[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Reduction in Diabetes-Related Hospitalizations and Medical Costs After Dexcom G6 Continuous Glucose Monitor Initiation in People with Type 2 Diabetes Using Intensive Insulin Therapy.

INTRODUCTION: Some people with type 2 diabetes (T2D) require intensive insulin therapy to manage their diabetes. This can increase the risk of diabetes-related hospitalizations. We hypothesize that initiation of real-time continuous glucose monitoring (RT-CGM), which continuously measures a user's glucose values and provides threshold- and trend-based alerts, will reduce diabetes-related emergency department (ED) and inpatient hospitalizations and concomitant costs. METHODS: A retrospective analysis of US healthcare claims data using Optum's de-identified Clinformatics® Data Mart database was performed. The cohort consisted of commercially insured, CGM-naïve individuals with T2D who initiated Dexcom G6 RT-CGM system between August 1, 2018, and March 31, 2021. Twelve months of continuous health plan enrollment before and after RT-CGM initiation was required to capture baseline and follow-up rates of diabetes-related hospitalizations and associated healthcare resource utilization (HCRU) costs. Analyses were performed for claims with a diabetes-related diagnosis code in either (1) any position or (2) first or second position on the claim. RESULTS: A total of 790 individuals met the inclusion criteria. The average age was 52.8 (10.5) [mean (SD)], 53.3% were male, and 76.3% were white. For claims with a diabetes-related diagnosis code in any position, the number of individuals with ≥ 1 ED visit decreased by 30.0% (p = 0.01) and with ≥ 1 inpatient visit decreased by 41.5% (p < 0.0001). The number of diabetes-related visits and average number of visits per person similarly decreased by at least 31.4%. Larger relative decreases were observed for claims with a diabetes-related diagnosis code in the first or second position on the claim. Total diabetes-related costs expressed as per-person-per-month (PPPM) decreased by $341 PPPM for any position and $330 PPPM for first or second position. CONCLUSION: Initiation of Dexcom G6 among people with T2D using intensive insulin therapy was associated with a significant reduction in diabetes-related ED and inpatient visits and related HCRU costs. Expanded use of RT-CGM could augment these benefits and result in further cost reductions.

Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes.

Background: This study aims to investigate the changes in circulating dipeptidyl peptidase-4 (DPP-4) activity following short-term intensive insulin therapy (SIIT) in newly diagnosed type 2 diabetes (T2D) patients and to assess its potential in predicting long-term remission. Methods: Ninety-five patients underwent SIIT for 2-3 weeks to attain and sustain near-normal glycemia. Insulin was then discontinued, and patients were followed for a year to evaluate glycemic outcomes. Biochemical tests, serum DPP-4 activity, and mixed meal tolerance tests were conducted at baseline, post-SIIT, and the 3-month follow-up. Results: DPP-4 activity decreased from 44.08 ± 9.58 to 40.53 ± 8.83 nmol/min/mL after SIIT (P<0.001). After three months post-SIIT, DPP-4 activity remained stable in the remission group (39.63 ± 8.53 nmol/L) but increased in the non-remission group (42.34 ± 6.64 nmol/L). This resulted in a more pronounced decrease in DPP-4 activity from baseline in the remission group (-3.39 ± 8.90 vs. -1.10 ± 8.95, P = 0.035). Logistic regression analyses showed that patients with greater DPP-4 activity reduction had a higher likelihood of 1-year remission (70% vs. 51.1%, OR: 7.939 [1.829, 34.467], P = 0.006 in the fully adjusted model). A non-linear relationship between △DPP-4 and 1-year remission rate was observed, with a clear threshold and saturation effect. Conclusion: Circulating DPP-4 activity significantly decreases after SIIT. The change in circulating DPP-4 activity during the 3-month post-treatment phase has the potential to predict long-term remission.

Association Between Adherence, A1C Improvement, and Type of Continuous Glucose Monitoring System in People with Type 1 Diabetes or Type 2 Diabetes Treated with Intensive Insulin Therapy.

