Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination

Abstract
OBJECTIVE: To examine the relationship of diabetes and functional disability in older adults and the possible mediating roles of comorbidities and A1C.

RESEARCH DESIGN AND METHODS: We analyzed data from a nationally representative sample of 6,097 participants aged >or=60 years in the National Health and Nutrition Examination Survey, 1999-2006. Diabetes was defined by self-report. Disability was defined as difficulty performing a physical task. We evaluated disability by grouping 19 physical tasks into five functional groups: lower-extremity mobility (LEM), general physical activities (GPA), activities of daily living (ADL), instrumental activities of daily living (IADL), and leisure and social activities (LSA).

RESULTS: Older U.S. adults with diabetes had the greatest disability in GPA (prevalence 73.6% [95% CI 70.2-76.9]), followed by LEM (52.2% [48.5-55.9]), IADL (43.6% [40.1-47.2]), ADL (37.2% [33.1-41.3]), and LSA groups (33.8% [30.8-36.9]). Diabetes was associated with two to three times increased odds of disability across functional groups (all P < 0.05). Comorbidities, mostly cardiovascular disease and obesity, and poor glycemic control (A1C >or=8%) together explained up to 85% of the excess odds of disability associated with diabetes, whereas poor glycemic control alone explained only approximately 10% of the excess odds. Adjustment for comorbidities, A1C, and diabetes duration fully attenuated the associations of diabetes with disability in all functional groups (all P > 0.05).

CONCLUSIONS: Older adults with diabetes have a high prevalence of disabilities with variable associations attributable to comorbidities and A1C. Aggressive management of cardiovascular risk factors and obesity may significantly reduce the burden of disability in this population.

Kalyani RR, Saudek CD, Brancati FL, Selvin E.

Division of Endocrinology and Metabolism, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA

Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of

Hemoglobin (Hb) uniquely associates with proinflammatory HDL in atherogenic mice and coronary heart disease (CHD) patients. In this paper, we report that Hb and its scavenger proteins, haptoglobin (Hp) and hemopexin (Hx) are significantly increased in apoA-1-containing particles of HDL both in mouse models of hyperlipidemia and in CHD patients, when compared with wild type mice and healthy donors, respectively. We further demonstrate that the association of Hb, Hp, and Hx proteins with HDL positively correlates with inflammatory properties of HDL and systemic inflammation in CHD patients. Interestingly, HDL from Hp(-/-) mice under atherogenic conditions does not accumulate Hb and is anti-inflammatory, suggesting that (i) Hp is required for the association of Hb with HDL and (ii) Hb.Hp complexes regulate the inflammatory properties of HDL. Moreover, treatment of apoE(-/-) mice with an apoA-1 mimetic peptide resulted in significant dissociation of Hb.Hp complexes from HDL and improvement of HDL inflammatory properties. Our data strongly suggest that HDL can become proinflammatory via the Hb.Hp pathway in mice and humans, and dissociation of Hb.Hp.Hx complexes from apoA-1-containing particles of HDL may be a novel target for the treatment of CHD.

Atherosclerosis Research Unit, Department of Medicine/Cardiology

Experts Recommend Using Haemoglobin A1C Levels for Making a Diabetes Diagnosis

HEMOGLOBIN A1C

By Bruce Sylvester

NEW ORLEANS -- June 6, 2009 -- A patient who reaches a glycosylated hemoglobin (Hb A1C) level of 6.5% should be diagnosed as a diabetic, according to a committee of experts from around the world meeting at the American Diabetes Association (ADA) 69th Scientific Sessions. This measurement, they added, should become a new international standard for the diagnosis of diabetes.

"A1C is a better measurement, technically, and in terms of convenience when compared to current glucose measurements -- and A1C correlates closely with the risk of diabetic retinopathy," said David M. Nathan, MD, Diabetes Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts. Dr. Nathan chaired the expert committee presentation here on June 5.

There are presently 2 standard tests used to diagnose diabetes: the fasting plasma glucose test or the oral glucose tolerance test. The committee examined the correlation between long-term glycaemic elevations and neuropathic complications like retinopathy, and found that Hb A1C, measuring average blood-glucose control over the past 2 to 3 months, would be a better diagnostic tool.

"We wanted a measure that would indicate where clinical complications could ensue, and elevation above Hb A1C 6.5% is where the danger of diabetic retinopathy actually begins," Dr. Nathan noted.

For individuals with an elevated risk of developing diabetes (genetically or due to obesity), the committee noted that an Hb A1C of 6% but less than 6.5% is likely to put these individuals at highest risk.

Paul Robertson, MD, president for medicine and science of the ADA, added comments at a press briefing after the guidelines were presented. He said that his organisation will develop a task force to study the report and to assess the new recommendation. The ADA did release an announcement on June 5, officially acknowledging the potential significance of Hb A1C as a potential diagnostic tool without officially endorsing the recommendations of the committee yet.

