[Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate]. / è‹¯ä¸é ¸ç”˜æ²¹é ¯æ²»ç–—å„¿ç«¥é¸Ÿæ°¨é ¸æ°¨ç”²é °åŸºè½¬ç§»é ¶ç¼ºä¹ç—‡1例.

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 µmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 µmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.

Screening/diagnosis of pediatric endocrine disorders through the artificial intelligence model in different language settings.

This study is aimed at examining the impact of ChatGPT on pediatric endocrine and metabolic conditions, particularly in the areas of screening and diagnosis, in both Chinese and English modes. A 40-question questionnaire covering the four most common pediatric endocrine and metabolic conditions was posed to ChatGPT in both Chinese and English three times each. Six pediatric endocrinologists evaluated the responses. ChatGPT performed better when responding to questions in English, with an unreliable rate of 7.5% compared to 27.5% for Chinese questions, indicating a more consistent response pattern in English. Among the reliable questions, the answers were more comprehensive and satisfactory in the English mode. We also found disparities in ChatGPT's performance when interacting with different target groups and diseases, with improved performance for questions posed by clinicians in English and better performance for questions related to diabetes and overweight/obesity in Chinese for both clinicians and patients. Language comprehension, providing incomprehensive answers, and errors in key data were the main contributors to the low scores, according to reviewer feedback. CONCLUSION: Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment. WHAT IS KNOWN: • The deep learning-based large-language model ChatGPT holds great promise for improving clinical practice for both physicians and patients and has the potential to increase the speed and accuracy of disease screening and diagnosis, as well as enhance the overall efficiency of the medical process. However, the reliability and appropriateness of AI model responses in specific field remains unclear. • This study focused on the reliability and appropriateness of AI model responses to straightforward and fundamental questions related to the four most prevalent pediatric endocrine and metabolic disorders, for both healthcare providers and patients, in different language scenarios. WHAT IS NEW: • The AI model performed better when responding to questions in English, with more consistent, as well as more comprehensive and satisfactory responses. In addition, we also found disparities in ChatGPT's performance when interacting with different target groups and different diseases. • Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment.

Genetic variants of ABCC8 and clinical manifestations in eight Chinese children with hyperinsulinemic hypoglycemia.

BACKGROUND: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). METHODS: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. RESULTS: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. CONCLUSIONS: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene. / 一例GATA6åŸºå› å˜å¼‚å¼•èµ·å„¿ç«¥ç‰¹æ®Šç±»åž‹ç³–å°¿ç— çš„ä¸´åºŠç‰¹ç‚¹åŠåŸºå› å˜å¼‚åˆ†æž.

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

Classic Type 1 Diabetes Mellitus and Fulminant Type 1 Diabetes Mellitus: Similarity and Discrepancy of Immunological Characteristics and Cytokine Profile.

PURPOSE: We aimed to explore the immunological characteristics and cytokine profile of the initial stage of type 1 diabetes. PATIENTS AND METHODS: In total, 123 age- and sex-matched subjects with newly diagnosed classic type 1 diabetes mellitus (T1ADM), fulminant type 1 diabetes mellitus (FT1DM), and normal glucose tolerance (NGT) were enrolled. Serum cytokine levels were measured using Milliplex MAP multifactor detection. RESULTS: There was a significant increase in the levels of transforming growth factor ß (TGFß1) and TGFß2 and decrease in programmed death-1 (PD-1), PD ligand 1 (PD-L1), pro-inflammatory cytokines, and anti-inflammatory cytokines in type 1 diabetes patients compared with the NGT subjects (all P < 0.05). There was no significant difference in C-reactive protein (CRP) and blood routine indicators between the two groups. Type 1 diabetes was further divided into T1ADM and FT1DM subgroups. FT1DM patients had much higher CRP levels than T1ADM patients (4.90 [0.95-26.05] mg/L vs 0.39 [0.20-0.74] mg/L, P < 0.01). Blood routine results showed that the number of leukocytes was significantly increased in FT1DM compared with that in T1ADM (9.2 [5.1-18.8] × 109 cells/L vs 5.4 [4.5-6.7] × 109 cells/L, P < 0.01). In FT1DM patients, neutrophil% was increased, and lymphocyte% was declined significantly, compared with that in T1ADM patients (neutrophil%: 80.2 [59.2-85.2]% vs 59.5 [54.8-64.0]%; lymphocyte%: 18.3 [10.1-32.3]% vs 32.6 [26.8-35.9]%; both P < 0.01). However, there was no difference between FT1DM and T1ADM in cytokine profile except for the decrease in CTLA-4 in T1ADM (P < 0.05). CONCLUSION: Compared with T1ADM, CRP and leukocytes' levels were increased significantly in FT1DM, with an increase in neutrophil% and decline in lymphocyte%, suggesting that FT1DM may have more abrupt onset and occur as a more serious subtype of type 1 diabetes mellitus.

