Prevalence and risk factors of microalbuminuria in a cohort of African-American women with gestational diabetes.

OBJECTIVE: To study the prevalence of microalbuminuria (MA) in African-American women with a history of gestational diabetes (GDM) who are at high risk for insulin resistance and renal dysfunction and to study MA's relation to insulin resistance, type 2 diabetes, and hypertension. RESEARCH DESIGN AND METHODS: MA was assessed using 24-h, timed, and/or random urine samples in a cross-sectional sample (n = 289) from a cohort of African-American women with a history of GDM and followed for a median of 11 years (range 3.0-18.4) since their diabetic pregnancy. Subjects with a urine albumin excretion rate of 30-300 g/24 h or 30-300 microg/mg creatinine in a random sample were classified as having MA if two of three samples over a 3- to 6-month period were positive. These women were evaluated for family history of diabetes, smoking and alcohol use, BMI, diabetes, hypertension, and lipid abnormalities. Insulin sensitivity was determined using the homeostasis model assessment (HOMA) estimates, which used fasting insulin and glucose measurements obtained at the same time as the MA urine sample. RESULTS: At MA assessment, the women ranged in age from 22 to 57 years, with a median of 39 years. The overall prevalence of MA was 20%; 36% in those with diabetes. Those women with MA had higher rates of diabetes (63.8 vs. 28.6%, odds ratio [OR] = 4.4, P < 0.05), hypertension (82.8 vs. 42.9%, OR = 6.4, P < 0.05), and family history of diabetes (85.7 vs. 61.7%, OR = 3.7, P < 0.05). The proportion of subjects with MA with a family history of hypertension was nonsignificantly increased (92.9 vs. 82.4%). Subjects with MA were more obese (BMI 37.2 +/- 8.9 vs. 34.4 +/- 8.6 kg/m(2)) and had higher levels of HbA(1c) (8.8 +/- 3.3 vs. 6.6 +/- 1.8%, P < 0.001) and systolic (144.3 +/- 25.9 vs. 122.8 +/- 17.2 mmHg, P < 0.0001) and diastolic (95.1 +/- 15.4 vs. 82.5 +/- 11.9 mmHg, P < 0.0001) blood pressures. Lipid fractions were similar in those with and without MA. Although fasting glucose was much higher in subjects with MA (10.3 +/- 5.8 vs. 7.1 +/- 4.2 mmol/l, P = 0.0002), insulin levels were not significantly higher in subjects with MA (17.4 +/- 21.2 vs. 15.2 +/- 12.4 pmol/l). Insulin sensitivity, as measured using log HOMA, was similar (1.5 +/- 0.6 vs. 1.6 +/- 0.6) in women with and without MA, respectively. Multivariable logistic regression analyses indicated that HbA(1c), OR = 1.16 (1.07, 1.27), and systolic blood pressure, OR = 1.27 (1.14, 1.41), were independent risk factors for MA. In those with diabetes, the subjects with MA had higher rates of hypertension-83.8 vs. 56.1%, OR = 4.1 (1.5, 11.10)-which was reflected by their higher systolic and diastolic blood pressures, 146.1 mmHg (P = 0.001) and 94.8 mmHg (P = 0.002), respectively, and lower levels of VLDL (0.45 +/- 0.22 vs. 0.61 +/- 0.33 mmol/l, P = 0.021). In the multivariable analyses of those with diabetes, the two independent risk factors for MA were similar: HbA(1c), OR = 1.13 (1.01, 1.28), and systolic blood pressure, OR = 1.21 (1.04, 1.41). CONCLUSIONS: African-American women with a history of GDM have one of the highest rates for MA. Presence of MA was not associated with insulin resistance but was significantly independently associated with HbA(1c) levels and hypertension. These results, taken in context of the literature, suggest that hypertension and glucose intolerance, in part, influence MA through different mechanisms. Because of the high prevalence of MA in this population and MA's relation to all-cause and cardiovascular mortality, screening for MA should be considered.

Genes within the major histocompatibility complex predict NIDDM in African-American women in Alabama.

OBJECTIVE: To test the hypothesis that genes within the major histocompatibility complex (MHC) are associated with gestational diabetes mellitus (GDM) and, subsequently, non-insulin-dependent diabetes mellitus (NIDDM) in African-American women. RESEARCH DESIGN AND METHODS: African-American women who presented with GDM were compared with pregnant African-American control subjects. Following pregnancy, GDM patients were assessed at various intervals of time (median = 6 years) to determine whether they had developed diabetes. RESULTS: GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects. GDM patients who subsequently developed NIDDM had a significantly higher frequency of B41, DR2, and BF-S and a lower frequency of DR1 and DR6 phenotypes than control subjects. Even after controlling for age and body mass index, B41 and DR2 were independent predictors of developing insulin-requiring GDM and NIDDM in GDM subjects. CONCLUSIONS: These results suggest that either one or more genes within the MHC are involved in the etiology of NIDDM.

Autoantibodies in black women with class A1 or class GB diabetes mellitus.

No marker except repeated fasting glucose determinations has proven useful to ascertain prospectively which women with gestational diabetes mellitus will remain euglycemic by diet modification or will require insulin therapy. We screened 183 black women with gestational diabetes mellitus to determine if the presence of islet cell, mitochondrial, nuclear, DNA, parietal cell, smooth muscle, thyroid microsomal, thyroid thyroglobulin autoantibodies, or rheumatoid factor predicted the need for insulin therapy to maintain euglycemia in women with gestational diabetes mellitus. One hundred forty-two women maintained normal fasting plasma glucose levels with dietary modifications and 41 required institution of split-dose insulin therapy. We found no significant differences in the prevalence of these autoantibodies in black women with Class GB versus Class A1 diabetes mellitus. We conclude that screening for autoantibodies in women with gestational diabetes mellitus is not useful in determining which patients will subsequently require insulin therapy during their pregnancies.

Histocompatibility antigen subtypes in black women with class A1 or class GB diabetes mellitus.

Insulin-dependent diabetes mellitus is associated with an increased frequency of certain histocompatibility antigens located on chromosome six, the most common types being B-8, B-15, DR-3, DR-4, and DR-7. We therefore theorized that screening for these subtypes may allow the identification of those women with gestational diabetes who will remain euglycemic on dietary modification (class A1) compared with those who will require insulin to achieve euglycemia (class GB). From 1982 to 1987, 228 black women with gestational diabetes were screened for the above histocompatibility antigens. As theorized, certain histocompatibility antigen subtypes were more common in women with class GB gestational diabetes mellitus; DR-2 (41.8% versus 23.7% p = 0.015), B-15 (p = 0.07), and DR-3 (p = 0.08). However, because of the low sensitivity (42%), specificity (75%), and positive predictive value (36%), this test is impractical in the clinical management of women with gestational diabetes mellitus.

Risk factors for gestational diabetes in black population.

In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis.