Coffee and Caffeine Consumption in Relation to Sex Hormone-Binding Globulin and Risk of Type 2 Diabetes in Postmenopausal Women

The reproducibility and validity of responses for 55 specific foods and beverages on a self-administered food frequency questionnaire were evaluated. One hundred and seventy three women from the Nurses' Health Study completed the questionnaire twice approximately 12 months apart and also recorded their food consumption for seven consecutive days, four times during the one-year interval. For the 55 foods, the mean of correlation coefficients between frequencies of intake for first versus second questionnaire was 0.57 (range = 0.24 for fruit punch to 0.93 for beer). The mean of correlation coefficients between the dietary records and first questionnaire was 0.44 (range = 0.09 for yellow squash to 0.83 for beer and tea) and between the dietary records and the second questionnaire was 0.52 (range = 0.08 for spinach to 0.90 for tea). Ratios of within- to between-person variance for the 55 foods were computed using the mean four one-week dietary records for each person as replicate measurements. For most foods this ratio was greater than 1.0 (geometric mean of ratios = 1.88), ranging from 0.25 (skimmed milk) to 14.76 (spinach). Correlation coefficients comparing questionnaire and dietary record for the 55 foods were corrected for the within-person variation (mean corrected value = 0.55 for dietary record versus first questionnaire and 0.66 versus the second). Mean daily amounts of each food calculated by the questionnaire and by the dietary record were also compared; the observed differences suggested that responses to the questionnaire tended to over-represent socially desirable foods. This analysis documents the validity and reproducibility of the questionnaire for measuring specific foods and beverages, as well as the large within-person variation for food intake measured by dietary records. Differences in the degree of validity for specific foods revealed in this type of analysis can be useful in improving questionnaire design and in interpreting findings from epidemiological studies that use the instrument.

Circulating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. We performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). Among women, higher plasma levels of sex hormone-binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone-binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone-binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex hormone-binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex hormone-binding globulin may have a causal role in the risk of type 2 diabetes. Low circulating levels of sex hormone-binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination. 2009 Massachusetts Medical Society

Standard categorical analysis is based on an unrealistic model for dose-response and trends and does not make efficient use of within-category information. This paper describes two classes of simple alternatives that can be implemented with any regression software: fractional polynomial regression and spline regression. These methods are illustrated in a problem of estimating historical trends in human immunodeficiency virus incidence. Fractional polynomial and spline regression are especially valuable when important nonlinearities are anticipated and software for more general nonparametric regression approaches is not available.