BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by ...BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by achieving tighter glycemic control.AIM To evaluate the efficacy of IIT for managing SIH in critically ill patients and to explore its potential effect on cardiac function.METHODS A retrospective study was conducted at our hospital from January 2021 to December 2024,adhering to STROBE guidelines.A total of 186 critically ill pa-tients were divided into normal glycemia(n=85)and SIH(n=101)groups.The SIH cohort was further subdivided into conventional treatment(n=50)and IIT(n=51)groups.Hemodynamic parameters-including right atrial pressure(RAP),pulmonary artery pressure(PAP),pulmonary capillary wedge pressure(PAWP),cardiac output(CO),cardiac index(CI),and B-type natriuretic peptide(BNP)-were measured at baseline and post-treatment.Clinical outcomes such as intensive care unit(ICU)length of stay,mechanical ventilation requirements,and mortality were also recorded.Statistical analyses were conducted using inde-pendent samples t-tests and χ^(2)/Fisher’s exact tests.RESULTS SIH markedly worsened haemodynamics versus normal glycaemia:RAP 9.8±5.1 vs 6.1±3.5 mmHg,PAP 35.2±16.0 vs 26.2±10.3 mmHg,PAWP 16.0±7.0 vs 8.6±6.4 mmHg,CO 3.3±2.3 vs 6.0±3.3 L/min,CI 1.88±0.24 vs 2.70±0.50 L/min/m2,BNP 465±250 vs 180±53 pg/mL(all P<0.001).Within the SIH cohort,IIT outperformed conventional therapy:RAP 7.0±2.2 vs 8.3±3.9 mmHg(P=0.04),PAP 21.6±3.7 vs 29.3±6.5 mmHg(P<0.001),PAWP 10.2±5.4 vs 13.8±5.3 mmHg(P=0.001),CO 4.9±2.2 vs 4.0±1.4 L/min(P=0.022),CI 2.58±0.32 vs 2.11±0.31 L/min/m2,P<0.001),BNP 202±62 vs 346±171 pg/mL(P<0.001).Clinically,IIT shortened ICU stay(10.3±3.4 vs 14.5±2.6 days,P<0.001),reduced ventilator use(56.9%vs 76.0%,P=0.042),and lowered mortality(23.5%vs 42.0%,P=0.048).CONCLUSION IIT significantly reduced cardiac filling pressures,improved cardiac function,and was associated with favorable clinical outcomes in SIH patients,suggesting potential benefits of stricter glycaemic control in critically ill patients.However,given the retrospective design and absence of glucose-variability monitoring,these findings should be interpreted with caution.展开更多
The influence of early-stage intensive insulin therapy on the plasma levels of vascular en- dothelial growth factor （VEGF） and the related parameters in patients with severe trauma and the clini- cal implication wer...The influence of early-stage intensive insulin therapy on the plasma levels of vascular en- dothelial growth factor （VEGF） and the related parameters in patients with severe trauma and the clini- cal implication were investigated. Sixty-four cases of severe trauma （injury severity score 〉20） with stress hyperglycemia （blood glucose 〉9 mmol/L） were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient grada- tion one-step process were used to determine plasma VEGF, endothelin-1 （ET-1）, and the number of circulating endothelial cells （CECs） at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF （ng/L）, 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P〈0.05, 0.01, 0.05, 0.05 respectively; for ET-1 （ng/L）, 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P〈0.05, 0.01, 0.01, 0.01 respectively; for CRP （mg/L）, 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P〈0.05; for CECs （/0.9 μL）, 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P〈0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.展开更多
The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined ...The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups： control group （n=56） treated with conventional therapy, and intensive insulin therapy group （n=58） treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells （WBC） counts, prothrombin time （PT）, serum creatinine （SCr）, alanine aminotransferase （ALT）, serum albumin and PaO2 were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced （P0.05）, but the level of serum albumin was significantly increased （P0.05） at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 （P0.01） after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased （P0.01）. The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.展开更多
AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care ...AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.展开更多
Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulati...Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a dosed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.展开更多
BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabet...BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.展开更多
