Thiazolidinedionese di Macam 2 penyakit gula

THIAZOLIDINEDIONES IN TYPE 2 PENYAKIT GULA

Kelas obat dikenal sebagai thiozolidinedionese secara luas dipakai sebagai sebagian kontra-perlakuan kencing manis (Mereda, 2001). Yang ini termasuk rosiglitazone, pioglitazone dan troglitazone yang dipakai untuk pengobatan non insulin penyakit gula tergantung mellitus. Agen ini bertindak dengan menjadikan perlawanan insulin sebagai sasaran lebih baik daripada merangsang insulin pengeluaran dengan bergaul dengan gamma sub-macam peroxisome berkembangbiak menggiatkan receptor (PPAR-y2). PPAR-Y, seorang anggota yang nuklir receptor sub-keluarga, merangsang perasaan gen protein yang dilibatkan di metabolisme glukosa (Lehman et al, 1998). Ini menghasilkan pertambahan di insulin kehalusan perasaan di kerangka otot, hati, dan adipose kertas tisu (Kumar et al, 1996). Obat pertama di kelas ini untuk disetujui di Amerika Serikat ialah troglitazone pada 1997. Sedangkan troglitazone menawarkan keuntungan klinis yang berarti kepada banyak pasien kencing manis, dihubungkan dengan ketinggian serum alanine aminotransferase di kira-kira 1-2% pasien dan di kasus langka, hepatic kegagalan dan ialah oleh karena itu ditarik kembali dari pasar pada 2000. Berikut sampai peluncuran troglitazone, dua lain thiozolidinedione obat pengganti memasuki pasar, rosiglitazone dan pioglitazone.

Macam 2 penyakit gula

Sifat utama macam 2 penyakit gula memasukkan penggunaan cacat glukosa dan perlawanan sampai kemampuan insulin untuk merangsang penyerapan glukosa dan pembuangan di kertas tisu. Ketidaktoleranan glukosa di macam 2 penyakit gula ditunjukkan oleh berbalik muka di angkutan glukosa ke dalam otot dan adipose kertas tisu. Di adipose kertas tisu dari subyek kencing manis, angkutan glukosa cacat sudah diperlihatkan untuk menghasilkan dari dikurangi komplemen dirangsang dengan insulin GLUT4 (glukosa yang diatur dengan insulin transporter isoform) di genangan-genangan intraseluler. Insulin receptor tyrosine kinase secara aktif juga dihalangi di adipocytes gemuk sekali macam 2 subyek kencing manis. Baik perasaan maupun dirangsang dengan insulin phosphorylation IRS-1 (insulin receptor substrates-1) dikurangi di adipose kertas tisu dari subyek kencing manis. Peristiwa di hilir IRS-1 juga terkena dampak, sebagai perangsangan insulin PI3k (phosphatidylinositol 3 kinase) aktivitas dan phosphorylation Akt dihalangi. Dengan begitu, adipose perlawanan insulin kertas tisu di macam 2 penyakit gula melibatkan berbalik muka di baik jalan setapak pemberian isyarat insulin maupun terakhir effector sistem, i.e., glukosa transporters.

Terapi

Sejumlah pendekatan terapi sudah ternyata berguna dalam menguasai hyperglycemia dan memperbaiki tindakan insulin di macam 2 pasien penyakit gula. Yang ini memasukkan penggunaan kehilangan berat, sulfonylureas, biguanides seperti metaformin, dan thiazolidinediones. Lebih baru-baru ini terapi kombinasi sudah dipakai dengan meningkat frekuensi dan keefektifan. Thiazolidinediones dipakai dengan diet dan penggunaan untuk mengobati orang dengan macam 2 penyakit gula, sendiri atau di kombinasi dengan obat lain. Mereka menurunkan gula darah dengan menolong sel badan mempergunakan insulin lebih efisien untuk menyingkirkan gula kelebihan dari darah. Efek kombinasi thiazolidinediones (TZDs) dan metformin sudah terbukti maksimum tyrosine phosphorylation insulin receptor (IR) dan insulin receptor substrate-1 (IRS-1) mencapai. Penyerapan glukosa secara signifikan tinggi di kombinasi konsentrasi lebih rendah. Meskipun diet, berat kehilangan, dan penggunaan tetap huruf awal yang paling impor berjalan di pimpinan macam 2 penyakit gula, karena terkena orang biasanya kelebihan berat. Terapi Pharmacological wajib bagi pasien yang tak dapat untuk mencapai glycemic menguasai dengan modifikasi gaya hidup atau yang mempunyai gejala berarti pada saat diagnosa.

