Type II Diabetes. Identication of Responders common in type II diabetes; there was no correlation between HbA1c levels, on subjects with type I diabetes …
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Postprandial Improvement of Gastric Dysrhythmias in Patients with Type II Diabetes
Identification of Responders and Nonresponders
RUCHI MATHUR, MD, MARK PIMENTEL, MD, COLLEEN L SAM, DO, JIAN DE Z CHEN, PhD, GEORGE G BONORRIS, MS, PHILIP S BARNETT, MD, and HENRY C LIN, MD
Using the technique known as electrogastrography, we studied the postprandial response of gastric myoelectrial activity in subjects with type II diabetes Seventy-one subjects with type II diabetes underwent 1 hr of fasting electrogastrography recording HbA1c and fasting serum glucose levels were obtained Subjects then underwent an additional 2 hr of electrogastrography recording in the post prandial state Sixty of the 71 patients 85 had gastric rhythm abnormalities in the fasting state Forty-six of 71 subjects 65 responded to the test meal by improving their electrogastrography tracings responders while 35 did not respond nonresponders The time spent in bradygastria during the fasting state by responders was 263 128 vs 109 85 for nonresponders P 00001 The percent tachygastria during the fasting state in responders was 198 130, which was less than
nonresponders 383 297 P 0001 Fasting plasma glucose and HbA1c could not be used to predict the gastric myoelectrical response to meal In conclusion, gastric rhythm disturbances are common in type II diabetes; there was no correlation between HbA1c levels, age, duration of diabetes, or fasting serum glucose and gastric dysrhythmia in response to meal; two groups of subjects emerged: those who became less dysrhythmic in the post pradial state responders and those who did not non-responders; and fasting bradygastria was associated with responders and fasting tachygastria was associated with nonresponders
KEY WORDS: Electrogastrography; gastrointestinal motility; responders; diabetes complications
Hyperglycemia impairs gastric motility and emptying in both normal subjects 15 and in subjects with diabetes 1, 6 Since the control of gastric emptying determines the rate of glucose delivery to the small intestine 7, glucose control may become erratic
Manuscript received April 24, 2000; accepted November 10, 2000 From the Division of Endocrinology and Metabolism and GI Motility Program, Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, CSMC Burns and Allen
Research Center, Los Angeles, California 90048; School of Medicine, University of California, Los Angeles, Los Angeles, California 90024; and Department of Medicine, University of Texas, Medical Branch at Galveston, Galveston, Texas 77555
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when gastric emptying is abnormal Hyperglycemia then further impairs gastric emptying to perpetuate a vicious cycle whereby hyperglycemia and abnormal gastric motility become interdependent The myoelectrical activity of the gastric antrum may be recorded using electrodes placed on the sur-
This study was supported in part by a GCRC grant M01RR00425, National Center for Research Resources, and the American Diabetes Association Address for reprint requests: Dr Henry C Lin, Cedars-Sinai Medical Center 8700 Beverly Blvd, Suite 7511 Los Angeles, California 90048
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face of the abdomen 8, 9 This noninvasive, easily reproducible technique, known as electrogastrography EGG provides information on the power and frequency of myoelectrical signals generated by the stomach The electrical activity of the distal stomach
is characterized by cyclic depolarizations at a rate of 3 cycles per minute cpm Studies performed on subjects with type I diabetes reveal a significant increase in dysrhythmia, both bradygastria 24 cpm and tachygastria 36 cpm, when compared to normal controls 10 12 Although EGG abnormalities in type I diabetes have been documented 13, type II diabetes has been less well characterized In this study we assess the rate of gastric dysrhythmia in type II diabetes and assess postprandial changes in EGG MATERIALS AND METHODS Study Subjects
Consecutive subjects with type II diabetes attending the outpatient diabetes program at Cedars-Sinai Medical Center and recruited through media advertisements who were over the age of 18, with a body mass index BMI less than 32 kg/m2 were eligible to participate in the study Exclusion criteria included previous gastric surgery, use of betablockers or prokinetic drugs, and unstable thyroid disease A symptom questionnaire was administered to each subject, which included demographic information
Study Design
Subjects underwent 1 hr of EGG recording after an overnight fast HbA1c and fasting serum glucose levels were obtained Following the administration
of a standardized meal, each subject underwent an additional 2 hr of EGG recording
Experimental Methods
Electrogastrography was performed using three silver silver surface electrodes 3M Health Care, St Paul, Minnesota, USA Two active electrodes were positioned over the distal antrum, one midway between the umbilicus and the xiphoid process, and the other 23 cm to the right of the first A bipolar EGG signal was derived from these two active electrodes The third electrode was used as an electrical ground and placed over the right mid-axillary costal margin The EGG signal was amplified with a cutoff frequency of 03 Hz, digitized with a sampling frequency of 2 Hz, on-line displayed on a computer monitor, and stored on hard disk for further analysis Lakeshore Technologies, Chicago, Illinois, USA The digitized EGG signal was first subjected to visual analysis for the deletion of motion artifacts and then analyzed by customized spectral analysis 14 to derive the following parameters: EGG Dominant Frequency/Power The frequency at which the EGG power spectrum had a peak power in the
