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Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes
Journal Pre-proofs Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes Xuyi Wang, Cong Xie, Chinmay S. Marathe, Charles-Henri Malbert, Michael Horowitz, Karen L. Jones, Christopher K. Rayner, Zilin Sun, Tongzhi Wu PII: DOI: Reference:
S0168-8227(19)31058-7 https://doi.org/10.1016/j.diabres.2019.107951 DIAB 107951
To appear in:
Diabetes Research and Clinical Practice
Received Date: Revised Date: Accepted Date:
26 July 2019 4 October 2019 27 November 2019
Please cite this article as: X. Wang, C. Xie, C.S. Marathe, C-H. Malbert, M. Horowitz, K.L. Jones, C.K. Rayner, Z. Sun, T. Wu, Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes, Diabetes Research and Clinical Practice (2019), doi: https://doi.org/10.1016/j.diabres. 2019.107951
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier B.V.
Title: Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes
Authors: Xuyi Wang MD 1,2, Cong Xie MD 2, Chinmay S Marathe PhD 2, Charles-Henri Malbert PhD 3, Michael Horowitz PhD 2, Karen L Jones PhD 2, Christopher K Rayner PhD 2, Zilin Sun PhD 1, Tongzhi Wu PhD 1,2
Affiliations: 1. Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China; 2. Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia; 3. Aniscan Unit, Department of Human Nutrition, INRA, Saint-Gilles, France.
Correspondence to: Name:
Dr Tongzhi Wu
Address:
Level 5 of Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, South Australia; 5000
Email:
[email protected]
Telephone:
+61 8 83136535
1
Name:
Prof Zilin Sun
Address:
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, 87 Ding Jia Qiao, Gulou, Nanjing, China; 210009
Email:
[email protected]
Telephone:
+86 25 83272363
2
Abstract: Aims Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM.
Methods 14 Han Chinese and 14 Caucasian T2DM patients, managed by diet and/or metformin monotherapy, underwent concurrent measurements of gastric emptying and blood glucose for 240min after a 99mTc-calcium phytate-labelled mashed potato meal.
Results Han Chinese patients were slightly younger (P<0.05), and had a lower BMI (P<0.05), than Caucasians. There were no differences in either HbA1c or fasting blood glucose between them. Gastric half-emptying time (T50) was shorter (P<0.05) and the postprandial blood glucose increment greater (P<0.05) in Han Chinese than Caucasian patients. Both the increment in blood glucose from baseline at 60min and peak blood glucose were related inversely to T50 (P<0.05 each).
Conclusions Han Chinese with relatively well-controlled T2DM have more rapid gastric emptying
3
compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. These differences may inform the choice of management, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.
Key words: ethnicity; gastric emptying; postprandial glycaemia; type 2 diabetes
4
1. Introduction Achieving good postprandial glycaemic control represents a major management goal in type 2 diabetes (T2DM), especially in patients who are relatively well controlled (i.e. glycated haemoglobin (HbA1c) < 8.0 % or 64 mmol/mol), in whom postprandial glycaemia makes the predominant contribution to overall glycaemic control [1]. Postprandial glycaemia is also an independent predictor of cardiovascular risk and allcause mortality [2]. Moreover, the glycaemic response to an oral glucose load at one hour is an independent predictor of type 2 diabetes in adults [3]. While the postprandial glycaemic excursion is determined by a number of factors including exogenous glucose absorption, endogenous glucose production and glucose disposal [4], it is now increasingly appreciated that gastric emptying, which exhibits substantial interindividual, but relatively low intra-individual, variation, is a major determinant of postprandial glycaemia in both health and T2DM [5-9]. Studies have shown that even relatively small differences in the rate of gastric emptying may have a major impact on the subsequent blood glucose profile [5, 10]. Gastric emptying is delayed in 30 - 50 % of patients with longstanding poorly controlled diabetes [5, 9], but is modestly accelerated in relatively well controlled, uncomplicated T2DM [11]. In the latter, dietary (e.g. nutrient preloads taken before the meal [12-14]) and pharmacological (e.g. short-acting GLP-1 receptor agonists [15]) interventions that slow gastric emptying are beneficial for improving postprandial glycaemic control.
T2DM occurs at a much lower mean body mass index (BMI) and younger age in East
5
Asians than Europeans [16], probably reflecting major pathophysiological differences between ethnic groups. While insulin resistance is common in many populations, impaired insulin secretion appears to be prominent in East Asians [17]. There is evidence that gastric emptying may be influenced by ethnicity; for example, gastric emptying has been reported to be relatively faster in Mexican Americans than nonHispanic Whites [18]. Moreover, the postprandial glycaemic excursion in response to a high carbohydrate meal has been shown to be greater in healthy individuals of Chinese ethnicity when compared with Caucasians [19, 20]. There is, however, a lack of comparative data on gastric emptying and postprandial glycaemic responses between Asian and Caucasian patients with T2DM.
In the present study, we compared gastric emptying of a standardised high carbohydrate meal in Han Chinese and Caucasian patients with T2DM, and evaluated the impact of these on the postprandial glycaemic excursion.
