Strict Glucose Control Research Articles

Intensity of peri-operative glycemic control and postoperative outcomes in patients with diabetes: a meta-analysis

AimsPeri-operative hyperglycemia is a risk factor for postoperative morbidity and mortality. However, the role of specific glycemic targets in reducing this risk has not been defined, particularly among patients with diabetes. Thus, our objective was to conduct a meta-analysis relating distinct peri-operative glycemic targets and postoperative outcomes in patients with diabetes. MethodsA systematic review was performed by two authors utilizing pre-specified terms: “diabetes mellitus” and “perioperative” and “mortality” and “blood glucose” or “strict glucose control” or “intensive insulin therapy” in PUBMED, CENTRAL and EMBASE. Glycemic control was considered strict when perioperative targets ranged between 100 and 150mg/dL (5.6–8.3mmol/l), moderate when the targets ranged between 150 and 200mg/dL 8.3–11.1mmol/l), and liberal when the target was >200mg/dL (11.1mmol/l). The data were combined utilizing the Dersimoan–Laird random-effects method. The primary endpoint was postoperative mortality with secondary endpoints of postoperative atrial fibrillation, wound infection, and stroke. ResultsThe literature search yielded 760 studies, of which only 6 met inclusion criteria. When compared with a liberal target, pooled data showed that a moderate glycemic target was associated with reduced postoperative mortality (OR=0.48, 95% CI 0.24–0.76) and stroke (OR=0.61, 95% CI 0.38–0.98), but no differences in atrial fibrillation or wound infection were found. There were no significant differences in postoperative outcomes between moderate versus strict perioperative glycemic target. ConclusionsPooled results suggest that in patients with diabetes, a moderate peri-operative glycemic target (150–200mg/dl [5.6–8.3mmol/l]) is associated with reduction in postoperative mortality and stroke compared with a liberal target (>200mg/dl [11.1mmol/l]), whereas no significant additional benefit was found with more strict glycemic control (<150mg/dl [5.6mmol/l]).

SAT0350 Glucose and Insulin Concentrations in Association with Hand Osteoarthritis: The Neo Study

BackgroundBody mass index (BMI) is an important risk factor for osteoarthritis (OA), however the underlying causal pathways are unclear. Earlier studies showed an association of diabetes mellitus and OA, suggesting...

Painful diabetic neuropathy management

Diabetic neuropathy is the most common complication of diabetes as it affects a significant number of patients. The management of patients with diabetic neuropathy is complicated by several factors including the varied symptoms and response to the various treatments available. Strict blood glucose control remains the key to the management thus far nonetheless; it is associated with complications such as hypoglycaemia. In order to provide the most up-to-date evidence-based clinical recommendations pertinent to the management of diabetic neuropathy, several databases and clinical practice guidelines were searched for this evidence-based report. The main outcome measures are reduction in pain associated with diabetic neuropathy and the number of withdrawal rates due to adverse effects of the medications both of which are discussed in this report. Various pharmacological and non-pharmacological treatments are available with varying degrees of success in pain relief. The current evidence suggests that use of tricyclics antidepressants and conventional anticonvulsants for the short term of pain relief is beneficial. Combination therapy of opioids and anticonvulsants has also been found to be superior to monotherapy. Other treatment modalities such as the use of alpha-lipoic acid as an antioxidant and evening primrose oil through increased PGE1 synthesis have also been trialled with evidence of improvement in neuropathic pain. Evidence also supports non-pharmacological treatment such as the use of percutaneous electrical nerve stimulation. There is a scope for further improvement of the reporting of rating pain scales and including various outcomes measures such as quality of life and physical function when trialling new therapies for better evaluation of future treatments.

Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials

The relationship between glucose control and cardiovascular outcomes in type 2 diabetes has been a matter of controversy over the years. Although epidemiological evidence exists in favor of an adverse role of poor glucose control on cardiovascular events, intervention trials have been less conclusive. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, the Action in Diabetes and Vascular Disease (ADVANCE) study, and the Veterans Affairs Diabetes Trial (VADT) have shown no beneficial effect of intensive glucose control on primary cardiovascular endpoints in type 2 diabetes. However, subgroup analysis has provided evidence suggesting that the potential beneficial effect largely depends on patients’ characteristics, including age, diabetes duration, previous glucose control, presence of cardiovascular disease, and risk of hypoglycemia. The benefit of strict glucose control on cardiovascular outcomes and mortality may be indeed hampered by the extent and frequency of hypoglycemic events and could be enhanced if glucose-lowering medications, capable of exerting favorable effects on the cardiovascular system, were used. This review examines the relationship between intensive glucose control and cardiovascular outcomes in type 2 diabetes, addressing the need for individualization of glucose targets and careful consideration of the benefit/risk profile of antidiabetes medications.

Technical Challenges and Clinical Outcomes of Using a Closed-Loop Glycemic Control System in the Hospital

According to large randomized trials, results suggest that maintaining normoglycemia postoperatively through tight glycemic control (TGC) and intensive insulin therapy (IIT) can improve surgical outcomes as well as reduce mortality and morbidity in critically ill patients. However, trials examining the effects of TGC have had conflicting results. Systematic reviews and meta-analyses have also led to differing conclusions. The main reason these clinical trials and meta-analyses show negative results for TGC is the high incidence of hypoglycemia induced by IIT. This could not be prevented because there is no reliable technique that can avoid this condition during IIT. The development of accurate, continuous blood glucose monitoring devices and closed-loop systems for computer-assisted blood glucose control in the intensive care unit (ICU) will probably help avoid hypoglycemia in these situations. The STG closed-loop glycemic control system was introduced to our department to be used and evaluated for strict serum glucose control with no hypoglycemic episodes during IIT in the surgical ICU, to reduce the workload of ICU nurses, and to decrease incidents related to the management of blood glucose levels according to manual conventional venous infusion insulin therapy. The goal of our team was to use the STG closed-loop glycemic control system for perioperative TGC in surgical patients to solve the complications of IIT and reduce risk of hypoglycemia. The challenge at our hospital demonstrated that the STG closed-loop glycemic control system can be expected to achieve TGC with no occurrence of hypoglycemia induced by IIT after surgery.

Case of Recurrent Diabetic Muscle Infarction Related to Strict Blood Glucose Control

Diabetic muscle infarction (DMI) is an uncommon complication in patients with diabetes and it tends to be underdiagnosed, or misdiagnosed, clinically. Recently, we experienced a case of recurrent diabetic muscle infarction that was unusual in that the patient was younger than other patients. The patient was a 21-year-old woman with a 9-year history of maturity-onset diabetes of the young (MODY) who was referred to our department complaining of pain and edema in her right thigh. Magnetic resonance imaging (MRI) showed an increased T2-weighted signal and edema in the affected muscle. The final diagnosis was DMI. However, when the patient had partially recovered and was receiving supportive care, she had a second attack on the other side of the same leg during her hospitalization, in spite of her blood glucose level being strictly controlled. We report the clinical characteristics and imaging findings of this patient with recurrent DMI. (Korean J Med 2013;84:737-741)

Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation

The purpose of this study was to evaluate the usefulness of the closed-loop system (STG-22; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose in patients undergoing liver transplantation. Sixteen patients undergoing living-donor liver transplantation were enrolled in this study. Glucose levels were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n=8) or a programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n=8). The target glucose level range was set at 80-150 mg/dl. The mean and SD of blood glucose concentration during surgery (Glu-Ave and Glu-SD, respectively) for the programmed insulin group were lower than for the manual insulin group. The coefficient of variability (Glu-CV=Glu-SD×100 /Glu-Ave) for the programmed insulin group was also lower than for the manual insulin group (20.1±4.9% vs. 26.9±6.1%; mean±SD). No hypoglycemia was detected in either group. The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration.

Risk Factors for Infection After Orthopaedic Spine Surgery at a High-Volume Institution

Surgical site infections are associated with increased morbidity, mortality, and resource utilization. To identify risk factors for infection, the authors reviewed all orthopaedic spine operations at Duke University Medical Center from 2005 to 2010. Of the 3138 patients treated during the study period, 115 developed a surgical site infection (3.7%). Demographics, comorbidities, and perioperative blood glucose levels were analyzed in the infected and uninfected cohorts. History of myocardial infarction, congestive heart failure, renal disease, pneumonia, urinary tract infection, and diabetes mellitus (DM) were associated with a higher risk of infection. Notably, a diagnosis of DM nearly doubled the risk of infection. Even in patients without DM, perioperative blood glucose levels greater than 140 mg/dL doubled the risk of infection. The authors propose that strict blood glucose control in both DM and non-DM patients may significantly reduce the risk of infection after spinal surgery.

