Tight Glycemic Control Research Articles

PPARγ Deacetylation Confers the Antiatherogenic Effect and Improves Endothelial Function in Diabetes Treatment.

Cardiovascular disease (CVD) is the leading cause of death in patients with diabetes, and tight glycemic control fails to reduce the risk of developing CVD. Thiazolidinediones (TZDs), a class of peroxisome proliferator–activated receptor γ (PPARγ) agonists, are potent insulin sensitizers with antiatherogenic properties, but their clinical use is limited by side effects. PPARγ deacetylation on two lysine residues (K268 and K293) induces brown remodeling of white adipose tissue and uncouples the adverse effects of TZDs from insulin sensitization. Here we show that PPARγ deacetylation confers antiatherogenic properties and retains the insulin-sensitizing effects of TZD while circumventing its detriments. We generated mice homozygous with mice with deacetylation-mimetic PPARγ mutations K268R/K293R (2KR) on an LDL-receptor knockout (Ldlr−/−) background. 2KR:Ldlr−/− mice showed smaller atherosclerotic lesion areas than Ldlr−/− mice, particularly in aortic arches. With rosiglitazone treatment, 2KR:Ldlr−/− mice demonstrated a residual antiatherogenic response and substantial protection against bone loss and fluid retention. The antiatherosclerotic effect of 2KR was attributed to the protection of endothelium, indicated by improved endothelium-dependent vasorelaxation and repressed expression of proatherogenic factors including inducible nitric oxide synthase, interleukin-6, and NADPH oxidase 2. Therefore, manipulating PPARγ acetylation is a promising therapeutic strategy to control risk of CVD in diabetes treatment.

MON-687 Diabetic Muscle Infarction (DMI) a Rare Under-Recognised Complication of Diabetes Mellitus (DM): A Series of Three Cases

Background: Diabetic muscle infarction (DMI) also known as diabetic myonecrosis is an acute, rare, microangiopathic complication of long-standing poorly controlled Diabetes Mellitus (DM). DMI presents as severe pain and swelling of the affected muscle group, usually of the lower extremities. It generally occurs in patients with established vasculopathy from uncontrolled diabetes including retinopathy and nephropathy. However, a clear association of DMI to long term mortality has not yet been defined. Proposed pathophysiologic mechanisms for DMI are microvascular endothelial damage complicated by thromboembolic events triggering an inflammatory cascade, leading to local tissue ischemia and eventual infarction. Alterations in the coagulation-fibrinolysis system and vasculitis have also been invoked. About 50% of the cases have DMI recurrence in the setting of uncontrolled DM.Clinical Case: We report 3 cases of DMI diagnosed in patients with long-standing poorly controlled DM with at least two established micro-vascular complications. The lower extremity muscle group was affected, especially the thigh muscles and paraspinal muscle in one case. Biochemical parameters were significant for normal white blood cell counts, elevated erythrocyte sedimentation rate (112, 105, 145 mm/hr respectively; n 0–15 mm/hr) and C-reactive protein (CRP) (54.3, 260, 162 mg/L respectively; n 0–5.0 mg/L) and elevated creatine kinase in two cases (539 and 379 U/L; n 5–150 U/L). Infectious work-up including blood cultures were negative. Lower extremity doppler was negative in all three cases. Diagnosis was established with the help of MRI in two cases showing diffuse hyperintensities of the muscle groups involved and muscle biopsy in the third showing neutrophilic and eosinophilic inflammation and areas of necrosis, fibrosis and hemorrhage. Treatment involved adequate pain management and anti-platelet therapy along with tight glycemic control. No recurrence thus far was noticed in all three patients.Conclusion: DMI should be considered in the differential diagnosis of patients with the aforementioned risk factors who did not show a response to antibiotics, as administered for presumed cellulitis. Though self-limiting, studies have shown a long term temporal correlation with increased all-cause mortality in patients with DMI. Hence DMI is considered as another cardiovascular risk equivalent. Further studies are needed to explore strategies aimed at preventing DMI and its recurrence.

