Abstract
Objectives:
Diabetic gastroparesis (Gp) occurs more often in T1DM than T2DM. Other end diabetic organ complications include peripheral neuropathy, nephropathy, and retinopathy (together, termed triopathy). Aims: determine prevalence of diabetic complications (retinopathy, nephropathy, peripheral neuropathy) in diabetic patients with symptoms of Gp; assessing differences between T1DM and T2DM, and delayed and normal gastric emptying (GE).
Methods:
Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy.
Results:
133 diabetic patients with symptoms of Gp were studied: 59 T1DM, 74 T2DM; 103 delayed GE, 30 not delayed. Presence of retinopathy (37 vs 24%; p=0.13), nephropathy (19 vs 11%; p=0.22), peripheral neuropathy (53 vs 39%; p=0.16) were not significantly higher in T1DM than T2DM; although triopathies (all 3 complications) were seen in 10% T1DM and 3% T2DM (p=0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36 vs 10%; p=0.006), and number of diabetic complications (1.0 vs 0.5; p=0.009), although 39% of diabetic patients with delayed GE did not have any diabetic complications.
Conclusions:
In diabetic patients with symptoms of Gp, delayed GE was associated with presence of retinopathy and total number of diabetic complications. Only 10% of T1DM and 3% of T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have diabetic complications. Thus, presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.
Keywords: diabetic gastroparesis, complications, neuropathy, nephropathy, retinopathy
Introduction
Diabetic gastroparesis (Gp) is commonly taught to occur primarily in patients with Type 1 diabetes mellitus (T1DM) along with other end organ complications of diabetes including peripheral neuropathy, nephropathy, and retinopathy (1). Taken together, these three complications are termed “diabetic triopathy”. Gp is also recognized in patients with Type 2 diabetes mellitus (T2DM) who are more prevalent than T1DM. In a single center study, manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, retinopathy) were uncommon in diabetic patients (both T1DM and T2DM) with upper gastrointestinal symptoms (2).
Gastric emptying (GE) in response to eating is a regulated process involving gastric accommodation, antral contractility, pyloric relaxation (3). Gastric accommodation is, in part, a vagally mediated reflex occurring with meal ingestion. Up to half of Gp patients have decreased gastric accommodation in response to satiety testing (4,5).
Diabetic Gp is associated with loss of interstitial cells of Cajal (ICCs), reduction of nerves, and inflammatory infiltrate (6). Vagal dysfunction has been shown in diabetic Gp by abnormal pancreatic polypeptide test (7). Vagal dysfunction can also be detected using autonomic function tests and on electrocardiograms by lack of R-R respiratory variation (8). In the Diabetes Control and Complications Trial (DCCT), delayed GE was associated with greater HgbA1c, longer duration of diabetes, lower R-R variability, nephropathy, retinopathy, and greater GI symptoms (9).
The aims of this study were to determine the prevalence of diabetic complications (retinopathy, nephropathy, peripheral neuropathy) in diabetic patients with symptoms of Gp; assessing if there are differences between T1DM and T2DM and between delayed and normal GE. This will address whether delayed GE correlates with other diabetic end-organ damage.
Methods
Overview
The NIH Gastroparesis Clinical Research Consortium Gastroparesis Registry 2 (GpR2) (ClinicalTrials.gov Identifier: ) was implemented as an observational study of patients with symptoms of Gp (4). Patients met entry criteria: 18 years or older with symptoms of at least 12 weeks duration, gastric emptying scintigraphy (GES), without structural abnormalities on upper endoscopy. Patients were enrolled at 7 centers from September 2012 to March 2018. Patients with delayed GE and patients with normal emptying were enrolled. Informed consent was obtained prior to screening participants for enrollment into the study. Patients could have had a prior upper endoscopy, blood work, or gastric emptying test for clinical purposes prior to signing the consent form. Patients underwent history and physical examination, GE scintigraphy, autonomic function testing, electrogastrography (EGG) with water load testing, and questionnaires assessing symptoms. Peripheral neuropathy was assessed by history and questionnaire; nephropathy was assessed by history and blood measurements of creatinine (Cr); retinopathy by history; autonomic dysfunction by autonomic function testing, vagal dysfunction by WLST, and enteric Interstitial cells of Cajal (ICC) dysfunction by EGG. This study evaluated patients with diabetes, either T1DM or T2DM, as defined by patient and physician.
Study Protocol
During interviews with subjects, study physicians or coordinators completed case report forms capturing Gp disease onset, symptoms, disease profile, associated medical and surgical conditions, including diabetes, and therapies. Patients were asked questions to help differentiate T1DM from T2DM (age of onset of diabetes, weight at time of diagnosis of diabetes, initial treatment for diabetes, current treatment for diabetes, and prior episodes of diabetic ketoacidosis). Patients were asked about complications of diabetes including retinopathy, prior laser eye treatment, nephropathy, and peripheral neuropathy. Laboratory measures included complete metabolic panel, complete blood count, hemoglobin A1C (HbA1c), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and vitamin B12 level.
Patients filled out Patient Assessment of Upper GI Symptoms (PAGI-SYM) questionnaire assessing symptoms of Gp, dyspepsia, and gastroesophageal reflux disease (11) which includes symptoms of Gastroparesis Cardinal Symptom Index (GCSI) (12).
Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire (13) was used to evaluate frequency and intensity of neuropathy sensory symptoms of diabetic peripheral neuropathy. NTSS-6 score >6 suggests diabetic peripheral neuropathy.
Disease-specific quality of life was assessed using Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QOL) (14). The Medical Outcomes Study 36-Item Short-Form Health Survey version 2 (SF-36v2) assessed overall physical and mental health (15). Depression was assessed with Beck Depression Index (BDI) (16) and anxiety with State-Trait Anxiety Inventory (STAI) (17).
Gastric emptying scintigraphy
Gastric emptying scintigraphy was performed using the low-fat, egg white meal with four hour imaging after meal ingestion (18,19). Diabetic patients had glucose levels checked to ensure <270 mg/dL. Gastric retention of technetium-99m >60 % at 2 hrs and/or >10% at 4 hrs was considered evidence of delayed gastric emptying of solids.
EGG with water load testing
EGG with water load satiety test of non-caloric liquid water, a standardized test to induce gastric distension and gastric responses (20), was performed. After overnight fast and checking blood glucose <270 gm/dl, subjects underwent cutaneous EGG (3CPM Company, Towson, MD) (20,21) with 15 minutes baseline EGG recording followed by water load test, ingesting water until they achieved the sensation of “completely full” during a five-minute time period (20). Volume of ingested water was recorded (normal >238 mL (21)). EGG was recorded for another 30 minutes.
The percentage distribution of gastric myoelectric activity (GMA) power in four frequency ranges: normal (2.5-3.5 cpm), tachygastria (3.5-10 cpm), bradygastria (1-2.5 cpm), and duodenal-respiration (10-15 cpm) were averaged for Time 0 (before meal ingestion) and 10-minute periods after water load.
Autonomic Function Testing (AFT)
Autonomic function testing was performed using ANX 3.0 autonomic monitoring system (ANSAR Medical Technologies, Inc., Philadelphia, PA) (22,23), measuring both branches of cardiovagal ANS using simultaneous spectral analysis of heart rate variability (HRV) and respiratory activity. The 15 minute recording includes 5 minutes of rest, 1 minute of deep breathing (parasympathetic challenge), 1 minute of short Valsalva maneuvers (sympathetic challenge), following by rapid stand then 5 minutes of standing quietly (sympathetic and parasympathetic challenge). Each challenge is separated by a 1 minute period of return to baseline. HRV and respiratory activity were measured concurrently with analyses performed independently and simultaneously to compute parasympathetic and sympathetic activity. HRV was computed measuring beat to beat R-R intervals, while respiratory activity was recorded using impedance plethysmography.
Statistical Methods
Baseline patient characteristics were compared by presence of T1DM vs T2DM, presence of delayed gastric emptying vs not delayed, presence of peripheral neuropathy or not, presence of retinopathy or not, and presence of nephropathy or not. Data are presented as means (SD) for normally distributed variables, median (interquartile range [IQR]) for variables with non-normal distributions, or N (%) for categorical measures. P-values were determined by two-sample t-tests for normally distributed continuous measures, Wilcoxon rank-sum test for skewed continuous measures, and Fisher’s exact test for categorical measures (24). We compared baseline characteristics by increasing degrees of gastric retention at 4 hours (≤10%, >10% to ≤25%, >25% to ≤40%, >40%), and by number of tri-opathies present (0, 1, 2, 3), with trend p-values presented. A multivariable logistic regression model for outcome of delayed gastric emptying (yes/no) assessed independent associations of diabetic complications, adjusting for diabetes type (T1DM vs. T2DM), diabetes duration, gender, and age. Two-sided p-values were considered statistically significant if P<0.05. Analyses were performed using SAS software (version 9.4, SAS Institute, Cary, NC) and Stata (Release 15.1, Stata Corporation, College Station, TX) (25).
Results
Patients
There were 158 diabetic patients in GpR2. Five patients had prior fundoplication, and 20 patients had diabetes develop after Gp diagnosis; these patients were excluded from the analysis, leaving a total of 133 patients with symptoms of Gp after development of their diabetes.
133 diabetic patients (59 T1DM and 74 T2DM; 103 delayed GE and 30 not delayed) with symptoms of Gp were studied (Table 1). Of the 133 diabetic patients, average age was 48.3 years with 76% being female; average BMI was 30.8 kg/m2.