2. Materials and methods 2.1 Participants 14 Han Chinese and 14 Caucasians patients with T2DM were studied after providing written informed consent. T2DM of both groups had been diagnosed according to the World Health Organization (WHO) criteria, and was relatively well controlled by diet and/or metformin monotherapy (i.e. HbA1c < 8.0 % or 64 mmol/mol, in consideration of the relevance of postprandial glycaemia to overall glycaemic control in this group of
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T2DM patients [1] and the potential influence of hyperglycaemia on gastric emptying [21]) (Table 1). The groups were otherwise not deliberately matched for age or BMI, since gastric emptying was shown to be quite stable over 10-25 years in patients with T1- and T2-DM [22, 23] and was not related to BMI in well-controlled T2DM [11]. Moreover, it would also not be possible to match these parameters between these two groups without introducing other confounding factors, given that T2DM typically occurs at a much lower BMI and younger age in East Asians than Europeans [16]. None had a history or evidence of gastrointestinal disease or prior surgery, or diabetic microvascular complications, including autonomic dysfunction as assessed using standardized cardiovascular reflex tests [24]. None was a smoker or taking medication known to affect gastrointestinal function. The protocols were approved by the Royal Adelaide Hospital Human Research Ethics Committee and the Human Research Ethics Committee of Zhongda Hospital, Affiliated to Southeast University, respectively, and registered on a clinical trials database (NCT02315495; NCT02324010).
2.2 Protocol Subjects were evaluated on a single study visit following an identical protocol, after an overnight fast (14 hours for solids, 12 hours for liquids). Metformin was ceased for 48 hours prior to the study day. On arrival at either the Department of Nuclear Medicine at Royal Adelaide Hospital or Zhongda Hospital (~ 9:00 AM), an intravenous cannula was placed for blood sampling and the subject seated in front of a gamma camera. Between t = -10-0 min, each subject consumed a high carbohydrate meal comprising
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65 g powdered potato (Deb, Epping, NSW, Australia) and 20 g glucose, reconstituted with 200 mL boiling water and an egg yolk (368.5 kcal: carbohydrate 61.4 g, protein 7.4 g, fat 8.9 g) and radio-labelled with 20 MBq 99mTc-calcium phytate; t = 0 min was defined as the time of completion of the meal. Venous blood was sampled immediately before, and at t = 15, 30, 45, 60, 90, 120, 150, 180 and 240 min after, the meal. Upon completion of the study, each subject was provided a light lunch prior to leaving the laboratory.
2.3 Measurements Blood glucose concentrations were measured using a glucometer (Optium Xceed, Abbott Laboratories, USA), and are reported as the mean of duplicate measurements at each time point. Scintigraphic data were acquired (3- min frames in the first 60 min and 5- min frames every 30 min thereafter) for 240 minutes after consumption of the meal (Genie; GE Healthcare Technologies, Milwaukee, WI, USA) [25]. Gastric emptying curves (expressed as % of the maximum content of the total stomach) were derived, and the content of the stomach at t = 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min, as well as T50, calculated.
2.4 Statistical analysis The iAUC over 240 min for blood glucose was calculated using the trapezoidal rule. Unpaired Student’s t-test was used to compare the demographic data, the iAUC for blood glucose and T50 between the two groups. The comparison of T50 between the
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two groups was also conducted while taking age and/or BMI as covariables. Blood glucose and gastric emptying curves were analyzed using two-factor repeated-measures ANOVA, with group and time as factors. Relationships of gastric emptying (T50) with demographic data (age, BMI and HbA1c) and blood glucose parameters (including the increments in blood glucose after the meal and the iAUC for blood glucose), were assessed using univariate linear regression analysis. All analyses were performed using Prism 8.0 software (GraphPad, La Jolla, CA, USA). Data are presented as means ± SEM; P < 0.05 was considered statistically significant.
3. Results All patients tolerated the protocol well. When compared with Caucasian T2DM patients, Han Chinese patients were ~ 10 years younger (P < 0.05) and had a lower BMI (P < 0.05). There were no differences in the duration of known diabetes, HbA1c or fasting glucose between the two groups (Table 1).
3.1 Blood glucose After the meal, blood glucose increased before returning to baseline in both groups (time effect: P < 0.001). The increment in peak blood glucose was greater in the Han Chinese than Caucasian (Han Chinese: 8.1 ± 0.8 mmol/L vs. Caucasian: 5.9 ± 0.6 mmol/L, P < 0.05). There was a tendency for a greater increase in postprandial blood glucose (i.e. the increments in blood glucose concentrations from baseline) in the Han Chinese than Caucasian patients (group effect: P = 0.09) (Figure 1A).
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3.2 Gastric emptying Gastric emptying was faster in the Han Chinese than Caucasian patients (group effect: P < 0.001), such that intragastric retention was less in the Han Chinese patients between t = 60-240 min (P < 0.05 for all time points) (Figure 1B). The T50 was shorter in Han Chinese patients than Caucasian Patients (Han Chinese: 56.8 ± 3.7 min vs. Caucasian: 71.1 ± 4.3 min, P < 0.05). The difference in T50 between the two groups remained significant after adjusting for the differences in age and/or BMI (P < 0.05 each). Accordingly, the rate of gastric emptying in this group of Han Chinese patients with T2DM was ~20% faster than Caucasian patients (Han Chinese: 3.4 ± 0.3 kcal/min vs. Caucasian: 2.7 ± 0.2 kcal/min, P < 0.05).
3.3 Relationships By pooling the data from the two groups, the T50 was not related to either age, BMI or HbA1c, but the increments in blood glucose from baseline at t=60min (r = - 0.42, P < 0.05) and the iAUC0-60min for blood glucose (r = - 0.39, P < 0.05), were related inversely to the T50 (Figure 2).
4. Discussion The pathophysiology underlying dysregulated blood glucose in T2DM is highly heterogenous and has major implications for the desired individualized, rather than currently empirical, management of T2DM. Here, we have shown that gastric emptying
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is faster in Han Chinese when compared with Caucasians with relatively wellcontrolled T2DM, and that this is predictably associated with a greater postprandial glycaemic excursion following a standardised carbohydrate meal. This ethnic disparity, accordingly, is likely to be relevant to the choice of management strategies for postprandial glycaemic control in T2DM in the two groups.
