Aggressive Glucose Control Research Articles

INCREASED MORTALITY ASSOCIATED WITH TREATMENT OF TYPE 2 DIABETES AMONG COVID-19 PATIENTS A SINGLE CENTER STUDY

Purpose: COVID-19 caused by SARS-COV-2 infection can lead to multi-organ injuries and significant mortality in severe and critical patients, especially among those individuals with type 2 diabetes (T2D) as a comorbidity. While attenuated mortality was observed with aggressive glucose control, it was unclear whether therapeutic regimens including insulin treatment were beneficial for patients with COVID-19 and T2D. This retrospective study investigated 320 patients with COVID-19 and T2D from a cohort of 2950 cases from Wuhan, China. Unexpectedly, we found that insulin treatment for patients with COVID-19 and T2D was associated with a significant increase in mortality (23.2% versus 2.5%; adjusted HR, 5.38 [2.75–10.54]). Further analysis showed that insulin treatment was associated with enhanced systemic inflammation and aggravated injuries of vital organs. Therefore, insulin treatment for patients with COVID-19 and T2D should be used with caution. Methodology: We performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (Google scholar, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95% CI data were used to assess relationships between antidiabetic agents and mortality.

Insulin Treatment Is Associated with Increased Mortality in Patients with COVID-19 and Type 2 Diabetes

COVID-19 caused by SARS-COV-2 infection can lead to multi-organ injuries and significant mortality in severe and critical patients, especially among those individuals with type 2 diabetes (T2D) as a comorbidity. While attenuated mortality was observed with aggressive glucose control, it was unclear whether therapeutic regimens including insulin treatment were beneficial for patients with COVID-19 and T2D. This retrospective study investigated 689 patients with COVID-19 and T2D from a cohort of 3,305 cases from Wuhan, China. Unexpectedly, we found that insulin treatment for patients with COVID-19 and T2D was associated with a significant increase in mortality (27.2% versus 3.5%; adjusted HR, 5.38 [2.75–10.54]). Further analysis showed that insulin treatment was associated with enhanced systemic inflammation and aggravated injuries of vital organs. Therefore, insulin treatment for patients with COVID-19 and T2D should be used with caution.

Review of the veteran affairs diabetes trial: Lessons learned.

Despite robust evidence linking long-term hyperglycemia with cardiovascular complications, several large randomized trials found only modest benefits from intensive compared to standard glucose control. Of these trials, the Veteran Affairs Diabetes Trial (VADT), offers a unique long-term perspective in that there were analyses of outcomes at the end of the intervention trial, 5-years post-trial, and after 10-years post-trial. From the VADT and other large trials, we draw several valuable lessons that are relevant to the care of patients with type 2 diabetes. Intensive glucose control reduces development of nephropathy and retinopathy but not neuropathy, though evaluations of neuropathy are less consistent and conclusions regarding outcomes less reliable. While the VADT did not demonstrate reduction in cardiovascular outcomes at completion of the glucose lowering intervention, it did demonstrate a 17% reduction 5-years post-trial, which waned by 10-years post-trial observation. Of interest, the 5-year post trial period included 3 additional years of HbA1c separation between treatment groups which suggests that longer-term glucose control may be needed before benefits are seen. Other factors including hypoglycemia and increased glucose variation are also associated with cardiovascular events and are more prevalent during intensive glucose control, potentially lessening the benefit of lowering average glucose levels. Finally, intensive glucose control requires substantial effort from both the patient and clinician perspective. All of these factors must be kept in mind when considering the benefits of aggressive glucose control for each patient.

SUN-342 Effect of Hyperglycemia on Bone Mineral Density and Fracture in Pre-Liver Transplant Recipients