HbA1c –Marker for Long Term Glycemic Control

Background: Protein glycation is a spontaneous reaction that is believed to play a key role in the pathogenesis of many clinical disorders. The glycation of proteins is enhanced by elevated blood glucose concentrations. The major form of protein glycation with a clinical consideration is glycatedhaemoglobin (HbA1c). HbA1c is majorly affected by the blood glucose levels alone. Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. Studies have suggested that HbA1c levels in type-2 diabetes mellitus patients mostly remains elevated, yet some such patients, with or without tight glycemic control, have HbA1c levels nearly close to or within the normal reference range.Subjects and Methods:In this study HbA1c, fasting blood glucose levels and post prandial blood glucose levels in normal subjects as well as in patients with Type-2 diabetes mellitus excluding the complicated ones were studied.Results:The present study confirms earlier studies that all these levels are tightly correlated and the corresponding p values were < 0.001 which were significant and was estimated by using student t-test.Conclusion: Thus indicating that glycated hemoglobin (HbA1c) can be used to assess the glycemic status of an individual for attaining the treatment goal of preventing long term complications of diabetes mellitus.

Early Combination Therapy with Linagliptin and Metformin in People with Type 2 Diabetes Improves Glycemic Control to HbA1c ≤ 6.5% without Increasing Hypoglycemia: Pooled Analysis of Two Randomized Clinical Trials.

IntroductionClinical guidelines suggest a glycated hemoglobin A1c (HbA1c) target of ≤ 6.5% for type 2 diabetes patients with short duration of disease, few comorbidities and/or long life expectancy—provided this goal can be achieved safely. We explored whether initial combination treatment with the dipeptidyl peptidase-4 inhibitor linagliptin and metformin could provide better glycemic control (HbA1c ≤ 6.5%) than metformin alone without increasing hypoglycemia.MethodsWe pooled and analyzed individual patient data from two randomized clinical trials of early combination therapy with linagliptin and metformin versus metformin monotherapy. The primary outcome in both trials was the change in HbA1c from baseline to week 24. We evaluated the percentage of patients who achieved HbA1c ≤ 6.5% at week 24 and the incidence of adverse events.ResultsMost (> 70%) of the 1160 patients analyzed were treatment naive, and more than half had had diabetes for ≤ 1 year; mean baseline HbA1c was approximately 8.7%. Combination therapy with linagliptin and metformin resulted in more patients achieving HbA1c ≤ 6.5% than metformin alone, both for a metformin dose of 500 mg (40.1 vs. 22.9%, respectively, odds ratio [OR] 2.84, 95% confidence interval [CI] 1.87–4.32) and 1000 mg (49.5 vs. 35.4%, respectively, OR 2.28, 95% CI 1.54–3.40). Hypoglycemia occurred in < 3% of patients, with a comparable incidence between treatment groups. Other adverse events were also balanced between groups.ConclusionEarly combination treatment with linagliptin and metformin can improve the chances of achieving tight glycemic control (HbA1c ≤ 6.5%) without increasing the risk of hypoglycemia or other adverse events.Trial RegistrationClinicalTrials.gov, NCT00798161 and NCT01708902.

SAT-153 CORRELATION BETWEEN HBA1c LEVEL AND RENAL FUNCTION IN DIABETIC NEPHROPATHY

Tight glycemic control may have limited effect on the protection of renal function. No large clinical trials conducted since 2000 have clearly shown that the management goal of HbA1C is 6% better than 7%. In addition, recent clinical trials of many new drugs have compared the HbA1c levels of 8% and 7% groups. Therefore, in this study, HbA1C was divided into each stratum by 1%, and the effect of HbA1c level on renal function was examined. This single-center retrospective observational study examined the HbA1C and Cr data of patients for five consecutive years between 2007 and 2017, beginning from the date of the first measurement of HbA1C. Annual mean values were used as representative values for blood tests. Considering the possibility of a high HbA1C level in the first year, the mean HbA1C level after year 2 was calculated, and the four groups (6%, 7%, 8% and 9%) were compared. Primary endpoints were mean estimated glomerular filtration rate (eGFR) slope and the proportion of patients with rapid renal insufficiency (≥ 5 mL/min/1.73 m2/year). Dialysis patients and those aged 18 years or younger were excluded from the study. The HbA1C 6%, 7%, 8% and 9% groups consisted of 630, 399, 95, and 23 subjects, respectively. The mean ages of these groups were 64.6, 65.0, 60.6, and 61.0 years, respectively, and the mean HbA1C during the course was 6.5 ± 0.3, 7.4 ± 0.3, 8.4 ± 0.3, and 9.4 ± 0.3, respectively. The mean eGFR at 1 year was 69.6, 70.7, 75.7, and 78.4 ml/min/1.73 m2, respectively. The higher the HbA1C level, the greater was the eGFR slope. The eGFR slopes were -1.2 ± 2.8, 1.2 ± 2.7, 1.5 ± 3.3, and 2.6 ± 3.6 mL/min/1.73 m2/year for the four groups, respectively. The incidence of rapid decreased renal function was 7.3%, 6.5%, 10.5% and 21.7% for HbA1C 6%, 7%, 8% and 9% groups, respectively, showing similar tendency with the eGFR slope. Furthermore, only the 6% and 7% groups were analyzed by matching background factors, but no significant difference was found (P = 0.74). In the present study, there was no significant difference in either the eGFR slope or the percentage of patients with rapid decreased renal function between HbA1C in the 6% and 7% ranges.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary and Renal Considerations: Executive Summary.

OBJECTIVES To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Virtual patient trials of a multi-input stochastic model for tight glycaemic control using insulin sensitivity and blood glucose data

ObjectiveSafe, effective glycaemic control (GC) requires accurate prediction of future patient insulin sensitivity (SI), balancing the risk of hyper- and hypo-glycaemia. The stochastic targeted (STAR) protocol combines a clinically validated metabolic model and SI metric with a risk-based stochastic approach to optimise patient specific insulin and feed rates. Validated virtual trials comparing a novel 3D stochastic model for prediction of future patient SI using current patient SI and current blood glucose (BG) to an existing 2D stochastic model for SI prediction were conducted. MethodsThe virtual trials involved 1477 retrospective patients across two hospitals and two GC protocols. They were conducted using five-fold cross-validation to build each stochastic model, ensuring independent test data. ResultsThe 3D stochastic model shifted BG from the 4.4–8.0 mmol/L target band towards the lower 4.4–6.5 mmol/L band, providing a decrease from 12.31 % to 11.19 % in hyperglycaemic hours (BG > 8.0 mmol/L), but only a 0.24 % increase, from 1.01 % to 1.25 %, in light hypoglycaemic hours (BG < 4.0 mmol/L). Simultaneously, the 3D stochastic model enabled greater patient nutrition, and required negligible increase in computational or clinical workload. ConclusionsThe 3D stochastic model provided greater personalisation and better realised STAR’s design philosophy of minimising hyperglycaemic events for an acceptable clinical risk of 5.0 % BG < 4.4 mmol/L. Thus, this model could provide better clinical conformity to design targets if implemented within the STAR protocol.

Tight glycemic control in critically ill children

Hyperglycemia is a common metabolic derangement in critically ill patients. In 2001, investigators from Leuven, Belgium published results of a randomized study conducted in an adult surgical ICU testing the benefit of intensive insulin therapy, with the goal of maintaining serum glucose 80-110 mg/deciliter (N Engl J Med 2001;345:1359-67). This strategy, labelled “tight glycemic control,” resulted in a statistically detectable survival benefit compared with the more conventional approach of maintaining serum glucose values near 200 mg/deciliter. Almost from the start, however, this strategy came under scrutiny. The Leuven study was single-center, it was difficult to blind, and the physiologic basis for the benefit (prevention of hyperglycemia versus advantages of exogenous insulin versus something else) was unclear. Additionally, several subsequent attempts to replicate the Leuven experience in adult patients were met with inconsistent results. More worrisome was a hint in both the original and subsequent trials that tight glycemic control was associated with an increased incidence, albeit small, of significant hypoglycemia, which independently was associated with higher mortality. Scrupulous testing of tight glycemic control in children was particularly crucial given the vulnerability of developing brains to low serum glucose. The largest and most definitive of these studies was the HALF-PINT (Heart and Lung Failure Pediatric Insulin Titration) Trial, a 32-center federally funded project that assigned children requiring vasoactive or mechanical ventilatory support to 1 of 2 glucose targets, namely, 80-110 mg/deciliter versus 150-180 mg/deciliter. HALF-PINT enrolled children between 2012-2016 and was stopped prematurely due to a low likelihood of benefit and a signal that the lower glucose-target group experienced a higher incidence of hypoglycemia (N Engl J Med 2017;366:729-41). A critical a priori extension of HALF-PINT, measuring 1-year neurodevelopmental outcomes in enrollees, appears in this volume of The Journal. The results of extensive testing indicated similar outcomes in both groups, but they again supported that hypoglycemia from any cause had adverse effects, establishing the superiority of the higher glucose target. The HALF-PINT follow-up study has limitations: only 2- to 17-year-old subjects were tested given constraints of the instruments used, and only 60% of eligible subjects completed the 1-year follow-up testing. It should be emphasized that the HALF-PINT protocol did not test tight glycemic control versus “conventional” insulin therapy in critically ill children, but 2 different strategies of tight glycemic control differing in target serum glucose ranges. Indeed, the authors understood that hyperglycemia has its own neurotoxic effects in children and should be avoided. The HALF-PINT investigators should be commended for the commission of this difficult yet extremely important study, which likely will serve to established serum glucose levels of 150-180 mg/deciliter as the upper-limit standard in critically ill children. Article page 57▸

