Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Study: Baseline Characteristics of Enrolled Subjects

Abstract

Background:

The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study is a prospective evaluation of the natural history impaired glucose regulation.

Design and Methods:

The eligibility requirements include age 18–65 yr, history of type 2 diabetes in one or both parents, normal fasting plasma glucose (FPG) or normal glucose tolerance, and African-American or Caucasian status. Participants underwent assessments (including dietary and exercise behavior, clinical examination, glucose tolerance, insulin sensitivity, β-cell function, body composition, energy expenditure) during 2.25–5.5 yr of quarterly follow-up. The primary outcome is the occurrence of prediabetes. Baseline data are presented for the 376 enrolled participants. The cohort was also compared with National Health and Nutrition Examination Survey 2007/2008 participants meeting the age and glycemic criteria for the POP-ABC study.

Results:

The POP-ABC cohort [mean (±sd) age was 44.2 ± 10.6 yr] was 57.7% African-Americans, 42.3% Caucasians, and 70.7% females; 86% had one parent with diabetes and 14% had both parents affected. Although greater than 70% of the cohort were employed and 75% had more than 13 yr of education, more African-Americans reported incomes less than $20,000 and fewer reported incomes more than $75,000 compared with Caucasians. Compared with Caucasians, African-Americans had a higher body mass index (31.3 ± 7.8 vs. 28.8 ± 7.8 kg/m², P = 0.001), a lower FPG (90.0 ± 7.72 vs. 92.2 ± 7.60 mg/dl, P = 0.008), higher glycosylated hemoglobin, lower triglycerides, and similar blood pressure, and homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function, high-density lipoprotein, and low-density lipoprotein cholesterol levels. Compared with a cross-section of U.S. subjects (National Health and Nutrition Examination Survey 2007/2008) with normal FPG and normal glucose tolerance, participants in the POP-ABC study had similar lipid profile but were more educated and had higher body mass index, glycosylated hemoglobin, and blood pressure.

Conclusions:

The POP-ABC study has successfully enrolled healthy African-American and Caucasian adults with parental type 2 diabetes mellitus. The study will generate novel data on incidence rates and predictors of prediabetes, and clarify the role of race/ethnicity on early dysglycemia.

National survey data indicate that the prevalence of type 2 diabetes is higher among African-Americans and other ethnic groups compared with European-Americans or Caucasians (1–3). The development of type 2 diabetes is punctuated by a variable interlude of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (4–6). Persons with prediabetes progress to diabetes at an annual rate of approximately10%, which is similar for African-Americans, Hispanics, Asian Americans, Native Americans, and Caucasians (7). The lack of racial/ethnic disparities in the rate of development of diabetes among persons with prediabetes (despite the marked ethnic disparities in diabetes prevalence) suggests that the effects of race/ethnicity might occur more proximally [i.e. during the transition from normal glucose regulation to prediabetes]. Testing that notion requires knowledge of the incident rates of prediabetes in prospective cohorts of persons from different racial/ethnic groups. Among initially normoglycemic Pima Indians of Arizona, the incident rate of prediabetes was 7.8% per year during 4 yr of follow-up (8). However, prospective data on the incident prediabetes rates are lacking for African-Americans and other demographic groups in addition to the Pima Indians.

The Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) Study is a longitudinal study of incident prediabetes among initially normoglycemic African-Americans and Caucasians who are offspring of parents with type 2 diabetes. The rationale, design, and methods of the study have been described in detail (9). Prospective study subjects underwent a screening oral glucose tolerance test (OGTT) during an outpatient visit to the General Clinical Research Center (GCRC) and were enrolled if they had normal fasting plasma glucose (FPG) and/or normal 2-h plasma glucose during the OGTT (2 h PG). Enrollment of participants in the POP-ABC study began in September 2006 and was concluded in December 2009. After the baseline visit for screening OGTT, each enrolled subject had repeated metabolic assessments during quarterly visits to the GCRC. The final follow-up assessment visits occurred in March 2012. The assessments included anthropometry, OGTT, body composition, energy expenditure, insulin sensitivity, β-cell function, cardiometabolic profile, adipocytokines, and behavioral and socioeconomic measures (9). Participants were followed up for 2.25–5.5 yr, the primary outcome being the development of prediabetes (IFG and/or IGT) (9). The final sample size (376 subjects) provides 85% power to detect a hazard ratio of 1.75 between African-American and Caucasian offspring in the primary outcome (alpha = 0.05).