range of 0590 cpm was defined as the EGG dominant frequency The power at the dominant frequency in the
power spectrum was defined as the EGG dominant power These two parameters were calculated using the smooth power spectral analysis method 15 Percentage of Normal Gastric Slow Waves The percentage of normal gastric slow waves was defined as the percentage of time during which regular 24- to 36-cpm slow waves were present over the entire recording period It was computed using the adaptive spectral analysis method 14 In this method, each EGG recording was divided into blocks of 2 min without overlapping The 2-min EGG was called normal if the peak power was within the 24- to 36-cpm range The power spectrum of each 2-min EGG was calculated and examined to see if the peak power was within the range of 24 36 cpm 16 Otherwise it was defined as bradygastria 0523 cpm or tachygastria 37 90 cpm Postprandial responders and nonresponders were identified This was done by determining the standard deviation of the 2-min interval dominant frequencies in the pre- and postprandial states for each subject Responders were arbitrarily defined as subjects who achieved a postprandial standard deviation less than their fasting standard deviation, thus identifying subjects with less variation in dominant
frequency during each 2-min interval in the postprandial state Nonresponders were defined as subjects who had a postprandial standard deviation greater than their fasting standard deviation Hence, these subjects had more variability in dominant frequency of each 2-min interval in the postprandial state compared to fasting Serum glucose measurements were analyzed by the hexokinase enzyme method Endocrine Sciences Laboratory, Calabasas, California, USA Hemoglobin A1c measurements were performed using affinity chromatography Endocrine Sciences Laboratory The standardized test meal was based on an 1800 kcal/ day diet, and therefore contained 550 600 calories The meal consisted of three starches, three proteins, two vegetables, one fruit, and one fat exchange This led to the consumption of approximately 77 g of carbohydrate, 30 g of protein, and 16 g of fat
Statistical Analysis
The percent of bradygastria, tachygastria, and normal rhythm were compared by two-tailed t test Values were expressed as mean standard deviation Significance was determined by p 005 Correlation between HbA1c, fasting glucose and percent of time spent in abnormal rhythm was compared using Pearson correlation In
addition, subjects were divided into three groups according to their fasting HbA1c levels 51 60, 6170 and 71 Comparisons of the time spent in bradygastria, tachygastria and total dysrhythmia were compared with one-way ANOVA The amount of time spent in tachygastria and bradygastria in the fasting state was compared between responders and nonresponders by a two-tailed t test
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TABLE 1 PATIENT CHARACTERISTICS Age yr Sex M/F Duration of diabetes yrs Body mass index kg/m2 Symptoms of autonomic dysfunction Gastroparesis Postural dizziness Impotence N 44 Peripheral neuropathy Nephropathy Retinopathy Cardiovascular disease Average fasting glucose Hemoglobin A1c No on insulin No on oral medications N 71, except N 44 for impotence 62 119 44:27 77 76 267 31 20 28 33 46 30 67 41 58 3 4 7 10 7 10 142 48 71 16 18 25 45 63
RESULTS Patient Demographics Seventy-one subjects with type II diabetes were enrolled in this study Table 1 Males represented 619 of the group The average age was 620 119 years and the average duration of diabetes since the time of diagnosis was 77 76 years The body mass index was 267
31 kg/m2 The mean Hb A1c was 71 16 Abnormal EGG Sixty of the 71 type II diabetic subjects 85 had fasting gastric rhythm abnormalities 30 time spent in dysrhythmia The dominant frequency for all subjects was 32 10 while fasting and 31 09 in the postprandial period The amount of time spent in tachygastria and bradygastria during the fasting state was 210 136 and 261 217, respectively The mean percentage
of dysrhythmia for all patients was 554 203 in the fasting state and 516 201 in the postprandial state The amount of time of normal gastric rhythm was 447 202 while fasting and 485 199 postprandially The change in power for all subjects was 04 66 Fifty-nine of the 71 subjects 83 had gastric rhythm abnormalities in the postprandial period The percent tachygastria and bradygastria during the postprandial state was 245 163 and 211 192, respectively EGG and Diabetes Control There was no correlation between the percent bradygastria, percent tachygastria, and HbA1c levels Figure 1 No difference was seen in percent bradygastria, tachygastria, or total dysrhythmia when subjects were grouped according to their fasting HbA1c levels Responders vs Nonresponders Forty-six of the 71 subjects 65
responded to the meal stimulus by improving their EGG trac 
ings, and reducing the amount of gastric dysrhythmia seen responders Figure 2 Twenty-five of the 71 subjects 35 subjects studied did not respond by normalizing EGG tracings after a meal stimulus nonresponders Figure 3 Fasting bradygastria was predictive of subjects responding to a meal stimulus Figure 4 The percent bradygastria in the fasting state of Responders was 263 128 compared to 109 85 in nonresponders P 00001 In contrast, fasting tachygastria was predictive of nonresponders The percent tachygastria during the fasting state in nonresponders
Fig 1 HbA1c vs percent bradygastria and percent tachygastria Bradygastria: r Tachygastria: r 012, P NS
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001, P
NS
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Fig 2 EGG of a nonresponder: a fasting, b postprandial
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Fig 3 EGG of a responder: a fasting, b postprandial