Table 1.
Baseline characteristics and prevalence of diabetes complications by diabetic etiology (T1DM vs. T2DM)
| Baseline characteristics | T1DM (N=59) |
T2DM (N=74) |
Total (N=133) |
P |
|---|---|---|---|---|
| Age (years), mean (SD) | 42.8 (13.3) | 52.6 (9.8) | 48.3 (12.4) | <0.001 |
| Gender | ||||
| Female | 43 (73%) | 58 (78%) | 101 (76%) | 0.54 |
| Male | 16 (27%) | 16 (22%) | 32 (24%) | |
| BMI, mean (SD) | 27.8 (6.3) | 33.1 (8.6) | 30.8 (8.1) | <0.001 |
| Duration of Gp symptom onset (years), median (IQR) | 4.7 (2.3, 10.4) | 3.1 (1.6, 5.5) | 3.8 (1.8, 6.5) | 0.003 |
| Duration of diabetes (years), median (IQR) | 22.2 (15.1, 33.3) | 15.5 (11.4, 20.5) | 17.6 (11.7, 24.9) | <0.001 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 13.8 (8.9, 24.3) | 11.7 (6.2, 15.1) | 12.0 (7.6, 20.0) | 0.03 |
| Diabetes Complications | ||||
| Retinopathy | 22 (37%) | 18 (24%) | 40 (30%) | 0.13 |
| Nephropathy | 11 (19%) | 8 (11%) | 19 (14%) | 0.22 |
| Peripheral neuropathy | 31 (53%) | 29 (39%) | 60 (45%) | 0.16 |
| Laser treatment for diabetic retinopathy | 17 (29%) | 7 (9%) | 24 (18%) | 0.006 |
| Diabetic ketoacidosis | 28 (47%) | 9 (12%) | 37 (28%) | <0.001 |
| Number of triopathies present | 0.15 | |||
| 0 | 21 (36%) | 38 (51%) | 59 (44%) | |
| 1 | 18 (31%) | 19 (26%) | 37 (28%) | |
| 2 | 14 (24%) | 15 (20%) | 29 (22%) | |
| 3 | 6 (10%) | 2 (3%) | 8 (6%) | |
| Mean (SD) number of triopathies present | 1.1 (1.0) | 0.7 (0.9) | 0.9 (0.9) | 0.04 |
| Migraine headaches | 13 (22%) | 19 (26%) | 32 (24%) | 0.69 |
| Gastric Emptying Scintigraphy - % retained at: | ||||
| 1 hour (%), mean (SD) | 76.9 (16.9) | 75.8 (20.2) | 76.3 (18.7) | 0.75 |
| 2 hours (%), mean (SD) | 58.2 (25.3) | 58.5 (26.6) | 58.4 (26.0) | 0.94 |
| 4 hours (%), mean (SD) | 33.3 (26.2) | 34.0 (28.5) | 33.7 (27.4) | 0.88 |
| Delayed gastric emptying | 48 (81%) | 55 (74%) | 103 (77%) | 0.41 |
| GCSI | ||||
| GCSI total score, mean (SD) | 2.8 (1.2) | 2.4 (1.1) | 2.6 (1.2) | 0.04 |
| Nausea/vomiting/retching, mean (SD) | 2.2 (1.5) | 1.8 (1.4) | 2.0 (1.5) | 0.14 |
| Bloating, mean (SD) | 3.0 (1.8) | 2.4 (1.7) | 2.7 (1.7) | 0.04 |
| Fulless/early satiety, mean (SD) | 3.2 (1.4) | 2.9 (1.2) | 3.0 (1.3) | 0.31 |
| PAGI-SYM individual scores | ||||
| Nausea, mean (SD) | 3.0 (1.6) | 2.6 (1.6) | 2.8 (1.6) | 0.14 |
| Retching, mean (SD) | 1.7 (1.7) | 1.3 (1.5) | 1.5 (1.6) | 0.24 |
| Vomiting, mean (SD) | 1.9 (1.9) | 1.5 (1.7) | 1.7 (1.8) | 0.21 |
| Stomach fullness, mean (SD) | 3.4 (1.5) | 3.0 (1.4) | 3.2 (1.4) | 0.10 |
| Unable to finish normal meal, mean (SD) | 2.9 (1.7) | 2.9 (1.5) | 2.9 (1.6) | 0.99 |
| Feel excessively full after meals, mean (SD) | 3.4 (1.7) | 3.4 (1.3) | 3.4 (1.5) | 0.86 |
| Loss of appetite, mean (SD) | 2.9 (1.7) | 2.4 (1.6) | 2.6 (1.7) | 0.10 |
| Bloating, mean (SD) | 3.2 (1.8) | 2.6 (1.6) | 2.8 (1.7) | 0.05 |
| Stomach visibly larger, mean (SD) | 2.9 (1.9) | 2.3 (1.8) | 2.5 (1.9) | 0.05 |
| Upper abdominal pain, mean (SD) | 2.5 (1.6) | 2.1 (1.8) | 2.3 (1.7) | 0.20 |
| Upper abdominal discomfort, mean (SD) | 2.7 (1.6) | 2.6 (1.6) | 2.7 (1.6) | 0.78 |
| NTSS-6, mean (SD) | 7.8 (7.0) | 7.8 (7.1) | 7.8 (7.1) | 0.99 |
| NTSS-6 score >6 | 28 (48%) | 36 (49%) | 64 (49%) | 1.00 |
| Laboratory Results | ||||
| Glucose (mg/dL), median (IQR) | 181.0 (129.0, 276.0) | 162.0 (112.0, 233.0) | 172.0 (122.0, 255.0) | 0.11 |
| HbA1c (%), median (IQR) | 8.8 (7.6, 9.7) | 8.0 (6.4, 9.5) | 8.3 (7.0, 9.6) | 0.01 |
| Creatinine (mg/dL) – mean (SD) | 1.1 (0.6) | 0.9 (0.4) | 1.0 (0.5) | 0.05 |
| Creatine>1.5 mg/dL | 9 (15%) | 5 (7%) | 14 (11%) | 0.16 |
| ESR (mm/hr), median (IQR) | 15.5 (7.0, 30.0) | 31.0 (17.0, 47.0) | 24.0 (10.0, 42.0) | 0.001 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.5 (0.2, 2.0) | 1.6 (0.4, 3.7) | 0.9 (0.3, 3.1) | 0.03 |
| Vitamin B12 (pg/mL), median (IQR) | 609.0 (488.0, 878.0) | 518.0 (396.0, 755.0) | 559.0 (427.0, 835.0) | 0.04 |
| Water load test – volume consumed (mL), mean (SD) | 390.9 (228.5) | 403.7 (244.6) | 398.1 (236.9) | 0.76 |
| Abnormal water load test (≤238 mL consumed) | 14 (24%) | 18 (24%) | 32 (24%) | 1.00 |
Duration of diabetes averaged 17.6 years, being greater in T1DM than T2DM (22.2 vs 15.5 years; p<0.001). Duration from diabetes diagnosis to onset of Gp symptoms was 12.0 years, being longer for T1DM than T2DM (13.8 for T1DM and 11.7 for T2DM; p=0.03). At enrollment into registry, duration of Gp symptoms averaged 3.8 years, being longer in T1DM than T2DM (4.7 vs 3.1 years; p=0.003). GCSI total score averaged 2.6 and was greater in T1DM than T2DM (2.8 vs 2.4; p=0.04) along with higher bloating subscore (3.0 vs 2.4; p=0.04). HgbA1c averaged 8.3%; greater in T1DM than T2DM (8.8 vs 8.0%; p=0.01).
Diabetic Complications
In these diabetic patients with symptoms of Gp, history of retinopathy occurred in 30%, nephropathy in 14%, and peripheral neuropathy in 45% (Table 1). Presence of retinopathy (37 vs 24%; p=0.13), nephropathy (19 vs 11%; p=0.22), peripheral neuropathy (53 vs 39%; p=0.16) were not significantly higher in T1DM than in T2DM. Mean number of the complications making up triopathies (retinopathy, nephropathy, peripheral neuropathy) was greater in T1DM than in T2DM (1.1 vs 0.7; p=0.04). Triopathies (combination of retinopathy, nephropathy, and peripheral neuropathy) were seen in 10% of T1DM and 3% of T2DM (p=0.04). At least one of the individual triopathies was seen in 56% of the diabetic patients in this study (64% for T1DM and 49% for T2DM; p=0.05). For delayed vs. not delayed emptying: 61% of patients with delayed gastric emptying have at least one of the individual triopathies, while 37% of patients without delay have one of the individual triopathies (p=0.02).
Average score of the NTSS-6 for diabetic peripheral neuropathy was similar in T1DM and T2DM patients (7.8 vs 7.8; p=0.99). There was also similar percentages of patients with NTSS-6 score >6 (48% vs 49%; p=1.00).
Table 2 shows characteristics of patients by increasing number of complications making up triopathies present. Increasing number of triopathies in these diabetic patients was associated with higher prevalence of T1DM compared to T2DM (p=0.046).
Table 2.
Baseline characteristics by number of tri-opathies
| Number of tri-opathies present | |||||
|---|---|---|---|---|---|
| Baseline characteristics | 0 (N=59) |
1 (N=37) |
2 (N=29) |
3 (N=8) |
P |
| Age at enrollment (yrs), mean (SD) | 47.4 (13.9) | 46.1 (11.6) | 51.9 (9.4) | 51.4 (12.5) | 0.16 |
| Gender | 0.71 | ||||
| Female | 46 (78%) | 26 (70%) | 25 (86%) | 4 (50%) | |
| Male | 13 (22%) | 11 (30%) | 4 (14%) | 4 (50%) | |
| BMI, mean (SD) | 31.7 (7.9) | 31.7 (9.8) | 28.7 (5.4) | 27.0 (7.5) | 0.08 |
| Diabetes Type | 0.046 | ||||
| T1DM | 21 (36%) | 18 (49%) | 14 (48%) | 6 (75%) | |
| T2DM | 38 (64%) | 19 (51%) | 15 (52%) | 2 (25%) | |
| Duration of Gp symptom onset (years), median (IQR) | 3.8 (1.5, 6.4) | 3.3 (1.6, 5.8) | 4.1 (2.5, 6.7) | 4.5 (2.2, 10.1) | 0.22 |
| Duration of diabetes (years), median (IQR) | 15.5 (8.7, 21.0) | 17.0 (11.4, 23.0) | 23.1 (18.3, 34.7) | 24.3 (21.2, 32.9) | <0.001 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 10.6 (5.9, 15.2) | 11.7 (6.8, 14.5) | 16.8 (12.1, 28.1) | 22.6 (11.9, 28.5) | <0.001 |
| Diabetes Complications | |||||
| Retinopathy | 0 (0%) | 7 (19%) | 25 (86%) | 8 (100%) | <0.001 |
| Nephropathy | 0 (0%) | 2 (5%) | 9 (31%) | 8 (100%) | <0.001 |
| Peripheral neuropathy | 0 (0%) | 28 (76%) | 24 (83%) | 8 (100%) | <0.001 |
| Laser treatment for diabetic retinopathy | 0 (0%) | 4 (11%) | 14 (48%) | 6 (75%) | <0.001 |
| Diabetic ketoacidosis | 1 (2%) | 16 (43%) | 14 (48%) | 6 (75%) | <0.001 |
| Migraine headaches | 14 (24%) | 9 (24%) | 7 (24%) | 2 (25%) | 0.94 |
| Gastric Emptying Scintigraphy - % retained at: | |||||
| 1 hour (%), mean (SD) | 72.2 (20.4) | 77.4 (17.3) | 81.1 (15.6) | 83.5 (19.4) | 0.01 |
| 2 hours (%), mean (SD) | 52.0 (28.3) | 60.1 (23.1) | 65.3 (23.3) | 72.1 (20.6) | 0.005 |
| 4 hours (%), mean (SD) | 26.1 (26.7) | 39.5 (28.5) | 39.7 (24.0) | 41.2 (30.7) | 0.008 |
| Delayed gastric emptying | 40 (68%) | 29 (78%) | 27 (93%) | 7 (88%) | 0.009 |
| GCSI | |||||
| GCSI total score, mean (SD) | 2.5 (1.2) | 2.6 (1.0) | 2.6 (1.3) | 2.6 (1.2) | 0.71 |
| Nausea/vomiting/retching, mean (SD) | 2.1 (1.4) | 1.9 (1.4) | 1.9 (1.7) | 1.7 (1.5) | 0.45 |
| Bloating, mean (SD) | 2.4 (1.8) | 2.8 (1.6) | 2.9 (1.8) | 3.1 (1.6) | 0.12 |
| Fulless/early satiety, mean (SD) | 3.1 (1.3) | 3.0 (1.3) | 3.0 (1.3) | 3.1 (1.2) | 0.83 |
| PAGI-SYM individual scores | |||||
| Nausea, mean (SD) | 3.0 (1.6) | 2.6 (1.5) | 2.5 (1.7) | 2.4 (1.7) | 0.07 |
| Retching, mean (SD) | 1.4 (1.5) | 1.5 (1.6) | 1.6 (1.9) | 1.5 (1.9) | 0.79 |
| Vomiting, mean (SD) | 1.7 (1.8) | 1.7 (1.8) | 1.6 (1.8) | 1.3 (1.4) | 0.58 |
| Stomach fullness, mean (SD) | 3.2 (1.4) | 3.4 (1.4) | 3.1 (1.8) | 3.3 (0.5) | 0.97 |
| Unable to finish normal meal, mean (SD) | 3.1 (1.5) | 2.6 (1.6) | 3.0 (1.6) | 3.3 (1.7) | 0.90 |
| Feel excessively full after meals, mean (SD) | 3.3 (1.6) | 3.4 (1.4) | 3.6 (1.6) | 3.3 (1.3) | 0.55 |
| Loss of appetite, mean (SD) | 2.8 (1.7) | 2.4 (1.6) | 2.4 (1.7) | 2.8 (1.6) | 0.26 |
| Bloating, mean (SD) | 2.5 (1.8) | 3.0 (1.6) | 3.1 (1.8) | 3.1 (1.5) | 0.10 |
| Stomach visibly larger, mean (SD) | 2.3 (1.9) | 2.6 (1.8) | 2.8 (2.0) | 3.0 (1.8) | 0.18 |
| Upper abdominal pain, mean (SD) | 2.3 (1.8) | 2.4 (1.7) | 2.1 (1.7) | 2.5 (1.9) | 0.90 |
| Upper abdominal discomfort, mean (SD) | 2.7 (1.7) | 2.8 (1.4) | 2.5 (1.8) | 2.6 (1.8) | 0.65 |
| NTSS-6, mean (SD) | 3.5 (4.7) | 10.5 (6.6) | 11.7 (7.2) | 11.6 (7.0) | <0.001 |
| NTSS-6 score >6 | 12 (21%) | 25 (68%) | 21 (72%) | 6 (75%) | <0.001 |
| Laboratory Results | |||||
| Glucose (mg/dL), median (IQR) | 148.0 (107.0, 225.0) | 193.0 (161.0, 275.0) | 173.0 (137.0, 259.0) | 157.5 (119.0, 276.5) | 0.15 |
| HbA1c (%), median (IQR) | 8.0 (6.4, 9.5) | 8.6 (7.4, 9.8) | 8.7 (7.6, 9.5) | 7.9 (7.3, 8.8) | 0.20 |
| Creatinine (mg/dL) – mean (SD) | 0.8 (0.2) | 0.9 (0.4) | 1.0 (0.4) | 2.2 (0.6) | <0.001 |
| Creatine>1.5 mg/dL | 2 (3%) | 2 (5%) | 4 (14%) | 6 (75%) | <0.001 |
| ESR (mm/hr), median (IQR) | 19.5 (9.0, 30.0) | 28.5 (9.0, 49.5) | 35.0 (15.0, 53.0) | 48.5 (16.0, 90.0) | 0.01 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.8 (0.3, 2.8) | 1.2 (0.3, 4.8) | 0.8 (0.5, 3.0) | 0.3 (0.2, 1.0) | 0.54 |
| Vitamin B12 (pg/mL), median (IQR) | 533.0 (342.0, 826.0) | 552.0 (488.0, 756.0) | 599.0 (429.0, 864.0) | 730.5 (592.5, 1348.0) | 0.06 |
| Autonomic Function | |||||
| Low resting parasympathetic activity | 26 (45%) | 21 (57%) | 17 (59%) | 5 (63%) | 0.13 |
| Resting parasympathetic excess | 6 (10%) | 5 (14%) | 2 (7%) | 0 (0%) | 0.54 |
| Challenge parasympathetic excess | 16 (28%) | 12 (33%) | 8 (29%) | 1 (13%) | 0.83 |
| Water load test – volume consumed (mL), mean (SD) | 417.3 (254.7) | 364.7 (225.9) | 418.0 (216.9) | 341.1 (237.9) | 0.55 |
| Abnormal water load test (≤238 mL consumed) | 15 (26%) | 9 (24%) | 5 (17%) | 3 (38%) | 0.74 |
P-values derived from ordinal logistic regression.
Gastric emptying
Overall 103 diabetic patients had delayed GE (48 T1DM patients and 55 T2DM patients) and 30 had nondelayed GE (11 T1DM and 19 T2DM) (Table 3). Three of the 30 patients with nondelayed GE had rapid gastric emptying and 27 had normal gastric emptying.
Table 3.