INTRODUCTION: Use of continuous glucose monitoring (CGM) systems by people with diabetes is associated with improved glycemic outcomes, including lower glycated hemoglobin (A1C). Less is known about adherence to CGM systems, whether glycemic outcomes are impacted by levels of adherence, or whether adherence rates differ between types of CGM systems-intermittently scanned CGM (isCGM) or real-time CGM (rtCGM). METHODS: A retrospective analysis of de-identified US administrative health claims and linked laboratory data was conducted using the Merative™ MarketScan® Research Database. The cohort included CGM-naïve people with type 1 diabetes (T1D) or type 2 diabetes treated with intensive insulin therapy (T2D-IIT) who initiated rtCGM or isCGM between August 1, 2019 and March 31, 2021 (defined as the index date). Adherence was calculated over a 12-month period using the proportion of days covered (PDC) with PDC ≥ 0.8 defined as adherent. A1C values were obtained within 6 months of the index date. RESULTS: A total of 7669 individuals were identified. Subgroups included T1D using isCGM (n = 1578), T1D using rtCGM (n = 1244), T2D-IIT using isCGM (n = 3567), and T2D-IIT using rtCGM (n = 1280). After 12 months, PDC was 0.71 (0.30)-0.72 (0.31) (mean(SD)) for T1D and T2D-IIT rtCGM users and 0.55 (0.34)-0.56 (0.34) for T1D and T2D-IIT isCGM users. The proportion of adherent users (PDC ≥ 0.8) was 56.8-59.7% for rtCGM users and 36.3-37.6% for isCGM users. Overall, regardless of diabetes type, the odds of adherence were over two times higher for rtCGM users compared to isCGM users. For those with available A1C information (T1D n = 213; T2D-IIT n = 346), independent of CGM type, adherence to CGM was associated with a greater reduction in A1C and more people reaching A1C targets of < 7.0% or < 8.0%. CONCLUSION: For people with T1D or T2D-IIT, higher adherence to CGM is associated with greater reductions in A1C, and higher adherence rates were observed with rtCGM systems than with isCGM systems.

A Review on Latent Autoimmune Diabetes in Adults.

Latent autoimmune diabetes (LADA) is an unique form of diabetes that has characteristics of both type 1 and type 2 diabetes. Type 1.5 diabetes also known as LADA is occasionally confused for type 2 diabetes because there is delay in presenting features and early insulin independence. LADA, on the other hand, is an autoimmune disorder that differs from type 2 diabetes in that autoantibodies against pancreatic beta cells are what characterise it. Insulin production eventually diminishes due to the autoimmune destruction of pancreatic beta cells as a result of the pathophysiology of LADA. Autoantibodies to glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2), and insulin are frequently detected in LADA patients. These autoantibodies have important implications for therapy strategies and are essential in differentiating LADA from type 2 diabetes. LADA clinical management is very challenging. The aim of this article is to view the characteristics, disease presentation, diagnostic challenges, progression and treatment modalities of LADA.

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

BACKGROUND: Extrachromosomal circular DNA (eccDNA) has emerged as a promising biomarker for disease diagnosis and prognosis prediction. However, its role in type 2 diabetes remains unexplored. OBJECTIVE: To investigate the characteristics and dynamics of circulating eccDNAs in newly diagnosed type 2 diabetes mellitus (T2DM) patients undergoing short-term intensive insulin therapy (SIIT), a highly effective treatment for inducing long-term glycemic remission. METHODS: We conducted Circle-Seq analysis on plasma samples from 35 T2DM patients at three time points: pre-SIIT, post-SIIT, and 1-year post-SIIT. Our analysis encompassed the characterization of eccDNA features, including GC content, eccDNA length distribution, genomic distribution, and the genes in eccDNAs. RESULTS: Following SIIT, we observed an increase in plasma eccDNA load, suggesting metabolic alterations during therapy. Notably, a correlation was identified between eccDNA profiles and glycemia in T2DM, both quantitatively and genetically. Our analysis also revealed the frequent presence of metabolism-related genes within T2DM plasma eccDNAs, some of which spanned gene exons and/or fractions. CONCLUSION: This study represents the first report of cell-free eccDNA in T2DM and underscores a compelling association between cell-free eccDNA and profound glycemic changes. These findings highlight the potential of eccDNAs as crucial players in the context of T2DM and glycemic control.

A self-controlled, cross-over study of intensive insulin treatment with needle-based injection versus needle-free injection in hospitalized patients with type 2 diabetes.

