Intensive Insulin Therapy In Patients Research Articles

Efficacy of switching from basal-bolus insulin therapy to twice-daily insulin degludec/insulin aspart co-formulation plus insulin aspart in patients with poorly controlled type 2 diabetes.

The aim of this study was to evaluate the efficacy of twice-daily (BID) insulin degludec/insulin aspart (IDegAsp) co-formulation + once-daily (OD) bolus insulin aspart (IAsp) injection (IDegAsp BID-Plus) as simplified intensive insulin therapy in patients with poorly controlled type 2 diabetes mellitus (T2DM) with basal-bolus insulin therapy (BBIT). The retrospective study included 155 patients who switched from BBIT to IDegAsp BID-Plus. After the initiation of the treatment, 73 patients continued regular follow-up and insulin doses, number of injections, hemoglobin A1c (HbA1c) levels, and other parameters were recorded from their files at baseline, 24, and 52 weeks. The mean age of the study population was 54.3±10.2 years, the duration of T2DM was 9.7±5.7 years, fasting plasma glucose (FPG) was 252.7±66.7 mg/dl, and HbA1c levels were 10.5±1.5%. Among the included patients, 15 patients received five injections, 51 patients received four injections, and 7 patients received three injections per day. There was a significant decrease in HbA1c (respectively; 10.46±1.54%, 7.97±1.24%, 7.98±1.23%, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001), FPG (respectively; 251.6±66.5 mg/dl, 136.1±34.7 mg/dl, 125.4±67.0 mg/dl, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001) and daily dose of insulin (respectively; 102.9±29.0 Unit, 73.2±18.2 U, 63.7±20.3 Unit, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001) at the end of week 24 and 52. Based on real-world data, this study demonstrated that IDegAsp BID-Plus treatment provides rapid and sustainable blood glucose control with lower insulin doses and fewer injections than previous intensive insulin therapy.

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.

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.

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)

Continuous subcutaneous insulin infusion ameliorates bone structures and mechanical properties in type 2 diabetic rats by regulating bone remodeling.

Continuous subcutaneous insulin infusion (CSII) is an intensive insulin therapy for patients with type 2 diabetes mellitus (T2DM) who have poor glycemic control, but its effect on T2DM-related bone disorder is unclear. This study described the possible mechanisms by which CSII affects bone remodeling, structures, and mechanical properties in T2DM rats. Herein, male rats (6-week-old) were assigned randomly to 4-week and 8-week administration groups, each of which included healthy control, T2DM, CSII, and Placebo groups. Then, metabolic markers, bone formation and resorption markers in serum and protein expressions of osteoclastogenesis regulators in tibias were detected. Meanwhile, microstructures, nanostructures, macro-mechanical properties, nano-mechanical properties, and mineral compositions in femurs were evaluated. 4-week later, CSII treatment restored circulatory metabolites, bone formation and resorption markers, and osteoclastogenesis regulators, improved certain bone microstructures, decreased matrix mineralization, and increased fracture toughness in T2DM rats. For 8-week group, CSII treatment restored bone formation and resorption markers, osteoclastogenesis regulators, and bone microstructures, besides improved bone mineral compositions and nanostructures, enhanced bone mechanical properties such as fracture toughness, maximum load, elastic modulus, indentation modulus and hardness. Collectively, 8-week CSII treatment is more conducive to ameliorating bone structures and mechanical properties in T2DM rats by regulating bone remodeling compared with 4-week CSII treatment, thus improving whole bone quality and providing valuable information for clinical prevention and treatment of T2DM-related bone disorders.

Long Term Evaluation of Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus

Background: This study aimed to determine long-term effect of intensive insulin therapy on prevention, progression, and development of chronic diabetes complications, both micro and macrovascular events. This study also aimed to evaluate long-term sustainability of glycemic control of patients on intensive insulin treatment. Methods: A retrospective review of adult type 2 diabetes mellitus (T2DM) patients on intensive insulin therapy for ≥7 years. Demographic data, co-morbidities, body mass index (BMI), hemoglobin A1c (HbA1c), hospitalization were collated. Majority received intensive insulin therapy with combination of premixed 70/30 given two times a day and fast short acting analogue given premeal three times a day, with the addition of glargine or degludec once a day in some. Results: Among 76 patients, 62% were males and 38% were females. Mean age at diagnosis and last visit were 53 and 65 years, respectively. At time of diagnosis, patient had the following co-morbidities: hypertension (32%), dyslipidemia (13%), non-dialyzable chronic kidney disease (CKD) (4%), thyroid disease (1%), pulmonary tuberculosis (1%). In terms of long-term complications, event rates during follow up period are as follows: 0.001 per person-year for acute coronary event; 0.002 per person-year for CKD needing dialysis, 0.009 per person-year for cerebrovascular accident. There were no blindness and amputation observed. There is a statistical difference between HbA1c levels at time of diagnosis (8.53 ± 1.86) and last follow up (7.83 ± 1.71) (P = 0.00). After a median follow up of 12 years (7–22 years), glycemic control was sustained with an HbA1c of ≤7% and ≤8% in 32% and 45% of patients, respectively. Conclusion: With intensive insulin therapy, micro and macrovascular complications can be prevented significantly. Long-term sustainability of glycemic control was also achieved.

