Jorge Calles

Similarities and Differences Between Diabetic and Idiopathic Gastroparesis

BACKGROUND & AIMS Gastroparesis can be diabetic or idiopathic, yet little is known about differences in their presentation. We compared clinical characteristics, symptoms, and gastric emptying in patients with type 1 or type 2 diabetic (DG) or idiopathic (IG) gastroparesis. METHODS We analyzed data from 416 patients with gastroparesis who were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry; 254 had IG (most were female and white), and 137 had DG (78 had type 1 and 59 had type 2). Registry data included detailed histories, physical examinations, results from gastric emptying scintigraphy, and responses to validated symptom questionnaires. RESULTS Patients with type 2 diabetes mellitus (DM) were an average of 13 years older at the onset of symptoms of gastroparesis and heavier than patients with IG. Patients with type 1 DM had more hospitalizations in the past year than patients with IG. Symptoms that prompted evaluation more often included vomiting for DG and abdominal pain for IG. Patients with DG had more severe retching and vomiting than those with IG, whereas patients with IG had more severe early satiety and postprandial fullness subscores. Compared with IG, gastric retention was greater in patients with type 1 DM. More than 50% of patients with type 1 DM had severe retention (>35% at 4 hours); they took prokinetic agents more frequently and were more likely to receive gastric electric stimulation. CONCLUSIONS There are similarities and differences in clinical characteristics of DG and IG. Gastroparesis is a heterogeneous disorder; its etiology affects symptoms and severity. Long-term studies are needed to determine whether the differences in symptoms and gastric emptying affect progression and treatment responses.

Dietary Intake and Nutritional Deficiencies in Patients With Diabetic or Idiopathic Gastroparesis

BACKGROUND & AIMS Gastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis. METHODS Patients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed. RESULTS Caloric intake averaged 1168 ± 801 kcal/day, amounting to 58% ± 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B(6), C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08). CONCLUSIONS Many patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies.

Diabetic Retinopathy, Its Progression, and Incident Cardiovascular Events in the ACCORD Trial

OBJECTIVE Both the presence of diabetic retinopathy and its severity are significantly associated with future cardiovascular (CV) events. Whether its progression is also linked to incident CV outcomes hasn’t been assessed. RESEARCH DESIGN AND METHODS The relationship between retinopathy, its 4-year progression, and CV outcomes (CV death or nonfatal myocardial infarction or stroke) was analyzed in participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who also participated in the ACCORD Eye Study. Retinopathy was classified as either none, mild, moderate, or severe, and worsening was classified as a <2-step, 2–3-step, or >3-step change (that included incident laser therapy or vitrectomy). RESULTS Participants (n = 3,433) of mean age 61 years had baseline retinal photographs (seven stereoscopic fields). Compared with no retinopathy, the adjusted HRs (95% CI) for the CV outcome rose from 1.49 (1.12–1.97) for mild retinopathy to 2.35 (1.47–3.76) for severe retinopathy. A subset of 2,856 was evaluated for progression of diabetic retinopathy at 4 years. The hazard of the primary outcome increased by 38% (1.38 [1.10–1.74]) for every category of change in retinopathy severity. Additional adjustment for the baseline and follow-up levels of A1C, systolic blood pressure, and lipids either individually or together rendered the relationships between worsening and CV outcomes nonsignificant. CONCLUSIONS Both the severity of retinopathy and its progression are determinants of incident CV outcomes. The retina may provide an anatomical index of the effect of metabolic and hemodynamic factors on future CV outcomes.

Determinants of Weight Gain in the Action to Control Cardiovascular Risk in Diabetes Trial

OBJECTIVE Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS We studied determinants of weight gain over 2 years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation. RESULTS There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25–35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for <15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6–5.3 kg at 2 years. CONCLUSIONS Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain.

Diabetes Medication Satisfaction Tool A focus on treatment regimens

OBJECTIVE—To develop and test a patient questionnaire on treatment satisfaction with diabetes regimens. RESEARCH DESIGN AND METHODS—Survey items were developed from community clinic focus groups, pretested in patients with diabetes, and examined in two samples of treated patients. RESULTS—Sixteen items performed well in assessing treatment experiences: ease and convenience, lifestyle burdens, well-being, and medical control. Construct validity was supported by associations (P < 0.05) with treatment complexity, self-rated glucose control, health worries, and A1C. Internal consistency ranged from 0.89 to 0.95. CONCLUSIONS—The Diabetes Medication Satisfaction Tool offers a comprehensive assessment of patient acceptability, with diabetes therapy useful for individualizing therapeutic decision making.

The Diabetes Medication Satisfaction Tool (DMSAT): A Focus on Treatment Regimens

OBJECTIVE—To develop and test a patient questionnaire on treatment satisfaction with diabetes regimens. RESEARCH DESIGN AND METHODS—Survey items were developed from community clinic focus groups, pretested in patients with diabetes, and examined in two samples of treated patients. RESULTS—Sixteen items performed well in assessing treatment experiences: ease and convenience, lifestyle burdens, well-being, and medical control. Construct validity was supported by associations (P < 0.05) with treatment complexity, self-rated glucose control, health worries, and A1C. Internal consistency ranged from 0.89 to 0.95. CONCLUSIONS—The Diabetes Medication Satisfaction Tool offers a comprehensive assessment of patient acceptability, with diabetes therapy useful for individualizing therapeutic decision making.