The major strengths of the study were that gastric emptying was quantified precisely using the “gold standard” measurement of scintigraphy, and that the patients studied did not have evidence of diabetic complications and had relatively good glycaemic control with diet and/or metformin monotherapy. This is a group where it is appreciated that postprandial, rather than fasting or preprandial, glycaemia makes the major contribution to the overall glycaemic control [1]. Moreover, the potential influence of overall glycaemic control on gastric emptying is minimised [21].
In keeping with the established role of gastric emptying in determining postprandial glycaemia, we observed an inverse relationship between the gastric half-emptying time and the rises in postprandial blood glucose, and that the postprandial increment in blood glucose was greater in the Han Chinese than the Caucasian. Given that the postprandial glycaemic response to carbohydrate meals was also shown to be greater in healthy Chinese than Caucasian subjects [19], evaluation of gastric emptying and its relevance to the development of glucose intolerance in a Chinese population is now warranted.
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Several limitations should be noted. First, Han Chinese patients were ~10 years younger, and had a lower BMI that Caucasians, in line with epidemiological data indicative of an earlier onset of T2DM at a lower BMI in East Asians than Caucasians [16]. For this reason, it is almost impossible to have two groups of comparable age and BMI without introducing other variables (e.g. duration of diabetes, glycaemic status). However, neither BMI nor age correlated with the rate of gastric emptying. Longitudinal studies have shown that gastric emptying in patients with T1 or T2DM remains remarkably stable over 12-25 years [5, 22, 23, 26], although healthy aging may be associated with a modest slowing of gastric emptying [11]. There is some evidence [27], albeit inconsistent [28], that obesity may be associated with accelerated emptying. Therefore, the lower BMI in the Han Chinese patients is most unlikely to account for emptying being more rapid than in Caucasians. Not surprisingly, after adjusting the effects of age and BMI, the difference in the rate of gastric emptying between the two groups remained statistically significant. Second, previous dietary habits would be expected to be different between the two groups – the Asian diet usually contains a higher proportion of carbohydrate than Caucasian diet [20] – which may influence gastric emptying. Third, the two groups of patients were studied in two different research centers, although an identical protocol was used under the direction of the same investigators. Furthermore, a high carbohydrate meal was used in the present study, which may not be typical for patients with T2DM, but is ideal to investigate the relationship between gastric emptying and postprandial glycaemia. Finally, the sample size of the two groups was relatively small; a study in a larger cohort to confirm the
12
current observations is warranted.
In summary, Han Chinese patients with relatively well-controlled T2DM have more rapid gastric emptying compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. Such ethnic differences inform the choice of treatment in different populations, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.
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Funding: The study in Caucasian patients with T2DM was funded by a Royal Adelaide Hospital Research Foundation Clinical Project Grant. The study in Han Chinese patients with T2DM was funded by AstraZeneca through an investigator-initiated program. TW is supported by a Royal Adelaide Hospital Florey Fellowship. KLJ is supported by a William T Southcott Research Fellowship. XW and CX are supported by a postgraduate scholarship from the China Scholarship Council.
Conflicts of interest: MH has participated in advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. KLJ has received research funding from Sanofi, AstraZeneca, Omniblend Innovations and trial medication from Merck Sharp & Dohme. CKR has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly, Novartis, and Sanofi. ZS has received research funding from AstraZeneca. TW has received research funding from Novartis and AstraZeneca. None of the other authors has any personal or financial conflict of interest to declare.
Contribution statement: XW was involved in conception, design and coordination of the study, subject recruitment, data collection and interpretation, statistical analysis and writing of the manuscript; CX, CSM, CHM, MH, KLJ, CKR and ZS were involved in conception and design of the study and data interpretation. TW was involved in the conception and conduct of the study, data interpretation, statistical analysis and drafting
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of the manuscript. All authors critically reviewed the manuscript, and have approved the publication of this final version of the manuscript.
Acknowledgements: The authors wish to thank Ms Lu Liu, Ms Yan Xie, Mr Qiang Wang and Mr Xuanfei Xu (Staff of the Department of Nuclear Medicine, Zhongda Hospital) for excellent technical support on the collection of scintigraphic data in Han Chinese patients with T2DM, Ms Michelle Bound and Ms Seva Hatzinikolas (research officers of the Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, the University of Adelaide) for excellent technical support on the analysis of the gastric emptying data, and Ms Kylie Lange (a biostatistician of the CRE) for her expert statistical advice.
