Increase In Hypoglycemic Events Research Articles

Treatment of glucocorticoid- induced hyperglycemia in hospitalized patients - a systematic review and meta- analysis

PurposeGlucocorticoid (GC)-induced hyperglycemia is a frequent issue, however there are no specific guidelines for this diabetes subtype. Although treat-to-target insulin is recommended in general to correct hyperglycemia, it remains unclear which treatment strategy has a positive effect on outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess whether treating GC-induced hyperglycemia improves clinical outcomes.MethodsMEDLINE and EMBASE were systematically searched for RCTs on adults reporting treatment and outcomes of GC-induced hyperglycemia since the beginning of the data bases until October 21, 2023. Glucose-lowering strategies as compared to usual care were investigated.ResultsWe found 17 RCTs with 808 patients and included seven trials in the quantitative analysis. Patients with an intensive glucose-lowering strategy had lower standardized mean glucose levels of – 0.29 mmol/l (95%CI -0.64 to -0.05) compared to usual care group patients. There was no increase in hypoglycemic events in the intensively treated groups (RR 0.91, 95%CI 0.70–1.17). Overall, we did not have enough trials reporting clinical outcomes for a quantitative analysis with only one trial reporting mortality.ConclusionIn GC-induced hyperglycemia, tight glucose control has a moderate effect on mean glucose levels with no apparent harmful effect regarding hypoglycemia. There is insufficient data whether insulin treatment improves clinical outcomes, and data on non-insulin based treatment regimens are currently too sparse to draw any conclusions.Systematic review registrationRegistered as CRD42020147409 at PROSPERO (https://www.crd.york.ac.uk/prospero/) on April 28, 2020

Perioperative Insulin Regimens in Patients With Insulin-Treated Type 2 Diabetes Mellitus Hospitalized for a Short Time for Minor Eye Surgery.

Elective surgery in patients with insulin-treated type 2 diabetes mellitus (T2D) and the admission period in the hospital, comprise a distinctive and challenging situation for physicians, nurses, as well as for the patients themselves. There is a lack of widely accepted evidence-based and standardized approach of care in regard to perioperative management of patients with insulin-treated T2D. The main purpose of this proof-of-concept study was to investigate whether a standardized insulin and meal regimen on the day of surgery leads to a better management of diabetes in terms of blood glucose (BG) levels. Two different insulin and meal regimens-group A with half of insulin dose given with a standardized postoperative meal and group B with a custom preoperative breakfast and full insulin dose-were compared with Group C with routine care (no meal and no insulin injection on the day of surgery). Each group consisted of 12 to 15 patients. BG measurements were performed pre- and immediately postoperatively, before meals and at bedtime. Both standardized and well-defined insulin and meal regimens resulted in better average BG levels in the perioperative period, especially in the morning after the surgery. In this study, we observed that a standardized perioperative insulin regimen efficiently lowered postoperative BG levels. Providing a custom breakfast and a full insulin dose resulted in lower postoperative BG levels. These approaches were not associated with an increase in hypoglycemic events. Physicians and nursing staff gave positive feedback to the structured and well-defined approaches.

Implementation of self-monitoring of blood glucose for patients with insulin-dependent diabetes at a rural non-communicable disease clinic in Neno, Malawi.