Could the appropriate anti-diabetic therapy be mixed insulin in dialysis patients?

A good glycemic regulation should be provided to reduce mortality and morbidity in patients with end-stage renal failure due to diabetes mellitus. However, the use of insulin therapies in patients with renal failure is troublesome due to the increased rate of side effects. In our study, we investigated the frequency of hypoglycemia and its symptoms in patient groups receiving intensive and mixed insulin therapies. This prospective study included 89 hemodialysis patients with DM-related stage 5 chronic kidney disease who were followed up in a nephrology clinic of a university hospital between January 2013 and August 2015. Our study group was divided into two groups as those receiving intensive insulin therapy and mixed insulin therapy. Group 1 and group 2 consisted of 46 patients and 43 patients, respectively. Hypoglycemia (glucose 0.05). Hypoglycemia was detected in 27 patients (58.7%) in the intensive insulin therapy group and 14 patients (32.6%) in the mixed insulin therapy group. There was a significant level of hypoglycemia in the group receiving intensive insulin therapy (p < 0.05). In our study, the group receiving intensive insulin therapy had higher frequency and severity of common hypoglycemia symptoms such as confusion, sweating, weakness, dysphasia, palpitations, blurred vision, and feeling hungry. There was a higher frequency of hypoglycemia under intensive insulin therapy in patients undergoing dialysis due to chronic kidney failure, which suggests that mixed insulin therapy is the ideal treatment to avoid hypoglycemia in this group of patients.

Outsourcing glucose management to AI

An automated decision support tool could expand access to intensive insulin therapy for patients with type 1 diabetes.

Development and Validation of a Hypoglycemia Risk Model for Intensive Insulin Therapy in Patients with Type 2 Diabetes.

Aims To develop a simple hypoglycemic prediction model to evaluate the risk of hypoglycemia during hospitalization in patients with type 2 diabetes treated with intensive insulin therapy. Methods We performed a cross-sectional chart review study utilizing the electronic database of the Third Affiliated Hospital of Sun Yat-sen University, and included 257 patients with type 2 diabetes undergoing intensive insulin therapy in the Department of Endocrinology and Metabolism. Logistic regression analysis was used to derive the clinical prediction rule with hypoglycemia (blood glucose ≤ 3.9 mmol/L) as the main result, and internal verification was performed. Results In the derivation cohort, the incidence of hypoglycemia was 51%. The final model selected included three variables: fasting insulin, fasting blood glucose, and total treatment time. The area under the curve (AUC) of this model was 0.666 (95% CI: 0.594–0.738, P < 0.001). Conclusions The model's hypoglycemia prediction and the actual occurrence are in good agreement. The variable data was easy to obtain and the evaluation method was simple, which could provide a reference for the prevention and treatment of hypoglycemia and screen patients with a high risk of hypoglycemia.

2320-PUB: Effects of Sequential Therapy Using Metformin plus Pioglitazone following Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed T2DM

Aims: Short-term intensive insulin therapy (SIIT) reverses β cell dysfunction in early T2DM, but this effect vanes overtime. This study aimed to investigate the effects of metformin plus pioglitazone sequential therapy on maintenance of the effect of SIIT. Methods: SIIT were applied in 50 patients with newly diagnosed T2DM to normalize blood glucose for 2 weeks. Patients were then randomly assigned to receive either sequential therapy (metformin 0.5g bid plus pioglitazone 15mg bid) or lifestyle change alone for 3 months. OGTTs were performed with plasma glucose and insulin measured. Results: As showed in the figure, plasma glucose profiles and insulin response during OGTT were improved similarly by SIIT in both groups. At 3 months of follow-up, GHbA1c (6.2±0.6% vs. 6.5±0.4%, P=0.12) in the sequential treatment group was slightly lower though without statistical significance. In OGTT, blood glucose 30, 60 and 90 minutes was significantly lower in the sequential treatment group, which led to lower AUCglucose (1456.1±266.3 vs. 1644.8±184.5 mmol/L*min, P=0.03) and higher AUCinsulin to AUCglucose ratio (2.5±1.9 vs. 1±1.1, P=0.01). HOMA B, HOMA IR, Mesuda index and ISSI-2 were all similar between the two groups. Conclusion: Metformin plus pioglitazone as sequential therapy might improve glycemic control and β cell function after SIIT in newly diagnosed T2DM. Disclosure L. Liu: None. L. Hai: None. W. Ke: None. Y. Li: None. Funding National Key Research and Development Program of China (2018YFC1314102)

