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We introduce a new approach for automated guideline-based-care quality assessment, the bidirectional knowledge-based assessment of compliance (BiKBAC) method, and the DiscovErr system, which implements it. Our methodology compares the guideline's Asbru-based formal representation, including its intentions, with the longitudinal medical record, using a top-down and bottom-up approach. Partial matches are resolved using fuzzy temporal logic. The system was evaluated in the type 2 Diabetes management domain, comparing it to three expert clinicians, including two diabetes experts. The system and the experts commented on the management of 10 patients, randomly selected from 2,000 diabetes patients. On average, each record spanned 5.23 years; the data included 1,584 medical transactions. The system provided 279 comments. The experts made 181 different unique comments. The completeness (recall) of the system was 91% when the gold standard was comments made by at least two of the three experts, and 98%, compared to comments made by all three experts. The experts also assessed all of the 114 medication-therapy-related comments, and a random 35% of the 165 tests-and-monitoring-related comments. The system's correctness (precision) was 81%, compared to comments judged as correct by both diabetes experts, and 91%, compared to comments judged as correct by one diabetes expert and at least as partially correct by the other. 89% of the comments were judged as important by both diabetes experts, 8% were judged as important by one expert, and 3% were judged as less important by both experts. Adding the validated system comments to the experts' comments, the completeness scores of the experts were 75%, 60%, and 55%; the expert correctness scores were respectively 99%, 91%, and 88%. Thus, the system could be ranked first in completeness and second in correctness. We conclude that systems such as DiscovErr can effectively assess the quality of continuous guideline-based care. [ABSTRACT FROM AUTHOR]

Human mitochondrial RNase P (mt-RNase P) is responsible for 5′ end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP , the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations. [ABSTRACT FROM AUTHOR]

Aims: Diabetes is often diagnosed late. This study aimed to assess the possibility for earlier detection of diabetes from search data, using predictive models trained on large-scale data. Methods: We extracted all English-language queries made by people in the USA to Bing during 1 year and identified queries containing symptoms of diabetes. We compared the ability of four different prediction models (linear regression, logistic regression, decision tree and random forest) to distinguish between users who stated that they were diagnosed with diabetes and users who did not refer to diabetes or diabetes drugs but queried about at least one of the symptoms. Results: We identified 11,050 "new diabetes users" who stated they had been diagnosed with diabetes and approximately 11.5 million "control users" who queried about symptoms without querying for terms related to diabetes. Both the logistic regression and the random forest models were able to distinguish between the populations with an area under curve of 0.92 which translates to a positive predictive value of 56% at a false-positive rate of 1%. The model could identify patients up to 240 days before they mentioned being diagnosed. Conclusions: Some undiagnosed diabetes patients can be detected accurately according to their symptom queries to a search engine. Such earlier diagnosis, especially in cases of type 1 diabetes, could be clinically meaningful. The ability of search engines to serve as a population-wide screening tool could potentially be improved using additional data provided by users. [ABSTRACT FROM AUTHOR]

A 20-year-old female patient was admitted to hospital because of bilateral leg weakness. Laboratory investigation showed metabolic alkalosis and severe hypokalemia. Differential diagnosis included mineralocorticoid or apparent mineralocorticoid excess diseases, with a high aldosterone-to-renin ratio (ARR) after correcting hypokalemia. After confirmatory tests, imaging studies revealed a unilateral adrenocortical adenoma consistent with Conn's disease. Surgery was curative. [ABSTRACT FROM AUTHOR]

Diabetes and hyperglycemia are present in over one-third of inpatients in internal medicine units and are associated with worse prognosis in multiple morbidities. Treatment of inpatient hyperglycemia is usually with basal bolus insulin in a dose calculated by the patient's weight, with lower doses recommended in patients who are at a higher risk for hypoglycemia. Other antihyperglycemic medications and insulin regimens can be used in selected patients. There are no adequately powered studies on the effect of improving glycemic control on hospitalization outcomes in non-critically ill patients in internal medicine units, and in most patients a modest glucose target of 140-180 mg/dL is recommended. A structured discharge plan should intensify antihyperglycemic treatment as needed and include an outpatient follow-up appointment shortly after discharge. [ABSTRACT FROM AUTHOR]

The article offers information on association between insulin detemir use and higher occurrence of hypoglycemia in hospitalized patients with Hypoalbuminemia. Topics discussed include information on use of insulin analogs detemir and glargine in patients with hypoalbuminemia; observation of higher rate of hypoglycemia in determir-treated compared with glargine-treated inpatients; and information on risk of hypoglycemia associated with minimal albumin and length of stay in hospitals.

Glucocorticoids have major effects on adipose tissue metabolism. To study tissue mRNA expression changes induced by chronic elevated endogenous glucocorticoids, we performed RNAsequencingonthe subcutaneousadipose tissue frompatientswithCushing's disease(n=5) compared to patients with nonfunctioning pituitary adenomas (n=11).We found a higher expression of transcripts involved in several metabolic pathways, including lipogenesis, proteolysis and glucose oxidation as well as a decreased expression of transcripts involved in inflammation and protein synthesis. To further study this in amodel system,we subjectedmice todexamethasone treatment for 12weeks andanalyzedtheir inguinal (subcutaneous) fat pads, which led to similar findings. Additionally, mice treated with dexamethasone showed drastic decreases in lean body mass as well as increased fat mass, further supporting the human transcriptomic data. These data provide insight to transcriptional changes that may be responsible for the comorbidities associated with chronic elevations of glucocorticoids. [ABSTRACT FROM AUTHOR]

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. [ABSTRACT FROM AUTHOR]

Abstract: Alveolar fluid clearance (AFC) is important in keeping the airspaces free of edema. This process is accomplished via passive and active transport of Na+ across the alveolo-capillary barrier mostly by apical Na+ channels and basolateral Na,K-ATPases, respectively. Patterns of alveolar fluid clearance were found to be decreased in acutely elevated left atrial pressures, possibly due to the inhibition of alveolar epithelial active sodium transport. On the other hand, chronic elevation of pulmonary capillary pressure, such as seen in experimental and clinical congestive heart failure, increases alveolar fluid clearance most likely secondary to upregulation of active sodium transport. [Copyright &y& Elsevier]

Background A 42-year-old obese man presented with acute pulmonary edema. He had a history of chronic residual schizophrenia for which he had been taking clozapine for 7 years, but had no known prior cardiac disease. Echocardiography demonstrated severe biventricular systolic and diastolic dysfunction with severe left ventricular enlargement. Cardiac catheterization showed no coronary artery disease. Investigations Physical examination, chest radiography, electrocardiography, transthoracic echocardiography, laboratory testing, viral serology, cardiac catheterization, coronary angiography and abdominal and renal ultrasonography. Diagnosis Clozapine-induced dilated cardiomyopathy. Management Intravenous nesiritide, furosemide and morphine followed by oral heart-failure therapy comprising ramipril, metoprolol succinate, spironolactone, and furosemide. Clozapine therapy was withdrawn. [ABSTRACT FROM AUTHOR]

: ObjectivesThe goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM).: BackgroundCardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications.: MethodsWe sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years.: ResultsIn multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype.: ConclusionsThis study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient. [Copyright &y& Elsevier]

Cross-cultural epidemiological studies of incident cardiovascular disease in the diabetic patient have demonstrated marked differences in susceptibility that may be due to a genetic factor. The coronary artery collateral circulation is the chief determinant of the size of a myocardial infarction and is highly variable between patients. We recently demonstrated that a functional allelic polymorphism in the haptoglobin gene is correlated with a number of diabetic vascular complications. We thus set out to test the hypothesis that haptoglobin phenotype is associated with collateral formation in the setting of diabetes. We correlated the Hp phenotype (1-1, 2-1 or 2-2) as determined by polyacrylamide electrophoresis with the presence or absence of coronary collaterals by angiography in 82 consecutive diabetic patients and 138 consecutive non-diabetic patients undergoing catheterization. We found that diabetic patients with the Hp phenotype 2-1 were more likely to have collaterals than diabetic patients with the Hp phenotype 2-2 (P=0.007). There was no correlation between Hp phenotypes and the presence of collaterals in non-diabetic patients. Hp phenotype thus appears to be associated with the development of the coronary collateral circulation in diabetic patients with coronary artery disease. Haptoglobin 2-2 may predispose to less compensation for coronary artery stenosis in diabetic patients, and thereby portend a worse prognosis. [Copyright &y& Elsevier]

