Injectable protease-operated depots of glucagon-like peptide-1 provide extended and tunable glucose control.

Peptide drugs are an exciting class of pharmaceuticals increasingly used for the treatment of a variety of diseases; however, their main drawback is a short half-life, which dictates multiple and frequent injections and an undesirable "peak-and-valley" pharmacokinetic profile, which can cause undesirable side-effects. Synthetic prolonged release formulations can provide extended release of biologically active native peptide, but their synthetic nature can be an obstacle to production and utilization. Motivated by these limitations, we have developed a new and entirely genetically encoded peptide delivery system--Protease Operated Depots (PODs)--to provide sustained and tunable release of a peptide drug from an injectable s.c. depot. We demonstrate proof-of-concept of PODs, by fusion of protease cleavable oligomers of glucagon-like peptide-1, a type-2 diabetes drug, and a thermally responsive, depot-forming elastin-like-polypeptide that undergoes a thermally triggered inverse phase transition below body temperature, thereby forming an injectable depot. We constructed synthetic genes for glucagon-like peptide-1 PODs and demonstrated their high-yield expression in Escherichia coli and facile purification by a nonchromatographic scheme we had previously developed. Remarkably, a single injection of glucagon-like peptide-1 PODs was able to reduce blood glucose levels in mice for up to 5 d, 120 times longer than an injection of the native peptide drug. These findings demonstrate that PODs provide the first genetically encoded alternative to synthetic peptide encapsulation schemes for sustained delivery of peptide therapeutics.

Risk vs benefit in diabetes pharmacotherapy: a rational approach to choosing pharmacotherapy in type 2 diabetes.

Type 2 diabetes now affects more than 1 in 10 US adults and is a leading cause of morbidity, mortality, and healthcare expense. There are increasing numbers of available pharmacotherapies, with established agents as well as newer drugs developed from hormones in the incretin pathway, among others. New data are accumulating continuously with respect to potential benefits of both long-standing and new agents, as well as risks identified through post-marketing surveillance. Here we review the commonly prescribed pharmacotherapy options with attention to recently published information and provide a rational approach to choice of therapy.

Robertsite, Ca(2)Mn(III) (3)O(2)(PO(4))(3)·3H(2)O.

Robertsite, ideally Ca(2)Mn(3)O(2)(PO(4))(3)·3H(2)O [calcium manganese(III) tris-(orthophosphate) trihydrate], can be associated with the arseniosiderite structural group characterized by the general formula Ca(2)A(3)O(2)(TO(4))(3)·nH(2)O, with A = Fe, Mn; T = As, P; and n = 2 or 3. In this study, single-crystal X-ray diffraction data were used to determine the robertsite structure from a twinned crystal from the type locality, the Tip Top mine, Custer County, South Dakota, USA, and to refine anisotropic displacement parameters for all atoms. The general structural feature of robertsite resembles that of the other two members of the arseniosiderite group, the structures of which have previously been reported. It is characterized by sheets of [MnO(6)] octa-hedra in the form of nine-membered pseudo-trigonal rings. Located at the center of each nine-membered ring is a PO(4) tetra-hedron, and the other eight PO(4) tetra-hedra sandwich the Mn-oxide sheets. The six different Ca(2+) ions are seven-coordinated in form of distorted penta-gonal bipyramids, [CaO(5)(H(2)O)(2)], if Ca-O distances less than 2.85 Šare considered. Along with hydrogen bonding involving the water mol-ecules, they hold the manganese-phosphate sheets together. All nine [MnO(6)] octa-hedra are distorted by the Jahn-Teller effect.

Hostility and minimal model of glucose kinetics in African American women.

OBJECTIVE: To explore the underlying physiology of hostility (HOST) and to test the hypothesis that HOST has a greater impact on fasting glucose in African American (AA) women than it does on AA men or white men or women, using an intravenous glucose tolerance test (IVGTT) and the minimal model of glucose kinetics. METHODS: A total of 115 healthy subjects selected for high or low scores on the 27 item Cook Medley HOST Scale underwent an IVGTT. Fasting nonesterified fatty acids (NEFA) levels were measured before the IVGTT. Catecholamine levels were measured 10 minutes into the IVGTT. RESULTS: Moderation by group (AA women versus others) of HOST was found for glucose effectiveness (Sg, p = .02), acute insulin response (AIRg, p = .02), and disposition index (DI, p = .02). AA women showed a negative association between HOST and both Sg (beta = -0.45, p = .04) and DI (beta = -0.49, p = .02), controlling for age and body mass index. HOST was also associated with changes in epinephrine (beta = 0.39, p = .05) and fasting NEFA (beta = 0.44, p = .02) in the AA women. Controlling for fasting NEFA reduced the effect of HOST on both Sg and DI. CONCLUSIONS: This study shows that HOST is related to decreased DI, a measure of pancreatic compensation for increased insulin resistance as well as decreased Sg, a measure of noninsulin-mediated glucose transport compared in AA women. These effects are partly mediated by the relationship of HOST to fasting NEFA.

Hostility and fasting glucose in African American women.

OBJECTIVE: To examine whether the relationship of hostility (HOST) to fasting glucose indices is moderated by sex and race. HOST has been associated with abnormalities in glucose metabolism. Prior studies suggested that this association may be more prevalent in women and in African American (AA) individuals. METHODS: A total of 565 healthy AA and white (W) men and women (mean age = 33 +/- 6 years) were assessed. HOST was measured by the 27-item version of the Cook Medley HOST Scale. The moderating effects of sex and race were evaluated for the associations of HOST to fasting glucose, insulin, and insulin sensitivity (HOMA-IR). RESULTS: Analysis showed a moderating effect of sex and race on the association of HOST to fasting glucose (p = .03), but not for insulin (p = .12). Analysis of HOMA-IR revealed a trend (p = .06) for the interaction. Stratified analyses by race and sex revealed a positive association between HOST and fasting glucose only in AA women, which remained significant after controlling for age and body mass index. CONCLUSION: A relationship between HOST and fasting glucose was evident in AA women only, a group that has twice the risk of developing Type 2 diabetes compared with W women. Further studies are needed to elucidate the mechanisms by which HOST may affect glucose metabolism in AA women.

The growing burden of diabetes mellitus in the US elderly population.

BACKGROUND: The prevalence of diabetes mellitus is growing worldwide. Consequently, there has been increased emphasis on primary and secondary prevention of diabetes. To our knowledge, whether there have been actual improvements in outcomes in the last decade or so has not been documented in a nationally representative sample. METHODS: We undertook this study to examine trends in rates of occurrence of diabetes and its complications in persons older than 65 years in the United States. National longitudinal analysis of Medicare claims and other Medicare program data for persons first diagnosed as having diabetes during 1994 (n=33 164), 1999 (n=31 722), or 2003 (n=40 058) were compared with 2 control groups of persons of approximately equal sample size who were not diagnosed as having diabetes, alternatively during 1994, 1999, or 2003 or for the entire period from 1994 to 1999 or from 1999 to 2004. The main outcome measures were death and complications of diabetes including cardiovascular, cerebrovascular, ophthalmic, renal, and lower extremity events. RESULTS: The annual incidence of diabetes increased by 23% between 1994-1995 and 2003-2004, and prevalence increased by 62%. The mortality rate after diagnosis in persons having diagnosed diabetes decreased by 8.3% compared with that in the control groups. Complication rates among persons diagnosed as having diabetes generally increased or stayed the same compared with those in the control groups during 1994 to 2004 except for ophthalmic diseases associated with diabetes. Rates for some major complications were high; for example, the rate for congestive heart failure in the diabetes group during 1999 to 2004 was 475 per 1000 persons. In some cases, most notably renal events, including the most serious complications, there were increases in prevalence in both the diabetes and control groups. CONCLUSION: The burden of financing and providing medical care for persons older than 65 in the United States having diagnosed diabetes is growing rapidly as a result of increased incidence and, especially, prevalence of diagnosed diabetes, decreased mortality, and overall lack of improvement in rates of complications in persons having diagnosed diabetes.

Longitudinal incidence and prevalence of adverse outcomes of diabetes mellitus in elderly patients.

