Short-term Intensive Insulin Therapy Research Articles

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

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. 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. 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. 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.

Empagliflozin combined with short-term intensive insulin therapy improves glycemic variability and 1,5-anhydroglucitol in patients with type 2 diabetes: a randomized clinical trial

Empagliflozin combined with short-term intensive insulin therapy improves glycemic variability and 1,5-anhydroglucitol in patients with type 2 diabetes: a randomized clinical trial

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

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. 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. 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. 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. 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.

Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes

In early type 2 diabetes, the strategy of “induction” with short-term intensive insulin therapy followed by “maintenance” with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this secondary analysis of ClinicalTrials.Gov NCT02192424, adults with ≤5-years diabetes duration were randomized to 3-weeks induction insulin therapy (glargine/lispro) followed by metformin maintenance either with or without intermittent 2-week courses of insulin every 3-months for 2-years. Sustained stabilization (higher beta-cell function at 2-years than at baseline) was achieved in 55 of 99 participants. Independent predictors of sustained stabilization were the change in beta-cell function during induction and changes in hepatic insulin resistance and alanine aminotransferase during maintenance. Thus, initial reversibility of beta-cell dysfunction during induction and subsequent preservation of hepatic insulin sensitivity during maintenance are associated with sustained stabilization of beta-cell function following short-term insulin and metformin.ClinicalTrials.Gov NCT02192424

814-P: Intensive Insulin Therapy within One Week Can Improve ß-Cell Function in T2D Patients

Objective: Short-term intensive insulin therapy (IIT), usually over 2 weeks, can improve β-cell function in T2D. However, whether shorter duration of IIT could also have impact on β-cell function remained unclear. This study was thus designed to explore this question. Methods: One hundred and ninety-two T2D patients who received continuous subcutaneous insulin infusion within 1 week and underwent comprehensive evaluation of β-cell function before and after IIT were included. β-cell function indices including HOMA-β, insulinogenic index, disposition index (DI), fasting and postprandial C-peptide index (CPI), AUC of insulin and C-peptide were adopted. In a subset patients underwent CGM, the correlation of glucose variability and β-cell function were analyzed. Results: The patients were 56.2±13.7 (mean±SD) years old, with diabetic duration of 6.0 (12.1) [median (interquartile)] years, HbA1c of 9.3±2.0%. After 3-7 days (median: 5 days) of IIT, insulinogenic index [3.6 (5.3) mU/mmol vs. 2.9 (4.4) mU/mmol, p=0.005], DI [358.3 (398.5) vs. 233.3 (275.5), p&amp;lt;0.001], fasting CPI [1.2 (0.8) nmol/mmol vs. 1.0 (0.8) nmol/mmol, p&amp;lt;0.001], postprandial CPI [1.8 (1.5) nmol/mmol vs. 1.4 (1.2) nmol/mmol, p&amp;lt;0.001] and AUC of C-peptide [113.0 (67.1) nmol∙min/L vs. 103.7 (55.9) nmol∙min/L, p=0.002] were significantly improved compared with baseline. Among these patients, 45 subjects underwent CGM. It was found that changes in DI from baseline (ΔDI) were negatively correlated with TAR (r=-0.417, P=0.004), standard deviation (r=-0.366, P=0.013), MAGE (r=-0.295, P=0.049), glucose coefficient of variation (r=-0.321, P=0.031) and positively correlated with TIR (r=0.359, P=0.004). Multiple linear regression revealed that duration of IIT (β=0.453, P=0.009) and TIR (β=0.527, P=0.006) were independent factors of ΔDI. Conclusions: IIT within 1 week can also improved β-cell function in T2D patients. Duration of IIT and TIR could be the independent factors responsible for the improvement of β-cell function. Disclosure W.Jiang: None. X.Chen: None. Z.Liu: None. B.Lin: None. W.Xu: None. L.Zeng: None.

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.

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. 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 0.5units/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. 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. 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.

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.

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. 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; 2h 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. 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, β-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%. These findings advocate TIRPIR ≥ 65% as a novel glycemic target during SIIT for clinical decision-making.

Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.

ObjectiveOur previous study has found that short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM) increased serum testosterone levels, but the underlying mechanisms remain unclear.Design and methodsIn this self-controlled study, 43 men with newly diagnosed drug naïve T2DM, aged 18-60 years, with HbA1c >9.0% were treated with continuous subcutaneous insulin infusion (CSII) to normalize blood glucose within one week. Venous blood specimens were collected for measuring of serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), 3β- and 17β-hydroxysteroid dehydrogenase (3β- and 17β-HSD) concentrations before and after insulin therapy.ResultsTestosterone increased from 13.0 (11.3, 14.6) nmol/L to 15.7 (13.9, 17.5) nmol/L after intensive insulin therapy (p<0.001), while the levels of DHEA-S decreased significantly after treatment (from 6.5 (5.7, 7.3) μmol/L to 6.0 (5.3, 6.7) μmol/L, p=0.001). The ratio of testosterone/DHEA-S increased significantly (2.4 (2.0, 2.8) vs. 3.1 (2.6, 3.7) nmol/μmol, p<0.001). After blood glucose normalization with the short-term CSII therapy, 3β-HSD increased from 11.0 (9.5, 12.5) pg/mL to 14.6 (13.5, 15.7) pg/mL, p=0.001, and 17β-HSD increased from 20.7 (16.3, 25.2) pg/mL to 28.2 (23.8, 32.5) pg/mL, p=0.009.ConclusionsBlood glucose normalization via short-term intensive insulin therapy increases plasma total testosterone levels in men with newly diagnosed type 2 diabetes, associated with a decreased level of DHEA-S, probably because of the enhanced conversion from DHEA to testosterone catalyzed by 3β-HSD and 17β-HSD.

Effects of dapagliflozin combined with short-term intensive insulin therapy on β-cell function in patients with newly diagnosed type 2 diabetes mellitus—a randomized controlled study

Effects of dapagliflozin combined with short-term intensive insulin therapy on β-cell function in patients with newly diagnosed type 2 diabetes mellitus—a randomized controlled study

1373-P: Changes in Body Composition Are Associated with Improvement of ß-Cell Function and Insulin Sensitivity after Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed Type 2 Diabetes

Objective: To investigate the change of muscle strength and body composition during short-term intensive insulin therapy (SIIT) and their association with treatment effects in patients with newly diagnosed type 2 diabetes (T2DM) . Research Design and Method: Patients with newly diagnosed T2DM were treated with SIIT to normalized blood glucose for at least 1 week. Physical examination including measurement of body diameters (neck circumference, upper arm circumference, waist circumference, hip circumference, thigh circumference, and calf circumference) , muscle strength (grip strength, the five-repetition sit-to-stand test, and the 30-second sit-to-stand test) , and body composition (body fat mass, muscle mass) , were performed. HbA1c and standardized mixed meal challenge tests were performed before and after the therapy. Results: A total of 53 patients were included. After SIIT, the muscle strength of the lower limbs was significantly enhanced. The average time of the five-repetition sit-to-stand test was shortened from 7.24s±1.58s to 6.15±1.21 (P&amp;lt;0.001) , and the average number of the 30-second sit-to-stand test increased from 24.23±5.56 to 27.69±5.96 (P&amp;lt;0.001) . The HOMA-IR and β-cell function also improved after SIIT. And the baseline thigh circumference was correlated with the change of both HOMA-IR (rs=-0.296 P=0.035) and the insulinogenic index (IGI) (rs=0.373 P=0.006) after SIIT. The fat mass at baseline was also correlated with improvements in both HOMA-IR (rs=-0.368 P=0.021) and the IGI (rs=0.424 P=0.007) after therapy. Conclusion: The muscle strength of the lower limbs was promoted after SIIT. Improvements in β-cell function and insulin sensitivity after SIIT in newly diagnosed T2DM patients are associated with changes in body composition but there are no relations with muscle strength. Disclosure C.Xu: None. Y.Li: None. L.Liu: None. Funding the National Natural Science Fund of China (81800716) , the science and technology program of Guangzhou, (202002020053)

803-P: Serum Adiponectin Level Is Reduced after Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed Type 2 Diabetes

