Associations of weight loss with obesity-related comorbidities in a large integrated health system.

AIMS: To determine the health outcomes associated with weight loss in individuals with obesity, and to better understand the relationship between disease burden (disease burden; ie, prior comorbidities, healthcare utilization) and weight loss in individuals with obesity by analysing electronic health records (EHRs). 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 and 2018. Patients were aged ≥20 years with body mass index ≥30 kg/m2 and had ≥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 3, 5 and 10 years prior to an event. RESULTS: Weight loss was associated with reduced incidence of many outcomes (eg, type 2 diabetes, nonalcoholic steatohepatitis/nonalcoholic fatty liver disease, obstructive sleep apnoea, hypertension; P < 0.05). Weight loss >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 the 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.

Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.

BACKGROUND AND AIMS: A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial. METHODS: 19 healthy adults (age:28.4 ±â€¯1.7 years; BMI:22.7 ±â€¯0.3 kg/m2) received an overnight intravenous infusion of lipid (20% Intralipid) or saline followed by a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity using a randomized crossover design. Skeletal muscle biopsies were obtained after the overnight lipid infusion to evaluate activation of mitochondrial dynamics proteins, ex-vivo mitochondrial membrane potential, ex-vivo oxidative phosphorylation and electron transfer capacity, and mitochondrial ultrastructure. RESULTS: Overnight lipid infusion increased dynamin related protein 1 (DRP1) phosphorylation at serine 616 and PTEN-induced kinase 1 (PINK1) expression (P = 0.003 and P = 0.008, respectively) in skeletal muscle while reducing mitochondrial membrane potential (P = 0.042). The lipid infusion also increased mitochondrial-associated lipid droplet formation (P = 0.011), the number of dilated cristae, and the presence of autophagic vesicles without altering mitochondrial number or respiratory capacity. Additionally, lipid infusion suppressed peripheral glucose disposal (P = 0.004) and hepatic insulin sensitivity (P = 0.014). CONCLUSIONS: These findings indicate that activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. Targeting mitochondrial dynamics and quality control represents a promising new pharmacological approach for treating insulin resistance and type 2 diabetes. CLINICAL TRIAL REGISTRATION: NCT02697201, ClinicalTrials.gov.

The Probability of A1C Goal Attainment in Patients With Uncontrolled Type 2 Diabetes in a Large Integrated Delivery System: A Prediction Model.

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 <8% by 31 December 2017, and subgroups were compared on a number of demographic and clinical variables. On the basis of these variables, a nomogram was created for predicting probability of A1C goal attainment. 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 <8%. Predictors of increased probability of A1C goal attainment were older age, white/non-Hispanic race/ethnicity, Medicare health insurance, lower baseline A1C, higher frequency of endocrinology/primary care visits, dipeptidyl peptidase 4 inhibitor use, thiazolidinedione use, metformin use, glucagon-like peptide 1 receptor agonist use, and fewer classes of antidiabetes drugs. Factors associated with lower probability included insulin use and longer time in the T2D database (both presumed as likely surrogates for duration of T2D). CONCLUSIONS: A minority of patients with an A1C >9% achieved an A1C <8% at 1 year. While most identified predictive factors are nonmodifiable by the clinician, pursuit of frequent patient engagement and tailored drug regimens may help to improve A1C goal attainment.

Effect of glycemic control on the Diabetes Complications Severity Index score and development of complications in people with newly diagnosed type 2 diabetes.

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 (<7%, <8%, ≥8%). The DCSI scores were determined for each study year, and the cumulative incidence of diabetes-related complications was assessed. A Cox proportional hazard model was used to evaluate the effect of baseline HbA1c and worsening glycemic (HbA1c) control on longitudinal changes in DCSI scores. RESULTS: Of 32 174 people identified as having newly diagnosed T2D, 14 016 (44%), 21 657 (67%), and 9983 (31%) had an initial or baseline HbA1c <7%, <8%, and ≥8%, respectively. Ten years after diabetes diagnosis, retinopathy, chronic kidney disease, coronary heart disease, and neuropathy were diagnosed in 22%, 29%, 24%, and 36% of people. Baseline HbA1c did not affect the observed trend in longitudinal changes in DCSI scores throughout the 11-year period. For people in each of the initial HbA1c groups (<7%, <8%, ≥8%), worsening or persistently poor glycemic control was significantly associated with a 10%, 19%, or 16% increase in the risk of experiencing an increased DCSI score, respectively (all P < 0.01). CONCLUSIONS: Baseline glycemic control had no apparent effect on longitudinal changes in DCSI score. Worsening or persistently poor glycemic control was associated with an increased risk of an increase in the DCSI score.

Prevalence and recognition of obesity and its associated comorbidities: cross-sectional analysis of electronic health record data from a large US integrated health system.

OBJECTIVE: To 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. DESIGN: The 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. SETTING: A large US integrated health system. RESULTS: A 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 <29.9), 75 199 (23.2%) had BMI 30-34.9, 34 152 (10.5%) had BMI 35-39.9 and 25 137 (7.8%) had BMI ≥40. There was a higher prevalence of type 2 diabetes, pre-diabetes, hypertension and cardiovascular disease (P value<0.0001) within higher BMI compared with lower BMI categories. In patients with a BMI >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. CONCLUSIONS: This 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.

TRAMOMTANA (Tratamiento Multidisciplinar de la Obesidad Mórbida: Medicamentos, Terapia de comportamiento, Apoyo Nutricional y Actividad física). De la pregunta a la realidad de un ensayo clínico investigador iniciado (II) / TRAMOMTANA (Multidisciplinary treatment of morbid obesity: Medication, behavioral therapy, nutritional support, and physical activity). From question to reality in an investigator-initiated clinical trial (II)

Comunicamos la puesta en marcha de un programa intensivo y multidisciplinar de pérdida de peso en pacientes con obesidad mórbida (OM). Este ensayo clínico se basa en la educación para la salud, el apoyo en el proceso de cambio, los medicamentos y las sesiones de terapia de grupo. Nuestra intención es demostrar que los resultados obtenidos con este programa de pérdida de peso a 2 años son, cuando menos, comparables a los resultados que se obtienen con la cirugía bariátrica en estos pacientes con OM. Es nuestra intención igualmente (..) (AU)

Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system (AU)

[TRAMOMTANA (Multidisciplinary treatment of morbid obesity: medication, behavioral therapy, nutritional support, and physical activity). From question to reality in an investigator-initiated clinical trial (II)]. / TRAMOMTANA (Tratamiento Multidisciplinar de la Obesidad Mórbida: Medicamentos, Terapia de comportamiento, Apoyo Nutricional y Actividad física). De la pregunta a la realidad de un ensayo clínico investigador iniciado (II).

Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system.