Baseline characteristics and prevalence of diabetes complications by gastric emptying scintigraphy (delayed vs. not delayed)
| Gastric Emptying | ||||
|---|---|---|---|---|
| Baseline Characteristics | Delayed (N=103) |
Not delayed (N=30) |
Total (N=133) |
P |
| Age (years), mean (SD) | 47.9 (11.3) | 49.6 (15.8) | 48.3 (12.4) | 0.51 |
| Gender | ||||
| Female | 77 (75%) | 24 (80%) | 101 (76%) | 0.63 |
| Male | 26 (25%) | 6 (20%) | 32 (24%) | |
| BMI, mean (SD) | 30.2 (7.5) | 32.8 (9.6) | 30.8 (8.1) | 0.12 |
| Diabetes Type | ||||
| T1DM | 48 (47%) | 11 (37%) | 59 (44%) | 0.34 |
| T2DM | 55 (53%) | 19 (63%) | 74 (56%) | |
| Duration of Gp symptom onset (years), median (IQR) | 3.8 (1.9, 6.5) | 3.9 (1.5, 6.7) | 3.8 (1.8, 6.5) | 0.92 |
| Duration of diabetes (years), median (IQR) | 19.0 (12.6, 27.9) | 14.4 (8.3, 20.5) | 17.6 (11.7, 24.9) | 0.02 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 12.5 (8.2, 20.8) | 9.6 (6.0, 13.8) | 12.0 (7.6, 20.0) | 0.03 |
| Diabetes Complications | ||||
| Retinopathy | 37 (36%) | 3 (10%) | 40 (30%) | 0.006 |
| Nephropathy | 16 (16%) | 3 (10%) | 19 (14%) | 0.56 |
| Peripheral neuropathy | 51 (50%) | 9 (30%) | 60 (45%) | 0.06 |
| Laser treatment for diabetic retinopathy | 22 (21%) | 2 (7%) | 24 (18%) | 0.10 |
| Diabetic ketoacidosis | 33 (32%) | 4 (13%) | 37 (28%) | 0.06 |
| Number of triopathies present | 0.045 | |||
| 0 | 40 (39%) | 19 (63%) | 59 (44%) | |
| 1 | 29 (28%) | 8 (27%) | 37 (28%) | |
| 2 | 27 (26%) | 2 (7%) | 29 (22%) | |
| 3 | 7 (7%) | 1 (3%) | 8 (6%) | |
| Mean (SD) number of triopathies present | 1.0 (1.0) | 0.5 (0.8) | 0.9 (0.9) | 0.009 |
| Migraine headaches | 23 (22%) | 9 (30%) | 32 (24%) | 0.47 |
| Gastric Emptying Scintigraphy - % retained at: | ||||
| 1 hour (%), mean (SD) | 82.4 (13.6) | 55.4 (19.0) | 76.3 (18.7) | <0.001 |
| 2 hours (%), mean (SD) | 67.6 (20.4) | 26.7 (16.2) | 58.4 (26.0) | <0.001 |
| 4 hours (%), mean (SD) | 41.9 (25.6) | 4.5 (2.7) | 33.7 (27.4) | <0.001 |
| GCSI | ||||
| GCSI total score, mean (SD) | 2.7 (1.2) | 2.3 (1.1) | 2.6 (1.2) | 0.12 |
| Nausea/vomiting/retching, mean (SD) | 2.1 (1.5) | 1.7 (1.3) | 2.0 (1.5) | 0.21 |
| Bloating, mean (SD) | 2.8 (1.7) | 2.3 (1.9) | 2.7 (1.7) | 0.15 |
| Fulless/early satiety, mean (SD) | 3.1 (1.3) | 2.9 (1.5) | 3.0 (1.3) | 0.40 |
| PAGI-SYM individual scores | ||||
| Nausea, mean (SD) | 2.8 (1.6) | 2.7 (1.6) | 2.8 (1.6) | 0.77 |
| Retching, mean (SD) | 1.6 (1.7) | 1.1 (1.3) | 1.5 (1.6) | 0.12 |
| Vomiting, mean (SD) | 1.8 (1.8) | 1.3 (1.6) | 1.7 (1.8) | 0.14 |
| Stomach fullness, mean (SD) | 3.2 (1.4) | 3.0 (1.5) | 3.2 (1.4) | 0.48 |
| Unable to finish normal meal, mean (SD) | 3.0 (1.6) | 2.8 (1.6) | 2.9 (1.6) | 0.56 |
| Feel excessively full after meals, mean (SD) | 3.5 (1.4) | 3.0 (1.7) | 3.4 (1.5) | 0.13 |
| Loss of appetite, mean (SD) | 2.6 (1.7) | 2.6 (1.6) | 2.6 (1.7) | 0.91 |
| Bloating, mean (SD) | 3.0 (1.6) | 2.3 (1.9) | 2.8 (1.7) | 0.07 |
| Stomach visibly larger, mean (SD) | 2.6 (1.9) | 2.2 (1.9) | 2.5 (1.9) | 0.31 |
| Upper abdominal pain, mean (SD) | 2.4 (1.7) | 1.8 (1.5) | 2.3 (1.7) | 0.06 |
| Upper abdominal discomfort, mean (SD) | 2.8 (1.7) | 2.4 (1.4) | 2.7 (1.6) | 0.27 |
| NTSS-6, mean (SD) | 8.3 (7.3) | 6.1 (6.1) | 7.8 (7.1) | 0.13 |
| NTSS-6 score >6 | 51 (50%) | 13 (43%) | 64 (49%) | 0.54 |
| Laboratory Results | ||||
| Glucose (mg/dL), median (IQR) | 176.0 (118.0, 263.0) | 163.0 (126.0, 234.0) | 172.0 (122.0, 255.0) | 0.66 |
| HbA1c (%), median (IQR) | 8.5 (7.1, 9.6) | 8.0 (7.0, 9.0) | 8.3 (7.0, 9.6) | 0.17 |
| Creatinine (mg/dL) – mean (SD) | 1.0 (0.5) | 0.9 (0.3) | 1.0 (0.5) | 0.17 |
| Creatine>1.5 mg/dL | 13 (13%) | 1 (3%) | 14 (11%) | 0.19 |
| ESR (mm/hr), median (IQR) | 24.0 (10.0, 44.0) | 24.0 (9.0, 30.0) | 24.0 (10.0, 42.0) | 0.28 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.9 (0.3, 3.4) | 0.7 (0.3, 1.9) | 0.9 (0.3, 3.1) | 0.24 |
| Vitamin B12 (pg/mL), median (IQR) | 562.0 (429.0, 837.0) | 527.5 (411.0, 826.0) | 559.0 (427.0, 835.0) | 0.94 |
| Autonomic Function | ||||
| Low resting parasympathetic activity | 54 (53%) | 15 (50%) | 69 (52%) | 0.84 |
| Resting parasympathetic excess | 9 (9%) | 4 (13%) | 13 (10%) | 0.49 |
| Challenge parasympathetic excess | 34 (34%) | 3 (10%) | 37 (28%) | 0.02 |
| Water load test – volume consumed (mL), mean (SD) | 385.9 (245.5) | 441.3 (201.2) | 398.1 (236.9) | 0.27 |
| Abnormal water load test (≤238 mL consumed) | 28 (27%) | 4 (14%) | 32 (24%) | 0.22 |
Diabetic patients with delayed GE had higher prevalence of retinopathy (36 vs 10%; p=0.006) and higher proportion of peripheral neuropathy (50 vs 30%; p=0.06) (Table 3). The number of diabetic complications were greater in delayed GE than normal GE (1.0 vs 0.5; p=0.009). Increasing number of triopathies present was associated with increased gastric retention at 2 hours (p=0.005) and 4 hours (p=0.008). Of note, 39% of the diabetic patients with delayed GE did not have any complications of diabetes.
Supplemental Table 1 divides patients by T1DM versus T2DM and then by presence of delayed or normal GE. For both T1DM and T2DM, the presence of delayed GE was associated with an increase prevalence of retinopathy (p=0.02) and an increase of number of complications that make up the triopathies (p=0.02).
Table 4 shows diabetic patients by increasing degrees of gastric retention at 4 hours. As gastric retention at 4 hours increased, the proportion of patients with retinopathy and peripheral neuropathy increased (P for trend=0.002 and 0.02, respectively), and mean number of triopathies increased (P for trend=0.001).
Table 4.
