Acylcarnitine suppression test: a novel method for the early diagnosis of insulin resistance
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Date
2020
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Ievads
Insulīna rezistence ir viena no svarīgākajām 2. tipa cukura diabēta patoģenēzes sastāvdaļām. Insulīna rezistencei ir saikne arī ar arteriālu hipertensiju un dislipidēmiju. Agrīnai insulīna rezistences nodrošina laicīgu un veiksmīgu ārstēšanu. Pašlaik pieejamās diagnostiskās metodes nav spējīgas noteikt agrīnu insulīna rezistenci, jo to pamatā ir glikozes un C-peptīda koncentrāciju izvērtēšana. Pētot dzīvniekus, kuriem ir adipozitāte un diabēts atklāta saikne starp acilkarnitīnu metabolismu un insulīna rezistenci. Iepriekšējos pētījumos atklāts, ka šūnas, kurās notiek acilkarnitīnu uzkrāšanās ir mazāk jūtīgas pret insulīnu. Mēs piedāvājam plazmas acilkarnitīnu postprandiālās nomākšanas testu kā metodi agrīnai insulīna rezistences noteikšanai.
Mērķis
Izveidot modeli plazmas acilkarnitīnu nomākšanas testam un izvērtēt tā potenciālu agrīnas insulīna rezistences izvērtēšanai.
Metodes
Pētījumā tika iekļauti 23 pieauguši brīvprātīgie, kuru ķermeņa masas indekss (ĶMI) ir >25 kg/m2. Paraugi laboratorai izvērtēšanai tika ievākti bada periodā un 2 stundas pēc maltītes, kas saturēja 36 g ogļhidrātu. Paraugos tika izvērtētas koncentrācijas glikozei, C-peptīdam, kā arī īsķēžu (C2-C4), vidējo ķēžu (C5-C12) un garķēžu (C14-C18:2) plazmas acilkarnitīniem. Papildus tika iegūts brīvprātīgo vecums, augums un svars. Insulīna rezistences indekss tika iegūts izmantojot Oksfordas Universitātes piedāvāto HOMA2-IR modeli, tajā ievietojot badošanās laikā iegūtās glikozes un C-peptīda plazmas koncentrācijas. HOMA2-IR indekss >1,8 tika uzskatīts par insulīna rezistences stāvokli. Datu statistiskā apstrāde tika veikta ar IBM SPSS v22. Pētījumā izmantotās analītiskās statistikas metodes: Pīrsona korelācija un neatkarīgais t-tests. Iegūtie rezultāti tika uzskatīti par statistiski nozīmīgiem, ja p<0,05.
Rezultāti
Vidējais svars iekļautajiem dalībniekiem bija 94,1 kg (Standartnovirze (SD)±12,0). Vidējais ĶMI bija 31,81 (SD±3,95). Vidējais HOMA2 insulīna rezistences indekss bija 2,50 (SD±1,67). 14 no 23 dalībniekiem tika atklāts insulīna rezistences stāvoklis (HOMA2-IR >1,8). Jo augstāks bija HOMA2 insulīna rezistences indekss, jo mazāks bija postprandiālais koncentrācijas nomākums sekojošajiem acilkarnitīniem: C14 (Pīrsona korelācija (r)=-0,61; p=0,007), C16 (r=-0,67; p=0,002), C18:0 (r=-0,77; p<0,001), C18:1 (r=-0,71; p=0,01), un C18:2 (r=-0,79; p=0,001). Jo augstāks bija ĶMI, jo zemāks bija postprandiālais koncentrācijas nomākums sekojošajiem acilkarnitīniem: C14 (r=-0,47; p=0,048) un C16 (r=-0,50; p=0,035). Nebija statistiski nozīmīgas korelācijas starp insulīna rezistenci un postprandiālās koncentrācijas nomākumu īsķēžu un vidējo ķēžu acilkarnitīniem.
Secinājumi
Paaugstināts ĶMI indekss ir saistīts ar mazāku garķēžu acilkarnitīnu postprandiālo nomākumu. Samazināts garķēžu acilkarnitīnu postprandiālais nomākums ir saistīts ar insulīna rezistenci, kas norāda, ka acilkarnitīnu nomākšanas testu iespējams izmantot agrīnai insulīna rezistences noteikšanai.