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References: [1] Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881-5. [2] Cavalot F, Pagliarino A, Valle M, Di Martino L, Bonomo K, Massucco P, et al. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes Study. Diabetes Care. 2011;34:2237-43. [3] Trico D, Galderisi A, Mari A, Santoro N, Caprio S. One-hour post-load plasma glucose predicts progression to prediabetes in a multi-ethnic cohort of obese youths. Diabetes Obes Metab. 2019;21:1191-8. [4] Riddle MC. Basal glucose can be controlled, but the prandial problem persists-it's the next target! Diabetes Care. 2017;40:291-300. [5] Phillips LK, Deane AM, Jones KL, Rayner CK, Horowitz M. Gastric emptying and glycaemia in health and diabetes mellitus. Nat Rev Endocrinol. 2015;11:112-28. [6] Wu T, Rayner CK, Young RL, Horowitz M. Gut motility and enteroendocrine secretion. Current opinion in pharmacology. 2013;13:928-34. [7] Camilleri M, Iturrino J, Bharucha AE, Burton D, Shin A, Jeong ID, et al. Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants. Neurogastroenterol Motil. 2012;24:1076-e562. [8] Horowitz M, Harding PE, Maddox AF, Wishart JM, Akkermans LM, Chatterton BE, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulindependent) diabetes mellitus. Diabetologia. 1989;32:151-9. [9] Mussa BM, Sood S, Verberne AJ. Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis. World J Gastroenterol. 2018;24:3821-33. [10] Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiological reviews. 2017;97:411-63. [11] Watson LE, Xie C, Wang X, Li Z, Phillips LK, Sun Z, et al. Gastric emptying in patients with well-controlled type 2 diabetes compared with young and older control subjects without diabetes. J Clin Endocrinol Metab. 2019;104:3311-9. [12] Wu T, Little TJ, Bound MJ, Borg M, Zhang X, Deacon CF, et al. A protein preload enhances the glucose-lowering efficacy of vildagliptin in type 2 diabetes. Diabetes Care. 2016;39:511-7. [13] Wu T, Bound MJ, Zhao BR, Standfield SD, Bellon M, Jones KL, et al. Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes. Diabetes Care. 2013;36:19138. [14] Wu T, Zhao BR, Bound MJ, Checklin HL, Bellon M, Little TJ, et al. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. Am J Clin Nutr. 2012;95:78-83. 16
[15] Jones KL, Rigda RS, Buttfield MDM, Hatzinikolas S, Pham HT, Marathe CS, et al. Effects of lixisenatide on postprandial blood pressure, gastric emptying and glycaemia in healthy people and people with type 2 diabetes. Diabetes Obes Metab. 2019;21:1158-67. [16] Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006;368:1681-8. [17] Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care. 2013;36:1789-96. [18] Schwartz JG, Mcmahan CA, Green GM, Phillips WT. Gastric emptying in Mexican Americans compared to non-Hispanic whites. Digestive Diseases & Sciences. 1995;40:624-30. [19] Kataoka M, Venn BJ, Williams SM, Te Morenga LA, Heemels IM, Mann JI. Glycaemic responses to glucose and rice in people of Chinese and European ethnicity. Diabet Med. 2013;30:e101-7. [20] Venn BS, Williams SM, Mann JI. Comparison of postprandial glycaemia in Asians and Caucasians. Diabet Med. 2010;27:1205-8. [21] Laway BA, Malik TS, Khan SH, Rather TA. Prevalence of abnormal gastric emptying in asymptomatic women with newly detected diabetes and its reversibility after glycemic control-a prospective case control study. J Diabetes Complications. 2013;27:78-81. [22] Watson LE, Phillips LK, Wu T, Bound MJ, Jones KL, Horowitz M, et al. Longitudinal evaluation of gastric emptying in type 2 diabetes. Diabetes Res Clin Pract. 2019;154:27-34. [23] Chang J, Russo A, Bound M, Rayner CK, Jones KL, Horowitz M. A 25-year longitudinal evaluation of gastric emptying in diabetes. Diabetes Care. 2012;35:25946. [24] Piha SJ. Cardiovascular autonomic reflex tests: normal responses and age-related reference values. Clinical physiology. 1991;11:277-90. [25] Collins PJ, Horowitz M, Cook DJ, Harding PE, Shearman DJ. Gastric emptying in normal subjects--a reproducible technique using a single scintillation camera and computer system. Gut. 1983;24:1117-25. [26] Chang J, Rayner CK, Jones KL, Horowitz M. Prognosis of diabetic gastroparesis-a 25-year evaluation. Diabet Med. 2013;30:e185-8. [27] Dubois A, . Obesity and gastric emptying. Gastroenterology. 1983;84:875-6. [28] Verdich C, Madsen JL, Toubro S, Buemann B, Holst JJ, Astrup A. Effect of obesity and major weight reduction on gastric emptying. Int J Obes Relat Metab Disord. 2000;24:899-905.
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Table 1. Demographics and the gastric half-emptying time of Han Chinese and Caucasian patients with type 2 diabetes.
Gender (male/female) Gastrointestinal disorder or surgery Smokers Use of medications known to affect gastrointestinal function Diabetic complications Treatments Age (years) BMI (kg/m2) HbA1c (%) HbA1c (mmol/mol) Fasting blood glucose (mmol/L) Duration of known diabetes (years)
Han Chinese (n=14) 10/4 None None None
Caucasians (n=14) 9/5 None None None
P value
None diet
None diet (n=7), metformin (n=7) 67.8 ± 1.5 31.2 ± 0.9 6.4 ± 0.2 46.1 ± 1.8 7.9 ± 0.4 3.8 ± 0.8
-
58.0 ± 2.4 23.6 ± 0.6 6.8 ± 0.2 51.2 ± 1.8 7.9 ± 0.4 3.0 ± 0.5
18
ns -
P < 0.05 P < 0.05 ns ns ns ns
Figure legends: Figure 1. Blood glucose (A) and gastric emptying (B) in response to a high carbohydrate meal in Han Chinese (n = 14) and Caucasian (n = 14) patients with type 2 diabetes. Two factor-repeated measures ANOVA, with group and time as factors, was used to determine the statistical significance. Data are mean ± SEM.
Figure 2. The relationships of the increments in blood glucose at t = 60 min (A) and the iAUC0-60min for blood glucose (B) with the gastric half-emptying time (T50) in patients with type 2 diabetes (n = 28).
19
Figure 1.
Figure 2.
