Contribution of body mass index, waist circumference, and 25-OH-D3 on the risk of pre-diabetes mellitus in the Chinese population.

This study aimed to investigate the associations between body mass index (BMI), waist circumference (WC), 25-hydroxy-vitamin D3 (25-OH-D3), and the risk of pre-diabetes mellitus (PDM), as well as their predictive values in identifying PDM. A total of 1688 participants were included in this cross-sectional investigation. Spearman's correlation analysis was used to assess the relationships between candidate indicators and PDM. The impact of indicators on PDM risk was determined by multivariate logistic regression. The receiver operating characteristic (ROC) analysis was performed to evaluate the prognostic value of indicators. Our study indicated a positive correlation between WC, BMI, and 25-OH-D3 and PDM. WC (OR = 1.05, 95% CI = 1.04-1.06, p < 0.001), BMI (OR = 1.11, 95% CI = 1.08-1.15, p < 0.001), and 25-OH-D3 (OR = 1.01, 95% CI = 1.00-1.02, p = 0.037) and an increased risk of PDM. Additionally, the ROC analysis demonstrated that WC (AUC = 0.651, Specificity = 55.00%, Sensitivity = 67.900%) had a higher diagnostic value for predicting PDM compared to the other variables (BMI, 25-OH-D3, TG, TC, LDL-C, HDL-C, and UA). A cut-off value of WC > 80.5 cm predicted PDM with both good sensitivity and specificity. Additionally, the cut-off value of waist circumference (WC) for men with prediabetes was 86.500, while for women with prediabetes, it was 76.500.

A genome-wide association study identifies 25(OH)D3-associated genetic variants in the prediabetic Chinese population.

OBJECTIVES: Diabetes mellitus has been a significant public health problem, associated with high rates of morbidity, disability, and mortality. Prediabetes is a crucial period for preventing and managing diabetes. 25(OH)D3 is an important risk factor for prediabetes. However, there is limited genetic knowledge of 25(OH)D3 in the Chinese population. This study was designed to identify genetic variants associated with 25(OH)D3 and explore the potential pathogenesis of prediabetes. METHODS: In this study, 451 individuals with prediabetes were recruited to determine the genetic variants associated with 25(OH)D3 through a genome-wide association study (GWAS). Gene mapping and overrepresentation analysis (ORA) were further performed to explore the candidate genes and their biological mechanisms. RESULTS: In this study, we identified two independent significant loci (rs9457733 and rs11243373, p < 5 × 10-6 and r2 < 0.6) and 37 candidate genes associated with 25(OH)D3 in prediabetes. Furthermore, the ORA analysis revealed that two genes in the gene sets, SLC22A1 and SLC22A3, were found to be significantly enriched in monoamine transmembrane transporter activity and quaternary ammonium group transmembrane transporter activity, as determined by WebGestalt and g:Profiler (padj < 0.05). CONCLUSION: The identification of potential genes associated with 25(OH)D3 provides a foundation for a better understanding of the pathogenesis, diagnosis, and treatment of prediabetes.

MRPS6 modulates glucose-stimulated insulin secretion in mouse islet cells through mitochondrial unfolded protein response.

Lack of efficient insulin secretion from the pancreas can lead to impaired glucose tolerance (IGT), prediabetes, and diabetes. We have previously identified two IGT-associated single nucleotide polymorphisms (SNPs) rs62212118 and rs13052524 located at two overlapping genes: MRPS6 and SLC5A3. In this study, we show that MRPS6 but not SLC5A3 regulates glucose-stimulated insulin secretion (GSIS) in primary human ß-cell and a mouse pancreatic insulinoma ß-cell line. Data mining and biochemical studies reveal that MRPS6 is positively regulated by the mitochondrial unfolded protein response (UPRmt), but feedback inhibits UPRmt. Disruption of such feedback by MRPS6 knockdown causes UPRmt hyperactivation in high glucose conditions, hence elevated ROS levels, increased apoptosis, and impaired GSIS. Conversely, MRPS6 overexpression reduces UPRmt, mitigates high glucose-induced ROS levels and apoptosis, and enhances GSIS in an ATF5-dependent manner. Consistently, UPRmt up-regulation or down-regulation by modulating ATF5 expression is sufficient to decrease or increase GSIS. The negative role of UPRmt in GSIS is further supported by analysis of public transcriptomic data from murine islets. In all, our studies identify MRPS6 and UPRmt as novel modulators of GSIS and apoptosis in ß-cells, contributing to our understanding of the molecular and cellular mechanisms of IGT, prediabetes, and diabetes.