Treatment Intensification With Insulin Pumps and Other Technologies in Patients With Type 2 Diabetes: Results of a Physician Survey in the United States.

An online survey was conducted to assess the perspectives and use of diabetes technologies by a sample of U.S. primary care physicians (PCPs) and endocrinologists to optimize intensive insulin therapy in patients with type 2 diabetes. Overall, endocrinologists reported using diabetes technologies more frequently than PCPs for patients with type 2 diabetes requiring basal-bolus insulin therapy. PCPs and endocrinologists who were highly focused on diabetes management with insulin therapy reported using insulin delivery devices (insulin pumps and wearable tube-free patches) when patients are not achieving their A1C target while taking basal plus three or more prandial injections of insulin daily.

Effect of rosiglitazone on inflammatory cytokines and oxidative stress after intensive insulin therapy in patients with newly diagnosed type 2 diabetes

ObjectiveTo evaluate the effect of insulin sensitizer on inflammatory cytokines and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsAfter intensive insulin therapy, patients with newly diagnosed T2DM were continuously treated with either insulin sensitizer or insulin for 48 weeks, and then their inflammatory cytokine and oxidative stress levels were measured.ResultsTumor necrosis factor alpha (TNF-α), interleukin (IL)-6, hypersensitive C reactive protein (hs-CRP), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (8-iso-PGF2α) levels of the rosiglitazone (RSG) group and the rosiglitazone combined with metformin (RSG + metformin) group were significantly reduced after the treatments (P < 0.05). Hs-CRP, MDA, and 8-iso-PGF2α levels of the metformin group were significantly reduced after the treatments (P < 0.05). Superoxide dismutase (SOD) and total antioxidant capacity (TAC) were significantly increased after the treatments in all three groups (P < 0.05 and P < 0.01).ConclusionEarly application of insulin sensitizers improved inflammation and oxidative stress in patients with newly diagnosed T2DM.

Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review

ObjectivesWhat is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy?DesignWe conducted a...

SUN-162 Long-Term Evaluation of Intensive Insulin Therapy in Patients with Type 2 Diabetes Mellitus (Value-It Study)

Background: This study aimed to determine long-term effect of intensive insulin therapy on prevention, progression, and development of chronic diabetes complications, both micro- and macrovascular events. This study also aimed to evaluate long-term sustainability of glycemic control of patients on intensive insulin treatment. Methods: A retrospective review of adult Type 2 diabetes mellitus (T2DM) patients on intensive insulin therapy for ≥7 years. Demographic data, co-morbidities, body mass index (BMI), HbA1c, hospitalization were collated. Majority received intensive insulin therapy with combination of premixed 70/30 given two times a day and fast short acting analogue given premeals three times a day, with the addition of glargine or degludec once a day in some. Results: Among 76 patients, 62% were males and 38% were females. Mean age at diagnosis and last visit were 53 and 65 years, respectively. At time of diagnosis, patient had the following co-morbidities: hypertension (32%), dyslipidemia (13%), non-dialyzable chronic kidney disease (4%), thyroid disease (1%), pulmonary tuberculosis (1%). In terms of long-term complications, only one patient had an acute coronary event, 2 patients had CKD needing dialysis with only 9% recorded to have cerebro-vascular accident during follow-up. There were no blindness and amputation observed. There is a statistical difference between HbA1c levels at time of diagnosis (8.53 ± 1.86) and last follow up (7.83 ± 1.71) (P = 0.00). After a median follow up of 12 years (7-22 years), glycemic control was sustained with an HbA1c of ≤ 7% and ≤ 8% in 32% and 45% of patients, respectively. Conclusion: With intensive insulin therapy, micro- and macrovascular complications can be prevented significantly. Long-term sustainability of glycemic control was also achieved.