Benefits of intensive insulin therapy in post-operative intensive care patients

Patients without diabetes who have surgery often develop elevated blood glucose levels. This article describes the effects of stress on blood glucose levels and the importance of treating stress-induced hyperglycaemia in surgical patients. It suggests that all patients with or without diabetes could benefit from the maintenance of strict blood glucose control within set parameters during and after surgery. The evidence suggests that strict control of blood glucose levels and frequent monitoring and maintenance of normoglycaemia may reduce post-operative complications and promote better patient long-term outcomes. The use of intensive insulin therapy is recommended for all post-operative patients in intensive care.

La variabilité glycémique en réanimation

Hyperglycemia is significantly associated with increased mortality in critically ill patients and then, strict control of blood glucose (BG) concentration is important. Lowering of BG levels with intensive insulin therapy (IIT) was recommended in order to improve patient outcomes. But recently, some recent prospective trials failed to confirm the initial data, showing conflicting results (significantly increased mortality with IIT, more hypoglycemic episodes). So there is no consensus about efficiency and safety of IIT. Significant associations between glucose variability and mortality have been confirmed by several recent studies. A difference in variability of BG control could explain why the effect of IIT varied from beneficial to harmful. Managing and decreasing this BG variability could be an important goal of BG control in critically ill patients. Clinicians have to consider definitions, physiopathology and impacts of glucose variability, in order to improve patient outcomes.

Aspekte der perioperativen Behandlung von Diabetespatienten

Diabetes is a common disease in Germany. Due to diabetes-associated end-organ disease, such as large and small vessel disease and neuropathy, diabetic patients require more intense anesthesia care during the perioperative phase. An in-depth and comprehensive medical history focusing on hemodynamic alterations, gastroparesis, neuropathy and stiff joint syndrome is a cornerstone of perioperative care and may affect outcome of diabetes patients more than specific anesthetic medications or the anesthetic procedure. Intraoperative anesthetic care needs to focus on preservation of hemodynamic stability, perioperative infection control and maintenance of glucose homeostasis. Whereas some years ago strict glucose control by aggressive insulin therapy was adamantly advocated, the results of recent studies have put the risk of such therapeutic algorithms into perspective. Therefore, optimized perioperative care of diabetic patients consists of setting a predefined targeted blood glucose level, evidence-based therapeutic approaches to reach that goal and finally adequate and continuous monitoring and amendment of the therapeutic approach if required.

Comprehensive Intensive Therapy for Chinese Gestational Diabetes Benefits Both Newborns and Mothers

This study identified the impact of intensive therapy on neonatal outcomes in women with gestational diabetes mellitus (GDM) and determined the effects on the postpartum metabolic status of the mothers. In total, 127 pregnant women with GDM were randomly selected to receive an intensive treatment regimen, which included one-to-one education, lifestyle intervention, scheduled clinic visits, strict glucose control, and frequent glucose self-monitoring. Meanwhile, 148 age-matched pregnant women with GDM were selected as controls and given the standard treatment regimen. Pregnancy outcomes including parameters related to the GDM mothers and to their neonates were comparatively analyzed between the two treatment groups. GDM patient follow-up (range, 1-3 years after delivery) included an oral glucose tolerance test and measurements of lipid concentration and insulin secretion. The insulinogenic index (ΔInsulin(30 min)/ΔBlood glucose(30 min)) and homeostasis model assessment index of β-cell function and insulin resistance were calculated. The patients' demographic and anthropometric data were also recorded for comparative analysis. Compared with GDM patients receiving standard treatment, GDM patients receiving intensive treatment had lower instances of premature delivery (2.4% vs. 8.3%, P<0.05) and neonatal care unit admission (21.3% vs. 33.3%, P<0.05) and lower neonatal birth weight (3.26±0.53 vs. 3.45±0.55 kg, P<0.0001). At follow-up, GDM patients from the intensive treatment group had a smaller waist circumference (75.83±3.11 vs. 78.34±4.20 cm, P<0.01), lower 30-min glucose levels after a 75-g glucose load (8.26±1.85 vs. 9.46±2.74 mmol/L, P<0.05), and higher high-density lipoprotein levels (1.30±0.24 vs. 1.18±0.23 mmol/L, P<0.05). The intensive GDM treatment regimen led to healthier outcomes for the women, the neonates, and the birth event and was associated with better maternal metabolic situations in the months and years after delivery.

