HPA axis genetic variation, cortisol and psychosis in major depression.

Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depression (PMD); 26 patients with non-psychotic major depression (NPMD); and 29 HCs. Collection of genetic material was added one third of the way into a larger study on cortisol, cognition and psychosis in major depression. Subjects were assessed using the Brief Psychiatric Rating Scale, the Hamilton Depression Rating Scale and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Blood was collected hourly for determination of cortisol from 1800 to 0900 h and for the assessment of alleles for six genes involved in HPA axis regulation. Two of the six genes contributed significantly to cortisol levels, psychosis measures or depression severity. After accounting for age, depression and psychosis, and medication status, only allelic variation for the glucocorticoid receptor (GR) gene accounted for a significant variance for mean cortisol levels from 1800 to 0100 h (r(2)=0.288) and from 0100 to 0900 h (r(2)=0.171). In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.

Effects of activation on lipoprotein lipase secretion by macrophages. Evidence for autoregulation.

Lipoprotein lipase (LPL) activity was measured in the media of cultured mouse peritoneal macrophages that were isolated after the intraperitoneal injection of inflammatory agents in order to yield a variety of states of activation. Fully activated macrophages obtained from Corynebacterium parvum-injected mice secreted very low levels of LPL when compared to unstimulated macrophages, while inflammatory and primed macrophages had increased LPL secretion. When inflammatory macrophages were incubated with conditioned medium obtained from fully activated macrophages, LPL secretion decreased in a time- and dose-dependent fashion. The factor(s) secreted by fully activated macrophages that inhibited LPL secretion was shown to be thermolabile and distinct from tumor necrosis factor. These results demonstrate that activation dramatically alters macrophage LPL secretion.

Author Correction: WNT-activated bone grafts repair osteonecrotic lesions in aged animals.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Overexpression of hormone-sensitive lipase prevents triglyceride accumulation in adipocytes.

Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that hydrolyzes intracellular stores of triglycerides within adipocytes and is thought to be the rate limiting enzyme in lipolysis; however, direct evidence to prove this concept has been lacking. The present study was designed to establish the function of HSL in adipocytes. A 2360-bp fragment containing the entire HSL coding region was cloned into the vector pCEP4 and was used to transfect the 3T3-F442A adipogenic cell line. Nondifferentiated, transfected cells were screened for HSL overexpression by indirect immunofluorescence microscopy and confirmed by immunoblotting cell extracts with anti-HSL/fusion protein antibodies and by Northern blots for HSL mRNA. Stable transfectants overexpressing HSL were obtained and cloned. Compared with undifferentiated 3T3-F442A cells transfected with pCEP4 not containing the insert (vector alone) where HSL expression was very low, undifferentiated HSL transfectants had up to a 100-fold increase in HSL activity. Likewise, immunoreactive HSL protein and HSL mRNA levels were increased up to 100-fold in HSL transfectants. When confluent cells were allowed to differentiate by exposure to insulin, HSL expression increased in vector alone transfected cells, but remained below that observed in HSL transfectants. A similar degree of differentiation was seen in both vector alone and HSL transfectants when based on the induction of lipoprotein lipase. Cellular triglyceride content increased dramatically in the vector alone transfected cells while triglyceride content was markedly reduced in the HSL transfectants. The expression of late markers of adipocyte differentiation, such as aP2 and GPDH, was diminished and appeared to vary with the degree to which HSL was overexpressed and the cellular triglyceride content was reduced. Thus, the overexpression of HSL in 3T3-F442A cells prevents differentiated adipocytes from taking on the appearance of fat cells, i.e., accumulating triglyceride. Furthermore, the overexpression of HSL directly or indirectly attenuates the expression of several genes that appear during late adipocyte differentiation.

Regulation of lipoprotein lipase in the diabetic rat.