Advanced glycation end products via skin autofluorescence as potential marker of carotid atherosclerosis in patients with type 2 diabetes.

BACKGROUND AND AIMS: Advanced glycation end products (AGEs) are reported to be correlated with diabetic vascular complications. This study aimed to investigate the association between AGEs and carotid atherosclerosis (CAS) as a surrogate marker of cardiovascular disease (CVD). METHODS AND RESULTS: A total of 1006 patients with type 2 diabetes were included. CAS was defined as the presence of carotid arterial atherosclerotic plaque in any of bilateral carotid artery segments measured by ultrasonography. AGEs were measured by the noninvasive skin autofluorescence method. AGEage index was calculated as AGEs × age/100. Patients with CAS showed a significantly higher AGEage (P < 0.01), and the prevalence of CAS increased with ascending AGEage levels (P for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with odds of CAS, and the odds ratios of the presence of CAS across quartiles of AGEage were 1.00, 3.00 [95% confidence interval (CI) 1.90-4.74], 4.04 (95%CI 2.50-6.53) and 4.99 (95%CI 2.97-8.40) for the multivariable-adjusted model (P for trend <0.001), respectively. In the fully adjusted model, each 5.0 increase in AGEage was associated with a 0.019 mm increment in carotid intima-media thickness. Furthermore, AGEage presented an acceptable predictive value for CAS, with an optimal cutoff point of 43.2, and the sensitivity, specificity and area under the curve (AUC) were 74.5% (95%CI 70.7-78.1%), 61.9% (95%CI 57.2-66.4%) and 0.735 (0.706-0.762), respectively. CONCLUSION: AGEage, the noninvasive measurement of AGEs combined with age is a promising approach for triaging patients at high risk of CVDs.

Association of Advanced Glycation End Products With Lower-Extremity Atherosclerotic Disease in Type 2 Diabetes Mellitus.

Aims: Advanced glycation end products (AGEs) were reported to be correlated with the development of diabetes, as well as diabetic vascular complications. Therefore, this study aimed at investigating the association between AGEs and lower-extremity atherosclerotic disease (LEAD). Methods: A total of 1,013 type 2 diabetes patients were enrolled. LEAD was measured through color Doppler ultrasonography. The non-invasive skin autofluorescence method was performed for AGEs measurement. Considering that age plays an important role in both AGEs and LEAD, age-combined AGEs, i.e., AGEage index (define as AGEs × age/100) was used for related analysis. Results: The overall prevalence of LEAD was 48.9% (495/1,013). Patients with LEAD showed a significantly higher AGEage (p < 0.001), and the prevalence of LEAD increased with ascending AGEage levels (p for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with risk of LEAD, and the odds ratios of presence of LEAD across quartiles of AGEage were 1.00, 1.72 [95% confidence interval (CI) = 1.14-2.61], 2.72 (95% CI = 1.76-4.22), 4.29 (95% CI = 2.69-6.85) for multivariable-adjusted model (both p for trend < 0.001), respectively. The results were similar among patients of different sexes, body mass index, and with or without diabetes family history. Further, AGEage presented a better predictive value for LEAD than glycated hemoglobin A1c (HbA1c), with its sensitivity, specificity, and area under the curve of 75.5% (95% CI = 71.6-79.2%), 59.3% (95% CI = 54.9-63.6%), and 0.731 (0.703-0.758), respectively. Conclusion: AGEage, the non-invasive measured skin AGEs combined with age, seems to be a more promising approach than HbA1c in identifying patient at high risk of LEAD.

