HbA1c is the standard measure by which to monitor long-term (2-3 months) glucose control in people with diabetes and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are ...markers of short-term (2-4 weeks) glycaemic control that might add complementary prognostic information to HbA1c. Our aim was to clarify the performance of fructosamine and glycated albumin measurements for identifying people at risk of incident diabetes or diabetic complications.
We measured glycated albumin and fructosamine in blood samples from 11 348 adults without diabetes and 958 adults diagnosed with diabetes mellitus (both type 1 and 2) who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) study in 1990-92 (baseline). We assessed the associations of fructosamine and glycated albumin with risk of incident diabetes, retinopathy, and risk of incident chronic kidney disease (CKD), during two decades of follow-up. We compared these associations with those of HbA1c with incident diabetes, retinopathy, and CKD. For analyses of associations with incident diabetes and CKD, adjusted hazard ratios (HRs) and their corresponding 95% CIs were estimated using Cox proportional hazards models. Model discrimination was assessed using Harrell's C statistic.
The HRs for incident diabetes were 4·96 (4·36-5·64) for fructosamine above the 95th percentile and 6·17 (5·45-6·99) for glycated albumin above the 95th percentile. Associations were attenuated but persisted after adjustment for HbA1c. Fructosamine and glycated albumin were strongly associated with retinopathy (p<0·0001 for trend). The multivariable-adjusted HRs for CKD for people with fructosamine and glycated albumin above the 95th percentile were 1·50 (95% CI 1·22-1·85) and 1·48 (1·20-1·83), respectively, when compared with people with no diabetes and fructosamine or glycated albumin below the 75th percentile. Prediction of incident CKD by fructosamine (C statistic 0·717) and glycated albumin (0·717) were nearly as strong as by HbA1c (0·726), but HbA1c outperformed fructosamine and glycated albumin for prediction of incident diabetes with C statistics of 0·760, 0·706, and 0·703, respectively.
Fructosamine and glycated albumin were strongly associated with incident diabetes and its microvascular complications, with prognostic value comparable to HbA1c.
National Heart, Lung, and Blood Institute.
To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.
Findings were pooled from 5 ...population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.
After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.
Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: The term prediabetes is used to identify individuals at increased risk for diabetes. However, the natural history of prediabetes in older age is not well characterized. OBJECTIVES: To ...compare different prediabetes definitions and characterize the risks of prediabetes and diabetes among older adults in a community-based setting. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort analysis of 3412 older adults without diabetes from the Atherosclerosis Risk in Communities Study (baseline, 2011-2013), participants were contacted semiannually through December 31, 2017, and attended a follow-up visit between January 1, 2016, and December 31, 2017 (median range follow-up, 5.0 0.1-6.5 years). EXPOSURES: Prediabetes defined by a glycated hemoglobin (HbA1c) level of 5.7% to 6.4%, impaired fasting glucose (IFG) level (FG level of 100-125 mg/dL), either, or both. MAIN OUTCOMES AND MEASURES: Incident total diabetes (physician diagnosis, glucose-lowering medication use, HbA1c level ≥6.5%, or FG level ≥126 mg/dL). RESULTS: A total of 3412 participants without diabetes (mean SD age, 75.6 5.2 years; 2040 60% female; and 572 17% Black) attended visit 5 (2011-2013, baseline). Of the 3412 participants at baseline, a total of 2497 participants attended the follow-up visit or died. During the 6.5-year follow-up period, there were 156 incident total diabetes cases (118 diagnosed) and 434 deaths. A total of 1490 participants (44%) had HbA1c levels of 5.7% to 6.4%, 1996 (59%) had IFG, 2482 (73%) met the HbA1c or IFG criteria, and 1004 (29%) met both the HbA1c and IFG criteria. Among participants with HbA1c levels of 5.7% to 6.4% at baseline, 97 (9%) progressed to diabetes, 148 (13%) regressed to normoglycemia (HbA1c, <5.7%), and 207 (19%) died. Of those with IFG at baseline, 112 (8%) progressed to diabetes, 647 (44%) regressed to normoglycemia (FG, <100 mg/dL), and 236 (16%) died. Of those with baseline HbA1c levels less than 5.7%, 239 (17%) progressed to HbA1c levels of 5.7% to 6.4% and 41 (3%) developed diabetes. Of those with baseline FG levels less than 100 mg/dL, 80 (8%) progressed to IFG (FG, 100-125 mg/dL) and 26 (3%) developed diabetes. CONCLUSIONS AND RELEVANCE: In this community-based cohort study of older adults, the prevalence of prediabetes was high; however, during the study period, regression to normoglycemia or death was more frequent than progression to diabetes. These findings suggest that prediabetes may not be a robust diagnostic entity in older age.
