Insulin-requiring Type Research Articles

Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Māori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. Sixty-seven participants entered the RCT phase (54% Māori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

Predictors of Responsiveness to GLP-1 Receptor Agonists in Insulin-Treated Patients with Type 2 Diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are potent antihyperglycemic agents with beneficial effects on weight, cardiovascular, and renal outcomes. Physicians lack guidance as to which patients with insulin-requiring type 2 diabetes will respond best to GLP-1 RAs with respect to glycemic control, insulin dose reduction, and weight loss. This study evaluated the efficacy of GLP-1 RAs in patients with type 2 diabetes on insulin and patient factors that may predict a beneficial clinical response. Adults with type 2 diabetes treated with insulin who had a GLP-1 RA added to their regimen were evaluated retrospectively. Baseline parameters and outcomes at 3, 6, and 12 months were collected. Among the 81 patients included, there was a mean reduction in hemoglobin A1C of 0.94% (SD, 0.26; p = 0.0007), 0.40% (SD, 0.21; p = 0.0636), and 0.58% (SD, 0.23, p = 0.0154) at 3, 6, and 12 months, respectively, following the addition of a GLP-1 RA. There was also a reduction in body weight noted at each time point. Baseline characteristics including BMI, duration of diabetes, and insulin requirement did not significantly affect A1C reduction when GLP-1 RA was added. At 3 months, patients with a random C-peptide that was normal (≥0.8 ng/ml) were significantly more likely to have discontinued insulin than those with random C-peptide that was low (<0.8 ng/ml) (11 of 23 vs. 0 of 7 patients, p = 0.029). The addition of a GLP-1 RA reduced HbA1C, weight, and insulin requirements in this cohort of patients with type 2 diabetes on insulin. BMI, baseline insulin dose, and diabetes duration did not predict response. A C-peptide level ≥ 0.8 ng/ml predicted a beneficial response after 3 months of therapy.

Tolerogenic dendritic cells in type 1 diabetes: no longer a concept.

Tolerogenic dendritic cells (tDC) arrest the progression of autoimmune-driven dysglycemia into clinical, insulin-requiring type 1 diabetes (T1D) and preserve a critical mass of β cells able to restore some degree of normoglycemia in new-onset clinical disease. The safety of tDC, generated ex vivo from peripheral blood leukocytes, has been demonstrated in phase I clinical studies. Accumulating evidence shows that tDC act via multiple layers of immune regulation arresting the action of pancreatic β cell-targeting effector lymphocytes. tDC share a number of phenotypes and mechanisms of action, independent of the method by which they are generated ex vivo. In the context of safety, this yields confidence that the time has come to test the best characterized tDC in phase II clinical trials in T1D, especially given that tDC are already being tested for other autoimmune conditions. The time is also now to refine purity markers and to "universalize" the methods by which tDC are generated. This review summarizes the current state of tDC therapy for T1D, presents points of intersection of the mechanisms of action that the different embodiments use to induce tolerance, and offers insights into outstanding matters to address as phase II studies are imminent. Finally, we present a proposal for co-administration and serially-alternating administration of tDC and T-regulatory cells (Tregs) as a synergistic and complementary approach to prevent and treat T1D.

Perioperative blood glucose variability and autonomic nervous system activity in on-pump cardiac surgery patients: Study protocol of a single-center observational study.

On-pump coronary artery bypass graft (CABG) and surgical valve replacement (SVR) are high-risk procedures. Several studies reported that perioperative blood glucose (BG) variability was independently associated with impaired postoperative outcome. However, the underlying mechanisms contributing to increased perioperative BG variability and to its deleterious impact remain unknown. The hypothesis of the study is that perioperative BG variability could be related to perioperative alteration of the autonomic nervous system (ANS) activity and to preoperative BG variability. We designed a prospective observational single-center study. Four groups of 30 patients will be studied: group 1, including insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 2, including non-insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 3, including non-diabetic patients undergoing aortic SVR; and group 4, including non-diabetic patient undergoing on-pump CABG. Preoperative (baseline) and postoperative BG variability will be quantified using the Abbott's Freestyle Libre Pro sensor allowing for continuous subcutaneous BG monitoring. Preoperative (baseline) and postoperative ANS activity will be measured using noninvasive continuous heart rate monitoring (Mooky HR memory®). Blood level and urinary concentration of inflammatory and endothelial dysfunction biomarkers will be measured from blood and urinary samples at the end of the surgery and on postoperative day 1 and 2. The primary objective is to describe the relationship between baseline BG variability and postoperative BG variability. The secondary objectives are to describe the relationship: between baseline and postoperative BG variability according to the diabetes phenotype and to the type of surgery; between the ANS activity and the BG variability; and between postoperative BG variability and, urinary and blood biomarkers.