Saliva 1,5-anhydroglucitol is associated with early-phase insulin secretion in Chinese patients with type 2 diabetes.

INTRODUCTION: Saliva collection is a non-invasive test and is convenient. 1,5-anhydroglucitol (1,5-AG) is a new indicator reflecting short-term blood glucose levels. This study aimed to explore the relationship between saliva 1,5-AG and insulin secretion function and insulin sensitivity. RESEARCH DESIGN AND METHODS: Adult patients with type 2 diabetes who were hospitalized were enrolled. Based on blood glucose and C-peptide, homeostasis model assessment 2 for ß cell secretion function, C-peptidogenic index (CGI), △2-hour C-peptide (2hCP)/△2-hour postprandial glucose (2hPG), ratio of 0-30 min area under the curve for C-peptide and area under the curve for glucose (AUCCP30/AUCPG30), and AUC2hCP/AUC2hPG were calculated to evaluate insulin secretion function, while indicators such as homeostasis model assessment 2 for insulin resistance were used to assess insulin sensitivity. RESULTS: We included 284 subjects (178 men and 106 women) with type 2 diabetes aged 20-70 years. The saliva 1,5-AG level was 0.133 (0.089-0.204) µg/mL. Spearman's correlation analysis revealed a significantly negative correlation between saliva 1,5-AG and 0, 30, and 120 min blood glucose, glycated hemoglobin A1c, and glycated albumin (all p<0.05), and a significantly positive association between saliva 1,5-AG and CGI (r=0.171, p=0.004) and AUC CP30 /AUC PG30 (r=0.174, p=0.003). The above correlations still existed after adjusting for age, sex, body mass index, and diabetes duration. In multiple linear regression, saliva 1,5-AG was an independent factor of CGI (standardized ß=0.135, p=0.015) and AUC CP30 /AUC PG30 (standardized ß=0.110, p=0.020). CONCLUSIONS: Saliva 1,5-AG was related to CGI and AUCCP30/AUCPG30 in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ChiCTR-SOC-17011356.

Macrophage LAMTOR1 Deficiency Prevents Dietary Obesity and Insulin Resistance Through Inflammation-Induced Energy Expenditure.

Here, we studied the metabolic function of LAMTOR1 from macrophages using LAMTOR1 macrophage-specific knockout (MKO) mice. LAMTOR1 MKO mice showed resistance to high-fat diet (HFD)-induced obesity, lipid steatosis, and glucose metabolic disorders, with elevated levels of pro-inflammatory cytokines. The energy expenditure, oxygen consumption, and CO2 production increased significantly in HFD-fed MKO vs. wild-type (WT) mice. HE and immunohistochemistry staining showed a remarkable CD68+ Kupffer cell accumulation in the liver. Additionally, flow cytometry revealed that the proportion of macrophages and monocytes increased significantly in the liver of MKO mice. Of note, these macrophages were probably derived from the bone marrow since the proportion of CD11b+ cells as well as the proliferative activity was also increased in the context of femoral bone marrow cells. In addition, the Kupffer cells of both WT and KO mice were double-positive for the M1 (CD86) and M2 (CD206) markers. However, the expression of both M1 and M2 macrophage-related genes was increased in the liver of HFD-fed KO mice. Murine primary hepatocytes and Kupffer cells were further isolated and incubated with oleic acid for 24 h. The glucose output of primary hepatocytes from MKO mice was not affected. However, decreased lipid tolerance was observed in LAMTOR1-deficient Kupffer cells. Overall, our results suggest that LAMTOR1 deficiency in macrophages prevents obesity and metabolic disorders via the accumulation of Kupffer cells in the liver and the consequent hyper-inflammation and increased energy expenditure. Therefore, our results provide a new perspective for macrophage-derived LAMTOR1 in the context of systemic metabolism.