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele. [ABSTRACT FROM AUTHOR]

Introduction: People with T1DM and their healthcare providers perceive that mood and sleep quality influence blood glucose (BG). Artificial pancreas algorithms use only BG estimates to predict future BG and determine insulin requirements. We aimed to improve the understanding of the effect of emotional states and personality on temporal BG changes using machine learning. Methods: Patients with T1DM using continuous glucose monitoring (CGM) completed questionnaires on demographic, socioeconomic and medical information and personality characteristics. For several days, using a mobile app, patients recorded their present valence, arousal state and sleep quality. The data was synced with patient CGM readings and evaluated using gradient boosting decision tree (GBDT) over 5-fold cross-validation. Area under the receiver operating characteristic curve (AUROC) and marginal contribution were used to determine model feature importance. BG was divided into three classes: normal (70-180), high (>180), low (<70). For normal BG values, models were trained to predict BG class in the next 15, 30, and 45 minutes. Results: A total of 64 participants (age 48±15 years SEM, years of T1D 18±13, 59% women) from two medical centers participated for 17.3±15.2 SEM days, each reporting valence and arousal 56±53 times. Models using personality and emotional features to predict future BG outperformed models using only BG, albeit by a small margin. Following BG and time-of-day features, both neuroticism and arousal were found to be predictive. Neuroticism levels and sleep were significantly different between participants with HbA1c values under 7.6% and over 9.5%. (p=0.001, p=0.02, respectively). Discussion: Our results show that personality and present arousal are associated with BG fluctuations, while the effect of valence, while detectible, is minute. Integrating personality trait information using standard questionnaires may improve artificial pancreas algorithms. Disclosure: G. Shoham: None. I. Hochberg: None. R. Eldor: Consultant; Self; Oramed , Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, MSD Corporation, Novo Nordisk, Sanofi. R. Gilad-bachrach: None. [ABSTRACT FROM AUTHOR]

The article presents research aimed at encouraging physical activity in patients with diabetes through an automatic reinforcement learning algorithm. A total of 27 patients who did not perform regular physical activity has been provided with a pedometer on their personal smartphones and a personal plan for physical activity The results suggest that a mobile phone application with a learning algorithm has the capability to improve adherence to exercise in patients with diabetes.

Background and purpose: Advanced analysis of electroencephalography (EEG) data has become an essential tool in brain research. Based solely on resting state EEG signals, a data‐driven, predictive and explanatory approach is presented to discriminate painful from non‐painful diabetic polyneuropathy (DPN) patients. Methods: Three minutes long, 64 electrode resting‐state recordings were obtained from 180 DPN patients. The analysis consisted of a mixture of traditional, explanatory and machine learning analyses. First, the 10 functional bivariate connections best differentiating between painful and non‐painful patients in each EEG band were identified and the relevant receiver operating characteristic was calculated. Later, those connections were correlated with selected clinical parameters. Results: Predictive analysis indicated that theta and beta bands contain most of the information required for discrimination between painful and non‐painful polyneuropathy patients, with area under the receiver operating characteristic curve values of 0.93 for theta and 0.89 for beta bands. Assessing statistical differences between the average magnitude of functional connectivity values and clinical pain parameters revealed that painful DPN patients had significantly higher cortical functional connectivity than non‐painful ones (p = 0.008 for theta and p = 0.001 for alpha bands). Moreover, intra‐band analysis of individual significant functional connections revealed a positive correlation with average reported pain in the previous 3 months in all frequency bands. Conclusions: Resting state EEG functional connectivity can serve as a highly accurate biomarker for the presence or absence of pain in DPN patients. This highlights the importance of the brain, in addition to the peripheral lesions, in generating the clinical pain picture. This tool can probably be extended to other pain syndromes. [ABSTRACT FROM AUTHOR]