Hemoglobin A
(HbA
), a measure of average blood glucose level, is associated with the risk of dementia and cognitive impairment. However, the role of glycemic variability or glucose excursions in ...this association is unclear. We examined the association of glucose peaks in midlife, as determined by the measurement of 1,5-anhydroglucitol (1,5-AG) level, with the risk of dementia and 20-year cognitive decline.
Nearly 13,000 participants from the Atherosclerosis Risk in Communities (ARIC) study were examined. Dementia was ascertained from surveillance, neuropsychological testing, telephone calls with participants or their proxies, or death certificate dementia codes. Cognitive function was assessed using three neuropsychological tests at three visits over 20 years and was summarized as
scores. We used Cox and linear mixed-effects models. 1,5-AG level was dichotomized at 10 μg/mL and examined within clinical categories of HbA
.
Over a median time of 21 years, dementia developed in 1,105 participants. Among persons with diabetes, each 5 μg/mL decrease in 1,5-AG increased the estimated risk of dementia by 16% (hazard ratio 1.16,
= 0.032). For cognitive decline among participants with diabetes and HbA
<7% (53 mmol/mol), those with glucose peaks had a 0.19 greater
score decline over 20 years (
= 0.162) compared with those without peaks. Among participants with diabetes and HbA
≥7% (53 mmol/mol), those with glucose peaks had a 0.38 greater
score decline compared with persons without glucose peaks (
< 0.001). We found no significant associations in persons without diabetes.
Among participants with diabetes, glucose peaks are a risk factor for cognitive decline and dementia. Targeting glucose peaks, in addition to average glycemia, may be an important avenue for prevention.
BACKGROUND—Hemoglobin A1c (HbA1c) is the standard measure to monitor glucose control in diabetes mellitus and is a marker of future cardiovascular risk. Fructosamine and glycated albumin are markers ...of short-term glycemic control, but their associations with cardiovascular outcomes are uncharacterized.
METHODS AND RESULTS—We measured glycated albumin and fructosamine in 11 104 participants with and without diabetes in the community-based Atherosclerosis Risk in Communities (ARIC) Study in 1990 to 1992 (baseline). We evaluated associations of fructosamine and glycated albumin with risk of coronary heart disease, ischemic stroke, heart failure, and mortality. We compared associations with those observed for HbA1c. During two decades of follow-up there were 1096 new cases of coronary heart disease, 605 of ischemic stroke, 1432 of heart failure, and 2860 deaths. Elevated baseline concentrations of fructosamine and glycated albumin were significantly associated with each of the outcomes even after adjustment for traditional cardiovascular risk factors, with especially strong associations in persons with diabetes mellitus. Associations were of similar magnitude to those observed for HbA1c and—as has been previously observed for HbA1c—the associations tended to be J-shaped, with an elevation of risk at the lowest levels of each biomarker.
CONCLUSIONS—The acceptance of new measures of hyperglycemia is partly dependent on establishing their association with long-term outcomes. We found that fructosamine and glycated albumin were associated with vascular outcomes and mortality and that these associations were similar to those observed for HbA1c.
Advanced glycation end products (AGEs) and their receptors are strongly implicated in the development of diabetes complications. When stimulated by AGEs, the receptors for AGEs (RAGEs) induce ...inflammation and are thought to fuel disease progression. Soluble circulating RAGE (sRAGE) may counteract the detrimental effects of RAGE. We measured sRAGE in stored plasma from a random sample of 1,201 participants in the Atherosclerosis Risk in Communities (ARIC) Study who were aged 47-68 years, had normal kidney function, and had no history of cardiovascular disease. In cross-sectional analyses, black race, male sex, higher BMI, and higher C-reactive protein were independently associated with low sRAGE. The racial difference was striking, with blacks approximately three times more likely to have low sRAGE compared with whites even after adjustment. During ~18 years of follow-up, there were 192 incident coronary heart disease events, 53 ischemic strokes, 213 deaths, and 253 cases of diabetes (among the 1,057 persons without diabetes at baseline). In multivariable Cox models comparing risk in the first quartile with that in the fourth quartile of baseline sRAGE, low levels of sRAGE were significantly associated with risk of diabetes (hazard ratio 1.64 95% CI 1.10-2.44), coronary heart disease (1.82 1.17-2.84), and mortality (1.72 1.11-2.64) but not ischemic stroke (0.78 0.34-1.79). In conclusion, we found that low levels of sRAGE were a marker of future chronic disease risk and mortality in the community and may represent an inflammatory state. Racial differences in sRAGE deserve further examination.