Association of advanced glycation end products with diabetic retinopathy in type 2 diabetes mellitus.

AIMS: Advanced glycation end products (AGEs) were reported to be associated with diabetes development and diabetes related complications when accumulated in high levels. This study investigated the association between AGEs and diabetic retinopathy (DR). METHODS: A total of 1,471 patients with type 2 diabetes were enrolled. Fundus radiography was used for DR measurement. AGEs were detected through non-invasive skin autofluorescence method. RESULTS: Patients with more advanced DR showed a much higher AGEs, and the prevalence of DR (based on the severity) increase with ascending AGEs quartiles (all P for trend < 0.001). The multivariable-adjusted odds ratios of any DR across AGEs quartiles were 1.00, 1.69 (95% confidence interval [CI] 1.16-2.47), 1.58 (95%CI 1.06-2.37) and 1.60 (95%CI 1.05-2.44) (P for trend = 0.044), respectively. Similar results were found in vision-threatening DR (VTDR) subgroup (P for trend = 0.009). When AGEs was considered as a continuous variable by using restricted cubic splines, a graded positive association of AGEs with the odds of any presence of DR was observed (P for trend < 0.001). Further, we found that AGEs presented the similar predictive value for any DR with glycated hemoglobin A1c (HbA1c). When it comes to VTDR, AGEs showed a significantly higher efficacy in early screening than HbA1c (P = 0.002). With a cut-off point of 77.1, the sensitivity, specificity and area under the curve of AGEs were 90.0% (95%CI 76.3-97.2%), 49.4% (95%CI 46.8-52.0%), and 0.728 (95%CI 0.704-0.750), respectively. CONCLUSION: Non-invasive measured skin AGEs, associated with the prevalence of all stages of DR, might be a more suitable indicator than HbA1c for mimicking the poor prognosis of hyperglycemia.

Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway.

BACKGROUND: The regulation of vascular smooth muscle cell (VSMC) phenotype plays an important role in intracranial aneurysm (IA) formation and progression. However, the underlying mechanism remains unclear. Metformin is a 5' AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature. The present study investigated whether metformin modulates VSMC phenotype switching via the AMPK/acetyl-CoA carboxylase (ACC) pathway during IA pathogenesis. METHODS: Adult male Sprague-Dawley rats (n = 80) were used to establish an elastase-induced IA model. The effects of metformin on AMPK activation and VSMC phenotype modulation were examined. We also established a platelet-derived growth factor (PDGF)-BB-induced VSMC model and analyzed changes in phenotype including proliferation, migration, and apoptosis as well as AMPK/ACC axis activation under different doses of metformin, AMPK antagonist, ACC antagonist, and their combinations. RESULTS: Metformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines. AMPK/ACC axis activation inhibited the proliferation, migration, and apoptosis of VSMCs, in which phenotypic switching was induced by PDGF-BB. CONCLUSIONS: Metformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA.

Serum 1,5-Anhydroglucitol to Glycated Albumin Ratio Can Help Early Distinguish Fulminant Type 1 Diabetes Mellitus from Newly Onset Type 1A Diabetes Mellitus.

BACKGROUND: Fulminant type 1 diabetes mellitus (FT1DM) onsets abruptly and usually occurs within 1 week after the onset of hyperglycemic symptoms. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) are indicators that reflect short-term glucose levels. This study was aimed at investigating whether the 1,5-AG/GA index (AGI) is a suitable indicator for early FT1DM identification. METHODS: A total of 226 subjects were enrolled, all with glycated hemoglobin A1c (HbA1c) < 8.7%. FT1DM was diagnosed based on the 2012 Japan Diabetes Society criteria. RESULTS: The AGI level was 0.54 (0.17-1.36) in the whole group. It was lower in FT1DM patients (0.16 [0.10-0.25]). Among the participants whose HbA1c did not exceed 7.0%, the AGI of FT1DM decreased significantly compared to type 1A diabetes (T1ADM) and latent autoimmune diabetes in adults (LADA) patients (0.16 [0.12-0.26] vs. 0.46 [0.24-0.72] vs. 0.46 [0.24-0.72] P < 0.05). The receiver operating characteristic (ROC) curve showed that AGI can be used to distinguish FT1DM and T1ADM patients with HbA1c < 8.7%. Diagnosing FT1DM based on AGI ≤ 0.3 only can help narrow down suspected FT1DM by up to 26.87%. If we diagnosed FT1DM when AGI was ≤0.3 and HbA1c was ≤7.0%, the success rate further increased to 86.57%, among which 85.00% of FT1DM and 87.23% of T1ADM patients were successfully identified. Therefore, using the combination criteria of AGI and HbA1c would improve the differential diagnosis efficacy by 61.11% compared with the AGI criterion only. CONCLUSION: AGI can help facilitate the early differential diagnosis of FT1DM and T1ADM when HbA1c < 8.7%, with an optimal cut-off point of 0.3.