By limiting enrollment to persons with parental type 2 diabetes, we hoped to dampen the influence of putative genetic factors on incident prediabetes, thereby improving the ability to detect interaction of environmental factors with race/ethnicity. Furthermore, by specifying progression to prediabetes (rather than diabetes) as the primary outcome measure, the POP-ABC study aimed to identify individuals who may benefit from interventions to prevent diabetes and restore normal glucose regulation. In this report, we present the demographic, clinical, biochemical, and socioeconomic characteristics and the major metabolic variables that were measured at entry in the enrolled subjects.

Research Design and Methods

Participants

We recruited study participants from several sources including mass mailings of brochures, community events, religious gatherings, health fairs, advertisements, and referrals from health care professionals. Eligibility criteria (9) included age 18–65 yr, self-reported non-Hispanic white or non-Hispanic black race/ethnicity status, having one or both biological parents with type 2 diabetes, and normal FPG and/or normal 2-h PG at baseline and good overall health status. Excluded from participation were persons with diabetes or using antidiabetic medications or other medications known to alter glucose metabolism or body weight (9). Other exclusion criteria were enrollment in behavioral, pharmacological, or combined weight loss program; history of liposuction or bariatric surgery; current pregnancy or being within 12 months postpartum; and recent hospitalization (within 6 wk of the screening visit) (9). Self-report of race/ethnicity was based on the questions used in the 1990 U.S. Census questionnaire (10). The parental history of type 2 diabetes was documented using a diabetes-focused history, including information on the number of affected biological parents, parent's gender, age at diagnosis, use of diabetes medications, diabetic complications, and contact information of the parents' physicians. The goal was to enroll the offspring of diabetic parents who have normal FPG and/or normal 2-h PG during OGTT at baseline to permit the detection of progression to prediabetes (IFG and/or IGT) during follow-up. IFG (100–125 mg/dl) was defined according to the 2003 revised American Diabetes Association criteria (6) and IGT by the World Health Organization criteria, based on a 75-g OGTT (11). The POP-ABC study protocol was approved by the University of Tennessee Health Science Center Institution Review Board. All subjects gave their written informed consent before the initiation of the study, which was conducted in accordance with the principles of the Declaration of Helsinki.

Procedures and measurements

Participants arrived at the GCRC after an overnight fast. Initial procedures consisted of a structured medical interview; measurement of weight, height, waist circumference, and blood pressure; a general physical examination; a pregnancy test (where appropriate); and a standard 75-g OGTT (9). Standardized questionnaires were used to obtain data on personal and family medical history, education, employment, marital status, family income, medications, drug or alcohol use, and smoking. Weight was measured in duplicate on a calibrated balance beam scale. Standing height was determined in duplicate with a standard stadiometer. Body mass index (BMI) was calculated as the weight in kilograms divided by the height in meters squared. Waist circumference was determined to the nearest 0.1 cm at the midpoint between the highest point of the iliac crest and the lowest costal margin in the midaxillary line, using a Gulick II tape measure. Blood pressure was recorded in the seated position, using an automated sphygmomanometer; the average of two readings was used for calculations.