The liver plays an important role in bone and mineral metabolism of patients with end-stage liver disease. These patients are known to have an increased risk of osteoporosis and fractures before liver transplant (LT) with reported fracture incidence of 10-56%. The cause is multifactorial, which includes their underlying liver disease, chronic illness, vitamin D deficiency, and hyponatremia. The impact of hyperglycemia and diabetes mellitus on bone health in liver transplant recipients is not known. Hypothesis: Hyperglycemia increases risk of fracture and osteoporosis in pre- LT patients undergoing LT. Methods: To answer this question, we did a retrospective chart review of consecutive first time, single organ LT recipients at our institution from 2011-2014, who had BMD performed prior to transplantation. We identified 393 patients but included only 209 patients who carried a diagnosis of hyperglycemia or diabetes (type 2 DM, type 1 DM, steroid induced DM and hyperglycemia). BMD was defined based on WHO criteria as Normal, osteopenia and osteoporosis. Hemoglobin A1C was divided into 4 quartiles (A1C ≤5.6%, 5.7-6.4%, 6.5-7.9%, and ≥8%); fasting blood glucose was defined as any venous glucose checked before 9am and labeled as a fasting lab in the chart. Fasting blood glucose was divided into those with BG<100, 101-125, 126-200, >200 mg/dL. We chose labs closest to the transplant date. Pre LT fracture was compared with hemoglobin A1C and BMD as well as fasting glucose. STATA statistical program was used to calculate Fisher T-test. Results: Baseline characteristics of our cohort were as follows. Median BMI was 27.9 (16.2, 45.6). Majority had hepatitis C (33%), NASH 12%, and alcoholic liver disease 23%. Average MELD score was 15 (6-40). Average wait time to transplant was 90 days. 29% of patients had normal BMD, 46% osteopenia and 25% osteoporosis. From the total 209 patients reviewed, 17 had a fracture prior to transplant of which 14/17 had vertebral fractures. The only variable that correlated with risk of fracture was hemoglobin A1C. Higher level of Hemoglobin A1C correlated with the presence of fracture p= 0.04. BMD did not correlate with fracture p= 0.28. There was no association between BMD and Fasting glucose level p=0.55. There was no correlation between fasting glucose and risk of fracture p=0.44. Discussion: This study suggests that a correlation between the presence of pre LT fracture and HgA1C exists. Other factors such as BMD and fasting BG did not correlate with fracture. Those with higher hemoglobin A1C prior to liver transplant might be at risk for fracture compared to those without diabetes or hyperglycemia (A1C <5.7). Benefit of diabetes control for bone health in this population is not known, however we speculate that those with lower A1C, thus better glucose control, have a lower risk of fracture thus aggressive glucose control should be part of the pre transplant care.

Intensive vs. standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: The SHINE randomized clinical trial

Emergency Medicine Physicians are often the first to evaluate and treat patients with acute ischemic strokes. Clinical outcomes decline when there is associated hyperglycemia and thus hyperglycemic control is crucial. There are few studies however, that demonstrate a favorable association between aggressive blood glucose control and clinical outcome compared to standard glucose control.

MON-LB045 Inaccurate Hemoglobin A1c in a Transman Patient with Diabetes: Implications for Treatment and Surveillance

Background: HbA1c is the standard biomarker to monitor glycemic control and to prevent diabetes complications. Conditions (hemolysis, reticulocytosis), or drugs (erythropoietin, dapsone), known to affect the lifespan of red blood cells have an impact on HbA1c’s accuracy. Testosterone therapy (TT) is the mainstay of treatment in transmen. Testosterone regulates erythropoiesis, increasing hemoglobin and hematocrit in a dose dependent manner. There is currently no data on the effect of TT on HbA1c accuracy in transmen with diabetes. Methods: we present a 52 year-old well virilized transman evaluated for polycythemia in the setting of 10 years of TT; “well controlled” type 2 diabetes, on diet alone for 11 years; diabetic neuropathy, hypertension, CKD stage 3, and rheumatoid arthritis. Medications included weekly testosterone cypionate, lisinopril, gabapentin, and etanercept. Creatinine was 1.6mg/dL, GFR 55mL/min, +microalbuminuria. Hb was 18.7g/dL, Hematocrit 56%, RBCs 6.30/uL, HbA1c 6.2%-6.4% in the last 2 years. Data from SMBG indicated 58.4% of readings to be above the fasting target of 70-130mg/dL, and postprandial target of 70-180mg/dL. Given the discrepancies of capillary glucose and HbA1c, and the presence of complications, the patient was evaluated with a 5-day professional CGM, and alternative glycemic markers. CGM average glucose was 163mg/dL, equivalent to HbA1c of 7.3%. Fructosamine was 316umol/L (ref: 200-285umol/L), equivalent HbA1c 7.5%; 1, 5-anhydroglucytol was 8.9 (ref: 10.7-32.0ug/mL) indicating postprandial hyperglycemia. Discussion: We hypothesize that the patient had unrecognized long-term suboptimal diabetes control, secondary to inaccurate HbA1c in the context of TT. Diabetes is a major risk factor for CV disease. In cisgender men the data on TT and the risk of major CV events is controversial and long-term effects from TT on CV health are unknown. TT in transmen is associated with an increase in triglycerides, systolic blood pressure and a decrease in HDL cholesterol. These risk factors in combination, in a diabetes background may augment the risk of CV disease in transmen, as such early and aggressive glucose control and management of risk factors is of critical importance. Clinicians need to be aware of HbA1c’s limitations in this population with diabetes, to prevent delays in diagnosis and timely intensification of treatment. Better tools for screening and monitoring diabetes in transmen are needed. Conclusion: This is the first case showing the inaccuracy of HbA1c in a transman patient with diabetes, raising awareness of the need for alternative methods of diabetes screening and monitoring, in this growing and potentially high-risk for CV disease population. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Glucose control in the ICU.