Introduction: In Senegal, with the CDIC “Changing Diabetes In children” project, insulin has been made free. The objective of this study was to evaluate the accessibility and modalities of insulin therapy in the man...Introduction: In Senegal, with the CDIC “Changing Diabetes In children” project, insulin has been made free. The objective of this study was to evaluate the accessibility and modalities of insulin therapy in the management of type 1 diabetes. Methodology: This was a retrospective study including patients followed for type 1 diabetes (T1DM) in hospital between April 2018 and December 2020. Results: 281 patients were included. The mean age was 14.22 years. The mean age at diagnosis was 11.28 years. Ketoacidosis was the main mode of discovery of diabetes at 51.6%. Premix and rapid insulins were most commonly used at 84.7% and 82.9% respectively, most often in combination. The most commonly used treatment regimen was three injections/day in 82.5% of cases. The average daily insulin dose was 0.62 IU/Kg/dr. Of the patients, 219 (78%) were self-monitoring of blood glucose. The average number of blood glucose checks was 1.78 per day. 76 patients (27%) went days without an insulin injection and up to 7 days in 51% of cases. The main reasons were forgetfulness, therapeutic errors and stock-outs. Hypoglycaemia was observed in 14.2%. The average glycated haemoglobin was 10%. Conclusion: Despite the efforts made, there are still challenges to improve access to insulin. The reinforcement of therapeutic education on insulin therapy is essential for a better quality of life of diabetic children and adolescents.展开更多
Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy ...Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178;p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696;p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155;p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720;p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.展开更多
Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type...Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type 1 diabetes still needs more data. The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes. Methods This 1：2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology, Beijing Children＇s Hospital from 2009-2010. The case group included 14 patients, who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010. The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization. We compared the baseline and follow-up data of them, including ketoacidosis onset, clinical variables （glycosylated hemoglobin （HbAlc）, insulin dosage and serum C-peptide）. Results The clinical characteristics of the patients was comparable between the case group and the control group. At 6-12 months （（10.7±4.2） months） after AHST treatment, we found 11 patients in the case group did not stop the insulin therapy, three cases stopped insulin treatment for 2, 3 and 11 months, respectively. No diabetic ketoacidosis （DKA） occurred after transplantation in all the patients in the case group. HbAlc in the control group was significant lower than that in the case group （P 〈0.01）, while the insulin dosage and serum C-peptide were not significant different between the two groups （P 〉0.05）. In order to eliminate the honeymoon effect, we performed final follow-up at the 3-5 years （（4.2±1.8） years） after AHST treatment, and found that HbAlc in the control group was still lower than that in the case group （P 〈0.01）; however, the insulin dosage and serum C-peptide were not significantly different between the two groups （P 〉0.05）. Moreover, the insulin dosage was not significant different from baseline to follow-up period in the case group. Conclusion AHST treatment showed no advantage in effectiveness in children with newly diagnosed type 1 diabetes, both in insulin dose and long term blood glucose control. Chin med J2014;（14）：2618-2622展开更多
Background Intensive insulin therapy has been found to lessen the progress of diabetic retinopathy （DR） to some extent,while it has also been implicated to be responsible for decrease of DR.We investigated visual fu...Background Intensive insulin therapy has been found to lessen the progress of diabetic retinopathy （DR） to some extent,while it has also been implicated to be responsible for decrease of DR.We investigated visual function and morphological changes in the macular area in short-term follow-up of patients with type 2 diabetes mellitus after intensive insulin therapy.Methods This was a prospective clinical study of nonproliferative DR patients （102 eyes,120 patients） undergoing intensive insulin therapy.The Contrast Glare Tester （Takagi CGT-1000） was used to examine contrast sensitivity （CS） and Heidelberg Retina Tomograph （HRT） Ⅱ and Stratus Model 3000 OCT were used to observe the changes of morphology in the macular area.Follow-up times were pre-intensive therapy,3 and 6 months post-intensive therapy.Results CS at low and middle frequencies was higher at 3 and 6 months post-therapy compared with pre-therapy （P 〈0.05）.Significant differences in CS at low frequency were found between 6 and 3 months post-therapy （P 〈0.05）.Macular edema index was lower in the first,second,and third rings of the macular area after intensive therapy compared with pre-therapy （P 〈0.05）.Compared with 3 months post-therapy,the macular edema index was lower in the first,second,and third rings of the macular area at 6 months post-therapy （P 〉0.05）.No significant differences in the thickness of the first,second,and third rings of the macular area were detected between 3 and 6 months post-therapy and pre-therapy （P〉0.05）.Conclusion CS and macular edema indexes were significantly improved in nonproliferative diabetic retinopathy patients after intensive insulin therapy,but thickness of the macular area was unchanged.展开更多
Background The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioper...Background The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioperative period, insulin therapy is usually advised to be used for surgical patients with type 2 diabetes. However, the insulin regimen which one is better remains controversial. In this study, we estimated the efficacy, safety and advantage of different insulin therapy strategy during perioperative period.展开更多
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient ...BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.展开更多
Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases...Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases,zinc finger nucleases,transcription activator-like effector nucleases and RNA-guided engineered nucleases(RGENs),which create double-strand breaks at specific target sites in the genome,and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism.A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype,without the need for the reengineering of the specific enzyme when targeting different sequences.CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function.RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes,as summarized and exemplified in this manuscript.展开更多
BACKGROUND Insulin pump therapy is a real breakthrough in managing diabetes Mellitus,particularly in children. It can deliver a tiny amount of insulin and decreases the need for frequent needle injections. It also hel...BACKGROUND Insulin pump therapy is a real breakthrough in managing diabetes Mellitus,particularly in children. It can deliver a tiny amount of insulin and decreases the need for frequent needle injections. It also helps to maintain adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.Children are suitable candidates for pump therapy as they need a more freestyle and proper metabolic control to ensure adequate growth and development.Therefore, children and their caregivers should have proper education and training and understand the proper use of insulin pumps to achieve successful pump therapy. The pump therapy continuously improves to enhance its performance and increase its simulation of the human pancreas. Nonetheless, there is yet a long way to reach the desired goal.AIM To review discusses the history of pump development, its indications, types, proper use, special conditions that may enface the children and their families while using the pump, its general care,and its advantages and disadvantages.METHODS We conducted comprehensive literature searches of electronic databases until June 30, 2022,related to pump therapy in children and published in the English language.RESULTS We included 118 articles concerned with insulin pumps, 61 were reviews, systemic reviews, and meta-analyses, 47 were primary research studies with strong design, and ten were guidelines.CONCLUSION The insulin pump provides fewer needles and can provide very tiny insulin doses, a convenient and more flexible way to modify the needed insulin physiologically, like the human pancreas, and can offer adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.展开更多
Insulin autoantibody (IAA) mediated insulin resistance (AMIR) is very rare in human insulin era.Here we report a typical case of a 90-year-old Chinese man who suffered from heart and renal dysfunction,lung infection a...Insulin autoantibody (IAA) mediated insulin resistance (AMIR) is very rare in human insulin era.Here we report a typical case of a 90-year-old Chinese man who suffered from heart and renal dysfunction,lung infection and very poor blood glucose control,and meanwhile injected with higher than 200 U human insulin for his diabetes.His IAA was posi-tive with high affinity to insulin,as insulin antigen-antibody binding rate was 52% in vitro.Serum insulin level and the binding rate decreased dramatically with cession of insulin injection; also blood glucose profile restored to response to pre-vious dose insulin injection and remained during follow-up.Both the reason for the IAA formation and the solution to the AMIR were discussed in detail.展开更多
Insulin therapy is an integral part of the pharmacological management of Type 2 diabetes mellitus. Guidelines recommended insulin therapy for those patients with suboptimal glycaemic control despite optimal medical tr...Insulin therapy is an integral part of the pharmacological management of Type 2 diabetes mellitus. Guidelines recommended insulin therapy for those patients with suboptimal glycaemic control despite optimal medical treatments. Studies show that insulin therapy with the human and regular insulins improve glycaemic control, reduce the chronic complications, and inevitably improve patient’s quality of life. The new analogue insulin has a better safety profile and efficacies, and has been shown to achieve better outcomes and patient’s acceptability compared with the human and regular insulins. The diabetic guidelines also recommend the intensity of insulin therapy in a personalised glycaemic control strategy based on the patient’s profiles and their preferences. However, the guidelines do not recommend any standardised approach to the principles of insulin initiation, titration, and monitoring. This review summarises the essential principles of insulin initiation, titration, and monitoring in Type 2 diabetes mellitus.展开更多
AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a sy...AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.展开更多
Objective To construct a single plasmid vector mediating doxycycline-inducible recombined human insulin gene expr-ession in myotube cell line. Methods An expression cassette of rtTAnls driven by promoter of human cyto...Objective To construct a single plasmid vector mediating doxycycline-inducible recombined human insulin gene expr-ession in myotube cell line. Methods An expression cassette of rtTAnls driven by promoter of human cytomegalovirus and a furin-cuttable recom-bined human insulin expression cassette driven by a reverse poly-tetO DNA motif were cloned into a single plasmid vector (prTR-tetO-mINS). The prTR-tetO-mINS and pLNCX were co-transfected into a myotube cell line (C2C12) and pLNCX vector were used as a control. After selection with G418, the transfected cells were induced with doxycycline at concentra-tions of 0, 2, and 10 μg/mL. RT-PCR was used to determine expression levels of recombinant insulin mRNA at the 5th day. Insulin production in cell cultures medium (at different incubation time) and cell extracts (at the 7th day) were analyzed with human pro/insulin RIA kits. Results Immune reactive insulin (IRI) level in cell medium was found increased at 24 hours of doxycycline incubation, and still increased at the 5th day. After withdrawn of doxycycline, IRI decreased sharply and was at baseline three days later. IRI and human insulin mRNA levels were positively related to different levels of doxycycline. A 25-fold increase in IRI was found against background expression at the 7th day. Conclusion Human insulin expression can be successfully regulated by doxycycline and the background was very low. This single tet-on insulin expression system may provide a new approach to a controlled insulin gene therapy in skeletal muscle.展开更多
Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rat...Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rats were randomized into normal control, model, acupuncture and medication groups, with 20 cases in each group. Hypothalamic obesity model was established by subcutaneous injection of 15% sodium glutamate (0.2 mL/10 g body weight), once daily and continuously for 5 days. “Zusanli” (足三里 ST 36), “Sanyinjiao”(三阴交 SP 6), “Guanyuan”(关元 CV 4) and “Zhongwan”(中脘 CV 12) were punctured and stimulated electrically (100 Hz, dense-sparse waves, and a suitable strength inducing local muscular tremor) for 15 min, once daily. In medication group, rats were fed with Sibutramine 4 mg/kg, once daily. After 4 weeks’ treatment, Lee’s index was detected, and serum leptin and insulin contents were determined by radioimmunoassay (RIA). Results: Compared with normal control group, Lee’s index, serum leptin and insulin contents of model group increased significantly (P<0.01). Comparison between acupuncture and model groups, Lee’s index and serum leptin of acupuncture group decreased significantly (P<0.01), and serum insulin level also lowered. In comparison with model group, Lee’s index, serum leptin and insulin levels of medication group also lowered. Comparison between acupuncture and medication groups showed that Lee’s index and serum leptin level of acupuncture group were significantly lower than those of the later group (P<0.01), displaying that the therapeutic effect of acupuncture is better than that of Sibutramine in lowering Lee’s index and serum leptin. No significant differences were found between acupuncture and medication groups in body weight and length and serum insulin(P>0.05). Conclusion: Acupuncture can effectively reduce Lee’s index, serum leptin and insulin contents in fasting obese rats, which may contribute to its effect in anti-obesity.展开更多
Pancreatogenic diabetes,also known as type 3c diabetes,arises from pancreatic dysfunction due to conditions such as chronic pancreatitis and pancreatic cancer.This form of diabetes is characterized by both endocrine a...Pancreatogenic diabetes,also known as type 3c diabetes,arises from pancreatic dysfunction due to conditions such as chronic pancreatitis and pancreatic cancer.This form of diabetes is characterized by both endocrine and exocrine pancreatic insufficiency,leading to insulin deficiency,glycemic variability,and maldigestion.The diagnostic process remains complex,as it shares clinical features with type 2 diabetes,and there are no standardized diagnostic criteria.Current treatment approaches include insulin therapy and pancreatic enzyme replacement therapy,along with nutritional support.However,the efficacy of oral hypoglycemic agents is limited,particularly in the presence of exocrine insufficiency.Epidemiological data indicate a significant overlap between pancreatogenic diabetes and pancreatic cancer,necessitating enhanced screening in high-risk populations.In this minireview,we highlight the pathophysiological mechanisms,diagnostic challenges,and current management strategies,emphasizing the need for improved diagnostic criteria and individualized treatment regimens.展开更多
文摘BACKGROUND Stress-induced hyperglycemia(SIH)is common in critically ill patients and has been associated with adverse cardiovascular outcomes.Intensive insulin therapy(IIT)has been proposed to mitigate these risks by achieving tighter glycemic control.AIM To evaluate the efficacy of IIT for managing SIH in critically ill patients and to explore its potential effect on cardiac function.METHODS A retrospective study was conducted at our hospital from January 2021 to December 2024,adhering to STROBE guidelines.A total of 186 critically ill pa-tients were divided into normal glycemia(n=85)and SIH(n=101)groups.The SIH cohort was further subdivided into conventional treatment(n=50)and IIT(n=51)groups.Hemodynamic parameters-including right atrial pressure(RAP),pulmonary artery pressure(PAP),pulmonary capillary wedge pressure(PAWP),cardiac output(CO),cardiac index(CI),and B-type natriuretic peptide(BNP)-were measured at baseline and post-treatment.Clinical outcomes such as intensive care unit(ICU)length of stay,mechanical ventilation requirements,and mortality were also recorded.Statistical analyses were conducted using inde-pendent samples t-tests and χ^(2)/Fisher’s exact tests.RESULTS SIH markedly worsened haemodynamics versus normal glycaemia:RAP 9.8±5.1 vs 6.1±3.5 mmHg,PAP 35.2±16.0 vs 26.2±10.3 mmHg,PAWP 16.0±7.0 vs 8.6±6.4 mmHg,CO 3.3±2.3 vs 6.0±3.3 L/min,CI 1.88±0.24 vs 2.70±0.50 L/min/m2,BNP 465±250 vs 180±53 pg/mL(all P<0.001).Within the SIH cohort,IIT outperformed conventional therapy:RAP 7.0±2.2 vs 8.3±3.9 mmHg(P=0.04),PAP 21.6±3.7 vs 29.3±6.5 mmHg(P<0.001),PAWP 10.2±5.4 vs 13.8±5.3 mmHg(P=0.001),CO 4.9±2.2 vs 4.0±1.4 L/min(P=0.022),CI 2.58±0.32 vs 2.11±0.31 L/min/m2,P<0.001),BNP 202±62 vs 346±171 pg/mL(P<0.001).Clinically,IIT shortened ICU stay(10.3±3.4 vs 14.5±2.6 days,P<0.001),reduced ventilator use(56.9%vs 76.0%,P=0.042),and lowered mortality(23.5%vs 42.0%,P=0.048).CONCLUSION IIT significantly reduced cardiac filling pressures,improved cardiac function,and was associated with favorable clinical outcomes in SIH patients,suggesting potential benefits of stricter glycaemic control in critically ill patients.However,given the retrospective design and absence of glucose-variability monitoring,these findings should be interpreted with caution.
基金supported by the National Natural Science Foundation of China (No. 30700869)
文摘The influence of early-stage intensive insulin therapy on the plasma levels of vascular en- dothelial growth factor （VEGF） and the related parameters in patients with severe trauma and the clini- cal implication were investigated. Sixty-four cases of severe trauma （injury severity score 〉20） with stress hyperglycemia （blood glucose 〉9 mmol/L） were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient grada- tion one-step process were used to determine plasma VEGF, endothelin-1 （ET-1）, and the number of circulating endothelial cells （CECs） at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF （ng/L）, 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P〈0.05, 0.01, 0.05, 0.05 respectively; for ET-1 （ng/L）, 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P〈0.05, 0.01, 0.01, 0.01 respectively; for CRP （mg/L）, 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P〈0.05; for CECs （/0.9 μL）, 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P〈0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.
基金supported by a grant from National Natural Sciences Foundation of China (No. 30870951)
文摘The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups： control group （n=56） treated with conventional therapy, and intensive insulin therapy group （n=58） treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells （WBC） counts, prothrombin time （PT）, serum creatinine （SCr）, alanine aminotransferase （ALT）, serum albumin and PaO2 were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced （P0.05）, but the level of serum albumin was significantly increased （P0.05） at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 （P0.01） after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased （P0.01）. The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.
基金Supported by The Health Science and Technology Development Project of Shandong, No. 2005HZ024
文摘AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.
文摘Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a dosed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.
基金Supported by The National Key R and D Program of China,No.2018YFC1314103The National Natural Science Foundation of China,No.81870563 and No.82270838.
文摘BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.
文摘Introduction: In Senegal, with the CDIC “Changing Diabetes In children” project, insulin has been made free. The objective of this study was to evaluate the accessibility and modalities of insulin therapy in the management of type 1 diabetes. Methodology: This was a retrospective study including patients followed for type 1 diabetes (T1DM) in hospital between April 2018 and December 2020. Results: 281 patients were included. The mean age was 14.22 years. The mean age at diagnosis was 11.28 years. Ketoacidosis was the main mode of discovery of diabetes at 51.6%. Premix and rapid insulins were most commonly used at 84.7% and 82.9% respectively, most often in combination. The most commonly used treatment regimen was three injections/day in 82.5% of cases. The average daily insulin dose was 0.62 IU/Kg/dr. Of the patients, 219 (78%) were self-monitoring of blood glucose. The average number of blood glucose checks was 1.78 per day. 76 patients (27%) went days without an insulin injection and up to 7 days in 51% of cases. The main reasons were forgetfulness, therapeutic errors and stock-outs. Hypoglycaemia was observed in 14.2%. The average glycated haemoglobin was 10%. Conclusion: Despite the efforts made, there are still challenges to improve access to insulin. The reinforcement of therapeutic education on insulin therapy is essential for a better quality of life of diabetic children and adolescents.
文摘Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178;p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696;p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155;p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720;p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.
文摘Background It has been indicated that autologous hematopoietic stem cell transplantation （AHST） is a promising treatment to adults with type 1 diabetes, however, the application of AHST therapy to children with type 1 diabetes still needs more data. The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes. Methods This 1：2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology, Beijing Children＇s Hospital from 2009-2010. The case group included 14 patients, who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010. The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization. We compared the baseline and follow-up data of them, including ketoacidosis onset, clinical variables （glycosylated hemoglobin （HbAlc）, insulin dosage and serum C-peptide）. Results The clinical characteristics of the patients was comparable between the case group and the control group. At 6-12 months （（10.7±4.2） months） after AHST treatment, we found 11 patients in the case group did not stop the insulin therapy, three cases stopped insulin treatment for 2, 3 and 11 months, respectively. No diabetic ketoacidosis （DKA） occurred after transplantation in all the patients in the case group. HbAlc in the control group was significant lower than that in the case group （P 〈0.01）, while the insulin dosage and serum C-peptide were not significant different between the two groups （P 〉0.05）. In order to eliminate the honeymoon effect, we performed final follow-up at the 3-5 years （（4.2±1.8） years） after AHST treatment, and found that HbAlc in the control group was still lower than that in the case group （P 〈0.01）; however, the insulin dosage and serum C-peptide were not significantly different between the two groups （P 〉0.05）. Moreover, the insulin dosage was not significant different from baseline to follow-up period in the case group. Conclusion AHST treatment showed no advantage in effectiveness in children with newly diagnosed type 1 diabetes, both in insulin dose and long term blood glucose control. Chin med J2014;（14）：2618-2622
文摘Background Intensive insulin therapy has been found to lessen the progress of diabetic retinopathy （DR） to some extent,while it has also been implicated to be responsible for decrease of DR.We investigated visual function and morphological changes in the macular area in short-term follow-up of patients with type 2 diabetes mellitus after intensive insulin therapy.Methods This was a prospective clinical study of nonproliferative DR patients （102 eyes,120 patients） undergoing intensive insulin therapy.The Contrast Glare Tester （Takagi CGT-1000） was used to examine contrast sensitivity （CS） and Heidelberg Retina Tomograph （HRT） Ⅱ and Stratus Model 3000 OCT were used to observe the changes of morphology in the macular area.Follow-up times were pre-intensive therapy,3 and 6 months post-intensive therapy.Results CS at low and middle frequencies was higher at 3 and 6 months post-therapy compared with pre-therapy （P 〈0.05）.Significant differences in CS at low frequency were found between 6 and 3 months post-therapy （P 〈0.05）.Macular edema index was lower in the first,second,and third rings of the macular area after intensive therapy compared with pre-therapy （P 〈0.05）.Compared with 3 months post-therapy,the macular edema index was lower in the first,second,and third rings of the macular area at 6 months post-therapy （P 〉0.05）.No significant differences in the thickness of the first,second,and third rings of the macular area were detected between 3 and 6 months post-therapy and pre-therapy （P〉0.05）.Conclusion CS and macular edema indexes were significantly improved in nonproliferative diabetic retinopathy patients after intensive insulin therapy,but thickness of the macular area was unchanged.
文摘Background The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioperative period, insulin therapy is usually advised to be used for surgical patients with type 2 diabetes. However, the insulin regimen which one is better remains controversial. In this study, we estimated the efficacy, safety and advantage of different insulin therapy strategy during perioperative period.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.
基金the Akdeniz University Scientific Research Commission and the Scientific and Technological Research Council of Turkey,No.TUBITAK-215S820.
文摘Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change,insert,or remove a genomic sequence of interest.These advanced molecular tools include meganucleases,zinc finger nucleases,transcription activator-like effector nucleases and RNA-guided engineered nucleases(RGENs),which create double-strand breaks at specific target sites in the genome,and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism.A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype,without the need for the reengineering of the specific enzyme when targeting different sequences.CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function.RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes,as summarized and exemplified in this manuscript.
文摘BACKGROUND Insulin pump therapy is a real breakthrough in managing diabetes Mellitus,particularly in children. It can deliver a tiny amount of insulin and decreases the need for frequent needle injections. It also helps to maintain adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.Children are suitable candidates for pump therapy as they need a more freestyle and proper metabolic control to ensure adequate growth and development.Therefore, children and their caregivers should have proper education and training and understand the proper use of insulin pumps to achieve successful pump therapy. The pump therapy continuously improves to enhance its performance and increase its simulation of the human pancreas. Nonetheless, there is yet a long way to reach the desired goal.AIM To review discusses the history of pump development, its indications, types, proper use, special conditions that may enface the children and their families while using the pump, its general care,and its advantages and disadvantages.METHODS We conducted comprehensive literature searches of electronic databases until June 30, 2022,related to pump therapy in children and published in the English language.RESULTS We included 118 articles concerned with insulin pumps, 61 were reviews, systemic reviews, and meta-analyses, 47 were primary research studies with strong design, and ten were guidelines.CONCLUSION The insulin pump provides fewer needles and can provide very tiny insulin doses, a convenient and more flexible way to modify the needed insulin physiologically, like the human pancreas, and can offer adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.
文摘Insulin autoantibody (IAA) mediated insulin resistance (AMIR) is very rare in human insulin era.Here we report a typical case of a 90-year-old Chinese man who suffered from heart and renal dysfunction,lung infection and very poor blood glucose control,and meanwhile injected with higher than 200 U human insulin for his diabetes.His IAA was posi-tive with high affinity to insulin,as insulin antigen-antibody binding rate was 52% in vitro.Serum insulin level and the binding rate decreased dramatically with cession of insulin injection; also blood glucose profile restored to response to pre-vious dose insulin injection and remained during follow-up.Both the reason for the IAA formation and the solution to the AMIR were discussed in detail.
文摘Insulin therapy is an integral part of the pharmacological management of Type 2 diabetes mellitus. Guidelines recommended insulin therapy for those patients with suboptimal glycaemic control despite optimal medical treatments. Studies show that insulin therapy with the human and regular insulins improve glycaemic control, reduce the chronic complications, and inevitably improve patient’s quality of life. The new analogue insulin has a better safety profile and efficacies, and has been shown to achieve better outcomes and patient’s acceptability compared with the human and regular insulins. The diabetic guidelines also recommend the intensity of insulin therapy in a personalised glycaemic control strategy based on the patient’s profiles and their preferences. However, the guidelines do not recommend any standardised approach to the principles of insulin initiation, titration, and monitoring. This review summarises the essential principles of insulin initiation, titration, and monitoring in Type 2 diabetes mellitus.
基金Supported by A grant from Innovative Research Institute for Cell Therapy Project,South Korea,No.A062260
文摘AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.
基金Supported by a grant from the Educational Department of Liaoning Province (99022067).
文摘Objective To construct a single plasmid vector mediating doxycycline-inducible recombined human insulin gene expr-ession in myotube cell line. Methods An expression cassette of rtTAnls driven by promoter of human cytomegalovirus and a furin-cuttable recom-bined human insulin expression cassette driven by a reverse poly-tetO DNA motif were cloned into a single plasmid vector (prTR-tetO-mINS). The prTR-tetO-mINS and pLNCX were co-transfected into a myotube cell line (C2C12) and pLNCX vector were used as a control. After selection with G418, the transfected cells were induced with doxycycline at concentra-tions of 0, 2, and 10 μg/mL. RT-PCR was used to determine expression levels of recombinant insulin mRNA at the 5th day. Insulin production in cell cultures medium (at different incubation time) and cell extracts (at the 7th day) were analyzed with human pro/insulin RIA kits. Results Immune reactive insulin (IRI) level in cell medium was found increased at 24 hours of doxycycline incubation, and still increased at the 5th day. After withdrawn of doxycycline, IRI decreased sharply and was at baseline three days later. IRI and human insulin mRNA levels were positively related to different levels of doxycycline. A 25-fold increase in IRI was found against background expression at the 7th day. Conclusion Human insulin expression can be successfully regulated by doxycycline and the background was very low. This single tet-on insulin expression system may provide a new approach to a controlled insulin gene therapy in skeletal muscle.
文摘Objective: To observe the effect of acupuncture on hyperleptinaemia and hyperinsulinemia for studying its underlying mechanism about anti-obesity and reducing blood lipid in obesity rats. Methods: A total of 80 SD rats were randomized into normal control, model, acupuncture and medication groups, with 20 cases in each group. Hypothalamic obesity model was established by subcutaneous injection of 15% sodium glutamate (0.2 mL/10 g body weight), once daily and continuously for 5 days. “Zusanli” (足三里 ST 36), “Sanyinjiao”(三阴交 SP 6), “Guanyuan”(关元 CV 4) and “Zhongwan”(中脘 CV 12) were punctured and stimulated electrically (100 Hz, dense-sparse waves, and a suitable strength inducing local muscular tremor) for 15 min, once daily. In medication group, rats were fed with Sibutramine 4 mg/kg, once daily. After 4 weeks’ treatment, Lee’s index was detected, and serum leptin and insulin contents were determined by radioimmunoassay (RIA). Results: Compared with normal control group, Lee’s index, serum leptin and insulin contents of model group increased significantly (P<0.01). Comparison between acupuncture and model groups, Lee’s index and serum leptin of acupuncture group decreased significantly (P<0.01), and serum insulin level also lowered. In comparison with model group, Lee’s index, serum leptin and insulin levels of medication group also lowered. Comparison between acupuncture and medication groups showed that Lee’s index and serum leptin level of acupuncture group were significantly lower than those of the later group (P<0.01), displaying that the therapeutic effect of acupuncture is better than that of Sibutramine in lowering Lee’s index and serum leptin. No significant differences were found between acupuncture and medication groups in body weight and length and serum insulin(P>0.05). Conclusion: Acupuncture can effectively reduce Lee’s index, serum leptin and insulin contents in fasting obese rats, which may contribute to its effect in anti-obesity.
文摘Pancreatogenic diabetes,also known as type 3c diabetes,arises from pancreatic dysfunction due to conditions such as chronic pancreatitis and pancreatic cancer.This form of diabetes is characterized by both endocrine and exocrine pancreatic insufficiency,leading to insulin deficiency,glycemic variability,and maldigestion.The diagnostic process remains complex,as it shares clinical features with type 2 diabetes,and there are no standardized diagnostic criteria.Current treatment approaches include insulin therapy and pancreatic enzyme replacement therapy,along with nutritional support.However,the efficacy of oral hypoglycemic agents is limited,particularly in the presence of exocrine insufficiency.Epidemiological data indicate a significant overlap between pancreatogenic diabetes and pancreatic cancer,necessitating enhanced screening in high-risk populations.In this minireview,we highlight the pathophysiological mechanisms,diagnostic challenges,and current management strategies,emphasizing the need for improved diagnostic criteria and individualized treatment regimens.
