Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: Early programming of cortisol axis

Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life, although the: mechanisms of this effect remain unc ertain. There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort, but whether this is primary or secondar y to other aspects of the phenotype is unclear. We investigated the associa tion between low birth weight and glucose intolerance, blood pressure, and dyslipidemia in young, nonobese adults from a community undergoing the heal th transition with a high prevalence of both noncommunicable diseases and l ow birth weight. Additionally, we investigated whether altered basal and st imulated cortisol levels as a marker of hypothalamic-pituitary-adrenal resp onsiveness or cortisol metabolism were associated with low birth weight in these young adults. Twenty-year-old, historically disadvantaged, urbanized South Africans (n = 137) with birth weights either below the 10th percentile [underweight for a ge (UFA)] or between the 25th and 75th percentiles [appropriate for gestati onal age (AFA)] had anthropometry, blood pressure, lipid levels, and glucos e tolerance measured. In a subset (n = 62), 0900 h plasma cortisol concentr ations, cortisol responses to 1 mug ACTH, and urinary glucocorticoid metabo lites were measured. The mothers of UFA infants were themselves lighter and had a lower body mas s index (P = 0.0016). At age 20 yr, although the UFA group was still smalle r and lighter, with a lower body mass index, they had higher fasting plasma glucose levels (P = 0.047), and a greater proportion demonstrated glucose intolerance (11.9% vs. 0%; P < 0.01). The UFA group also had higher systoli c [UFA, 126.0 +/- 13.3 (+/-SD); AFA, 122.0 +/- 11.7 mm Hg; P = 0.007] and d iastolic (72.3 +/- 8.4 vs. 69.5 +/- 8.7 mm Hg; P = 0.02) blood pressures, a fter covarying for current weight and gender. Plasma cortisol levels determ ined at 0900 h were higher in the UFA group (484.9 +/- 166.3 vs. 418.6 +/- 160.6 nmol/L) and showed a greater plasma cortisol response to low dose ACT H stimulation (area under the curve for cortisol: UFA, 77,238 +/- 19,511; A FA, 66,597 +/- 16,064 nmol/L.min; P = 0.04). In conclusion, the link betwee n low birth weight and adult glucose intolerance and blood pressure elevati on occurs in young adults in a high risk, disadvantaged population despite a lack of full catch-up growth. Moreover, cortisol axis activation is an ea rly feature in the process linking low birth weight with adult cardiovascul ar and metabolic disease and is not dependent upon adult obesity or full ca tch-up growth, at least in this population undergoing the health transition .