Professional guidelines recommend insulin therapy for treatment of type 2 diabetes (T2D) in the hospital. However, oral antidiabetes drugs (OAD) are commonly used despite the lack of safety and efficacy data. We analyzed individual level data from non-critically ill patients with T2D admitted to three large healthcare systems between 2008-2018 (N=187,396). We conducted propensity score matching analyses to determine the relative efficacy and safety of OAD. Patients were treated with basal insulin (20%), sliding scale insulin alone (28%), basal insulin with OADs (23%), metformin (21%), sulfonylureas (11%), or DPP-4 inhibitors (4%). Less than 1% were treated with thiazolidinediones or SGLT2 inhibitors. Patients started on basal insulin had more comorbidities and had higher glucose levels on admission. After matching for age, BMI, Charlson Comorbidity Index, and admission blood glucose, exposure to OADs, with or without basal insulin, was associated with non-clinically meaningful differences in glycemic control compared to basal insulin use alone (183.1± 53.8 vs. 175.7± 53.9 vs. 180.3± 54.9, p<0.001). The use of OADs with SSI was associated with a lower incidence of hypoglycemia. However, among OADs without basal insulin, sulfonylureas were associated with the highest rate of hypoglycemia (30%), compared to Metformin (16%), DPP-4i (15%) or TZDs (14%), p<0.001. There were no differences in lactic acidosis between groups. Patients treated with basal insulin had a higher mortality (2%) compared to basal insulin+ OAD (0.3%) or OAD alone (0.6%). In summary, the use of OADs with or without basal insulin is associated with acceptable glycemic control compared to insulin therapy. Basal insulin use and the use of sulfonylureas is associated with a high incidence of hypoglycemia. Disclosure: F.J. Pasquel: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. Research Support; Self; Dexcom, Inc., Merck Sharp & Dohme Corp., National Institutes of Health. M.F. Magee: Consultant; Self; Mytonomy. Employee; Spouse/Partner; U.S. Food and Drug Administration. Research Support; Self; AstraZeneca, Eli Lilly and Company, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; American Diabetes Association, Pri-Med LLC. Other Relationship; Self; Endocrine Society. I. Hochberg: None. C. Fortin: None. A. Migdal: None. S. Cardona: None. M. Fayfman: None. Y. Guo: None. L. Peng: None. G.E. Umpierrez: None. Funding: Jacobs Family Funds [ABSTRACT FROM AUTHOR]