Development of the Extended Infusion Set and Its Mechanism of Action.

Continuous subcutaneous insulin infusion (CSII, or insulin pump) and continuous glucose monitoring (CGM) sensors have been increasingly used and associated with improved glycemic control by people with type 1 diabetes and insulin-requiring type 2 diabetes. Commonly used infusion sets in most CSII systems are limited to a wear time of 3 days. In contradistinction, CGM sensors are currently approved for seven and more days of wear. With the motivation to provide a 7-day infusion set that matches the CGM wear time and to improve patient experience, the recently CE-marked and FDA 510k-cleared Medtronic extended infusion set (EIS) was designed.s The EIS offers enhanced new features that include use for up to 7 days, improved convenience, comfort, and better quality of life for insulin pump users.

Was It a Case of “Flatbush Diabetes” with Severe Hypertriglyceridemia?

AbstractWe present a case of a morbidly obese 27 years male patient who was admitted with sudden onset abdominal pain and crashed into diabetic ketoacidosis as new-onset diabetes and discuss the possible etiology of this combined picture of acute pancreatitis and severe hypertriglyceridemia. Flatbush diabetes was, meanwhile, thought of due to his morbid obesity that in turn raised our suspicion of acute insulin-requiring type 2 diabetes mellitus versus T1 diabetes mellitus. Ketosis-prone diabetes or Flatbush diabetes is a syndrome in which diabetes commences with ketoacidosis in patients who are glutamic acid decarboxylase and antiislet cell antibody negative and have no known precipitating causes. They are usually middle-aged, overweight, or mildly obese, and in many reports, they are likely to be male with a family history of type 2 diabetes mellitus; they present with new-onset severe hyperglycemia and ketosis or frank diabetic ketoacidosis. After intensive initial insulin therapy, many patients become insulin-independent and can be well controlled on diet plus oral medications or, more rarely, diet alone.

Adapting Protocols or Models for Use in Insulin-Requiring Diabetes and Islet Transplant Recipients.

The authors’ perspective is described regarding modifications made in their clinic to glucose challenge protocols and mathematical models in order to estimate insulin secretion, insulin sensitivity and glucose effectiveness in patients living with Insulin-Requiring Diabetes and patients who received Pancreatic Islet Transplants to treat Type I diabetes (T1D) with Impaired Awareness of Hypoglycemia. The evolutions are described of protocols and models for use in T1D, and Insulin-Requiring Type 2 Diabetes (T2D) that were the basis for studies in the Islet Recipients. In each group, the need for modifications, and how the protocols and models were adapted is discussed. How the ongoing application of the adaptations is clarifying the Islet pathophysiology in the Islet Transplant Recipients is outlined.

Insulin Dose Adjustment Following Bariatric Surgery, a Review of Available Literature.

Bariatric surgery is a known and effective treatment for type 2 diabetes mellitus. Patients with type 1 diabetes mellitus and exogenous insulin-requiring type 2 diabetes mellitus require adjusted insulin dosing after surgery to avoid hypoglycemia. This review describes insulin dose adjustments following a variety of bariatric procedures. After searching the available literature and assessing for eligibility, 8 articles were included. The Johns Hopkins Research Evidence Appraisal Tool for literature appraisal was used. The results of this review reveal insulin dose adjustment varies based upon surgical procedure type and time of follow-up from the procedure.

HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

Aims/hypothesisThe study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes.MethodsA total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing.ResultsThe susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years.Conclusions/interpretationIn addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies.Graphical abstract

2180-PUB: Integration of Continuous Glucose Monitoring in Diabetes Self-Management Education for Type 2 Diabetes Improves Glycemic Control