Critically ill patients usually develop hyperglycemia, which is associated with adverse outcome. Controversy exists whether the relationship is causal or not. This review summarizes recent evidence regarding glucose control in the ICU. Despite promising effects of tight glucose control in pioneer randomized controlled trials, the benefit has not been confirmed in subsequent multicenter studies and one trial found potential harm. This discrepancy could be explained by methodological differences between the trials rather than by a different case mix. Strategies to improve the efficacy and safety of tight glucose control have been developed, including the use of computerized treatment algorithms. The ideal blood glucose target remains unclear and may depend on the context. As compared with tolerating severe hyperglycemia, tight glucose control is well tolerated and effective in patients receiving early parenteral nutrition when provided with a protocol that includes frequent, accurate glucose measurements and avoids large glucose fluctuations. All patient subgroups potentially benefit, with the possible exception of patients with poorly controlled diabetes, who may need less aggressive glucose control. It remains unclear whether tight glucose control is beneficial or not in the absence of early parenteral nutrition.

Comparison of Hemichorea-Hemiballism between Acute Stroke and Nonketotic-Hyperglycinemia in the Clinical Scenario: Report of a Rare Diabetic Complication

Diabetes mellitus is the major cause of retinopathy, nephropathy and neuropathy. Hyperglycemia is one of major major advised effect on diabetes mellitus. Hemichorea-hemiballism, a rare manifestation of nonketotic hyperglycemia, characterized by involuntary arrhythmic motions in one side of the body which results from focal lesions in the contralateral basal ganglia. Here, we present a 39-year-old woman with violent involuntary rapid and irregular movements of left limbs three days prior to emergency department. Nonketotic hyperglycemia related hemichorea-hemiballism had been confirmed by biochemistry examination and brain computed tomography (CT). Aggressive glucose control with insulin was administered. Her symptoms got improvement gradually after euglycemia two weeks later.

Results of a multicenter prospective pivotal trial of the first inline continuous glucose monitor in critically ill patients.

We have previously demonstrated that tight glycemic control (80-120 mg/dL) improves outcome in critically injured patients. However, many centers have gotten away from aggressive glucose control due to the workload and risk of hypoglycemia. The objective of this pivotal trial is to evaluate the first in human continuous inline glucose monitor (OptiScanner) in critically ill patients. A multicenter pivotal trial was conducted over a 1-year period (2014-2015) at four major academic centers in 200 critically ill patients. Three thousand seven hundred thirty-five glucose measurements were obtained and measured. A paired blood sample was then collected to coincide with the OptiScan measurement. The OptiScanner withdraws 0.13 mL of blood every 15 minutes from a central venous line, centrifuges the sample, and uses midinfrared spectroscopy to directly measure glucose levels in blood plasma. We plotted a Clarke Error Grid, calculated mean absolute relative difference (MARD) to analyze trend accuracy, and population coefficient of variation (PCV) to measure deviations. OptiScanner and Yellow Springs Instrument values were "blinded" from clinicians. Treatment was guided by the standard point of care meters. 95.4% of the data points were in zone A of the Clarke Error Grid and 4.5% in zone B. The MARD was 7.6%, the PCV 9.6%. The majority of data points achieved the benchmark for accuracy. The MARD was below 10%, which is the first inline continuous glucose monitor to achieve this result in a clinical trial. The PCV was less than 10%. We confirmed that the OptiScanner outperformed every 1- to 3-hour glucose measurements using point of care meters which prevents glucose excursions and variability and achieves a higher amount of time the patient's glucose values remain in range. This pivotal multicenter trial demonstrates that the first inline CGM monitor is safe and accurate for use in critically ill surgical and trauma patients. Diagnostic study, level I.