Objective: Short-term intensive insulin therapy (SIIT) can induce remission of type 2 diabetes (T2D) , and the improvement of insulin sensitivity is considered essential. This study aimed to evaluate the role of adiponectin change during SIIT in patients with newly diagnosed T2D. Methods: SIIT was given to 42 patients with newly diagnosed T2D to normalize blood glucose (4.4-6.0 mmol/L for fasting blood glucose [FBG], 4.4-8.0 mmol/L for 2h-postprandial blood glucose [2hBG]) for two weeks. Serum lipids, adiponectin, and high-sensitive C reactive protein levels, insulin resistance and β-cell function were evaluated before and after SIIT. Results:After the therepy, FBG (11.8±2.9 mmol/L vs. 6.8±1.3mmol/L,P&amp;lt;0.001) and 2hPG (18.4mmol/L± 6.4mmol/L vs. 9.7±2.4mmol/L, P&amp;lt;0.001) were both significantly decreased, with β-cell function (measured by acute insulin response [AIR], HOM-B) and insulin sensitivity (measured by HOMA-IR) improved. Serum adiponectin raised from 2.9±1.2mg/L to 3.4±1.1mg/L (P&amp;lt;0.001) ,while serum triglyceride and LDL-C decreased significantly. Serum adiponectin after treatment was correlated with baseline triglyceride (r = -0.33, P = 0.04) , HDL-C (r = 0.34, P = 0.03) , LDL-C (r = -0.31, P = 0.05) and Hs-CRP (r = -0.33, P = 0.05) ; the change of adiponectin (Δadiponectin) after treatment were significantly correlated with the level of Δtriglyceride (r = 0.38, P = 0.03) . There was no notable correlation between adiponectin and β-cell function index or HOMA-IR. Adiponectin levels were similar between patients who obtained diabetes remission (defined as FBG&amp;lt; 7.0mmol/L, 2hBG&amp;lt;10.0mmol/L without hypoglycemic agents) and those who did not (baseline:3.0±1.5mg/L vs. 2.9±1.0 mg/L; after SIIT:3.4±1.0mg/L vs. 3.3±0.9 mg/L,both P&amp;gt;0.05) . Conclusion: Adiponectin level was significantly increased after SIIT in patients with newly diagnosed T2D. The change of adiponectin is related to the improvement of lipid metabolism and reduced inflammation. Disclosure L.Liu: None. W.Ke: n/a. J.Chen: None. Y.Li: None. Funding The National Key R&amp;D Program of China (2018YFC1314100) , the Key-Area Research and Development Program of Guangdong Province (2019B020230001) , the National Natural Science Fund of China (81800716) , the science and technology program of Guangzhou, 202002020053.

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

BackgroundDiabetes 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).MethodsThirty‐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.ResultsFive 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‐1β), 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%.ConclusionsA 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.

Short-term Intensive Insulin Therapy Induces Long-term Good Control of Blood Glucose in Newly Diagnosed Type 2 Diabetes Mellitus

Short-term Intensive Insulin Therapy Induces Long-term Good Control of Blood Glucose in Newly Diagnosed Type 2 Diabetes Mellitus

721-P: Efficacy and Safety of Basal-First Titration Order in Patients with Type 2 Diabetes (T2D) Receiving Short-Term Intensive Insulin Therapy (SIT)

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naive Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding Sanofi China (NCT03359837)

730-P: Basal Insulin Regimen vs. Twice-Daily Premix Insulin Regimen after Short-Term Intensive Insulin Therapy (SIT) in Patients with Type 2 Diabetes (T2D): A Multicenter, Open-Label Randomized Controlled Trial

730-P: Basal Insulin Regimen vs. Twice-Daily Premix Insulin Regimen after Short-Term Intensive Insulin Therapy (SIT) in Patients with Type 2 Diabetes (T2D): A Multicenter, Open-Label Randomized Controlled Trial

Short-term intensive insulin as induction and maintenance therapy for the preservation of beta-cell function in early type 2 diabetes (RESET-IT Main): A 2-year randomized controlled trial.

To test the hypothesis that the addition of periodic courses of short-term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta-cell function following induction IIT. In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration; HbA1c 6.6% ± 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2-week courses of IIT every 3 months for 2 years. Beta-cell function was assessed by the Insulin Secretion Sensitivity Index-2 (ISSI-2) at an oral glucose tolerance test every 3 months. In both arms, induction IIT increased ISSI-2, improved whole-body insulin sensitivity and reduced hepatic insulin resistance (all P ≤ .0004). The primary outcome of baseline-adjusted ISSI-2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline-adjusted difference -35 [95% CI: -66, -3]), with three additional beta-cell measures showing no significant differences. Baseline-adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% ± 0.1% vs. 6.4% ± 0.1%, P=.46), with 32.6% of participants in each arm maintaining HbA1c of6.0% or less at 2 years. Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta-cell function.

The effect of short-term intensive insulin therapy in newly-diagnosed Type-2 diabetic patients.

Objectives:We aimed to determine the effect of short-term intensive insulin therapy (SIIT) on long-term glycemic control in newly-diagnosed Type-2 diabetes mellitus (nT2DM) patients.Methods:In this retrospectively study conducted at Sakarya University Medical Faculty Training and Research Hospital Outpatient Clinic between 2016 and 2019, 65 nT2DM patients were enrolled soon after their SIIT was initiated and were followed for at least a year. Intensive insulin treatment was discontinued after three or 12 months in a total of 65 (23–73-year-old) patients who had been newly diagnosed with T2DM. Intensive insulin therapy was discontinued when glycemic control and the target Glycated Hemoglobin (HbA1c) level had been attained, after which oral anti-diabetic drug (OAD), long-term insulin, and diet therapies were pursued.Results:There was a significant decrease in mean HbA1c from 11.25±1.96% to 6.67±1.07%. Fasting plasma glucose (FPG) was found to be an independent predictor of whether intensive insulin therapy could be discontinued after three months in a model that included FPG, HbA1c, and body mass index measured at baseline. Patients with FPG>13.8 mmol/L were 7.6 times more likely to require intensive insulin therapy beyond three months. There were significant decreases in HbA1c and low-density lipoprotein-cholesterol concentration, but no change in C-peptide between baseline and 3 months of therapy.Conclusion:These results demonstrate that in nT2DM patients, intensive insulin therapy could be effective on long-term glycemic control and high FPG prior to three months of SIIT may predict poor long-term glycemic control.

