Teriparatide in patients with osteoporosis and type 2 diabetes.

Despite evidence for higher fracture risk, clinical effects of osteoporosis treatments in type 2 diabetes (T2D) are largely unknown. Post hoc analyses of the DANCE observational study compared T2D patients and patients without diabetes to assess the effect of teriparatide, an osteoanabolic therapy on skeletal outcomes and safety. Patients included ambulatory men and women with osteoporosis receiving teriparatide 20µg/day SQ up to 24months followed by observation up to 24months. Main outcome measures included nonvertebral fracture incidence comparing 0-6months with 6+ months of teriparatide, change from baseline in BMD and back pain severity, and serious adverse events. Analyses included 4042 patients; 291 with T2D, 3751 without diabetes. Treatment exposure did not differ by group. For T2D patients, fracture incidence was 3.5 per 100 patient-years during 0-6months treatment, and 1.6 during 6months to treatment end (47% of baseline, 95% CI 12-187%); during similar periods, for patients without diabetes, fracture incidence was 3.2 and 1.8 (57% of baseline, 95% CI 39-83%). As determinants of fracture outcome during teriparatide treatment, diabetes was not a significant factor (P=0.858), treatment duration was significant (P=0.003), and the effect of duration was not significantly different between the groups (interaction P=0.792). Increases in spine and total hip BMD did not differ between groups; increase in femoral neck BMD was greater in T2D patients than in patients without diabetes (+0.34 and +0.004g/cm(2), respectively; P=0.014). Back pain severity decreased in both groups. Teriparatide was well tolerated without new safety findings. In conclusion, during teriparatide treatment, reduction in nonvertebral fracture incidence, increase in BMD, and decrease in back pain were similar in T2D and non-diabetic patients.

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer's disease.

BACKGROUND: The burden on caregivers of patients with Alzheimer's disease (AD) is associated with the patient's functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. METHODS: Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. RESULTS: Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). CONCLUSIONS: This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden.

Early Glycemic Response Predicts Achievement of Subsequent Treatment Targets in the Treatment of Type 2 Diabetes: A Post hoc Analysis.

INTRODUCTION: American Diabetes Association consensus guidelines emphasize individualized treatment in the management of type 2 diabetes mellitus (T2DM). Early glycemic response is a clinical marker that may predict longer term efficacy for individual patients and provide a clinical tool to enhance personalized treatment. This analysis evaluated whether glycemic response measured at week 12 ("early") could serve as a reliable predictor of glycemic control at weeks 24 and 52 of therapy in patients with T2DM. METHODS: We used data from 3 randomized, controlled clinical trials that evaluated patients with T2DM treated with 3 commonly prescribed glucose-lowering medications: metformin (n = 597), sulfonylurea (n = 626), and insulin glargine (n = 1046). The gradient boosting method was used to identify predictors of subsequent response; predictive accuracy was represented by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Treatment success at weeks 24 and 52 was assessed for each patient and defined as achieving a glycated hemoglobin (HbA1c) level of <7.0% or a reduction from baseline of ≥1.0%. RESULTS: The predictive parameters (sensitivity, specificity, PPV, and NPV) for improvements in HbA1c at week 24 for metformin were 0.83, 0.81, 0.44, and 0.96; for sulfonylurea, 0.79, 0.94, 0.71, and 0.96; and for insulin glargine, 0.67, 0.89, 0.65, and 0.90. The predictive parameters for improvements in HbA1c at week 52 for metformin were 0.73, 0.84, 0.56, and 0.92 and for sulfonylurea, 0.45, 0.94, 0.74, and 0.82. CONCLUSION: High predictive values identified in this analysis support "early" response as an appropriate tool for predicting treatment success at weeks 24 and 52. The high NPV (lack of early glycemic response) appears to be an effective indicator of the likely need for change in (or intensification of) therapy. These data support the current guideline recommendations that clinicians evaluate therapeutic responses to pharmacologic interventions with metformin, sulfonylureas, or insulin glargine as early as week 12.

Associations Between Glycemic Control, Depressed Mood, Clinical Depression, and Diabetes Distress Before and After Insulin Initiation: An Exploratory, Post Hoc Analysis.

INTRODUCTION: Although depression is often associated with poor glycemic control in patients with type 2 diabetes mellitus (T2DM), this observation has been inconsistent. This exploratory, post hoc analysis investigated associations between depression parameters and glycemic control using data from a 24-month, prospective, observational, non-interventional study evaluating glycemic response following insulin initiation for T2DM. METHODS: We analyzed data from a 24-month, prospective, observational study that evaluated glycemic response in patients with T2DM who initiated insulin therapy (N = 985) in 5 European countries. Secondary measures included patient-reported diagnosis of depression at baseline, severity of depressed/anxious mood (EuroQol (EQ)-5D item) and diabetes-related distress (Psychological Distress domain of the Diabetes Health Profile, DHP-18). The latter two measures were assessed at baseline and 5 time points throughout the study. Glycemic control was measured by glycated hemoglobin (HbA1c) at these same time points. Analyses employed t tests to assess the unadjusted baseline difference in HbA1c between patients with and without the respective depression parameter. The potential effect of demographic and clinical confounding variables was controlled through a linear model structure. Patient HbA1c levels were analyzed by presence/absence of a history of diagnosed depression, depressed mood, and diabetes-related distress. RESULTS: Patients with higher depression parameters or distress at baseline had significantly higher rates of microvascular complications at baseline. Patients with a history of diagnosed depression or high diabetes-related distress had higher HbA1c than patients without. HbA1c of patients with or without depressed mood was not significantly different at baseline. The proportion of patients with depressed mood declined after insulin initiation, whereas the proportion of patients with high diabetes-related distress did not significantly change. HbA1c improved following insulin initiation, regardless of presence/absence of studied depression/distress parameters at baseline. CONCLUSION: History of diagnosed depression, diabetes-related distress, and depressed mood were associated with a higher rate of microvascular complications. Diagnosed depression and diabetes-related distress also showed higher HbA1c at baseline when insulin was initiated. Insulin therapy improved glycemic control, while preexisting depressed mood declined and diabetes-related distress remained unchanged.

Cognitive and Functional Decline in Patients With Mild Alzheimer Dementia With or Without Comorbid Diabetes.

PURPOSE: Although diabetes is recognized as a risk factor for the development of cognitive impairment and for accelerated progression to Alzheimer disease (AD), it is unclear whether patients with diabetes who have already progressed to AD have a different rate of cognitive and functional decline compared with that in those without diabetes. This post hoc exploratory analysis compared cognitive and functional decline over an 18-month period in patients with mild AD dementia with and without comorbid diabetes. Decline in quality of life was assessed as a secondary objective. METHODS: In a post hoc exploratory analysis, we analyzed data from the placebo groups of three 18-month, randomized, placebo-controlled trials of solanezumab and semagacestat in patients with AD. Data from patients with mild AD dementia (Mini-Mental State Examination [MMSE] score, 20-26) and comorbid diabetes at baseline were compared with data from patients with mild AD dementia without diabetes at baseline. Cognition was assessed using the 14-item AD Assessment Scale-Cognitive Subscale (ADAS-Cog14) and the MMSE. Functioning was assessed with the AD Cooperative Study-Activities of Daily Living Inventory (instrumental subset) (ADCS-iADL). Quality of life was assessed using the European Quality of Life-5 Dimensions scale, proxy version (proxy utility score and visual analog scale score), and the Quality of Life in AD scale, self-report and proxy (caregiver) versions. Group comparisons of changes from baseline to 18 months in cognitive, functional, and quality-of-life measures employed a repeated-measures model adjusted for propensity score, study, baseline cognition score (functional or quality of life), age, sex, level of education, genotype of the apolipoprotein E gene, and concurrent use of an acetylcholinesterase inhibitor or memantine. FINDINGS: At baseline, patients with mild AD dementia with and without diabetes did not significantly differ on the cognitive measures, but those without diabetes were functioning at a significantly higher level. At 18 months, compared with patients without diabetes, those with diabetes showed a numerically but statistically nonsignificantly lesser cognitive decline (least squares mean between-group differences: ADAS-Cog14 score, 1.61 [P = 0.21]; MMSE score, -0.40 [P = 0.49]) and a statistically significantly lesser functional decline (least squares mean between-group difference in ADCS-iADL score, -3.07; P = 0.01). The 2 groups did not differ on declines in the quality-of-life measures. IMPLICATIONS: The present findings suggest that diabetes may influence the rate of functional decline among patients with mild AD dementia. These results require replication in studies that address the limitations of the present post hoc exploratory analysis and that explore the potential causes of the observed differences.