Thiazolidinediones

Thiazolidinediones are the drug presently used in treatment of type2 diabetes. Various studies suggests good side of its effectiveness in controlling hyperglycemia but there are even side effects reported which inhibits many of the physician to fully accept this as drug of today in treatment of non insulin dependent diabetes mellitus. Although majority of the clinician still suggests the treatment with thiazolidinedionese. Only thiazolidinediones (TZDs) have been shown to consistently improve estimates of beta cells function. The TZDs are able to provide durable glycemic control. TZDs have also been found to reduce inflammatory markers, improve vascular function and lipid profiles and decrease blood pressure in patients with type 2 diabetes, which may improve long term cardiovascular outcomes.

Currently two thiazolidinediones, rosiglitazone and pioglitazone are approved in US for treatment of type 2 diabetes. Rosiglitazone is approved for monotherapy and for use in combination therapy with metformin or sulfonylureas. Pioglitazone is approved for monotherapy as well as for use in combination therapy with metformin, insulin or sulfonylureas. But the most serious effect is said to have is hepatotoxicity. Although, rosiglitazone and pioglitazone were not associated with hepatotoxicity in pre-marketing clinical trial. However, post clinical trial and marketing data suggests that a TZD should generally not be used as monotherapy, until evidence is available showing its superiority.

There is growing concern and one of the many suggestion concluded that, thiozolidindiones can cause or exacerbate heart failure and pulmonary oedema and should be avoided in patients with left ventricle dysfunction or chronic renal insufficiency. At present, there is little evidence to suggest such a direct negative effect of TZDs on cardiac performance, and in most patients fluid retention appears to be independent of baseline cardiac function. A recent examining the use of TZDs in patients with diabetes who had established chronic heart failure discovered with fluid retention in 17% ( predominantly peripheral, not central), and there was no direct association between the risk of fluid retention and the severity of heart failure while these patients were taking TZDs.

However there is a growing evidence to suggest that TZDs may have many positive side effects on cardiac functions including diminished vascular resistance, improved cardiac metabolism, positive intropic effect, coronary vasodialation, increased natriuretic peptide production, improved endothelial function, and attenuation of cytokines. All these effects may possibly prevent HF in patients with diabetes, especially if TZDs are used before cardiac dysfunction develops. One of the studies conducted represents the first demonstration of the anti-atherogenic effect of pioglitazone in both nonrespondents and responders and responders with respect to its antidiabetic effect and suggest that pioglitazone can exert its anti-athergenic effect independently of its antidiabetic effect. Rosiglitazone and pioglitazone are also contraindicated in pregnancy and lactation and have not been tested in children. In woman with polycystic ovarian syndrome with insulin resistance, treatment with these drugs may restore ovulation.

The use of conventional medications such as sulfonylureas or insulin to lower HbA1c levels may lead to hypoglycemia. Additionally, the UKPDS showed that these agents do not maintain durable glycemic control when used alone. The potential to achieve target HbA1c levels without producing hypoglycemia makes TZDs offer a variety of benefits that support early use in the management of type 2 diabetes. They effectively lower glucose levels, improve insulin sensitivity, preserve beta cell function, and may exert beneficial cardiovascular effects. The UKPDS showed that the lower the HbA1c level, the lower the risk for long term complication.

The treatment of diabetics has advanced greatly during the past few years with a better understanding of the disease itself and development of new medications. Unfortunately, many patients are still unable to maintain glycemic control because of inappropriate treatment or inability to follow an appropriate diet or pharmacological regimen. This combined with the progression of the disease, leads to development of multiple complications including cardiovascular disease, which is the leading cause of death in patients with diabetes.

Currently there are several classes of drugs that are used to manage type 2 diabetes. However, only thiazolidinediones(TZDs) have been shown to consistently improve estimates of beta cells function, the TZDs are able to provide durable glycemic control The TZDs also been found to reduce inflammatory markers, improve vascular function and lipid profiles and decrease blood pressure in patients with type 2 diabetes, which may improve long term cardiovascular outcomes. The effectiveness of these agents in cardiovascular surrogate markers makes the TZDs particularly appealing as a pivotal treatment option and suggests that they be considered a cornerstone of therapy in the management of type 2 diabetes.


The dramatic increase in the number of classes of oral antidiabetic agents has provided physicians with more tools to help patients manage type 2 diabetes, of course glycemic control must remain paramount when choosing an oral agent. However, the mechanism of action of an agent, its side effect profile, and the potential for various non glycemic benefits may help determine which one is the best drug for an individual patient The evidence and practice though presently indicates that there are more dependence and majority has choice for thiazolidinediones in type 2 diabetes treatment than any other drug. The use of these drugs moreover remains in the hands of physicians whether to go for monotherapy or in combination, based on the evidences and conditions of the patients.