Self-monitoring of blood glucose (SMBG) is a widely accepted standard of practice for management of insulin-dependentdiabetes, yet is largely unavailable in rural sub-Saharan Africa (SSA). This prospective cohort study is the first known report ofimplementation of SMBG in a rural, low-income country setting. To evaluate adherence and change in clinical outcomes with SMBG implementation at two rural hospitals in Neno, Malawi. Forty-eight patients with type 1 and insulin-dependent type 2 diabetes were trained to use glucometers and logbooks. Participantsmonitored preprandial glucose daily at rotating times and overnight glucose once a week. Healthcare providers were trained to evaluateglucose trends, and adjusted insulin regimens based on results. Adherence was measured as the frequency with which patients checked anddocumented blood glucose at prescribed times, while clinical changes were measured by change in glycated haemoglobin (HbA1c) over a6-month period. Participants brought their glucometers and logbooks to the clinic 95 - 100% of the time. Adherence with measuring glucose valuesand recording them in logbooks eight times a week was high (mean (standard deviation) 69.4% (15.7) and 69.0% (16.6), respectively). MeanHbA1c decreased from 9.0% (75 mmol/mol) at enrolment to 7.8% (62 mmol/mol) at 6 months (mean difference 1.2% (95% confidenceinterval (CI) 0.6 - 2.0; p=0.0005). The difference was greater for type 1 diabetes (1.6%; 95% CI 0.6 - 2.7; p=0.0031) than for type 2 diabetes(0.9%; 95% CI 0.1 - 1.9; p=0.0630). There was no documented increase in hypoglycaemic events, and no hospitalisations or deaths occurred. SMBG is feasible for patients with insulin-dependent diabetes in a rural SSA population, and may be associated with improvedHbA1c levels. Despite common misconceptions, all patients, regardless of education level, can benefit from SMBG. Further research onlong-term retention of SMBG activities and the benefits of increasing frequency of monitoring is warranted.

Modeling the variability of insulin sensitivity during the menstrual cycle in women with type 1 diabetes to adjust open-loop insulin therapy.

Women with type 1 diabetes (T1D) typically experience a decrease in insulin sensitivity (SI) during the second half of their menstrual cycle (or the luteal phase (LP)), which oftentimes is not properly addressed by insulin therapy, therefore leading to increased exposure to hyperglycemia. This study proposes a suitable way to model SI variability due to the menstrual cycle in the FDA-accepted University of Virginia (UVA)/Padova T1D Simulator, to determine to what extent the inclusion of menstrual cycle information to fine-tune insulin therapy could help improve glycemic control in the LP of the menstrual cycle. In-silico tests were performed considering different simulation scenarios, and the obtained results show that hyperglycemic excursions can be largely reduced when SI variability is taken into account for planning insulin therapy, without a relevant increase in hypoglycemic events.

Electronic Glycemic Management System and Endocrinology Service Improve Value in Cardiac Surgery.

Postoperative glycemic control improves cardiac surgery outcomes but insulin protocols are limited by complexity and inflexibility. We sought to evaluate the effect of implementing an electronic glycemic management system (eGMS) in conjunction with a cardiac surgery endocrinology consult service on glycemic control and outcomes after cardiac surgery. All patients with a calculated preoperative risk of mortality who underwent cardiac surgery before and after implementation of an eGMS and an endocrinology consult service were identified. Glycemic control and surgical outcomes were compared using univariate analysis, and multivariate regression was used to model the risk-adjusted effects of the interventions on glycemic control, surgical outcomes, and resource utilization. The health care-related value added by the interventions was calculated by dividing risk-adjusted outcomes by total hospital costs. A total of 2612 patients were identified, with 1263 patients in the preimplementation cohort and 1349 in the postimplementation cohort. Multivariate regression demonstrated fewer postoperative hyperglycemic events (odds ratio [OR] 0.8, 95% CI, 0.65-0.99) after protocol implementation without an increase in hypoglycemic events (OR 0.96, 95% CI, 0.71-1.3). Average day-weighted mean glucose decreased from 144 to 138 mg/dL (P < .001). The improved glycemic control correlated with a risk-adjusted decrease in composite morbidity or mortality (OR 0.61, 95% CI, 0.47-0.79). Although hospital costs increased after implementation, the protocol increased health care-related value by 38%. Implementation of a protocol consisting of an eGMS paired with a cardiac surgery-specific endocrinology consult service was associated with improved glycemic control and reduced morbidity. Despite higher costs health care-related value increased as a result of eGMS implementation.

868-P: Live Coaching Improves Glycemic Control and DSMQ Scale in People with Type 2 Diabetes