Fasting Plasma Glucose Indicates Reversibility of the Acute Insulin Response after Short-Term Intensive Insulin Therapy in Patients with Various Duration of Type 2 Diabetes.

Recovery of acute insulin response (AIR) is shown to be associated with long-term outcomes of patients with early type 2 diabetes treated with short-term intensive insulin therapy (SIIT). However, the complexity of measuring an AIR limits its utility in a real-world clinical setting. The aim of the study was to assess fasting indicators that may estimate recovery of the AIR after SIIT. We enrolled 62 patients with type 2 diabetes mellitus (T2DM) of varying disease duration who had poor glycemic control. Participants were treated with SIIT using insulin pumps to achieve near normoglycemia for 7 days. The AIR before and after the therapy were measured by intravenous glucose tolerance tests. After the therapy, AIR increased from −16.7 (−117.4, 52.4) pmol/L·min to 178.7 (31.8, 390.7) pmol/L·min (P < 0.001) while hyperglycemia was alleviated; this improvement was observed in all disease duration categories. AIR was almost absent when fasting plasma glucose (FPG) > 10 mmol/L, while both AIR (R = −0.53, P < 0.001) and its improvement from baseline (△AIR, R = −0.52, P < 0.001) were negatively associated with FPG after SIIT when FPG < 10 mmol/L. In multivariate analyses, FPG after SIIT and baseline fasting C peptide were independent indicators of both AIR after the therapy and ∆AIR; HDL-C after the therapy also predicted AIR after the therapy. We concluded that recovery of the AIR could be obtained in T2DM patients of varying disease duration by SIIT and it could be conveniently estimated using posttreatment fasting plasma glucose and other fasting indicators.

Male Patients with Longstanding Type 2 Diabetes Have a Higher Incidence of Hypoglycemia Compared with Female Patients.

IntroductionTo explore whether there was a gender difference in the risk of hypoglycemia during intensive insulin therapy in patients with longstanding type 2 diabetes (T2D). This was a post hoc analysis of a single-center, open-label and prospective trial.MethodsAll subjects were admitted as inpatients, underwent a standard bread meal test at baseline and received a 7-day continuous subcutaneous insulin infusion (CSII) therapy for achieving glycemic control. Patients then were randomized 1:1 to two groups receiving (1) 4 days of Novo Mix 30 followed by 2 days of Humalog Mix 50; (2) 4 days of Humalog Mix 50 followed by 2 days of Novo Mix 30. All patients were subjected to 4-day retrospective continuous glucose monitoring (CGM) during the last 4 days in this study. The primary outcome was the incidences of hypoglycemia monitored by CGM at the end point.ResultsA total of 102 patients met the inclusion criteria and completed the study. Our data revealed that 29 patients (28%) experienced hypoglycemia as detected by CGM at the end point. Binary logistic stepwise regression analysis showed that only gender significantly correlated with hypoglycemia (B = 1.17, p = 0.017). Importantly, male patients had a significantly higher incidence of hypoglycemia than female patients (male = 20/52, female = 9/50, p = 0.022), although male patients required significantly lower insulin doses to maintain glycemic control than female patient (p = 0.00).ConclusionMale patients with longstanding T2D had a higher incidence of hypoglycemia than female patients during intensive insulin therapy.Trial registrationClinicalTrials.gov identifier, ChiCTR-IPR-15007340.

Fasting Plasma Glucose Indicates Reversibility of Acute Insulin Response after Short-Term Intensive Insulin Therapy in Patients with Type 2 Diabetes of Various Duration

Objective: In patients with early type 2 diabetes, short-term intensive insulin therapy (SIIT) reverses ß cell dysfunction measured by acute insulin response (AIR). However, the complicated procedures limit large-scale use of AIR. Also unclear is whether SIIT is effective in patients with longer duration. This study is performed to assess fasting indicators estimating recovery of AIR after SIIT for type 2 diabetes of various duration. Research Design and Methods: Patients with type 2 diabetes (n=62) who had poor glycemic control were enrolled. Near-nomoglycaemia was achieved and maintained for 7 days with insulin pump. AIR was measured by intravenous tolerance tests before and after SIIT. Results: Both fasting plasma glucose (FPG, 12.0 ± 3.0 vs. 7.71± 1.6 mmol/L, P&amp;lt;0.001) and 2h-postprandial glucose (17.3 ± 5.2 vs. 11.5 ± 3.7 mmol/L, P&amp;lt;0.001) decreased significantly after SIIT. AIR was improved from -16.7 (-117.4, 52.4) pmol/L·min to 178.7 (31.8, 390.7) pmol/L·min (P&amp;lt;0.001). Increase of AIR (?AIR)was observed in all disease duration categories (329.2±380.6, 312.8±347.8, and 123.8 ±186.3 pmol/L·min for patients with disease duration of &amp;lt;2 years, 2-6 years, and &amp;gt;6 years respectively, P=0.10). AIR was almost absent when FPG was over 10 mmol/L. However, when FPG after SIIT was less than 10 mmol/L it was negatively associated with AIR (R= -0.53, P&amp;lt;0.001) and ?AIR (R= -0.52, P&amp;lt;0.001). In multivariate analysis, AIR after the therapy and ?AIR could be estimated as follows: Estimated AIR (pmol/L·min) = 447.6 × baseline fasting C peptide (nmol/L) - 138.0× FPG after SIIT (mmol/L) + 925.2 (R2=0.42); estimated ?AIR (pmol/L·min) = 401.4 × baseline fasting C peptide (nmol/L) - 136.8 × FPG after SIIT (mmol/L) -357.6 × HDL-C after SIIT (mmol/L) + 1380.0(R2=0.50). Conclusions: Recovery of AIR could be obtained in patients with various duration of type 2 diabetes, and it could be estimated conveniently by FPG and other fasting indicators. Disclosure L. Liu: None. S. Yang: None. J. Liu: None. L. Hai: None. J. Liu: None. Y. Li: None.

Lower Glucose Target Is Associated With Improved 30-Day Mortality in Cardiac and Cardiothoracic Patients

Practice guidelines recommend against intensive insulin therapy in patients who are critically ill based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized IV insulin protocol that allows choice of blood glucose (BG) targets (80-110 vs90-140mg/dL) and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac ICUs that have very low rates of severe hypoglycemia. Critically ill patients receiving IV insulin were treated with either of two BG targets (80-110 vs90-140mg/dL). We created a propensity score for BG target using factors thought to have influenced clinicians' choice, and then we performed a propensity score-adjusted regression analysis for 30-day mortality. There were 1,809 patients who met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110mg/dL group (104 vs122mg/dL, P< .001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs 0.35%,P= .051). Unadjusted 30-day mortality was lower in the 80-110mg/dL group (4.3%vs9.2%, P< .001). This remained after propensity score-adjusted regression (OR, 0.65; 95%CI, 0.43-0.98; P= .04). Tight glucose control can be achieved with low rates of severe hypoglycemia and is associated with decreased 30-day mortality in a cohort of largely patients in cardiac ICUs. Although such findings should not be used to guide clinical practice at present, the use of tight glucose control should be reexamined using a protocol that has low rates of severe hypoglycemia.

GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia.

Insulin-induced hypoglycemia in diabetes is associated with impaired glucagon secretion. In this study, we tested whether stimulation of GPR119, a G-protein-coupled receptor expressed in pancreatic islet as well as enteroendocrine cells and previously shown to stimulate insulin and incretin secretion, might enhance glucagon secretion during hypoglycemia. In the study, GPR119 agonists were applied to isolated islets or perfused pancreata to assess insulin and glucagon secretion during hypoglycemic or hyperglycemic conditions. Insulin infusion hypoglycemic clamps were performed with or without GPR119 agonist pretreatment to assess glucagon counterregulation in healthy and streptozotocin (STZ)-induced diabetic rats, including those exposed to recurrent bouts of insulin-induced hypoglycemia that leads to suppression of hypoglycemia-induced glucagon release. Hypoglycemic clamp studies were also conducted in GPR119 knockout (KO) mice to evaluate whether the pharmacological stimulatory actions of GPR119 agonists on glucagon secretion during hypoglycemia were an on-target effect. The results revealed that GPR119 agonist-treated pancreata or cultured islets had increased glucagon secretion during low glucose perfusion. In vivo, GPR119 agonists also significantly increased glucagon secretion during hypoglycemia in healthy and STZ-diabetic rats, a response that was absent in GPR119 KO mice. In addition, impaired glucagon counterregulatory responses were restored by a GPR119 agonist in STZ-diabetic rats that were exposed to antecedent bouts of hypoglycemia. Thus, GPR119 agonists have the ability to pharmacologically augment glucagon secretion, specifically in response to hypoglycemia in diabetic rodents. Whether this effect might serve to diminish the occurrence and severity of iatrogenic hypoglycemia during intensive insulin therapy in patients with diabetes remains to be established.