Abstract 221: Renoprotective Effects of SGLT2 Inhibitor, Luseogliflozin, on the Progression of Diabetic Nephropathy in T2DN Rats

This study examined the effect of long term control of hyperglycemia with a new selective SGLT2 inhibitor, luseogliflozin (TS-071), given alone and in combination with lisinopril on the development of renal injury in a rat model of type 2 diabetic nephropathy (T2DN). Chronic treatment of 14-month old T2DN rats with luseogliflozin (10 mg/Kg/day) reduced plasma glucose levels from 285.7±17.7 mg/dL to 161.7±5.5 mg/dL and HbA1c from 8.9±0.4% to 6.4±0.2% in 17-month old T2DN rats but it had no effect on mean arterial pressure (MAP). Chronic treatment with lisinopril (10 mg/Kg/day) markedly reduced MAP (113.0±4.6 mmHg) compared with 17-month old T2DN rats (140.0±4.1 mmHg) but it had no effect on plasma glucose levels. Combination therapy with luseogliflozin and lisinopril significantly reduced MAP (92.9±4.0 mmHg) more than that seen in lisinopril treated rats. The kidneys of T2DN rats exhibited marked focal glomerulosclerosis with a glomerular injury score of 3.1±0.1 on a 0-4 scale and renal cortical fibrosis of 27.9±0.9%. Control of hyperglycemia with luseogliflozin reduced the glomerular injury score (2.6±0.1) and the renal cortical fibrosis (20.8±0.8%). Reducing blood pressure with lisinopril also reduced the glomerular injury score (2.5±0.1) but not the renal cortical fibrosis (29.0±1.5%). Combination therapy with luseogliflozin and lisinopril markedly reduced the glomerular injury score (2.0±0.1) and the renal cortical fibrosis (15.6±1.0%) more than either drug alone. GFR decreased from 0.44±0.04 to 0.29±0.03 mL/min/g- kwt and RBF decreased from 2.7±0.2 to 2.2±0.2 mL/min/g-kwt in T2DN rats over the course of this study. Chronic treatment of luseogliflozin or lisinopril prevented the decrease of GFR (0.44±0.05 and 0.54±0.05 mL/min/g-kwt) and RBF (3.2±0.2 and 6.7±1.1 mL/min/g-kwt). These results suggest that strict control of blood glucose with the luseogliflozin slows the progression of diabetic nephropathy and combination therapy with luseogliflozin and lisinopril is more effective at lowering blood pressure and is more renoprotective than administration of lisinopril alone.

Morphormetric changes of optic nerve in experimentally induced type 2 diabetic rats

AbstractPurpose To investigate the morphometric changes of optic nerve and evaluate the effect of restriction of diet in experimentally‐induced type 2 diabetic rats.Methods Thirty Strague‐Dawley(S.D.) rats were divided into three groups. At 13‐week old age, control group (group A) was performed to just open and close the abdominal cavity and partial pancreatectomy was done in group B and C. Group B(ad libitum) was admitted to intake normal diet and group C(restriction) was restricted to intake from 6 week post‐operation until to be sacrificed at 24‐week old age. We measured the size of optic nerve, axon, the thickness of the myelin sheath, the ratio of axon per myelin, the histologic findings of the optic nerve in electron microscopy.Results From the 19th week to 24th week‐old‐age mean blood glucose (mg/dl) was 99.9±11.10 in group A, 399.8±108.42 in group B and 197 ±83.48 in group C(p&lt;0.05). Mean axon size (µm2) was 0.699±0.094 in group A, 0.579±0.089 in group B and 0.672±0.023 in group C(p&gt;0.05). The mean ratio of myelin to axon was 1.155 ±0.121 in group A, 1.667±0.075 in group B and 1.070±0.324 in group C(p&lt;0.05). Disappearance of regular axonal shape was found in group B and lamellar separation of myelin sheath was found in group C.Conclusion Experimentally‐induced type 2 diabetic rats showed morphometric changes of optic nerve during early diabetes even if strict control of blood glucose was performed.