Continuous glucose monitors (CGM) are an integral aspect in the glucose management of many individuals with type 1 diabetes, and a growing number of people with insulin-requiring type 2 diabetes (T2D). A 2019 meta-analysis of 7 randomized controlled trials that investigated CGMs for T2D reported that CGM users had significantly lower HbA1c and shorter time spent with hypoglycemia compared with self-monitoring blood glucose comparison groups. However, little is known about optimal, real world approaches for integrating CGM in the routine management of patients with T2D. A pragmatic, feasibility pilot (n=6) was conducted to document the preliminary effectiveness and acceptability of introducing CGM in the context of a 5-class diabetes self-management education (DSME) series at Scripps Health, a large, non-profit, private insurance-based health system in San Diego, CA. Prior to class 2, English- (n = 3) and Spanish-speaking (n = 3) adults with T2D self-inserted the CGM and received enough sensors to wear the CGM until 6 weeks post-DSME (10 weeks total). During classes 3-5, time was devoted to reviewing the past week’s CGM data report and participants were encouraged to make associations between glucose trends and eating and exercise patterns. CGM wear ranged from 5 to 10 weeks (M =7.8 ± 1.7 weeks). Time-in-range (70-180 mg/dL) and mean average glucose improved from 54% and 185.1 ± 67.9 mg/dL at baseline to 74% and 159.1 ± 50.5 mg/dL by the end of DSME, and to 84% and 142.7 ± 30.6 mg/dL at 4-weeks post-DSME. Self-report surveys indicated improvements in healthful eating and physical activity over this time, and participants reported very high satisfaction with the CGM; the majority expressed a desire to continue CGM use post-study. Findings highlight DSME as a promising environment for effectively integrating CGM in the management of T2D. Future research should pinpoint the duration and frequency of CGM use for optimal clinical benefit in the general T2D population. Disclosure A.L. Fortmann: None. A. Bastian: None. C.J. Lensing: Employee; Self; UnitedHealth Group. Employee; Spouse/Partner; UnitedHealth Group. S. Hoversten: Employee; Self; UnitedHealth Group. K. Luu: None. K. Barger: None. L. Talavera: None. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Funding UnitedHealth Group; Dexcom, Inc.

Optimizing Postprandial Glucose Management in Adults With Insulin-Requiring Diabetes: Report and Recommendations.

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with type 1 and insulin-requiring type 2 diabetes: (i) the role of PPG management in reducing the risk of diabetes complications; (ii) barriers preventing effective PPG management; (iii) strategies to reduce PPG excursions and improve patient quality of life; and (iv) education and clinical tools to support endocrinologists in improving PPG management. We concluded that managing PPG to minimize or prevent diabetes-related complications will require elucidating fundamental questions about optimal ways to quantify and clinically assess the metabolic dysregulation and consequences of the abnormal postprandial state in diabetes and recommend research strategies to address these questions. We also identified practical strategies and tools that are already available to reduce barriers to effective PPG management, optimize use of new and emerging clinical tools, and improve patient self-management and quality of life.

Mobile application intervention to promote self-management in insulin-requiring type 1 and type 2 diabetes individuals: protocol for a mixed methods study and non-blinded randomized controlled trial.

Background: Mobile applications (apps) have proven to be useful in supporting diabetes self-care, but non-consideration of users’ needs and non-inclusion of educational features are reasons for low continual use. Well-designed mobile apps that meet the needs of diabetes patients and provide ongoing self-management education and support are required. It was hypothesized that apps designed with such features can improve a range of measures including clinical outcomes, knowledge of diabetes, medication adherence, perceived ability for self-management, and quality-of-life. This may eventually facilitate a more robust and cost-effective approach for improving skills and motivation for the management of diabetes.Methods: This project will be conducted in two phases. It will initially employ a mixed methods study design to investigate the self-management needs and perceptions of diabetes patients on the use of mobile apps to support diabetes self-management. Results of the mixed methods study will inform the content and design of an app which will be employed as an intervention tool in a 12-month parallel randomized controlled trial (RCT). The RCT will compare outcomes in relation to standard-of-care alone with standard-of-care plus a mobile phone diabetes app among 150 insulin-requiring types 1 and 2 diabetes patients. The primary outcome measures are clinical parameters such as hemoglobin A1c (HbA1c), lipids, urine albumin-to-creatinine ratio, blood pressure, frequency in events of emergency hyperglycemia and hypoglycemia. Secondary outcomes include knowledge of diabetes, medication intake and adherence, perception of self-care, and quality-of-life.Discussion: Results from this study will provide empirical evidence on the usefulness of a mobile app developed based on self-management needs analysis of diabetic patients. The long-term goal is to harness knowledge gained from this study to provide evidenced-based data, which promote the scale-up or adoption of mobile applications that provide regular, ongoing education and self-management support to people living with diabetes.Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000065291, Registered on 17 January, 2018 (prospectively registered).