Baseline characteristics and prevalence of diabetes complications by gastric retention at 4 hours
| Gastric Retention at 4 hours (%) | |||||
|---|---|---|---|---|---|
| Baseline Characteristics | ≤10% (N=34) |
>10% - ≤25% (N=29) |
>25% - ≤40% (N=23) |
>40% (N=46) |
P |
| Age at enrollment (yrs), mean (SD) | 49.1 (15.2) | 47.0 (11.0) | 48.1 (11.6) | 48.5 (11.9) | 0.96 |
| Gender | |||||
| Female | 26 (76%) | 21 (72%) | 21 (91%) | 32 (70%) | 0.62 |
| Male | 8 (24%) | 8 (28%) | 2 (9%) | 14 (30%) | |
| BMI, mean (SD) | 32.0 (8.9) | 31.6 (7.6) | 27.3 (6.2) | 30.7 (8.0) | 0.31 |
| Duration of Gp symptom onset (years), median (IQR) | 3.5 (1.1, 6.5) | 3.5 (2.2, 7.8) | 4.3 (2.4, 6.7) | 3.9 (1.0, 5.6) | 0.70 |
| Duration of diabetes (years), median (IQR) | 12.8 (8.1, 19.5) | 21.3 (13.8, 27.9) | 19.9 (16.1, 30.3) | 17.8 (11.9, 25.3) | 0.13 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 8.9 (6.0, 13.8) | 12.9 (10.0, 20.8) | 14.0 (11.0, 26.2) | 12.7 (8.0, 20.0) | 0.15 |
| Diabetes Complications | |||||
| Retinopathy | 3 (9%) | 8 (28%) | 10 (43%) | 19 (41%) | 0.002 |
| Nephropathy | 3 (9%) | 2 (7%) | 5 (22%) | 9 (20%) | 0.10 |
| Peripheral neuropathy | 8 (24%) | 15 (52%) | 11 (48%) | 25 (54%) | 0.02 |
| Laser treatment for diabetic retinopathy | 2 (6%) | 7 (24%) | 5 (22%) | 10 (22%) | 0.14 |
| Diabetic ketoacidosis | 4 (12%) | 8 (28%) | 9 (39%) | 16 (35%) | 0.03 |
| Number of triopathies present | 0.003 | ||||
| 0 | 24 (71%) | 13 (45%) | 9 (39%) | 13 (28%) | |
| 1 | 7 (21%) | 8 (28%) | 5 (22%) | 16 (35%) | |
| 2 | 2 (6%) | 7 (24%) | 6 (26%) | 14 (30%) | |
| 3 | 1 (3%) | 1 (3%) | 3 (13%) | 3 (7%) | |
| Mean (SD) number of triopathies present | 0.4 (0.7) | 0.9 (0.9) | 1.1 (1.1) | 1.2 (0.9) | 0.001 |
| Migraine headaches | 10 (29%) | 9 (31%) | 5 (22%) | 7 (15%) | 0.09 |
| Gastric Emptying Scintigraphy - % retained at: | |||||
| 1 hour (%), mean (SD) | 60.7 (21.1) | 71.4 (13.4) | 81.6 (13.9) | 89.0 (9.2) | <0.001 |
| 2 hours (%), mean (SD) | 34.0 (23.0) | 47.4 (13.7) | 63.5 (19.3) | 81.6 (12.9) | <0.001 |
| 4 hours (%), mean (SD) | 4.6 (2.9) | 18.6 (4.6) | 31.8 (4.3) | 65.5 (18.4) | <0.001 |
| GCSI | |||||
| GCSI total score, mean (SD) | 2.4 (1.0) | 2.7 (1.1) | 2.7 (1.2) | 2.6 (1.3) | 0.55 |
| Nausea/vomiting/retching, mean (SD) | 1.8 (1.2) | 2.0 (1.6) | 2.0 (1.5) | 2.1 (1.6) | 0.39 |
| Bloating, mean (SD) | 2.3 (1.8) | 3.1 (1.7) | 3.0 (1.8) | 2.6 (1.7) | 0.74 |
| Fulless/early satiety, mean (SD) | 3.0 (1.4) | 3.0 (1.2) | 3.3 (1.3) | 3.0 (1.4) | 0.83 |
| PAGI-SYM individual scores | |||||
| Nausea, mean (SD) | 2.9 (1.5) | 2.7 (1.6) | 2.7 (1.4) | 2.8 (1.7) | 0.87 |
| Retching, mean (SD) | 1.2 (1.3) | 1.5 (1.6) | 1.6 (1.9) | 1.6 (1.8) | 0.26 |
| Vomiting, mean (SD) | 1.4 (1.6) | 1.7 (1.8) | 1.7 (1.7) | 1.9 (1.9) | 0.21 |
| Stomach fullness, mean (SD) | 3.1 (1.5) | 3.4 (1.2) | 3.3 (1.3) | 3.1 (1.6) | 0.91 |
| Unable to finish normal meal, mean (SD) | 2.9 (1.6) | 2.6 (1.6) | 3.3 (1.4) | 3.0 (1.6) | 0.40 |
| Feel excessively full after meals, mean (SD) | 3.2 (1.7) | 3.5 (1.4) | 3.6 (1.5) | 3.4 (1.5) | 0.66 |
| Loss of appetite, mean (SD) | 2.8 (1.6) | 2.3 (1.7) | 3.0 (1.6) | 2.5 (1.7) | 0.67 |
| Bloating, mean (SD) | 2.4 (1.8) | 3.3 (1.6) | 3.1 (1.8) | 2.7 (1.6) | 0.54 |
| Stomach visibly larger, mean (SD) | 2.3 (1.8) | 2.9 (1.9) | 2.8 (2.0) | 2.4 (1.9) | 0.97 |
| Upper abdominal pain, mean (SD) | 1.9 (1.6) | 2.1 (1.7) | 2.6 (1.8) | 2.5 (1.8) | 0.15 |
| Upper abdominal discomfort, mean (SD) | 2.6 (1.5) | 2.6 (1.7) | 2.9 (1.6) | 2.7 (1.7) | 0.64 |
| NTSS-6, mean (SD) | 5.9 (6.0) | 7.1 (7.4) | 9.7 (7.5) | 8.5 (7.1) | 0.09 |
| NTSS-6 score >6 | 14 (41%) | 13 (45%) | 12 (57%) | 24 (52%) | 0.28 |
| Laboratory Results | |||||
| Glucose (mg/dL), median (IQR) | 163.5 (122.0, 238.0) | 189.0 (122.0, 280.0) | 163.0 (101.0, 280.0) | 174.0 (132.0, 228.0) | 0.91 |
| HbA1c (%), median (IQR) | 8.0 (6.5, 9.2) | 8.4 (7.1, 9.4) | 8.6 (7.0, 9.7) | 8.6 (7.1, 9.6) | 0.30 |
| Creatinine (mg/dL) – mean (SD) | 0.8 (0.3) | 1.0 (0.4) | 1.0 (0.6) | 1.0 (0.6) | 0.11 |
| Creatine>1.5 mg/dL | 1 (3%) | 2 (7%) | 3 (13%) | 8 (17%) | 0.03 |
| ESR (mm/hr), median (IQR) | 24.0 (9.0, 30.0) | 21.0 (10.0, 34.0) | 17.0 (6.0, 42.0) | 33.5 (17.0, 55.0) | 0.12 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.6 (0.3, 1.9) | 1.9 (0.6, 4.8) | 0.5 (0.2, 3.0) | 0.9 (0.3, 3.0) | 1.00 |
| Vitamin B12 (pg/mL), median (IQR) | 513.0 (396.0, 826.0) | 531.0 (313.0, 739.0) | 646.0 (463.0, 960.0) | 592.5 (453.0, 837.0) | 0.36 |
| Autonomic Function | |||||
| Low resting parasympathetic activity | 15 (45%) | 17 (59%) | 11 (48%) | 25 (54%) | 0.60 |
| Resting parasympathetic excess | 4 (12%) | 2 (7%) | 3 (13%) | 4 (9%) | 0.79 |
| Challenge parasympathetic excess | 3 (9%) | 9 (31%) | 7 (30%) | 18 (40%) | 0.007 |
| Water load test – volume consumed (mL), mean (SD) | 430.1 (207.8) | 422.1 (213.4) | 440.0 (315.8) | 338.5 (223.3) | 0.10 |
| Abnormal water load test (≤238mL consumed) | 6 (18%) | 3 (10%) | 6 (26%) | 17 (37%) | 0.02 |
P-values derived from ordinal logistic regression.
Retinopathy
Table 5 divides patients by the presence of retinopathy. Presence of retinopathy was associated with greater duration of diabetes (23.7 vs 15.5 years; p<0.001) and duration between diabetes diagnosis and onset of gastroparesis symptoms (16.1 vs 11.0 years; p<0.001). Presence of retinopathy was associated with increased gastric retention at 2 and 4 hours (P=0.02 and P=0.03, respectively). Presence of retinopathy was associated with presence of neuropathy and nephropathy, and higher NTSS-6 scores.
Table 5.
