Table 2.

Association of Traditional Glycemic and Non-Glycemic Risk Factors and Micro- and Macrovascular Complications with Cognitive Domains^*

	Immediate Memory				Delayed Recall				Psychomotor and Mental Efficiency
	β	SE	t- value	p-value	β	SE	t- value	p-value	β	SE	t- value	p-value
Treatment group (conventional vs. intensive)	0·027	0·041	0·65	0·52	−0·010	0·054	−0·19	0·85	0·028	0·052	0·53	0·59
Demographic Characteristics
Age (per 1 year)	−0·014	0·003	−4·55	<0·0001	−0·011	0·004	−2·90	0·0039	−0·041	0·004	−11·48	<0·0001
Sex (men vs. women)	−0·016	0·041	−0·38	0·70	−0·074	0·054	−1·36	0·17	−0·323	0·051	−6·37	<0·0001
Education (per 1 year)	0·034	0·006	5·23	<0·0001	0·039	0·008	4·80	<0·0001	0·104	0·010	10·96	<0·0001
Risk Factors
Glycemic
HbA1c (per 1 %)†	−0·023	0·012	−1·84	0·066	−0·015	0·016	−0·98	0·33	−0·114	0·018	−6·38	<0·0001
Severe hypoglycemia‡
Cumulative (≥1 vs. 0 events)	−0·047	0·029	−1·59	0·11	−0·019	0·037	−0·51	0·61	−0·152	0·044	−3·49	0·0006
1-5 events vs. 0 events	−0·039	0·029	−1·32	0·19	−0·013	0·037	−0·34	0·73	−0·139	0·044	−3·14	0·0018
>5 events vs. 0 events	−0·178	0·062	−2·90	0·0040	−0·124	0·078	−1·60	0·11	−0·320	0·094	−3·40	0·0007
Recent (≥1 vs. 0 events)	−0·006	0·061	−0·10	0·92	0·020	0·076	0·27	0·79	−0·242	0·098	−2·48	0·015
Non-glycemic
Body mass index (per 1 kg/m2)†	0·002	0·005	0·42	0·68	0·005	0·006	0·76	0·45	−0·018	0·007	−2·70	0·0071
Blood pressure (per 5 mm Hg)†
Systolic	−0·008	0·010	−0·88	0·38	−0·014	0·012	−1·18	0·24	−0·157	0·013	−11·91	<0·0001
Diastolic	0·018	0·014	1·22	0·22	0·013	0·018	0·72	0·47	−0·030	0·020	−1·46	0·15
Pulse rate (per 1 bpm)†	−0·001	0·002	−0·32	0·75	0·002	0·002	0·85	0·39	−0·012	0·003	−4·42	<0·0001
Plasma lipids (per 10 mg/dl)†
Total cholesterol	−0·010	0·006	−1·83	0·067	−0·013	0·007	−1·81	0·070	−0·014	0·008	−1·79	0·074
HDL cholesterol	0·008	0·012	0·65	0·51	0·001	0·015	0·06	0·95	0·063	0·017	3·77	0·0002
LDL cholesterol	−0·005	0·006	−0·95	0·34	−0·009	0·007	−1·32	0·19	−0·008	0·008	−1·00	0·32
Triglycerides (log)	−0·259	0·317	−0·82	0·41	−0·704	0·403	−1·75	0·080	−2·254	0·467	−4·83	<0·0001
Complications
Kidney Disease
Sustained AER ≥30 mg/24 hr (yes vs. no)§	−0·016	0·034	−0·46	0·65	−0·041	0·043	−0·95	0·34	−0·331	0·050	−6·61	<0·0001
eGFR <60 mL/min/1·73 m2 (yes vs. no)§	−0·198	0·050	−3·95	0·0001	−0·162	0·063	−2·57	0·011	−0·866	0·080	−10·88	<0·0001
Retinopathy
PDR (yes vs. no)§	−0·012	0·035	−0·34	0·74	−0·035	0·044	−0·80	0·42	−0·561	0·054	−10·34	<0·0001
CSME (yes vs. no)§	−0·081	0·033	−2·43	0·016	−0·094	0·042	−2·25	0·025	−0·455	0·051	−8·85	<0·0001
Neuropathy
Confirmed clinical neuropathy (yes vs. no)§	−0·041	0·035	−1·16	0·25	−0·121	0·045	−2·71	0·0072	−0·527	0·052	−10·05	<0·0001
Cardiovascular autonomic neuropathy (yes vs. no)§	−0·091	0·032	−2·85	0·0047	−0·119	0·040	−2·96	0·0033	−0·476	0·049	−9·74	<0·0001
Cardiovascular
Cardiovascular disease (yes vs. no)§	−0·124	0·046	−2·71	0·0075	−0·071	0·057	−1·23	0·22	−0·577	0·073	−7·91	<0·0001

^*Data are beta coefficients, standard errors, t-values, and p-values from individual generalized linear mixed models evaluating the association of each domain with each covariate of interest, with no adjustment for other factors. With the exception of treatment group, age, and sex, each covariate was entered into the model as a time-dependent covariate. Beta estimates are equal to the difference in means between groups or the slope of the association (e.g. increase or decrease in mean domain score for every 1-unit change in the time-dependent covariate). The signed t-value corresponds to the magnitude and directionality of the association. HDL denotes high-density lipoprotein, LDL low-density lipoprotein, AER albumin excretion rate, eGFR estimated glomerular filtration, PDR proliferative diabetic retinopathy, and CSME clinically-significant macular edema.

^†Risk factors were characterized by the time-weighted mean of all follow-up values since DCCT baseline up to each visit, weighting each value by the time interval since the last measurement.

^‡Severe hypoglycemia was defined as events leading to coma or seizure documented by self-report for the 3-month period prior to each annual study visit. “Cumulative” refers to the running sum of all events up to each cognitive evaluation. “Recent” refers to the number of events recorded at the time of each cognitive evaluation.

^§Any report between DCCT baseline and each annual study visit.