B 15
r = -0.42 P < 0.05
Caucasian Han Chinese
10 5 0 20
40
60 80 T50 (min)
Blood glucose iAUC (t=0-60min, mmol/L*h-1)
Blood glucose, mmol/L (Δ baseline at t=60min)
A
100
20
8 6
r = -0.39 P < 0.05
4 2 0 20
40
60 80 T50 (min)
100
S0168-8227(19)31058-7 https://doi.org/10.1016/j.diabres.2019.107951 DIAB 107951
To appear in:
Diabetes Research and Clinical Practice
Received Date: Revised Date: Accepted Date:
26 July 2019 4 October 2019 27 November 2019
Please cite this article as: X. Wang, C. Xie, C.S. Marathe, C-H. Malbert, M. Horowitz, K.L. Jones, C.K. Rayner, Z. Sun, T. Wu, Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes, Diabetes Research and Clinical Practice (2019), doi: https://doi.org/10.1016/j.diabres. 2019.107951
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2019 Published by Elsevier B.V.
Title: Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes
Authors: Xuyi Wang MD 1,2, Cong Xie MD 2, Chinmay S Marathe PhD 2, Charles-Henri Malbert PhD 3, Michael Horowitz PhD 2, Karen L Jones PhD 2, Christopher K Rayner PhD 2, Zilin Sun PhD 1, Tongzhi Wu PhD 1,2
Affiliations: 1. Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China; 2. Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia; 3. Aniscan Unit, Department of Human Nutrition, INRA, Saint-Gilles, France.
Correspondence to: Name:
Dr Tongzhi Wu
Address:
Level 5 of Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, South Australia; 5000
Email:
[email protected]
Telephone:
+61 8 83136535
1
Name:
Prof Zilin Sun
Address:
Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, 87 Ding Jia Qiao, Gulou, Nanjing, China; 210009
Email:
[email protected]
Telephone:
+86 25 83272363
2
Abstract: Aims Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM.
Methods 14 Han Chinese and 14 Caucasian T2DM patients, managed by diet and/or metformin monotherapy, underwent concurrent measurements of gastric emptying and blood glucose for 240min after a 99mTc-calcium phytate-labelled mashed potato meal.
Results Han Chinese patients were slightly younger (P<0.05), and had a lower BMI (P<0.05), than Caucasians. There were no differences in either HbA1c or fasting blood glucose between them. Gastric half-emptying time (T50) was shorter (P<0.05) and the postprandial blood glucose increment greater (P<0.05) in Han Chinese than Caucasian patients. Both the increment in blood glucose from baseline at 60min and peak blood glucose were related inversely to T50 (P<0.05 each).
Conclusions Han Chinese with relatively well-controlled T2DM have more rapid gastric emptying
3
compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. These differences may inform the choice of management, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.
Key words: ethnicity; gastric emptying; postprandial glycaemia; type 2 diabetes
4
1. Introduction Achieving good postprandial glycaemic control represents a major management goal in type 2 diabetes (T2DM), especially in patients who are relatively well controlled (i.e. glycated haemoglobin (HbA1c) < 8.0 % or 64 mmol/mol), in whom postprandial glycaemia makes the predominant contribution to overall glycaemic control [1]. Postprandial glycaemia is also an independent predictor of cardiovascular risk and allcause mortality [2]. Moreover, the glycaemic response to an oral glucose load at one hour is an independent predictor of type 2 diabetes in adults [3]. While the postprandial glycaemic excursion is determined by a number of factors including exogenous glucose absorption, endogenous glucose production and glucose disposal [4], it is now increasingly appreciated that gastric emptying, which exhibits substantial interindividual, but relatively low intra-individual, variation, is a major determinant of postprandial glycaemia in both health and T2DM [5-9]. Studies have shown that even relatively small differences in the rate of gastric emptying may have a major impact on the subsequent blood glucose profile [5, 10]. Gastric emptying is delayed in 30 - 50 % of patients with longstanding poorly controlled diabetes [5, 9], but is modestly accelerated in relatively well controlled, uncomplicated T2DM [11]. In the latter, dietary (e.g. nutrient preloads taken before the meal [12-14]) and pharmacological (e.g. short-acting GLP-1 receptor agonists [15]) interventions that slow gastric emptying are beneficial for improving postprandial glycaemic control.
T2DM occurs at a much lower mean body mass index (BMI) and younger age in East
5
Asians than Europeans [16], probably reflecting major pathophysiological differences between ethnic groups. While insulin resistance is common in many populations, impaired insulin secretion appears to be prominent in East Asians [17]. There is evidence that gastric emptying may be influenced by ethnicity; for example, gastric emptying has been reported to be relatively faster in Mexican Americans than nonHispanic Whites [18]. Moreover, the postprandial glycaemic excursion in response to a high carbohydrate meal has been shown to be greater in healthy individuals of Chinese ethnicity when compared with Caucasians [19, 20]. There is, however, a lack of comparative data on gastric emptying and postprandial glycaemic responses between Asian and Caucasian patients with T2DM.
In the present study, we compared gastric emptying of a standardised high carbohydrate meal in Han Chinese and Caucasian patients with T2DM, and evaluated the impact of these on the postprandial glycaemic excursion.