1088 Outcomes and Predictors of Improvement in Patients With Gastroparesis Followed Prospectively for 48 Weeks

and SMW total scores remained when analysis was limited to normal or delayed gastric emptying (p<0.05, p<0.05). Only 13% (3/24) needed tube feeds and 13% (3/24) parenteral nutrition after GES. School absences decreased from 57% to 31% of school days. Overall, 65% (13/20) reported their health was much improved after GES versus 15% (3/20) the same or worse. The majority (15/20) were satisfied with GES. Three were not satisfied due to lack of improvement, one developed back pain and another was later diagnosed with an eating disorder. Five reported complications. Four had discomfort or tenderness at the implantation site and another had a dead battery. Conclusions: In the largest series to date of pediatric patients who have undergone GES for GP and/or FD, we have found significant and sustained improvement not only in upper GI symptoms but also in quality of life and perception of global health. Patients were less dependent on tube feeding or parenteral nutrition and had fewer school absences. The majority is satisfied with the decision to place GES. Future studies are needed to assess for possible placebo effect and to evaluate predictors of outcome and long-term prognosis.

Su1449 Incidence and Clinical Significance of Delayed Gastric Emptying for Liquids in Gastroparesis and Chronic Unexplained Nausea and Vomiting (CUNV)

Introduction. Diabetic gastroparesis is defined as delayed gastric emptying not caused by obstruction or structural abnormality. Normal function of the gastric and intestinal mechanical activity is mediated by slow wave electrical activity in the stomach and small bowel. Previous studies using both electrogastrogram and magnetogastrogram have shown gastric slowwave dysrhythmias associated with gastroparesis, but no study has yet examined possible effects of gastroparesis on the intestinal slow wave. Methods. We recorded intestinal slow waves in diabetic patients with gastroparesis (N=7) and healthy controls (N=7) using the magnetoenterogram (MENG), which uses a Superconducting QUantum Interference Device (SQUID) to convert magnetic fields associated with intestinal slow waves into voltage signals. Second Order Blind Identification (SOBI) was used to reduce noise and isolate the intestinal slow wave signal from confounding magnetic artifact, and we computed the power spectrum of the intestinal slow wave using a Fast Fourier Transform technique. We analyzed dominant frequency, amplitude and percentage of power distributed (PPD) in brady, normo and tachyarrhythmic frequency ranges. Results. In gastroparesis patients, we found a significant decrease in postprandial dominant intestinal slow wave frequency from 10.2 ± 0.4 cpm to 8.8 ± 0.5 cpm (p<0.05) whereas the dominant frequency for control subjects increased from 9.9 ± 0.5 cpm to 10.8 ± 0.4 cpm (p<0.05). We did not observe significant differences in preand postprandial PPDs computed from controls or patients. Conclusions. Diabetic gastroparesis is associated with bradyarrhythmia, but not uncoupling, of the intestinal slow wave. Biomagnetic measurements of the MENG can assess intestinal slow wave activity in healthy and diseased tissue noninvasively.

Islet cell associated autoantibodies and C-peptide levels in patients with diabetes and symptoms of gastroparesis

Introduction Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA). Objective To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity. Design 113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide. Results Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide. Conclusion GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity. ClinicalTrials.gov Identifier NCT01696747.

Tu1486 Towards a Wellness Index for Motility Disorders: the use of Desirability Functions to Evaluate Health Status in Patients With Gastroparesis

G A A b st ra ct s research. Oral domperidone has been reported in some cases to prolong the QT interval and predispose to ventricular arrhythmias (Reddymasu et al. Am J Gastro 2007;102:20362045). The aims: 1) To establish an indications and clinical profile of patients receiving domperidone through the limited access protocol 2) to investigate possible side effects of domperidone 3) to analyze ECG reports and the duration of QT intervals. Methods: Study involved a retrospective chart review of 163 patients referred to a single physician at the tertiary GI Motility Center. Patients demographics, GI diagnosis, cardiovascular complain and ECG tracings were obtained. Prolonged QTc were verified if they were longer than 470 ms in females and longer than 450 ms in male patients. Results: Overall 23 out of 163 (13%) patients (15 F; mean age 47, range 18-73) presenting with chief complaints of nausea and vomiting were enrolled in FDA approved protocol and received doses of domperidone ranging from 10 to 30mg QID for at least 6 up to 12 months. 8 (36%) patients were Hispanic, 12 (52%) Caucasian, and 3(12%) African American. A total 16 (60%) of these patients (9F) were diagnosed with GP, 4 females met the criteria for Cyclic Vomiting Syndrome and 3 patients had symptoms of unexplained nausea. 6 (27%) ECG reports showed non-significant sinus arrhythmias, and one male patient had an irregular rhythm. Women had mean heart rates of 82 (range 52-112) and mens average HR was 86 (range 55-105) bpm. Overall the mean value of QTc for all domperidone patients was 427 ms (ranges 383 507 ms). Further analysis of ECGs for females showed, mean QTc duration of 425 (394-507) ms and in males it was 429 (383-469) ms. Two patients (9%), one of each gender, had QTc prolongation above the normal respected value. No patients complained about palpitation or cardiac/ chest pain. Two patients noticed breast discomfort. No other potential adverse events including extra-pyramidal side effects were reported during this investigation. Conclusions:1) Domperidone is legally available in USA under the FDAIND approved protocol and can be prescribed for patients with symptoms of nausea and vomiting related to gastroparesis and other motility disorders 2) No clinically relevant cardiac complaints and ECG changes including QTc prolongations were discovered during this observation 3) Domperidone can be regarded as a safe prokinetic and antiemetic agent.