Background and Aims: Needle injection and needle-free injection were proven effective in improving glycated hemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) patients. However, it is unclear if needle-free and needle injections of insulin during intensive insulin therapy in hospitalized patients provide similar efficacy and safety benefits. Methods: A self-controlled cross-over study was conducted on 62 patients with T2DM who received intensive long-acting and short-acting insulin injections with or without needles. The 7-point blood glucose test was performed on the 6th day after insulin administration and the injection method switched on the 7th day of hospitalization. The difference was compared in 7-point blood glucose levels. Results: The blood glucose levels at fasting (mean difference=-1.09 ± 2.38mmol/L, 95% CI, -1.69 to -0.48, p=0.0007) and post-breakfast (-1.14 ± 3.02mmol/L, 95%CI, -1.91 to -0.37, p=0.004) were better when patients were receiving needle-free injections compared to when receiving a needle injection. Indeed, daily blood glucose fluctuation, which presented as the area under the curve of glycemia, was decreased in needle-free injection periods (-0.3.48 ± 9.64, 95%CI, -5.95 to -1.01, p=0.0065). There was no significant difference in the dose of long-acting insulin between the two injection methods (-0.32 ± 2.69, 95%CI, -0.99 to 0.37, p>0.05). The dose of fast-acting insulin during the needle-free period was lower than that of when patients received needle injections (-1.66 ± 6.45, 95%CI, -3.29 to -0.025, p<0.05). There was no significant difference in satisfaction between the two regimens (-0.59 ± 1.55,95%CI, -0.938 to 0.509, p=0.557), but there was a significant difference in pain experience, favoring needle-free injections (p < 0.001). Conclusion: Glycemia was better controlled by needle-free insulin injections in hospitalized T2DM patients subjected to intensive glycemic control. These patients also experienced less pain than when insulin was injected with a needle.

[Investigation of diabetic retinopathy progression in women with diabetes mellitus during pregnancy]. / Issledovanie osobennostei progressirovaniya diabeticheskoi retinopatii u zhenshchin, stradayushchikh sakharnym diabetom, v period beremennosti.

PURPOSE: The study evaluates the transient and stationary diabetic retinal changes in pregnant women with diabetes mellitus (DM) based on the analysis of individual clinical cases of diabetic retinopathy (DR) progression. MATERIAL AND METHODS: The study examined 24 pregnant women with DM. The examination was carried out in each trimester of pregnancy and 6 months after delivery. In 10 pregnant women DR was not detected, and 14 (58%) were diagnosed with DR. RESULTS: Progression of DR during pregnancy was observed in 9 patients with pre-proliferative and proliferative DR (PPDR and PDR) and uncompensated glycemia, 3 patients developed macular edema (ME) in both eyes. Panretinal laser coagulation (PRLC) was performed in patients with ongoing DR progression. In the postpartum period, the manifestations of DR did not regress. ME turned out to be transient in one patient with PPDR. Three clinical cases of DR manifesting in the first trimester of pregnancy are presented: PPDR with transient ME, PDR with ME, non-proliferative DR with a stable course. CONCLUSION: 1. DR detected at the beginning of gestation in women with decompensated glycemic status progressed in 64% of cases. 2. Progression of DR during pregnancy was noted in patients with PPDR and PDR. 3. Progression of DR during pregnancy is more often true than transient. 4. Detection of PPDR and PDR during pregnancy is a direct indication for laser coagulation of the retina.

Intensive insulin therapy in sepsis patients: Better data enables better intervention.

In clinics, sepsis is a critical disease that often develops into shock and multiple organ dysfunction, leading to a serious threat of death. Patients with sepsis are often accompanied by stress hyperglycemia which is an independent risk factor for poor prognosis in sepsis. Thus, the treatment for stress hyperglycemia has attracted more and more attention, among which intensive insulin therapy is widely concerned. However, the benefits and harms of intensive insulin therapy for sepsis patients remain controversial. What the existing literature discusses mostly are the clinical benefit and hypoglycemia risk of intensive insulin therapy, but there is no conclusion on the target range of blood glucose control, the applicable patients, the timing of treatment initiation, and how to avoid the risk. In this study, we have analyzed and summarized the existing literature, hoping to determine the adverse and clinical benefit of intensive insulin therapy in sepsis. And we attempt to assemble better evidence to propose a better recommendation on hyperglycemia intervention for sepsis patients.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Evaluating the role of time in range as a glycemic target during short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Tight glycemic control during short-term intensive insulin therapy (SIIT) is critical for inducing diabetes remission in patients with newly diagnosed type 2 diabetes (T2D). This work aimed to investigate the role of time in range (TIR) during SIIT as a novel glycemic target by predicting clinical outcomes. METHODS: SIIT was given to 116 patients with newly diagnosed T2D, with daily eight-point capillary glucose monitored. Glycemic targets (fasting/premeal glucose, 3.9-6.0 mmol/L; 2 h postprandial blood glucose, 3.9-7.8 mmol/L) were achieved and maintained for 2 weeks. TIRPIR was calculated as the percentage of glucose points within these glycemic targets during the maintenance period and was compared to TIR3.9-7.8mmol/L and TIR3.9-10.0mmol/L . Acute insulin response (AIR), HOMA-IR, HOMA-B, and disposition index (DI) were measured. Patients were followed up for 1 year to observe clinical outcomes. RESULTS: TIRPIR , TIR3.9-7.8mmol/L , and TIR3.9-10.0mmol/L were 67.2 ± 11.2%, 80.8 ± 9.2%, and 90.1 ± 6.2%, respectively. After SIIT, ß-cell function and insulin sensitivity improved remarkably, and the 1-year remission rate was 55.2%. △AIR and △DI were positively correlated with all the TIR values, whereas only TIRPIR was correlated with △HOMA-IR (r = -0.22, p = 0.03). Higher TIRPIR but not TIR3.9-7.8mmol/L or TIR3.9-10.0mmol/L was robustly associated with diabetes remission; patients in the lower TIRPIR tertile had an elevated risk of hyperglycemia relapse (hazard ratio 3.4, 95% confidence interval 1.6-7.2， p = .001). Only those with TIRPIR ≥ 65% had a one-year remission rate of over 60%. CONCLUSIONS: These findings advocate TIRPIR ≥ 65% as a novel glycemic target during SIIT for clinical decision-making.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Effect of intensive insulin therapy on inflammatory response after cardiac surgery using bedside artificial pancreas: A propensity score-matched analysis.

BACKGROUND: Perioperative hyperglycemia leads to poor postoperative clinical outcomes, including compromised immune function, cardiovascular events, and mortality. The optimal perioperative blood glucose levels during cardiac surgery remain unclear. A closed-loop glycemic control system (artificial pancreas, target blood glucose range:120-150 mg/dl) prevents postoperative inflammatory response more effectively than conventional insulin therapy (<200 mg/dl). However, the clinical effects of intensive insulin therapy with strict glycemic control (80-110 mg/dl) are controversial. This study aimed to determine whether intensive insulin therapy would further suppress postoperative inflammatory reactions. METHODS: This study analyzed 262 patients who underwent cardiovascular surgery with cardiopulmonary bypass. The patients were divided into two groups according to their target blood glucose range: 80-110 mg/dl and 120-150 mg/dl. The primary outcome was the difference in the C-reactive protein levels between the two groups. RESULTS: Propensity score matching resulted in 95 patients in each group based on their covariates. There was no difference in the postoperative maximum C-reactive protein levels between the two groups (14.81 ± 5.93 mg/dl vs. 14.34 ± 5.52 mg/dl; p = 0.571) following propensity score matching. Hypoglycemia did not occur during intensive insulin therapy. CONCLUSIONS: Intensive insulin therapy following cardiac surgery with cardiopulmonary bypass did not demonstrate significant advantages in the suppression of postoperative inflammatory reactions compared to that with mild glycemic control. However, intensive insulin therapy using an artificial pancreas was found to be safe, with no hypoglycemic events.

Glycaemic Control Achieves Sustained Increases of Circulating Endothelial Progenitor Cells in Patients Hospitalized for Decompensated Diabetes: An Observational Study.

BACKGROUND AND AIM: Diabetes reduces the levels of circulating endothelial progenitor cells (EPCs), which contribute to vascular homeostasis. In turn, low EPCs levels predict progression of chronic complications. Several studies have shown that hyperglycaemia exerts detrimental effects on EPCs. Improvement in glucose control with glucose-lowering medications is associated with an increase of EPCs, but only after a long time of good glycaemic control. In the present study, we examined the effect of a rapid glycaemic amelioration on EPC levels in subjects hospitalized for decompensated diabetes. METHODS: We used flow cytometry to quantify EPCs (CD34+/CD133+KDR+) in patients hospitalized for/with decompensated diabetes at admission, at discharge, and 2 months after the discharge. During hospitalization, all patients received intensive insulin therapy. RESULTS: Thirty-nine patients with type 1 or type 2 diabetes were enrolled. Average (± SEM) fasting glucose decreased from 409.2 ± 25.9 mg/dl at admission to 190.4 ± 12.0 mg/dl at discharge and to 169.0 ± 10.3 at 2 months (both p < 0.001). EPCs (per million blood cells) significantly increased from hospital admission (13.1 ± 1.4) to discharge (16.4 ± 1.1; p = 0.022) and remained stable after 2 months (15.5 ± 1.7; p = 0.023 versus baseline). EPCs increased significantly more in participants with newly-diagnosed diabetes than in those with pre-existing diabetes. The increase in EPCs was significant in type 1 but not in type 2 diabetes and in those without chronic complications. CONCLUSION: In individuals hospitalized for decompensated diabetes, insulin therapy rapidly increases EPC levels for up to 2 months. EPC defect, reflecting impaired vascular repair capacity, may be reversible in the early diabetes stages.

Efficacy and safety of a basal insulin + 2-3 oral antihyperglycaemic drugs regimen versus a twice-daily premixed insulin + metformin regimen after short-term intensive insulin therapy in individuals with type 2 diabetes: The multicentre, open-label, randomized controlled BEYOND-V trial.

AIM: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China. MATERIALS AND METHODS: This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). RESULTS: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group. CONCLUSIONS: Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

Relationship Between Glucose Time in Range in Diabetic and Non-Diabetic Patients and Mortality in Critically Ill Patients.

Background: Shorter time spent in specific blood glucose ranges is associated with mortality benefit in critically ill patients. However, various time in range values are reported, each based on a specific blood glucose range. Objective: To evaluate relationship between percentage of time spent at various blood glucose ranges (TIR) and mortality in critically ill patients. Methods: Single-center, retrospective, cohort study that included adult patients admitted to ICU for at least one day. We evaluated the relationship between TIR at prespecified blood glucose ranges and hospital mortality in diabetic and non-diabetic patients Results: Of the 5287 patients included, 3705 (70.0%) were non-diabetic and 1582 were diabetic (29.9%). Diabetic patients had higher in-hospital mortality rate (15.8%) compared to non-diabetic patients (11.3%), p < 0.0001, and with higher incidence of hyperglycemia (77.8% vs. 39.4%) and hypoglycemia (14.3% vs. 10%) compared to non-diabetic patients, p < 0.0001. The highest median TIR for both diabetic [76% (49.1 - 97.8%)] and non-diabetic patients [100% (92.3--100%)] was at blood glucose range of 70-180 mg/dL. In non-diabetic cohort, the only optimal TIR of 40% at blood glucose range of 70-120 mg/dL was identified. Non-diabetic patients stratified into TIR 70-120 mg/dL > 40% reported significantly lower mortality (7.0%) rate compared to patients with TIR 70-120 mg/dL < 40% (15.7%), OR 0.52, 95% CI 0.27-0.97, adjusted-p = 0.03. In diabetic patients, no relationship was detected between TIR at all predefined glucose ranges and hospital mortality. Conclusion: Critically ill non-diabetic patients who spent at least 40% of time in blood glucose range of 70-120 mg/dL had improved survival. This association was not observed in diabetic patients.

Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study.

BACKGROUND: We examined the retinal microvascular changes and associated factors in type 2 diabetes mellitus (T2DM) before and after intensive insulin therapy. METHODS: This prospective observational study recruited patients with T2DM and divided them into intensive insulin therapy and oral hypoglycemic agent groups. All patients enrolled in this study had diabetes without retinopathy or non-proliferative diabetic retinopathy. Optical coherence tomography angiography (OCTA) was used in all patients before treatment and at 1, 3, and 6 months after treatment. Vessel density (VD) and thickness changes in the macular and optic disc areas were assessed. RESULTS: The study included 36 eyes in the intensive insulin therapy group and 36 in the oral hypoglycemic agent group. One month after treatment, VD in the deep capillary plexus (DCP) and peripapillary capillary VD (ppVD) were significantly decreased by intensification (P = 0.009, 0.000). At three months after treatment, decreases in VD induced by intensification were found in the superficial capillary plexus (SCP), DCP, foveal density in a 300-µm-wide region around the foveal avascular area (FD-300), and ppVD (P = 0.032, 0.000, 0.039, 0.000). Six months after treatment, decreases in VD by intensification were observed in the DCP and ppVD groups (P = 0.000, 0.000). Vessel density showed no significant change in the oral hypoglycemic agent group after treatment. The amount of DCP-VD reduction was correlated with macular thickening (r = 0.348, P = 0.038; r = 0.693, P = 0.000 and r = 0.417, P = 0.011, respectively) after intensive insulin therapy. CONCLUSIONS: Insulin-intensive treatment caused a transient reduction in vessel density in the macular and optic disc areas. DCP-VD and ppVD were more susceptible at an earlier stage. Retinal microvasculature monitoring using OCTA is vital for patients with type 2 diabetes receiving intensive insulin therapy.

The effect of short-term intensive insulin therapy on inflammatory cytokines in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Diabetes mellitus was a chronic low-grade inflammatory disease and had increased circulating inflammatory cytokines and acute phase proteins. We aimed to identify the changes of inflammatory cytokines in newly diagnosed type 2 diabetic patients after short-term intensive insulin therapy using continuous subcutaneous insulin infusion (CSII). METHODS: Thirty-three newly diagnosed type 2 diabetic patients were enrolled between September 2020 to December 2020. Expression of 40 inflammatory cytokines of the patients were tested with RayBiotech antibody array before and after 1 week of intensive insulin therapy of CSII. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out to explore the signaling pathway involved in the therapy. RESULTS: Five inflammatory cytokines were downregulated significantly after 1 week of CSII therapy. They were interleukin-6 receptor (IL-6R), regulated upon activation normal T-cell expressed and secreted (RANTES), intercellular adhesion molecule-1 (ICAM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and platelet-derived growth factor type BB (PDGF-BB) (p < 0.05 and foldchange <0.83). Among patients with baseline glycated hemoglobin (HbA1c) < 10%, three proinflammatory cytokines were decreased significantly after therapy: IL-6R, RANTES, and ICAM-1. As for the patients with baseline HbA1c ≥ 10%, eight inflammatory cytokines were inhibited significantly after the treatment, including ICAM-1, IL-6R, RANTES, TIMP-1, TIMP-2, macrophage inflammatory protein-1 beta (MIP-1ß), PDGF-BB, and tumor necrosis factor receptor type II (TNF RII). No matter which subgroup of baseline HbA1c level was considered, the decreased cytokines after CSII therapy were significantly involved in TNF signaling pathway. Nuclear factor-kappa B (NF-κB) signaling pathway was mainly enriched in patients with baseline HbA1c ≥ 10%. CONCLUSIONS: A panel of 40 inflammatory cytokines, measured by protein microarray, were evaluated for 1 week of CSII treatment in newly diagnosed type 2 diabetic patients. After treatment, many proinflammatory cytokines decreased. In the higher baseline HbA1c subgroup, more proinflammatory cytokines improved. No matter which subgroup of HbA1c level was considered, IL-6R, RANTES, and ICAM-1, which were involved in TNF signaling pathway, decreased significantly after CSII therapy. This was the first report showing that the cytokines of IL-6R, TIMP-2, PDGF-BB, and TNF RII decreased after the CSII therapy.

Optimizing type 1 diabetes after multiple daily injections and capillary blood monitoring: Pump or sensor first? A meta-analysis using pooled differences in outcome measures.

AIMS: Most people living with type 1 diabetes self-manage using multiple daily injection (MDI) insulin regimens and self-monitoring of blood glucose (SMBG). Continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) are adjuncts to education and support self-management optimization. The aim of this systematic review and meta-analysis was to assess which first-line technology is most effective. METHODS: Electronic databases (MEDLINE, EMBASE and WEB OF SCIENCE) were systematically searched from 1999 to September 2020. Randomized controlled trials comparing either CSII with MDI or CGM with SMBG in adults with type 1 diabetes were included. Data were extracted in duplicate by two reviewers, and were analysed to assess individual and overall treatment effect measures (PROSPERO registration: CRD42020149915). RESULTS: Glycated haemoglobin was significantly reduced for CGM when compared with SMBG [Cohen's d - 0.62 (95% CI -0.79 to -0.45)] and for CSII when compared with MDI [Cohen's d - 0.44 (95% CI -0.67 to -0.22)]. Rates of severe hypoglycaemia were significantly reduced with CGM compared with SMBG, but did not change for CSII when compared with MDI. Episodes of diabetic ketoacidosis were more likely to occur with CSII than MDI. Both CSII and CGM reduced glucose standard deviation, compared with MDI and SMBG respectively. CONCLUSIONS: Both CGM and CSII remain impactful interventions compared with SMBG and MDI but in adults with type 1 diabetes and in the contexts in which they have been studied, CGM might have a greater positive impact on glycaemic variability and severe hypoglycaemia than CSII, when added to MDI and SMBG. A head-to-head study, including patient reported outcomes, is required to explore these findings further.