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Fig 4 Fasting bradygastria and tachygastria in responders and nonresponders
was 383 297 compared to 198 130 in
responders P 0001 There was no significant difference between responders and nonresponders in HbA1c levels, age, duration of diabetes, or fasting serum glucose In addition, symptoms of autonomic dysfunction as elicited by questionnaire did not differ significantly between the two groups DISCUSSION This study describes the EGG abnormalities in the largest group of type II diabetics to date We observed that 85 of subjects with type II diabetes were found to have gastric dysrhythmia in the fasting state Despite previous literature suggesting a relationship between tachygastria and hyperglycemia 3, we found no relationship between fasting glucose and any rhythm pattern In addition, there was no relationship to HbA1c levels In the postprandial state, however, two groups were defined: subjects with improvement in gastric dysrhythmia responders and subjects who fail to improve or worsen after meal ingestion nonresponders Bradygastria in the fasting state appeared to be predictive of subject response, while tachygastria was predictive of failed response This is the first study to define two distinct groups of subjects with type II diabetes according to their gastric myoelectrical
improvement in response to a meal stimulus
The observation of gastric myoelectrical disturbances in hyperglycemia and in diabetes mellitus is not new A significant increase in fasting tachygastria is observed in normal subjects during hyperglycemic clamping to levels greater than 170 mg/dl 3 In hyperglycemic subjects with type I diabetes, dysrhythmia is reported to be as high as 63 13 However, the prevalence of gastric myoelectrical disturbances in subjects with type II diabetes is not well characterized In our study, dysrhythmia in the fasting state is present in 96 of subjects tested On average the percent of time spent in tachygastria is 21 136 and bradygastria, 261 217 Since carbohydrate delivery to the small intestine affects glycemic control, electrogastrographic observations in the postprandial state may be important In normal subjects given a meal stimulus, a predictable increase in amplitude of myoelectrical signal is observed 10, 17 The mechanism for these changes in normal subjects is not entirely clear but may be related to distension or a nutrient-driven response 14, 16 EGG studies in type I diabetes reveal a failure of this normal effect of a meal stimulus 17 Fischer
et al note a lack of expected increase in antral myoelectrical activity in response to meal with type I diabetes 17 Whether this is a reflection of diabetes related autonomic dysfunction is not clear In our study of subjects with type II diabetes, we identified two distinct groups in the postprandial state These groups were termed responders and nonDigestive Diseases and Sciences, Vol 46, No 4 April 2001
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responders as they relate to a nutrient-driven gastroversion or improvement in dysrhythmia with a meal Since the effects of clinical gastroparesis are evident mainly in the fed state, the failure of conversion to a less dysrhythmic gastroelectrical signal may be of clinical importance In addition, the degree of correcting response to meal may in some way be related to the state of vagal dysfunction However, in our study, a correlation among diabetes control, gastrointestinal complaints, and symptoms of autonomic dysfunction is not seen Since previous work has suggested some relationship between autonomic function and EGG changes 1720, further studies using objective autonomic function testing are needed to assess the vagal contribution to the
effect seen in these two groups of diabetic subjects A correlation of responders and nonresponders to an objective assessment of gastric function such as gastric emptying using scintigraphic techniques may also provide further physiologic information on the nature of these two groups and their role Finally, the fasting EGG appears to be predictive of whether subjects with type II diabetes are responders or nonresponders Subjects defined as responders show higher degrees of fasting bradygastria than subjects that fail to respond 236 vs 10 in responders and nonresponders, respectively; P 00001 Likewise, fasting tachygastria predicts nonresponse to meal stimulus This observational difference is important since it points out that further research is necessary to understand the fundamental etiologic difference between the generation of these two rhythm abnormalities In addition, the differing responses to a meal may indicate specific therapeutic and dietary treatment modalities may be beneficial, depending on baseline rhythm abnormalities In conclusion, gastric dysrhythmia is very common in subjects with type II diabetes The dysrhythmia does not appear to correlate with the duration or
degree of diabetes, gastrointestinal symptoms, or subjective symptoms of autonomic neuropathy We defined two groups of subjects based on improved gastric myoelectrical rhythm after meal stimulus with fasting levels of bradygastria and tachygastria predictive of responders and nonresponders, respectively If responders have improved gastric emptying compared to nonresponders, this could imply a mechanism for delayed gastric emptying Furthermore, the role of fasting bradygastria and tachygastria in predicting this response may provide a noninvasive means of determining gastric emptying in these type II subjects More studies are needed to identify furDigestive Diseases and Sciences, Vol 46, No 4 April 2001
ther the differences between these two groups and to explore the relationship between objective autonomic testing and gastric myoelectrical response in the post prandial state REFERENCES
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