Characteristics of the pathophysiology of type 2 diabetes in Asians
Review Article

Characteristics of the pathophysiology of type 2 diabetes in Asians

Young Min Cho

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Young Min Cho, MD, PhD. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Email: ymchomd@snu.ac.kr.

Abstract: Asia is considered as the epicenter of recent worldwide epidemic of diabetes owing to its large population and high prevalence of diabetes. In Asia, type 1 diabetes is relatively rare in comparison with European countries. Therefore, the rapid increase in the prevalence of type 2 diabetes is the driving force of the epidemic. Interestingly, the phenotypes of Asian type 2 diabetes are distinct as compared by non-Asians, particularly Caucasians. Asian type 2 diabetes patients are generally non-obese, have a prominent impairment in insulin secretion and a better insulin sensitivity than non-Asians. Whereas incretin effect is remarkably reduced in European patients with type 2 diabetes, Asian patients with type 2 diabetes exhibited a similar incretin effect compared to non-diabetic subjects. Type 2 diabetes diagnosed by isolated postprandial hyperglycemia is more common in Asia than in Europe. Interestingly, glucose lowering efficacy is greater in Asians than in non-Asians. Genetic backgrounds in both nuclear and mitochondrial genome are different among ethnic groups, which may contribute to unique features of type 2 diabetes found in Asians. Considering the differences in pathophysiology and clinical features of Asian type 2 diabetes, we need to use different approach in diagnosis and management of type 2 diabetes including selecting patients eligible for bariatric/metabolic surgery.

Keywords: Asian; type 2 diabetes mellitus; pathophysiology; insulin secretion; insulin sensitivity


Received: 04 December 2016; Accepted: 20 December 2016; Published: 08 February 2017.

doi: 10.21037/ales.2017.01.03


Introduction

Asia, where 60% of world population live, is the epicenter of the current worldwide epidemic of diabetes. Because type 1 diabetes is relatively rare in Asia compared to Western countries, the driving force of recent diabetes epidemic in Asia is the steep increase in the prevalence of type 2 diabetes. Type 2 diabetes is a result of the interplay among multiple genetic and environmental factors. Considering that Asians have different genetic backgrounds and culture including food and other lifestyle factors, it is not surprising that they have different characteristics of type 2 diabetes. In addition, the differences in pathophysiology of type 2 diabetes may result in different responses to anti-diabetes drugs compared to other ethnic groups. In the same line, increasing evidence suggests that the cutoff for body mass index (BMI) for bariatric/metabolic surgery needs to be reduced in Asians.


Characteristics of the pathophysiology of Asian type 2 diabetes

A lower BMI

Prevalence of obesity, which is defined by a BMI cutoff of 30 kg/m2, is approximately 30% in diabetes patient in the US (1). Notably, the prevalence of obesity in East Asian diabetes patients is only 3–4% (1). However, the prevalence of diabetes between the US and East Asia is similar, around 8% (1). The precise mechanism of increased diabetes risk in spite of a lower BMI in East Asians is not clearly understood. Intriguingly, East Asians have a higher visceral fat area, which is related to insulin resistance, at a given waist circumference than in Caucasians (2,3). In a cross-sectional study of 490,288 UK Biobank participants including 1,534 Chinese, a BMI cutoff of 24.0 kg/m2 for Chinese women and 26.0 kg/m2 for Chinese men was estimated to show a similar prevalence of diabetes at a BMI cutoff of 30 kg/m2 for white people (4). The equivalent waist circumference for a same prevalence of diabetes was 88 and 74 cm in white and Chinese women; 102 and 88 cm in white and Chinese men, respectively (4). Further studies are necessary to elucidate the mechanism of increased diabetes risk at a lower degree of obesity in Asians.

Impaired insulin secretion rather than insulin resistance is the major defect

From an insulinocentric view point, type 2 diabetes is a result of the interplay of insulin secretion and action. A meta-analysis compared insulin sensitivity and acute insulin response during frequently sampled intravenous glucose tolerance tests in Africans, Caucasians, and East Asians (5), showed a higher insulin sensitivity and a lower acute insulin response in East Asians than other races across all glucose tolerance categories [normal glucose tolerance (NGT), impaired glucose regulation, and type 2 diabetes].

