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Insulin Resistance Syndrome in the Elderly Assessment of Functional, Biochemical, Metabolic, and Inflammatory Status

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Insulin Resistance Syndrome in the Elderly Assessment of Functional, Biochemical, Metabolic, and Inflammatory Status Cardiovascular and Metabolic Risk ORIGINAL ARTICLE Insulin Resistance Syndrome in the Elderly Assessment of functional, biochemical, metabolic, and inflammatory status 1,2 2 WILLIAM A. BANKS, MD DAVID R. THOMAS, MD nosing IRS is difficult. As such, diagnosis 3 1,2 LISA M. WILLOUGHBY, PHD JOHN E. MORLEY, MB, BCH is often made based on the presence of secondary criteria, such as hypertension, history of glucose intolerance, or elevated OBJECTIVE — Hyperinsulinemic euglycemia, or insulin resistance syndrome (IRS), is asso- BMI (2). As these are also associated with ciated with increased morbidity and mortality. Although thought to be associated with proin- diabetes and likely are sequella develop- flammatory states, little work has been done in this area. Here, we determined the impact of IRS ing from IRS, such a diagnostic approach on functional, biochemical, metabolic, and inflammatory status in a high-risk population: el- makes it difficult to ascertain incidence of derly women in nursing homes. IRS or to study early pathological events that may be unique to it. These difficulties RESEARCH DESIGN AND METHODS — Functional, biochemical, metabolic, and are magnified in the elderly, as many of inflammatory parameters were measured in 100 consecutive ambulatory, elderly women who resided in nursing homes. Diabetic subjects and residents with fasting blood glucose Ն110 mg/dl the secondary criteria are independently were excluded. Remaining residents were classified as insulin resistant (IR) (insulin Ͼ100 associated with aging. pmol/l) or non-IR (NIR). Here, we studied a population of el- derly, ambulatory women living in long- RESULTS — A total of 16 residents were IR and 53 NIR. No differences in functional status, term care facilities in a Midwestern BMI, renal function, C-reactive protein, or immune cell levels were found. Fasting blood glucose metropolitan area. We assessed in the eu- was higher in IR subjects ([means Ϯ SD] 94.1 Ϯ 8.1 vs. 87.9 Ϯ 8.2, P Ͻ 0.05), indicating a very glycemic subset their functional, bio- mild glucose intolerance. Serum C-peptide (P Ͻ 0.05), amylin (P Ͻ 0.01), and leptin (P Ͻ 0.01), chemical, metabolic, and inflammatory but not adiponectin or resistin, were higher in IR subjects. Higher leptin-to-BMI and insulin– parameters as a function of endogenous to–C-peptide ratios suggested an increased percent body fat mass and altered clearance of serum insulin levels. insulin, respectively. Eleven of 13 cytokines had arithmetic elevations, but only tumor necrosis factor-␣ (TNF) reached statistical significance (P Ͻ 0.01). TNF and insulin levels were highly correlated. RESEARCH DESIGN AND CONCLUSIONS — IRS in the healthiest of long-term care residents is relatively rare but is METHODS — Studies were approved associated with mild glucose intolerance, increased percent body fat, altered insulin clearance, by the local institutional review board, and a proinflammatory status as evidenced by an elevated TNF. and consent forms were obtained on all participants. One hundred elderly ambu- Diabetes Care 30:2369–2373, 2007 latory women aged Ն65 years were re- cruited from eight long-term care facilities nsulin resistance syndrome (IRS) is IRS is defined on the basis of serum insu- in the St. Louis metropolitan area. Exclu- characterized by a decreased tissue lin levels regardless of glucose status. The sion criteria for the study were nonambu- I sensitivity to the action of insulin, lead- population of IRS that clearly does not latory status or a contraindication for ing to a compensatory increase in insulin overlap with diabetes is that with eugly- exercise. A fasting morning blood sample secretion (1). It is thought that most cemic hyperinsulinemia. Residents with was drawn and measured for glucose, adults with IRS maintain normal glucose IRS, despite euglycemia, are at increased electrolytes, blood urea nitrogen, creati- levels and will never develop overt type 2 risk for hypertension, stroke, polycystic nine, blood urea nitrogen–to–anion gap diabetes but are nonetheless at increased ovary syndrome, and nonalcoholic ste- ratio, anion gap, C-reactive protein, pre- risk for cardiovascular disease. Whereas atohepatitis (2). albumin, albumin, transferrin, white diabetes is defined on the basis of serum Because measuring serum insulin is blood cells (further assessed as percent- glucose levels