2. Materials and methods 2.1 Participants 14 Han Chinese and 14 Caucasians patients with T2DM were studied after providing written informed consent. T2DM of both groups had been diagnosed according to the World Health Organization (WHO) criteria, and was relatively well controlled by diet and/or metformin monotherapy (i.e. HbA1c < 8.0 % or 64 mmol/mol, in consideration of the relevance of postprandial glycaemia to overall glycaemic control in this group of
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T2DM patients [1] and the potential influence of hyperglycaemia on gastric emptying [21]) (Table 1). The groups were otherwise not deliberately matched for age or BMI, since gastric emptying was shown to be quite stable over 10-25 years in patients with T1- and T2-DM [22, 23] and was not related to BMI in well-controlled T2DM [11]. Moreover, it would also not be possible to match these parameters between these two groups without introducing other confounding factors, given that T2DM typically occurs at a much lower BMI and younger age in East Asians than Europeans [16]. None had a history or evidence of gastrointestinal disease or prior surgery, or diabetic microvascular complications, including autonomic dysfunction as assessed using standardized cardiovascular reflex tests [24]. None was a smoker or taking medication known to affect gastrointestinal function. The protocols were approved by the Royal Adelaide Hospital Human Research Ethics Committee and the Human Research Ethics Committee of Zhongda Hospital, Affiliated to Southeast University, respectively, and registered on a clinical trials database (NCT02315495; NCT02324010).
2.2 Protocol Subjects were evaluated on a single study visit following an identical protocol, after an overnight fast (14 hours for solids, 12 hours for liquids). Metformin was ceased for 48 hours prior to the study day. On arrival at either the Department of Nuclear Medicine at Royal Adelaide Hospital or Zhongda Hospital (~ 9:00 AM), an intravenous cannula was placed for blood sampling and the subject seated in front of a gamma camera. Between t = -10-0 min, each subject consumed a high carbohydrate meal comprising
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65 g powdered potato (Deb, Epping, NSW, Australia) and 20 g glucose, reconstituted with 200 mL boiling water and an egg yolk (368.5 kcal: carbohydrate 61.4 g, protein 7.4 g, fat 8.9 g) and radio-labelled with 20 MBq 99mTc-calcium phytate; t = 0 min was defined as the time of completion of the meal. Venous blood was sampled immediately before, and at t = 15, 30, 45, 60, 90, 120, 150, 180 and 240 min after, the meal. Upon completion of the study, each subject was provided a light lunch prior to leaving the laboratory.
2.3 Measurements Blood glucose concentrations were measured using a glucometer (Optium Xceed, Abbott Laboratories, USA), and are reported as the mean of duplicate measurements at each time point. Scintigraphic data were acquired (3- min frames in the first 60 min and 5- min frames every 30 min thereafter) for 240 minutes after consumption of the meal (Genie; GE Healthcare Technologies, Milwaukee, WI, USA) [25]. Gastric emptying curves (expressed as % of the maximum content of the total stomach) were derived, and the content of the stomach at t = 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min, as well as T50, calculated.
2.4 Statistical analysis The iAUC over 240 min for blood glucose was calculated using the trapezoidal rule. Unpaired Student’s t-test was used to compare the demographic data, the iAUC for blood glucose and T50 between the two groups. The comparison of T50 between the
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two groups was also conducted while taking age and/or BMI as covariables. Blood glucose and gastric emptying curves were analyzed using two-factor repeated-measures ANOVA, with group and time as factors. Relationships of gastric emptying (T50) with demographic data (age, BMI and HbA1c) and blood glucose parameters (including the increments in blood glucose after the meal and the iAUC for blood glucose), were assessed using univariate linear regression analysis. All analyses were performed using Prism 8.0 software (GraphPad, La Jolla, CA, USA). Data are presented as means ± SEM; P < 0.05 was considered statistically significant.
3. Results All patients tolerated the protocol well. When compared with Caucasian T2DM patients, Han Chinese patients were ~ 10 years younger (P < 0.05) and had a lower BMI (P < 0.05). There were no differences in the duration of known diabetes, HbA1c or fasting glucose between the two groups (Table 1).
3.1 Blood glucose After the meal, blood glucose increased before returning to baseline in both groups (time effect: P < 0.001). The increment in peak blood glucose was greater in the Han Chinese than Caucasian (Han Chinese: 8.1 ± 0.8 mmol/L vs. Caucasian: 5.9 ± 0.6 mmol/L, P < 0.05). There was a tendency for a greater increase in postprandial blood glucose (i.e. the increments in blood glucose concentrations from baseline) in the Han Chinese than Caucasian patients (group effect: P = 0.09) (Figure 1A).
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3.2 Gastric emptying Gastric emptying was faster in the Han Chinese than Caucasian patients (group effect: P < 0.001), such that intragastric retention was less in the Han Chinese patients between t = 60-240 min (P < 0.05 for all time points) (Figure 1B). The T50 was shorter in Han Chinese patients than Caucasian Patients (Han Chinese: 56.8 ± 3.7 min vs. Caucasian: 71.1 ± 4.3 min, P < 0.05). The difference in T50 between the two groups remained significant after adjusting for the differences in age and/or BMI (P < 0.05 each). Accordingly, the rate of gastric emptying in this group of Han Chinese patients with T2DM was ~20% faster than Caucasian patients (Han Chinese: 3.4 ± 0.3 kcal/min vs. Caucasian: 2.7 ± 0.2 kcal/min, P < 0.05).
3.3 Relationships By pooling the data from the two groups, the T50 was not related to either age, BMI or HbA1c, but the increments in blood glucose from baseline at t=60min (r = - 0.42, P < 0.05) and the iAUC0-60min for blood glucose (r = - 0.39, P < 0.05), were related inversely to the T50 (Figure 2).
4. Discussion The pathophysiology underlying dysregulated blood glucose in T2DM is highly heterogenous and has major implications for the desired individualized, rather than currently empirical, management of T2DM. Here, we have shown that gastric emptying
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is faster in Han Chinese when compared with Caucasians with relatively wellcontrolled T2DM, and that this is predictably associated with a greater postprandial glycaemic excursion following a standardised carbohydrate meal. This ethnic disparity, accordingly, is likely to be relevant to the choice of management strategies for postprandial glycaemic control in T2DM in the two groups.