In a prospective cohort study with a median follow-up duration of 9.7 years (Whitehall II study), which included 6,538 British civil servants without diabetes at baseline, insulin sensitivity decreased during the 5 years before the onset of diabetes whereas beta-cell function increased 3–4 years before the onset and thereafter decreased in a rapid pace (6). In this study, insulin sensitivity and beta-cell function were estimated by the homeostasis model assessment (HOMA) methods, which use fasting plasma insulin and glucose levels. The biphasic beta-cell response to decreasing insulin sensitivity observed in this study suggests a compensatory effort of pancreatic beta-cells to meet the increased insulin demand to overcome prevailing insulin resistance, which is not sustainable over a long period of time for people who develop diabetes.

Our group also followed up 4,106 Koran subjects with NGT for 10 years with biennial oral glucose tolerance tests (OGTT) (the Korean Genome and Epidemiology Study) (7). Pancreatic beta-cell function and insulin sensitivity were estimated by the 60-min insulinogenic index and composite insulin sensitivity index (Matsuda index), which utilize both fasting and post-challenge levels of glucose and insulin during the OGTT. At baseline, even though all the subjects had NGT, beta-cell function was lower by 35.4% and insulin sensitivity was also lower by 18.0% in subjects who developed diabetes than in those who remained as NGT. Those who remained as NGT showed a decline in insulin sensitivity but they showed a compensatory increase in beta-cell function (7). In contrast, those who developed diabetes also showed a decline in insulin sensitivity over the 10-year time period. However, they did not show such compensatory increase in beta-cell function (7). Therefore, most Korean people who develop type 2 diabetes do not exhibit beta-cell compensation to meet the increased demand for insulin with decreasing insulin sensitivity over time.

Despite the striking differences in insulin secretion and insulin sensitivity between Caucasians and East Asians, direct comparison in a large scale has been done only recently. A cross-sectional study with 120 Japanese (mean BMI was 25.0 kg/m2) and 150 Europeans (mean BMI was 30.8 kg/m2) with NGT, impaired glucose tolerance (IGT), and type 2 diabetes, 5-hour OGTTs with the same protocol and the same analytic methods were performed (8). As was shown in other previous studies, Japanese subjects exhibited a higher insulin sensitivity, which was assessed by HOMA insulin resistance and Matsuda index, and a lower insulin secretory capacity, which was assessed by 30-min insulinogenic index and HOMA beta-cell function, than Europeans. However, after adjusting the difference in BMI between the two ethnic groups, all these indices of beta-cell function and insulin sensitivity became comparable, which indicated that the BMI is a main determinant of the differences in those indices between Japanese and Europeans. Intriguingly, the disposition index (the product of insulinogenic index and Matsuda index), which indicates the beta-cell function considering insulin sensitivity, was comparable between Japanese and Europeans. Therefore, it is conceivable that the apparently lower beta-cell function is appropriate for the higher insulin sensitivity in Japanese to maintain normal glucose homeostasis. However, it is unknown whether Japanese or other East Asian people can further increase beta-cell function to maintain NGT when they have a higher insulin resistance similar to Europeans.

Morphometric quantification of beta-cell area from pathology specimens in Korea (9) and Japan (10) showed that beta-cell mass was reduced in patients with type 2 diabetes compared to non-diabetic controls. In association with decreased beta-cell mass, increased alpha-cell mass (9) and increased oxidative stress (10) were noted in the pancreas of type 2 diabetes. In a Chinese autopsy study with 235 patients with type 2 diabetes and 533 non-diabetic subjects, islet amyloid deposits and pancreatic arteriosclerosis were more frequently found in patients with type 2 diabetes (11). However, whether beta-cell mass is lower in Asians than in Caucasians has not been directly evaluated.

