Association of uncalibrated and calibrated energy and protein intakes with risk of diabetes in postmenopausal women (36.5)
Authors: Tinker L.F. , Zheng C , Sarto G , Heiss G , Neuhouser M.L. , Di C , Johnson K.C. , Beasley J.M. , Eaton C.B. , Chen B.H. , Agha G , LaMonte M.J. , Rodriguez B , Seguin R , Wylie‐Rosett J , Calhoun D , Prentice R.L. 
Published: June 2021

Excess body mass and higher protein intake have been associated with an increased risk of type 2 diabetes. Dietary self‐report may under estimate energy & protein intake. The analyses examine uncalibrated (self‐report) & biomarker‐calibrated energy & protein intakes on risk of diabetes in postmenopausal women. Data are from Women’s Health Initiative (WHI) Observational Study (OS) n=93676 & Dietary Modification Trial Comparison (DMC) n=29294. Diet was assessed by food frequency questionnaire (FFQ) in OS & DMC & 4‐day food record (4DFR) in a 4.6% DMC subset. Calibration equations from a doubly labeled water & 24‐hr urinary nitrogen substudy (n=450 OS, n=544 DMC) were applied to diet self‐report (T 1).

Table 1. Dietary Intakes at Baseline, Uncalibrated and Calibrated

OSn=59,670
DMCn=17,603
DMCn=2,621

Dietary Self‐Report
FFQ(Geometric mean, 95% CI)
4DFR(Geometric mean, 95% CI)

Energy, kcal

Uncalibrated
1469 (711, 2962)
1517 (734, 3063)
1655 (977, 2635)

Calibrated
2098 (1795, 2574)
2144 (1826, 2602)
2180 (1768, 2752)

Protein, g

Uncalibrated
60.9 (26.3, 129.1)
62.6 (27.6, 131.2)
64.7 (36.7, 104.0)

Calibrated
77 (56.4, 101.5)
78.8 (58.5, 102.2)
77.1 (54.8, 103.0)

Protein Density, % energy from protein

Uncalibrated
16.6 (11.0, 23.7)
16.5 (11.3, 23.4)
15.8 (10.8, 22.9)

Calibrated
14.5 (11.8, 17.3)
14.4 (11.8, 17.1)
14.1 (11.6, 17.6)

Incident diabetes was assessed after baseline 1993‐2012. Hazard ratios (HR) were computed for incident diabetes associated with 20% higher energy (kcal/d), protein (g/d) or protein density (% energy from protein/d) with & without BMI adjustment (T 2). Without BMI, HRs in OS FFQ uncalibrated energy, protein & protein density were 1.06, 1.03 & 1.03 and after calibration were 2.46, 2.40 & 0.90. Calibration & BMI adjustment absorbed some association yet HRs remained significant in the OS for energy by FFQ (1.61) & DMC for protein density by FFQ (1.15).

Table 2. Association of a 20% Higher Intake of Energy or Protein with Risk of Diabetes in the Womenâ€™s Health Initiative

HR (95% CI) a, b

OSn=59,670Incident diabetes: 4819
DMCn=17,603Incident diabetes: 2009
DMCn=2,621Incident diabetes: 336

FFQ
4DFR

Energy, kcal

Uncalibrated HR
1.06 (1.04, 1.07)
1.03 (1.00, 1.05)
1.03 (0.95, 1.12)

Uncalibrated HR adjusted for BMI (kg/m2)c
1.03 (1.02, 1.04)
1.01 (0.99, 1.03)
1.00 (0.92, 1.08)

Calibrated HR
2.46 (2.09, 2.88)
2.40 (2.04, 2.84)
2.09 (1.67, 2.62)

Calibrated HR adjusted for BMI (kg/m2) c
1.61 (1.09, 2.37)
1.12 (0.78, 1.61)
1.00 (0.64, 1.58)

Protein, g

Uncalibrated HR
1.06 (1.04, 1.07)
1.04 (1.02, 1.07)
1.08 (1.00, 1.17)

Uncalibrated HR adjusted for BMI (kg/m2) c
1.03 (1.01, 1.04)
1.02 (1.00, 1.04)
1.04 (0.96, 1.12)

Calibrated HR
2.00 (1.67, 2.39)
1.77 (1.50, 2.09)
1.45 (1.23, 1.69)

Calibrated HR adjusted for BMI (kg/m2) c
1.12 (0.99, 1.27)
1.10 (0.99, 1.23)
1.07 (0.91, 1.26)

Protein Density, % energy from protein

Uncalibrated HR
1.03 (1.00, 1.07)
1.10 (1.05, 1.15)
1.10 (0.98, 1.23)

Uncalibrated HR adjusted for BMI (kg/m2) c
1.01 (0.98, 1.04)
1.06 (1.02, 1.11)
1.07 (0.96, 1.19)

Calibrated HR
0.90 (0.66, 1.24)
0.98 (0.75, 1.28)
1.10 (0.83, 1.46)

Calibrated HR adjusted for BMI (kg/m2) c
1.02 (0.95, 1.10)
1.15 (1.02, 1.29)
1.14 (0.91, 1.42)

a. Analyses excluded prevalent diabetes (n=2996 for OS; n=704 for DMC analyzed with FFQ; n=165 analyzed with 4DFR).b. Analyses additionally adjusted for potential covariates or confounders of age, race/ethnicity, education, physical activity, smoking, alcohol, hormone use, hypertension, history of cardiovascular disease, randomization to Hormone Trial for the DMC.c. BMI was on average 26.9 (19.6, 40.8 95% CI) in the OS and 28.7 ( 20.3, 41.6 95% CI) in the DMC for the FFQ analyses. BMI was on average 28.9 ( 20.4, 42.0 95% CI) for the 4DFR analyses.

In conclusion, the use of calibrated FFQ or 4DFR dietary intakes may enhance the ability to reveal diet‐diabetes associations compared to self‐reported uncalibrated intakes.

Grant Funding Source: Supported by R01 CA119171‐04A1, R01 CA119171