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Aims Little is known about the impact of weight loss on developing comorbidities in patients with obesity in real-world settings. Understanding health benefits and associated comorbidities with weight loss are critical to addressing the global obesity health epidemic. This study aimed to determine health outcomes associated with weight loss in individuals with obesity, and to better understand the relationship between disease burden (i.e., prior comorbidities, healthcare utilization) and weight loss in individuals with obesity. Electronic health records (EHRs) represent an important resource to investigate these impacts. Materials and methods We conducted a case-control study using deidentified EHR-derived information from 204,921 patients seen at the Cleveland Clinic between 2000-2018. Patients were ≥20 years of age with BMI ≥30 kg/m2 and ≥7 weight measurements, over ≥3 years. Thirty outcomes were investigated, including chronic and acute diseases, as well as psychological and metabolic disorders. Weight change was investigated three, five, and ten years prior to an event. Results Weight loss was associated with reduced incidence of many outcomes (e.g., type 2 diabetes, non-alcoholic steatohepatitis/non-alcoholic fatty liver disease, obstructive sleep apnea, hypertension) (P 10% was associated with increased incidence of certain outcomes including stroke and substance abuse. However, many outcomes that increased with weight loss were attenuated by disease burden adjustments. Conclusions This study provides the most comprehensive real-world evaluation of health impacts of weight change to date. After comorbidity burden and healthcare utilization adjustments, weight loss was associated with an overall reduction in risk of many adverse outcomes. This article is protected by copyright. All rights reserved.

OBJECTIVE To assess patient characteristics and treatment factors associated with uncontrolled type 2 diabetes (T2D) and the probability of hemoglobin A1c (A1C) goal attainment. RESEARCH DESIGN AND METHODS This was a retrospective cohort study using the electronic health record at Cleveland Clinic. Patients with uncontrolled T2D (A1C >9%) were identified on the index date of 31 December 2016 (n = 6,973) and grouped by attainment (n = 1,653 [23.7%]) or nonattainment (n = 5,320 [76.3%]) of A1C RESULTS For the entire population, median age at index date was 57.7 years (53.3% male), and the majority were white (67.2%). Median A1C was 10.2%. Obesity (50.6%), cardiovascular disease (46.9%), and psychiatric disease (61.1%) were the most common comorbidities. Metformin (62.7%) and sulfonylureas (38.7%) were the most common antidiabetes medications. Only 1,653 (23.7%) patients achieved an A1C CONCLUSIONS A minority of patients with an A1C >9% achieved an A1C

OBJECTIVE To determine if natural language processing (NLP) improves detection of nonsevere hypoglycemia (NSH) in patients with type 2 diabetes and no NSH documentation by diagnosis codes and to measure if NLP detection improves the prediction of future severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS From 2005 to 2017, we identified NSH events by diagnosis codes and NLP. We then built an SH prediction model. RESULTS There were 204,517 patients with type 2 diabetes and no diagnosis codes for NSH. Evidence of NSH was found in 7,035 (3.4%) of patients using NLP. We reviewed 1,200 of the NLP-detected NSH notes and confirmed 93% to have NSH. The SH prediction model (C-statistic 0.806) showed increased risk with NSH (hazard ratio 4.44; P < 0.001). However, the model with NLP did not improve SH prediction compared with diagnosis code–only NSH. CONCLUSIONS Detection of NSH improved with NLP in patients with type 2 diabetes without improving SH prediction.

The risk of adverse cardiovascular events and mortality associated with testosterone replacement therapy is controversial. The purpose of this report was to evaluate the effect of testosterone replacement therapy (TRT) in men with secondary hypogonadism on the risk of myocardial infarction (MI), stroke (CVA) or all-cause mortality.A retrospective cohort study was conducted using the Cleveland Clinic's electronic health record. Men ≥40 years of age, with at least two testosterone levels 220 ng/dL, with one level obtained between 7 am and 10 am, were identified. Men with primary hypogonadism, secondary hypogonadism related to overt hypothalamic pituitary pathology, human immunodeficiency virus infection, metastatic cancer, and select contraindications to TRT, were excluded. Men exposed to TRT were matched to controls that were not exposed. A survival analysis was performed on the composite outcome of MI, CVA, or all-cause mortality.One hundred sixty-five patients exposed to TRT (treatment group) were matched with 210 not exposed to TRT (comparison group). The prevalence of established cardiovascular disease (CVD) was 20.0% in the treatment group vs. 17.1% in the comparison group (In hypogonadal men with a modest prevalence of established CVD, TRT was not observed to confer a protective or adverse effect on the risk of MI, CVA or all-cause mortality.Le risque d’événements cardiovasculaires indésirables et de mortalité associé au traitement de substitution de la testostérone est controversé. Le but du présent article est d’évaluer chez les hommes qui présentent un hypogonadisme secondaire l’effet du traitement de substitution de la testostérone (TST) sur le risque d’infarctus du myocarde (IM), d’accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues.Une étude de cohorte rétrospective a été menée en utilisant les dossiers de santé électroniques de la Clinique Cleveland. Ont été identifiés les hommes âgés de plus de 40 ans qui avaient au moins deux dosages de testostérone inférieurs à 220ng/dl, dont l’un obtenu le matin entre 7 et 10 heures. Ont été exclus les hommes qui présentaient un hypogonadisme primaire, un hypogonadisme secondaire lié à une pathologie hypothalamo-hypophysaire évidente, une infection par le virus de l’immunodéficience humaine, un cancer métastatique, et ceux qui présentaient des contrindications déterminées au TST. Les hommes exposés au TST ont été appariés à des témoins non exposés au TST. Une analyse de survie a été réalisée sur le paramètre composite incluant l’IM, l’AVC et la mortalité toutes causes confondues.165 patients exposés au TST (groupe traité) ont été appariés à 210 hommes non exposés au TST (groupe de référence). La prévalence de maladie cardiovasculaire (MCV) établie était de 20.0% dans le groupe traité versus 17.1% dans le groupe de référence (P=0.478). La médiane (écart interquartile (EI)) de l’âge et de l’indice de masse corporelle (IMC) était respectivement de 55 (49, 62) ans et de 35.6 (32.1, 40.1) kg/m2 dans le groupe traité, et respectivement de 55 (49, 61.7) ans et 36.3 (32.1, 40.8) kg/m2 dans le groupe de référence. Il y eut 12 événements indésirables (7.3%) dans le groupe traité, et 16 (7.6%) dans le groupe de référence. La médiane du temps (en années) des événements composites était de 2.1 (EI 0.9, 4.6) et de 1.8 (EI 0.6, 3.4) respectivement pour les groupes traité et de référence. Aucune différence n’a été observée en ce qui concerne le risque cardiovasculaire entre le groupe traité et le groupe de référence, rapport de risque (RR) 0.81 (Intervalle de Confiance à 95% [IC]: 0.38-1.71;Chez les hommes qui présentent un hypogonadisme et une faible prévalence de maladie cardiovasculaire (MCV) établie, le TST n’apparait pas conférer un effet protecteur ou défavorable sur le risque de d’infarctus du myocarde (IM), d’accident cérébrovasculaire (ACV) ou de mortalité toutes causes confondues.Traitement de substitution de la testostérone, Hypogonadisme masculin, Risque cardiovasculaire, Mortalité.