People with diabetes face numerous challenges to effective self-management of blood glucose (BG) including access to diabetes education and support. This study explores how a coaching program structured around the AADE7 Self-Care Behaviors™ and evidence-based behavior change strategies optimized for remote interaction between the coach and participant can improve glycemic control. Certified Diabetes Educator coaches used a care management platform, Welkin Health, that displays BG test results from integration with the OneTouch Reveal diabetes mobile app. Welkin supports communication methods with patients including email, SMS and telephone communication. The software platform also uses logic to prioritize patients who need attention so the coach can better manage their relationship with the participant. Adult participants with type 2 diabetes and HbA1c ≥8.0% received an AccuBase A1c mail-in test kit at baseline and weeks 12 and 24 to measure their HbA1c levels. Each participant used a OneTouch Verio Flex glucose meter connected by Bluetooth to OneTouch Reveal app. After 12 weeks (n=67), mean HbA1c declined by 0.85% from 9.19% to 8.34% (p&amp;lt;0.05) and 65% of subjects had an HbA1c decrease of &amp;gt;0.5%. After 24 weeks, mean change in HbA1c was still 0.78% less than baseline (p&amp;lt;0.05) with 51% of participants experiencing a decline of &amp;gt;0.5%. The decline in HbA1c occurred without any increase in hypoglycemic events. There was a 14.1% increase in % of results in range (p&amp;lt;0.05). Improvement in HbA1c came without any substantial change in testing frequency. In addition, there were various positive changes in the Diabetes Self-Management Questionnaire (DSMQ) scale. In conclusion, live coaching using the Welkin Patient Relationship Management technology in conjunction with the OneTouch Reveal diabetes app resulted in significant improvement in glycemic control in participants with type 2 diabetes who were in relatively poor control. Disclosure L.B. Katz: Employee; Self; LifeScan, Inc. K.D. Neland: Research Support; Self; LifeScan, Inc. D.J. Rolando: None. D.M. Shearer: None.

Improving the Quality of Outpatient Diabetes Care Using an Information Management System: Results From the Observational VISION Study.

This study aimed to evaluate the effects of information management system (IMS) use with individuals with type 1 and type 2 diabetes who were treated in outpatient settings. In this 7-month, prospective, observational study, 965 adults with diabetes, mean (SD) baseline HbA1c 8.61(1.2)% (70.6[13.1] mmol/mol), were recruited from 132 outpatient care centers in Germany and Denmark. HbA1c was measured at baseline, month 4, and month 7. IMS reports were generated from uploaded self-monitored blood glucose data and therapy adjustments were documented at months 1 and 4. Hypoglycemic events were documented. Mean (SD) HbA1c decreased from baseline in type 1 and type 2 diabetes patients at month 4 (-0.61[1.03]% (-6.7[11.3] mmol/mol), n = 213; -0.88[1.22]% (-9.6[13.3] mmol/mol), n = 589, respectively) and month 7 (-0.64[1.02]% (-7.0[11.1] mmol/mol), n = 219; -0.93[1.27]% (-10.2[13.9] mmol/mol), n = 594, respectively), all P < .0001, with no increase in hypoglycemic events. Therapy was adjusted in 106(42.7)% type 1 and 349(52.4)% type 2 diabetes patients at months 1 and 105(42.3)% type 1 and 282(42.3)% type 2 diabetes patients at month 4. Physicians used IMS reports to make therapy adjustments in 90% of patients at month 1 and 86% of patients at month 4. Integration of the IMS into outpatient care facilitates significant improvements in glycemic control.

An Overview of the Therapeutic Effects of Camel Milk in the Treatment of Type 1 Diabetes Mellitus

The main treatment of type 1 diabetes mellitus (DM) is insulin replacement via parenteral routes, which is far fromsatisfactory. Camel milk is an alternative to current insulin treatment. This paper discusses the chemical constituentsand properties of camel milk, recent experimental evidences about the effectiveness of camel milk in the treatmentof insulin dependent diabetes mellitus, role of the camel milk in the restoration of damaged beta-cells of thepancreas and in the improvement of disturbed lipid metabolism associated with type 1 DM as well as the effects ofcamel milk in the improvement of clinical function parameters of the kidneys and liver of subjects with insulindependent diabetes mellitus. This paper demonstrates that, camel milk causes significant reduction in insulin dosages in insulindependentdiabetic subjects to obtain glycemic control along with significant improvement in HbA1c level, and improvement inmicro albuminuria. Significant improvements were also observed in lipid metabolism, body mass index (BMI),biochemical parameters of the liver and kidney functions of camel milk fed experimental subjects with type-1diabetes. Camel milk works as a regulator of blood sugar in the absence of original insulin, and it seems to worktogether with the body’s own restorative andregenerative abilities. Camel milk is well tolerated and its uses are notassociated with an increase in hypoglycemic events. Camel milk may be able to eliminate the alloxan and other chemicals’ induced-toxicity on pancreas and on other body organs via regenerative effects on damaged cells and could be used as a restorative treatment of diabetes.The main treatment of type 1 diabetes mellitus (DM) is insulin replacement via parenteral routes, which is far from satisfactory. Camel milk is an alternative to current insulin treatment. This paper discusses the chemical constituents and properties of camel milk, recent experimental evidences about the effectiveness of camel milk in the treatment of insulin dependent diabetes mellitus, role of the camel milk in the restoration of damaged beta-cells of the pancreas and in the improvement of disturbed lipid metabolism associated with type 1 DM as well as the effects of camel milk in the improvement of clinical function parameters of the kidneys and liver of subjects with insulin dependent diabetes mellitus.This paper demonstrates that, camel milk causes significant reduction in insulin dosages in insulin dependent diabetic subjects to obtain glycemic control along with significant improvement in HbA1c level, and improvement in micro albuminuria. Significant improvements were also observed in lipid metabolism, body mass index (BMI),biochemical parameters of the liver and kidney functions of camel milk fed experimental subjects with type-1diabetes. Camel milk works as a regulator of blood sugar in the absence of original insulin, and it seems to work together with the body’s own restorative and regenerative abilities. Camel milk is well tolerated and its uses are not associated with an increase in hypoglycemic events. Camel milk may be able to eliminate the alloxan and other chemicals’ induced-toxicity on pancreas and on other body organs via regenerative effects on damaged cells and could be used as a restorative treatment of diabetes.

SWITCHING FROM PREMIXED INSULIN TO BASAL–BOLUS INSULIN GLARGINE PLUS RAPID-ACTING INSULIN: THE ATLANTIC STUDY

Introduction: Data on switching from premixed insulin to a basal–bolus regimen in routine clinical practice are sparse. The aim was to evaluate the efficacy and safety of switching from twice-daily premixed insulin to basal glargine plus rapid-acting insulin in a “real-world” clinical practice setting in Belgium and The Netherlands.Methods: This prospective, 6-month, noninterventional, observational study was conducted in 37 centres in Belgium and 19 centres in The Netherlands. Adults (≥ 18 years of age) with type 2 diabetes were eligible if they were not taking oral antihyperglycaemic drugs or only taking metformin. The primary objective was the proportion of patients attaining glycated haemoglobin (HbA1c) < 7% at months 3 and 6. Secondary objectives included changes in HbA1c, weight, body mass index (BMI), insulin doses, hypoglycaemic events, and treatment satisfaction.Results: There were 214 patients from Belgium and The Netherlands enrolled. Mean age was 64.6 years, weight was 89.5 kg, BMI was 31.4 kg/m2, and duration of diabetes was 12.1 years. At month 6, the percentage of patients with HbA1c < 7% increased from 3.3% to 24.9% (p < 0.001). Mean HbA1c at baseline was 8.9%; mean change from baseline was -1.5% (p < 0.001). Glargine and prandial insulin doses increased (p < 0.001, each), while body weight and BMI were unchanged. Hypoglycaemic events did not increase. Overall treatment satisfaction improved significantly (p < 0.001).Conclusions: In a Belgian and Dutch clinical practice setting, patients with type 2 diabetes that is poorly controlled on premixed insulin experienced significant improvements in glycaemic control, without a concomitant increase in hypoglycaemic events or weight, when switched from premixed insulin to basal–bolus glargine plus rapid-acting insulin. As a result, treatment satisfaction significantly improved.

Addition of exenatide twice daily to basal insulin for the treatment of type 2 diabetes: clinical studies and practical approaches to therapy.