BACKGROUND: The natural history of type 2 diabetes mellitus (DM) in the elderly has not been previously described in a national longitudinal sample. METHODS: This national longitudinal analysis (January 1, 1991, to December 31, 2004) examines mortality and morbidity rates in a representative sample of elderly patients newly diagnosed as having DM. Medicare beneficiaries diagnosed as having DM in 1994 (n=33,772) were compared with a control group (n=25,563) regarding death, lower extremity complications, nephropathy, retinopathy, cardiovascular complications, and cerebrovascular complications. RESULTS: The DM group had excess mortality of 9.2% by year 11 compared with the control group. By 2004, 91.8% of the DM group experienced an adverse complication compared with 72.0% of the control group. The DM group had a higher prevalence and incidence of microvascular and macrovascular complications at all time points compared with controls. Patients with DM were at increased risk for all lower extremity complications, particularly those requiring surgical intervention (gangrene, debridement, and amputation). Cardiovascular complications were a leading cause of morbidity, with 57.6% of the DM group diagnosed as having heart failure compared with 34.1% of the controls. CONCLUSION: Elderly persons newly diagnosed as having DM experienced high rates of complications during 10-year follow-up, far in excess of elderly persons without this diagnosis, implying a substantial burden on the individual and on the health care system.

Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

There is an independent progressive epidemiologic relation between glycemia and cardiovascular disease (CVD) events; however, whether lowering glucose levels with currently available therapies can reduce CVD events remains unknown. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is designed to answer this question in high-risk patients with type 2 diabetes mellitus. In ACCORD, 10,251 patients with type 2 diabetes and other CVD risk factors or CVD were randomly allocated to intensive glycemic control, targeting a glycosylated hemoglobin (HbA1c) level <6%, or standard glycemic control, targeting an HbA1c level of 7.0%-7.9%. All participants are provided with diabetes education, glucose-monitoring equipment, and antidiabetic medications. All participants in the intensive glycemic control group are started on > or = 2 classes of agents. Doses are intensified or a new medication class is added every month if HbA1c levels are > or = 6% or if >50% of premeal or postmeal capillary glucose readings are >5.6 mmol/L (100 mg/dL) or >7.8 mmol/L (140 mg/dL), respectively. All drug combinations are permitted, and drugs are reduced only because of side effects or contraindications. Annual training, menus of approaches for intensification, regular electronic messaging, audits of achieved glycemia, and central feedback to sites support glycemic intensification strategies in intensive participants. In participants in the standard glycemic control group, therapy is intensified whenever HbA1c is > or = 8%, and antihyperglycemic drugs that promote hypoglycemia (ie, insulin or insulin secretagogues) are reduced if HbA1c persistently decreases to <7% in the setting of hypoglycemia. ACCORD addresses the hypothesis that aggressive glucose lowering prevents CVD events in patients with type 2 diabetes. It is focused on the levels of glycemia achieved using a variety of strategies, not on the specific therapies used. It will also provide information on how to safely approach near-normal levels of glucose control in clinical practice and evidence to support future clinical guidelines for diabetes management in older adults.

Changes in depressive symptoms and glycemic control in diabetes mellitus.

OBJECTIVE: To investigate if changes in depressive symptoms would be associated with changes in glycemic control over a 12-month period in patients with Type 1 and Type 2 diabetes. METHODS: Ninety (Type 1 diabetes, n = 28; Type 2 diabetes, n = 62) patients having Beck Depression Inventory (BDI) levels of >10 were enrolled in the study. Of those 90 patients, 65 patients completed a 12-week cognitive behavioral therapy intervention. BDI was assessed at baseline and thereafter biweekly during 12 months. Hemoglobin (HbA1c) and fasting blood glucose levels were assessed at baseline and at four quarterly in-hospital follow-up visits. Linear mixed-model analysis was applied to determine the effects of time and diabetes type on depressive symptoms, HbA1c levels, and fasting glucose levels. RESULTS: Mean and standard deviation baseline BDI and HbA1c levels were 17.9 +/- 5.8 and 7.6 +/- 1.6, respectively, with no significant difference between patients with Type 1 and Type 2 diabetes. Mixed-model regression analysis found no difference between the groups with Type 1 and Type 2 diabetes in the within-subject effect of BDI score on HbA1c or fasting glucose levels during the study. Depressive symptoms decreased significantly (p = .0001) and similarly over a 12-month period in both patients with Type 1 and Type 2 diabetes, whereas HbA1c and fasting glucose levels did not change significantly over time in either group. CONCLUSION: Changes in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in either patients with Type 1 or Type 2 diabetes.

