Diabetes mellitus (DM) is a major global health issue, with glycated hemoglobin levels serving as the gold standard for evaluating glucose level control in DM patients. However, it has limitations in reflecting glucose oscillations (i.e. glycemic variability, GV). Increasing evidence suggests that GV is closely related to the progression of diabetes complications and patient prognosis. As people realize the importance of avoiding hypoglycemia while achieving target glycated hemoglobin levels in treatment, the clinical significance of GV becomes more obvious. This article systematically reviewed the concept and connotation of GV, summarized the latest research on its role in the complications of diabetes, and revealed the biochemical and pathophysiological abnormalities caused by excessive glycemic oscillation, aiming to provide a theoretical basis for the risk warning and early intervention of DM patients.
Humans ; Blood Glucose/metabolism* ; Diabetes Complications/physiopathology* ; Glycated Hemoglobin/metabolism* ; Hypoglycemia ; Diabetes Mellitus, Type 2/complications*

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

OBJECTIVE: To analyze the influence of type 2 diabetes mellitus (DM) on the prognosis of oral squamous cell carcinoma (OSCC) patients with surgical treatment. METHODS: The clinical data of 309 patients, who were diagnosed with OSCC and admitted to the same ward of Peking University Hospital of Stomatology from January 2014 to December 2017 were retrospectively reviewed, of whom, 104 were classified into DM group and 205 into non-DM group. The basic clinical data and follow-up results of the patients were analyzed and compared. Propensity score matching (PSM) was used to reduce confounding bias between the DM group and the non-DM group. Kaplan-Meier was used to calculate the survival rate of the two groups. Proportional hazards model was used to analyze the independent prognostic factors. The effect of glucose level on survival was analyzed. RESULTS: After PSM, 77 patients in each group were matched and the variables were balanced. There were statistically significant differences in postoperative oral dysplasia and local recurrence between the two groups (P < 0.05). There was no significant difference in survival analysis between the two groups, but the survival rate of the DM group had the tendency to be lower than that of the non-DM group after matching. Univariate analysis and multiva-riate analysis both revealed that the tumor stage was an independent factor influencing the overall survival rate and tumor-specific survival rate of the OSCC patients (P < 0.05), while diabetes had no significant influence on the survival of the OSCC patients (P>0.05). Multivariate analysis showed that tumor stage, triglyceride level, preoperative mean capillary fasting blood glucose, postoperative mean postprandial blood glucose were indepen-dent prognostic factors for overall survival in the DM group. Tumor stage and mean postoperative postprandial blood glucose were independent prognostic factors for tumor-specific survival in the DM group. The risk of postoperative complications and distant metastasis in the DM group with poor glycemic control was higher than that in the good glycemic controls. CONCLUSION There is no significant difference in overall survival and tumor-specific survival of the patients with or without DM. However, the possibility of mucosal dysplasia or local recurrence in the DM group is higher than that in the non-DM group. The tumor stage, triglyceride level and glycemic control of the patients with DM may affect their prognosis.
Humans ; Diabetes Mellitus, Type 2/complications* ; Mouth Neoplasms/mortality* ; Retrospective Studies ; Prognosis ; Carcinoma, Squamous Cell/mortality* ; Male ; Female ; Survival Rate ; Neoplasm Recurrence, Local ; Propensity Score ; Proportional Hazards Models ; Blood Glucose/analysis* ; Middle Aged ; Kaplan-Meier Estimate

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q₁ to Q₄ according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q₁, subjects in group Q₄ with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q₄ with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q₄ with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (P_trend=0.018, P_trend=0.010) and increased with the increase of serum IgA concentrations (P_trend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, P_trend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.
Humans ; Adult ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Blood Glucose ; Inflammation/complications* ; Immunoglobulin A ; Immunoglobulin M ; Immunoglobulin G ; Immunoglobulin E ; Risk Factors

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q₁ to Q₄ according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q₁, subjects in group Q₄ with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q₄ with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q₄ with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (P_trend=0.018, P_trend=0.010) and increased with the increase of serum IgA concentrations (P_trend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, P_trend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.
Humans ; Adult ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Blood Glucose ; Inflammation/complications* ; Immunoglobulin A ; Immunoglobulin M ; Immunoglobulin G ; Immunoglobulin E ; Risk Factors

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Animals ; Rats ; Caspase 1/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-18 ; Blood Glucose ; Pyroptosis ; Tumor Necrosis Factor-alpha ; Diabetes Complications ; Vascular Diseases ; Inflammasomes ; Cholesterol ; Lipids ; Diabetes Mellitus

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30^th, 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.
Male ; Child ; Humans ; Child, Preschool ; Infant ; Diabetes Mellitus, Type 2/complications* ; Mutation, Missense ; C-Peptide/genetics* ; China ; Insulin/genetics* ; Glucose ; Blood Glucose ; GATA6 Transcription Factor/genetics*

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.
Male ; Humans ; Middle Aged ; Blood Glucose ; Diabetes Mellitus, Type 2/complications* ; Pancreaticoduodenectomy/adverse effects* ; Pancreatitis, Chronic/complications* ; Malnutrition/complications*

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.
Blood Platelets ; Diabetes Mellitus, Type 2/drug therapy* ; Humans ; Hyperglycemia/complications* ; Insulin Resistance ; Obesity/complications*