Introduction Insulin resistance is a precursor for the development of type 2 diabetes mellitus and is associated with hypertension and dyslipidemia. Early detection of insulin resistance is important for successful therapeutic intervention. The currently available diagnostic tools are not capable to perform early detection of insulin resistance since they rely on glucose and insulin or C peptide concentrations. Research suggests that the accumulation of acylcarnitines may interfere with insulin sensitivity. Studies on obese and diabetic animal models have shown links between acylcarnitine metabolism and insulin resistance. We propose the evaluation of postprandial plasma acylcarnitine suppression as a potential method for early diagnosis of insulin resistance. Aim To outline a potential model for a plasma acylcarnitine suppression test and assess its potential as an early predictive marker for insulin resistance. Methods This study enrolled adult volunteers with a body mass index >25 kg/m2. The laboratory samples were obtained while fasting and 2 hours after a controlled (36 g) carbohydrate meal. The laboratory samples include plasma glucose and C-peptide as well as short-chain (C2-C4), medium-chain (C5-C12) and long chain (C14-C18:2) plasma acylcarnitines. Additional data such as weight, height and age was obtained through measurements and inquiry. Insulin resistance was derived from fasting plasma C-peptide and glucose using the HOMA2-IR model made publicly available by The University of Oxford. Individuals were described as having insulin resistance if fasting HOMA2 insulin resistance index was >1.8. Methods of statistical analysis such as Pearson correlation and independent t-test were performed using IBM SPSS 22.0. Results were considered significant if p<0.05. Results For the 23 participants included in this study the mean body weight was 94.1 kg (Standard Deviation (SD)±12.0), the mean body mass index (BMI) was 31.81 (SD±3.95) and the mean HOMA2 insulin resistance index was 2.50 (SD±1.67). 14 out of the 23 volunteers were described as having insulin resistance (HOMA2-IR >1.8). The higher was the HOMA2 insulin resistance index, the lower was the postprandial decrease of C14 (Pearson correlation (r)=-0.61, p=0.007), C16 (r=-0.67, p=0.002), C18:0 (r=-0.77, p=0.0002), C18:1 (r=-0.71, p=0.01), and C18:2 (r=-0.79, p=0.001). The higher was the BMI, the lower was the postprandial decrease of C14 (r=-0.47, p=0.048), C16 (r=-0.50, p=0.035). There are no significant correlations between insulin resistance and the postprandial suppression of short chain and medium chain plasma acylcarnitine concentrations. Conclusions Individuals with a higher body mass index had a decreased suppression of several long chain plasma acylcarnitines. Decreased postprandial suppression of long chain acylcarnitines is linked to insulin resistance presenting the postprandial acylcarnitine suppression test as a viable method for the early diagnosis of insulin resistance.
Introduction Insulin resistance is a precursor for the development of type 2 diabetes mellitus and is associated with hypertension and dyslipidemia. Early detection of insulin resistance is important for successful therapeutic intervention. The currently available diagnostic tools are not capable to perform early detection of insulin resistance since they rely on glucose and insulin or C peptide concentrations. Research suggests that the accumulation of acylcarnitines may interfere with insulin sensitivity. Studies on obese and diabetic animal models have shown links between acylcarnitine metabolism and insulin resistance. We propose the evaluation of postprandial plasma acylcarnitine suppression as a potential method for early diagnosis of insulin resistance. Aim To outline a potential model for a plasma acylcarnitine suppression test and assess its potential as an early predictive marker for insulin resistance. Methods This study enrolled adult volunteers with a body mass index >25 kg/m2. The laboratory samples were obtained while fasting and 2 hours after a controlled (36 g) carbohydrate meal. The laboratory samples include plasma glucose and C-peptide as well as short-chain (C2-C4), medium-chain (C5-C12) and long chain (C14-C18:2) plasma acylcarnitines. Additional data such as weight, height and age was obtained through measurements and inquiry. Insulin resistance was derived from fasting plasma C-peptide and glucose using the HOMA2-IR model made publicly available by The University of Oxford. Individuals were described as having insulin resistance if fasting HOMA2 insulin resistance index was >1.8. Methods of statistical analysis such as Pearson correlation and independent t-test were performed using IBM SPSS 22.0. Results were considered significant if p<0.05. Results For the 23 participants included in this study the mean body weight was 94.1 kg (Standard Deviation (SD)±12.0), the mean body mass index (BMI) was 31.81 (SD±3.95) and the mean HOMA2 insulin resistance index was 2.50 (SD±1.67). 14 out of the 23 volunteers were described as having insulin resistance (HOMA2-IR >1.8). The higher was the HOMA2 insulin resistance index, the lower was the postprandial decrease of C14 (Pearson correlation (r)=-0.61, p=0.007), C16 (r=-0.67, p=0.002), C18:0 (r=-0.77, p=0.0002), C18:1 (r=-0.71, p=0.01), and C18:2 (r=-0.79, p=0.001). The higher was the BMI, the lower was the postprandial decrease of C14 (r=-0.47, p=0.048), C16 (r=-0.50, p=0.035). There are no significant correlations between insulin resistance and the postprandial suppression of short chain and medium chain plasma acylcarnitine concentrations. Conclusions Individuals with a higher body mass index had a decreased suppression of several long chain plasma acylcarnitines. Decreased postprandial suppression of long chain acylcarnitines is linked to insulin resistance presenting the postprandial acylcarnitine suppression test as a viable method for the early diagnosis of insulin resistance.
Description
Medicīna
Medicine
Veselības aprūpe
Health Care
Medicine
Veselības aprūpe
Health Care
Keywords
2. tipa cukura diabēts; Insulīna rezistence, Type 2 diabetes mellitus; Insulin resistance