Prof. Ji Linong: Where does the saying that "East Asians have poor β-cell function" come from?

This article is published with the authorization of Professor Linong's team, please do not reprint without permission
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In the past, there has been a view in the academic community that "compared to Caucasians, East Asians have poor β-cell function", and on top of this, some scholars believe that "Asian type diabetes" is an independent subtype, treatment and management.
Strategies need to be differentiated from other ethnic groups with diabetes
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So, is the above view correct? Recently, Professor Ji Linong, director of the Endocrinology Department of Peking University People's Hospital, gave an academic speech on the topic of "2022 Peking University Hospital Standardized Diagnosis and Treatment Forum for Endocrine and Metabolic Diseases", and made a scientific inventory of relevant evidence
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 Expert introduction Professor Ji Linong, director of the Department of Endocrinology, Peking University People's Hospital, director of the Diabetes Center of Peking University, doctoral tutor
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As the principal investigator, he led 50 clinical trials of new drugs, including 3 in Phase I, 6 in Phase II, 31 in Phase III, and 9 in Phase IV, of which 10 were registered clinical studies of Class 1 new drugs independently developed by China.
He is the expert who has led the most clinical trials of new drugs in the field of endocrine and metabolic diseases so far, and the evidence-based medical evidence provided has contributed to major changes in international diabetes guidelines and clinical practice
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The team led by him, as a "Key Clinical Specialty of the Ministry of Health" and "Beijing Clinical Research Center in Diabetes Field", has been supported by a number of National Natural Science Foundation of China, and has served as national major scientific research projects including 863, key research and development projects, and Beijing Municipal Science and Technology Commission.
Chief Scientist of Major Projects
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Published more than 400 papers in first-class professional journals at home and abroad (including New England Journal of Medicine, Lancet, British Medical Journal, Lancet Diabetes & Metabolism, Diabetes Care, Nat Rev Endocrinol, Genetic Medicine, Diabetes, Cardiovascular Diabetology, etc.
) Elsevier Highly Cited Scholars in 2020 and 2021
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He has twice won the second prize of the National Science and Technology Progress Award (the second and third winners respectively) and the Chinese Medicine Award (the second finisher)
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At the same time, he is also the only expert in China who has held important leadership positions in several authoritative international diabetes academic organizations
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Professor Ji Linong is committed to introducing advanced disease diagnosis and treatment technologies and management concepts, and extensively conducting clinical research on the evaluation of new diabetes drugs
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 Where does the idea that East Asians have poor beta cell function come from? Previous studies have suggested that whether using the insulin secretion index calculated by continuous venous blood glucose monitoring [such as acute insulin response (AIR), etc.
] or using the fasting HOMA-β index, it was found that compared with Europeans and Americans, Africans, Asians ( Mainly East Asians) β-cell secretion indicators are relatively low
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 However, these studies have obvious limitations such as small sample size; only focusing on insulin secretion does not take into account the real situation of insulin resistance; β-cell function is also affected by age, gender,
etc.

For example, BMI is one of the strongest indicators associated with insulin resistance, and Asians have lower BMI levels and less insulin resistance than some ethnic groups
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So, is the decrease in insulin secretion in Asians due to the poor function of the beta cells themselves, or is it because the insulin resistance is mild and they don’t need as much insulin? Therefore, to understand whether there are ethnic differences in β-cell function, it is necessary to evaluate the relative relationship between β-cell secretion and insulin resistance under the influence of factors such as age, gender, and BMI, rather than just looking at insulin secretion itself
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 After "correcting" for insulin sensitivity, β-cell function in East Asians is similar to that in other ethnic groups.
Previous studies have used IVGTT results to analyze the relationship between β-cells and insulin resistance.