Baseline characteristics of diabetic patients with and without retinopathy
| Retinopathy | ||||
|---|---|---|---|---|
| Baseline Characteristics | Yes (N=40) |
No (N=93) |
Total (N=133) |
P |
| Age at enrollment (yrs), mean (SD) | 51.4 (9.7) | 46.9 (13.2) | 48.3 (12.4) | 0.06 |
| Gender | 1.00 | |||
| Female | 30 (75%) | 71 (76%) | 101 (76%) | |
| Male | 10 (25%) | 22 (24%) | 32 (24%) | |
| BMI, mean (SD) | 28.7 (5.4) | 31.6 (8.9) | 30.8 (8.1) | 0.05 |
| Diabetes Type | 0.13 | |||
| T1DM | 22 (55%) | 37 (40%) | 59 (44%) | |
| T2DM | 18 (45%) | 56 (60%) | 74 (56%) | |
| Duration of Gp symptom onset (years), median (IQR) | 4.3 (2.4, 8.6) | 3.8 (1.7, 5.8) | 3.8 (1.8, 6.5) | 0.16 |
| Duration of diabetes (years), median (IQR) | 23.7 (17.9, 32.7) | 15.5 (10.1, 21.3) | 17.6 (11.7, 24.9) | <0.001 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 16.1 (11.6, 27.6) | 11.0 (6.0, 14.5) | 12.0 (7.6, 20.0) | <0.001 |
| Diabetes Complications | ||||
| Nephropathy | 13 (33%) | 6 (6%) | 19 (14%) | <0.001 |
| Peripheral neuropathy | 28 (70%) | 32 (34%) | 60 (45%) | <0.001 |
| Laser treatment for diabetic retinopathy | 24 (60%) | 0 (0%) | 24 (18%) | <0.001 |
| Diabetic ketoacidosis | 18 (45%) | 19 (20%) | 37 (28%) | 0.006 |
| Migraine headaches | 8 (20%) | 24 (26%) | 32 (24%) | 0.52 |
| Gastric Emptying Scintigraphy - % retained at: | ||||
| 1 hour (%), mean (SD) | 81.1 (16.5) | 74.2 (19.3) | 76.3 (18.7) | 0.05 |
| 2 hours (%), mean (SD) | 66.4 (22.8) | 54.9 (26.6) | 58.4 (26.0) | 0.02 |
| 4 hours (%), mean (SD) | 41.6 (25.3) | 30.2 (27.7) | 33.7 (27.4) | 0.03 |
| Delayed gastric emptying | 37 (93%) | 66 (71%) | 103 (77%) | 0.006 |
| GCSI | ||||
| GCSI total score, mean (SD) | 2.6 (1.2) | 2.6 (1.1) | 2.6 (1.2) | 0.97 |
| Nausea/vomiting/retching, mean (SD) | 1.7 (1.5) | 2.1 (1.5) | 2.0 (1.5) | 0.14 |
| Bloating, mean (SD) | 2.9 (1.8) | 2.6 (1.7) | 2.7 (1.7) | 0.30 |
| Fulless/early satiety, mean (SD) | 3.1 (1.3) | 3.0 (1.3) | 3.0 (1.3) | 0.72 |
| PAGI-SYM individual scores | ||||
| Nausea, mean (SD) | 2.4 (1.6) | 2.9 (1.5) | 2.8 (1.6) | 0.07 |
| Retching, mean (SD) | 1.3 (1.7) | 1.5 (1.6) | 1.5 (1.6) | 0.49 |
| Vomiting, mean (SD) | 1.4 (1.5) | 1.8 (1.9) | 1.7 (1.8) | 0.15 |
| Stomach fullness, mean (SD) | 3.3 (1.4) | 3.1 (1.5) | 3.2 (1.4) | 0.50 |
| Unable to finish normal meal, mean (SD) | 3.1 (1.7) | 2.9 (1.5) | 2.9 (1.6) | 0.54 |
| Feel excessively full after meals, mean (SD) | 3.6 (1.4) | 3.3 (1.6) | 3.4 (1.5) | 0.26 |
| Loss of appetite, mean (SD) | 2.4 (1.8) | 2.7 (1.6) | 2.6 (1.7) | 0.29 |
| Bloating, mean (SD) | 3.0 (1.7) | 2.7 (1.7) | 2.8 (1.7) | 0.33 |
| Stomach visibly larger, mean (SD) | 2.8 (1.9) | 2.4 (1.9) | 2.5 (1.9) | 0.30 |
| Upper abdominal pain, mean (SD) | 2.2 (1.7) | 2.3 (1.8) | 2.3 (1.7) | 0.73 |
| Upper abdominal discomfort, mean (SD) | 2.6 (1.7) | 2.7 (1.6) | 2.7 (1.6) | 0.78 |
| NTSS-6, mean (SD) | 10.3 (7.1) | 6.7 (6.8) | 7.8 (7.1) | 0.008 |
| NTSS-6 score >6 | 26 (65%) | 38 (42%) | 64 (49%) | 0.02 |
| Laboratory Results | ||||
| Glucose (mg/dL), median (IQR) | 174.0 (125.5, 266.5) | 171.0 (119.0, 238.0) | 172.0 (122.0, 255.0) | 0.70 |
| HbA1c (%), median (IQR) | 8.6 (7.5, 9.6) | 8.1 (6.9, 9.6) | 8.3 (7.0, 9.6) | 0.33 |
| Creatinine (mg/dL) – mean (SD) | 1.2 (0.7) | 0.9 (0.3) | 1.0 (0.5) | <0.001 |
| Creatine>1.5 mg/dL | 11 (28%) | 3 (3%) | 14 (11%) | <0.001 |
| ESR (mm/hr), median (IQR) | 32.5 (15.0, 56.5) | 20.0 (9.0, 38.0) | 24.0 (10.0, 42.0) | 0.03 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.7 (0.3, 2.6) | 1.0 (0.3, 3.3) | 0.9 (0.3, 3.1) | 0.54 |
| Vitamin B12 (pg/mL), median (IQR) | 628.5 (429.5, 1080.0) | 531.0 (424.0, 822.0) | 559.0 (427.0, 835.0) | 0.14 |
| Water load test – volume consumed (mL), mean (SD) | 382.0 (214.3) | 405.1 (246.8) | 398.1 (236.9) | 0.61 |
| Abnormal water load test (≤238 mL consumed) | 11 (28%) | 21 (23%) | 32 (24%) | 0.66 |
Nephropathy
Table 6 describes patients by presence of nephropathy. Presence of nephropathy was associated with longer duration of diabetes (24.2 vs 17.1 years; p=0.01), but not duration of gastroparesis symptoms (4.3 vs 3.8; p=0.40). Nephropathy associated with presence of retinopathy (68 vs 24%; p<0.001). Mean creatinine was higher in patients with nephropathy (1.7) compared to those without nephropathy (0.8 mg/dl; p<0.001). The creatinine of the patients with delayed gastric emptying (1.0) was not significantly different from those with normal gastric emptying (0.9; p=0.17).
Table 6.
Baseline characteristics of diabetic patients with and without nephropathy
| Nephropathy | ||||
|---|---|---|---|---|
| Baseline Characteristics | Yes (N=19) |
No (N=114) |
Total (N=133) |
P |
| Age at enrollment (yrs), mean (SD) | 49.5 (12.2) | 48.1 (12.5) | 48.3 (12.4) | 0.64 |
| Gender | 0.24 | |||
| Female | 12 (63%) | 89 (78%) | 101 (76%) | |
| Male | 7 (37%) | 25 (22%) | 32 (24%) | |
| BMI, mean (SD) | 27.3 (6.4) | 31.3 (8.2) | 30.8 (8.1) | 0.045 |
| Diabetes Type | 0.22 | |||
| T1DM | 11 (58%) | 48 (42%) | 59 (44%) | |
| T2DM | 8 (42%) | 66 (58%) | 74 (56%) | |
| Duration of Gp symptom onset (years), median (IQR) | 4.3 (2.4, 9.1) | 3.8 (1.7, 6.3) | 3.8 (1.8, 6.5) | 0.40 |
| Duration of diabetes (years), median (IQR) | 24.2 (15.6, 34.1) | 17.1 (11.4, 23.1) | 17.6 (11.7, 24.9) | 0.01 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 14.4 (11.7, 29.4) | 11.7 (6.8, 18.8) | 12.0 (7.6, 20.0) | 0.02 |
| Diabetes Complications | ||||
| Retinopathy | 13 (68%) | 27 (24%) | 19 (14%) | <0.001 |
| Peripheral neuropathy | 12 (63%) | 48 (42%) | 60 (45%) | 0.13 |
| Laser treatment for diabetic retinopathy | 8 (42%) | 16 (14%) | 24 (18%) | 0.007 |
| Diabetic ketoacidosis | 12 (63%) | 25 (22%) | 37 (28%) | <0.001 |
| Migraine headaches | 4 (21%) | 28 (25%) | 32 (24%) | 1.00 |
| Gastric Emptying Scintigraphy - % retained at: | ||||
| 1 hour (%), mean (SD) | 81.9 (16.6) | 75.4 (19.0) | 76.3 (18.7) | 0.16 |
| 2 hours (%), mean (SD) | 67.4 (21.9) | 56.9 (26.4) | 58.4 (26.0) | 0.10 |
| 4 hours (%), mean (SD) | 41.3 (27.9) | 32.4 (27.3) | 33.7 (27.4) | 0.19 |
| Delayed gastric emptying | 16 (84%) | 87 (76%) | 103 (77%) | 0.56 |
| GCSI | ||||
| GCSI total score, mean (SD) | 2.5 (1.1) | 2.6 (1.2) | 2.6 (1.2) | 0.92 |
| Nausea/vomiting/retching, mean (SD) | 1.9 (1.6) | 2.0 (1.5) | 2.0 (1.5) | 0.79 |
| Bloating, mean (SD) | 2.8 (1.7) | 2.7 (1.8) | 2.7 (1.7) | 0.78 |
| Fulless/early satiety, mean (SD) | 2.9 (1.2) | 3.1 (1.3) | 3.0 (1.3) | 0.73 |
| PAGI-SYM individual scores | ||||
| Nausea, mean (SD) | 2.5 (1.6) | 2.8 (1.6) | 2.8 (1.6) | 0.37 |
| Retching, mean (SD) | 1.6 (1.9) | 1.5 (1.6) | 1.5 (1.6) | 0.76 |
| Vomiting, mean (SD) | 1.6 (1.7) | 1.7 (1.8) | 1.7 (1.8) | 0.89 |
| Stomach fullness, mean (SD) | 3.0 (1.5) | 3.2 (1.4) | 3.2 (1.4) | 0.52 |
| Unable to finish normal meal, mean (SD) | 2.9 (1.5) | 2.9 (1.6) | 2.9 (1.6) | 1.00 |
| Feel excessively full after meals, mean (SD) | 3.4 (1.5) | 3.4 (1.5) | 3.4 (1.5) | 0.93 |
| Loss of appetite, mean (SD) | 2.5 (1.6) | 2.7 (1.7) | 2.6 (1.7) | 0.66 |
| Bloating, mean (SD) | 2.9 (1.6) | 2.8 (1.7) | 2.8 (1.7) | 0.85 |
| Stomach visibly larger, mean (SD) | 2.7 (1.9) | 2.5 (1.9) | 2.5 (1.9) | 0.72 |
| Upper abdominal pain, mean (SD) | 2.5 (1.7) | 2.2 (1.7) | 2.3 (1.7) | 0.50 |
| Upper abdominal discomfort, mean (SD) | 2.4 (1.6) | 2.7 (1.6) | 2.7 (1.6) | 0.44 |
| NTSS-6, mean (SD) | 9.3 (7.4) | 7.5 (7.0) | 7.8 (7.1) | 0.32 |
| NTSS-6 score >6 | 11 (58%) | 53 (47%) | 64 (49%) | 0.46 |
| Laboratory Results | ||||
| Glucose (mg/dL), median (IQR) | 175.0 (137.0, 270.0) | 167.0 (119.0, 251.0) | 172.0 (122.0, 255.0) | 0.50 |
| HbA1c (%), median (IQR) | 8.2 (7.0, 9.2) | 8.4 (7.1, 9.6) | 8.3 (7.0, 9.6) | 0.54 |
| Creatinine (mg/dL) – mean (SD) | 1.7 (0.7) | 0.8 (0.3) | 1.0 (0.5) | <0.001 |
| Creatine>1.5 mg/dL | 9 (47%) | 5 (4%) | 14 (11%) | <0.001 |
| ESR (mm/hr), median (IQR) | 40.0 (14.0, 71.0) | 22.0 (9.5, 38.0) | 24.0 (10.0, 42.0) | 0.05 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 0.5 (0.2, 2.3) | 1.0 (0.3, 3.3) | 0.9 (0.3, 3.1) | 0.26 |
| Vitamin B12 (pg/mL), median (IQR) | 609.0 (477.0, 864.0) | 550.5 (414.0, 835.0) | 559.0 (427.0, 835.0) | 0.46 |
| Water load test – volume consumed (mL), mean (SD) | 425.3 (273.6) | 393.5 (231.2) | 398.1 (236.9) | 0.59 |
| Abnormal water load test (≤238 mL consumed) | 5 (26%) | 27 (24%) | 32 (24%) | 0.78 |
Peripheral Neuropathy
Table 7 divides patients by presence or absence of peripheral neuropathy. Presence of peripheral neuropathy was associated with greater duration of diabetes (20.9 vs 15.8 years; p=0.005) and duration between diabetes diagnosis and onset of gastroparesis symptoms (13.7 vs 11.4 years; p=0.006). NTSS-6 score was greater in patients with peripheral neuropathy by patient report (12.7 vs 3.7; p<0.001) as well as percent patients with NTSS-6 score >6 (80% vs 23%; p<0.001). Presence of peripheral neuropathy was associated with increased gastric retention at 2 hours (63.4% vs. 54.2%, p=0.04) and 4 hours (38.4 vs 27.6; p=0.07), and number of patients with gastroparesis (85 vs 71%; p=0.06).