LASSO-based machine learning algorithm to predict the incidence of diabetes in different stages.

BACKGROUND: Formal risk assessment is crucial for diabetes prevention. We aimed to establish a practical nomogram for predicting the risk incidence of prediabetes and prediabetes conversion to diabetes. METHODS: A cohort of 1428 subjects was collected to develop prediction models. The LASSO was used to screen for important risk factors in prediabetes and diabetes and was compared with other algorithms (LR, RF, SVM, LDA, NB, and Treebag). Multivariate logistic regression analysis was used to construct the prediction model of prediabetes and diabetes, and drawn the predictive nomogram. The performance of the nomograms was evaluated by receiver-operating characteristic curve and calibration. RESULTS: These findings revealed that the other six algorithms were not as good as LASSO in terms of diabetes risk prediction. The nomogram for individualized prediction of prediabetes included "Age," "FH," "Insulin_F," "hypertension," "Tgab," "HDL-C," "Proinsulin_F," and "TG" and the nomogram of prediabetes to diabetes included "Age," "FH," "Proinsulin_E," and "HDL-C". The results showed that the two models had certain discrimination, with the AUC of 0.78 and 0.70, respectively. The calibration curve of the two models also indicated good consistency. CONCLUSIONS: We established early warning models for prediabetes and diabetes, which can help identify prediabetes and diabetes high-risk populations in advance.

Genome-wide association study of blood lipid levels in Southern Han Chinese adults with prediabetes.

Background: Dyslipidemia is highly prevalent among individuals with prediabetes, further exacerbating their cardiovascular risk. However, the genetic determinants underlying diabetic dyslipidemia in Southern Han Chinese remain largely unexplored. Methods: We performed a genome-wide association study (GWAS) of blood lipid traits in 451 Southern Han Chinese adults with prediabetes. Fasting plasma lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assayed. Genotyping was conducted using the Precision Medicine Diversity Array and Gene Titan platform, followed by genotype imputation using IMPUTE2 with the 1000 Genomes Project (Phase 3, Southern Han Chinese) as reference. Single nucleotide polymorphisms (SNPs) associated with lipid levels were identified using mixed linear regression, with adjustment for covariates. Results: We identified 58, 215, 74 and 81 novel SNPs associated with TG, TC, HDL-C and LDL-C levels, respectively (P < 5×10-5). Several implicated loci were located in or near genes involved in lipid metabolism, including SRD5A2, PCSK7, PITPNC1, IRX3, BPI, and LBP. Pathway enrichment analysis highlighted lipid metabolism and insulin secretion. Conclusion: This first GWAS of dyslipidemia in Southern Han Chinese with prediabetes identified novel genetic variants associated with lipid traits. Our findings provide new insights into genetic mechanisms underlying heightened cardiovascular risk in the prediabetic stage. Functional characterization of implicated loci is warranted.

Genome-wide association study of fasting proinsulin, fasting insulin, 2-hour postprandial proinsulin, and 2-hour postprandial insulin in Chinese Han people.

INTRODUCTION: Fasting proinsulin (FPI) and fasting insulin (FI) have been demonstrated to be associated with impaired b cell function, T2DM, and insulin resistance. This genome-wide association study (GWAS) was performed to contribute to our understanding of the genetic basis of FPI, FI, 2-hour postprandial proinsulin (2hPI), and 2-hour postprandial insulin (2hI) of the pathophysiology of prediabetes in the Chinese population. MATERIAL AND METHODS: The levels of fasting plasma glucose (FPG), FPI, FI, 2hPI, and 2hI were examined by an automatic biochemical analyser. The Applied BiosystemsTM AxiomTM Precision Medicine Diversity Array, the Gene Titan Multi-Channel instrument, and Axiom Analysis Suite 6.0 Software were used for genotyping. Imputation was performed with IMPUTE 2.0 software from HapMap, 1000 Genomes Phase 3 as a reference panel. RESULTS: Six single nucleotide polymorphisms (SNPs) in DLG1-AS1, SORCS1, and CTAGE11P for FPI, and 27 SNPs in ZNF718, MARCHF2, and HNRNPM for 2hPI reached genome-wide significance. Genome-wide significance was reached for associations of 6 SNPs in KRT71 to FI. Also, 14 SNPs in UBE2U, ABO, and GRID1-AS1 were genome-wide significant in their relationship with 2hI. Among these, the genetic loci of CTAGE11P, MARCHF2, KRT71, and ABO have the strongest association with FPI, 2hPI, FI, and 2hI. CONCLUSIONS: The genetic variants of CTAGE11P, MARCHF2, KRT71, and ABO are significantly correlated with FPI, 2hPI, FI, and 2hI, respectively, in Chinese Han people. These genetic variants may serve as new biomarkers for the prevention of prediabetes.