The OGTT was preceded by written instructions to consume a usual diet with adequate carbohydrates, refrain from strenuous exercise and alcohol consumption for 24 h, and avoid smoking in the morning of the test. The test was initiated between 0700 and 1100 h after an overnight fast: venous blood specimens for measurement of glucose and insulin were obtained before (0 min) and at 30 and 120 min after ingestion of 75 g flavored glucose (Trutol 75; Custom Laboratories, Baltimore, MD). Lipid profile, glycosylated hemoglobin (HbA1c) and other analytes in fasting plasma specimens were also measured per protocol (9). The homeostasis model assessment (HOMA) method was used to calculate indices of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) from fasting plasma glucose and insulin values (12). Furthermore, assessment of insulin sensitivity by hyperinsulinemic euglycemic clamp and β-cell function by frequently sampled intravenous glucose tolerance test were performed, but those data are not included in this report. Plasma glucose was measured with a glucose oxidase method (Yellow Spring Instruments Co., Inc., Yellow Spring, OH). Plasma insulin was measured immunochemically in our Endocrine Research Laboratory, using commercially available kits. Fasting plasma lipid profiles [including total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and triglycerides] were measured using standard techniques in a commercial clinical laboratory. Additionally, food habits, physical activity, body fat distribution, and energy expenditure at baseline were assessed (9), but they are not reported here.

Outcome measures

The primary outcome measure was progression from normal FPG or normal 2-h PG to prediabetes (IFG or IGT). For subjects with normal FPG whose 2-h PG was greater than 140 but less than 200 mg/dl at baseline, progression of FPG to 100 mg/dl or greater constituted an end point occurrence. For those enrolled on the basis a 2-h PG level of less than 140 mg/dl (with FPG > 100 but < 126 mg/dl at baseline), progression to 2-h PG level of 140 mg/dl or greater constituted an end point occurrence. For participants enrolled with normal FPG and 2-h PG, the occurrence of IFG and/or IGT constituted an end point. For all subjects, any occurrence of diabetes (FPG ≥ 126 mg/dl, 2-h PG ≥ 200 mg/dl, or prescription of a diabetes medication) was an end point. During each visit, an interval medical history was obtained and concomitant medications were recorded. If initial tests during a scheduled visit showed the occurrence of a prediabetes end point, a confirmatory test was performed within approximately 6 wk. The standard OGTT was the method of confirmation. If the second test was nonconfirmatory, the subject continued in the study as scheduled. For all subjects with confirmed end point occurrence, the date of the initial endpoint occurrence was recorded as the confirmed end point date. For subjects whose interval glucose tests remained within the normal range throughout the study period, a 20-mg/dl or greater increase in FPG from baseline was recorded as a prespecified surrogate end point (9). Persons with evidence of diabetes from FPG values or through interval prescription of diabetes medications were not retested with an OGTT.

Secondary outcomes

The secondary outcome measures include body composition (weight, waist circumference, total and abdominal body fat, fat free mass), food habits, physical activity, insulin sensitivity, insulin secretion, energy expenditure, metabolic syndrome components, adipocytokines, and socioeconomic status.

Data management and analyses

Data from each participant were double entered into a central database by trained research personnel and checked for allowed ranges and internal consistency. The central database was maintained, and all analyses were performed using the Statistical Analysis System (SAS Institute, Cary, NC). The data reported here were obtained following close-out visits and are based on the database as of March 31, 2012. Baseline characteristics of study participants were examined by race and gender. Data are reported as means ± sd unless sem is specified. Black/white differences were analyzed using unpaired t tests for continuous variable and the χ² test for categorical variables. Significance level was set at P < 0.05. The POP-ABC baseline data were also compared with the weighted National Health and Nutrition Examination Survey (NHANES) 2007/2008 data from a cross-section of the United States population matching the major POP-ABC eligibility criteria (9, 13).

Results

Clinical and demographic characteristics

More than 1550 individuals underwent initial verbal screening by telephone or in person during community health fairs. A total of 624 persons without a history of diabetes but whose biological parents had type 2 diabetes underwent OGTTs. Of those, 376 subjects who met all eligibility criteria were enrolled in the study. Of all participants, 57.7% were African-American and 42.3% were Caucasian; their mean age was 44.2 ± 10.6 yr, and approximately 70% were female. Most participants (86%) reported having only one parent with diabetes, whereas approximately 14% reported having both parents diabetes. The proportion of subjects having both parents with diabetes was similar for African-Americans and Caucasians; however, more African-Americans reported having a maternal history of diabetes, whereas more Caucasians reported having a paternal history of diabetes (Table 1). Of the participants, 282 (75%) were enrolled with normal FPG and normal 2-h PG, and 94 (25%) with either normal FPG (18%) or normal 2-h PG (7%) (Table 1). The distribution of enrollment glycemic status was similar in African-Americans and Caucasians for the 93% of participants who had normal FPG (Table 1). However, Caucasians comprised a higher proportion among the 7% of enrolled subjects who met the NGT inclusion criterion but had IFG at baseline (Table 1).