BackgroundType 2 diabetes is a progressive disease that requires stepwise additions of non-insulin and insulin therapies to meet recommended glycaemic goals. The final stage of intensification may require prandial insulin, adding complexity and increased risks of hypoglycaemia and weight gain.AimsThis review assesses the benefits and risks of adding exenatide twice daily, a glucagon-like peptide 1 receptor agonist, in patients with type 2 diabetes who are currently treated with basal insulin, but have failed to reach their glycaemic goals.Methods and ResultsBased on data from published studies, exenatide has a number of actions that complement basal insulin therapy. Exenatide has been shown to increase glucose-dependent insulin production, suppress abnormal plasma glucagon production, slow gastric emptying, enhance liver uptake of glucose and promote satiety. A recently published randomised clinical trial reported that the addition of exenatide twice daily to titrated basal insulin provided greater glycaemic control than titrated basal insulin alone, and did so without an increase in hypoglycaemic events and with modest weight loss. Exenatide use was associated with gastrointestinal side effects. The recent randomised trial confirmed and extended data from a number of prior observational studies that demonstrated the efficacy and safety of insulin/exenatide combination therapy. Practical considerations for adding exenatide twice daily to ongoing basal insulin are discussed.

Clinical decision support systems in the care of inpatients with diabetes in non‐critical care setting: systematic review

Computerized clinical decision support systems have been claimed to reduce prescription errors and improve patient care. They may play an important role in the care of hospitalized patients with diabetes. To collate evidence for the use of clinical decision support systems in improving the care of hospitalized patients with diabetes in a non-critical care setting and to assess their effectiveness. We searched four databases from 1980 to 2010 without language restrictions. All types of studies other than case reports were included. Data extraction and quality assessment were carried out based on the Centre for Review and Dissemination guidance. A narrative synthesis was conducted. Fourteen studies met the inclusion criteria, including two cluster randomized controlled trials, eight before-and-after studies and four other descriptive studies. Generally, the quality of the studies was not very high. Nine out of 10 studies reported reduction in mean blood glucose or similar measures (patient-day-weighted mean blood glucose) during inpatient stay. The reduction using computerized physician order entry system in patient-day-weighted mean blood glucose ranged from 0.6 to 0.8 mmol/l (10.8-15.6 mg/dl). Other beneficial effects during inpatient stay included reduced use of sliding scale insulin and greater use of basal-bolus insulin regimen. Only one study found a significant increase in hypoglycaemic events. Clinical decision support systems have been used, often as part of a complex programme, to improve the care of hospitalized patients with diabetes. There is some evidence that they may have a beneficial effect, but this needs further confirmation.

Evaluation of an intensive insulin transition protocol in the intensive care unit setting: a before and after study

The benefits of controlling blood glucose levels in intensive care units (ICUs) are well documented. This study determined the effectiveness and safety of a standardized transition order set for converting a continuous insulin infusion to a subcutaneous insulin regimen in non-cardiovascular surgery ICUs patient population. A retrospective study was conducted. Patients presenting with diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome were excluded. One hundred patients were included prior to and 100 patients were included after initiating the transition order set. Blood glucose control was reviewed for up to 72 hours following the transition. A total of 115 patients were included in data analysis: 85 prior to and 30 after transition protocol. All patients transitioned using the protocol were transitioned to basal insulin, compared to only 40% of the prior to protocol group. Patients transitioned correctly per the transition order set, "per protocol," had 54% of blood sugars within the desired range, no increase in hypoglycemic events, and on average 5.56 hyperglycemic events (blood glucose >180 mg/dL) per person during the 72 hours compared to 6.68 and 9.00 for the prior to protocol group and the "off protocol" group (transitioned different than the protocol recommended), respectively (p= 0.05). There were significant differences in blood sugar control at 48 and 72 hours between the "per protocol" and "off protocol" groups (p= 0.01) and a 40% reduction in sliding scale or correctional insulin coverage. The addition of basal insulin to transition regimens resulted in fewer hyperglycemic events with no increase in hypoglycemic events. Patients transitioned "per protocol" had better glucose control demonstrated by: less hyperglycemic events, lower mean blood glucose levels at 48 and 72 hours, and lower need for correctional insulin. These findings showed benefits of glycemic control in the ICU by following a standardized transition protocol.

Review of insulin and its analogues in diabetes mellitus.

Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested.