An Investigation on the Risk Factors of Thyroid Diseases in Community Population in Hainan.

Background: In recent years, the incidence of thyroid diseases has increased significantly, which has seriously affected people's work and life. The purpose of this study was to explore the epidemiological characteristics of thyroid diseases and autoantibodies. Method: According to the principle of overall sampling, resident residents ≥18 years and who will not move within 5 years are randomly selected. A total of 2136 eligible individuals were divided into case and control groups according to whether they have thyroid disease. Finally, the impact of potential risk factors on thyroid diseases was evaluated. Results: The overall prevalence of thyroid disease was 58.3%, and there was a significant difference in the prevalence of thyroid disease between women and men (p = 0.004). Except for the age group ≥70 years, with the increase in age, the prevalence gradually increased (p < 0.05). Participants with positive thyroid autoantibodies (TPOAb or TgAb) had a higher prevalence than participants with negative autoantibodies. The positive rate of autoantibodies in women was higher than that in men (p < 0.05). UIC (p = 0.004) and free thyroid hormone (FT4) (p = 0.001) levels of men were higher than those of women, and the TSH level of women was higher than that of men (p = 0.002). The regression analysis showed that women, older age, and family history of thyroid disease were independent risk factors for thyroid disease. Conclusion: The prevalence of thyroid diseases in Hainan was high. Women are more susceptible to thyroid disease than men, and the prevalence increased with age.

Genetic Variants Relate to Fasting Plasma Glucose, 2-Hour Postprandial Glucose, Glycosylated Hemoglobin, and BMI in Prediabetes.

Diabetes mellitus (DM) is a chronic disease that seriously threatens human health. Prediabetes is a stage in the progression of DM. The level of clinical indicators including fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), and glycosylated hemoglobin (HbA1C) are the diagnostic markers of diabetes. In this genome-wide association study (GWAS), we aimed to investigate the association of genetic variants with these phenotypes in Hainan prediabetes. In this study, we recruited 451 prediabetes patients from the residents aged ≥18 years who participated in the National Diabetes Prevalence Survey of the Chinese Medical Association in 2017. The GWAS of FPG, 2hPG, HbA1C, and body mass index (BMI) in prediabetes was analyzed with a linear model using an additive genetic model with adjustment for age and sex. We identified that rs13052524 in MRPS6 and rs62212118 in SLC5A3 were associated with 2hPG in Hainan prediabetes (p = 4.35 × 10-6, p = 4.05 × 10-6, respectively). Another six variants in the four genes (LINC01648, MATN1, CRAT37, and SLCO3A1) were related to HbA1C. Moreover, rs11142842, rs1891298, rs1891299, and rs11142843 in TRPM3/TMEM2 and rs78432036 in MLYCD/OSGIN1 were correlated to BMI (all p < 5 × 10-6). This study is the first to determine the genome-wide association of FPG, 2hPG, and HbA1C, which emphasizes the importance of in-depth understanding of the phenotypes of high-value susceptibility gene markers in the diagnosis of prediabetes.

A de novo pure 21q22.3 deletion in a 9-year-old boy with buried penis: a case report and literature review.