OBJECTIVE Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals. RESEARCH DESIGN AND METHODS ACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes. Using a novel approach to cluster HbA1c trajectories, we identified groups in the intensive glycemia arm with modified CVD risk. Genome-wide analysis and polygenic score (PS) were developed to predict group membership. Mendelian randomization was performed to infer causality. RESULTS We identified four clinical groupings in the intensive glycemia arm, and clinical group 4 (C4) displayed fewer CVD (hazard ratio [HR] 0.34; P = 2.01 × 10−3) and microvascular outcomes (HR 0.86; P = 0.015) than those receiving standard treatment. A single-nucleotide polymorphism, rs220721, in MAS1 reached suggestive significance in C4 (P = 4.34 × 10−7). PS predicted C4 with high accuracy (area under the receiver operating characteristic curve 0.98), and this predicted C4 displayed reduced CVD risk with intensive versus standard glycemia treatment (HR 0.53; P = 4.02 × 10−6), but not reduced risk of microvascular outcomes (P < 0.05). Mendelian randomization indicated causality between PS, on-trial HbA1c, and reduction in CVD outcomes (P < 0.05). CONCLUSIONS We found evidence of a T2D clinical group in ACCORD that benefited from intensive glycemia treatment, and membership in this group could be predicted using genetic variants. This study generates new hypotheses with implications for precision medicine in T2D and represents an important development in this landmark clinical trial warranting further investigation.

Diabetes risk increases with age due to changes in β-cell function and increased insulin resistance and is one of the most common chronic medical conditions in the elderly. Diabetes management in this population requires a multidisciplinary, patient-centric approach due to wide heterogeneity in patients' health and functional capacities. Meticulous assessment of each patient before formulating a regimen and thorough patient education are keys to success in achieving glycemic goals, which should be individualized. Lifestyle modification is recommended for every patient.

Guidelines recommend individualized treatment for patients with type 2 diabetes (T2D), avoidance of clinical inertia, and specific therapeutic choices for patients at risk for cardiovascular disease, congestive heart failure, or chronic kidney disease. However, a gap exists in translating these guidelines into practice. We created an electronic medical record (EMR) tool to improve evidence-based treatment intensification for T2D and studied its implementation in endocrinology and primary care (PC). The tool included a best practice alert (BPA) informing providers at an office visit of an A1C ≥ 8% and prompted providers, within the tool, to make therapeutic choices based upon five priority care goals- cardiovascular risk reduction, A1c lowering, low hypoglycemia risk, cost, or weight loss. After a 3-month pilot at one site, the tool was implemented using a stepped-wedge approach from March-November 2019 to all PC (N=52) and endocrinology (N=17) sites in our health system with 1903 eligible patient visits by November 2019. Within endocrinology, provider tool usage ranged from 94% of visits at the pilot site to 34% after full rollout; in PC, usage ranged from 52% during the pilot to just above 5%. Usage varied by practice site (range Uptake of a point of care EMR tool to promote treatment intensification for T2D in endocrinology and PC demonstrated variation at the specialty, practice site, and provider levels. Our findings also suggest that, given time pressures, provider focused point of care EMR-based interventions to improve T2D care may need to be supplemented with tools asynchronous to the office visit and should address patient factors in adherence. Further analyses will focus on tool effects on A1c control. Disclosure A.D. Misra-Hebert: Research Support; Self; Agency for Healthcare Research and Quality, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. K.M. Pantalone: Consultant; Self; Bayer Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. S. Rajpathak: Employee; Self; Menarini Group. T. Weiss: Employee; Self; Merck & Co., Inc. M. Hamaty: Research Support; Self; Merck & Co., Inc. R.S. Zimmerman: Research Support; Self; Bayer U.S., Merck & Co., Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; LifeScan, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Baxter, Bristol-Myers Squibb, Pfizer Inc., Procter & Gamble Company.

Background: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and is associated with an increased risk of thromboembolic events, heart failure, and frequent hospitalizations. Type 2 diabetes mellitus (T2DM) has one of the strongest associations with AF with an overall 35% increased risk. Metformin is the first-line medication for T2DM and it has been proposed to have anti-inflammatory, pro-metabolic and cardioprotective benefits, but its effect on AF is not well studied. Our objective was to investigate whether the initial metformin monotherapy was associated with reduced AF rates compared to other non-insulin agents. Methods: This retrospective cohort analysis involved adults with newly diagnosed T2DM between 2007 and 2017, without any history of arrhythmias or contraindications to metformin use including GFR less than 30 ml/min who initiated a single antidiabetes therapy (except insulin). A multivariate analysis was performed to control for other variables that may have impacted the association between initial therapy with metformin and the outcomes of interest. Results: Out of 42384 cases with newly diagnosed diabetes, 5664 patients met the inclusion criteria. The majority of patients initiated monotherapy with metformin (81%), followed by sulfonylureas (13%) and thiazolidinediones (4%). The 10-year cumulative incidence of AF in the metformin group was 5.2% vs. 8.1% with others. Competing risk analysis did not demonstrate reduced rates of AF with metformin use (HR 0.92 95% CI 0.69 to 1.21; P = 0.55). Increased age and the presence of CHF were associated with significantly higher risk of AF (HR: 1.29, 95% CI: 1.21 to 1.37; P Conclusion: In this observational study following patients with newly diagnosed T2DM, first-line therapy with metformin, when compared to other non-insulin antidiabetes therapies, was not found to be associated with a decreased risk of developing AF. Disclosure Z. Tekin: None. A. Milinovich: Research Support; Self; Novartis AG, Novo Nordisk Inc. X. Ji: Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. J. Bauman: None. M. Kattan: Consultant; Self; GlaxoSmithKline plc. Research Support; Self; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc. K.M. Pantalone: Consultant; Self; Bayer Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. R.S. Zimmerman: Research Support; Self; Bayer U.S., Merck & Co., Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; LifeScan, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Baxter, Bristol-Myers Squibb, Pfizer Inc., Procter & Gamble Company. M.K. Chung: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc.