IMPORTANCE: The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following ...prolonged hypertension may be associated with poor cognitive outcomes. OBJECTIVE: To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017. EXPOSURES: Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5. MAIN OUTCOMES AND MEASURES: Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation. RESULTS: Among 4761 participants (2821 59% women; 979 21% black race; visit 5 mean SD age, 75 5 years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio HR, 1.49 95% CI, 1.06-2.08) and in the midlife hypertension and late-life hypotension group (HR, 1.62 95% CI, 1.11-2.37) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 95% CI, 1.17-1.71). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 95% CI, 1.01-2.69). There was no significant association of BP patterns with late-life cognitive change. CONCLUSIONS AND RELEVANCE: In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.
Type 2 diabetes is associated with dementia risk, but evidence is limited for possible associations of diabetes and prediabetes with cognitive decline.
To determine whether diabetes in midlife is ...associated with 20-year cognitive decline and to characterize long-term cognitive decline across clinical categories of hemoglobin A1c (HbA1c) levels.
Prospective cohort study.
The community-based ARIC (Atherosclerosis Risk in Communities) study.
13,351 black and white adults aged 48 to 67 years at baseline (1990 to 1992).
Diabetes was defined by self-reported physician diagnosis or medication use or HbA1c level of 6.5% or greater. Undiagnosed diabetes, prediabetes, and glucose control in persons with diagnosed diabetes were defined by clinical categories of HbA1c level. Delayed word recall, digit symbol substitution, and word fluency tests were used to assess cognitive performance and were summarized with a global Z score.
Diabetes in midlife was associated with a 19% greater cognitive decline over 20 years (adjusted global Z-score difference, -0.15 ;95% CI, -0.22 to -0.08;) compared with no diabetes. Cognitive decline was significantly greater among persons with prediabetes (HbA1c level of 5.7% to 6.4%) than among those with an HbA1c level less than 5.7%. Participants with poorly controlled diabetes (HbA1c level ≥ 7.0%) had greater decline than those whose diabetes was controlled (adjusted global Z-score difference, -0.16; P = 0.071). Longer-duration diabetes was also associated with greater late-life cognitive decline (P for trend < 0.001). Rates of decline did not differ significantly between white and black persons (P for interaction = 0.44).
Single HbA1c measurement at baseline, 1 test per cognitive domain, and potential geographic confounding of race comparisons.
Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline.
National Institutes of Health.
The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic ...screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.
We sought to examine associations in older adults among diabetes, glycemic control, diabetes duration, and biomarkers of hyperglycemia with incident mild cognitive impairment (MCI) and incident ...dementia.
We conducted a prospective analysis of 5,099 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended the fifth (2011-2013) exam. Cognitive status was assessed during follow-up via telephone calls, death certificate codes, surveillance, and a follow-up examination (2016-2017). We defined incident cognitive impairment as incident MCI or incident dementia in persons dementia-free at the index examination; we also examined each outcome separately. Diabetes was defined using self-report, medications, or HbA
≥6.5%; poor glycemic control in persons with diabetes was defined as HbA
≥7%. We examined the following biomarkers of hyperglycemia: HbA
, fructosamine, glycated albumin, and 1,5-anhydroglucitol.
Mean age at baseline was 76 years, 59% were female, and 21% were black. Diabetes (hazard ratio HR 1.14 95% CI 1.00, 1.31), poor glycemic control in persons with diabetes (HR 1.31 95% CI 1.05, 1.63), and longer diabetes duration (≥5 vs. <5 years; HR 1.59 95% CI 1.23, 2.07) were significantly associated with incident cognitive impairment. We found a J-shaped association between HbA
and incident dementia. Glycated albumin and fructosamine were also associated with incident dementia, independently of HbA
. HbA
and fructosamine were also associated with incident MCI.
Diabetes status, poor glycemic control, and longer diabetes duration were associated with worse cognitive outcomes over a median follow-up of 5 years.
PDF