21q deletion has been associated with a wide range of clinical signs, from very mild to severe phenotypes, and with the progress of genetic technology, more patients with this deletion are being diagnosed. This study reports on a 9-year-old boy with a terminal deletion of 4.5 Mb on chromosome 21 in the locus of chr21: 43531239-48119895 (GRCh37/hg19). Dark skin, a buried penis, small testes, dental caries, microcephaly, a low auricle, mental and intellectual retardation, balance disorder and pituitary and callosum dysplasia were observed. The results of a literature review and observation of similar abnormalities, including hypoplasia of corpus callosum, in two patients with non-overlapping deletion regions suggest that there are multiple gene loci regulating brain development on 21q. By comparing the overlapped deletion region in 21q22.3 cases of brain anomalies and/or gonadal dysgenesis, we concluded there were two overlapped microdeletion regions (chr21:43531239-43792093 and chr21:46625055-46884297) that may be related to brain and gonadal development. The same 16.49 Mb deletion of chr21:31578129-48119895 (GRCh37/hg19) was shared in 10 cases, and 24 cases shared the same 5.59 Mb deletion of chr21:42478130-48119895 (GRCh37/hg19) in DECIPHER (Database of Chromasomal Imbalance and Phenotype in Humans using Ensembl Resources), suggesting these were two commonly deleted regions of pure partial 21q. Those patients with the same breakpoints had different phenotypes suggesting the heterogeneity of 21q deletion.

The Impact of Different Insulin-Related Measures on the Risk of Prediabetes Among the Chinese Han Population.

INTRODUCTION: Diabetes mellitus (DM) has a serious impact on people's lives in the world. Interventions that affect risk factors for prediabetes can prevent and reduce diabetes occurrence. Proinsulin (PI), true insulin (TI), and proinsulin to insulin ratio (PI/TI) are risk factors for diabetes. The roles of these indicators in prediabetes are unclear. This study aimed to evaluate the impact of PI, TI, PI/TI, 2-h proinsulin (2hPI), 2-h true insulin (2hTI), and 2hPI/2hTI on the risk of prediabetes among the Chinese Han population. METHODS: This cross-sectional study recruited 1688 subjects including 718 prediabetes cases and 970 non-prediabetes controls from Hainan Affiliated Hospital of Hainan Medical University. The cases involved 292 men and 426 women. The controls involved 324 men and 646 women. The mean age was 53.62 ± 12.43 years in the prediabetes group and 44.24 ± 12.87 years in the non-prediabetes group. RESULTS: Our results showed that PI, TI, PI/TI, 2hPI, 2hTI, and 2hPI/2hTI were significantly correlated with prediabetes (all p < 0.05). Logistic regression analysis revealed that PI (OR 1.022, 95% CI 1.014-1.031, p = 0.00011), TI (OR 1.005, 95% CI 1.003-1.007, p = 0.00012), PI/TI (OR 1.517, 95% CI 1.080-2.131, p = 0.016), and 2hTI (OR 1.000, 95% CI 1.000-1.001, p = 0.002) were significantly associated with an increased risk of prediabetes. Receiver operating characteristic curve (ROC) analysis indicated that the area under the ROC curve (AUC) of the combination (PI + TI + PI/TI + 2hPI + 2hTI + 2hPI/2hTI) in diagnosing prediabetes was 0.627, which was larger than the diagnostic value of HOMA-IR (AUC 0.614) and HOMA-ß (AUC 0.387). CONCLUSIONS: Our study showed that PI, TI, PI/TI, and 2hTI could significantly enhance the risk of prediabetes in the Chinese Han population, which suggested that PI, TI, PI/TI, and 2hTI might be available risk factors for prediabetes.

Low prevalence of vitamin D deficiency in adult residents in Hainan, the tropical island province of China.

BACKGROUND: Vitamin D deficiency is considered to be a global health problem. The purpose of this study was to evaluate the prevalence of vitamin D deficiency and analyze its related factors among adult residents in Hainan, a tropical island province of southern China. METHODS: A total of 1,700 healthy adults, aged 18-86 years (617 men and 1,073 women), were enrolled in our cross-sectional descriptive study. Binomial logistic regression analyses were performed to identify possible predictors of vitamin D status. RESULTS: The average serum 25-hydroxyvitamin D [25(OH)D] concentration was 37.66±10.77 ng/mL (males 43.60±11.8 ng/mL, females 34.20±8.40 ng/mL; I<0.001). The proportions of vitamin D sufficiency [25(OH)D ≥30 ng/mL], insufficiency [20 ng/mL ≤25(OH)D <30 ng/mL], and deficiency [25(OH)D <20 ng/mL] were 76.6%, 20.5%, and 2.9%, respectively. Vitamin D deficiency in the young, middle-aged, and elderly groups were 4.2%, 2.7%, and 1.7%, respectively. Vitamin D sufficiency was found to be positively associated with male sex (P<0.0001), age >40 years (P=0.014), habitation in a rural area (P<0.0001), summer/autumn seasons (P<0.0001), and having <13 years of formal education (P<0.0001). CONCLUSIONS: Our study was the first to assess the vitamin D status and analyze related factors among adult residents in Hainan Province, China. We found that vitamin D deficiency has low prevalence in this population, suggesting that before developing a strategy for the clinical use of vitamin D supplements in a region, the levels of vitamin D in generally healthy populations of that region should be assessed, to avoid unnecessary supplementation.

Type 2 diabetes is more predictable in women than men by multiple anthropometric and biochemical measures.

Men and women are sexually dimorphic but whether common anthropometric and biochemical parameters predict type 2 diabetes (T2D) in different ways has not been well studied. Here we recruit 1579 participants in Hainan Province, China, and group them by sex. We compared the prediction power of common parameters of T2D in two sexes by association, regression, and Receiver Operating Characteristic (ROC) analysis. HbA1c is associated with FPG stronger in women than in men and the regression coefficient is higher, consistent with higher prediction power for T2D. Age, waist circumference, BMI, systolic and diastolic blood pressure, triglyceride levels, total cholesterol, LDL, HDL, fasting insulin, and proinsulin levels all predict T2D better in women. Except for diastolic blood pressure, all parameters associate or tend to associate with FPG stronger in women than in men. Except for diastolic blood pressure and fasting proinsulin, all parameters associate or tend to associate with HbA1c stronger in women than in men. Except for fasting proinsulin and HDL, the regression coefficients of all parameters with FPG and HbA1c were higher in women than in men. Together, by the above anthropometric and biochemical measures, T2D is more readily predicted in women than men, suggesting the importance of sex-based subgroup analysis in T2D research.

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): A Report of a Chinese Family.

Maturity-onset diabetes mellitus of the young (MODY) is a monogenic diabetes characterized by autosomal dominant inheritance. Its atypical clinical features make diagnosis difficult and it can be misdiagnosed as type 1 or type 2 diabetes. Fourteen subtypes of MODY have been diagnosed so far, of which MODY12 is caused by mutation of the ABCC8 (ATP Binding Cassette Subfamily C Member 8) gene, which is rarely reported in China. This paper reports a Chinese family of MODY12 caused by a rare missense mutation on the ABCC8 gene, which has not been reported to be associated with MODY in China or in other countries, with the aim of increasing clinicians' awareness and attention to the disease.

An adolescent girl with premature ovarian failure, Graves' disease, and chronic urticaria: a case report.

BACKGROUND: Premature ovarian failure is characterized by amenorrhea, hypoestrogenism, and hypergonadotropinism, and occurs in women under 40 years of age. The prevalence of premature ovarian failure in women younger than 20 years of age is only 0.01%. Immune disorders are one of the causes of premature ovarian failure. Graves' disease and chronic urticaria are also associated with immune disorders. CASE PRESENTATION: We report a case of a 15-year-old Han Chinese girl with premature ovarian failure complicated by Graves' disease and chronic urticaria. She experienced menarche at 13 years of age and presented with amenorrhea after 7 months of irregular menstruation. Laboratory examinations indicated hypoestrogenism and hypergonadotropinism. Ultrasound imaging revealed that her uterus and ovaries were small in size. Gene and antibody tests related to premature ovarian failure returned negative results. Both thyroid peroxidase autoantibody and thyrotropin receptor antibody were positive. After reviewing the literature on the relationship between these three diseases and immune disorders, our patient was diagnosed as having atypical autoimmune polyglandular syndrome. After taking small doses of estrogen for 6 months, the size of her uterus increased, and her psychological anxiety was relieved. CONCLUSIONS: We report a case of an unusual association of premature ovarian failure, Graves' disease, and chronic urticaria. This case presents an atypical combination of adolescent autoimmune polyglandular syndrome, which is worthy of the attention of clinicians and presents an important lesson for them. Our case highlights that premature ovarian failure in adolescents requires long-term follow-up and medical treatment as well as psychological counselling.

The correlation between proinsulin, true insulin, proinsulin: True insulin ratio, 25(OH) D3, waist circumference and risk of prediabetes in Hainan Han adults.

PURPOSE: Diabetes mellitus is a kind of highly prevalent chronic disease in the world. The intervention measures on the risk factors of prediabetes contribute to control and reduce the occurrence of diabetes. This study aimed to investigate the correlation between proinsulin (PI), true insulin (TI), PI/TI, 25(OH) D3, waist circumference (WC), and risk of prediabetes. METHODS: In this cross-sectional study, 1662 subjects including 615 prediabetes and 1047 non-prediabetes were recruited. Spearman's correlation analysis was used to explore the association of PI, TI, PI/TI, 25(OH) D3, and waist circumference with prediabetes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Receiver-Operator Characteristic (ROC) curve was used to evaluate the risk of prediabetes. RESULTS: Our study showed that FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC could enhance the risk of prediabetes (OR 1.034; OR 1.007; OR 1.005; OR 1.002; OR 3.577, OR 1.053, respectively; all p< 0.001). Stratified analyses indicated that FPI/FTI associated with an increased risk of prediabetes in men (OR 2.080, p = 0.042). FTI have a weak association with prediabetes risk in men and women (OR 0.987, p = 0.001; OR 0.994, p = 0.004, respectively). 2hPI could decrease prediabetes in women (OR 0.995, p = 0.037). Interesting, the sensitivity (86.0%) and AUC (0.942, p< 0.001) of combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) were higher than the diagnostic value of these alone diagnoses. The optimal cutoff point of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC for indicating prediabetes were 15.5 mU/l, 66.5 mU/l, 71.5 mU/l, 460.5 mU/l, 35.5 ng/ml, and 80.5 cm, respectively. What's more, the combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) significantly improved the diagnostic value beyond the alone diagnoses of prediabetes in men and women (AUC 0.771; AUC 0.760, respectively). CONCLUSION: The FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC significantly associated with an increased risk of prediabetes. The combination of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC might be used as diagnostic indicators for prediabetes.

Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic ß-cells via MAPK/NF-kb signaling pathway.

Cyclophilin A is increased in the plasm of diabetic patients, while its effects on high glucose (HG)-stimulated pancreatic ß-cells are still pending. The aim of this research is to investigate the effects of cyclophilin A inhibition on HG-challenged pancreatic ß-cells. For investigating the effects of cyclophilin A decrease on HG-induced pancreatic ß-cells, the cells were separated into normal glucose (NG), Mannitol, HG, HG + shRNA-NC, and HG + shRNA-Cyclophilin A-1 groups. The protein and mRNA expression were detected via Western blot and qRT-PCR. CCK-8 assay and flow cytometry were employed for assessing cell viability and apoptosis. The levels of oxidative stress, inflammation, and insulin secretion were detected by corresponding kits. The cyclophilin A was higher in HG group. Knockdown of cyclophilin A was able to increase insulin secretion, decrease cell apoptosis, and alleviate inflammation as well as oxidant stress in HG-treated pancreatic ß-cells via MAPK/NF-kb pathway. Taken together, Cyclophilin A, highly expressed in pancreatic ß-cells induced by HG, is a promising therapeutic target for diabetes. Knockdown of cyclophilin A has protective effects against HG-challenged pancreatic ß-cells via regulation of MAPK/NF-kb pathway. The findings in this study provided a new strategy for diabetic treatment and paved the way for future researches on diabetes treatment.

Subgroup analysis of proinsulin and insulin levels reveals novel correlations to metabolic indicators of type 2 diabetes.

Proinsulin, insulin and proinsulin/insulin (P/I) ratio have been reported to be correlated with fasting plasma glucose (FPG) and Hemoglobin A1c (HbA1c) in whole population study therefore sensitive predictors of T2D progression. However, by analyzing data collected from 2018-2019 from a cohort of 1579 East Asian individuals from Hainan Province of China, we find that the associations of proinsulin, insulin and P/I ratio with diabetic indicators have distinct, sometimes opposite regression patterns in normal, prediabetic and diabetic subgroups. The strength of the associations are generally weak in normal and prediabetic groups, and only moderate in diabetic group between postprandial proinsulin and HbA1c, between postprandial insulin and FPG or HbA1c, and between postprandial P/I ratio and FPG or HbA1c. Receiver operating characteristic (ROC) curve analysis shows these parameters are weaker than age in predicting diabetes development, with P/I ratio being the weakest. Proinsulin and insulin levels are tightly associated with insulin sensitivity across all subgroups, as measured by Matsuda index. Together, our results suggest that proinsulin, insulin or P/I ratio are weak predictors of diabetes development in the whole population, urging the need for stratifying strategies and novel perspectives in evaluating and predicting hyperglycemia progression.