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity and development of hypertriglyceridemia. In the current experiments the mechanisms involved in the regulation of LPL have been examined in control rats, streptozocin-induced diabetic rats, and diabetic rats treated chronically or with a single injection of insulin. Diabetes decreased adipose tissue LPL activity partially by decreasing immunoreactive LPL protein and the steady-state levels of LPL mRNA, but primarily by reducing the catalytic activity of LPL. Both chronic and acute insulin increased adipose tissue LPL activity by correcting the defect in the catalytic activity of LPL and increasing immunoreactive LPL protein; however, only chronic insulin restored LPL mRNA levels to normal. In the heart, LPL activity tended to be elevated with diabetes in parallel to an increase in immunoreactive LPL protein even though levels of LPL mRNA declined. Both chronic and acute insulin normalized LPL activity and immunoreactive LPL protein, while only chronic insulin corrected the levels of LPL mRNA. No changes in the catalytic activity of LPL in heart were detected among the groups. Thus, diabetes and insulin treatment regulate LPL expression pretranslationally, translationally, and post-translationally, with tissue-specific differences apparent in the mechanisms involved.

WNT-activated bone grafts repair osteonecrotic lesions in aged animals.

The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.

The regulation of hydroxymethylglutaryl-CoA reductase in cultured cells.

Growth-stimulated synchronized cells exhibit a rapid increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.88) activity prior to the onset of DNA synthesis. Under normal culture conditions, HMG-CoA reductase activity exhibits wide variations among experiments. To determine whether this phenomenon is dependent on cell replication, we used J774 macrophage-like cells to compare changes in reductase activity in cells synchronized by serum deprivation and then growth-stimulated by fresh media containing serum to unsynchronized cells treated with fresh media and serum. Under these conditions, no increase in [3H]thymidine incorporation into cell DNA was seen in unsynchronized cells, but a large increase was observed in synchronized cells 10-12 h after media change. Although the growth characteristics differed between the cells, reductase activity was low at the time of media change and increased 10 to 20-fold 5-10 h after media change, returning to basal levels by 24 h in both synchronized and unsynchronized cells. This pattern of reductase activity was observed in unsynchronized cells from a variety of cell lineages, although the magnitude of the changes varied. Fluctuations of [14C]acetate incorporation into cholesterol were observed in parallel to alterations in reductase activity. LDL receptor expression also paralleled the changes in reductase activity, but scavenger receptor expression was not affected. Addition of lipoproteins at the time of media change inhibited the rise in reductase activity by 80-90%. The increase in reductase activity was not due to a stimulation of cholesterol efflux into the medium, but evidence for the secretion into the media of an inhibitory factor was obtained. These results suggest that cell requirements for cholesterol are not always directly related to replication, and that standard culture conditions induce transient fluctuations in reductase activity and lipoprotein receptor expression.

Regulation of the secretion of lipoprotein lipase by mouse macrophages.

The regulation of the secretion of lipoprotein lipase was studied in primary cultures of mouse peritoneal macrophages and in the murine macrophage cell line J774. As previously reported, both cell types secrete a lipase with the characteristics of lipoprotein lipase. Incubation of macrophages with insulin, insulin-like growth factor, and L-thyroxine had no effect on lipoprotein lipase secretion. Incubation with dexamethasone and with several agents which increase intracellular cyclic AMP led to a decrease in lipoprotein lipase secretion by mouse peritoneal macrophages. These results suggest that the hormonal regulation of lipoprotein lipase in macrophages is different from that in adipose tissue and heart muscle. Incubation of the macrophages with heparin caused a marked increase in the secretion of lipoprotein lipase. Short incubations with heparin (5 min) caused a release of the enzyme into the media, while longer incubations caused a 2-8-fold increase in net lipoprotein lipase secretion which was maximal after 2-16 h depending on cell type, and persisted for 24 h. The effect of heparin was dose-dependent and specific (it was not duplicated by other glycosaminoglycans). The mechanism of heparin-induced increase in lipoprotein lipase secretion was explored. The increase was not caused by the release of a presynthesized intracellular pool of lipoprotein lipase or by the stabilization of lipoprotein lipase by heparin after secretion. The heparin-induced increase in lipoprotein lipase secretion was dependent on protein synthesis. The secretion of lipoprotein lipase by macrophages in response to low levels of heparin may be a significant factor in the formation of atherosclerotic lesions.

Regulation of macrophage lipoprotein lipase secretion by the scavenger receptor.

The effects of ligand binding to the scavenger receptor on the secretion of lipoprotein lipase by murine macrophages were examined. Inflammatory macrophages exposed to acetylated low-density lipoprotein (AcLDL) exhibited a dose-dependent, 40-80% increase in lipoprotein lipase secretion. This stimulation appeared to be unrelated to intracellular cholesterol and triacylglycerol levels and to phagocytosis in general. Resident and inflammatory macrophages treated with maleylated bovine serum albumin (Mal-BSA) showed a 3-fold increase in lipoprotein lipase secretion in a dose-dependent and time-dependent fashion. In contrast, dextran sulfate, which is another ligand recognized by the scavenger receptor, caused a dose-dependent decrease in lipoprotein lipase secretion. Casein, a ligand recognized by the Mal-BSA receptor, did not affect lipoprotein lipase secretion nor the ability of Mal-BSA to stimulate the enzyme, while dextran sulfate abolished the stimulatory effects of Mal-BSA. Since ethylamine, an inhibitor of receptor-mediated endocytosis, attenuated the increase in lipoprotein lipase secretion induced by AcLDL and Mal-BSA, but did not affect the inhibition induced by dextran sulfate, it is suggested that receptor-mediated endocytosis of ligands via the scavenger receptor might play a key role in the stimulation of lipoprotein lipase secretion in macrophages. This study reveals another mechanism for regulation of macrophage lipoprotein lipase secretion.

Characterization of a partially purified diacylglycerol lipase from bovine aorta.

A partially-purified diacylglycerol (DG) lipase from bovine aorta has been characterized with respect to the effects of lipid metabolites and two lipase inhibitors, phenylboronic acid and tetrahydrolipstatin (THL). DG lipase activity was determined by the hydrolysis of the sn-1 position of 1-[1-14C]palmitoyl-2-oleoyl-sn-glycerol. The products of the lipase reaction, 2-monoacylglycerol (2-monoolein) and non-esterified fatty acids (oleate, archidonate) produced a concentration-dependent (20-200 microM) inhibition of DG lipase activity. Oleoyl-CoA and dioleoylphosphatidic acid also inhibited aortic DG lipase activity, but lysophosphatidylcholine had little or no effect. The inhibition of aortic DG lipase by phenylboronic acid was competitive, with a Ki of approx. 4 mM. THL was a very potent inhibitor of aortic DG lipase; the concentration required for inhibition to 50% of control was 2-6 nM. THL inhibition was reduced when the concentration of substrate in the assay was increased. Attempts to identify the aortic DG lipase by covalent-labelling with [14C]THL were unsuccessful. Immunoblotting experiments revealed that hormone-sensitive triacylglycerol lipase (HSL) could not be detected in bovine aorta.

Role of lipoprotein lipase and apolipoprotein E secretion by macrophages in modulating lipoprotein uptake. Possible role in acceleration of atherosclerosis in diabetes.

Because the accumulation of lipid in macrophages is a characteristic feature of atherosclerosis, the mechanisms by which this lipid accumulation occurs have been intensively studied. This paper reviews the receptor- and non-receptor-mediated pathways that promote lipid accumulation in macrophages. Particular emphasis is placed on the contributions of two secretory products of macrophages, lipoprotein lipase and apolipoprotein E, to both receptor- and non-receptor-mediated uptake of triglyceride-rich lipoproteins by macrophages. The hormonal, lipid, and immunological factors that regulate the secretion of LpL and apoE by macrophages are discussed, as are how changes in the secretion of apoE and LpL that can modulate the uptake of triglyceride-rich lipoproteins by macrophages might influence the atherosclerotic process in people with diabetes.

Insulin deficiency alters cellular cholesterol metabolism in murine macrophages.