The report of the international expert committee was published online ahead of print on June 5 at http://care.diabetesjournals.org; it will appear in the July issue of Diabetes Care.

Diabetes experts on the committee represented the ADA, the International Diabetes Federation, and the European Association for the Study of Diabetes.

Hemoglobin as a potential source of natural regulatory oligopeptides.

Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia. aaz@inbi.ras.ru

Theoretical structure-function analysis of all possible hemoglobin molecule fragments was performed to determine sites that could be potential sources of regulatory oligopeptides. Known data on bovine hemoglobin primary structure and information of the EROP-Moscow database concerning structure and functions of natural oligopeptides were used along with a computer program complex. A total of 6750 natural non-hemoglobin oligopeptides with hemoglobin fragments of 2-14 amino acid residues were found. Structures of 20 of them were completely identical to hemoglobin fragments. Most of the revealed oligopeptides exhibit properties of neuropeptides, antimicrobial agents, and hormones. A number of them exhibit functions previously not known for hemoglobin fragments. The possibility of natural formation of regulatory oligopeptides from hemoglobin and other food protein molecules, generation of the exogenous oligopeptide pool, their participation in regulation processes as well as accordance of results obtained here with the oligopeptide continuum concepts are discussed.

Porous nanosheet-based ZnO microspheres for the construction of direct electrochemical biosensors

Nanosheet-based ZnO microsphere with porous nanostructures was synthesized by a facile chemical bath deposition method followed by thermal treatment, which was explored for the construction of electrochemical biosensors. Spectroscopic and electrochemical researches revealed the ZnO-based composite was a biocompatible immobilization matrix for enzymes with good enzymatic stability and bioactivity. With advantages of nanostructured inorganic–organic hybrid materials, a pair of stable and well-defined quasi-reversible redox peaks of hemoglobin was obtained with a formal potential of −0.345 V (vs. Ag/AgCl) in pH 7.0 buffer. Facilitated direct electron transfer of the metalloenzymes with an apparent heterogeneous electron transfer rate constant (ks) of 3.2 s−1 was achieved on the ZnO-based enzyme electrode. Comparative studies demonstrated the nanosheet-based ZnO microspheres were more effective in facilitating the electron transfer of immobilized enzyme than solid ZnO microspheres, which may result from the unique nanostructures and larger surface area of the porous ZnO. The prepared biosensor displayed good performance for the detection of H2O2 and NaNO2 with a wide linear range of 1–410 and 10–2700 μM, respectively. The entrapped hemoglobin exhibits high peroxidase-like activity for the catalytic reduction of H2O2 with an apparent Michaelis-Menten constant of 143 μM. The nanosheet-based ZnO could be a promising matrix for the fabrication of direct electrochemical biosensors, and may find wide potential applications in biomedical detection and environmental analysis.
Xianbo Lua, Haijun Zhanga, Yuwen Nia, Qing Zhanga and Jiping Chen, a,

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China

Blood counts at time of complete remission provide additional independent prognostic information in acute myeloid leukemia

Prognostic relevance of blood counts at complete remission (CR) in acute myeloid leukemia (AML) is not clear. To address this issue, we analyzed 891 AML patients in first CR. From the data of randomly selected 446 patients (training set), we first established optimal cutoffs for neutrophil and platelet counts and hemoglobin level at CR in terms of relapse-free survival (RFS). Patients whose counts were higher than each optimal cutoff were shown to have significantly better RFS (p < 0.01 for neutrophil and platelets, and p = 0.02 for hemoglobin). Then we tested whether these cutoffs were, after accounting for better known prognostic covariates, also predictive of RFS in the remaining 445 patients (validation set). Our data revealed that higher neutrophil count was independently predictive of longer RFS in the validation set (hazard ratio 1.38, p = 0.02), as was higher platelet count (hazard ratio 1.35, p = 0.04). These findings suggest that blood counts at CR, information readily available, are useful in prognostication in AML.

ARTICLE

Non-functionalized carbon nanotube binding with hemoglobin

Carbon nanotube has a high potential to be used as a biosensor and drug carrier. However, its binding behavior with proteins needs to be studied before the full potential of carbon nanotube in biological studies can be realized. Although many studies have been conducted to characterize the affinity of functionalized carbon nanotube to various types of proteins, our present study for the first time reported that hemoglobin can bind with non-functionalized carbon nanotube, and this binding can be identified by Raman spectrum. Further, this binding has not changed Raman luminescence with specific excitation and emission wavelengths. The immediate application of these findings is to use non-functionalized carbon nanotube as a biosensor to measure H2S in blood in which hemoglobin takes about 37% of the total blood volume. Other potential uses of non-functionalized carbon nanotube to bind selective groups of proteins are also hinted.

ARTICLE