Blood glucose level impact on biometric parameters, refraction and intraocular pressure in patients with subcompensated insulin-requiring type II diabetes

Purpose. To study the relationship of biometric parameters, visual acuity, eye refraction and intraocular pressure (IOP) with blood glucose levels and glycated hemoglobin (HbA1c) in patients with subcompensated insulin-requiring type II diabetes mellitus. Material and methods. Ophthalmic monitoring lasted 3 years, the experience of insulin therapy — 6 years. 32 patients (27 women and 5 men) with insulin-requiring diabetes mellitus and no severe general diabetic complications or concomitant eye pathology were monitored for 3 years. The patients’ average age was 60.4 ± 5.3 years; average weight 94.3 ± 16.5 kg; average height 163.4 cm; average BMI (body mass index) was 29.93 kg/m2, all received insulin treatment for 6 years. Patients determined the level of blood glucose themselves on a daily basis using individual “Accu-Check” and/or “OneTouch select” glucometers, supplemented by endocrinologist checks on scheduled examinations once a month. The level of glycated hemoglobin (HbA1c) was determined once every 3–6 months. The 3-year ophthalmic monitoring involved both eyes and included biomicroscopy, autorefractometry, pneumotonometry, measurement of the anterior-posterior axis, the depth of the anterior chamber and lens thickness; pachymetry of the cornea in the central optical zone, and ophthalmoscopy. Visometry was performed according to ETDRS (Early Treatment Diabetic Retinopathy Study Research Group) requirements. Results. The impact of blood glucose level on visual acuity (Spearman R = 0.18/-0.23, t (N-2) = 1.07/-1.34, p = 0.1) is higher than that of HbA1c (Spearman R = 0.07/-0.15, t (N-2) = 0.4/-0.8, p = 0.65) The higher the glucose level, the lower the depth of the anterior chamber and the shorter the APA. In contrast, the higher the level of HbA1c, the thicker the cornea in the central optical zone. Both the glucose and the HbA1c levels reveal a similar positive correlations with IOP. A refraction shift toward myopia from 42 % to 55 % was shown to correlate to HbA1c, and a corresponding reduction of hyperopia share was revealed. Conclusions. In patients with subcompensated insulin-requiring diabetes mellitus type II, biometric parameters, refraction and intraocular pressure are determined by changes in the level of blood glycemia.

Combination therapy in patients with concomitant macular edema and proliferative diabetic retinopathy

To study the effectiveness of the combination of intravitreal administration of the drug Ozurdex with subsequent individually selected laser therapy in the treatment of the proliferative stage of diabetic retinopathy in patients with concomitant chronic DME, and its relationship with morphological changes in the retina observed with optical coherence tomography. This retrospective study included 18 patients with insulin-requiring type II diabetes mellitus complicated by diabetic retinopathy in the proliferative stage and refractory DME. According to morphological changes observed with optical coherence tomography of the retina, the patients were divided into 3 groups: 6 patients with diffuse macular edema, 6 patients with cystic macular edema, and 6 patients with serous detachment of the retinal neuroepithelium. All patients underwent intravitreal injection of 0.7 mg Ozurdex followed by panretinal laser coagulation. The choice of laser applicates with the minimal parameters giving a therapeutic effect was carried out according to the procedure described previously (Patent No. RU2611887C1 d.d. 12/25/2015). The combination of intravitreal administration of Ozurdex followed by individually selected laser coagulation is effective against various morphological types of DME. However, the greatest visual acuity was achieved in patients with diffuse macular edema and retinal neuroepithelial detachment. The higher the initial visual acuity, the better the functional outcomes of the treatment. Baseline retinal thickness did not affect the effectiveness of the proposed method of treatment. Cystic macular edema was an unfavorable prognostic factor for improving visual acuity.

Frequency and associated risk factors of cardiovascular autonomic neuropathy among patients with type 2 Diabetes.

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes and is associated with cardiovascular morbidity and mortality. Despite its prevalence, it is usually underdiagnosed. Objective to assess frequency of CAN in type 2 diabetes, treated at the Diabetology Service at Cordoba Hospital, Argentina. Cross-sectional study was conducted from May 2015 to May 2016. Cardiovascular Autonomic Tests (Ewing´s battery) were performed: response to Valsalva maneuver, expiration-to-inspiration ratio (E/I ratio), standing to lying flat and postural hypotension. 100 type 2 diabetes patients, 53% females. The mean age and diabetes duration 52 years old and 8.4 years, respectively. Hemoglobin A1c level of 8.7% and 47% were insulin-requiring type 2 diabetes patients. 29% had early CAN, 54% confirmed CAN (10% severe CAN) and 17% normal cardiovascular tests. Confirmed CAN was higher in those with longer duration of diabetes; longer duration of insulin therapy, older patients and severe hypoglycemia events was higher in those with confirmed CAN versus without CAN or early CAN (p 0.003). The risk factors associated were hypertension OR 2.55 (p 0.02), peripheral neuropathy OR 11.7 (p <0.0001), diabetic retinopathy OR 9.03 (p 0.001), diabetic nephropathy OR 3.12 (p 0.03) and hemoglobin A1c > 7% OR 2.57 (p 0, 03). frequency of CAN was high, was associated with hypertension, microvascular complications, older age, poor metabolic control, longer duration of disease and insulin therapy. Patients with a higher risk of developing CAN should be identified, in order to reduce the impact of this complication.