AIMS To assess the effects of 'clinical' and 'intensification inertia' by evaluating the impact of different intensification interventions on the probability of HbA1c goal attainment using real-world data. METHODS Electronic health records (Cleveland Clinic, 2005-2016) were used to identify 7389 people with Type 2 diabetes mellitus and HbA1c ≥53 mmol/mol (≥7.0%), despite a stable regimen of two oral antihyperglycaemic drugs for ≥6 months. The participants were stratified by index HbA1c and analysed over a 6-month period for pharmacological intensification, and then for 12 additional months for HbA1c goal attainment (

Background: Ring chromosome 13 is a rare genetic disorder in which the two ends of chromosome 13 are fused together to form a ring shape. Ring formation subsequently leads to gene deletions on both the long and short arms of the chromosome. Observed phenotypes among these patients are variable due to differences in the number of genetic deletions that occur with fusion. Common clinical features seen in ring chromosome 13 include micro- or anencephaly, severe mental retardation (MR), ambiguous genitalia, growth retardation, and facial dysmorphism. To our knowledge, diabetes mellitus (DM) has only been reported in two published case reports of patients with ring chromosome 13. It has been proposed that development of DM in this syndrome may be due to deletion of the IRS2 gene on the long arm of chromosome 13. This hypothesis is based on evidence from knockout mice studies and genetic comparisons of ring chromosome 13 patients with and without DM. Clinical Case: We present a case of a 23-year-old woman with a known history of mosaic ring chromosome 13 abnormality who was diagnosed with DM at age 21. Diagnosis was made incidentally based on laboratory data obtained at a routine outpatient visit. Hemoglobin A1c at that time was 13.1%. Glutamic acid decarboxylase and insulin antibodies were negative. She has been on a basal-bolus insulin regimen since diagnosis with overall good glycemic control (average hemoglobin A1c 6.5%). She has no known micro- or macrovascular complications of DM. She has no family history of chromosome 13 syndrome or DM. Other notable clinical features associated with her ring chromosome 13 disorder include MR, spastic encephalopathy, delayed puberty (menarche at age 18), scoliosis, facial dysmorphism, and deficiencies in clotting factors 7 and 10. Conclusion: DM is a common disorder that is typically multifactorial in etiology. In rare cases, DM can be the result of monogenic mutations or deletions. We present a case of a young woman with early-onset antibody-negative DM thought to be related to gene deletions resulting from her underlying ring chromosome 13 abnormality. There is some evidence from prior case reports and rodent studies to suggest that DM in patients with this disorder may be the result of IRS2 deletion from the long arm of chromosome 13. Although DM is a rare complication of ring chromosome 13 disorder, early screening should be considered in these patients to prevent development of downstream complications. References: 1. Babaya N, Noso S, Hiromine Y, Ito H, Taketomo Y, Yamamoto T, Kawabata Y, Ikegami H. Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including IRS2. J Endocr Soc. 2018 Sep 11;2(10):1207-1213. 2. Lagergren M, Börjeson M, Mitelman F. Prophase analysis of ring chromosome 13--an attempt at phenotype-karyotype correlation. Hereditas. 1980;93(2):231-3.

Background: Glycogen storage disease type 1b (GSD1b) is caused by a deficiency of glucose 6 phosphatase leading to glycogen deposition. The hallmark findings of GSD1b are hypoglycemia and lactic acidosis. GSD1b can be associated with hepatomegaly, hypertriglyceridemia, hematologic abnormalities, hypothyroidism, inflammatory bowel disease, proteinuria, and hypoglycemic seizures. Main stay of therapy is to avoid fasting and to ingest frequent feeds high in complex CHO. Raw cornstarch (CS) has been used for the treatment of hypoglycemia in GSD1b since the early 1980s. CS is digested slowly, providing a steady release of glucose allowing for more stable glucose levels over a longer period of time as compared with other sources of CHO. Adults may require more CS to maintain BG >70 mg/dL and lactate Clinical Case: A 31 year old female with a history of GSD1b complicated by hypoglycemia, Crohn’s disease, chronic pancreatitis and neutropenia was admitted for abdominal pain, emesis and inability to tolerate CS. She was made NPO and was started on a dextrose drip to avoid hypoglycemia and hyperlactatemia. The rate of dextrose infusion was adjusted to maintain lactate levels Conclusion: We report a rare case of GSD1b and diabetes. The pathogenesis may be related to effects of chronic pancreatitis or metabolic syndrome. Treatment of hyperglycemia in patients with GSD1b is challenging given the heightened risk of fasting hypoglycemia. Treatment options are limited, and there are no data regarding the safe use of insulin in this patient population.

Objective: Titration of desmopressin can be challenging during complex, lengthy surgical procedures in patients with chronic central diabetes insipidus (DI). Arginine vasopressin (AVP) may be the preferred treatment modality in these settings. No data currently exist on the use of AVP during lengthy operations.Methods: We report a novel AVP infusion protocol for the management of chronic DI during a 27-hour total facial transplantation surgery.Results: A 21-year-old woman was admitted for a total facial transplantation surgery. Her medical history was significant for severe facial injuries and panhypopituitarism, both secondary to a ballistic trauma sustained 3 years prior. For the management of her chronic central DI during the complex surgery, a unique AVP infusion protocol was developed. Intraoperatively, the infusion was adjusted hourly following an internally developed algorithm with pre-specified goal parameters for urine output (50 to 200 mL/hour) and serum sodium levels (136 to 144 mmol/L; reference range: 136 to 144 mmol/L). The short half-life of AVP provided ease of dose titration. Under this protocol, the patient's hemodynamic values and serum sodium levels remained stable throughout the 27-hour transplantation surgery.Conclusion: We describe the successful use of a novel AVP infusion protocol for the management of DI during a 27-hour facial transplantation surgery. This protocol may also be effective in managing other patients with chronic central DI during lengthy intraoperative periods.Abbreviations: AVP = arginine vasopressin; DDAVP = 1-deamino-8-D-arginine vasopressin; DI = diabetes insipidus

BACKGROUND The aim of the present study was to assess the longitudinal accumulation of diabetes-related complications and the effect of glycemic control on the Diabetes Complications Severity Index (DCSI) score in people with newly diagnosed type 2 diabetes (T2D). METHODS A retrospective cohort study was conducted using electronic health records from a large integrated healthcare system. People with newly diagnosed T2D were identified between 2005 and 2016 and stratified by initial HbA1c category (

Aims To assess the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. Research Design and Methods Patients who had T2D between 2005 and 2014 (N = 105 862) were identified from the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes. The findings were further evaluated by assessing the effect of GLP-1RAs on the same variables in patients with and without prior CVD. The model adjusted for differences in demographic information, hypertension, laboratory/vital signs, history of outcomes, and T2D medications. Results There were significantly lower rates of AMI (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65 to 0.99; P = .045), CVA (HR 0.82, 95% CI 0.74 to 0.91, P

Objective: Clomiphene citrate-induced hypertriglyceridemia causing acute pancreatitis is rare. The aim of this case report is to alert physicians to the possibility of clomiphene citrate-induced hypertriglyceridemia that can lead to acute, and even chronic, pancreatitis.Methods: We describe a patient with known mild hypertriglyceridemia who presented with acute pancreatitis and severe hypertriglyceridemia after initiation of clomiphene citrate.Results: The patient had mid-epigastric tenderness with radiation around her bilateral flanks in a band-like distribution. Lab studies showed a triglyceride level greater than 4,425 mg/dL, a lipase level greater than 3,000 U/L, and computed tomography of the abdomen showed acute interstitial edematous pancreatitis. The patient's Naranjo Adverse Drug Reaction score was calculated to be a 7, and was therefore probable as clomiphene being the causative agent. The patient's triglyceride levels improved after initiation of fibrate therapy and discontinuation of clomiphene at first; however, she continued to develop acute episodes of pancreatitis that progressed to chronic pancreatitis despite stopping clomiphene citrate. This is the second report of recurrent pancreatitis with hypertriglyceridemia induced by clomiphene citrate and, in this case specifically, each episode of pancreatitis was associated with hypertriglyceridemia.Conclusion: Clomiphene citrate-induced hypertriglyceridemia rarely occurs and can progress to acute, and even chronic, pancreatitis with significant morbidity. Clomiphene citrate should be used with caution in patients with elevated triglycerides, and should be avoided in patients with triglyceride levels greater than 400 mg/dL.