Table 1.

Demographic, parental, and enrollment characteristics by race/ethnicity

	Overall	African-American	Caucasian
n	376	217	159
Age (yr)	44.2 ± 10.6	43.5 ± 10.3	46.6 ± 10.5a
Gender
Male	109 (29.0%)	61 (28.1%)	48 (32.2%)
Female	267 (71.0%)	156 (71.9%)	111 (69.8%)
Parental DM history
Father	143 (38.0)	66 (30.4%)	77 (48.4%)
Mother	181 (48.1%)	119 (54.8)	62 (39%)
Both	52 (13.8%)	32 (14.8%)	20 (12.6%)
Enrollment criteria (n, %)
Normal FPG and 2-h PG	282 (75%)	168 (77.4%)	114 (71.7%)
Normal FPG only	68 (18%)	39 (18%)	29 (18.2%)
Normal 2-h PG only	26 (7%)	10 (4.6%)	16 (10.1%)

DM, Diabetes mellitus.

^aP = 0.005.

Adiposity and cardiometabolic measures

The mean BMI, waist circumference, glycemia, blood pressure and lipid levels of POP-ABC participants at enrollment are shown in Table 2. Compared with their Caucasian counterparts, African-American offspring of parents with type 2 diabetes had higher BMI, lower FPG, similar 2-h PG levels, and higher HbA1c at enrollment. Waist circumference was similar among men but higher in African-American women compared with Caucasian women (Table 2). The HDL and LDL cholesterol levels and blood pressure were similar, but triglycerides were lower in African-American compared with Caucasian offspring. Fasting plasma insulin levels, HOMA-IR, and HOMA-B were similar in the African-American and Caucasian offspring (Table 2).

Table 2.

Cardiometabolic and glucoregulatory characteristics

	Overall	African-American	Caucasian	P value
BMI (kg/m2)	30.2 ± 7.23	31.2 ± 7.36	28.8 ± 6.81	0.001
Waist circumference (cm)
Male	96.8 ± 18.0	97.0 ± 18.2	96.6 ± 18.0	0.97
Female	92.8 ± 15.5	94.6 ± 15.1	90.3 ± 15.9	0.03
FPG (mg/dl)	90.9 ± 7.70	90.0 ± 7.70	92.2 ± 7.60	0.008
2-h PG (mg/dl)	125 ± 26.5	124 ± 28.5	125 ± 23.4	0.620
Fasting insulin (μU/ml)	7.82 ± 6.85	7.54 ± 5.89	8.21 ± 8.03	0.382
HbA1c (%)	5.56 ± 0.45	5.66 ± 0.47	5.44 ± 0.32	<0.0001
Blood pressure (mm Hg)
Systolic	121 ± 16.1	122 ± 16.1	120 ± 16.0	0.217
Diastolic	72.8 ± 9.10	73.2 ± 8.90	72.2 ± 9.30	0.310
Total cholesterol (mg/dl)	176 ± 32.7	174 ± 33.2	179 ± 32.0	0.224
LDL cholesterol (mg/dl)	108 ± 60.8	111 ± 78.6	104 ± 27.9	0.353
HDL cholesterol (mg/dl)	52.9 ± 14.2	53.5 ± 14.9	52.1 ± 13.4	0.405
Triglycerides (mg/dl)	94.8 ± 53.3	78.9 ± 37.3	113 ± 64.6	<0.0001
HOMA-IR	1.92 ± 1.66	1.93 ± 1.80	1.91 ± 1.50	0.93
HOMA-B	98.8 ± 81.9	97.2 ± 69.6	101 ± 94.7	0.98

To convert glucose to millimoles per liter, multiply by 0.05551; to convert insulin to picomoles per liter, multiply by 6; to convert total, LDL, and HDL cholesterol to millimoles per liter, multiply by 0.0259; to convert triglycerides to millimoles per liter, multiply by 0.0133.