One size does not fit all glycemic targets for type 2 diabetes.

The United Kingdom Prospective Diabetes Study, and Diabetes Control and Complications Trial have shown that aggressive glucose control, especially early in the natural history of the disease, might result in a significant reduction of microvascular as well as macrovascular complications. However, more recent trials have increased the level of complexity of the relationship between 'tight glucose control/chronic complications', with several factors influencing the risk-to-benefit ratio to be considered, such as age, presence of established complications and diabetes duration. According to this strategy, a more intensive goal is desirable for young patients with no cardiovascular disease, whereas less stringent control is suitable for all people who are relatively late in the natural history of diabetic complications. Numerous calls for an individualized therapy have been proposed during the past years, but still debated is the level of glucose lowering necessary to reduce complications balanced by the risk and costs of the means used. The present paper briefly reviews the rationale and the clinical trials that support specific glycemic goals towards a 'tailored' approach for the management of hyperglycemia in diabetes.

Abstract 18710: Improvements in Glycemic Control in Type 2 Diabetes Do Not Lead to Reductions in Circulating Cardiac Troponin

Objective: Concentrations of cardiac troponin T, when measured with a high-sensitivity assay (hsTnT), have emerged as a strong marker of cardiovascular mortality, and are frequently elevated in patients with type 2 diabetes. Whether glycemic control affects concentrations of this marker is unknown. Methods and Results: We measured hsTnT in patients from the LANCET trial, a 14 week, 2x2 factorial, randomized, placebo-controlled trial of insulin glargine and metformin in early type 2 diabetes. Baseline and 14-week follow up samples were available from 438 participants. At baseline, 408 out of 438 (93.2%) had detectable circulating hsTnT, while 59 (13.5%) had hsTnT levels above the established upper reference limit (≥ 14 ng/L). At baseline, the median (IQR) HbA1c was 6.9% (6.3-7.7%) with no significant differences by treatment group. Statistically significant associations with baseline natural logarithm transformed hsTnT were noted for age (ρ=0.09, P&lt;0.05), but not fasting glucose, HbA1c, body mass index, interleukin-6, or high-sensitivity C-reactive protein (each P&gt;0.26). After 14 weeks of randomly allocated therapy, we observed a significant reduction in HbA1c in all treatment groups except placebo (Figure). In models adjusted for baseline hsTnT and baseline antihyperglycemic therapy we observed no over all change in hsTnT by random treatment allocation (P=0.92) and no individual treatment group differences relative to placebo (Figure; each P≥0.37). Conclusions: These data suggest that aggressive glucose control with insulin glargine, metformin, or the combination does not alter concentrations of circulating cardiac troponin T. Our findings are concordant with the results of large randomized controlled trials showing that glycemic control alone may not suffice to substantively lower cardiovascular risk. (Clinicaltrials.gov Identifier: NCT00366301 )

Dose- and time-dependent effect of high glucose concentration on viability of notochordal cells and expression of matrix degrading and fibrotic enzymes

Diabetes mellitus is an important aetiological factor in intervertebral disc degeneration. The disappearance of notochordal cells in the nucleus pulposus is thought to be the starting point for intervertebral disc degeneration. A cellular effect of diabetes mellitus on apoptosis of notochordal cells and intervertebral disc degeneration has been recently reported. However, how the duration and severity of diabetes mellitus affects viability of notochordal cells and intervertebral disc degeneration is still unknown . Rat notochordal cells were isolated, cultured, and placed in either 10 % foetal bovine serum (FBS) (normal control) or 10 % FBS plus three different high glucose concentrations (0.1 M, 0.2 M, and 0.4 M) (experimental conditions) for one, three, five and seven days, respectively. We identified and quantified the degree of proliferation and apoptosis, caspase activities, and cleavages of Bid and cytochrome-c. In addition, we examined the cells for expression of matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs). Each three high glucose concentrations significantly decreased proliferation and increased apoptosis of notochordal cells from culture days one to seven in a dose-dependent manner. Compared with those of 10 % FBS, caspase-9 and -3 activities and cleavage of Bid and cytochrome-c were significantly increased in each three high glucose concentrations, accompanied by increased expression of MMP-1, -2, -3, -7, -9, and -13 and TIMP-1 and -2. High glucose concentration significantly decreased proliferation and increased apoptosis of notochordal cells via the intrinsic pathway with dose- and time-dependent effects. We also found that expression of MMPs and TIMPs was increased with dose- and time-dependent effects. Therefore, these results suggest that aggressive glucose control from an early stage of diabetes mellitus should be recommended to prevent or limit intervertebral disc degeneration.