Background/Aim Episodes of non-severe hypoglycemia can be captured through diagnoses documented in the electronic medical record. We aimed to create a clinically useful prediction model for a severe hypoglycemia event, requiring an emergency department visit or hospitalization, in patients with Type 2 diabetes with a history of non-severe hypoglycemia. Methods Using electronic medical record data from 50,439 patients with Type 2 diabetes in one health system, number of severe hypoglycemia events and associated patient characteristics from 2006 to 2015 were previously defined. Using the landmarking method, a dynamic prediction model was built using the subset of 1876 patients who had a documented non-severe hypoglycemia diagnosis code, using logistic regression to obtain landmark-specific odds of severe hypoglycemia in this group. For model performance, the bootstrap procedure was employed for internal validation and area under the curve (AUC) and index of prediction accuracy (IPA) were calculated. Results Glycosylated hemoglobin (HbA1c) less than 7% (53 mmol/mol) was associated with increased odds ratio (OR) of severe hypoglycemia at 3 months (OR 1.92 95% Confidence Interval (CI) 1.19–3.10 at HbA1c 5% (31 mmol/mol) and OR 1.21, CI 1.03–1.41 at HbA1c 6%(42 mmol/mol).) History of non-severe hypoglycemia within the past 3 months increased odds for severe hypoglycemia (OR 2.58 95% CI 1.80–3.70) as did Black race, insulin use with the past 3 months, and comorbidities. Metformin and sulfonlylurea use in the past 3 months, increasing age and body mass index had lower odds of a future severe hypoglycemia event. For the prediction model for 3 month risk of severe hypoglycemia, the AUC was 0.890 (CI 0.843–0.907) and the IPA was 10.8% (CI 4.4% - 12.4%). Conclusion In patients with a documented diagnosis of non-severe hypoglycemia, a dynamic prediction model identifies patients with Type 2 diabetes with 3-month increased risk of severe hypoglycemia, allowing for preventive efforts, such as medication changes, at the point of care.

An electronic health record (EHR)-based tool was developed for EPIC My Practice at Cleveland Clinic to aid treatment decisions and combat therapeutic inertia in patients with type 2 diabetes (T2D) and suboptimal glycemic control (A1C ≥8%). The tool consists of three separate components activated during an office visit: a best practice alert (BPA) if a patient had an A1C ≥ 8% within the past 6 months, a Smartform (patient summary and order entry form), and a Smartset for T2D medications to achieve patient-centered treatment goals, supplies, laboratory, and consult orders. The provider may acknowledge the BPA and pursue therapy intensification or defer. The tool was piloted for 3 months (primary care providers (PCP) n=12, endocrinology providers n=5). BPA acknowledgement and utilization practices were recorded by specialty. The CollaboRATE survey (3 items, scale 0-9) was used to assess patient perceptions of shared decision-making afforded by the tool. The BPA appeared for 420/1,766 T2D patients at an office-based encounter with a PCP or endocrinology provider. While the BPA was acknowledged at most endocrinology visits (95%) and approximately 50% of primary care visits, use of all three components of the tool only occurred in ∼10% of eligible encounters. The CollaboRATE survey was administered to a subset of 83 patients exposed to the tool. Most chose the highest rating for questions assessing if efforts were made to: 1. help them better understand their health issue (87%), 2. listen to what matters most to them about their health issue (93%) and 3. integrate what matters to them into next steps (92%). Use of an EHR-based tool to aid treatment decisions is variable by specialty, though appears to lead to a high perception of shared decision-making for T2D patients. Additional provider education and improved incorporation of the tool into PCP work-flow may help to address therapeutic inertia in routine clinical practice. Disclosure K.M. Pantalone: Consultant; Self; Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. A.D. Misra-Hebert: Research Support; Self; Agency for Healthcare Research and Quality, Merck & Co., Inc., Novo Nordisk Inc. S. Rajpathak: None. T. Weiss: Employee; Self; Merck & Co., Inc. M. Hamaty: Consultant; Self; Applied Clinical Intelligence, LLC. R.S. Zimmerman: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Johnson & Johnson Diabetes Institute, Merck & Co., Inc.

Background: Comprehensive medication management (CMM) ensures an individualized plan for medication appropriateness, effectiveness, safety, and adherence. It is most often performed by pharmacists within a pharmacist-physician collaborative agreement. Published studies on CMM are few and mostly conducted in primary care settings. The aim of our study was to determine the impact of CMM on the proportion of patients that achieve ≥ 1% A1c reduction in an interprofessional specialty clinic. Methods: This is a retrospective study comparing 2 groups: group 1-without pharmacist collaboration, group 2-with pharmacist collaboration. Subjects were adults with diabetes and most recent A1c ≥ 8.5% with at least one visit in the interprofessional endocrinology clinic between 1/2016-12/2017. Exclusion criteria were pregnancy, no A1c within 6 weeks of initial visit, and no follow-up A1c. The 2 groups were matched for initial A1c, type of diabetes, age, and BMI. Results: A total of 162 participants were included. Baseline characteristics were similar between groups: Group 1: (mean age: 57.6 ± 15.8 years, BMI: 34.3 ± 8.1 kg/m2, A1c: 10.2 ± 1.2%, T1DM: 26%), Group 2 (mean age: 56.0 ±16.4 years, BMI: 32.6 ± 8.1 kg/m2, A1c: 10.1± 1.3%, T1DM: 26%). The percentage of subjects achieving ≥1% A1c reduction at 6 months was 58.0% in Group 2 compared to 40.7% in Group 1, p=0.041. More subjects achieved A1c < 8% in group 2 (32.1%) vs. Group 1 (18.5%), p=0.047. The frequency of endocrinologist visits was more in group 1 (2.37/patient) vs. group 2 (1.89/patient), p=0.01. Group 2 averaged 3.0 pharmacist visits per patient. Discussion: Physician-pharmacist collaboration led to greater A1c reduction compared to usual endocrinologist care in patients with uncontrolled A1c. However, frequency of total provider visits may account for some differences. Overall, utilizing pharmacists within diabetes health care models may reduce frequency of endocrinologist visits while improving glycemic control. Disclosure D. Isaacs: Advisory Panel; Self; BD, Sanofi-Aventis. R.S. Zimmerman: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Johnson & Johnson Diabetes Institute, Merck & Co., Inc. M. Lansang: None.

OBJECTIVE “Clinical inertia” has been used to describe the delay in the intensification of type 2 diabetes treatment among patients with poor glycemic control. Previous studies may have exaggerated the prevalence of clinical inertia by failing to adequately monitor drug dose changes and nonmedication interventions. This project evaluated the intensification of diabetes therapy and hemoglobin A1c (A1C) goal attainment among patients with newly diagnosed type 2 diabetes when metformin monotherapy failed. RESEARCH DESIGN AND METHODS The electronic health record at Cleveland Clinic was used to identify patients with newly diagnosed type 2 diabetes between 2005 and 2013 who failed to reach the A1C goal after 3 months of metformin monotherapy. A time-dependent survival analysis was used to compare the time until A1C goal attainment in patients who received early intensification of therapy (within 6 months of metformin failure) or late intensification. The analysis was performed for A1C goals of 7% (n = 1,168), 7.5% (n = 679), and 8% (n = 429). RESULTS Treatment was intensified early in 62%, 69%, and 72% of patients when poor glycemic control was defined as an A1C >7%, >7.5%, and >8%, respectively. The probability of undergoing an early intensification was greater the higher the A1C category. Time until A1C goal attainment was shorter among patients who received early intensification regardless of the A1C goal (all P < 0.05). CONCLUSIONS A substantial number of patients with newly diagnosed type 2 diabetes fail to undergo intensification of therapy within 6 months of metformin monotherapy failure. Early intervention in patients when metformin monotherapy failed resulted in more rapid attainment of A1C goals.

Many employers offer worksite wellness programs, including financial incentives to achieve goals. Evidence supporting such programs is sparse.To assess whether diabetes and cardiovascular risk factor control in employees improved with financial incentives for participation in disease management and for attaining goals.Retrospective cohort study using insurance claims linked with electronic medical record data from January 2008-December 2012.Employee patients with diabetes covered by the organization's self-funded insurance and propensity-matched non-employee patient comparison group with diabetes and commercial insurance.Financial incentives for employer-sponsored disease management program participation and achieving goals.Change in glycosylated hemoglobin (HbA1c), low-density lipoprotein (LDL), systolic blood pressure (SBP), and weight.A total of 1092 employees with diabetes were matched to non-employee patients. With increasing incentives, employee program participation increased (7 % in 2009 to 50 % in 2012, p 0.001). Longitudinal mixed modeling demonstrated improved diabetes and cardiovascular risk factor control in employees vs. non-employees [HbA1c yearly change -0.05 employees vs. 0.00 non-employees, difference in change (DIC) p0.001]. In their first participation year, employees had larger declines in HbA1c and weight vs. non-employees (0.33 vs. 0.14, DIC p = 0.04) and (2.3 kg vs. 0.1 kg, DIC p 0.001), respectively. Analysis of employee cohorts corresponding with incentive offerings showed that fixed incentives (years 1 and 2) or incentives tied to goals (years 3 and 4) were not significantly associated with HbA1c reductions compared to non-employees. For each employee cohort offered incentives, SBP and LDL also did not significantly differ in employees compared with non-employees (DIC p 0.05).Financial incentives were associated with employee participation in disease management and improved cardiovascular risk factors over 5 years. Improvements occurred primarily in the first year of participation. The relative impact of specific incentives could not be discerned.

Background To evaluate real-world patient characteristics, medication use, and health care utilization patterns in patients with type 2 diabetes with established cardiovascular disease (CVD). Methods Cross-sectional analysis of patients with type 2 diabetes seen at Cleveland Clinic from 2005 to 2016, divided into two cohorts: with-CVD and without-CVD. Patient demographics and antidiabetic medications were recorded in December 2016; department encounters included all visits from 1/1/2016 to 12/31/2016. Comorbidity burden was assessed by the diabetes complications severity index (DCSI) score. Results Of 95,569 patients with type 2 diabetes, 40,910 (42.8%) were identified as having established CVD. Patients with CVD vs. those without were older (median age 69.1 vs. 58.2 years), predominantly male (53.8% vs. 42.6%), and more likely to have Medicare insurance (69.4% vs. 35.3%). The with-CVD cohort had a higher proportion of patients with a DCSI score ≥ 3 than the without-CVD cohort (65.0% vs. 10.3%). Utilization rates of glucagon-like peptide-1 receptor agonists and sodium–glucose co-transporter-2 inhibitors were low in both with-CVD (4.1 and 2.5%) and without-CVD cohorts (5.4 and 4.1%), respectively. The majority of patient visits (75%) were seen by a primary care provider. During the 1-year observation period, 81.9 and 62.0% of patients with type 2 diabetes and CVD were not seen by endocrinology or cardiology, respectively. Conclusions These data indicated underutilization of specialists and antidiabetic medications reported to confer CV benefit in patients with type 2 diabetes and CVD. The impact of recently updated guidelines and cardiovascular outcome trial results on management patterns in such patients remains to be seen.

Background The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent. Methods A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13 185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group. Results The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55 100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04–1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74–1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30–1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified. Conclusions Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i.

The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascu...

OBJECTIVE To identify severe hypoglycemia events, defined as emergency department visits or hospitalizations for hypoglycemia, in patients with type 2 diabetes receiving care in a large health system and to identify patient characteristics associated with severe hypoglycemia events. RESEARCH DESIGN AND METHODS This was a retrospective cohort study from January 2006 to December 2015 using the electronic medical record in the Cleveland Clinic Health System (CCHS). Participants included 50,439 patients with type 2 diabetes receiving care in the CCHS. Number of severe hypoglycemia events and associated patient characteristics were identified. RESULTS The incidence proportion of severe hypoglycemia increased from 0.12% in 2006 to 0.31% in 2015 (P = 0.01). Compared with patients who did not experience severe hypoglycemia, those with severe hypoglycemia had similar median glycosylated hemoglobin (HbA1c) levels. More patients with severe hypoglycemia versus those without had a prior diagnosis of nonsevere hypoglycemia (9% vs. 2%, P < 0.001). Logistic regression confirmed an increased odds for severe hypoglycemia with insulin, sulfonylureas, increased number of diabetes medications, history of nonsevere hypoglycemia (odds ratio [OR] 3.01, P < 0.001), HbA1c CONCLUSIONS In this retrospective study of patients with type 2 diabetes with severe hypoglycemia, patient characteristics were identified. Patients with severe hypoglycemia had previous nonsevere hypoglycemia diagnoses more frequently than those without. Identifying patients at high risk at the point of care can allow for change in modifiable risk factors and prevention of severe hypoglycemia events.

Inadequate glycemic control remains the leading cause of blindness, kidney failure, and nontraumatic lower-limb amputation.

