Variation in the Calculation of Allostatic Load Score: 21 Examples from NHANES.

After decades of resistance, there is now a genuine consensus that disease cannot be prevented or even successfully treated unless the role of stress is addressed alongside traditionally recognized factors such as genes and the environment. Measurement of allostatic load, which is quantified by the allostatic load score (ALS), is one of the most frequently used methods to assess the physiologic response to stress. Even though there is universal agreement that in the calculation of ALS, biomarkers from three categories should be included (cardiovascular, metabolic and immune), enormous variation exists in how ALS is calculated. Specifically, there is no consensus on which biomarkers to include or the method which should be used to determine whether the value of a biomarker represents high risk. In this perspective, we outline the approach taken in 21 different NHANES studies.

The Association between Stress Measured by Allostatic Load Score and Physiologic Dysregulation in African Immigrants: The Africans in America Study.

INTRODUCTION: Allostatic load score (ALS) summarizes the physiological effect of stress on cardiovascular, metabolic and immune systems. As immigration is stressful, ALS could be affected. OBJECTIVE: Associations between age of immigration, reason for immigration, and unhealthy assimilation behavior and ALS were determined in 238 African immigrants to the United States (age 40 ± 10, mean ± SD, range 21-64 years). METHODS: ALS was calculated using 10 variables from three domains; cardiovascular (SBP, DBP, cholesterol, triglyceride, homocysteine), metabolic [BMI, A1C, albumin, estimated glomerular filtration rate (eGFR)], and immunological [high-sensitivity C-reactive protein (hsCRP)]. Variables were divided into sex-specific quartiles with high-risk defined by the highest quartile for each variable except for albumin and eGFR, which used the lowest quartile. One point was assigned if the variable was in the high-risk range and 0 if not. Unhealthy assimilation behavior was defined by a higher prevalence of smoking, alcohol consumption, or sedentary activity in immigrants who lived in the US for ≥10 years compare to <10 years. RESULTS: Sixteen percent of the immigrants arrived in the US as children (age < 18 years); 84% arrived as adults (age ≥ 18 years). Compared to adulthood immigrants, childhood immigrants were younger (30 ± 7 vs. 42 ± 9, P < 0.01) but had lived in the US longer (20 ± 8 vs. 12 ± 9 years, P < 0.01). Age-adjusted ALS was similar in childhood and adulthood immigrants (2.78 ± 1.83 vs. 2.73 ± 1.69, P = 0.87). For adulthood immigrants, multiple regression analysis (adj R2 = 0.20) revealed older age at immigration and more years in the US were associated with higher ALS (both P < 0.05); whereas, current age, education, income, and gender had no significant influence (all P ≥ 0.4). The prevalence of smoking, alcohol intake, and physical activity did not differ in adulthood immigrants living in the US for ≥10 years vs. <10 years (all P ≥ 0.2). Reason for immigration was available for 77 participants. The reasons included: family reunification, lottery, marriage, work, education, and asylum. Compared to all other reasons combined, immigration for family reunification was associated with the lowest ALS (1.94 ± 1.51 vs. 3.03 ± 1.86, P = 0.03). CONCLUSION: African immigrants do not appear to respond to the stress of immigration by developing unhealthy assimilation behaviors. However, older age at immigration and increased duration of stay in the US are associated with higher ALS; whereas, family reunification is associated with lower ALS. CLINICAL TRIALSGOV IDENTIFIER: NCT00001853.

Glycated Albumin Identifies Prediabetes Not Detected by Hemoglobin A1c: The Africans in America Study.

BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high-normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A1c (Hb A1c) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m2]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A1c and glycated albumin was determined by thresholds at the upper quartile for each [Hb A1c ≥5.7% (39 mmol/mol), glycated albumin ≥13.77%]. RESULTS: Based on glucose criteria for the OGTT, prediabetes was detected in 36% (85/236). BMI and Hb A1c were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A1c alone(72% vs 37%, P < 0.01). In the obese, Hb A1c was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A1c in nonobese African immigrants. ClinicalTrials.gov Identifier: NCT00001853.

A1C Combined With Glycated Albumin Improves Detection of Prediabetes in Africans: The Africans in America Study.

OBJECTIVE: Slowing the diabetes epidemic in Africa requires improved detection of prediabetes. A1C, a form of glycated hemoglobin A, is recommended for diagnosing prediabetes. The glycated proteins, fructosamine and glycated albumin (GA), are hemoglobin-independent alternatives to A1C, but their efficacy in Africans is unknown. Our goals were to determine the ability of A1C, fructosamine, and GA to detect prediabetes in U.S.-based Africans and the value of combining A1C with either fructosamine or GA. RESEARCH DESIGN AND METHODS: Oral glucose tolerance tests (OGTT) were performed in 217 self-identified healthy African immigrants (69% male, age 39 ± 10 years [mean ± SD], BMI 27.6 ± 4.5 kg/m(2)). A1C, fructosamine, and GA were measured. Prediabetes was diagnosed by American Diabetes Association criteria for glucose obtained from a 2-h OGTT. The thresholds to diagnose prediabetes by A1C, fructosamine, and GA were the cutoff at the upper tertile for each variable: ≥5.7% (39 mmol/mol) (range 4.2-6.6% [22.4-48.6 mmol/mol]), ≥230 µmol/L (range 161-269 µmol/L), and ≥13.35% (range 10.20-16.07%), respectively. RESULTS: Prediabetes occurred in 34% (74 of 217). The diagnostic sensitivities of A1C, fructosamine, and GA were 50%, 41%, and 42%, respectively. The P values for comparison with A1C were both >0.3. Combining A1C with either fructosamine or GA increased sensitivities. However, the sensitivity of A1C combined with fructosamine was not better than for A1C alone (72% vs. 50%, P = 0.172). In contrast, the sensitivity of A1C combined with GA was higher than for A1C alone (78% vs. 50%, P < 0.001). CONCLUSIONS: As individual tests, A1C, fructosamine, and GA detected ≤50% of Africans with prediabetes. However, combining A1C with GA made it possible to identify nearly 80% of Africans with prediabetes.