Tesis

Korelasi Lipotoksisitas dengan Resistensi Insulin dan Disfungsi Sel β Pankreas pada Pasien Diabetes Melitus Tipe 2 Awitan Muda = Association of Lipotoxicity with Insulin Resistance and Pancreatic β-Cell Dysfunction Among Patients with Early-Onset Type 2 Diabetes Mellitus.

Latar Belakang: Diabetes melitus (DM) tipe 2 awitan muda memiliki karakteristik patofisiologi yang khas, termasuk disfungsi sel β yang lebih cepat dan resistensi insulin yang menonjol, terutama pada kondisi obesitas. Lipotoksisitas, akibat akumulasi lemak ektopik dan gangguan fungsi jaringan adiposa, diketahui berperan dalam terjadinya resistensi insulin dan disfungsi sel β. Namun, peran lipotoksisitas pada DM tipe 2 awitan muda belum banyak diteliti. Tujuan: Mengetahui hubungan antara lipotoksisitas, yang dinilai melalui visceral adiposity index (VAI) dan lipid accumulation product (LAP), dengan resistensi insulin (homeostasis model assessment of insulin resistance; HOMA-IR) dan fungsi sel β (homeostasis model assessment of β-cell function; HOMA-β) pada pasien DM tipe 2 awitan muda. Metode: Penelitian ini merupakan studi potong lintang yang menggunakan data dasar dari registri studi Genomik di RS Cipto Mangunkusumo (September 2022– Desember 2023). Subjek penelitian sebanyak 135 pasien DM tipe 2 dengan usia awitan ≤40 tahun dan tidak menggunakan insulin. VAI dan LAP dihitung berdasarkan data antropometri dan biokimia. HOMA-IR dan HOMA-β dihitung dari kadar glukosa dan insulin puasa. Analisis korelasi dan regresi linier berganda dilakukan dengan penyesuaian faktor perancu. Hasil: VAI dan LAP menunjukkan korelasi positif signifikan dengan HOMA-IR (r = 0,33 dan r = 0,47; p < 0,001), yang mencerminkan korelasi lemah hingga sedang dengan resistensi insulin. Faktor-faktor selain lipotoksisitas kemungkinan berkontribusi terhadap proses resistensi insulin. Tidak ditemukan korelasi signifikan antara VAI maupun LAP dengan HOMA-β. Analisis multivariat menunjukkan bahwa hubungan antara VAI/LAP dengan HOMA-IR tidak dipengaruhi oleh jenis kelamin, durasi DM, riwayat keluarga, kadar LDL, atau obat antidiabetes. Simpulan: Lipotoksisitas yang dinilai melalui VAI dan LAP berkorelasi dengan resistensi insulin, namun tidak dengan disfungsi sel β pada DM tipe 2 awitan muda.
Kata kunci: Diabetes melitus tipe 2 awitan muda; lipotoksisitas; visceral adiposity index; lipid accumulation product; resistensi insulin; disfungsi sel β


Background: Early-onset type 2 diabetes mellitus (T2DM) presents distinct pathophysiological characteristics, including accelerated β-cell dysfunction and prominent insulin resistance, often in the context of obesity. Lipotoxicity, resulting from ectopic fat accumulation and impaired adipose tissue function, is believed to contribute to both insulin resistance and β-cell dysfunction. However, its role in early-onset T2DM remains understudied. Objective To examine the association between lipotoxicity, assessed by visceral adiposity index (VAI) and lipid accumulation product (LAP), with insulin resistance (homeostasis model assessment of insulin resistance; HOMA-IR) and β- cell function (homeostasis model assessment of β-cell function; HOMA-β) in patients with early-onset T2DM. Methods: This was a cross-sectional study using baseline data from the Genomic Study registry at Dr. Cipto Mangunkusumo Hospital (September 2022–December 2023). Subjects included 135 patients diagnosed with T2DM at age ≤40 years and not on insulin therapy. VAI and LAP were calculated from anthropometric and biochemical parameters. HOMA-IR and HOMA-β were derived from fasting glucose and insulin levels. Correlation and multiple linear regression analyses were conducted, adjusting for potential confounders. Results: VAI and LAP showed significant positive correlations with HOMA-IR (r = 0.33 and r = 0.47, respectively; p < 0.001), indicating a weak and moderate correlation with insulin resistance. Factors other than lipotoxicity may contribute to the development of insulin resistance. No significant correlations were found between either VAI or LAP and HOMA-β. Multivariate analysis showed that the associations between VAI/LAP and HOMA-IR were not confounded by sex, diabetes duration, family history, LDL levels, or antidiabetic medications. Conclusions: Lipotoxicity, as assessed by VAI and LAP, is associated with insulin resistance but not β-cell dysfunction in early-onset T2DM.
Keywords: Early-onset type 2 diabetes mellitus; lipotoxicity; visceral adiposity index; lipid accumulation product; insulin resistance; β-cell dysfunction