Mice made insulin deficient by the injection of streptozocin develop hyperglycemia and hypertriglyceridemia with triglyceride-rich, very-low-density lipoproteins (VLDLs). Thioglycolate-elicited peritoneal macrophages freshly isolated from insulin-deficient mice have increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is reflected in a greater rate of cholesterol synthesis by these macrophages. In contrast, thioglycolate-elicited macrophages from control mice with diet-induced hypertriglyceridemia had normal levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Cell surface receptors responsible for VLDL uptake are decreased in macrophages isolated from insulin-deficient mice, although receptors for acetylated low-density lipoproteins are not altered. Insulin treatment of insulin-deficient mice lowers plasma glucose and triglyceride concentrations. Additionally, insulin treatment returns the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and the rate of cholesterol synthesis in thioglycolate-elicited macrophages to normal while increasing the number of receptors responsible for VLDL uptake. It is suggested that the increases in 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and the rate of cholesterol synthesis in macrophages isolated from insulin-deficient mice are secondary to the reduction in the number of receptors responsible for VLDL uptake induced by insulin deficiency. These alterations in the cholesterol metabolism of macrophages occurring with insulin deficiency may have important implications for the atherosclerotic process in diabetes mellitus.

Insulin deficiency decreases lipoprotein lipase secretion by murine macrophages.

We investigated the effects of insulin deficiency and insulin treatment on the secretion of lipoprotein lipase (LPL) by murine macrophages. Streptozocin-induced insulin deficiency caused hyperglycemia and hypertriglyceridemia in mice. Peritoneal macrophages isolated from insulin-deficient mice secreted 70% less LPL activity than control mice. A 65% decrease in LPL activity in epididymal adipose tissue, without any changes in heart LPL activity, was also seen with insulin deficiency. One week of insulin treatment lowered plasma glucose and triglyceride levels in insulin-deficient mice. Additionally, 1 wk of insulin treatment increased LPL secretion by macrophages, but to only one-half of control, while normalizing adipose tissue LPL activity. One injection of insulin also increased LPL secretion by macrophages to one-half of control and normalized adipose tissue LPL activity, even though plasma glucose and triglyceride levels were not affected. In vitro insulin treatment of macrophages isolated from control or insulin-deficient mice had no effect on LPL secretion. The results suggest that insulin does not exert a direct effect on the LPL secretion by macrophages but that deficiency of insulin indirectly causes a profound decrease in macrophage LPL secretion. These changes in macrophage LPL secretion may contribute to the atherosclerotic process in diabetes mellitus.

Dissociation between plasma triglyceride concentration and tissue lipoprotein lipase deficiency in insulin-deficient rats.

Insulin deficiency was produced by streptozotocin in young (5-6 wk old) male rats, and measurements were made of plasma triglyceride and glucose concentrations and of lipoprotein lipase (LPL) activity of adipose tissue (epididymal) and muscle (gastrocnemius and soleus). Rats with streptozotocin-induced diabetes underwent a significant reduction in adipose tissue LPL activity (both total and heparin releasable), but the fall in LPL activity in these rats bore little relationship to their rise in plasma triglyceride concentration. Furthermore, muscle LPL activity was essentially unchanged in diabetic rats. Qualitatively similar changes were observed when measurements were made at either 8 a.m. (after the normal evening access to food) or 2 p.m. (6 h after food withdrawal). It is concluded that the hypertriglyceridemia that occurs secondary to insulin deficiency is not a simple function of decreased tissue LPL activity.

Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-1 null mice.