Accuracy of Blood Glucose Measurement and Blood Glucose Targets.

To summarize new evidence regarding the methodological aspects of blood glucose control in the intensive care unit (ICU). We reviewed the literature on blood glucose control in the ICU up to August 2019 through Ovid Medline and Pubmed. Since the publication of the Leuven studies, the benefits of glycemic control have been recognized. However, the methodology of blood glucose control, notably the blood glucose measurement accuracy and the insulin titration protocol, plays an important but underestimated role. This may partially explain the negative results of the large, pragmatic multicenter trials and made everyone realize that tight glycemic control with less-frequent glucose measurements on less accurate blood glucose meters is neither feasible nor advisable in daily practice. Blood gas analyzers remain the gold standard. New generation point-of-care blood glucose meters may be an alternative when using whole blood of critically ill patients in combination with a clinically validated insulin dosing algorithm. When implementing blood glucose management in an ICU one needs to take into account the interaction between aimed glycemic target and blood glucose measurement methodology.

Annals for Educators - 4 February 2020.

Annals for Educators - 4 February 2020.

Abstract WP378: Insulin in the Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: The role of tight glycemic control in the management of acute ischemic stroke remains uncertain. Objective: Our goal is to evaluate the effects of tight glucose control with insulin therapy after acute ischemic stroke. Methods: We searched PubMed, CENTRAL, and EMBASE for randomized controlled trials (RCTs) that evaluated the effects of tight glycemic control (70 - 135 mg/dL) in acute ischemic stroke. Analysis was performed using fixed- and random-effects models. Outcomes were death, independence and modified Rankin Scale (mRS) score at ≥90 days follow-up, and symptomatic or severe hypoglycemia during treatment. Results: Twelve RCTs including 2,734 patients were included. When compared to conventional therapy or placebo, tight glycemic control was associated with similar rates of mortality at ≥90 days follow-up (pooled odds ratio [pOR], 0.99 [95% CI, 0.79 - 1.22], I 2 0%), independence at ≥90 days follow-up (pOR, 0.95 [0.79 - 1.14], I 2 0%) and mRS scores at ≥90 days follow-up (standardized mean difference, 0.014 [-0.15 - 0.17], I 2 0%). In contrast, tight glycemic control was associated with increased rates of symptomatic or severe hypoglycemia during treatment (pOR 5.2 [1.87 - 14.42], I 2 20%). Conclusion: Tight glucose control after acute ischemic stroke is not associated with improvements in mortality, independence or mRS score and leads to higher rates of symptomatic or severe hypoglycemia.

Adjusted tight control blood glucose management in diabetic patients undergoing on pump coronary artery bypass graft. A randomized clinical trial.