regardless of insulin status, not part of routine clinical practice, diag- ages of neutrophils, lymphocytes, eosino- phils, and segments), platelets, red cell ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● indexes, and hemoglobin. Blood samples From the 1Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, St. Louis, 2 were also measured blinded with multi- Missouri; the Division of Geriatrics, Department of Internal Medicine, St. Louis University School of plex kits (Millipore, St. Charles, MO) for Medicine, St. Louis, Missouri; and the 3Center for Outcomes Research, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri. insulin, C-peptide, leptin, total amylin, Address correspondence and reprint requests to William A. Banks, MD, 915 N. Grand Blvd., St. Louis, adiponectin, resistin, interleukin (IL)-1␣, MO 63106. E-mail: [email protected]. IL-1␤, IL-1 receptor antagonist, IL-2, Received for publication 3 April 2007 and accepted in revised form 21 May 2007. IL-4, IL-6, IL-8, IL-10, interferon-␥, tu- Published ahead of print at http://care.diabetesjournals.org on 29 May 2007. DOI: 10.2337/dc07-0649. ␣ Abbreviations: IL, interleukin; IR, insulin resistant; IRS, insulin resistance syndrome; MAP, macrophage mor necrosis factor (TNF)- , eotaxin, inflammatory protein; NIR, non–insulin resistant; RANTES, regulated on activation, normal T-cell expressed macrophage inflammatory protein and secreted; TNF, tumor necrosis factor. (MAP)-1␣, and regulated on activation, A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion normal T-cell expressed and secreted factors for many substances. (RANTES). Any multiplex levels above © 2007 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby the detection limit were diluted and as- marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. sayed again. Any multiplex levels below DIABETES CARE, VOLUME 30, NUMBER 9, SEPTEMBER 2007 2369 Insulin resistance syndrome in the elderly Table 1—Resident characteristics elevated in the IR group (Table 2). Adi- ponectin showed a statistical trend (P ϭ IR group NIR group P 0.08) toward being lower in the IR group. The proinflammatory cytokine TNF was n 16 53 ϳ50% higher (P Ͻ 0.01) (Table 2); al- Age (years) 81.9 Ϯ 6.8 83.8 Ϯ 6.6 0.43 though the other cytokines except for Height (cm) 155.7 Ϯ 5.5* 156.7 Ϯ 7.3 0.61 MIP-1␣ and RANTES were arithmetically Weight (kg) 65.6 Ϯ 9.3* 62.3 Ϯ 13.5 0.20 higher in the IR group, none reached sta- BMI (kg/m2) 26.6 Ϯ 2.9* 25.1 Ϯ 5.3 0.09 tistical significance. C-reactive protein, Charlson index score 2.8 Ϯ 0.8 2.9 Ϯ 1.4 0.89 immune cell measures, and neither of the Smoker status 0.6 proinflammatory indexes were signifi- Current smoker 0 (0) 3 (6)† cantly different between the IR and NIR Never smoked 5 (31) 14 (28) groups. Former smoker 11 (69) 33 (66) Ratios of leptin to BMI (P Ͻ 0.01), Consumes alcohol 0 (0) 10 (20)† 0.052 insulin to C-peptide (P Ͻ 0.001), insulin Mini–mental state examination 22.3 Ϯ 6.4* 21.4 Ϯ 7.2‡ 0.82 to BMI (P Ͻ 0.001), and insulin to TNF Functional independence measure 99.4 Ϯ 20.4 94.2 Ϯ 20.6 0.23 (P Ͻ 0.001) were significantly higher in Mini–nutritional assessment 21.1 Ϯ 4.1‡ 21.7 Ϯ 4.4 0.77 the IR group (Table 3). The ratios for in- ADL 12.2 Ϯ 4.1 12.8 Ϯ 4.5 0.79 sulin to leptin, TNF to BMI, and insulin to GDS 8.5 Ϯ 7.0† 7.1 Ϯ 5.2§ 0.65 amylin were not different between the Get-up-and-go test 30.6 Ϯ 21.4† 32.7 Ϯ 18.2࿣ 0.31 two groups. At 6 meters 13.9 Ϯ 6.7† 17.4 Ϯ 14.4§ 0.39 Significant positive correlations were At 6 min 148.9 Ϯ 34.2‡ 138.8 Ϯ 67.9¶ 0.45 found between BMI and leptin (P Ͻ 0.001, Data are means Ϯ SD or n (%). *Based on n Ϫ1. †Based on n Ϫ 3. ‡Based on n Ϫ 2. §Based on n Ϫ 5. ࿣Based r ϭ 0.68), TNF and insulin (P Ͻ 0.01, r ϭ on n Ϫ 7. ¶Based on n Ϫ 13. ADL, activities of daily living; GDS, geriatric depression scale. 0.36), leptin and insulin (P Ͻ 0.01, r ϭ 0.31), and insulin and the leptin-to-BMI ratio (P Ͻ 0.01, r ϭ 0.34). Figure 1 shows the detection limit were assigned the and values ranged from 0 to 4. The second the relation between TNF and log insulin value of 1.0. Residents were weighed, inflammatory score excluded C-reactive (Y ϭ 9.21x ϩ 5.36, r ϭ 0.533, n ϭ 69, P Ͻ their height measured, and their BMI cal- protein for a measure based entirely on 0.01). Adiponectin and leptin were in- culated as weight (in kilograms) divided cytokine measures. versely correlated (P Ͻ 0.001, r ϭ by the square of height (in meters). Mini– Ϫ0.50). There were trends for associations mental status examination (3), mini– Analysis of data between C-reactive protein versus TNF nutritional assessment (4), activities of Means are reported with their SDs and n.
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