Socioeconomic characteristics

Table 3 summarizes the distribution of age brackets and socioeconomic characteristics of the enrolled cohort. Approximately one third of the POP-ABC participants were aged 18–39 yr, 58.5% were aged 40–59 yr, and approximately 7% were 60 yr of age or older. More than one quarter of the cohort had more than 17 yr of education, 58.3% had 13–17 yr of education, and 16% had less than 13 yr. The proportion with less than 13 yr of education was 24% in African-Americans compared with 5.9% in Caucasians; however, racial differences were less marked at the higher end of attained education (Table 3). The proportion with full- or part-time employment was similar (∼70%) for African-Americans and Caucasians, but more African-Americans had household incomes less than $20,000 (20 vs. 7.8%), and fewer African-Americans had incomes greater than $75,000 (21.1 vs. 47.1%) compared with Caucasians. More Caucasian offspring of parents with type 2 diabetes reported being married compared with African-American offspring. Overall, approximately 75% of the cohort denied a history of smoking, and 16% were current smokers. Twice as many Caucasian offspring reported current smoking habit compared with African-Americans. Among POP-ABC female participants, 64% were premenopausal and 35.9% were in surgical or natural menopause. African-Americans women were more likely to be premenopausal (70.5 vs. 55%) and less likely to be postmenopausal compared with Caucasians (Table 3).

Table 3.

Age distribution and socioeconomic characteristics by race/ethnicity

	Overall	Caucasian	African-American
Age (yr)
n	376	159	217
18 to < 40	130 (34.6)	45 (28.3)	85 (39.2)
0 to < 60	220 (58.5)	97 (61.0)	123 (56.7)
≥60	26 (6.9)	17 (10.7)	9 (4.2)
Employment status
n	343	153	190
Employed (full or part time)	244 (71.1)	111 (72.6)	133 (70.0)
Retired	20 (5.8)	13 (8.5)	7 (3.7)
Homemaker	21 (6.1)	10 (6.5)	11 (5.8
Not employed	32 (9.3)	10 (6.5)	22 (11.6)
Seasonally employed	5 (1.5)	1 (0.7)	4 (2.1)
Student	10 (2.9)	3 (2.0)	7 (3.7)
Other	8 (2.3)	4 (2.6)	4 (2.1)
Never worked	3 (0.9)	1 (0.7)	2 (1.1)
No data	33 (8.8)	6 (3.8)	27 (12.4)
Education (yr)
n	343	153	190
< 13	55 (16.0)	9 (5.8)	46 (24.2)
13–16	200 (58.3)	99 (64.7)	101 (53.2)
≥17	88 (25.7)	45 (29.4)	43 (22.6)
No data	33 (8.8)	6 (3.8)	27 (12.4)
Menopausal status
n	267	111	156
Premenopausal	171 (64.0)	61 (55.0)	110 (70.5)
Postmenopausal	96 (35.9)	50 (45.0)	46 (29.5)
Annual family income
n	343	153	190
<$20,000	50 (14.6)	12 (7.8)	38 (20.0)
$20,000 to < $35,000	43 (12.5)	12 (7.8)	31 (16.3)
$35,000 to < $50,000	55 (16.0)	19 (12.4)	36 (19.0)
$50,000 to < $75,000	68 (19.8)	31 (20.3)	37 (19.5)
>$75,000	112 (32.7)	72 (47.1)	40 (21.1)
Refused	15 (4.4)	7 (4.6)	8 (4.2)
No data	33 (8.8)	6 (3.8)	27 (12.4)
Marital status
n	343	153	190
Never married	78 (22.7)	24 (15.7)	54 (28.4)
Living together	14 (4.1)	7 (4.6)	7 (3.7)
Married	188 (54.8)	104 (68.0)	84 (44.2)
Separated	4 (1.17)	0 (0.0)	4 (2.1)
Divorced	49 (14.3)	17 (11.1)	32 (16.8)
Widowed	10 (2.92)	1 (0.65)	9 (4.7)
No data	33 (8.8)	6 (3.8)	27 (12.4)

Data are n (%) unless otherwise stated. Percentages may not add up to 100 because of rounding.