Many of the patients who are undergoing Coronary Artery Bypass Graft have diabetes mellitus or metabolic syndrome and are at risk for hyperglycemia events. The present study aimed to compare conventional glucose control with adjusted tight control in patients undergoing on-pump CABG. This double -blind randomized clinical trial study was conducted in Shiraz, Iran, from September 2017-March 2018. Two consecutive groups of 75 patients undergoing elective on- pump coronary artery bypass graft surgery. The patients were divided into adjusted tight control of the blood glucose between 100 and 120mg/dl and conventional method that the blood glucose maintained ≤200mg/dl. mortality, sternal wound infection, cardiac arrhythmia, cerebrovascular attack, and acute renal failure. duration of mechanical ventilation and length of ICU staying. The same main outcomes were evaluated after one month. The data were analyzed using SPSS version 20(SPSS, Chicago, IL). Group comparisons were performed using t-tests and Chi-square tests. Repeated measurement test was used for comparing blood glucose in two groups. Mann Whitney U test was compared duration of the mechanical ventilation and length of ICU staying. Statistical significance was defined as a p value <0.05. There were no significant differences between main and secondary outcomes. About late outcomes, sternal wound infection was in the control group (7 patients) more than intervention (1 patient) (P < 0.05). No differences between other complications in both groups were observed. The occurrence of hypoglycemia was low in both groups. Hypokalemia was significantly higher in the intervention than in control (P < 0.001). The findings showed using adjusted tight glycemic control to a level that is nearby to normal values during cardiac surgery may reduce episodes of hypoglycemia and thus reduces its side effects. As well as reduce hyperglycemic complications such as sternal wound infection. IRCT2013041713052N1). 2013-07-09.

Insulin in the Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

The role of tight glycemic control in the management of acute ischemic stroke remains uncertain. Our goal is to evaluate the effects of tight glucose control with insulin therapy after acute ischemic stroke. We searched PubMed, CENTRAL, and Embase for randomized controlled trials (RCTs) that evaluated the effects of tight glycemic control (70-135 mg/dL) in acute ischemic stroke. Analysis was performed using fixed-effects and random-effects models. Outcomes were death, independence, and modified Rankin Scale (mRS) score at ≥90 days follow-up, and symptomatic or severe hypoglycemia during treatment. Twelve RCTs including 2734 patients were included. Compared with conventional therapy or placebo, tight glycemic control was associated with similar rates of mortality at ≥90 days follow-up (pooled odds ratio [pOR], 0.99; 95% confidence interval [CI], 0.79-1.22]; I2= 0%), independence at ≥90 days follow-up (pOR, 0.95; 95% CI, 0.79-1.14; I2= 0%) and mRS scores at ≥90 days follow-up (standardized mean difference, 0.014; 95% CI, -0.15 to 0.17; I2= 0%). In contrast, tight glycemic control was associated with increased rates of symptomatic or severe hypoglycemia during treatment (pOR, 5.2; 95% CI, 1.7-15.9; I2=28%). Tight glucose control after acute ischemic stroke is not associated with improvements in mortality, independence, or mRS score and leads to higher rates of symptomatic or severe hypoglycemia.

Long-Term Neurobehavioral and Quality of Life Outcomes of Critically Ill Children after Glycemic Control

To investigate adaptive skills, behavior, and quality health-related quality of life in children from 32 centers enrolling in the Heart And Lung Failure-Pediatric INsulin Titration randomized controlled trial. This prospective longitudinal cohort study compared the effect of 2 tight glycemic control ranges (lower target, 80-100mg/dL vs higher target, 150-180mg/dL) 1-year neurobehavioral and health-related quality of life outcomes. Subjects had confirmed hyperglycemia and cardiac and/or respiratory failure. Patients aged 2-16years old enrolled between April 2012 and September 2016 were studied at 1year after intensive care discharge. The primary outcome, adaptive skills, was assessed using the Vineland Adaptive Behavior Scale. Behavior and health-related quality of life outcomes were assessed as secondary outcomes using the Pediatric Quality of Life and Child Behavior Checklist at baseline and 1-year follow-up. Group differences were evaluated using regression models adjusting for age category, baseline overall performance, and risk of mortality. Of 369 eligible children, 358 survived after hospital discharge and 214 (60%) completed follow-up. One-year Vineland Adaptive Behavior Scale-II composite scores were not different (mean±SD, 79.9±25.5 vs 79.4±26.9, lower vs higher target; P=.20). Improvement in Pediatric Quality of Life total health from baseline was greater in the higher target group (adjusted mean difference, 8.2; 95% CI, 1.1-15.3; P=.02). One-year adaptive behavior in critically ill children with lower vs higher target glycemic control did not differ. The higher target group demonstrated improvement from baseline in overall health. This study affirms the lack of benefit of lower glucose targeting. ClinicalTrials.gov: NCT01565941.

Surgical Site Infection Prevention Following Spine Surgery.