Factors associated with increased healthcare costs in Medicare Advantage patients with type 2 diabetes enrolled in a large representative health insurance plan in the US.

AIM: The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology. METHODS: Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period. RESULTS: The sample included 83,705 patients (mean age = 70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US). CONCLUSIONS: These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.

An individualized inpatient diabetes education and hospital transition program for poorly controlled hospitalized patients with diabetes.

OBJECTIVE: To evaluate predictors of outcomes associated with an inpatient diabetes education and discharge support program for hospitalized patients with poorly controlled diabetes (glycated hemoglobin [HbA1c]>9%). METHODS: Patients participated in individualized diabetes education conducted by a certified diabetes educator (CDE) that included an exploration of barriers and goal setting during hospitalization with telephone follow-up and communication with primary providers at discharge. Predictors of HbA1c reduction, successful follow-up, and readmission were analyzed. RESULTS: There were 82 subjects, and 48% were insulin naïve. Patients with type 2 diabetes (T2D, n = 58) had a significant decrease in HbA1c at follow-up (-2.8%, P<.0001), while those with type 1 diabetes (T1D, n = 19) did not (+0.02%, P = .96). However, after adjustment for other factors, only increasing age, higher baseline HbA1c, earlier education, and initiation of basal insulin were significant predictors of reduction in HbA1c. Higher area level income and empowerment and earlier education were significant predictors of outpatient follow-up within 30 days. While 28% were admitted for severe hyperglycemia, only 1 patient was readmitted with severe hyperglycemia. Successful phone contact was 77% and 57% with and without the support of non-CDE assistants respectively, but all outcomes were similar. CONCLUSION: The study suggests that an individualized inpatient diabetes education and transition program is associated with a significant reduction in HbA1c that is dependent on baseline HbA1c, older age, initiation of insulin, and earlier enrollment. Additional interventions are needed to ensure better continuity of care.

Treatment patterns among older patients with type 2 diabetes in the United States: a retrospective cohort study.

BACKGROUND: The American Diabetes Association consensus statement on the treatment of type 2 diabetes mellitus (T2DM) in older patients highlights the need for treatment pattern and effectiveness data from real-world settings and populations. This retrospective cohort study assessed the relative frequency of use of four commonly prescribed antihyperglycemia treatments for T2DM and quantified their effectiveness up to 2 years post-initiation. SUBJECTS AND METHODS: Within a large, U.S.-based, electronic health record database, we investigated usage of insulin, sulfonylureas, glucagon-like peptide-1(GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with T2DM, focusing on those ≥65 years old, although younger patients were included for comparative purposes. RESULTS: Inclusion criteria were met by 77,440 patients. Mean baseline glycosylated hemoglobin (HbA1c) levels for patients ≥65 years old varied among treatments: insulin (7.7% [61 mmol/mol]; n=3,311), sulfonylureas (7.0% [53 mmol/mol]; n=5,706), GLP-1 receptor agonists (7.1% [54 mmol/mol]; n=260), and DPP-4 inhibitors (7.1% [54 mmol/mol]; n=1,096). Older patients demonstrated good glycemic control at therapy initiation and were prescribed glucose-lowering agents at lower HbA1c values compared with younger patients. A large proportion of older patients were prescribed sulfonylureas (56%) and insulin (34%) compared with GLP-1 receptor agonists (3.4%) and DPP-4 inhibitors (12%), despite the associated risk of hypoglycemia. CONCLUSIONS: Patients initiating insulin and sulfonylureas demonstrated more sustained glycemic control compared with GLP-1 receptor agonists and DPP-4 inhibitors. A majority of older patients with T2DM was initiated on sulfonylureas and insulin at relatively low levels of HbA1c, a practice not entirely consistent with the recommendations of published guidelines.

The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) achieves sustainable weight loss possibly by altering the gut microbiota. The effect of a proton pump inhibitor (PPI) on weight loss and the gut microbiota has not been explored. PPI use and the gut microbiota were assessed before and 6 months after LRYGB in eight patients. Bacterial profiles were generated by 16S ribosomal RNA (rRNA) gene sequencing. Prior to LRYGB, PPI users had a higher percent relative abundance (PRA) of Firmicutes compared to nonusers. PPI users at 6 months post-LRYGB had a higher PRA of Firmicutes [48.6 versus 35.6%, p = nonsignificant (NS)] and a trend toward significantly lower percent excess weight loss (49.3 versus 61.4%, p = 0.067) compared to nonusers. PPI use post-LRYGB may impair weight loss by modifying gut microbiota.

