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Chronic kidney disease, insulin resistance, and incident diabetes in older adults.

TitleChronic kidney disease, insulin resistance, and incident diabetes in older adults.
Publication TypeJournal Article
Year of Publication2012
AuthorsPham, H, Robinson-Cohen, C, Biggs, ML, Ix, JH, Mukamal, KJ, Fried, LF, Kestenbaum, B, Siscovick, DS, de Boer, IH
JournalClin J Am Soc Nephrol
Volume7
Issue4
Pagination588-94
Date Published2012 Apr
ISSN1555-905X
KeywordsAge Factors, Aged, Aged, 80 and over, Biomarkers, Chronic Disease, Creatinine, Diabetes Mellitus, Female, Glomerular Filtration Rate, Glucose Tolerance Test, Health Surveys, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin Resistance, Insulin-Secreting Cells, Kidney, Kidney Diseases, Linear Models, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, United States
Abstract<p><b>BACKGROUND AND OBJECTIVES: </b>Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic β cell, effects on glucose tolerance, and risk of diabetes are not clear.</p><p><b>DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: </b>The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, β cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose ≥126 mg/dl, nonfasting glucose ≥200 mg/dl, or use of glucose-lowering medications.</p><p><b>RESULTS: </b>Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2% higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%; P<0.001) and a 1.1% lower insulin sensitivity index (95% CI, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented β cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437 participants (9.3%) developed diabetes. eGFR was not associated with the risk of incident diabetes.</p><p><b>CONCLUSIONS: </b>Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased.</p>
DOI10.2215/CJN.11861111
Alternate JournalClin J Am Soc Nephrol
PubMed ID22383749
PubMed Central IDPMC3315343
Grant ListR01 DK087726 / DK / NIDDK NIH HHS / United States
R01 DK088762 / DK / NIDDK NIH HHS / United States
UL1 TR000005 / TR / NCATS NIH HHS / United States
UL1 RR024153 / RR / NCRR NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
DK-087726 / DK / NIDDK NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States