Study Design:Literature review.Objectives:Surgical site infection (SSI) following spine surgery leads to significant patient morbidity, mortality, and increased health care costs. The purpose of this article is to identify risk factors and strategies to prevent SSIs following spine surgery, with particular focus on avoiding infections in posterior cervical surgery.Methods:We performed a literature review and synthesis to identify methods that can be used to prevent the development of SSI following spine surgery. Specific pearls for preventing infection in posterior cervical spine surgery are also presented.Results:SSI prevention can be divided into patient and surgeon factors. Preoperative patient factors include smoking cessation, tight glycemic control, weight loss, and nutrition optimization. Surgeon factors include screening and treatment for pathologic microorganisms, skin preparation using chlorhexidine and alcohol, antimicrobial prophylaxis, hand hygiene, meticulous surgical technique, frequent irrigation, intrawound vancomycin powder, meticulous multilayered closure, and use of closed suction drains.Conclusion:Prevention of SSI following spine surgery is multifactorial and begins with careful patient selection, preoperative optimization, and meticulous attention to numerous surgical factors. With careful attention to various patient and surgeon factors, it is possible to significantly reduce SSI rates following spine surgery.

Individualizing Glycemic Control in the Critically Ill.

Hyperglycemia is a common phenomenon in critically ill patients, even in those without diabetes. Two landmark studies established the benefits of tight glucose control (blood glucose target 80-110 mg/dL) in surgical and medical patients. Since then, literature has consistently demonstrated that both hyperglycemia and hypoglycemia are independently associated with increased morbidity and mortality in a variety of critically ill patients. However, tight glycemic control has subsequently come into question due to risks of hypoglycemia and increased mortality. More recently, strategies targeting euglycemia (blood glucose ≤180 mg/dL) have been associated with improved outcomes, although the risk of hypoglycemia remains. More complex targets (ie, glycemic variability and time within target glucose range) and the impact of individual patient characteristics (ie, diabetic status and prehospital glucose control) have more recently been shown to influence the relationship between glycemic control and outcomes in critically ill patients. Although our understanding has increased, the optimal glycemic target is still unclear and glucose management strategies may require adjustment for individual patient characteristics. As glucose management increases in complexity, we realize that traditional means of using meters and strips and paper insulin titration algorithms are potential limitations to our success. To achieve these complex goals for glycemic control, the use of continuous or near-continuous glucose monitoring combined with computerized insulin titration algorithms may be required. The purpose of this review is to discuss the evidence surrounding the various domains of glycemic control and the emerging data supporting the need for individualized glucose targets in critically ill patients.

Artificial Intelligence Based Insulin Sensitivity Prediction for Personalized Glycaemic Control in Intensive Care

Stress-induced hyperglycaemia is a frequent complication in the intensive therapy that can be safely and efficiently treated by using the recently developed model-based tight glycaemic control (TGC) protocols. The most widely applied TGC protocol is the STAR (Stochastic-TARgeted) protocol which uses the insulin sensitivity (SI) for the assessment of the patients state. The patient-specific metabolic variability is managed by the so-called stochastic model allowing the prediction of the 90% confidence interval of the future SI value of the patients. In this paper deep neural network (DNN) based methods (classification DNN and Mixture Density Network) are suggested to implement the patient state prediction. The deep neural networks are trained by using three years of STAR treatment data. The methods are validated by comparing the prediction statistics with the reference data set. The prediction accuracy was also compared with the stochastic model currently used in the clinical practice. The presented results proved the applicability of the neural network based methods for the patient state prediction in the model based clinical treatment. Results suggest that the methods’ prediction accuracy was the same or better than the currently used stochastic model. These results are the initial successful step in the validation process of the proposed methods which will be followed by in-silico simulation trials.

Predisposing factors of hypoglycemia in patients with type 2 diabetes mellitus presented with symptomatic hypoglycemia in a tertiary hospital of Bangladesh