Identifying factors associated with hypoglycemia-related hospitalizations among elderly patients with T2DM in the US: a novel approach using influential variable analysis.

OBJECTIVE: Healthcare providers managing older patients with type 2 diabetes mellitus (T2DM) face a complex milieu of medical conditions and comorbidities, which increase the risk of unintended treatment consequences. The objective of this study was to understand factors associated with hypoglycemia-related hospitalizations among adults with T2DM with an emphasis on older patients. RESEARCH DESIGN AND METHODS: A large retrospective cohort study using claims data from the United States was undertaken identifying actively registered patients diagnosed with T2DM and at least one diabetes medication prescription. MAIN OUTCOME MEASURES: The main outcomes included hypoglycemia-related hospitalization and frequency of comorbidities. RESULTS: Of patients with T2DM and hospitalization records (n = 887,182), 52.3% were male and 30.7% were aged ≥65 years. At baseline, the proportion of patients taking metformin was 52.4%, insulin 7.3%, and sulfonylurea 26.4%. Among those with diabetes-related hospitalizations, the incidence of hospitalization-related hypoglycemia in patients ≥65 years of age was greater than in patients <65 years of age (0.59 compared to 0.16 per 1000 person years). Using boosted regression tree modeling, age (older vs. younger), sulfonylurea use, insulin use, and renal disease were variables most associated with predicting hospitalizations associated with hypoglycemia. Elderly patients prescribed both insulin and sulfonylurea were most likely to experience hypoglycemia-related hospitalizations (odds ratio = 4.7; 95% CI 3.7-6.1). CONCLUSIONS: Older patients using both insulin and sulfonylurea were most likely to experience a hypoglycemia-related hospitalization. Age, sulfonylurea use, insulin use, renal disease, a history of hypoglycemia-related hospitalization and general hospitalization were the leading variables associated with hypoglycemia-related hospitalization. Glucagon-like peptide and dipeptidyl peptidase-4 medication use was not significantly associated with hypoglycemia-related hospitalizations. The strength of this analysis, compared to similar studies, lies in the large and generalizable sample size and statistical methodology, which control for the interdependence of predictive variables. Limitations include lack of information, such as dietary intake and exercise habits, which are known to influence the rate of hypoglycemia in certain patients. Given the frequency of use of insulin and sulfonylurea in a population at risk for hypoglycemia (older patients with diabetes), care should be taken when balancing cost and efficacy against safety and increased risk of hospitalization due to hypoglycemia.

Long-term safety and efficacy of a universal nursing-run intravenous insulin guideline.

BACKGROUND: Despite the plethora of data in the critical care setting, there are few studies to guide clinicians in the hospitalwide care of patients with hyperglycemia. METHODS: Patients 18 years of age and older who had a discharge diagnosis code for diabetes were admitted between January 1, 2005, and December 31, 2010, and received an insulin infusion for any reason were included in the analysis. Patients were receiving noncritical care or cardiac care (with interchangeable critical and noncritical care capacity). The effect of an insulin infusion guideline introduced in 2006 with a target glucose of 5.6-8.3 mmol/L was measured. Hyperglycemic (> 11.1 mmol/L) and hypoglycemic (< 3.9 or < 2.8 mmol/L) events were analyzed using multivariable models. RESULTS: After adjusting for age, gender, race, and nutrition, there was a significant decrease in time to first glucose < 8.3 mmol/L in hours (T8.3; p = .01) and hyperglycemia (p < .0001) in the year following implementation of the guideline in cardiac but not noncritical beds, which persisted through 2010. There was a significant decrease in hypoglycemic events by Year 3 in cardiac beds and by Year 5 in noncritical beds. Compared with patients who received nothing by mouth, patients eating discrete meals had significantly longer T8.3, greater variability, and more hyperglycemic and hypoglycemic events in cardiac and noncritical beds. CONCLUSIONS: Following the hospitalwide implementation of a nursing-run insulin infusion guideline, rapid, stable reduction in hyperglycemia was achieved in cardiac beds (having interchangeable ICU and non-ICU status), and the frequency of hypoglycemia steadily decreased over time in both cardiac and noncardiac beds. Oral intake and enteral feeding were associated with worse glycemic control.

