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

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.

Fig. 1. Burden of diabetes mellitus and its correlates in India and China.

a | Estimated number of adults with diabetes mellitus (millions) aged 20–79 years in India and China from 2000 with projections to 2030. b | Percentage of population residing in urban areas in India and China from 2000 with projections to 2030. c | Average daily dietary energy supply in India and China from 2000 with projections to 2030. Dietary energy supply indicates the amount of calories available for consumption in a given country; measures of individual caloric intake are not available at the national population level^,. d | Crude prevalence of diabetes mellitus in the states of India (2016) and provinces of China (2015–2017). Crude prevalence rates are shown to illustrate spatial distribution. Rates are not directly comparable between countries owing to differences in the age distribution between countries (comparable age-standardized data unavailable). In China and India, the rising prevalence of diabetes mellitus is driven by rapid urbanization, increased caloric intake and reduced physical activity^–. The high crude prevalence and number of people with diabetes mellitus in China relative to India is driven in part by China’s older age distribution^,. Panel a is derived from data from the International Diabetes Federation Atlas. Panel b is derived from data from the United Nations, Department of Economic and Social Affairs, & Population Division. Panel c is derived from data from the Food and Agriculture Organization of the United Nations^,. Panel d is derived from data from Tandon et al. and Li et al..

Fig. 2. Distinctive pathways of T2DM development commonly observed among Indian and Chinese populations.

This conceptualization is based on the epidemiological patterns of impaired fasting glucose (IFG) versus impaired glucose tolerance (IGT) prevalence observed in India and China, the known pancreatic β-cell defects associated with IFG and IGT and evidence from single-ethnic and multi-ethnic studies. In Indian populations, β-cell dysfunction often causes reduced first-phase insulin secretion. In the presence of increased insulin resistance, especially hepatic insulin resistance, Indian people have an increased risk of developing IFG, which might ultimately lead to type 2 diabetes mellitus (T2DM). In Chinese populations, β-cell dysfunction might predispose to globally impaired insulin secretion (reduced first-phase and second-phase insulin secretion). In the presence of insulin resistance, especially skeletal muscle insulin resistance, Chinese people have an increased risk of developing IGT, which might lead to T2DM. Hepatic insulin resistance and adiposity can be more severe in Indian people than in Chinese people, thus exacerbating insulin deficiency and causing relatively early (before age 40 years) and increased incidence of T2DM. Given the heterogeneous nature of T2DM pathogenesis, these features sometimes intersect within or vary between Indian and Chinese individuals.

Fig. 3. Key factors influencing the development of T2DM.

According to the developmental origins of health and disease hypothesis, fetal or early life exposure to undernutrition results in low birthweight and adaptive responses characterized by reduced β-cell secretion and increased insulin resistance. Genetic predisposition to type 2 diabetes mellitus (T2DM) probably also contributes to these changes, as proposed by the fetal insulin hypothesis. In the context of the rapid pace of urbanization in India and China, the postnatal environment often provides excess nutrition, which further exacerbates the risk of T2DM. Health-related behaviours such as low levels of physical activity, high caloric intake, poor sleep and smoking independently raise the risk of T2DM^–. Some genetic variants that predispose to T2DM seem to be unique among populations of east and south Asian ancestry. However, currently identified genetic variants explain <10% of the estimated 30–70% heritability of T2DM^–. This figure is not exhaustive; concepts have been simplified here for the purposes of illustration.