Use of a postoperative insulin protocol decreases wound infection in diabetics undergoing lower extremity bypass

Strict glucose control in patients undergoing coronary bypass grafting has been shown to decrease infectious complications, arrhythmias, and mortality. Our objective was to determine if strict glucose control reduced morbidity after lower extremity bypass (LEB). A prospective pilot study at a single institution within the Vascular Study Group of New England was conducted from January 2009 to December 2010. Patients with diabetes and without undergoing LEB were placed on an intravenous (IV) insulin infusion for 3 days after surgery with titration of blood glucose from 80 to 150 mg/dL. The IV insulin study group (n = 104) was compared to a historic control group (n = 189) that received standard insulin treatment from the preceding 3 years. The Fisher exact test, t-tests, Wilcoxon rank-sum tests, χ(2), and logistic regression analyses were used to compare in-hospital morbidity. Stratified analyses were conducted to determine if findings differed based on the presence or absence of diabetes. There was no difference in postoperative complications between the two groups with regard to graft infection, myocardial infarction, dysrhythmia, primary patency at discharge, or mortality. Patients in the IV insulin group had significantly fewer in-hospital wound infections (4% vs 11%; odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.96; P = .047). This association strengthened after adjusting for potentially confounding baseline differences in gender, body mass index, and smoking status (adjusted OR, 0.22; 95% CI, 0.05-0.84; P = .03). When stratified by presence of diabetes, wound infections were decreased in the IV insulin group (0/44 [0%] vs 9/90 [10%]; P = .03). In patients without diabetes treated with IV insulin, there was no significant difference in wound infections (7% vs 12%; P = .42). Strict glucose control with a postoperative insulin infusion protocol significantly decreased the incidence of postoperative in-hospital wound infection in the diabetic population. These previously unreported findings from this single-institution prospective study warrant further investigation.

Elevated Preoperative Glucose Levels and Survival in Elderly Newly Diagnosed Glioblastoma Patients (P07.111)

Objective: This retrospective study was undertaken to assess the relationship between preoperative glucose level and survival in elderly patients with newly diagnosed glioblastoma (GBM). Background Hyperglycemia has been associated with poor outcomes in many disease states. Furthermore, hyperglycemia augments in vitro astrocytoma cell growth. Design/Methods: We retrospectively reviewed 315 GBM patients, treated between July, 1998 and June, 2010. 18% (58/315) of the patients with known diabetes were excluded. The analysis was performed based on a recursive partitioning. Results: 242 GBM patients with a median age of 74 (range 65-91) were included in the final analysis. Among patients with performance status data (88%, 214/242) 23% had a KPS of 90-100 preoperatively, in 44% KPS was 70-80, and 34% had KPS scores 70, age 70, age 90 mg/dL), group three (KPS>70, age>75, any glucose level), and group four (KPS Conclusions: In our study, higher preoperative glucose level was associated with decreased overall survival in elderly patients diagnosed with GBM. Strict glucose control may contribute to improved outcome in treatment of these patients. Disclosure: Dr. Stevens has received personal compensation for activities with UCB Pharma. Dr. Ahluwalia has received personal compensation for activities with Elekta, Monteris Medical, and Merl.