Despite clinical practice guidelines that recommend frequent monitoring of HbA1c (every 3 months) and aggressive escalation of antihyperglycemic therapies until glycemic targets are reached (1,2), the intensification of therapy in patients with uncontrolled type 2 diabetes (T2D) is often inappropriately delayed. The failure of clinicians to intensify therapy when clinically indicated has been termed “clinical inertia.” A recently published systematic review found that the median time to treatment intensification after an HbA1c measurement above target was longer than 1 year (range 0.3 to >7.2 years) (3). We have previously reported a rather high rate of clinical inertia in patients uncontrolled on metformin monotherapy (4). Treatment was not intensified early (within 6 months of metformin monotherapy failure) in 38%, 31%, and 28% of patients when poor glycemic control was defined as an HbA1c >7% (>53 mmol/mol), >7.5% (>58 mmol/mol), and >8% (>64 mmol/mol), respectively. Using the electronic health record system at Cleveland Clinic (2005–2016), we identified a cohort of 7,389 patients with T2D who had an HbA1c value ≥7% (≥53 mmol/mol) (“index HbA1c”) despite having been on a stable regimen of two oral antihyperglycemic drugs (OADs) for at least 6 months prior to the …

Aims To analyse the association between cancer incidence and oral diabetes therapy (biguanide, sulphonylurea, thiazolidinedione and meglitinide) in men and women with type 2 diabetes mellitus. Methods A retrospective analysis of the electronic health record-based Cleveland Clinic Diabetes Registry (25 613 patients) was cross-indexed with the histology-based tumour registry (48 051 cancer occurrences) over an 8-year period (1998–2006). Multiple imputations were used to account for missing data. Cox regression with propensity scores was used to model time for the development of incident cancer in each of the imputed datasets and the results were pooled. Results During 51 994 person follow-up years, 892 incident cancer cases were identified; prostate (14.5%) and breast (11.7%) malignancies were most frequent. In women, thiazolidinedione use was associated with a 32% decreased cancer risk compared with sulphonylurea use [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.48–0.97, in the adjusted analysis]. Comparison of insulin secretagogues (sulphonylurea and meglitinide) versus insulin sensitizers (biguanide and thiazolidinedione) demonstrated a 21% decreased cancer risk in insulin sensitizers [HR 0.79 (95% CI 0.64–0.98) in the adjusted analysis]. Oral diabetes therapy showed no significant difference in men. Adjustments were made for age, body mass index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, coronary heart disease (CHD), diabetes oral monotherapy, race, gender, haemoglobin A1c, statin use, income, insulin use, glomerular filtration rate (GFR), new diabetes status, prior cancer, prior cerebrovascular accident (stroke or transient ischaemic event), systolic/diastolic blood pressure, tobacco use (ever/never) and the propensity score for receiving a biguanide. Conclusions Oral insulin sensitizers, particularly thiazolidinedione, are associated with decreased malignancy risk in women with type 2 diabetes mellitus.

Objective This study retrospectively compared the effects of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) as classes with respect to overall mortality and cardiovascular and renal events in patients with type 2 diabetes. Methods An electronic database of medical records was reviewed. A total of 16,489 patients with type 2 diabetes were enrolled and divided into ACEI (n = 12,351) or ARB (n = 4,138) groups. Baseline patient characteristics were compared using univariable analysis. A chi-square test was used for categorical outcomes, and the propensity class was calculated using multivariable logistic regression. Survival analysis was performed to evaluate the effect of ACEIs/ARBs on overall survival, coronary artery disease (CAD), and renal events via Cox regression analysis, adjusting for propensity class and baseline variables. All statistical analyses were conducted using R 2.15.1 software. Results No significant differences in overall survival (P = .16) and CAD (P = .81) events were observed between groups. With respect to renal events, ARBs increased the risk of creatinine doubling compared with ACEIs, but the difference was not significant (hazard ratio [HR], 1.207; 95% confidence interval [CI], 0.921-1.583; P = .173). Patients who received ARBs had a significantly higher rate of albuminuria than patients who received ACEIs (HR, 1.303; 95% CI, 1.053-1.612; P = .015). Conclusion The early effects of ACEIs and ARBs on albuminuria outcome seem to be different in type 2 diabetes, favoring the use of ACEIs. A well-designed prospective study is warranted to evaluate this finding. (Endocr Pract. 2013;19:579-586)

Diabet. Med. 29, 1029–1035 (2012) Abstract Aims Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin. Methods A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. Results No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89–1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90–1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95–1.15). Conclusions Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.

Given that preoperative hyperglycemia is associated with poor outcomes and many non-diabetic patients have high plasma glucose (PG) levels, the purpose of our study was to estimate the prevalence of undiagnosed diabetes among non-cardiac surgery patients and to identify predictors of hyperglycemia in non-diabetics.We included all non-cardiac surgery patients with complete records in the Clinical Database of the Anesthesiology Institute at the Cleveland Clinic during January 2007 to April 2009, and we estimated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) among the non-diabetic patients. The mean glucose levels for known diabetics and undiagnosed diabetics were compared using two-tailed Student's t tests, and we assessed the association between PG levels and demographic variables within the non-diabetics.Of the 39,434 patients analyzed, 5,511 (14%) were known diabetics. Of the 33,923 known non-diabetics, 3,426 (10 %) were undiagnosed diabetics and another 3,549 (11%) had IFG. Thus, 6,975 patients (21%) of the non-diabetic patients presented with abnormally high glucose. Previously undiagnosed diabetics had higher preoperative glucose levels compared with known diabetics, with a mean ± standard deviation (SD) of 161 ± 48 vs 146 ± 67 mg·dL⁻¹ (8.9 ± 2.7 vs 8.1 ± 3.7 mmoL·L⁻¹), respectively. The difference remained highly significant after adjusting for body mass index, age, sex, and American Society of Anesthesiologists (ASA) physical status (P0.001). Among non-diabetics, older age, obesity, male sex, and a higher ASA physical status were collectively significant predictors of hyperglycemia, with a c-statistic (95% confidence interval) of 0.67 (0.66-0.68).A significant proportion of non-cardiac surgery patients have previously undiagnosed diabetes and pre-diabetes. Previously undiagnosed patients have higher fasting glucose levels compared with diabetic patients. Further studies should be conducted to identify the implications of these findings on patient outcomes.

OBJECTIVE Sulfonylureas have historically been analyzed as a medication class, which may be inappropriate given the differences in properties inherent to the individual sulfonylureas (hypoglycemic risk, sulfonylurea receptor selectivity, and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the relationship of individual sulfonylureas and the risk of overall mortality in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141 patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with glipizide, and 2,537 initiators of monotherapy with glimepiride), ≥18 years of age with and without a history of coronary artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models were used to compare cohorts. RESULTS No statistically significant difference in the risk of overall mortality was observed among these agents in the entire cohort, but we did find evidence of a trend toward an increased overall mortality risk with glyburide versus glimepiride (hazard ratio 1.36 [95% CI 0.96–1.91]) and glipizide versus glimepiride (1.39 [0.99–1.96]) in those with documented CAD. CONCLUSIONS Our results did not identify an increased mortality risk among the individual sulfonylureas but did suggest that glimepiride may be the preferred sulfonylurea in those with underlying CAD.