The major strengths of the study were that gastric emptying was quantified precisely using the “gold standard” measurement of scintigraphy, and that the patients studied did not have evidence of diabetic complications and had relatively good glycaemic control with diet and/or metformin monotherapy. This is a group where it is appreciated that postprandial, rather than fasting or preprandial, glycaemia makes the major contribution to the overall glycaemic control [1]. Moreover, the potential influence of overall glycaemic control on gastric emptying is minimised [21].
In keeping with the established role of gastric emptying in determining postprandial glycaemia, we observed an inverse relationship between the gastric half-emptying time and the rises in postprandial blood glucose, and that the postprandial increment in blood glucose was greater in the Han Chinese than the Caucasian. Given that the postprandial glycaemic response to carbohydrate meals was also shown to be greater in healthy Chinese than Caucasian subjects [19], evaluation of gastric emptying and its relevance to the development of glucose intolerance in a Chinese population is now warranted.
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Several limitations should be noted. First, Han Chinese patients were ~10 years younger, and had a lower BMI that Caucasians, in line with epidemiological data indicative of an earlier onset of T2DM at a lower BMI in East Asians than Caucasians [16]. For this reason, it is almost impossible to have two groups of comparable age and BMI without introducing other variables (e.g. duration of diabetes, glycaemic status). However, neither BMI nor age correlated with the rate of gastric emptying. Longitudinal studies have shown that gastric emptying in patients with T1 or T2DM remains remarkably stable over 12-25 years [5, 22, 23, 26], although healthy aging may be associated with a modest slowing of gastric emptying [11]. There is some evidence [27], albeit inconsistent [28], that obesity may be associated with accelerated emptying. Therefore, the lower BMI in the Han Chinese patients is most unlikely to account for emptying being more rapid than in Caucasians. Not surprisingly, after adjusting the effects of age and BMI, the difference in the rate of gastric emptying between the two groups remained statistically significant. Second, previous dietary habits would be expected to be different between the two groups – the Asian diet usually contains a higher proportion of carbohydrate than Caucasian diet [20] – which may influence gastric emptying. Third, the two groups of patients were studied in two different research centers, although an identical protocol was used under the direction of the same investigators. Furthermore, a high carbohydrate meal was used in the present study, which may not be typical for patients with T2DM, but is ideal to investigate the relationship between gastric emptying and postprandial glycaemia. Finally, the sample size of the two groups was relatively small; a study in a larger cohort to confirm the
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current observations is warranted.
In summary, Han Chinese patients with relatively well-controlled T2DM have more rapid gastric emptying compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. Such ethnic differences inform the choice of treatment in different populations, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.
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Funding: The study in Caucasian patients with T2DM was funded by a Royal Adelaide Hospital Research Foundation Clinical Project Grant. The study in Han Chinese patients with T2DM was funded by AstraZeneca through an investigator-initiated program. TW is supported by a Royal Adelaide Hospital Florey Fellowship. KLJ is supported by a William T Southcott Research Fellowship. XW and CX are supported by a postgraduate scholarship from the China Scholarship Council.
Conflicts of interest: MH has participated in advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. KLJ has received research funding from Sanofi, AstraZeneca, Omniblend Innovations and trial medication from Merck Sharp & Dohme. CKR has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly, Novartis, and Sanofi. ZS has received research funding from AstraZeneca. TW has received research funding from Novartis and AstraZeneca. None of the other authors has any personal or financial conflict of interest to declare.
Contribution statement: XW was involved in conception, design and coordination of the study, subject recruitment, data collection and interpretation, statistical analysis and writing of the manuscript; CX, CSM, CHM, MH, KLJ, CKR and ZS were involved in conception and design of the study and data interpretation. TW was involved in the conception and conduct of the study, data interpretation, statistical analysis and drafting
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of the manuscript. All authors critically reviewed the manuscript, and have approved the publication of this final version of the manuscript.
Acknowledgements: The authors wish to thank Ms Lu Liu, Ms Yan Xie, Mr Qiang Wang and Mr Xuanfei Xu (Staff of the Department of Nuclear Medicine, Zhongda Hospital) for excellent technical support on the collection of scintigraphic data in Han Chinese patients with T2DM, Ms Michelle Bound and Ms Seva Hatzinikolas (research officers of the Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, the University of Adelaide) for excellent technical support on the analysis of the gastric emptying data, and Ms Kylie Lange (a biostatistician of the CRE) for her expert statistical advice.