Preventing diabetes complications: are we too glucocentric?

The prevention of macrovascular complications is a major goal of diabetes management. Control of hypertension and hyperlipidemia is a well supported means for preventing macrovascular events in people with and without diabetes. Data from large trials have questioned the macrovascular benefits of aggressive glucose control. Nevertheless, diabetes management has become increasingly focused on achieving tight glycemic control. New research highlights the growing concern that this 'glucocentric' approach may be coming at the eaqaense of controlling other cardiovascular risk factors such as hypertension and hyperlipidemia. Clinicians may need to reprioritise their efforts in diabetes management to better reflect the current evidence base.

Aggressive glucose control in acute stroke is the answer in the imaging?

Annals of NeurologyVolume 67, Issue 5 p. 557-558 Editorial Aggressive glucose control in acute stroke is the answer in the imaging? Karen C. Johnston MD, MSc, Karen C. Johnston MD, MSc University of Virginia, Department of Neurology and Public Health Sciences, University of Virginia, Charlottesville, VASearch for more papers by this authorMark Parsons PhD, Mark Parsons PhD Department of Neurology, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, Newcastle, AustraliaSearch for more papers by this author Karen C. Johnston MD, MSc, Karen C. Johnston MD, MSc University of Virginia, Department of Neurology and Public Health Sciences, University of Virginia, Charlottesville, VASearch for more papers by this authorMark Parsons PhD, Mark Parsons PhD Department of Neurology, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, Newcastle, AustraliaSearch for more papers by this author First published: 26 April 2010 https://doi.org/10.1002/ana.22046Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume67, Issue5May 2010Pages 557-558 RelatedInformation

DIABETES CONTROL – THE LEGACY OF A MEMORY

Achieving and maintaining good glycaemic control remains an important goal in the management of this common and prevalent disorder. Recent evidence from important megatrials, ACCORD, ADVANCE, VADT, UKPDS-10 year follow-up as well as the STENO-2 follow-up study, have cleared doubts concerning the benefits of targeting good glycaemic control. For the first time, we have the reassurance that macrovascular benefits can be realised from good glycaemic control. The legacy effect of prior good glucose control from the UKPDS-10 year follow-up, reinforces the results seen from the DCCT-EDIC (for Type 1 diabetes). The Intervention Phase of the UKPDS revealed benefits for reduction of microvascular complications, while it was only at the end of the Post-Trial Monitoring Phase where significant improvements in both micro and macrovascular outcomes were seen.(JUMMEC 2009; 12(2): 47-56)The other three Trials assessing the effect of glycaemic control on cardiovascular outcomes, although largely negative for CV benefit, give valuable insight towards appropriate patient characteristics for which aggressive glucose control can and should be instituted. Individualisingglycaemic targets, which has been the approach that many clinicians have been practising, has received new impetus albeit with clearer details.&nbsp;Getting to glycaemic goal early in the course of T2DM and Doing to Safely (Avoiding hypoglycaemia) are the key ingredients to successful management. The legacy of the memory of initial goodmetabolic/glycaemic control is investment in good health with benefits of reductions in both micro and more importantly, macrovascular disease, years later.&nbsp;Multifactorial interventions that include blood pressure, lipid lowering in addition to glucose control in these individuals with the Metabolic Syndrome result in more immediate beneficial additive effects on cardiovascular outcomes.

Glucose Control in the Intensive Care Unit: A Roller Coaster Ride or a Swinging Pendulum?

