Association of NEFA composition with insulin sensitivity and beta cell function in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort.
Diabetologia
; 61(4): 821-830, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29275428
ABSTRACT
AIMS/HYPOTHESIS:
Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes.METHODS:
In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years. Outcome variables were calculated using the OGTT values. At each visit, insulin sensitivity was assessed using the HOMA2 of insulin sensitivity (HOMA2-%S) and the Matsuda index, while beta cell function was assessed using the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion-sensitivity index-2 (ISSI-2). Generalised estimating equations were used, adjusting for time, waist, sex, ethnicity, baseline age, alanine aminotransferase (ALT) and physical activity. NEFA were analysed as both concentrations (nmol/ml) and proportions (mol%) of the total fraction.RESULTS:
Participants' (73% female, 70% with European ancestry) insulin sensitivity and beta cell function declined by 14-21% over 6 years of follow-up. In unadjusted models, several NEFA (e.g. 181 n-7, 224 n-6) were associated with lower insulin sensitivity, however, nearly all of these associations were attenuated in fully adjusted models. In adjusted models, total NEFA, 160, 181 n-9 and 182 n-6 (as concentrations) were associated with 3.7-8.0% lower IGI/IR and ISSI-2, while only 205 n-3 (as mol%) was associated with 7.7% higher HOMA2-%S. CONCLUSIONS/INTERPRETATION:
Total NEFA concentration was a strong predictor of lower beta cell function over 6 years. Our results suggest that the association with beta cell function is due to the absolute size of the serum NEFA fraction, rather than the specific fatty acid composition.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Ilhotas Pancreáticas
/
Células Secretoras de Insulina
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Ácidos Graxos não Esterificados
/
Teste de Tolerância a Glucose
/
Insulina
Tipo de estudo:
Diagnostic_studies
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Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article