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). RESEARCH DESIGN AND METHODS: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. RESULTS: Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). CONCLUSIONS: In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

Technosphere insulin: inhaled prandial insulin.

INTRODUCTION: Insulin therapy is a mainstay for treatment of diabetes mellitus; however, many barriers to insulin exist. Insulin human inhalation powder (technosphere insulin) is a new FDA-approved alternative to subcutaneous bolus insulin. AREAS COVERED: This is an overview of technosphere insulin (TI). Pharmacokinetics, clinical efficacy, safety and tolerability are discussed. EXPERT OPINION: TI is more quickly absorbed than subcutaneous insulin therapies and has a shorter duration of action. It appears to be noninferior compared with subcutaneous insulin regimens, and is associated with less hypoglycemia. Thus, it may serve as an alternative insulin agent in patients reluctant to administer multiple subcutaneous injections of insulin daily or in patients who experience late postprandial hypoglycemia with subcutaneous insulin. Cough is the most common side effect, but tends to be mild and transient. A small decrease in the forced expiratory volume has been demonstrated, but does not appear to progress and is reversible. Patients should have periodic pulmonary function tests. TI is contraindicated in patients with chronic lung disease. The long-term risk of lung cancer is being monitored but at this point does not appear to be higher than the expected incidence of lung cancer in this population.

Diabetes-related knowledge, atherosclerotic risk factor control, and outcomes in acute coronary syndromes.

Patients who have diabetes mellitus have 2 times the incidence of an acute coronary syndrome (ACS) and 2 times the mortality rate after ACS compared with patients who do not have diabetes. Poor patient understanding of diabetes is believed to impede appropriate self-management, thus accelerating cardiovascular complications. We investigated the relation between patients' diabetes-related knowledge (DRK) and measurements of risk factor control and cardiac outcomes. Two hundred patients who had diabetes mellitus and ACS and were admitted to a university hospital were enrolled over a 9-month period. At enrollment, clinical and demographic data were recorded, and each patient completed a previously validated DRK assessment. Clinical outcomes data were obtained 6 months after enrollment. Years of education and DRK assessment score were moderately correlated (r = 0.496, p <0.0001). Glycosylated hemoglobin, low-density lipoprotein cholesterol, and body mass index showed no correlation with DRK assessment score (r = -0.045, -0.005, and 0.175, respectively), even after multivariable adjustment for differences in age, race, insulin requirement, duration of diabetes, and years of education. Rates of 6-month death (6.2% vs 9.7%) and death or myocardial infarction (15.5% vs 19.4%) were not significantly different between groups of patients stratified by DRK assessment scores (high vs low scoring groups). Thus, among patients who have diabetes and ACS, there is a moderate correlation between years of education and DRK. We found no correlation between DRK and measurements of risk factor control or 6-month clinical outcomes. New strategies must be developed to translate understanding of disease into better risk factor modification among patients who have diabetes and ACS.

Neighborhood characteristics moderate effects of caregiving on glucose functioning.