To assess changes in the clinical characteristics and treatment patterns of patients with newly diagnosed type 2 diabetes (T2D), the electronic health record system at Cleveland Clinic was used to create cross-sectional summaries of all patients with new-onset T2D in 2008 and 2013. Differences between the 2008 and 2013 data sets were assessed after adjusting for age, gender, race, and income. Approximately one-third of patients with newly diagnosed T2D in 2008 and 2013 had an A1C ≤8%, suggesting the continued presence of a delayed recognition of the disease. Patients with newly diagnosed T2D in 2008 were older than those in 2013. Hypertension, cardiovascular disease, and neuropathy were highly prevalent among patients diagnosed with T2D. The prevalence of neuropathy, cerebrovascular disease, and peripheral vascular disease increased from 2008 to 2013. Metformin was the most commonly prescribed antidiabetic medication. Sulfonylurea usage remained unchanged, while use of thiazolidinediones decreased considerably.

To estimate the prevalence of the association between thyroid disease and idiopathic thrombocytopenia (ITP), and to examine the effect of treatment of the thyroid condition on platelet count.Retrospective cohort study performed in a tertiary care center setting. All patients who were diagnosed with ITP by a single provider at the Cleveland Clinic Hematology/Oncology Department between 1988 and 2005 were included.Among the 98 patients, thyroid function tests were available in 80 patients. Of these, 16 (20%) had abnormal thyroid function: 6 had hyperthyroidism and 10 had hypothyroidism. The median interval from the onset of the thyroid or hematological condition (whichever came first) was 84 months (range: 25-612). The autoimmune nature of the thyroid disease was proven in 12 cases (75%). Three patients showed a transient increase in the platelet count after restoring the euthyroid state; however, durable improvement of thrombocytopenia was not encountered.The prevalence of hypothyroidism in patients with ITP is higher than in the general population. Based on this observation, routine assessment of thyroid function should be done in patients with ITP. The long-term course of ITP was not influenced by the treatment of the thyroid condition.

Objective To report a case of recurrent acute suppurative thyroiditis (AST) caused by a piriform sinus fistula (PSF). Methods We review the related literature and describe the clinical presentation, diagnostic evaluation, and management of a patient with recurrent AST due to PSF. Results A 50-year-old woman presented with recurrent episodes of pain and swelling in the left anterior neck area and odynophagia. The initial episode, 1 year previously, lasted for 1 month, and her condition improved with a short course of prednisone. Subsequently, the neck pain recurred and extended upward to both sides of the neck. She was suspected of having thyroiditis and was treated with prednisone for 6 weeks, but the symptoms persisted. Physical examination showed tenderness and induration of the skin over the left lobe of the thyroid. Ultrasonography disclosed an ill-defined solid-cystic area in the left thyroid lobe. Fine-needle aspiration cytology revealed acute inflammation, consistent with an infected cyst. A computed tomographic scan of the neck showed obscuration of the fat planes involving the left strap musculature and evidence suggestive of microabscesses. Prolonged intravenous antibiotic treatment ultimately alleviated the symptoms. Direct laryngoscopy revealed a fistula extending anteriorly from the apex of the piriform sinus. The patient underwent complete fistulectomy and left thyroid lobectomy and was asymptomatic on followup. Conclusion PSF should be suspected as a cause of recurrent AST. Absence of fever, toxemia, and local erythema does not rule out the condition. Unresponsiveness to corticosteroid therapy in thyroiditis should suggest the diagnosis. Complete fistulectomy and resection of the involved thyroid lobe result in permanent cure. (Endocr Pract. 2007;13:662-666)

Over the last decade, much attention has focused on the reorganization of the roles and functions of public health to improve the health of communities. The Pennsylvania State Health Improvement Plan (SHIP) offers one example of how national, state, and local components of the public health system can effectively integrate their strategies and resources to improve responsiveness to local public health needs. This article reviews the policy action and planning process used to develop a community partnership, shared-responsibility model and the strategies and implementation plans that have been adopted to achieve substantial, measurable improvement in community health status.

ObjectiveTo determine the prevalence of obesity and its related comorbidities among patients being actively managed at a US academic medical centre, and to examine the frequency of a formal diagnosis of obesity, via International Classification of Diseases, Ninth Revision (ICD-9) documentation among patients with body mass index (BMI) ≥30 kg/m2.DesignThe electronic health record system at Cleveland Clinic was used to create a cross-sectional summary of actively managed patients meeting minimum primary care physician visit frequency requirements. Eligible patients were stratified by BMI categories, based on most recent weight and median of all recorded heights obtained on or before the index date of 1July 2015. Relationships between patient characteristics and BMI categories were tested.SettingA large US integrated health system.ResultsA total of 324 199 active patients with a recorded BMI were identified. There were 121 287 (37.4%) patients found to be overweight (BMI ≥25 and 30 (n=134 488), only 48% (64 056) had documentation of an obesity ICD-9 code. In those patients with a BMI >40, only 75% had an obesity ICD-9 code.ConclusionsThis cross-sectional summary from a large US integrated health system found that three out of every four patients had overweight or obesity based on BMI. Patients within higher BMI categories had a higher prevalence of comorbidities. Less than half of patients who were identified as having obesity according to BMI received a formal diagnosis via ICD-9 documentation. The disease of obesity is very prevalent yet underdiagnosed in our clinics. The under diagnosing of obesity may serve as an important barrier to treatment initiation.

This article has discussed the classic hormonal causes of hypertension. Pheochromocytoma and hyperaldosteronism have been discussed, and a clinical approach to evaluation of patients for these problems has been presented. Other humeral factors that influence volume pressure homeostasis have been discussed. It is likely that pharmacologic agents affecting these other factors will become available to patients with hypertension in the future.

Aims: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. Methods: A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. Results: An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39–1.94), glyburide (HR 1.59; 95% CI 1.35–1.88), and glimepiride (HR 1.68; 95% CI 1.37–2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07–1.87) and glyburide (HR 1.38; 95% CI 1.04–1.83) versus metformin. Conclusions: Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD.

The pituitary stalk transection syndrome was characterized after introducing the MRI scan in the evaluation of children with hypopituitarism. Its prevalence and natural history into adulthood have not been clearly established. We present 4 cases of stalk transection syndrome diagnosed by the adult endocrinologist that reflect its pleiotropic manifestations. In all cases, MRI showed pathognomonic findings with small anterior pituitary, diminutive or absent infundibulum and ectopic posterior pituitary at the median eminence. Clinical presentation occurred in childhood or the second decade of life. The hormonal deficits were variable in severity and onset, with adrenal insufficiency diagnosed in the second and forth decade in three patients, and absent in another. Growth hormone deficiency was diagnosed before age 10 in three cases and at age 20 in one case with normal spontaneous linear growth. Hypothyroidism had onset in the first or second decade of life and hypogonadism was diagnosed during work-up for lack of pubertal development in all cases. The pituitary stalk transection syndrome should be considered in patients who were previously thought to have idiopathic GH deficiency or multiple pituitary hormone deficiencies. Presence of MRI characteristics compatible with the pituitary stalk transection syndrome should prompt a full pituitary hormonal evaluation. Long-term follow-up by the adult endocrinologist is warranted as new hormone deficiencies might appear later in life.

