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
en 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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
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Islotes Pancreáticos
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Células Secretoras de Insulina
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Ácidos Grasos no Esterificados
/
Prueba de Tolerancia a la Glucosa
/
Insulina
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Diabetologia
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá