Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study.
To test whether average long-term glucose exposure is associated with cognitive and physical function in middle-aged and younger-old adults with type 2 diabetes mellitus.



Prospective cohort study.



Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Movement and Memory ancillary study (NCT01410097).



Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 at baseline (N = 879).



Glycosylated hemoglobin (HbA1c) was measured at regular intervals over 7 years, and objective measures of cognitive function (Trail-Making Test, Modified Stroop Color-Word Test, Digit Symbol-Coding, Rey Auditory Verbal Learning Test, Modified Mini-Mental State Examination) and physical function (Short Physical Performance Battery, expanded Physical Performance Battery, 400-m and 20-m gait speed) and strength (grip and knee extensor strength) were assessed at the Year 8 or 9 follow-up examination.



Average HbA1c exposure was 7.0 ± 1.1% (53 ± 11.6 mmol/mol), with 57% of participants classified as having HbA1c levels of less than 7% (<53 mmol/mol), 27% having levels of 7% to 8% (53-64 mmol/mol), and 16% having levels of greater than 8% (>64 mmol/mol). After adjustment for age, sex, race, education, smoking status, alcohol intake, knee pain, physical fitness, body mass index, diabetes mellitus medication and statin use, ancillary year visit, and study arm and site, higher HbA1c was associated with worse physical but not cognitive function. Further adjustment for prevalent diabetes mellitus-related comorbidities made all associations nonsignificant. Results did not differ when stratified according to participant baseline age (<60 vs ≥ 60).



Results presented here suggest that, in the absence of diabetes mellitus-related complications, longitudinal glucose exposure is not associated with future cognitive and physical function. Optimal management of diabetes mellitus-related comorbidities may prevent or reduce the burden of disability associated with type 2 diabetes mellitus.
Department of Health and Exercise Science, Wake Forest University, Winston-Salem, North Carolina.
Kristen M
KM
Beavers
Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, North Carolina.
Iris
I
Leng
Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, North Carolina.
Stephen R
SR
Rapp
Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, North Carolina.
Michael E
ME
Miller
Department of Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Denise K
DK
Houston
Department of Health and Exercise Science, Wake Forest University, Winston-Salem, North Carolina.
Anthony P
AP
Marsh
Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, North Carolina.
Don G
DG
Hire
Department of Psychiatry and Behavioral Medicine, Wake Forest University, Winston-Salem, North Carolina.
Laura D
LD
Baker
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana.
George A
GA
Bray
Division of Nutrition, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts.
George L
GL
Blackburn
Department of Physical Therapy, University of Pittsburgh, Pittsburgh, Pennsylvania.
Andrea L
AL
Hergenroeder
Department of Health and Physical Activity, University of Pittsburgh, Pittsburgh, Pennsylvania.
John M
JM
Jakicic
Department of Preventive Medicine, Health Science Center, University of Tennessee, Memphis, Tennessee.
Karen C
KC
Johnson
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Mary T
MT
Korytkowski
Department of Physical Medicine and Rehabilitation, School of Medicine, University of Colorado Denver, Aurora, Colorado.
Brent Van
BV
Dorsten
Department of Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Stephen B
SB
Kritchevsky
D000367:Age Factors; D000368:Aged; D003071:Cognition; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005080:Exercise Test; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009765:Obesity / Q000453:epidemiology; D050177:Overweight / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D006442:Glycated Hemoglobin
HbA1c; cognition; physical function; type 2 diabetes mellitus
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