Submitted for publication August 5, 2014 Accepted for publication August 5, 2014 From the Cleveland Clinic Foundation, Cleveland, Ohio. Address correspondence to Dr. Robert Zimmerman, Cleveland Clinic Foundation, Department of Endocrinology, Diabetes, and Metabolism, 9500 Euclid Avenue, Desk F-20, Cleveland, OH 44195-0001. E-mail: zimmerr@ccf.org. Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on October 8, 2014. DOI:10.4158/EP14364.CO To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2014 AACE. Schmidt et al (1) defined “dawn phenomenon” as the night to morning elevation of blood glucose (BG) before and, to a larger extent, after breakfast in subjects with type 1 diabetes (T1D). A similar observation was made in type 2 diabetes (T2D) by Bolli et al in 1984 (2). In normal, nondiabetic subjects (3-5), there is not a rise in glucose, due to a documented rise in insulin. Ever since the first description, the dawn phenomenon has been studied extensively. In T1D, the magnitude of BG elevation at dawn first reported was substantial, largely due to the decrease in plasma insulin concentration overnight (1), commonly observed with evening administration of Lente or Neutral Protamine Hagedorn insulins (6). Even early studies with the biostator suggested a significant dawn phenomenon, due in part to an artifact caused by degradation of insulin over time in the biostator (7). More recent studies using continuous subcutaneous insulin infusion (CSII) or longacting insulin analogs have suggested an increase of 25 to 50 mg/dL as the magnitude of the dawn phenomenon (8-10). A study by Campbell et al (11) found that in subjects treated with somatostatin, α-adrenergic blockade, and β-adrenergic blockade, that replacement of growth hormone and not the other counterregulatory hormones is the major factor causing the dawn phenomenon. Several studies have found that insulin sensitivity is higher after midnight until 3 am, as compared to the period 4 to 8 am (8-10). Recently, studies of T2D found that fasting hyperglycemia can be attributed to a transient increase in hepatic glucose production (both glycogenolysis and gluconeogenesis) at dawn in the absence of compensatory insulin secretion (12-14). Programming for an early morning increase in insulin delivery is frequently recommended to counteract the rise in glucose prior to breakfast (dawn phenomenon) (8,15). Indeed, one of the indications for utilizing an insulin pump has classically been patients who could not get fasting glucose levels controlled on long-acting insulins. However, neither the effectiveness nor the safety of this approach have been tested in the ambulatory setting.

Oral anti-diabetic agents have been associated with adverse cardiovascular events in type 2 diabetes (DM2). We investigated the risk of coronary artery disease (CAD), congestive heart failure (CHF), and mortality using multivariable Cox models in a retrospective cohort of 20,450 DM2 patients from our electronic health record (EHR). We observed no differences in CAD risk among the agents. Metformin was associated with a reduced risk of CHF (HR 0.76, 95% CI 0.64-0.91) and mortality (HR 0.54, 95% CI 0.46-0.64) when compared to sulfonylurea. Pioglitazone was also associated with a lower risk of mortality when compared to sulfonylurea (HR 0.59, 95% CI 0.43-0.81). No other significant differences were found between the oral agents. In conclusions, our results did not identify an increased CAD risk with rosiglitazone in clinical practice. However, the results do reinforce a possible increased risk of adverse events in DM2 patients prescribed sulfonylureas.

OBJECTIVE To describe a patient with a virilizing adrenal ganglioneuroma and subclinical Cushing syndrome. METHODS Detailed clinical, laboratory, radiologic, and pathologic findings are presented, and the pertinent literature is reviewed. RESULTS A 56-year-old postmenopausal woman was referred for evaluation of a 3.6- by 3.0-cm right adrenal mass, which had been diagnosed during a work-up for hirsutism. A bilateral oophorectomy done 2 months before the presentation failed to correct the elevated testosterone levels. On examination, she had severe hirsutism on her face, chest, back, and extremities, as well as male pattern baldness and clitoromegaly. Biochemical evaluation showed elevated total and free serum testosterone levels of 319 ng/dL (reference range, 20 to 70) and 78 pg/mL (reference range, 1 to 9), respectively, values in the adult male range. The serum dehydroepiandrosterone sulfate level was 117 microg/dL (reference range, 10 to 152), and the urine free cortisol was 10.4 microg/24 h (reference range

To report a case of hypercalcemia associated with parathyroid hormone-related protein (PTHrP) in large cell carcinoma of the lung.We present a case of PTHrP-mediated hypercalcemia in a patient with a large cell carcinoma of the lung and review the related literature.A 43-year-old African American man required medical attention because of lethargy, confusion, and poor oral intake. He had bullous emphysema attributable to a 50-pack-year smoking history. On physical examination, vital signs were normal, he was oriented to place and person but not time, and he had cachexia. Breath sounds were decreased in the left lower lung field. Findings on cardiac and abdominal examination were normal. Results of laboratory studies (and corresponding reference ranges) were as follows: calcium 12.1 mg/dL (8.5 to 10.5), albumin 2.0 g/dL (3.5 to 5.0), phosphorus 2 mg/dL (2.5 to 4.5), alkaline phosphatase 68 U/L (40 to 150), intact parathyroid hormone 5 pg/mL (10 to 60), PTHrP 7.0 pmol/L (0.0 to 1.5), 1,25-dihydroxyvitamin D 20.8 pg/mL (25.1 to 66.1), and 25-hydroxyvitamin D 3.7 ng/mL (10 to 60). Computed tomographic scans of the chest showed a large complex lesion in the left lower hemithorax, a small right pleural effusion, and extensive pulmonary emphysema bilaterally. Open lung biopsy revealed a large cell undifferentiated carcinoma. Abdominal and pelvic computed tomographic scans showed no evidence of metastatic involvement. A bone scan was negative for osseous metastatic lesions.Although the finding is rare, patients with large cell carcinoma of the lung and hypercalcemia may have humoral hypercalcemia mediated by PTHrP.

Purpose To compare the prevalence of diabetes-related complications and comorbidities, clinical characteristics, glycemic control, and treatment patterns in patients with type 2 diabetes (T2D) within a large integrated healthcare system in 2008 vs 2013. Methods An electronic health record system was used to create a cross-sectional summary of all patients with T2D as on 1 July 2008 and 1 July 2013. Differences between the two data sets were assessed after adjusting for age, gender, race, and household income. Results In 2008 and 2013, 24 493 and 41 582 patients with T2D were identified, respectively, of which the majority were male (52.3% and 50.1%) and Caucasian (79% and 75.2%). The mean ages (years) were 64.8 and 64.3. The percentages of patients across the defined A1C categories were 64.3 and 66.7 for