The impact of acute elevation of non-esterified fatty acids on insulin sensitivity and secretion in women with former gestational diabetes

It has long been recognized that acute elevation of non-esterified fatty acids (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in vivo. The effects of longer-term exposure to elevated fatty acids have, however, been investigated only recently. Our own studies in the rat have documented the time dependence of NEFA effects, with inhibition of glucose-induced insulin secretion being apparent after 6–24 h in vivo exposure to Intralipid or in vitro exposure to palmitate, oleate and octanoate. Evidence indicates that the inhibitory effects are coupled to fatty acid oxidation in B-cells, with ensuing reduction in glucose oxidation, in parallel with diminished activity of the pyruvate dehydrogenase enzyme. These findings were essentially confirmed in human pancreatic islets. In the db/db mouse, a model of type 2 diabetes with obesity, evidence was obtained for elevated NEFA playing a significant role in decreased glucose-induced insulin secretion. Evidence also indicates that elevated NEFA inhibit insulin biosynthesis and increase the proinsulin : insulin ratio of secretion. Results on experimentally induced elevations of NEFA in non-diabetic and diabetic humans are thus far inconclusive. Further studies are needed to ascertain the impact of elevated NEFA on insulin secretion in clinical settings.

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Relationship between lactation duration and insulin and glucose response among women with prior gestational diabetes

Acta Endocrinologica ◽

10.1530/eje-12-0939 ◽

2013 ◽

Vol 168 (4) ◽

pp. 515-523 ◽

Cited By ~ 30

Author(s):

Sarah Chouinard-Castonguay ◽

S John Weisnagel ◽

André Tchernof ◽

Julie Robitaille

Keyword(s):

Insulin Sensitivity ◽

Gestational Diabetes ◽

Area Under The Curve ◽

Bottle Feeding ◽

Oral Glucose ◽

Model Assessment ◽

Glucose Response ◽

History Of ◽

Lactation Duration ◽

The Impact

BackgroundFew studies have investigated whether favorable effects of lactation persist after weaning and protect women with prior gestational diabetes mellitus (GDM) against later development of insulin resistance and insulin secretion defects.ObjectiveTo investigate the impact of lactation duration on insulin and glucose response among women with prior GDM.Design/methodsThe study group comprised 144 women with a history of GDM between 2003 and 2010. Plasma insulin and glucose concentrations were obtained from a 75 g oral glucose tolerance test (OGTT). Total lactation duration (exclusive breastfeeding and breast and bottle-feeding) for all infants was self-reported in months.ResultsMean age was 36.5±5.0 years. Time between delivery and metabolic testing was 4.0±1.9 years. Women breastfed for an average of 13.9±16.8 months. Most women (80.6%) reported a history of lactation. Women who lactated had higher homeostasis model assessment for insulin sensitivity (HOMA-IS) and Matsuda indices and lower fasting and 2-h post-OGTT insulin concentrations as well as area under the curve (AUC) for insulin (P≤0.01 for all). Compared with women who lactated for <10 months, women who lactated for ≥10 months had improved insulin sensitivity–secretion index, higher HOMA-IS and Matsuda indices, lower fasting and 2-h post-OGTT insulin concentrations as well as AUC for insulin, and lower incidence of impaired glucose intolerance (P≤0.05 for all). In multiple linear regression analyses, lactation duration emerged as an independent predictor of fasting insulin concentrations (β=−0.02) and insulin sensitivity indices (β=0.02) (P≤0.05 for all).ConclusionsThese results suggest that longer duration of lactation is associated with improved insulin and glucose response among women with prior GDM.

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