Computer Decision Support Software Safely Improves Glycemic Control in the Burn Intensive Care Unit: A Randomized Controlled Clinical Study

The optimal method for glycemic control in the critically burned patient is unknown. The purpose of this randomized controlled study was to determine the safety and efficacy of computer decision support software (CDSS) to control serum glucose concentration in a burn intensive care unit. Eighteen adult burn/trauma patients receiving continuous insulin infusion were initially randomized to receive glucose management by a traditional paper protocol or a computer protocol (CP) for 72 hours and then crossed over to the alternate method for an additional 72 hours. Time in target glucose range (range: 80-110 mg/dl) was higher in the CP group (47 ± 17% vs 41 ± 16.6%; P ≤ .05); time over target range was not significantly reduced in the CP group (49 ± 17.8% vs 54 ± 17.1%; P = .08); and no difference was noted in time under target range of 80 mg/dl (CP: 4.5 ± 2.8%, paper protocol: 4.8 ± 3.3%; P = .8), less than 60 mg/dl (P = .7), and less than 40 mg/dl (P = 1.0). Severe hypoglycemic events (<40 mg/dl) did not differ from the CP group compared with historical controls for patients receiving no insulin (P = .6). More glucose measurements were performed in the CP group (P = .0003), and nursing staff compliance with CP recommendations was greater (P < .0001). Glycemic control using CDSS is safe and effective for the critically burned patient. Time in target range improved without increase in hypoglycemic events. CDSS enhanced consistency in practice, providing standardization among nursing staff.

Improved A1C by switching to continuous subcutaneous insulin infusion from injection insulin therapy in type 2 diabetes: A retrospective claims analysis

Aims This study was a real-world, retrospective evaluation of the clinical effectiveness of switching to continuous subcutaneous insulin infusion (CSII) among managed care enrollees with type 2 diabetes for whom multiple daily injections (MDI) had presumably failed. Methods Administrative claims with integrated A1C values from a large and geographically diverse health plan were analyzed. Results Statistically significant A1C reductions (from the baseline period to follow-up period, mean follow-up 17 months) were achieved with CSII. Among subjects using a long-acting and rapid-acting insulin regimen at baseline, A1C decreased to mean follow-up A1C by 0.8% and to minimum follow-up A1C by 1.2% ( p < 0.001). The proportion of subjects at target (A1C < 7%) increased significantly from baseline to follow-up (8.4–22.9% [using mean A1C] and 32.8% [using minimum A1C]; both p < 0.001). The rate of severe hypoglycemic events was similar from baseline to follow-up. Conclusions CSII was associated with significant reductions in A1C without an increase in hypoglycemic events in insulin-taking people with type 2 diabetes, including subjects previously using a long-acting and rapid-acting insulin regimen.

Insulinothérapie : insuline ou analogues ? Injection ou perfusion ? Boucle ouverte ou boucle fermée ?

Insulin has been purified, humanized and then synthesized by microorganisms. It is mandatory to be able to use insulin, whose kinetics and reproducibility allow glycemia near to normal without increasing hypoglycemia. Use of insulin analogs allows a slight improvement in glycemic control and decrease hypoglycemia frequency. Flexibility of treatment is also improved. “Continuous subcutaneous insulin infusion” (CSII) using rapid analogs mimics physiologic insulin secretion. Major indications are: high HbA1c despite well-managed basal-bolus regimen, severe hypoglycemia, brittle diabetes or “dawn phenomenon”. Children, adolescents as well as pregnancy are also good indications. “Continuous intraperitoneal insulin infusion” major interest is the predominant absorption via the portal system. Kinetic is comparable to rapid analogs delivered subcutaneously. The dramatic reduction of severe hypoglycemic events has been related to good reproducibility of insulin absorption and restoration of glucagon response. Hypoglycemia prone type 1 diabetic patients, uncontrolled with well-managed CSII as well as subcutaneous insulin resistance are the major indications. The association of optimized insulin therapy to “real time continuous glucose monitoring” allows better doses adaptation. Alarms can be set to avoid glycemic excursions and thus severe hypoglycemia. Using these devices, HbA1c is significantly improved without any increase in hypoglycemic events. These devices are one of the steps towards the “closed-loop insulin delivery” concept. Restoration of missing beta-cell function by an automated, glucose-modulated, insulin-delivery system would allow near normal glycemia without the risk of hypoglycemia. First studies show a good regulation of interprandial glycemia; prandial doses seem more difficult to assess. Nevertheless the “holy grail” might be closer than we think.