Postprandial hyperglycemia

Comparing the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia (DECODA) (12) and the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) (13) study, postprandial hyperglycemia is more common in Asians than in Caucasians. The prevalence of isolated postprandial hyperglycemia was 37% and 30% in DECODA and DECODE, respectively, whereas the prevalence of isolated impaired fasting glucose was 18% and 35% in DECODA and DECODE, respectively. In addition, more than half the patients with diabetes in the DECODA study was diagnosed by isolated postprandial hyperglycemia (14). The mechanism of prominent postprandial hyperglycemia found in Asians needs to be elucidated. However, it can be partly explained by the fact that both dynamic and static beta-cell responses during the OGTT are lower in Asians than in Caucasians (15). To explain the difference in postprandial glucose control, hepatic glucose production after glucose challenge should be compared between Asians and Caucasians.

Preserved incretin effect

We have two incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) (16-18). GIP and GLP-1 are secreted from enteroendocrine cells such as K-cells and L-cells, respectively, in response to absorption of glucose, fatty acids, and amino acids from the gut lumen. Thereafter, GIP and GLP-1 augment insulin secretion from pancreatic beta-cells triggered by hyperglycemia. In the past, decreased GLP-1 secretion was considered a contributing factor for the development of type 2 diabetes based on findings from earlier studies (19). However, a meta-analysis revealed that GLP-1 secretion is not decreased in type 2 diabetes (20). In addition, there is no evidence of altered GIP secretion in type 2 diabetes as shown in another meta-analysis (21). In East Asians, postprandial plasma levels of GLP-1 and GIP are also comparable between NGT and type 2 diabetes [reviewed in ref (22)].

The incretin effect is defined as the contribution of the gastrointestinal tract to postprandial insulin secretion in response to oral glucose challenge, which can be measured by two ways. Firstly, isoglycemic intravenous glucose infusion (IIGI), which reproduces the glucose excursion during the OGTT, is the gold standard method to measure incretin effect (23). Given the plasma glucose levels are identical (isoglycemic), the proportion of insulin secretion triggered by the gastrointestinal absorption of glucose can be calculated by subtracting insulin secretion during the IIGI from insulin secretion during the OGTT. Secondly, the hyperglycemic clamp with oral glucose challenge is the other option (24). After achieving steady state hyperglycemia at a certain plasma glucose level, 75 g of glucose is administered orally. By adjusting the glucose infusion rate, the plasma glucose levels can be maintained at the same steady state level after the glucose challenge. Because the plasma glucose levels are the same before and after the oral glucose challenge, we can estimate the effect of oral ingestion of glucose on insulin secretion by comparing the two different phases. In Europeans, the incretin effect measured by the IIGI method was consistently decreased in type 2 diabetes (10–40%) as compared by NGT (50–70%) (25-29). However, in Koreans (23) and Japanese (30), there is no difference in the incretin effect measured by the IIGI method between type 2 diabetes and NGT. With the hyperglycemic clamp with oral glucose challenge, there was no difference in the incretin effect between NGT and type 2 diabetes in Koreans (24). The mechanism of the discrepant results in terms of incretin effect between Asians and Caucasians may be partly explained by genetic factors (22), but further studies are warranted.

The lack of difference in the incretin effect between NGT and type 2 diabetes observed in Asians does not necessarily mean that there is no difference in the contribution of the gastrointestinal tract to postprandial glucose metabolism between NGT and type 2 diabetes. Whereas the incretin effect addresses the insulin secretion during the OGTT, the relatively new concept called gastrointestinally-mediated glucose disposal (GIGD) deals with the gastrointestinal contribution to the glucose homeostasis during the OGTT, which is calculated by the data from the OGTT and corresponding IIGI (31). Although there was no difference in the incretin effect between Korean subjects with NGT and type 2 diabetes (23), the GIGD during the OGTT was remarkably decreased in type 2 diabetes (~30%) as compared to NGT (~60%) in the same Korean study (23). In addition, the incretin effect is not an equivalent term to the effect of GLP-1 or GIP. We found the effect of intravenous GLP-1 infusion on insulin secretion during a hyperglycemic clamp is remarkably decreased in Korean subjects with type 2 diabetes compared to those with NGT (unpublished data).