OBJECTIVE: Adverse neighborhood environments and caregiving for a relative with dementia are both stressors that have been associated with poor health. The present study examined the extent to which three self-report measures of neighborhood characteristics interact with caregiving status (caregiver versus noncaregiver) to modify an important stress related health outcome: plasma glucose. METHODS: The study sample consisted of 147 community recruited caregivers and 147 participants who did not have caregiving responsibilities. We hypothesized that negative neighborhood characteristics would magnify effects of caregiving on plasma glucose levels. Regression analyses were conducted to examine the interaction of three neighborhood characteristic measures with caregiving status in predicting fasting plasma glucose (FPG) and glycosylated hemoglobin concentration (HbA1c), with control for age, race, gender, relation to care recipient (spouse or relative), body mass index, income, and education. RESULTS: Of the three neighborhood measures, the one reflecting crime concerns significantly moderated the effect of caregiving on FPG (p < .002) and HbA1c (p < .001). For participants with better neighborhood characteristics, caregivers and noncaregivers were similar with respect to indicators of glucose metabolism; however, for participants with worse neighborhood characteristics, caregivers had higher levels of FPG and HbA1c, as compared with noncaregivers. CONCLUSIONS: Poor health outcomes, such as impaired glucose control, may be found among caregivers who fear neighborhood crime.

Protease inhibitor-induced diabetic complications : incidence, management and prevention.

Protease inhibitors (PIs) have become a crucial element in the treatment of patients infected with HIV. However, the widespread use of PI therapy has also been associated with a number of metabolic adverse effects, including fat redistribution and hyperglycaemia. The objective of this review is a discussion of the incidence, pathophysiology, management and prevention of PI-associated hyperglycaemia. Initial case reports have been followed by large cross-sectional and cohort studies, which demonstrate that the incidence of PI-induced impaired glucose tolerance, as well as frank diabetes mellitus, is significant and demands attention. Investigations into the pathophysiology behind PI-associated hyperglycaemia have identified an underlying problem of insulin resistance that is presumably caused by both direct PI-induced mechanisms and lipotoxicity. Given this, clinical trials have explored the use of various classes of oral hypoglycaemic agents in the management of PI-induced diabetic complications, and the use of insulin therapy must be considered as well. Newer PI agents are also under development, with the hope of reducing metabolic adverse effects. In the meantime, prevention, in the form of dietary modification, regular physical activity and periodic screening for impaired glucose tolerance, must receive heightened attention in the care plan of patients receiving long-term PI therapy.

Treatment regimen determines the relationship between depression and glycemic control.

UNLABELLED: Several recent studies have suggested that depression is related to poorer glycemic control in patients with type 1 diabetes, but not in type 2 diabetes. We hypothesize that complexity of self-care regimen rather than the type of diabetes, is more important in determining this relationship of depression to glycemic control. METHODS: One thousand thirty-four adults with diabetes were recruited for the study. These patients were treated with: diet and exercise, oral medications, oral medications and insulin, 1-2 daily injections of insulin, and > or =3 daily injections. All participants completed the Beck depression inventory (BDI) and had a hemoglobin A(1c) (HbA(1c)) performed as part of routine clinical care. RESULTS: Pearson correlations between BDI scores and HbA(1c) were low and insignificant in all groups (0.015< or =r< or =0.066) except for those administering three or more daily shots of insulin (r=0.284; p=0.034). DISCUSSION: The results of this study clearly show that while depressive symptoms are significantly correlated to glycemic control in patients taking three or more insulin injections per day, there is no relationship in patients who are taking fewer than three injections per day.

Optimizing hospital use of intravenous insulin therapy: improved management of hyperglycemia and error reduction with a new nomogram.

OBJECTIVE: To assess the efficacy and safety of intravenous (IV) insulin administration with use of our institution's old protocol (pre-nomogram phase) as compared with our new insulin nomogram (post-nomogram phase), which titrates insulin dose based on the rate of change of plasma glucose values and uses multipliers to determine the new insulin infusion rate. METHODS: Hospitalized adults receiving an IV insulin infusion in our tertiary care medical center were enrolled in this study after informed consent was obtained. The study was an observational analysis conducted before and after implementation of the new insulin infusion nomogram. Measurements included episodes of hypoglycemia and incidence of the following errors in the insulin infusion process: (1) episodes of documented failure to increase insulin infusion rate despite persistent hyperglycemia and (2) number of times the IV infusion was stopped without subcutaneous administration of insulin. RESULTS: Overall, 66 patients were analyzed (38 in the pre-nomogram phase and 28 in the post-nomogram phase). The new nomogram reduced by nearly 3-fold (from 0.89 +/- 0.68 to 0.36 +/- 0.49 occurrence per patient per 24 hours; P<0.001) the mean incidence of failure to give insulin subcutaneously before discontinuation of IV insulin infusion. Moreover, the nomogram nearly eliminated the error of caregiver nonresponsiveness to persistent hyperglycemia: mean incidence 0.39 +/- 0.65 occurrence per patient per 24 hours before implementation of the new nomogram versus 0.02 +/- 0.09 afterward (P<0.002). There was no statistically significant difference in episodes of hypoglycemia between the 2 study groups. CONCLUSION: Safe IV administration of insulin through error prevention is essential. Implementation of a new IV insulin infusion nomogram, which adjusts insulin infusion using multipliers, reduces errors and improves glycemic control without increasing hypoglycemic episodes.