Insulin therapy is the preferred treatment for glycemic control in the hospital. Oral antidiabetes drugs (OAD) are commonly used despite the lack of safety and efficacy data. We analyzed individual patient-data of non-critically ill patients with T2D admitted to a teaching medical institution between 2008 - 2018 to determine the relative efficacy and safety of OAD. We did logistic regression analysis adjusting for relevant covariates. A total of 10,205 patients were included in the analysis, 970 patients (9.5%) were treated with OAD, 691 (6.8%) with OAD plus basal insulin, and 8,544 (83.7%) with basal insulin. Patients treated with OAD had lower admission BG and HbA1c and had less comorbidities compared to those receiving basal insulin. Hypoglycemia was less common with metformin (2.4%) and DPP-4i (0.0%) compared to sulfonylureas (13%) or insulin therapy (13%). After adjusting for age, gender, BMI, race, hospital setting, Charlson score, and admission creatinine, treatment with OADs was associated with better BG control and lower odds of complications compared to insulin use (Figure). Conclusion: The use of OAD in the hospital appears to be safe and effective and is not associated with higher odds of complications, with the exception of sulfonylurea use that is associated with a high rate of hypoglycemia. Residual confounding due to selection assignment to basal insulin therapy to sicker patients is probable. Disclosure: F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. M.F. Magee: Consultant; Self; Mytonomy. Research Support; Self; Lilly Diabetes, Mytonomy, Sanofi. Speaker's Bureau; Self; PRIMED. I. Hochberg: None. R.B. Hawthorne: None. L. Peng: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that inflammation provides a link between obesity and insulin resistance. The noncanonical IκB kinases IKK-ɛ and TANK-binding kinase 1 (TBK1) are induced in liver and fat by NF-κB activation upon high-fat diet feeding and in turn initiate a program of counterinflammation that preserves energy storage. Here we report that amlexanox, an approved small-molecule therapeutic presently used in the clinic to treat aphthous ulcers and asthma, is an inhibitor of these kinases. Treatment of obese mice with amlexanox elevates energy expenditure through increased thermogenesis, producing weight loss, improved insulin sensitivity and decreased steatosis. Because of its record of safety in patients, amlexanox may be an interesting candidate for clinical evaluation in the treatment of obesity and related disorders. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme (ACE)-2 is a newly described enzyme with antagonistic effects to those of the classical ACE (ACE-1). Both ANG II and aldosterone play an important role in the pathophysiology of congestive heart failure (CHF) and in the adverse cardiac remodeling during its development. In this study, we examined the effects of experimental CHF induced by an aortocaval fistula (ACF) and of its treatment with ANG II and aldosterone inhibitors on the relative levels of ACE-1 and ACE-2. We also compared the effects of spironolactone, an aldosterone antagonist, and eprosartan, an ANG II receptor antagonist, on heart hypertrophy and fibrosis in rats with ACF. Spironolactone (15 mg·kg-1·day-1 ip, via minipump) or eprosartan (5 mg·kg-1·day-1 ip, via minipump) was administered into rats with ACF for 14 and 28 days. Specific antibodies were used to determine the protein levels of myocardial ACE-1 and ACE-2. ACF increased the cardiac levels of ACE-1 and decreased those of ACE-2. Heart-to-body weight ratio significantly increased from 0.30 ± 0.004% in sham-operated controls to 0.50 ± 0.018% and 0.56 ± 0.044% (P < 0.001) in rats with ACF, 2 and 4 wk after surgery, respectively, in association with increased plasma levels of aldosterone The area occupied by collagen increased from 2.33 ± 0.27% to 6.85 ± 0.65% and 8.03 ± 0.93% (P < 0.01), 2 and 4 wk after ACF, respectively. Both spironolactone and eprosartan decreased cardiac mass and collagen content and reversed the shift in ACE isoforms. ACF alters the ratio between ACE isoforms in a manner that increases local ANG II and aldosterone levels. Early treatment with both ANG II and aldosterone antagonists is effective in reducing this effect. Thus ACE isoform shift may represent an important component of the development of cardiac remodeling in response to hemodynamic overload, and its correction may contribute to the beneficial therapeutic effects of renin-angiotensin-aldosterone system inhibitors. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article focusing on haptoglobin phenotype and vascular complications in patients with diabetes.

Introduction: The mortality rate in diabetic dialysis patients (DDPs) is over 15% per year, with the cause of death most often attributed to cardiovascular disease (CVD) or bacterial infection (sepsis). Identification of genetic markers predictive of early mortality would be useful in the evaluation of therapies for the reduction of mortality rate in this population. Haptoglobin (Hp) is a polymorphic protein which appears to confer differential susceptibility to bacterial infection and CVD. We therefore proposed that Hp phenotype can predict mortality in DDPs. Methods: We tested this hypothesis prospectively in a longitudinal study of 392 dialysis patients from eight medical centres in Israel. Hp was determined by polyacrylamide gel electrophoresis. Patients were followed for all-cause mortality over a 3-year period. Results: We found that Hp phenotype was a significant predictor of mortality in DDPs stratified by age. In diabetic individuals over 60 years of age there was a decrease in mortality associated with the Hp 1-1 phenotype (P = 0.03). However, in younger DDPs the Hp 2-2 phenotype was associated with a decreased mortality rate (P = 0.003). Conclusion: Hp phenotype may be useful in the risk stratification algorithm and management of DDPs. [ABSTRACT FROM AUTHOR]

Sliding scale insulin (SSI) continues to be widely used for glycemic management of inpatients with T2D despite condemnation in clinical guidelines. To confirm the accuracy of this clinical guideline recommendation, we determined the efficacy and safety of using SSI for the management hyperglycemia of non-critical patients with T2D in a large multinational, propensity-matched cohort study. A total of 53,516 patients with ICD 9/10 code of T2D were included in the dataset. Patients were categorized as having received SSI only vs. basal insulin, and were matched according to age, BMI, Charlson Comorbidity Index, and admission blood glucose (BG). Among patients with admission BG <180 mg/dL treated with SSI, 69% achieved and maintained good glycemic control (mean hospital BG <180 mg/dl), compared to 52% of patients treated with basal insulin (p <.001). Patients treated with basal insulin had higher rates of hypoglycemia than patients treated with SSI (30 vs. 16%, p <.001). There were no differences in rates of lactic acidosis, acute MI, pneumonia, or bacteremia (p=NS). A total of 14.93% of patients initially treated with SSI alone failed to achieve adequate glycemic control and were started on basal insulin during the hospital stay. Those who failed SSI had significantly higher admission BG (227.4±90 vs. 175.8±71 mg/dl), greater rates of CKD (31 vs. 24%), CHF (29 vs. 24%), CAD (35 vs. 31%), and higher Charlson score (4.3±2.7 vs. 3.8±2.7) than patients who remained well controlled on SSI alone (all, p<.001). Conclusion: In a multicenter, international, propensity-matched cohort study, 69% of patients with T2D with admission BG <180 mg/dL treated with SSI achieved good glycemic control. Patients admitted with higher BG and greater comorbidities are more likely to fail treatment with SSI alone. These data suggest that SSI may be appropriate for patients with mild/moderate hyperglycemia, thus simplifying recommendations for inpatient glycemic management. Disclosure: A. Migdal: None. C. Fortin: None. Y. Guo: None. I. Hochberg: None. M.F. Magee: Consultant; Self; Mytonomy. Employee; Spouse/Partner; U.S. Food and Drug Administration. Research Support; Self; AstraZeneca, Eli Lilly and Company, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; American Diabetes Association, Pri-Med LLC. Other Relationship; Self; Endocrine Society. F.J. Pasquel: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. Research Support; Self; Dexcom, Inc., Merck Sharp & Dohme Corp., National Institutes of Health. G.E. Umpierrez: None. Funding: Jacobs Research Foundation [ABSTRACT FROM AUTHOR]

Background: We recently reported that haptoglobin (Hp) phenotype 1-1 is protective against the development of nephropathy in normal creatinine diabetics. In the present study, we sought to determine if Hp phenotype also plays a role in renal deterioration by determining Hp phenotypes in a consecutive series of patients with chronic renal failure (CRF) in hemodialysis (HD) and predialysis clinics. Methods: Three hundred and ninety-two patients on HD for less than 2 years and 182 predialysis patients (creatinine clearance time [CCT] <35 ml/min) were subjected to Hp phenotyping. Age, gender and presence of diabetes or hypertension were recorded. Patients were stratified according to age (above and below 60 years) and severity of renal dysfunction (CRF or HD). Results: We observed a markedly lower prevalence of the Hp 1-1 phenotype in HD patients under 60 years of age compared to patients with CRF or compared to the general population. This was not due to differences in the threshold for dialysis initiation among patients with different Hp types or to decreased survival of patients with Hp 1-1 prior to entering HD. In HD patients 60 years and over, Hp 1-1 prevalence was increased, as observed with other diseases in this age group. Conclusions: The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age. This may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types. In addition, Hp 1-1 may provide a protective effect against mortality in elderly patients. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]