Intriguingly, the glucose-lowering response to incretin-based therapies for type 2 diabetes such as dipeptidyl peptidase-4 inhibitors and GLP-1 receptor agonists are generally greater in Asians than in non-Asians (32,33). However, this notion cannot be supported by the contradicting observations such as preserved incretin effect, preserved incretin secretion, decreased GIGD, and decreased insulinotropic effect of GLP-1 in Asian patients with type 2 diabetes, as explained above. Rather, the greater glucose-lowering efficacy of incretin-based therapies in Asians than in non-Asians can be explained by better insulin sensitivity and a lower BMI (22).

Genetic differences

With innovative advance in genotyping technology, the genetic landscape of type 2 diabetes has been largely revealed. In a trans-ancestry meta-analysis on genome-wide association studies performed in East Asians, South Asians, Europeans, and Mexican Americans exhibited similarities and differences in genetic makeups of type 2 diabetes among different ethnic groups (34). Among them, the risk allele frequency of a variant (rs7903146) in TCF7L2, a well-known type 2 diabetes gene, showed a striking difference between East Asians (5%) and Europeans (30%). Interestingly, TCF7L2 plays an important role in modulating beta-cell responses to GLP-1 and GIP by regulating the gene expression of respective receptors (35-39). Aside from nuclear DNA variants, mitochondrial DNA (mtDNA) polymorphisms/mutations are also important in conveying the susceptibility to diabetes as exemplified by mtDNA A3243G mutation (40) and mtDNA T16189C polymorphism (41). Because mtDNA is inherited exclusively through the maternal lineage and highly variable compared to nuclear DNA, it is a useful tool to explore the human migration out of Africa in prehistoric age. Highly variable mtDNAs can be grouped as mtDNA haplogroups, which show clear differences among ethnic groups. Although common mtDNAs are not associated with type 2 diabetes in Europeans (42), common Asian mtDNA haplogroups such as N9a, D5 and F confer susceptibility to type 2 diabetes in Koreans and Japanese (43). However, N9a, D5 and F did not show any apparent effects on mitochondrial function in a study with a cybrid cell system in vitro (44). Therefore, they may confer susceptibility to type 2 diabetes in a very complicated way influenced by other genetic and environmental factors (45). Taken together, differences in both nuclear and mitochondrial genome may contribute to the unique phenotype of Asian type 2 diabetes.


Conclusions

As explained in this review (Table 1), the phenotype of Asian type 2 diabetes is unique in comparison with that of non-Asians, particularly European descendants. Therefore, the different ethnic background should be considered in diagnosis and treatment of patients with type 2 diabetes. For example, most non-obese patients with diabetes have type 2 diabetes rather than type 1 diabetes and they can be effectively and safely managed with incretin-based therapies. Recent guidelines on bariatric/metabolic surgery recommend a lower BMI criteria for Asians. It is recommended that bariatric/metabolic surgery for patients with type 2 diabetes should be considered in cases with a BMI of 35 kg ⁄m2 or more or in cases with a BMI between 30 and 35 kg ⁄m2 and poor glycemic control despite medical treatment. For Asians, it is recommended that the BMI criteria can be lowered by 2.5 kg/m2 based on the clinical differences of type 2 diabetes among ethnic groups (46-48). Further studies are required to elucidate the underlying mechanisms of ethnic differences of the phenotypes of type 2 diabetes, which will improve personalized approach in the management of type 2 diabetes.

Table 1
Table 1 Summary of pathophysiologic characteristics of Asian type 2 diabetes
Full table

Acknowledgements

Funding: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277).


Footnote

Conflicts of Interest: The author has no conflicts of interest to declare.