1,5-Anhydroglucitol × glycated hemoglobin A1c/100 as a potential biomarker for islet ß-cell function among patients with type 2 diabetes.

AIMS: This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A1c/100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels. METHODS: Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes. RESULTS: The mean AHI level was 1.0 (0.7-1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9-1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-ß, insulin generation index, insulin sensitivity index, and DI increased (all Pfor trend < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), showing a decreasing trend (Pfor trend < 0.05). CONCLUSION: The AHI could reflect the variation in glycemic disorder and the function of islet ß cells. The lower the AHI, the worse the glycemic disorder, as well as the islet ß-cell function.

Fulminant type 1 diabetes: The clinical and continuous glucose monitoring characteristics in Chinese patients.

The purpose of the current study was to investigate the clinical characteristics of fulminant type 1 diabetes mellitus (FT1DM) in Chinese patients and to further determine their glycaemic profiles through continuous glucose monitoring (CGM). Thirty subjects who were diagnosed with FT1DM according to the 2012 JDS criteria were enrolled. Clinical characteristics were compared to those reported in Japanese FT1DM. All subjects received retrospective CGM for 3 days after being converted to subcutaneous insulin injection therapy. Chinese FT1DM patients presented with a shorter duration of symptoms (2.84 ± 2.42 days vs 4.4 ± 3.1 days, P < 0.01), worse islet function (fasting C-peptide, 0.09 ± 0.11 ng/mL vs 0.30 ± 0.21 ng/mL; 2-hour C-peptide, 0.13 ± 0.14 ng/mL vs 0.30 ± 0.30 ng/mL, both P < 0.01), lower prevalence of flu-like symptoms (46.7% vs 71.4%, P < 0.05), and a significantly higher GADA positive rate (23.3% vs 5.1%, P < 0.01) when compared with Japanese patients. The CGM results showed that the mean time in range (TIR) of FT1DM patients was 49.8 ± 22.1%, while mean amplitude of glycaemic excursion (MAGE) and standard deviations of sensor glucose (SDSG) were 7.58 ± 3.59 mmol/L and 3.19 ± 1.22 mmol/L, respectively, with nearly 1/3 participants coefficient of variation (CV) > 36% (all are male), suggesting a large glucose fluctuation. The female patients were further divided into pregnancy-related FT1DM (PF) and non-PF (NPF) subgroups (both n = 5), and we found that PF patients had a significantly higher TIR than NPF patients (77.0 ± 16.1% vs 41.0 ± 22.4%, P < 0.05). There were heterogeneities in the clinical characteristics of FT1DM patients, and the CGM results indicated a very low TIR and large glucose fluctuation which needs careful attention.

Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia.

There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (ß = 0.151, P = 0.035) and HOMA-IR (ß = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.

Glycemic variability assessed by continuous glucose monitoring and the risk of diabetic retinopathy in latent autoimmune diabetes of the adult and type 2 diabetes.