Insulin therapy in type 2 diabetes: what is the evidence?

To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal-bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.

Management of Diabetes Mellitus and Hospital-related Hyperglycemia in Patients of a Medical ICU, with the Use of Two “Down-to-Earth” Protocols: A Feasibility Study

Optimal control of blood glucose in the ICU has been shown to significantly decrease mortality and morbidity of severely ill patients. The purpose of the present project was to develop and implement undemanding, "down-to-earth" protocols, enabling tight glucose control in critically ill patients, in the setting of a city hospital ICU with limited personnel and facilities. From January 2003 to January 2006, a total of 745 patients (3197 patient-days) were treated for hyperglycemia in our medical ICU. On July 2003 two different intensive insulin therapy protocols were implemented: A protocol of continuous intravenous insulin, including specific algorithms for calculation of initial insulin bolus, initial infusion rate and further adjustment plan, was used for patients with compromised peripheral tissue perfusion. For patients with stable circulation, a protocol of subcutaneous intensive insulin therapy, including a formula for calculation of daily insulin dosage in previously non-insulin-treated diabetics, was adopted. 134 patients were treated during the run-in phase of the project and 539 patients were treated during the main treatment phase. 72 patients treated for hyperglycemia in our ICU prior to the implementation of the two protocols (from January 2003 to July 2003) served as controls. After the implementation of the two protocols, a marked overall increase of normoglycemic blood glucose values (64.7% vs. 48.5%, P<0.001), a decrease of manifest hyperglycemias (6.4% vs. 17.4%, P<0.001) and an increase in hypoglycemic events (1.8% vs. 0.7%, P<0.001) was observed. Seven cases of severe hypoglycemia requiring glucose infusion were observed during the main treatment phase (0.3%). No hypoglycemia-associated deaths occurred. The combined implementation of the two protocols presents a simple, safe and effective way of pursuing normoglycemia in critically ill patients.

Inhaled Insulin Improves Glycemic Control In Patients With Type 2 Diabetes Mellitus

Source: Weiss SR, Cheng SL, Kourides IA, et al. Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents. Arch Intern Med. 2003;163:2277–2282.Administration of subcutaneous insulin can be initially quite daunting for many diabetes mellitus (DM) patients. Investigators from San Diego Endocrine and Medical Clinic, San Diego, Calif., Pfizer Global Research and Development, New London, Conn., and Yale University School of Medicine, New Haven, Conn., studied 69 patients with type 2 DM, between the ages of 35 and 65 years, who were on oral hypoglycemic agents (OHA) and whose HbAlC levels were between 8 and 12%. They randomized patients to an open label treatment with preprandial inhaled insulin plus OHA versus OHA alone, and followed them weekly, titrating to a 2-hour post-prandial increase in glucose level of <60mg/dL. Both the treatment and control groups had an average HbAlC at the start of the trial of around 10%. At the end of the trial, the pa­tients in the control group still had an average HbAlC of 10%, whereas the patients in the treatment group had an average of 7.5% at the end of the 12-week trial. Seventeen percent of the patients in the control group had a hypoglycemic event compared to 69% of the patients in the treatment group. Those in the treatment group also had improvement in post-prandial blood sugar measurements and in their fasting lipid panels. Pulmonary function tests were unchanged in either group.The Diabetes Control and Complications Trial Research Group1 showed that tight and intensive treatment of blood sugar levels in patients with type 1 DM reduces microvascular complications of retinopathy and nephropathy. Attaining that control comes at the cost of increasing symptomatic hypoglycemic episodes. The authors of this study test whether inhaled insulin can benefit patients with type 2 DM who are not optimally controlled. Their results show that this mode of delivery can indeed be as effective as subcutaneous injection in this population. The increase in hypoglycemic events with insulin therapy comes as no surprise. Clearly, this study in adults would require follow-up in a pediatric population to determine if inhaled insulin can be as effective in children with type 1 and type 2 DM, and if long-term administration has any ill effects. Faced with an increasing rate of obesity and type 2 DM in adolescents, such a study may be worthwhile.

Recombinant DNA technology in the treatment of diabetes: insulin analogs.

After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed.