no statistically significant changes in total insulin doses during study period and mean blood glucose measurements (SBGM) taken at 8-point on 7 days and three meals fasting on three days before every visit, neither in groups nor between the groups. There were major hypoglycemic attack in two patients in group 1 and two keto asidosis in group 2. Mean minör hypoglycaemia per patient was 5,35 in the first group and 4,61 in the second group (p=0,437). In summary; there were slightly favor treatment effects for rosiglitazone on only fibrinogen and adiponectin levels. however patients weight were increased, no significant improvement was acheived on insulin resistance and frequency of hypoglycemia didn't decrease. The fact that the positive effects of rosiglitazone could not be seen in type 1 diabetic patients in our study suggested that these drugs may be effective only in the presence of endogenous hyperinsulinism.
Investigation of The Effects of Rosiglitazone and Insulin Combination Therapy on Glycemic Control, Inflammation Parameters, Free Fatty Acids and Serum Adipocytokine Levels in Type 1 Diabetic Patients in Whom Adequate Glycemic Regulation could not be Achieved It is suggested that in some patients with type 1 diabetes in whom adequate glycemic regulation could not be achieved insulin resistance may be present and this stiuation may prevent adequate response to the treatment The aim of our study is to prospectively investigate for 18 weeks, the effect of rosiglitazone and insulin combination therapy on glycemic regulation, metabolic parameters, free fatty acids (FFA), total daily insulin (TDI) requirement inflammation markers and serum adipocytokine levels in type 1 diabetic patients with inadequate glycemic regulation in spite of intensive insulin treatment, . Sixty-one type 1 diabetic patients who agree to do suitable life style changes and effective medical nutrition treatment and ages between 18–65 years, body mass indexes (BMI) > 27kg/m2 and/or daily insulin requirement>40U per day, glycosilated hemoglobin (A1c) >6,5%, with no history or findings of heart failure, liver and kidney disease were included to our study. The patients were randomized as open label into two groups, as having similar patients characteristics concerning age, duration of the disease, body weight (BW), BMI and initial A1c levels, as group 1 (n=30) 4 mg/day rosiglitazone combined with intensive insulin treatment (IIT) and group 2 (n=31) continuing IIT alone. In total of 4 visits during 18 week, the patients continued to their stable insulin doses, unless new acute metabolic complications develop, and all patients were followed for glycemic control, treatment changes, development of complications and adverse drug reactions. In both groups 28 patients completed the study and although there were statistically significant increases in BW and BMI there was no significant difference in waist circumfrences (WC) and waist to hip ratio (WHR) in both groups. Mean weight gain was 2,58±3,10 (p<0.05) in the first group and 1,47±1,53 (p<0,001) in the second.group. From the point of heart rate, sistolic (SBP) and diastolic blood pressure (DBP) there were significant SBP changes only in group 2. While mean fasting blood glucose (FBG) decreased by 30 mg/dl and A1c by %0,11 in group 1 (both p value >0,05), FBG decreased by 45 mg/dl (p=0,006), A1c by % 0,29 (p=0,05) in group 2. There were no statistically significant changes in kidney functions, albumin creatinin ratio in spot urine, aspartate amino transferase (AST) and alanine amino transferase (ALT). Total cholesterol (T Chol), LDL C and FFA levels found to be decreased and HDL C levels as increased in both groups while triglyceride (TG) levels were slightly decreased in group 1, slightly increased in group 2. These changes were statistically significant only for HDL levels in group 2 (p=0,038) but not for other parameters. Hemoglobin and fibrinojen levels were found to be decreased and platelet count increased statistically significantly only in group 2. Levels of erytrocyte sedimantation rate (ESR) and highly sensitive C reactive protein (hs-CRP) were not showed any significant changes in and between both groups. Resistin and leptin levels decreased significantly and adiponectin levels increased insignificantly in both groups. There were no statistically significant changes in total insulin doses during study period and mean blood glucose measurements (SBGM) taken at 8-point on 7 days and three meals fasting on three days before every visit, neither in groups nor between the groups. There were major hypoglycemic attack in two patients in group 1 and two keto asidosis in group 2. Mean minör hypoglycaemia per patient was 5,35 in the first group and 4,61 in the second group (p=0,437). In summary; there were slightly favor treatment effects for rosiglitazone on only fibrinogen and adiponectin levels. however patients weight were increased, no significant improvement was acheived on insulin resistance and frequency of hypoglycemia didn't decrease. The fact that the positive effects of rosiglitazone could not be seen in type 1 diabetic patients in our study suggested that these drugs may be effective only in the presence of endogenous hyperinsulinism.
Description
Keywords
Tip 1 diyabet, İnsülin direnci, Roziglitazon, Metabolik kontrol, İnflamasyon, Adipositokin, Type 1 diabetes, Insulin resistance, Rosiglitazone, Metabolic control, Inflammation, Adipocytokine
Citation
Güçlü, M. (2009). Yeterli kan şeker regülâsyonu sağlanamayan tip 1 diabetes mellituslu hastalarda insülin ile roziglitazon kombinasyon tedavisinin kan şeker regülâsyonu, inflamasyon parametreleri, serbest yağ asitleri ve serum adipositokin düzeyleri üzerine etkinliğinin incelenmesi. Yayınlanmamış uzmanlık tezi. Uludağ üniversitesi Tıp Fakültesi.