Automated Insulin Delivery: Taking the Guesswork out of Diabetes Management.

For individuals with Type 1 or insulin-requiring Type 2 diabetes, new technology may offer something they desperately need, but is now nigh impossible: the ability to maintain ideal blood glucose levels all day, every day.

Pasireotide in an insulin-requiring diabetic acromegalic patient without worsening of hyperglycemia.

Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin.Learning pointsLong-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide.Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled.Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.

The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

BackgroundIn critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aimed to explore this effect in patients with type 2 diabetes.MethodsWe prospectively enrolled a cohort of 45 critically ill patients with type 2 diabetes managed according to a liberal glucose protocol (target blood glucose 10–14 mmol/l). We recorded the administration of insulin and oral hypoglycemic agents and measured plasma c-peptide as surrogate marker of endogenous insulin secretion on the first two consecutive days in ICU.ResultsOverall, 20 (44.4%) patients required insulin to achieve target blood glucose. Insulin-treated patients had higher glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and greater blood glucose levels but lower c-peptide levels on admission. Premorbid insulin-requiring diabetes was independently associated with lower admission c-peptide, whereas greater plasma creatinine was independently associated with higher levels. Increases in c-peptide were positively correlated with an increase in blood glucose both in patients who did (r = 0.54, P = 0.01) and did not (r = 0.56, P = 0.004) receive insulin. However, insulin administration was independently associated with a greater increase in c-peptide (P = 0.04). This association was not modified by the use of oral insulin secretagogues.ConclusionsC-peptide, a marker of beta-cell response, responds to and is influenced by glycemia and renal function in critically ill patients with type 2 diabetes. In addition, in our cohort, exogenous insulin administration was associated with a greater increase in c-peptide in response to hyperglycemia.Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12615000216516).

Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity

The asymptomatic phase of type 1 diabetes is recognised by the presence of beta cell autoantibodies in the absence of hyperglycaemia. We propose that an accurate description of this stage is provided by the name ‘Autoimmune Beta Cell Disorder’ (ABCD). Specifically, we suggest that this nomenclature and diagnosis will, in a proactive manner, shift the paradigm towards type 1 diabetes being first and foremost an immune-mediated disease and only later a metabolic disease, presaging more active therapeutic intervention in the asymptomatic stage of disease, before end-stage beta cell failure. Furthermore, we argue that accepting ABCD as a diagnosis will be critical in order to accelerate pharmaceutical, academic and public activities leading to clinical trials that could reverse beta cell autoimmunity and halt progression to symptomatic insulin-requiring type 1 diabetes. We recognize that there are both opportunities and challenges in the implementation of the ABCD concept but hope that the notion of ‘asymptomatic autoimmune disease’ as a disorder will be widely discussed and eventually accepted.

WITHDRAWN: A Comparison of Internet Monitoring with Continuous Glucose Monitoring in Insulin-Requiring Type 2 Diabetes Mellitus

To compare the effects of real-time continuous glucose monitoring (RT-CGM) and an Internet blood glucose monitoring system (IBGMS) on glycated hemoglobin levels in patients with type 2 diabetes mellitus treated with insulin. Fifty-seven patients with type 2 diabetes treated with insulin were assigned randomly to 1 of 2 groups. Group 1 had the results of their self-monitoring of blood glucose level monitored biweekly using an IBGMS. Group 2 used RT-CGM and were monitored biweekly. Both groups used a secure website to upload data and to receive feedback from their endocrinologist. A1C and laboratory test results were collected at 0, 3 and 6 months. The baseline parameters were not significantly different. After a 6-month follow-up period, both IBGMS and RT-CGM showed significant within-group improvements in A1C level. In the IBGMS group, the A1C level decreased from 8.79%±1.25% to 7.96%±1.30% (p<0.05). The RT-CGM group decreased from 8.80%±1.37% to 7.49%±0.70% (p<0.001). IBGMS and RT-CGM did not show significantly different A1C levels at baseline, 3 and 6 months (p>0.05). The use of both IBGMS and RT-CGM significantly improved A1C levels in patients with type 2 diabetes treated with insulin in a randomized trial over a 6-month period. There were no significant differences in A1C values between groups after 6 months.