Table 7.
Baseline characteristics of diabetic patients with and without peripheral neuropathy
| Peripheral neuropathy | ||||
|---|---|---|---|---|
| Baseline Characteristics | Yes (N=60) |
No (N=73) |
Total (N=133) |
P |
| Age at enrollment (yrs), mean (SD) | 49.2 (11.2) | 47.5 (13.3) | 48.3 (12.4) | 0.43 |
| Gender | 1.00 | |||
| Female | 46 (77%) | 55 (75%) | 101 (76%) | |
| Male | 14 (23%) | 18 (25%) | 32 (24%) | |
| BMI, mean (SD) | 30.3 (8.9) | 31.1 (7.4) | 30.8 (8.1) | 0.58 |
| Diabetes Type | ||||
| T1DM | 31 (52%) | 28 (38%) | 59 (44%) | 0.16 |
| T2DM | 29 (48%) | 45 (62%) | 74 (56%) | |
| Duration of Gp symptom onset (years), median (IQR) | 3.9 (2.3, 6.1) | 3.8 (1.5, 6.7) | 3.8 (1.8, 6.5) | 0.50 |
| Duration of diabetes (years), median (IQR) | 20.9 (14.0, 31.6) | 15.8 (9.7, 21.7) | 17.6 (11.7, 24.9) | 0.005 |
| Duration between diabetes diagnosis and Gp symptom onset (years), median (IQR) | 13.7 (9.7, 24.9) | 11.4 (6.0, 15.2) | 12.0 (7.6, 20.0) | 0.006 |
| Diabetes Complications | ||||
| Retinopathy | 28 (47%) | 12 (16%) | 40 (30%) | <0.001 |
| Nephropathy | 12 (20%) | 7 (10%) | 19 (14%) | 0.13 |
| Laser treatment for diabetic retinopathy | 18 (30%) | 6 (8%) | 24 (18%) | 0.001 |
| Diabetic ketoacidosis | 32 (53%) | 5 (7%) | 37 (28%) | <0.001 |
| Migraine headaches | 17 (28%) | 15 (21%) | 32 (24%) | 0.32 |
| Gastric Emptying Scintigraphy - % retained at: | ||||
| 1 hour (%), mean (SD) | 79.5 (17.0) | 73.6 (19.7) | 76.3 (18.7) | 0.07 |
| 2 hours (%), mean (SD) | 63.4 (23.0) | 54.2 (27.6) | 58.4 (26.0) | 0.04 |
| 4 hours (%), mean (SD) | 38.4 (26.7) | 29.8 (27.6) | 33.7 (27.4) | 0.07 |
| Delayed gastric emptying | 51 (85%) | 52 (71%) | 103 (77%) | 0.06 |
| GCSI | ||||
| GCSI total score, mean (SD) | 2.6 (1.2) | 2.5 (1.2) | 2.6 (1.2) | 0.47 |
| Nausea/vomiting/retching, mean (SD) | 2.0 (1.6) | 2.0 (1.4) | 2.0 (1.5) | 0.94 |
| Bloating, mean (SD) | 3.0 (1.7) | 2.5 (1.8) | 2.7 (1.7) | 0.10 |
| Fulless/early satiety, mean (SD) | 3.0 (1.3) | 3.1 (1.3) | 3.0 (1.3) | 0.73 |
| PAGI-SYM individual scores | ||||
| Nausea, mean (SD) | 2.6 (1.6) | 2.9 (1.6) | 2.8 (1.6) | 0.35 |
| Retching, mean (SD) | 1.6 (1.8) | 1.4 (1.5) | 1.5 (1.6) | 0.36 |
| Vomiting, mean (SD) | 1.7 (1.9) | 1.7 (1.7) | 1.7 (1.8) | 0.85 |
| Stomach fullness, mean (SD) | 3.2 (1.5) | 3.2 (1.4) | 3.2 (1.4) | 0.83 |
| Unable to finish normal meal, mean (SD) | 2.9 (1.6) | 3.0 (1.5) | 2.9 (1.6) | 0.67 |
| Feel excessively full after meals, mean (SD) | 3.4 (1.5) | 3.4 (1.5) | 3.4 (1.5) | 0.99 |
| Loss of appetite, mean (SD) | 2.5 (1.6) | 2.7 (1.7) | 2.6 (1.7) | 0.61 |
| Bloating, mean (SD) | 3.1 (1.6) | 2.6 (1.8) | 2.8 (1.7) | 0.062 |
| Stomach visibly larger, mean (SD) | 2.8 (1.8) | 2.3 (1.9) | 2.5 (1.9) | 0.18 |
| Upper abdominal pain, mean (SD) | 2.2 (1.8) | 2.3 (1.7) | 2.3 (1.7) | 0.71 |
| Upper abdominal discomfort, mean (SD) | 2.7 (1.7) | 2.7 (1.6) | 2.7 (1.6) | 0.91 |
| NTSS-6, mean (SD) | 12.7 (6.4) | 3.7 (4.5) | 7.8 (7.1) | <0.001 |
| NTSS-6 score >6 | 48 (80%) | 16 (23%) | 64 (49%) | <0.001 |
| Laboratory Results | ||||
| Glucose (mg/dL), median (IQR) | 181.5 (135.5, 273.0) | 151.0 (113.0, 225.0) | 172.0 (122.0, 255.0) | 0.04 |
| HbA1c (%), median (IQR) | 8.6 (7.5, 9.8) | 8.0 (6.6, 9.5) | 8.3 (7.0, 9.6) | 0.14 |
| Creatinine (mg/dL) – mean (SD) | 1.1 (0.6) | 0.9 (0.3) | 1.0 (0.5) | 0.04 |
| Creatine>1.5 mg/dL | 8 (13%) | 6 (8%) | 14 (11%) | 0.40 |
| ESR (mm/hr), median (IQR) | 31.0 (15.0, 54.0) | 20.0 (9.0, 32.5) | 24.0 (10.0, 42.0) | 0.009 |
| C-reactive protein (CRP) (mg/dL), median (IQR) | 1.1 (0.4, 3.8) | 0.7 (0.3, 2.8) | 0.9 (0.3, 3.1) | 0.14 |
| Vitamin B12 (pg/mL), median (IQR) | 576.5 (458.5, 869.0) | 533.0 (360.0, 822.0) | 559.0 (427.0, 835.0) | 0.21 |
| Water load test – volume consumed (mL), mean (SD) | 376.0 (210.3) | 416.5 (256.9) | 398.1 (236.9) | 0.33 |
| Abnormal water load test (≤238 mL consumed) | 12 (20%) | 20 (28%) | 32 (24%) | 0.32 |
Water Load Satiety Testing
Volume ingested during water load satiety test was similar in patients with T1DM and T2DM (Table 1), between those with delayed and normal gastric emptying (Table 3), between those with and without retinopathy (Table 5), between those with and without nephropathy (Table 6), and between those with and without peripheral neuropathy (Table 7).
Electrogastrography (EGG)
EGG was assessed in fasting period and after the water load satiety testing (Supplemental Table 2). Patients with delayed gastric ssssssemptying had higher baseline tachygastria and less bradygastria than patients with normal gastric emptying. There were no EGG changes when patients were compared by presence or absence of retinopathy, nephropathy, peripheral neuropathy.
