Contribution of Non-Esterified Fatty Acids to Insulin Resistance in the Elderly with Normal Fasting but Diabetic 2h Post Challenge Plasma Glucose Levels: Baltimore Longitudinal Study of Aging

摘要

Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose (NFG) <100mg/dl and plasma glucose with diabetic 2h plasma glucose (DGT) ≥ 200mg/dl after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts them at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75g) on two or more occasions. We measured plasma levels of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines and their soluble receptors, as well as NEFAs. We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were >65 yrs old. They were then matched by age, sex and BMI to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose (NFG) levels <100mg/dl in accordance with American Diabetes Association (ADA): Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other two groups, except at the 2h time, when their insulin levels were higher than NGT (P<0.05). Although there was a clear trend for differences in the insulinogenic index (II0–20 min), the areas under the curves for insulin, systolic BP, adiponectin and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all three groups. NEFA levels were significantly elevated in the fasting state (P<0.05) in the IPH compared to NGT, with IGT intermediate between the other two groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (NGT-11.9 vs. IGT-7.6 vs. IPH-3.0, μmol/l·min⁻¹). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT.