Hyperinsulinemia and Cognitive Decline in a Middle-Aged Cohort

Pathophysiology/Complications

¹Department of Family Medicine, Medical University of South Carolina, Charleston, South Carolina
²Department of Family Medicine, Medical College of Georgia, Augusta, Georgia

Address correspondence and reprint requests to Sara E. Young, MD, Department of Family Medicine, Medical College of Georgia, HB-3032, Augusta, GA 30912-3500. E-mail: sayoung{at}mcg.edu

Diabetes Care 2006 Dec; 29(12): 2688-2693. https://doi.org/10.2337/dc06-0915

Article Figures & Tables

Table 1—

Characteristics of participants in the ARIC study who did not have diabetes, dementia, or stroke at baseline

Characteristics	n	Percent
Demographics
Age (years)	7,148	53.7 (mean)
Sex
Male	3,173	44.39
Female	3,975	55.61
Race
White	5,729	80.15
Nonwhite	1,419	19.85
Marital status
Married	5,819	81.41
Divorced	572	8.00
Widowed	449	6.28
Separated	174	2.43
Never married	134	1.87
Education level
Basic education (0–11 years)	1,184	16.58
Intermediate education (12–16 years)	3,057	42.80
Advanced education (17–21 years)	2,902	40.63
Diseases and expenses
Hypertension	2,878	40.26
No hypertension	4,270	59.74
Hyperlipidemia	3,811	53.32
No hyperlipidemia	3,337	46.68
Depression score	7,147	2.18 (mean)
Cigarette smoking status
Never smoked	3,228	45.18
Former smoker	2,424	33.93
Current smoker	193	20.90
Alcohol use status
No alcohol use	4,243	59.36
Alcohol use	2,894	40.49
Measures of insulin resistance
Baseline fasting insulin >12.2 mU/l	1,908	26.69
Baseline fasting insulin <12.2 mU/l	5,240	73.30
Baseline HOMA >2.6	2,600	36.37
Baseline HOMA <2.6	4,548	63.63

Table 2—

Mean baseline cognitive test scores and mean cognitive test change scores compared between those with and without hyperinsulinemia at baseline

	With hyperinsulinemia	Without hyperinsulinemia	P value
Fasting insulin (cutoff 75th percentile)
Baseline DWR	6.58 ± 1.42	6.83 ± 1.42	<0.0001*
DWR change score	−0.254 ± 1.53	−0.129 ± 1.54	0.0074*
Baseline DSS	43.0 ± 13.7	47.9 ± 13.1	<0.0001*
DSS change score	−2.74 ± 7.30	−2.51 ± 6.85	0.2954
Baseline WF	32.5 ± 12.3	35.1 ± 12.1	<0.0001*
WF change score	−1.19 ± 7.86	−0.532 ± 7.92	0.0064*
Fasting insulin (cutoff 12.2 mU/l)
Baseline DWR	6.59 ± 1.40	6.85 ± 1.43	<0.0001*
DWR change score	−0.205 ± 1.57	−0.134 ± 1.55	0.0906
Baseline DSS	43.7 ± 13.7	48.1 ± 13.1	<0.0001*
DSS change score	−2.66 ± 7.14	−2.51 ± 6.86	0.4348
Baseline WF	32.7 ± 12.2	35.3 ± 12.1	<0.0001*
WF change score	−1.035 ± 7.83	−0.520 ± 7.94	0.0164*
HOMA (cutoff 75th percentile)
Baseline DWR	6.56 ± 1.41	6.82 ± 1.43	<0.0001*
DWR change score	−0.277 ± 1.52	−0.128 ± 1.54	0.0025*
Baseline DSS	42.8 ± 13.8	47.8 ± 13.2	<0.0001*
DSS change score	−2.74 ± 7.26	−2.51 ± 6.87	0.3152
Baseline WF	32.3 ± 12.4	35.0 ± 12.1	<0.0001*
WF change score	−1.08 ± 7.84	−0.570 ± 7.93	0.0423*
HOMA (cutoff 2.6)
Baseline DWR	6.64 ± 1.41	6.86 ± 1.43	<0.0001*
DWR change score	−0.211 ± 1.54	−0.120 ± 1.54	0.0171*
Baseline DSS	44.4 ± 13.7	48.4 ± 13.0	<0.0001*
DSS change score	−2.57 ± 7.00	−2.54 ± 6.91	0.8335
Baseline WF	33.1 ± 12.1	35.5 ± 12.2	<0.0001*
WF change score	−0.88 ± 7.84	−0.53 ± 7.96	0.0799

Table 3—

Linear regression models for cognitive test scores and cognitive test change scores with hyperinsulinemia variables

	β Coefficient of hyperinsulinemia variable	P value
Baseline DWR
Fasting insulin (cutoff 75th percentile)	−0.0687	0.0962
Fasting insulin (cutoff 12.2 mU/l)	−0.0779	0.0351*
HOMA (cutoff 75th percentile)	−0.0677	0.1154
HOMA (cutoff 2.6)	−0.0315	0.3583
DWR change scores
Fasting insulin (cutoff 75th percentile)	−0.0929	0.0527
Fasting insulin (cutoff 12.2 mU/l)	−0.0335	0.4351
HOMA (cutoff 75th percentile)	−0.1135	0.0245*
HOMA (cutoff 2.6)	−0.0563	0.1604
Baseline DSS
Fasting insulin (cutoff 75th percentile)	−0.7665	0.0092*
Fasting insulin (cutoff 12.2 mU/l)	−0.4598	0.0834
HOMA (cutoff 75th percentile)	−0.7009	0.0218*
HOMA (cutoff 2.6)	−0.3405	0.1634
DSS change scores
Fasting insulin (cutoff 75th percentile)	−0.4039	0.0727
Fasting insulin (cutoff 12.2 mU/l)	−0.2931	0.1370
HOMA (cutoff 75th percentile)	−0.3753	0.1119
HOMA (cutoff 2.6)	−0.1140	0.5262
Baseline WF
Fasting insulin (cutoff 75th percentile)	−0.6618	0.0447*
Fasting insulin (cutoff 12.2 mU/l)	−0.7098	0.0161*
HOMA (cutoff 75th percentile)	−0.6867	0.0471*
HOMA (cutoff 2.6)	−0.6918	0.0115*
WF change scores
Fasting insulin (cutoff 75th percentile)	−0.5634	0.0226*
Fasting insulin (cutoff 12.2 mU/l)	−0.4105	0.0626
HOMA (cutoff 75th percentile)	−0.3952	0.1256
HOMA (cutoff 2.6)	−0.2296	0.2617

Reference levels being those without hyperinsulinemia at baseline. All regressions adjusted for age, sex, race, marital status, education level, smoking status, alcohol use, depression score, history of hypertension, and history of hyperlipidemia.
*
↵* Significant P values of Wald F test for hyperinsulinemia variables.