Autonomic Function Testing
Compared to T2DM patients, T1DM patients had lower resting parasympathetic activity (p=0.04) (Supplemental Table 3). Challenge, but not resting parasympathetic excess, was more prevalent in patients with delayed GE (34 vs 10%; p=0.02). As percent retention at 4 hours increased, there was a significantly greater percent of patients with challenge parasympathetic excess (Table 4). Autonomic dysfunction was not associated with number of triopathies or type of diabetic complication, although patients with peripheral neuropathy had lower resting parasympathetic activity (0.3 vs 0.6; p=0.05).
Multivariable Analysis
Multivariable logistic regression was performed for the independent factors associated with delayed gastric emptying (Table 8). Presence of retinopathy was significantly associated with delayed gastric emptying (OR=4.3; 95% CI: 1.1-16.0, p=0.03), controlling for diabetes type, duration, gender, and age.
Table 8.
Multivariable logistic regression analysis of delayed gastric emptying on diabetic complications, adjusted for diabetes type and duration, gender, and age (N=133)
| Odds ratio (OR) for delayed gastric emptying |
95% CI | P | |
|---|---|---|---|
| Presence of retinopathy | 4.3 | 1.1 – 16.0 | 0.03 |
| Diabetes type: Type 2 vs. Type 1 | 1.4 | 0.5 – 4.2 | 0.58 |
| Diabetes duration, per 5 year increase | 1.2 | 0.9 – 1.6 | 0.13 |
| Gender: Male vs. Female | 1.4 | 0.5 – 4.1 | 0.51 |
| Age, per 5 year increase | 0.9 | 0.7 – 1.1 | 0.16 |
Model variables selected from a candidate set of three variables (retinopathy, peripheral neuropathy, nephropathy) using AIC selection, adjusting for diabetes type, diabetes duration, gender, and age.
Discussion
This study demonstrates that in diabetic patients with symptoms of Gp, delayed GE was associated with presence of retinopathy and total number of diabetic complications. The presence of diabetic complications should raise awareness for Gp in diabetic patients either T1DM or T2DM. On the other hand, Gp can occur without complications as the majority of diabetic patients with Gp did not have a triopathy and 36% of diabetic patients with delayed GE had no complications.
Our study shows expected differences between T1DM and T2DM patients. The duration of diabetes was greater in T1DM than T2DM, the HgbA1c was greater in T1DM than T2DM. The duration from the diabetes diagnosis to the onset of Gp symptoms and the duration of Gp symptoms were also longer in T1DM than T2DM. Although gastric retention during GES was not significantly different, the GCSI total score was greater in T1DM than T2DM. Our prior studies have shown that gastric retention was greater in T1DM compared to idiopathic Gp (26). A subsequent study showed that baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse GE delays and higher HbA1c (27). Similar to our study, Chedid et al also found that symptomatic patients with T1DM had longer duration of disease prior to gastric motility evaluation than patients with T2DM; however, duration and glycemic control based on the most recent HbA1c in the past year were not significantly associated with abnormal gastric motor functions (2).
Defining, diagnosing, and treating diabetic Gp can be a challenge (28). Up to 75% of diabetic patients may experience gastrointestinal symptoms to some degree (29). Some patients with symptoms of Gp can have normal GE (30). Hyperglycemia may impact on GE results; hyperglycemia can delay GE (31). Diabetic Gp patients have increased mortality compared to other diabetic patients and this might reflect their associated complications from diabetes or associated comorbidities, such as cardiovascular disease (32,33,34).
Our study showed that diabetic patients with delayed GE had increased prevalence of retinopathy and number of diabetic complications compared to diabetic patients with normal GE. Increasing number of triopathies present was associated with increased gastric retention at 2 hours and 4 hours. In a study from Denmark, T1DM patients with symptoms of Gp had more retinopathy, peripheral polyneuropathy, and nephropathy (35). In the DCCT trial, delayed GE was associated with greater baseline HbA1c, duration of diabetes, lower R-R variability during deep breathing, severe nephropathy and a greater symptoms score; in multivariable analysis, retinopathy was the only DM complication associated with delayed GE (9).
Of diabetic patients with delayed GE, retinopathy occurred in 36%, nephropathy in 16%, and peripheral neuropathy in 50%; with triopathy (all three) in 7%. Interestingly, 36% of diabetic patients with delayed GE had no complications. Thus, while the presence of diabetic complications should raise awareness for pursuing Gp in either T1DM or T2DM, diabetic Gp frequently occurs without other diabetic complications. Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were also uncommon in a Mayo Clinic study assessing UGI symptoms and gastric motor function in diabetic patients (2).
Our study also shows that gastroparesis symptoms can occur in diabetic patients without delayed gastric emptying. This is pointed out in a prior manuscript of our GpC (30). Gastric emptying looks at overall gastric emptying. Abnormalities in fundic accommodation, gastric dysrhythmias, and other abnormalities may contribute to the genesis of gastroparesis symptoms in some individuals.
This study used water load as an indirect assessment of gastric accommodation, a reflex that is, in part, vagally mediated. Volumes of water ingested were similar between patients with T1DM and T2DM, between patients with delayed and normal gastric emptying, and between those with and without peripheral neuropathy, retinopathy, or nephropathy. Studies from the Mayo Clinic showed that abnormal gastric accommodation was present in 39% of patients with diabetes with upper GI symptoms, whereas 28% had normal GE and accommodation (2).
EGG was used as an indirect measure of ICC function (20,36). Patients with delayed GE had higher baseline tachygastria and less bradygastria than patients with normal GE. Other studies have also suggested EGG abnormalities are present in patients with delayed GE (37). Specifically, patients with gastroparesis often have gastric dysrhythmias and a lack of increase in amplitude or power of the EGG signal with ingestion (37). In patients with gastroparesis, a variety of gastric dysrhythmias, including tachygastrias, have been recorded when ICCs were depleted (38). There were no EGG differences when patients were compared by presence or absence of retinopathy, nephropathy, or peripheral neuropathy.
Using autonomic function testing, challenge parasympathetic excess, but not resting parasympathetic excess, was more prevalent in diabetic patients with delayed GE, but not associated with number of triopathies or type of diabetic complication. Challenge parasympathetic excess is an abnormality of the parasympathetic nervous system (PNS) associated with standing or valsalva (22,23). In other studies, vagal cholinergics were found to be affected to a greater degree in diabetic compared to idiopathic gastroparesis (32). This agrees with studies showing abnormal pancreatic polypeptide tests suggesting vagal dysfunction in diabetic Gp but not in idiopathic Gp (7).
Whether there is a biological mechanistic explanation for the specific association between delayed GE and retinopathy, but not with the peripheral neuropathy or nephropathy is not clear. Neurological damage has been thought to be the most important contributor to gastric dysfunction in diabetic patients. Diabetic gastroparesis is associated with vagal neuropathy as well as abnormalities in the enteric nervous system: loss of nNOS, loss of interstitial cells of Cajal (ICC), and an immune infiltrate (23,24). Microvascular complications are thought to relate to the neuropathy, retinopathy, and kidney disease in diabetic patients. Our current GpCRC studies are looking at genetic factors and proteomics associated with gastroparesis.
This study has strengths but also limitations. The patients enrolled were from several medical centers using consensus gastric emptying tests and validated questionnaires. There might be a bias in more severely affected diabetic patients are seen in the tertiary academic medical center. This study used patients’ reports about their diabetic complications. Patients did not undergo fundoscopic examination for detection of retinopathy, electromyographic studies for peripheral neuropathy, or urine collection for proteinuria or creatinine clearance. Patients’ knowledge of their complications coincided with other objective tests. Presence of peripheral neuropathy was associated with higher scores on NTSS-6 questionnaire. Patients’ knowledge of having nephropathy was associated with a higher creatinine level. Presence of retinopathy was associated with prior laser eye treatments. The study used a number of questionnaires; there may be recall bias in filling these out that pertain to past experiences.
In summary, this study demonstrates that in diabetic patients with symptoms of Gp, delayed GE was associated with presence of retinopathy and total number of diabetic complications in patients with either T1DM or T2DM. There are three important take home messages from this study. First, delayed gastric emptying occurs in both patients with T1DM and T2DM. Second, the presence of diabetic complications should raise awareness for pursuing Gp in diabetic patients with either T1DM or T2DM. Third, diabetic Gp can occur without other diabetic complications.
Supplementary Material
WHAT IS KNOWN
Diabetic gastroparesis occurs more often in T1DM than T2DM.
Other end diabetic organ complications include peripheral neuropathy, nephropathy, and retinopathy (together, termed triopathy).
How delayed gastric emptying associates with other end organ complications in T1DM and T2DM is not clear.
WHAT IS NEW HERE
In diabetic patients with symptoms of gastroparesis, delayed gastric emptying was associated with presence of retinopathy and total number of diabetic complications. Only 10% of T1DM and 3% T2DM with gastroparesis had triopathy of complications.
39% of diabetic patients with delayed gastric emptying did not have other diabetic complications.
Presence of diabetic complications should raise awareness for gastroparesis in either T1DM or T2DM patients. However, diabetic gastroparesis can still occur without other diabetic complications.
Acknowledgments
The NIH/NIDDK Gastroparesis Clinical Research Consortium is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK073975 [Parkman], U01DK073983 [Pasricha], U01DK074007 [Abell], U01DK073974 [Koch], U01DK074035 [McCallum], U01DK112193 [Kuo], U01DK074008 [Tonascia]).
Footnotes
ClinicalTrials.gov Identifier:
No conflicts of interest exist.
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