Comparison of POP-ABC and NHANES

To compare the POP-ABC participants with the general U.S. population, we examined the characteristics of the NHANES 2007/2008 participants, a representative sample of the U.S. population, who matched the age, race/ethnicity, and glycemic inclusion criteria for POP-ABC. We chose the NHANES 2007/2008 data for the comparison because those years coincided with the peak recruitment period for the POP-ABC Study. We identified 830 NHANES 2007/2008 (13) participants comprising non-Hispanic blacks (African-Americans) and non-Hispanic whites (Caucasians) who were aged 18–65 yr in the above years, completed an OGTT, and had normal FPG and/or normal 2-h PG. Subjects with diabetes and those with incomplete OGTT data were excluded from the analysis. In contrast to the POP-ABC, in which all subjects have parental history of diabetes, the NHANES 2007/2008 data did not have information on parental or family history of diabetes. For reference, 30.8% of NHANES 1999–2002 participants reported having a first-degree relative with diabetes (14). As shown in Table 4, the results indicate that the POP-ABC and NHANES 2007/2008 participants have a comparable age distribution, with 90% or more of subjects falling within the 18- to 60-yr age group. However, POP-ABC participants are more educated. Lipid profiles were similar, but the mean BMI, HbA1c, and blood pressures were higher in POP-ABC participants than their NHANES 2007/2008 counterparts (Table 4). The mean fasting plasma glucose (P < 0.0001) and insulin (P < 0.0001) levels were lower among POP-ABC subjects compared with NHANES 2007/2008 participants, as was the mean HOMA-IR (1.92 ± 1.66 vs. 2.48 ± 2.02, P < 0.0001) (Table 4). The pattern was consistent by race.

Table 4.

Comparison of POP-ABC and NHANES 2007/2008 participants' characteristics

	All subjects		Caucasian		African-American
	POP-ABC	NHANES	POP-ABC	NHANES	POP-ABC	NHANES
n	376	830	159	565	217	265
Race/ethnicity			42.3%	68.1%	57.7%	31.9%
Female	71.0%	50.6%	69.8%	51.9%	71.9%	47.9%
Age (yr)
18 to <40	34.6%	41.3%	28.3%	36.4%	39.2%	46.3%
40 to <60	58.5%	47.8%	61.0%	52.6%	56.7%	42.9%
≥60	6.9%	10.8%	10.7%	11.0%	4.2%	10.7%
BMI (kg/m2)	30.2	27.9	28.8	27.3	31.2	29.0
HbA1c (%)	5.57	5.34	5.44	5.29	5.67	5.45
Fasting glucose (mg/dl)	90.9	97.0	92.2	97.6	90.0	95.7
Fasting insulin (μU/ml)	7.82	10.2	8.21	9.83	7.54	10.9
HOMA-IR	1.92	2.48	1.91	2.48	1.93	2.62
Education
n	343	830	153	565	190	265
High school or less	16.0%	43.6%	5.9%	41.2%	24.2%	48.7%
Some college	29.2%	30.2%	31.4%	29.7%	27.4%	31.3%
College graduate or higher	54.8%	26.1%	62.8%	29.0%	48.4%	20.0%
Systolic BP (mm Hg)	121.2	117.2	120	116.2	122	119.5
Diastolic BP (mm Hg)	72.8	66.2	72.3	67.4	73.2	63.6
Lipids
n	338	827	151	563	187	264
Total cholesterol (mg/dl)	177.4	193.6	180.1	195.2	175.3	190.2
HDL cholesterol (mg/dl)	52.6	55.5	51.8	53.7	53.3	59.6
LDL cholesterol (mg/dl)	106.0	115.4	105.6	116.4	106.3	113.3
Triglycerides (mg/dl)	94.3	115.7	113.7	129.4	78.7	86.6

Continuous variables are given as mean values and categorical variables as percentages. To convert glucose to millimoles per liter, multiply by 0.05551; to convert insulin to picomoles per liter, multiply by 6; to convert total, LDL, and HDL cholesterol to millimoles per liter, multiply by 0.0259; and to convert triglycerides to millimoles per liter, multiply by 0.0133. BP, Blood pressure.

Discussion

The objective of the POP-ABC Study was to determine the rates and predictors of incident prediabetes among initially normoglycemic African-Americans and Caucasians with parental type 2 diabetes. Our target was to enroll a population-based sample comprising 50% non-Hispanic whites and 50% non-Hispanic Blacks. We recruited study participants from a variety of sources including mass mailings of brochures; print, radio and television advertisements; presentations at community events, religious gatherings, and health fairs; and referrals from health care professionals. Remarkably, the African-American target was reached and exceeded with relative ease, such that at the end of the recruitment period the cohort comprised 57.7% African American and 42.3% Caucasian. Designed as a natural history study, POP-ABC participants were required to have one or both biological parents with type 2 diabetes, be free of diabetes, and have normal FPG and/or normal 2-h PG. Beyond these criteria, there was no attempt to match African-American and Caucasian offspring in metabolic or other characteristics.

The baseline results indicate a biracial cohort that is surprisingly concordant in several important characteristics (parental diabetes burden, 2-h PG, serum insulin, blood pressure, cholesterol, HOMA-IR, HOMA-B) but divergent in certain demographic, metabolic, and socioeconomic factors (including mean age, FPG, BMI, triglycerides, education, and income). Thus, despite similar parental diabetes heritage, the African-Americans and Caucasians in POP-ABC harbor a mixed burden of environmental diabetogenic risk factors (15, 16). The mean age was 3 yr lower in African-American offspring compared with Caucasians (Table 1). Although type 2 diabetes risk increases with age (17), the metabolic significance of the Black/white age difference in the POP-ABC Study is unclear. Studies have shown higher rates of conversion from IGT to type 2 diabetes at a younger age among persons from certain ethnic minority groups compared with Caucasians (5). Thus, the slightly younger mean age of the African-American offspring may not necessarily be protective of the risk of glycemic progression.

The mean BMI of POP-ABC participants at baseline was 2.3 kg/m² higher in African-Americans than Caucasians, comparable with the 1.7-kg/m² Black/white difference in BMI among NHANES 2007/2008 participants (Table 4). Waist circumference did not differ by race among male participants but was greater in African-American women compared with Caucasian women. The POP-ABC gender/ethnic pattern in waist size is in accord with trends observed in the general U.S. population (18). Compared with NHANES 2007/2008 participants, the POP-ABC subjects had a lower mean HOMA-IR level (i.e. they are more insulin sensitive). This finding appears counterintuitive, given that POP-ABC subjects were all offspring of parents with type 2 diabetes and had a higher mean BMI than did the NHANES 2007/2008 population. The apparent paradox may be explained by the eligibility criteria that selected for survivors among a high-risk group. To be included in the POP-ABC study, offspring of diabetic parents had to be free from diabetes and have normal fasting glucose/normal glucose tolerance at enrollment. Those stringent glycemic criteria favored offspring with well-preserved glucoregulatory function, as indicated by the lower mean HOMA-IR, fasting glucose, and insulin data.

The African-American offspring in our study reported lower family income and had a higher proportion of persons with less than 13 yr of education, compared with the Caucasian offspring. Thus, by two key measures of socioeconomic status (SES), African-Americans appear to be disadvantaged because low SES has been identified as a risk factor for diabetes (15, 16). Subsequent analysis of outcome data in our cohort should clarify whether SES predicts progression from normoglycemia to prediabetes. In addition to demographic, glycemic, metabolic and SES data, the POP-ABC study obtained information on dietary habits, physical activity, body fat distribution, and energy expenditure. Analyses of these variables in relation to incident prediabetes rates may shed further light on the interactions among environmental factors, genetic risk and race/ethnicity in the development of dysglycemia.