Does short term intensive insulin therapy in newly diagnosed type 2 diabetes mellitus delay eventual insulin dependence?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

1032-P: Time-in-Range during Short-Term Intensive Insulin Therapy Is Associated with Clinical Outcomes in Patients with Newly Diagnosed Type 2 Diabetes

Background: Short-term intensive insulin therapy (SIIT) can reverse β cell dysfunction and induce glycemic remission in patients with newly diagnosed type 2 diabetes. Elimination of glucotoxicity to the maximum extent was considered the major mechanism. This study aimed to investigate the association of time in range (TIR) of predefined glycemic targets during SIIT with clinical outcomes after the therapy. Methods: SIIT was given to 95 patients with newly diagnosed T2DM using insulin pump. Strict glycemic control (premeal, bedtime or 3am BG 3.9-6.0 mmol/L, 2hBG 3.9- 8.0 mmol/L) was achieved and maintained for 2 weeks. TIR was defined by calculating the percentage of daily eight-point blood glucose values (before and 2 hours after each meal, at bedtime and 3am) within the above-mentioned near-normoglycemic targets. Intravenous glucose tolerance tests were performed before and after SIIT with acute insulin response (AIR), HOMA IR and HOMA B calculated. Patients were followed for 1 year after withdrawal of insulin. Results: Overall mean TIR was 68±11% during SIIT. After SIIT, both AIR and HOMA B increased while HOMA IR decreased. TIR during SIIT was significantly associated with improvement of AIR (r=0.36, P&amp;lt;0.001) but not with change of HOMA B (r=0.11, P=0.29) or HOMA IR (r=-0.17, P=0.11). One-year remission was observed in 59% (56/95) patients. Higher proportion of patients with TIR≥70% obtained glycemic remission for over 1 year compared with those with TIR&amp;lt;70% (71.4% vs. 49.1%, P=0.036) . In a logistic regression model, TIR≥70% was associated with higher 1- year glycemic remission after adjusting for Age, BMI and baseline A1c (OR 2.60, 95% CI 1.10-6. 13, P=0.03). Conclusion: Higher TIR during SIIT indicates better recovery of βcell function and long-term glycemic outcomes. Disclosure L. Liu: None. L. Xu: None. W. Ke: None. P. Zhang: None. C. Xu: None. D. Zang: None. Y. Li: None. Funding National Key Research and Development Program of China (2018YFC1314100); Key Research and Development Program of Guangdong Province (2019B020230001); National Natural Science Foundation of China (81800716)

1047-P: The Change of HOMA-IR Predicted the Remission Time in Patients with Newly Diagnosed Type 2 Diabetes after Intensive Insulin Therapy

Objectives: Insulin resistance is one of strong predictions on the remission in patients with newly diagnosed type 2 diabetes (T2DM) after short-term insulin intensive therapy (SIIT). Therefore, the purpose of this study is to explore if the short-term change of insulin resistance can predict the long-time remission. Methods: This study enrolled 160 patients with newly diagnosed type 2 diabetes mellitus (103 male, aged 49.8±10.4 yrs,HbA1c11±2.1%). All of them have been treated by 2-week continuous subcutaneous insulin infusion as SIIT when new diagnosed. HOMA-IR was compared just at the termination of SIIT and later then follow up every 3 months regularly for 5 years. Results: After short-term intensive treatment, up to 84.4%, 81.3% and 26.9% of patients achieved disease remission with T2DM at the termination of CSII, the 3rd month and 5th year follow up without use of medication. The average remission time were 27+/-615 months. The average changes of HOMA-IR in the first 3 months after SIIT were 30%+/-52%. This short-term change percent of HOMA-IR was positive related to the statue of remission at 5th-year follow-up (r = 0.778, p &amp;lt;0.0001). The ROC curve analysis showed below. Conclusions: Maintaining the improving insulin resistance after short-term insulin intensive therapy is essential for the long-time remission from T2DM. Lifestyle interventions might be helpful. Disclosure W. Xuesi: None. Z. Huang: None. L. Liu: None. Y. Li: None. Funding National Key Research and Development Program of China (2018YFC1314100)