Emerging care for type 2 diabetes: using insulin to reach lower glycemic goals.

Intensive control of blood glucose reduces the incidence and progression of many of the complications of type 2 diabetes. Newer insulin formulations that approach normal physiologic patterns have made it possible to achieve glycemic goals without excessive hypoglycemia.

Stress management improves long-term glycemic control in type 2 diabetes.

OBJECTIVE: There is conflicting evidence regarding the utility of stress management training in the treatment of diabetes. The few studies that have shown a therapeutic effect of stress management have used time-intensive individual therapy. Unfortunately, widespread use of such interventions is not practical. The aim of the present investigation is to determine whether a cost-effective, group-based stress management training program can improve glucose metabolism in patients with type 2 diabetes and to determine whether a particular subset of patients is more likely to get positive results. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes were randomized to undergo a five-session group diabetes education program with or without stress management training. Participants (n = 108) were followed for 1 year, during which HbA(1c) tests and questionnaires assessing perceived stress, anxiety, and psychological health were administered at regular intervals to evaluate treatment effects. RESULTS: Stress management training was associated with a small (0.5%) but significant reduction in HbA(1c). Compliance with the treatment regimen decreased over time but was similar to that seen in patients receiving stress management for other reasons in the clinic. Trait anxiety (a measure of stable individual differences in anxiety proneness) did not predict response to treatment, showing that highly anxious patients did not derive more benefit from training. CONCLUSIONS: The current results indicate that a cost-effective, group stress management program in a "real-world" setting can result in clinically significant benefits for patients with type 2 diabetes.

Hostility, race, and glucose metabolism in nondiabetic individuals.

OBJECTIVE: The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians. RESEARCH DESIGN AND METHODS: The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered. RESULTS: In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans. CONCLUSIONS: Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans.

Education, glucose control, and mortality risks among U.S. older adults with diabetes.

AIMS: Studies have shown that diabetes mellitus disproportionately afflicts persons of low socioeconomic status and that the burden of disease is greatest among the disadvantaged. However, our understanding of educational differences in the control of diabetes and its impact on survival is limited. This study investigated the associations among education, hemoglobin A1c (HbA1c), and subsequent mortality in adults with diabetes. METHODS: Prospective cohort data from the 2006, 2008, and 2010 Health and Retirement Study were linked with biomarker data for U.S. older adults with diabetes (n=3312). Weighted distributions were estimated for all subjects at baseline and by the American Diabetes Association's general guidelines for HbA1c control (<7.0% [53 mmol/mol] vs. ≥7.0% [53 mmol/mol]). Proportional hazard models were used to estimate educational differences in all-cause mortality by HbA1c level with sequential adjustments for contributing risk factors. RESULTS: Mortality risks associated with HbA1c≥7.0% [53 mmol/mol] were significantly greater in lower-educated adults than higher-educated adults (P<0.001). We found that the hazard ratios (HR) associated with HbA1c ≥7.0% [53 mmol/mol] were highest among low-educated adults (HR=2.18, 95% CI: 1.62, 2.94) and that a combination of socioeconomic, psychosocial, and behavioral factors accounted for most, but not all, of the associations. CONCLUSIONS: Educational differences in HbA1c control have significant implications for mortality and efforts to reduce these disparities should involve more vigilant screening and monitoring of lower-educated adults with diabetes.