Many studies of tight control of blood glucose in critically ill patients are associated with poor outcomes. However, randomized studies of tight glucose control in patients admitted to coronary care or surgical intensive care units showed a reduction in mortality rates; supported by recommendations from professional organizations, many intensive care units implemented protocols for tight glucose control. More recent studies in medical intensive care units did not confirm the benefits of tight control, however, and the most recent study suggests that tight control increases mortality rates. Furthermore, tight control significantly increases episodes of hypoglycemia. The sum of the recent literature suggests that a degree of glucose control lies between the extremes of the adverse outcomes related to poor glucose control and those related to overly aggressive glucose control.

Aggressive Glucose Control for Acute Ischemic Stroke Patients by Insulin Infusion

Background and PurposeHyperglycemia after acute ischemic stroke (AIS) is associated with poor outcomes. However, there is no consensus as to the optimal method for glycemic control. We designed an insulin infusion protocol for aggressive glucose control and investigated its efficacy and safety.MethodsWe applied our protocol to patients within 48 hours after AIS or transient ischemic attack (TIA) with an initial capillary glucose level of between 100 and 399 mg/dL (5.6-22.2 mmol/L). An insulin solution comprising 40 or 50 U of human regular insulin in 500 mL of 5% dextrose was administered for 24 hours. Capillary glucose was measured every 2 hours and the infusion rate was adjusted according to a nomogram with a target range of 80-129 mg/dL (4.4-7.2 mmol/L). Changes in glucose and overall glucose levels during insulin infusion were analyzed according to the presence of diabetes or admission hyperglycemia (admission glucose >139 mg/dL or 7.7 mmol/L) by the generalized estimating equation method.ResultsThe study cohort comprised 115 consecutive patients. Glucose was significantly lowered from 160±57 mg/dL (8.9±3.2 mmol/L) at admission to 93±28 mg/dL (5.2±1.6 mmol/L) during insulin infusion (p<0.05). Laboratory hypoglycemia (capillary glucose <80 mg/dL or 4.4 mmol/L) occurred in 91 (71%) patients, 11 (10%) of whom had symptomatic hypoglycemia. Although glucose levels were significantly lowered and maintained within the target range in all patients, overall glucose levels were significantly higher in patients with diabetes or hyperglycemia (p<0.05).ConclusionsOur insulin-infusion protocol was effective in glycemic control for patients with AIS or TIA. Further modification is needed to improve the efficacy and safety of this procedure, and tailored intervention should be considered according to glycemic status.

Effect of hyperglycemia on progressive paraparesis in a rat metastatic spinal tumor model

Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC. Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1-21). Animals were killed at time of paralysis (BBB Score < 7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours. Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 microg/dl), 6 (219 vs 102 microg/dl), 8 (169 vs 102 microg/dl), and 10 hours (118 vs 99 microg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 microg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 +/- 0.38 cm(3) vs 4 +/- 0.41 cm(3), p < 0.001) at time of paralysis. In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.

LDL Cholesterol Lowering in Type 2 Diabetes: What Is the Optimum Approach?

IN BRIEFManaging the high risk for cardiovascular morbidity and mortality in diabetic patients is a challenge for practicing clinicians. Reducing the burden of cardiovascular disease in diabetes should begin with assessment and treatment of elevated LDL cholesterol. Statins are the preferred treatment,and intensive statin therapy may be necessary to meet the current goal of &amp;lt;100 mg/dl or the optional goal of &amp;lt; 70 mg/dl recommended for high-risk patients and to address other components of diabetic dyslipidemia. Along with aggressive glucose and blood pressure control, intensive treatment of LDL cholesterol in patients with diabetes can substantially affect long-term health outcomes.

Diabetes mellitus, insulin resistance, hyperglycemia, and stroke

It is well established that diabetes is associated with an increased risk of stroke. Once a stroke has occurred, patients with diabetes experience poorer outcomes (functional status, mortality). Convincing data now support aggressive glucose control and comprehensive cardiovascular risk factor management to prevent stroke in patients with diabetes. However, there remains a distinct paucity of information concerning secondary stroke prevention. Hyperglycemia in the acute stroke setting is a marker for poor outcomes, but it remains unclear whether intensive in-hospital lowering of blood glucose levels improves clinical outcomes. Targeting insulin resistance as a modifiable risk factor for stroke is a novel strategy currently under investigation.