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Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

Nature Reviews Endocrinology volume 18, pages 413–432 (2022)Cite this article

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Abstract

Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China. These populations have an underlying predisposition to deficient insulin secretion, which has a key role in the pathogenesis of T2DM. Indian and Chinese people might be more susceptible to hepatic or skeletal muscle insulin resistance, respectively, than other populations, resulting in specific forms of insulin deficiency. Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian and Chinese people compared with European people. Individuals diagnosed earliest in life have the most aggressive course of disease and the highest risk of complications. These characteristics might contribute to distinctive responses to glucose-lowering medications. Incretin-based agents are particularly effective for lowering glucose levels in these populations; they enhance incretin-augmented insulin secretion and suppress glucagon secretion. Sodium–glucose cotransporter 2 inhibitors might also lower blood levels of glucose especially effectively among Asian people, while α-glucosidase inhibitors are better tolerated in east Asian populations versus other populations. Further research is needed to better characterize and address the pathophysiology and phenotypes of T2DM in Indian and Chinese populations, and to further develop individualized treatment strategies.

Key points

  • India and China account for nearly half of the global number of people with type 2 diabetes mellitus (T2DM), and incidence rates are rising rapidly among young people.

  • Indian and Chinese people seem to have increased susceptibility to reduced insulin secretion, which probably has a stronger or more frequent role than insulin resistance in the pathogenesis of T2DM than in other populations.

  • In many Indian people, deficient first-phase insulin secretion and increased hepatic insulin resistance result in impaired fasting glucose, while in many Chinese people, deficient first-phase and second-phase insulin secretion and increased skeletal muscle insulin resistance result in impaired glucose tolerance.

  • Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and demonstrate generally younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian people and Chinese people compared with European people.

  • Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists improve pancreatic β-cell function and reduce blood levels of glucose especially effectively in Indian and Chinese people compared with other populations.

  • Sodium–glucose cotransporter 2 inhibitors might lower blood levels of glucose more effectively in Asian people than in European people, while α-glucosidase inhibitors are better tolerated among east Asian people than in other populations.

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Fig. 1: Burden of diabetes mellitus and its correlates in India and China.
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Fig. 2: Distinctive pathways of T2DM development commonly observed among Indian and Chinese populations.
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Fig. 3: Key factors influencing the development of T2DM.
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Acknowledgements

C.K. was supported by the Canadian Institutes of Health Research and the South Asian Network Supporting Awareness and Research. The authors thank S. H. (Hana) Fu, Centre for Global Health Research, for her assistance in preparing the map and thank X. Zou for providing the numerical data underlying Figure A from her study114 for inclusion in Table 1.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Calvin Ke & Baiju R. Shah

  2. Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada

    Calvin Ke

  3. Centre for Global Health Research, Unity Health Toronto, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Calvin Ke & Prabhat Jha

  4. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

    Calvin Ke & Juliana C. N. Chan

  5. Asia Diabetes Foundation, Shatin, Hong Kong SAR, China

    Calvin Ke & Juliana C. N. Chan

  6. Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    K. M. Venkat Narayan

  7. Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA

    K. M. Venkat Narayan

  8. Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA

    K. M. Venkat Narayan

  9. Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

    Juliana C. N. Chan

  10. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

    Juliana C. N. Chan

  11. Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

    Baiju R. Shah

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Contributions

C.K. researched data for the article, wrote the article, contributed substantially to the discussion of content and reviewed and/or edited the manuscript before submission. K.M.V.N, J.C.N.C., P.J. and B.R.S. contributed substantially to the discussion of content and reviewed and/or edited the manuscript before submission.

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Correspondence to Calvin Ke.

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C.K. reports consulting fees and honoraria from Sanofi, Abbott, and AstraZeneca. The other authors declare no competing interests.

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Nature Reviews Endocrinology thanks Sanjay Kalra, who co-reviewed with Madhur Verma, and Yingli Lu for their contribution to the peer review of this work.

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Glossary

Person-years

The unit of measurement that accounts for the total amount of time that individuals are at risk of developing a condition, often used in the denominators of incidence rates.

Glucolipotoxicity

Toxicity to the pancreatic β-cells arising from chronically elevated levels of glucose and fatty acids.

Endogamy

The practice of marrying within one’s own social group.

Lipodystrophy

A rare group of disorders characterized by partial or generalized loss of adipose tissue.

Latent autoimmune diabetes mellitus of adulthood

A type of diabetes mellitus that presents in adulthood with immunogenetic markers of type 1 diabetes mellitus, but that does not require insulin at the time of diagnosis.

Glycaemic deterioration rate

An epidemiological measure of the speed of progression of diabetes mellitus, calculated as the slope of HbA1c over time after statistical adjustment for glucose-lowering drugs (this rate cannot be determined for people treated with insulin).

Glycaemic relapse

The recurrence of type 2 diabetes mellitus (T2DM) in an individual who previously had T2DM in remission.

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Ke, C., Narayan, K.M.V., Chan, J.C.N. et al. Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations. Nat Rev Endocrinol 18, 413–432 (2022). https://doi.org/10.1038/s41574-022-00669-4

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