The proportion of POP-ABC participants who had biparental diabetes was comparable between African-Americans and Caucasians (14.8 vs. 12.6%); however, African-American offspring were more likely to report maternal diabetes (54.8 vs. 39%), and Caucasians were more likely to report paternal diabetes (48.4 vs. 30.4%). In the Framingham Offspring Study (predominantly Caucasians), the risk of type 2 diabetes in offspring was similar when either the mother or the father had diabetes (19). However, offspring with maternal history of diabetes were more likely to have prediabetes compared with offspring with paternal diabetes (19). The Framingham data also showed that the risk of filial diabetes when both parents are affected equals the sum of risk when either parent is affected (19). Analysis of a large, ethnically diverse database from Kaiser Permanente Diabetes Registry showed that maternal history of diabetes conferred a modestly higher risk of type 2 diabetes than paternal history of diabetes for all races combined [odd ratio (OR) 1.62 (1.46–1.81)]. The maternal transmission effect was consistent in non-Hispanic whites [OR 1.65 (1.44–1.90)], Hispanics [OR 1.93 (1.45–2.58)], and Asians/Pacific Islanders [OR 1.47 (1.01–2.13)] but was not significant in African-Americans [OR 1.20 (0.87–1.67)] (20). Parental factors in relation to prediabetes were not reported in the Kaiser Permanente study. The POP-ABC outcomes data will determine whether the gender of the parent with type 2 diabetes exerts a discernible differential effect on incident prediabetes among the approximately 90% of participants with uniparental history of T2DM.

Compared with Caucasians, African-American offspring had a higher mean HbA1c level, despite having lower mean FPG and similar values for 2-h PG, fasting insulin, insulin sensitivity (HOMA-IR), and insulin secretion (HOMA-B). This finding is consistent with our previous report from this cohort (21) and several previous observations that indicate racial/ethnic disparities in the formation of glycated products (22, 23). The POP-ABC data confirm ethnic disparity in HbA1c among normoglycemic African-Americans and Caucasians with similar hereditary risk for diabetes and caution against the sole use of HbA1c for diagnosis of diabetes and prediabetes in diverse populations (24). At enrollment, surrogate measures of insulin resistance (HOMA-IR) and insulin secretion (HOMA-B) were similar among the African-American and Caucasians subjects in the POP-ABC study. Cross-sectional studies have reported greater insulin resistance in African-Americans than Caucasians (25–27), but those studies included subjects with variable familial history of type 2 diabetes. Our baseline HOMA data indicate that estimates of insulin resistance and insulin secretion from fasting glucose and insulin levels showed no ethnic disparity among normoglycemic African-Americans and Caucasians with parental diabetes. The POP-ABC subjects underwent serial hyperinsulinemic euglycemic clamps and frequently sampled iv glucose tolerance tests. When completed, the analysis of these more robust glucoregulatory measures should confirm whether a parental history of type 2 diabetes abrogates ethnic differences in insulin sensitivity.

Among persons with IGT, the rates of incident type 2 diabetes are similar (∼10%/yr) in African-Americans and Caucasians (7). The similar rate of progression from IGT to diabetes is in discord with the well-known higher prevalence of type 2 diabetes in African-Americans compared with Caucasians (1–3). Theoretically, if more African-Americans progress to prediabetes than Caucasians, and both groups then progress at similar rates to type 2 diabetes, that would explain the higher prevalence of type 2 diabetes among African-Americans. However, prospective data on incident rates of prediabetes are lacking for the general population. In a study of 254 initially normoglycemic Pima Indians, 79 (31%) developed prediabetes during a mean follow-up of 4 yr, yielding an incident prediabetes rate of 7.8/yr (8). Our POP-ABC study will generate novel data on the rates and predictors of incident prediabetes among African-Americans and Caucasians with parental type 2 diabetes and determine whether ethnic disparities are programmed early during the transition to prediabetes. In conclusion, the data obtained at baseline from the participants enrolled in the POP-ABC Study indicate that the study has recruited a valuable cohort comprising African-American and Caucasian offspring of parents with type 2 diabetes. Observations from this unique cohort should provide novel data on the natural history of prediabetes and the role of race/ethnicity in the pathogenesis of early glucose abnormalities.