Also lighter (Figure A)
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However, the study did not quantitatively analyze beta cells and insulin resistance
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 Figure A: Corresponding relationship between insulin sensitivity index and β-cell secretion (acute insulin response to glucose) in the IVGTT study, suggesting that the cohort of East Asians (●) is mainly distributed in the lower right corner, showing low insulin secretion and higher insulin sensitivity
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 In order to further investigate whether there are ethnic differences in β-cell function, Professor Ji Linong's team retrieved and collected 118 published research cohorts including Africans, East Asians, and Caucasians, including a total of 76,354 cases (2,392 cases in the African group, A meta-analysis of the data of normal glucose tolerance subjects (6,645 cases in the white group and 67,317 cases in the East Asian group) was published under the title "Do East Asians With Normal Glucose Tolerance Have Worse b-Cell Function? A Meta-Analysis of Epidemiological Studies" In the academic journal Frontiers in Endocrinology
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 The study used the HOMA model to evaluate β-cell function (HOMA-β) and insulin resistance (or insulin sensitivity) (HOMA-IR or HOMA-S, HOMA-IR and HOMA-S have an inverse relationship) and further study the relationship between the two in the above-mentioned ethnic groups.
the law of interaction
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 The results showed a hyperbolic relationship between β-cell function and insulin resistance in all races (Panel B)
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If only the function of HOMA-β was compared, the level of HOMA-β in East Asians was significantly lower than that in Africans and Caucasians.
There was no significant difference between the two ethnic groups (Africans vs.
Whites P=0.
0885; Africans vs.
East Asians P=0.
1092; Whites vs.
East Asians P=0.
6298), indicating that after "correcting" insulin sensitivity, East Asians β-cell function is similar to that of Africans and Caucasians
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Panel B: Correlation of various ethnic insulin sensitivity (HOMAS) and beta-cell secretion (HOMA-B) in epidemiological studies
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Hyperbolic distributions of HOMA-β and HOMAS in East Asian populations (○), African populations (●) and Caucasians (●)
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(Note: The size of the scatter is proportional to the number of study cases in the cohort
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) The Asian cohort is distributed throughout the curve
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 This study is the first in the world to be based on data from a large-sample epidemiological study and to compare the hyperbolic distribution of β-cell function and insulin sensitivity in multiple ethnic groups, while further correcting for the influence of age, gender and BMI confounding factors to further in-depth It revealed that the actual islet function of the East Asian population was not worse than that of other ethnic groups, which also suggested that we must also consider the effect of insulin sensitivity when comparing β-cell function between different ethnic groups
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 Is it true that "Asian people respond worse to certain hypoglycemic drugs"? Also from the team of Professor Ji Linong from Peking University People's Hospital, Professor Cai Xiaoling's series of studies have comprehensively expounded the responsiveness of Asians to different hypoglycemic drugs
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 Alpha-glucosidase inhibitors: After removing the placebo effect, for alpha-glucosidase inhibitors, the meta-analysis suggested that there was no significant difference in the reduction of glycated hemoglobin between Asians and Caucasians [HbA1c change from baseline: -0.
5% (-0.
66%) , -0.
34%) vs -0.
68% (-0.
76%, -0.
60%), p=0.
08]; DPP-4 inhibitors: DPP-4 inhibitors that depend on β-cell function are more effective in Asians than Caucasians People were better [HbA1c change from baseline: -0.
81% (-0.
95%, -0.
68%) vs -0.
65% (-0.
70%, -0.
60%), p=0.
011]; SGLT2 inhibitors: in Asians and non- In Asians, HbA1c change from baseline: -0.
65% (-0.
73%, -0.
56%) vs -0.
60% (-0.
64%, -0.
56%), p>0.
05; GLP-1RA: Asian and white Compared with different species, the change from baseline in HbA1c with GLP-1RA: -0.
76% (-1.
19%, -0.
33%) vs -0.
79% (-0.
89%, -0.
69%), p>0.
05; insulin and analogs : Asians use premixed insulin and basal insulin regimens, and there is no significant difference in the compliance rate with non-Asian people
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  Therefore, there is currently no clear evidence that Asians respond worse to certain hypoglycemic drugs
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 Summary of the paper Although Asians may have a lower HOMA-beta index, the correspondence between HOMA-beta and HOMA-IR (islet function after correction of insulin resistance) in Asians is not significantly different from that in other ethnic groups
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In addition, there is currently insufficient evidence to confirm that Asians respond worse to certain hypoglycemic agents than other ethnic groups
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 Therefore, combined with the current clinical evidence, we believe that there are no significant differences in mechanisms and management of diabetes among Asians and other ethnic groups
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