References

  1. Yoon KH, Lee JH, Kim JW, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006;368:1681-8. [Crossref] [PubMed]
  2. Kadowaki T, Sekikawa A, Murata K, et al. Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study. Int J Obes (Lond) 2006;30:1163-5. [Crossref] [PubMed]
  3. Tanaka S, Horimai C, Katsukawa F. Ethnic differences in abdominal visceral fat accumulation between Japanese, African-Americans, and Caucasians: a meta-analysis. Acta Diabetol 2003;40 Suppl 1:S302-4. [Crossref] [PubMed]
  4. Ntuk UE, Gill JM, Mackay DF, et al. Ethnic-specific obesity cutoffs for diabetes risk: cross-sectional study of 490,288 UK biobank participants. Diabetes Care 2014;37:2500-7. [Crossref] [PubMed]
  5. Kodama K, Tojjar D, Yamada S, et al. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care 2013;36:1789-96. [Crossref] [PubMed]
  6. Tabák AG, Jokela M, Akbaraly TN, et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009;373:2215-21. [Crossref] [PubMed]
  7. Ohn JH, Kwak SH, Cho YM, et al. 10-year trajectory of beta-cell function and insulin sensitivity in the development of type 2 diabetes: a community-based prospective cohort study. Lancet Diabetes Endocrinol 2016;4:27-34. [Crossref] [PubMed]
  8. Møller JB, Pedersen M, Tanaka H, et al. Body composition is the main determinant for the difference in type 2 diabetes pathophysiology between Japanese and Caucasians. Diabetes Care 2014;37:796-804. [Crossref] [PubMed]
  9. Yoon KH, Ko SH, Cho JH, et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003;88:2300-8. [Crossref] [PubMed]
  10. Sakuraba H, Mizukami H, Yagihashi N, et al. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia 2002;45:85-96. [Crossref] [PubMed]
  11. Zhao HL, Lai FM, Tong PC, et al. Prevalence and clinicopathological characteristics of islet amyloid in chinese patients with type 2 diabetes. Diabetes 2003;52:2759-66. [Crossref] [PubMed]
  12. DECODA Study Group; International Diabetes Epidemiology Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals--an evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med 2002;19:549-57. [Crossref] [PubMed]
  13. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. BMJ 1998;317:371-5. [Crossref] [PubMed]
  14. Qiao Q, Hu G, Tuomilehto J, et al. Age- and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts. Diabetes Care 2003;26:1770-80. [Crossref] [PubMed]
  15. Møller JB, Dalla Man C, Overgaard RV, et al. Ethnic differences in insulin sensitivity, beta-cell function, and hepatic extraction between Japanese and Caucasians: a minimal model analysis. J Clin Endocrinol Metab 2014;99:4273-80. [Crossref] [PubMed]
  16. Cho YM, Kieffer TJ. K-cells and glucose-dependent insulinotropic polypeptide in health and disease. Vitam Horm 2010;84:111-50. [Crossref] [PubMed]
  17. Cho YM, Fujita Y, Kieffer TJ. Glucagon-like peptide-1: glucose homeostasis and beyond. Annu Rev Physiol 2014;76:535-59. [Crossref] [PubMed]
  18. Cho YM, Merchant CE, Kieffer TJ. Targeting the glucagon receptor family for diabetes and obesity therapy. Pharmacol Ther 2012;135:247-78. [Crossref] [PubMed]
  19. Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717-23. [Crossref] [PubMed]
  20. Calanna S, Christensen M, Holst JJ, et al. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia 2013;56:965-72. [Crossref] [PubMed]
  21. Calanna S, Christensen M, Holst JJ, et al. Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes: systematic review and meta-analysis of clinical studies. Diabetes Care 2013;36:3346-52. [Crossref] [PubMed]
  22. Cho YM. Incretin physiology and pathophysiology from an Asian perspective. J Diabetes Investig 2015;6:495-507. [Crossref] [PubMed]
  23. Oh TJ, Kim MY, Shin JY, et al. The incretin effect in Korean subjects with normal glucose tolerance or type 2 diabetes. Clin Endocrinol (Oxf) 2014;80:221-7. [Crossref] [PubMed]
  24. Oh TJ, Park KS, Cho YM. Correlation of the incretin effect with first- and second-phase insulin secretions in Koreans with various glucose tolerance statuses. Clin Endocrinol (Oxf) 2015;83:59-66. [Crossref] [PubMed]