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References: [1] Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881-5. [2] Cavalot F, Pagliarino A, Valle M, Di Martino L, Bonomo K, Massucco P, et al. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes Study. Diabetes Care. 2011;34:2237-43. [3] Trico D, Galderisi A, Mari A, Santoro N, Caprio S. One-hour post-load plasma glucose predicts progression to prediabetes in a multi-ethnic cohort of obese youths. Diabetes Obes Metab. 2019;21:1191-8. [4] Riddle MC. Basal glucose can be controlled, but the prandial problem persists-it's the next target! Diabetes Care. 2017;40:291-300. [5] Phillips LK, Deane AM, Jones KL, Rayner CK, Horowitz M. Gastric emptying and glycaemia in health and diabetes mellitus. Nat Rev Endocrinol. 2015;11:112-28. [6] Wu T, Rayner CK, Young RL, Horowitz M. Gut motility and enteroendocrine secretion. Current opinion in pharmacology. 2013;13:928-34. [7] Camilleri M, Iturrino J, Bharucha AE, Burton D, Shin A, Jeong ID, et al. Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants. Neurogastroenterol Motil. 2012;24:1076-e562. [8] Horowitz M, Harding PE, Maddox AF, Wishart JM, Akkermans LM, Chatterton BE, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulindependent) diabetes mellitus. Diabetologia. 1989;32:151-9. [9] Mussa BM, Sood S, Verberne AJ. Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis. World J Gastroenterol. 2018;24:3821-33. [10] Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiological reviews. 2017;97:411-63. [11] Watson LE, Xie C, Wang X, Li Z, Phillips LK, Sun Z, et al. Gastric emptying in patients with well-controlled type 2 diabetes compared with young and older control subjects without diabetes. J Clin Endocrinol Metab. 2019;104:3311-9. [12] Wu T, Little TJ, Bound MJ, Borg M, Zhang X, Deacon CF, et al. A protein preload enhances the glucose-lowering efficacy of vildagliptin in type 2 diabetes. Diabetes Care. 2016;39:511-7. [13] Wu T, Bound MJ, Zhao BR, Standfield SD, Bellon M, Jones KL, et al. Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes. Diabetes Care. 2013;36:19138. [14] Wu T, Zhao BR, Bound MJ, Checklin HL, Bellon M, Little TJ, et al. Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans. Am J Clin Nutr. 2012;95:78-83. 16
[15] Jones KL, Rigda RS, Buttfield MDM, Hatzinikolas S, Pham HT, Marathe CS, et al. Effects of lixisenatide on postprandial blood pressure, gastric emptying and glycaemia in healthy people and people with type 2 diabetes. Diabetes Obes Metab. 2019;21:1158-67. [16] Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006;368:1681-8. [17] Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care. 2013;36:1789-96. [18] Schwartz JG, Mcmahan CA, Green GM, Phillips WT. Gastric emptying in Mexican Americans compared to non-Hispanic whites. Digestive Diseases & Sciences. 1995;40:624-30. [19] Kataoka M, Venn BJ, Williams SM, Te Morenga LA, Heemels IM, Mann JI. Glycaemic responses to glucose and rice in people of Chinese and European ethnicity. Diabet Med. 2013;30:e101-7. [20] Venn BS, Williams SM, Mann JI. Comparison of postprandial glycaemia in Asians and Caucasians. Diabet Med. 2010;27:1205-8. [21] Laway BA, Malik TS, Khan SH, Rather TA. Prevalence of abnormal gastric emptying in asymptomatic women with newly detected diabetes and its reversibility after glycemic control-a prospective case control study. J Diabetes Complications. 2013;27:78-81. [22] Watson LE, Phillips LK, Wu T, Bound MJ, Jones KL, Horowitz M, et al. Longitudinal evaluation of gastric emptying in type 2 diabetes. Diabetes Res Clin Pract. 2019;154:27-34. [23] Chang J, Russo A, Bound M, Rayner CK, Jones KL, Horowitz M. A 25-year longitudinal evaluation of gastric emptying in diabetes. Diabetes Care. 2012;35:25946. [24] Piha SJ. Cardiovascular autonomic reflex tests: normal responses and age-related reference values. Clinical physiology. 1991;11:277-90. [25] Collins PJ, Horowitz M, Cook DJ, Harding PE, Shearman DJ. Gastric emptying in normal subjects--a reproducible technique using a single scintillation camera and computer system. Gut. 1983;24:1117-25. [26] Chang J, Rayner CK, Jones KL, Horowitz M. Prognosis of diabetic gastroparesis-a 25-year evaluation. Diabet Med. 2013;30:e185-8. [27] Dubois A, . Obesity and gastric emptying. Gastroenterology. 1983;84:875-6. [28] Verdich C, Madsen JL, Toubro S, Buemann B, Holst JJ, Astrup A. Effect of obesity and major weight reduction on gastric emptying. Int J Obes Relat Metab Disord. 2000;24:899-905.
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Table 1. Demographics and the gastric half-emptying time of Han Chinese and Caucasian patients with type 2 diabetes.
Gender (male/female) Gastrointestinal disorder or surgery Smokers Use of medications known to affect gastrointestinal function Diabetic complications Treatments Age (years) BMI (kg/m2) HbA1c (%) HbA1c (mmol/mol) Fasting blood glucose (mmol/L) Duration of known diabetes (years)
Han Chinese (n=14) 10/4 None None None
Caucasians (n=14) 9/5 None None None
P value
None diet
None diet (n=7), metformin (n=7) 67.8 ± 1.5 31.2 ± 0.9 6.4 ± 0.2 46.1 ± 1.8 7.9 ± 0.4 3.8 ± 0.8
-
58.0 ± 2.4 23.6 ± 0.6 6.8 ± 0.2 51.2 ± 1.8 7.9 ± 0.4 3.0 ± 0.5
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ns -
P < 0.05 P < 0.05 ns ns ns ns
Figure legends: Figure 1. Blood glucose (A) and gastric emptying (B) in response to a high carbohydrate meal in Han Chinese (n = 14) and Caucasian (n = 14) patients with type 2 diabetes. Two factor-repeated measures ANOVA, with group and time as factors, was used to determine the statistical significance. Data are mean ± SEM.
Figure 2. The relationships of the increments in blood glucose at t = 60 min (A) and the iAUC0-60min for blood glucose (B) with the gastric half-emptying time (T50) in patients with type 2 diabetes (n = 28).
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Figure 1.
Figure 2.
B 15
r = -0.42 P < 0.05
Caucasian Han Chinese
10 5 0 20
40
60 80 T50 (min)
Blood glucose iAUC (t=0-60min, mmol/L*h-1)
Blood glucose, mmol/L (Δ baseline at t=60min)
A
100
20
8 6
r = -0.39 P < 0.05
4 2 0 20
40
60 80 T50 (min)
100