To clarify the roles of insulin receptor substrate (IRS) family proteins in phosphatidylinositol (PI) 3-kinase activation and insulin actions in adipocytes, we investigated the intracellular localization of IRS family proteins and PI 3-kinase activation in response to insulin by fractionation of mouse adipocytes from wild-type and IRS-1 null mice. In adipocytes from wild-type mice, tyrosine-phosphorylated IRS-1 and IRS-2, which were found to associate with PI 3-kinase in response to insulin, were detected in the plasma membrane (PM) and low-density microsome (LDM) fractions. By contrast, tyrosine-phosphorylated IRS-3 (pp60), which was found to associate with PI 3-kinase, was predominantly localized in the PM fraction. In adipocytes from IRS-1-null mice, insulin-stimulated PI 3-kinase activity in anti-phosphotyrosine (alphaPY) immunoprecipitates in the LDM fraction was almost exclusively mediated via IRS-2 and was reduced to 25%; however, insulin-stimulated PI 3-kinase activity in the PM fraction was primarily mediated via IRS-3 and was reduced to 60%. To determine the potential functional impact of the distinct subcellular localization of IRSs and associating PI 3-kinase activity on adipocyte-specific metabolic actions, we examined lipolysis in IRS-1 null mice. The level of isoproterenol-induced lipolysis was increased 5.1-fold in adipocytes from IRS-1 null mice as compared with wild-type mice. Moreover, hormone-sensitive lipase (HSL) protein was increased 4.3-fold in adipocytes from IRS-1-null mice compared with wild-type mice, and HSL mRNA expression was also increased. The antilipolytic effect of insulin in IRS-1 null adipocytes, however, was comparable to that in wild-type mice. Thus, discordance between these two insulin actions as well as the transcriptional and translational effect (HSL mRNA and protein regulation) and the PM effect (antilipolysis) of insulin may be explained by distinct roles of both PI 3-kinase activity associated with IRS-1/IRS-2 and PI 3-kinase activity associated with IRS-3 in insulin actions related to their subcellular localization.

Mechanism of intracellular calcium ([Ca2+]i) inhibition of lipolysis in human adipocytes.

We investigated the mechanisms responsible for the anti-lipolytic effect of intracellular Ca2+ ([Ca2+]i) in human adipocytes. Increasing [Ca2+]i inhibited lipolysis induced by b-adrenergic receptor activation, A1 adenosine receptor inhibition, adenylate cyclase activation, and phosphodiesterase (PDE) inhibition, as well as by a hydrolyzable cAMP analog, but not by a nonhydrolyzable cAMP analog. This finding indicates that the anti-lipolytic effect of [Ca2+]i may be mediated by the activation of adipocyte PDE. Consistent with this theory, [Ca2+]i inhibition of isoproterenol-stimulated lipolysis was reversed completely by the nonselective PDE inhibitor isobutyl methylxanthine and also by the selective PDE 3B inhibitor cilostamide, but not by selective PDE 1 and 4 inhibitors. In addition, phosphatidylinositol-3 kinase inhibition with wortmannin completely prevented insulin's anti-lipolytic effect but only minimally blocked [Ca2+]i's effect, which suggests that [Ca2+]i and insulin may activate PDE 3B via different mechanisms. In contrast, the antilipolytic effect of [Ca2+]i was not affected by inhibitors of calmodulin, Ca2+/calmodulin-dependent kinase, protein phosphatase 2B, and protein kinase C. Finally, [Ca2+]i inhibited significantly isoproterenol-stimulated increases in cAMP levels and hormone-sensitive lipase phosphorylation in human adipocytes. In conclusion, increasing [Ca2+]i exerts an antilipolytic effect mainly by activation of PDE, leading to a decrease in cAMP and HSL phosphorylation and, consequently, inhibition of lipolysis.

Microalbuminuria and increased plasma prorenin. Prevalence in diabetics followed up for four years.

When urinary albumin excretion was measured by radioimmunoassay, most diabetics excreted more albumin than nondiabetic subjects. Microalbuminuria was defined as an albumin excretion greater than 30 mg/g of urinary creatinine, more than twice the upper limit of normal. Intermittent microalbuminuria was found in 20% of patients with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM). Continuous microalbuminuria occurred in a similar percentage of patients with NIDDM, but less frequently in patients with IDDM. Rigorous control of glycemia was followed by cessation of microalbuminuria in nearly half of these patients. Microalbuminuria was associated with an increased incidence of other microvascular complications, as well as a distinctly higher plasma prorenin value in IDDM. Hypertension of 160/100 mm Hg or above was accompanied by increased albumin excretion and lower plasma prorenin values than in normotensive diabetics.

Milk-alkali syndrome in patients treated with calcium carbonate after cardiac transplantation.