Understanding the causes of hyperglycemia in burn patients

DOI of original article: 10.1016/j.jss.2012.0 * Corresponding author. Department of Surge Center, 10 Union Square East, Suite 2M, New E-mail address: mleitman@chpnet.org (I. 0022-4804/$ e see front matter a 2013 Elsev doi:10.1016/j.jss.2012.03.042 Hyperglycemia is commonly encountered in the critically ill patient. Although this is believed to be an adaptive stress response, hyperglycemia is in fact correlated with adverse outcomes [1]. Accordingly, critically ill patients are believed to benefit from enhanced glucose control. Several randomized controlled trials (RCTs) of strict glucose control with insulin therapy have been performed, most notably the 2001 landmark study by Van den Berghe et al., which found that intensive insulin therapy to maintain glucose at 80e110 mg/dL significantly reduced morbidity and mortality in intensive care unit (ICU) patients [2]. However, subsequent RCTs have reported conflicting results [1]. A metaanalysis of RCTs concluded that only surgical ICU patients, not medical ICU patients, enjoyed the benefit of strict glycemic control [3]. The large multicenter NICESUGAR trial demonstrated that an intermediate glucose target (140e180 mg/dL) was ideal, and resulted in lower mortality than stricter control (80e110 mg/dL) [4]. At the present time, due to conflicting data, the optimal target glucose level remains unclear. These data have been extrapolated to burn patients, despite the fact that burn patients were underrepresented in the RCTs of glycemic control in the ICU. Hyperglycemia was

A Lemierre syndrome variant caused by Klebsiella pneumoniae

Lemierre syndrome is an extremely rare disease characterized by oropharyngeal infection, septicemia, internal jugular vein thrombosis, and skip lesions. The most common causative pathogen is Fusobacterium necrophorum. We reported a 45-year-old woman who presented with left neck painful swelling and septicemia. Magnetic resonance imaging of the head and neck demonstrated venous thrombosis extending from the left internal jugular vein to the sigmoid sinus. During admission we discovered that the patient had uncontrolled diabetes mellitus. We also found a metastatic lesion through chest radiography. Klebsiella pneumoniae was cultivated from both blood samples and pus from deep neck spaces. Surgical drainage, early and adequate antibiotic treatment, anticoagulation, and strict control of blood glucose led to the patient's complete recovery. Because Lemierre syndrome is a forgotten disease in the era of antibiotics, awareness of the signs and symptoms of this disease is important because of its associated high mortality rate. This case illustrated that the presence of K pneumoniae can lead to Lemierre syndrome.

Strict glycaemic control improves skin microcirculation in patients with type 2 diabetes: A report from the Diabetes mellitus And Diastolic Dysfunction (DADD) study

Microcirculatory and endothelial dysfunction are signs of cardiovascular engagement in patients with type 2 diabetes. This study tested whether glucose normalisation may reverse this. Thirty-nine T2DM patients (age 61±7 years, 58% females) with signs of mild diastolic dysfunction were randomised to strict glucose control based on insulin (I-group; n=21) or oral agents (O-group; n=18) for four months. Skin microcirculation was studied with laser Doppler fluxmetry and endothelial function with brachial artery flow-mediated dilatation. Glucose control improved (reduction of HbA(1c) I-group = -0.5%; O-group -0.7%; p=0.69). Microcirculation improved in the entire group (n=39) determined by foot laser Doppler fluxmetry (32.2±13.6 vs. 35.3±13.1 perfusion units; p<0.001) and laser Doppler fluxmetry following heating (68.8±34.0 vs. 69.3±25.1 PU; p=0.007). Improvement was more consistent with oral agents than insulin. Endothelial function expressed as flow-mediated dilatation decreased in the I-group (6.0±2.2 to 4.7±3.0%; p=0.037) but remained unchanged in the O-group (4.8±2.3 to 5.0±3.7%; n.s.). Glycaemic normalisation improved skin microcirculation but not endothelial function in patients with type 2 diabetes with mild cardiovascular engagement.

Pay more attention to the balance between “treat to target” and risk of hypoglycemia——Comment on the strategy of glycemic control in diabetic patients with cardiovascular disease

Diabetes results in excess cardiovascular mortality.Unexpectedly,more strict glucose control induced more death in a large scale clinical trial and the increased hypoglycemia was a suspected offender.In order to decrease the risk of hypoglycemia,three steps should be taken into consideration in future treatment of hyperglycemia in diabetic patients with cardiovascular disease: ( 1 ) Identifying hypoglycemia early even in its paradoxical feature.( 2 )Achieving glucose targets with personality.( 3 ) Designing the strategy of lowering plasma glucose more carefully,to pay special attention avoiding hypoglycemia. Key words: Diabetes mellitus; Cardiovascular disease; Hyperglycemia; Hypoglycemia