Frequency and causes of hospitalization in older compared to younger adults with type 2 diabetes in the United States: a retrospective, claims-based analysis.

AIMS: This study assessed the frequency and most common causes of hospitalization in older compared to younger adults with type 2 diabetes mellitus (T2DM) in the US. METHODS: A retrospective study utilizing data from a nationally representative insurance claim database included patients who were diagnosed or treated for diabetes during or prior to the defined study period and who experienced hospitalization with or without re-hospitalization. RESULTS: Among 887,182 patients with T2DM, 31% were ≥ 65 years old and nearly 1 in 4 (23.5%) were hospitalized during the observation period. Only 2.3% of first hospitalizations were determined to be diabetes-related, and these events were most commonly associated with a history of pre-study hospitalization and increasing age. Hypoglycemia was a common cause for T2DM-related hospitalizations (22.9%), and older patients demonstrated a higher proportion of hypoglycemia-related hospitalizations (age ≥ 65 years: 38.3% vs. age < 65 years: 11.4%). Survival analysis predicting readmission within 6 months after first hospitalization showed that primary factors associated with first readmissions were history of prior hospitalization, malignancy, insulin use, and presence of pre-existing liver or renal disease. CONCLUSIONS: Hospitalization is common in patients with diagnosed diabetes, and nearly 1 in 4 diabetes-related hospital admissions were due to hypoglycemia. While the overall rate of hypoglycemia-associated admission was low, the age-specific rate was nearly 2.5-fold higher in older adults (≥ 65 years), affirming the need to carefully assess the potential benefit/risk of diabetes medications in those ≥ 65 years of age.

Regional and overall aortic function in nondiabetic individuals with insulin resistance and normal glucose tolerance.

CONTEXT: Insulin resistance is associated with altered vascular function in diabetes. OBJECTIVE: The objective of the study was to define the overall and regional aortic function as well as the changes of aortic function over time in nondiabetic individuals with insulin resistance and a normal oral glucose tolerance test (OGTT). DESIGN: This was a cross-sectional and longitudinal analysis with 12 months follow-up. SETTING: The setting of the study was in primary care. PATIENTS: Nondiabetic individuals (n = 181, mean age 42 ± 8 y) with a normal OGTT and insulin resistance as defined by the insulin sensitivity index (ISI) participated in the study. INTERVENTIONS: ISI was estimated from serial measurements of plasma insulin and glucose during an iv glucose tolerance test. Ascending and abdominal aortic distensibility (AoD) and stiffness index-ß (AoSI) were assessed using echocardiography. Carotid-to-femoral artery pulse wave velocity (PWVc-f; an index of overall aortic function) was measured from carotid and femoral arteries Doppler flow velocities recorded simultaneously with an electrocardiogram. Associations between ISI, AoD, AoSI, and PWVc-f were assessed using linear regression analyses and ANOVA. Differences between baseline and 12 months were compared using a paired t test. MAIN OUTCOME MEASURES: AoD and AoSI associations as well as changes over a 12-month period in relation to ISI were measured. RESULTS: Ascending AoD (P = .01) and ascending AoSI (P = .025) were significantly associated with ISI; in contrast, abdominal AoD and AoSI and PWVc-f did not. Changes in AoD, AoSI, and PWVc-f over time were more prominent in individuals with low ISI compared with those with high ISI. CONCLUSIONS: The significant associations between ISI and aortic function suggest that insulin resistance may affect the cardiovascular system, even when OGTT is normal.

Cardiovascular recovery following bariatric surgery in extremely obese adolescents: preliminary results using Cardiac Magnetic Resonance (CMR) Imaging.

PURPOSE: Baseline cardiovascular characteristics and longitudinal changes following weight loss surgery (WLS) in adolescents are not well defined. Recent data suggest that the use of transthoracic echocardiography (TTE) for preoperative cardiac assessment may provide suboptimal imaging fidelity secondary to excessive upper body adiposity. High fidelity imaging using cardiac magnetic resonance (CMR) is an extremely useful diagnostic tool. We report the use of CMR in a cohort of extremely obese adolescents undergoing WLS. METHODS: A retrospective analysis of adolescent WLS patients at a single institution was conducted. Data collection included mean age, sex, body mass index (BMI), and CMR measurements of left ventricular (LV) mass, LV end-diastolic volume (LVEDV), ejection fraction (EF), and myocardial perfusion reserve index (MPRI). Comparison of CMR results to normative data derived from lean subjects was performed. RESULTS: Ten subjects (9 female), with a mean age and BMI of 17.4 ± 1.9 years and 50.33 ± 10.21 kg/m(2) respectively, were studied. When compared to age, gender, and height matched normal weight (NW) controls, the obese (OB) subjects had evidence of increased LV mass (122 ± 25 g vs. 101 ± 10 g, OB vs. NW respectively, p<0.05), and increased LVEDV (156 ± 25 mL vs. 109 ± 9 mL, p<0.05), with an average EF of 61.5% ± 5% (range 52% to 67% vs. 71% to 74% expected EF for males and females, respectively, p=0.003). In addition, 60% of the OB subjects (6/10) demonstrated adenosine-induced sub-endocardial ischemia at baseline, the majority of whom underwent WLS (n=5) resulting in complete normalization of ischemia in 60% (3/5) and partial improvement in 40% (2/5). A reduction in mean LV mass (range 2 to 12 g) following WLS was observed. CONCLUSION: Extreme adolescent obesity is associated with significant cardiovascular abnormalities that include LV hypertrophy (i.e. increased LV mass) and LV dilatation. These findings, considered to be well-recognized cardiovascular disease risk factors in adults, were shown to be reversible after WLS in the small group of subjects studied here. Additional large-scale investigations designed to examine obesity-related cardiovascular disease in severely obese adolescents are required.

Characterization of metabolically unhealthy overweight/obese African American women: significance of insulin-sensitive and insulin-resistant phenotypes.

BACKGROUND: Obesity is often associated with high cardiovascular disease risk factors. Obesity is common in African American women. We investigated the characteristics of metabolically healthy and metabolically unhealthy overweight/obese African American women based on the presence of insulin resistance. MATERIALS/METHODS: We studied 196 apparently healthy overweight/obese African American women with family history of type 2 diabetes. Waist circumference, fasting glucose, insulin, c-peptide, lipids and lipoproteins, and systolic and diastolic blood pressure were obtained in each subject. In addition, insulin sensitivity was calculated using Bergman's Minimal Model Method. We defined insulin-sensitive metabolically healthy African American women as individuals with insulin sensitivity greater than 2.7 x 10(-4) x min(-1) (uU/ mL)(-1) and insulin resistant, metabolically unhealthy as insulin sensitivity less than 2.7 x 10(-4) x min(-1) (uU/mL)(-1). RESULTS: Thirty-three percent of our subjects were metabolically healthy African American women, while 67% were metabolically unhealthy African American women. The metabolically healthy subjects were significantly younger and less obese than the metabolically unhealthy subgroup. Mean fasting serum glucose, insulin, and c-peptide were significantly lower (P = .001) in the metabolically healthy than in metabolically unhealthy subjects. However, the mean blood pressures were within normal in both subgroups. Mean serum cholesterol (p < .05) and triglyceride (p < .001) levels were significantly lower, whereas high-density lipoprotein cholesterol (p < .03) was significantly higher in the metabolically healthy than in the metabolically unhealthy subjects. We found 25.5% of our subjects had metabolic syndrome (30.3% metabolically unhealthy and 15.6% metabolically healthy). CONCLUSION: We concluded that: (1) despite obesity, metabolically healthy African American women appear to be less prone to type 2 diabetes and cardiovascular disease and (2) in view of the higher prevalence of metabolic syndrome, metabolically unhealthy African American women should be targeted for primary prevention of type 2 diabetes and cardiovascular disease.

Correction of aberrant NADPH oxidase activity in blood-derived mononuclear cells from type II diabetes mellitus patients by a naturally fermented papaya preparation.

UNLABELLED: Supplementation of standardized fermented papaya preparation (FPP) to adult diabetic mice improves dermal wound healing outcomes. Peripheral blood mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a compromised respiratory burst activity resulting in increased risk of infections for the diabetic patients. AIMS: The objectives of the current study were to determine the effect of FPP supplementation on human diabetic PBMC respiratory burst activity and to understand underlying mechanisms of such action of FPP. RESULTS: When stimulated with phorbol 12-myristate 13-acetate, the production of reactive oxygen species by T2DM PBMC was markedly compromised compared to that of the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA expression of Rac2 was potently upregulated after FPP supplemention. The proximal human Rac2 gene promoter is G-C rich and contains consensus binding sites for Sp1 and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity, the Sp1 DNA binding activity was significantly upregulated in PBMC after treatment of the cells with FPP. INNOVATION: This work provided first evidence that compromised respiratory burst performance of T2DM PBMC may be corrected by a nutritional supplement. CONCLUSION: FPP can correct respiratory burst performance of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP supplementation in diabetic patients are warranted.

Comparison of 3 algorithms for Basal insulin in transitioning from intravenous to subcutaneous insulin in stable patients after cardiothoracic surgery.

OBJECTIVE: To determine the effectiveness of an algorithm containing 1 of 3 initial subcutaneous doses of insulin detemir and flexible prandial and supplemental insulin aspart in stable patients who have undergone cardiac surgery and are being transitioned off intravenous insulin infusion. METHODS: Patients were extubated, were not taking vasopressors, and were otherwise stable, requiring at least 1 unit per hour of intravenous insulin at least 48 hours after surgery. Patients were randomly assigned to once-daily insulin detemir at 50%, 65%, or 80% of intravenous basal insulin requirements and received insulin aspart according to carbohydrate intake. The dose of insulin detemir was adjusted daily over 72 hours. RESULTS: Eighty-two patients were included. The percentages of patients with an initial morning glucose concentration of 80 to 130 mg/dL were 36%, 63%, and 56% of patients at the 50%, 65%, and 80% doses, respectively (P = .12). However, the mean overall glucose value at 24 and 72 hours was similar between groups, and 86%, 93%, and 92% of patients in each group, respectively, achieved a mean glucose concentration of 80 to 180 mg/dL at 72 hours (P = .60). Hypoglycemia (glucose <65 mg/dL) only occurred in the 65% group (21%) and the 80% group (12%) over the first 72 hours (P = .02 in the 50% group compared with the 65% and 80% groups combined) with 1 event of a glucose concentration less than 40 mg/dL in the 80% group. There was no loss of glycemic control by the end of the once-daily dosing interval. CONCLUSIONS: Glycemic targets can be achieved without hypoglycemia by 72 hours in most patients who have undergone cardiac surgery and require intravenous insulin with a regimen consisting of an initial insulin detemir dose of 50% of basal intravenous insulin requirements and prandial and supplemental insulin.

The effect of glycaemic control and glycaemic variability on mortality in patients hospitalized with congestive heart failure.

BACKGROUND: diabetes and CHF are common comorbidities in hospitalized patients but the relationship between glycaemic control, glycaemic variability, and mortality in patients with both conditions is unclear. METHODS: we used administrative data to retrospectively identify patients with a diagnosis of CHF who underwent frequent glucose assessments. TWMG was compared with other measures of glycaemic control and a time-weighted measure of glycaemic variability, the glycaemic lability index. The outcome was hospital mortality. RESULTS: a total of 748 patients were included in the final analysis. Time-weighted mean glucose was higher than unadjusted mean glucose (137 + /- 44.7 mg/dL versus 167 + /- 54.9, p < 0.001), due in part to shorter sampling intervals at higher glucose levels. Hypoglycaemia, defined as a glucose level < 70 mg/dL, occurred during 6.3% of patient-days in survivors and 8.4% of patient-days among nonsurvivors (p = 0.05). Time-weighted mean glucose was similar (128 + /- 33.1 mg/dL versus 138 + /- 45.1 mg/dL) in nonsurvivors versus survivors, p = 0.19). However, relatively few patients had were significantly elevated readings. Median GLI was higher in nonsurvivors compared with that in survivors (18.1 versus 6.82, p = 0.0003). Increasing glycaemic lability index (odds ratio 1.32, 95% confidence interval 1.05-1.65), and hypoglycaemia (odds ratio 2.21, 95% confidence interval 1.07-4.65), were independently associated with higher mortality in logistic regression analysis. Respiratory failure was associated with mortality, but not standard deviation of glucose. CONCLUSIONS: future studies analysing glycaemic control should control for variable sampling intervals. In this analysis, glycaemic lability index was independently associated with increased mortality, independent of hypoglycaemia. Prospective studies are needed to evaluate these findings.