Background: Hypoglycemia is almost inevitable complication of diabetes treatment and the most important barrier in achieving tight glycemic control in diabetes patients. Objective: To describe characteristics of the patients with T2DM presenting with hypoglycemia and identify the predisposing factors of hypoglycemia in them. Materials and Methods: This cross-sectional study was conducted in a tertiary hospital of Bangladesh from January 2017 to March 2018. Venous plasma glucose was measured in all patients with T2DM presented with signs-symptoms of hypoglycemia, patients having biochemically confirmed hypoglycemia (venous plasma glucose <3.9 mmol/L) were finally selected for the study. A semi-structured data collection sheet was used to obtain the demographic and clinical data including hypoglycemic symptoms. Results: One hundred patients with T2DM were included in the study among whom 59% were female, 53% aged ≥60 years, 90% lived in rural and sub-urban areas, 60% had diabetes for ≥10 years, and 88% took insulin. Hypertension was the most common (45%) co-morbid condition followed by ischemic heart disease (28%). Adrenergic symptoms were present in the majority of the subjects and 62% lost consciousness before reaching the hospital. Their mean plasma glucose at presentation was 2.41 mmol/L (±0.48); mean HbA1c was 7.5% (±1.7) and 86% of them had eGFR <60 mL/min/1.73m2. Most of them (92%) received no education on hypoglycemia management and did not perform (95%) self-monitoring of blood glucose (SMBG). More than half had (51%) hypoglycemic episodes in the preceding 6 months and 28% were hospitalized for that. The meal-related factors (missed, inadequate or delayed meals) were the most common precipitating factors followed by drug overdose and excess exercise before hypoglycemia. Conclusion: Diabetes education emphasizing on appropriate lifestyle and dietary habit, and SMBG at recommended frequency are of utmost importance to prevent hypoglycemia.

Rhino-orbito-cerebral mucormycosis in patients with uncontrolled diabetes: A case series

IntroductionMucormycosis is a rare, aggressive, and invasive disease with a fatal outcome. It most commonly affects patients with compromised immunity, particularly those with poorly controlled diabetes. We present a case series of patients with uncontrolled diabetes and mucormycosis. Presentation of caseWe present a series of three patients with uncontrolled diabetes, with main symptoms of paranasal sinusitis, nasal discharge, ophthalmic changes, and facial nerve involvement. Diagnoses of mucormycosis were made via microbiological testing and computed tomography. These cases were managed by combination therapy of tight glycemic control, urgent endoscopic sinus debridement, and antifungal therapy. DiscussionDiagnosing rhino-orbito-cerebral mucormycosis requires a high degree of suspicion and both microbiologic and microscopic evidence. Better clinical outcomes can be obtained by combining medical and surgical management. ConclusionWe describe our experience in handling three cases of poorly controlled diabetes with rhino-orbito-cerebral mucormycosis.

The Efficacy of Intensive versus Conventional Insulin Therapy in Reducing Mortality and Morbidity in Medical and Surgical Critically Ill Patients: A Randomized Controlled Study.

Context:Stress hyperglycemia in critically ill patients has been a matter of debate for years without any conclusive answer till date regarding glucose management and treatment thresholds.Aims:We planned a study with an aim to compare the efficacy of intensive versus conventional insulin therapy in reducing the mortality and morbidity in critically ill patients. The primary objective was to compare mortality between the two groups. The secondary objective was to find out if intensive insulin therapy is better than conventional insulin therapy in terms of various outcomes such as infections and need for inotropes and transfusion requirements.Settings and Design:It was a prospective randomized controlled study. The study population included 100 patients who received mechanical ventilation and admitted to the intensive care department of a tertiary care institute.Subjects and Methods:Patients were randomly assigned to two groups: intensive insulin therapy (IIT) and conventional insulin therapy (CIT) to receive either intensive or conventional insulin therapy. Insulin infusion was started only when blood glucose levels exceeded 200 mg%. Blood glucose levels were maintained between 80 and 110 mg% in the IIG and between 180 and 200 mg% in the CIG.Statistical Analysis Used:The data collected were analyzed separately for both the groups using Student's t-test and Chi-square test.Results:The two groups were comparable in terms of baseline demographic data including age, sex, preadmission diabetic status, and HbA1c at the time of admission. The two groups were not comparable in terms of Acute Physiology and Chronic Health Evaluation-II scores, and the difference between them was statistically significant with higher scores in the conventional group. The primary outcome, that is, mortality, was higher in the CIG with 29 patients (58%) versus 3 (6%) in the IIG (P = 0.02). The secondary outcomes were the measures of morbidity including infections, need for inotropic support, and need for blood transfusions, and these were significantly higher in the conventional group (P < 0.05).Conclusions:We conclude that tight glycemic control significantly lowers mortality and morbidity in critically ill patients, both surgical and medical. These benefits appear with the maintenance of tight blood glucose control of 80–110 mg.dL − 1 and not due to administration of insulin.