AIMS/INTRODUCTION: The relationship between glycemic variability (GV) and diabetic complications has gained much interest and remains under debate. Furthermore, the association of GV with diabetic complications has not been examined in latent autoimmune diabetes of the adult (LADA). Therefore, we evaluated the relationships among several metrics of GV with diabetic retinopathy (DR) in patients with LADA and type 2 diabetes mellitus. MATERIALS AND METHODS: A total of 192 patients with LADA and 2,927 patients with type 2 diabetes mellitus were enrolled. After continuous glucose monitoring for 72 h, three metrics of GV including standard deviation, coefficient of variation and mean amplitude of glycemic excursions were calculated. DR was assessed by fundus photography performed with a digital non-mydriatic camera. RESULTS: The prevalence of DR was 20.3 and 26.4% in LADA and type 2 diabetes mellitus patients (P < 0.001), respectively. Generally, LADA patients had fewer cardiometabolic risk factors than type 2 diabetes mellitus patients, and all GV metrics were significantly higher in LADA than in type 2 diabetes mellitus. In the multivariate logistic regression analysis, no metrics for GV were identified as independent risk factors of DR (standard deviation: P = 0.175; coefficient of variation: P = 0.769; mean amplitude of glycemic excursions: P = 0.388) in LADA. However, the standard deviation was significantly associated with DR (OR 1.15, P = 0.017) in patients with type 2 diabetes mellitus after adjusting for confounders. The independent relationships of coefficient of variation and mean amplitude of glycemic excursions with DR (P = 0.194 and P = 0.251, respectively) did not reach statistical significance in type 2 diabetes mellitus. CONCLUSIONS: GV is more strongly associated with DR in type 2 diabetes than in LADA, suggesting that different glucose-lowering strategies should be used for these two types of diabetes.

Breakfast replacement with a liquid formula improves glycaemic variability in patients with type 2 diabetes: a randomised clinical trial.

There is emerging evidence that glycaemic variability (GV) plays an important role in the development of diabetic complications. The current study aimed to compare the effects of lifestyle intervention (LI) with and without partial meal replacement (MR) on GV. A total of 123 patients with newly diagnosed and untreated type 2 diabetes (T2D) were randomised to receive either LI together with breakfast replacement with a liquid formula (LI+MR) (n 62) or LI alone (n 61) for 4 weeks and completed the study. Each participant was instructed to have three main meals per d and underwent 72-h continuous glucose monitoring (CGM) both before and after intervention. Measures of GV assessed by CGM included the incremental AUC of postprandial blood glucose (AUCpp), standard deviation of blood glucose (SDBG), glucose CV and mean amplitude of glycaemic excursions (MAGE). After a 4-week intervention, the improvements in systolic blood pressure (P=0·046) and time in range (P=0·033) were more pronounced in the LI+MR group than in the LI group. Furthermore, LI+MR caused significantly greater improvements in all GV metrics including SDBG (P=0·005), CV (P=0·002), MAGE (P=0·016) and AUCpp (P<0·001) than did LI. LI+MR (v. LI) was independently associated with improvements in GV after adjustment of covariates (all P<0·05). Our study showed that LI+MR led to significantly greater improvements in GV compared with LI, suggesting that LI+MR could be an effective treatment to alleviate glucose excursions.

Association of Time in Range, as Assessed by Continuous Glucose Monitoring, With Diabetic Retinopathy in Type 2 Diabetes.

OBJECTIVE: Continuous glucose monitoring (CGM) has provided new measures of glycemic control that link to diabetes complications. This study investigated the association between the time in range (TIR) assessed by CGM and diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: A total of 3,262 patients with type 2 diabetes were recruited. TIR was defined as the percentage of time spent within the glucose range of 3.9-10.0 mmol/L during a 24-h period. Measures of glycemic variability (GV) were assessed as well. DR was determined by using fundus photography and graded as 1) non-DR; 2) mild nonproliferative DR (NPDR); 3) moderate NPDR; or 4) vision-threatening DR (VTDR). RESULTS: The overall prevalence of DR was 23.9% (mild NPDR 10.9%, moderate NPDR 6.1%, VTDR 6.9%). Patients with more advanced DR had significantly less TIR and higher measures of GV (all P for trend <0.01). The prevalence of DR on the basis of severity decreased with ascending TIR quartiles (all P for trend <0.001), and the severity of DR was inversely correlated with TIR quartiles (r = -0.147; P < 0.001). Multinomial logistic regression revealed significant associations between TIR and all stages of DR (mild NPDR, P = 0.018; moderate NPDR, P = 0.014; VTDR, P = 0.019) after controlling for age, sex, BMI, diabetes duration, blood pressure, lipid profile, and HbA1c. Further adjustment of GV metrics partially attenuated these associations, although the link between TIR and the presence of any DR remained significant. CONCLUSIONS: TIR assessed by CGM is associated with DR in type 2 diabetes.

Postload Glycated Albumin as an Alternate Measure for Diabetes Screening in a Chinese Population.

In previous epidemiological screening in China, glycated albumin (GA) was mostly detected during the fasting state. This strict restriction causes some problems with diabetes screening. It is unclear if GA could help improve the efficiency of screening for diabetes for subjects who are not in the fasting state. The present study analyzed the differences between fasting and postload (30, 60, 120, and 180 min) GA levels. A total of 691 participants were enrolled in the present study. The Bland-Altman difference plots revealed that 95.4, 94.8, 93.6, and 93.9% of data points were within the limits of agreement for each time point. The receiver operating characteristic curve showed that the areas under the curve (AUC) for baseline GA and postload GA for every time point were 0.822 (95% CI 0.791-0.849), 0.821 (95% CI 0.790-0.848), 0.833 (95% CI 0.803-0.860), 0.840 (95% CI 0.811-0.867), and 0.840 (95% CI 0.810-0.867), with sensitivities of 67.5, 68.1, 69.3, 71.6, and 69.3%, respectively. There was no difference between the baseline and postload GA levels in either AUC or sensitivity (all p > 0.05). In conclusion, postload serum GA levels were in good agreement with those at baseline, and thus, it may be reasonable to employ nonfasting measurements of GA levels for diabetes screening.

Associations of body mass index with glycated albumin and glycated albumin/glycated hemoglobin A1c ratio in Chinese diabetic and non-diabetic populations.

BACKGROUND: Recent studies have discussed the relationship between body mass index (BMI) and glycated albumin (GA) level. However, the extent of the influence of BMI on GA remains uncertain. We investigated the associations between BMI and GA, glycated hemoglobin A1c (HbA1c) and GA/HbA1c, and to analyze the influence of obesity on GA, HbA1c, and GA/HbA1c in both Chinese diabetic and non-diabetic populations. METHODS: A total of 2562 participants, including 1177 men and 1385 women (age 20-80 y), were enrolled. Each subject underwent a 75-g oral glucose tolerance test. Serum GA was detected using a liquid enzyme method, and HbA1c was assayed using high-performance liquid chromatography. RESULTS: In the diabetic patients (n = 1223), the GA, HbA1c, and GA/HbA1c levels were 16.7 ±â€¯3.0%, 6.6 ±â€¯.9% (49 ±â€¯9 mmol/mol), and 2.51 ±â€¯.33, respectively. In the non-diabetic subjects (n = 1339), the GA, HbA1c, and GA/HbA1c concentrations were 13.8 ±â€¯1.7%, 5.6 ±â€¯.4% (38 ±â€¯4 mmol/mol), and 2.47 ±â€¯.31, respectively. Decreasing trends in the GA and GA/HbA1c concentrations and an increasing trend in the HbA1c concentration (all P for trend <.05) were found to accompany with the increase in BMI, regardless of diabetes status. Multiple regression analysis revealed that BMI was independently related to HbA1c in the non-diabetic population (standardized ß = .158, P < .001); however, the relationship disappeared in the diabetic population (P > .05). Moreover, in the diabetic and non-diabetic populations, BMI was negatively correlated with GA (standardized ß = -.167 and - .231, both P < .001) and GA/HbA1c (standardized ß = -.273 and - .310, both P < .001). Further analysis showed that a 1 kg/m2 increment in BMI was associated with a .13% decrease in the absolute value of GA. CONCLUSIONS: In both diabetic and non-diabetic populations, GA and GA/HbA1c levels are independently and negatively associated with BMI. For every 1 kg/m2 increment in BMI, the absolute value of GA decreases approximately .13%.