  25. Nauck M, Stockmann F, Ebert R, et al. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986;29:46-52. [Crossref] [PubMed]
  26. Bagger JI, Knop FK, Lund A, et al. Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 2011;96:737-45. [Crossref] [PubMed]
  27. Nauck MA, Homberger E, Siegel EG, et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986;63:492-8. [Crossref] [PubMed]
  28. Choukem SP, Gautier JF. Comment on: Knop et al. (2007) Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 56:1951-1959. Diabetes 2008;57:e1; author reply e2-3.
  29. Meier JJ, Nauck MA. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes 2010;59:1117-25. [Crossref] [PubMed]
  30. Hamasaki AH, Muraoka A, Yamane S, et al. Not glucose tolerance but obesity impairs the numerical incretin effect in Japanese subjects. Diabetologia 2011;54:S1-S543. [PubMed]
  31. Holst JJ, Knop FK, Vilsboll T, et al. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 2011;34 Suppl 2:S251-7. [Crossref] [PubMed]
  32. Kim YG, Hahn S, Oh TJ, et al. Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis. Diabetes Obes Metab 2014;16:900-9. [Crossref] [PubMed]
  33. Kim YG, Hahn S, Oh TJ, et al. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 2013;56:696-708. [Crossref] [PubMed]
  34. Mahajan A, Go MJ, Zhang W, et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet 2014;46:234-44. [Crossref] [PubMed]
  35. Lyssenko V, Lupi R, Marchetti P, et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 2007;117:2155-63. [Crossref] [PubMed]
  36. Pilgaard K, Jensen CB, Schou JH, et al. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia 2009;52:1298-307. [Crossref] [PubMed]
  37. Schäfer SA, Tschritter O, Machicao F, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 2007;50:2443-50. [Crossref] [PubMed]
  38. Shu L, Matveyenko AV, Kerr-Conte J, et al. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 2009;18:2388-99. [Crossref] [PubMed]
  39. Villareal DT, Robertson H, Bell GI, et al. TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action. Diabetes 2010;59:479-85. [Crossref] [PubMed]
  40. Shin CS, Kim SK, Park KS, et al. A new point mutation (3426, A to G) in mitochondrial NADH dehydrogenase gene in Korean diabetic patients which mimics 3243 mutation by restriction fragment length polymorphism pattern. Endocr J 1998;45:105-10. [Crossref] [PubMed]
  41. Park KS, Chan JC, Chuang LM, et al. A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians. Diabetologia 2008;51:602-8. [Crossref] [PubMed]
  42. Saxena R, de Bakker PI, Singer K, et al. Comprehensive association testing of common mitochondrial DNA variation in metabolic disease. Am J Hum Genet 2006;79:54-61. [Crossref] [PubMed]
  43. Fuku N, Park KS, Yamada Y, et al. Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet 2007;80:407-15. [Crossref] [PubMed]
  44. Hwang S, Kwak SH, Bhak J, et al. Gene expression pattern in transmitochondrial cytoplasmic hybrid cells harboring type 2 diabetes-associated mitochondrial DNA haplogroups. PLoS One 2011;6:e22116. [Crossref] [PubMed]
  45. Cho YM, Park KS, Lee HK. Genetic factors related to mitochondrial function and risk of diabetes mellitus. Diabetes Res Clin Pract 2007;77 Suppl 1:S172-7. [Crossref] [PubMed]
  46. Dixon JB, Zimmet P, Alberti KG, et al. Bariatric surgery: an IDF statement for obese Type 2 diabetes. Diabet Med 2011;28:628-42. [Crossref] [PubMed]
  47. Rubino F, Nathan DM, Eckel RH, et al. Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. Diabetes Care 2016;39:861-77. [Crossref] [PubMed]
  48. National Clinical Guideline Centre (UK). Obesity: Identification, Assessment and Management of Overweight and Obesity in Children, Young People and Adults: Partial Update of CG43. National Institute for Health and Clinical Excellence: Guidance. London: National Institute for Health and Care Excellence (UK); 2014 Nov.
doi: 10.21037/ales.2017.01.03
Cite this article as: Cho YM. Characteristics of the pathophysiology of type 2 diabetes in Asians. Ann Laparosc Endosc Surg 2017;2:14.