Heart and heart-lung transplant recipients at Stanford (Calif) University Medical Center were routinely prescribed long-term calcium carbonate antacid therapy to aid in the prevention of peptic ulcer disease and osteoporosis associated with glucocorticoid immunosuppressive therapy. Patients consumed 4 to more than 10 g/d of elemental calcium. Since calcium carbonate also provides the essential ingredients for the development of the milk-alkali syndrome, the laboratory flow sheets of 297 heart and heart-lung transplant recipients were reviewed to examine the incidence of hypercalcemia. Sixty-five patients developed significant hypercalcemia after transplantation. Thirty-one patients were alkalotic at the time of hypercalcemia; 37 had impairment in renal function. It is likely that most of these patients had the milk-alkali syndrome. While most patients became eucalcemic by discontinuing calcium carbonate therapy, intravenous hydration and forced diuresis were used to treat severe cases. It is possible that the incidence of the milk-alkali syndrome will increase with the current popularity of prescribing calcium carbonate for the prevention and treatment of osteoporosis.

Impact of automated calls with nurse follow-up on diabetes treatment outcomes in a Department of Veterans Affairs Health Care System: a randomized controlled trial.

OBJECTIVE: We evaluated automated telephone disease management (ATDM) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs (VA) clinics. We also compared the results with those of a prior ATDM trial conducted in a county health care system. RESEARCH DESIGN AND METHODS: A total of 272 VA patients with diabetes using hypoglycemic medications were randomized. During the 1-year study period, intervention patients received biweekly ATDM health assessment and self-care education calls, and a nurse educator followed up with patients based on their ATDM assessment reports. Telephone surveys were used to measure patients' self-care, symptoms, and satisfaction with care. Outpatient service use was evaluated using electronic databases and self-reports, and glycemic control was measured by HbA1c and serum glucose testing. RESULTS: At 12 months, intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics. Intervention patients also were more likely than control patients to have had a cholesterol test. Among patients with baseline HbA1c levels > or =8%, mean end-point values were lower among intervention patients than control patients (8.7 vs. 9.2%, respectively; P = 0.04). Among intervention and control patients with baseline values > or =9%, mean end-point values were 9.1 and 10.2%, respectively (P = 0.04). At follow-up, intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care. CONCLUSIONS: This intervention improved the quality of VA diabetes care. Intervention effects for most end points replicated findings from the prior county clinic trial, although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study's enrollees.

Use of automated telephone disease management calls in an ethnically diverse sample of low-income patients with diabetes.

OBJECTIVE: We examined whether low-income patients with diabetes were able and willing to use automated telephone disease management (ATDM) calls to provide health status information that could improve the quality of their care. RESEARCH DESIGN AND METHODS: A total of 252 adults with diabetes, 30 of whom spoke Spanish as their primary language, were enrolled at the time of clinic visits in a Department of Veterans Affairs health care system (n = 132) or a county health care system (n = 120). Patients received ATDM calls for 12 months and responded to queries using their touch-tone telephones. We examined 1) whether patients completed ATDM assessments consistently over the year and used the calls to report their self-monitored blood glucose (SMBG) levels, 2) the characteristics of patients most likely to use the system frequently, 3) whether patients responded consistently within ATDM assessments, and 4) whether ATDM assessments differentiated among groups of patients with different clinical profiles at baseline. RESULTS: Half of all patients completed at least 77% of their attempted assessments, and one-fourth completed at least 91%. Half of all patients reported SMBG levels during at least 86% of their assessments. Patients completed assessments and reported glucose levels consistently over the year. Health status indicators were the most important determinants of assessment completion rates, while socioeconomic factors were more strongly associated with patients' likelihood of reporting SMBG data during assessments. Patients' responses within assessments were consistent, and the information they provided during their initial assessments identified groups with poor glycemic control and other health problems. CONCLUSIONS: Most low-income patients with diabetes can and will use ATDM calls as part of their care. The information they provide is reliable and has clinical significance. ATDM calls could improve the information base for diabetes management while relieving some of the pressures of delivering diabetes care under cost constraints.