Patients Receiving Insulin Therapy Research Articles

Pump insulin therapy for diabetes mellitus

Insulin therapy is a pharmaceutical treatment used for patients with diabetes to normalize blood glucose level. In patients receiving insulin therapy, optimization of blood glucose levels can be achieved using various types of insulin and various methods, such as MDI (multiple daily injections) and CSII (continuous subcutaneous insulin infusion). This review describes actual key features of CSII for diabetes patients.

Practice and perception—A nationwide survey of therapy habits in sepsis*

To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock. One-day cross-sectional survey. Representative sample of German intensive care units stratified by hospital size. Adult patients with severe sepsis or septic shock. None. Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses "always" and "frequently" were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilation < or = 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3% > 8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived adherence to low-tidal volume ventilation was 79.9%. Euglycemia (4.4-6.1 mmol/L) was documented in 6.2% of 355 patients. A total of 33.8% of patients had blood glucose levels < or = 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose > 8.3 mmol/L). Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levels < or = 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation. This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

Immunogenicity of Human and Bovine Insulin in Type 1 Diabetes Mellitus Patients

The advantages of synthetic insulin (human insulin) over bovine insulin in the treatment of type 1 diabetes mellitus (DM) are much debated in terms of potency and purity. Immunogenicity is one of several factors that determine potency and safety. This study was designed to investigate and study the difference in immunogenicity of human and bovine insulin. We investigated anti-insulin antibody (AIAB) status in 69 type 1 DM patients receiving insulin therapy. Group 1 had 33 patients treated with bovine insulin, and group 2 had 32 patients treated with human insulin. All patients had received their respective insulin therapy for a minimum period of 1 year and had no history of change in insulin type. Forty-three subjects from the normal population were the control group. AIABs were assayed in serum samples of all subjects using a semiquantitative radioimmunoassay kit. The Kruskal-Wallis non-parametric and Mann-Whitney U tests were used to study the difference in immunogenicity of human and bovine insulins. The Kruskal-Wallis test showed that antibody titers in the three groups significantly differed (P<0.001). The Mann-Whitney U test showed no significant difference in AIAB titer between the treatment groups. AIAB titers in the two treatment groups differed significantly from that of the control group, independently (P<0.001). High titers of AIABs are present in patients receiving bovine and human insulin compared to that of the normal population. Bovine and human insulins are antigenic, and there is no significant difference in AIAB titer. Prospective studies are required to determine the long-term clinical significance of these antibodies.

Effects of Glucagon on Islet β Cell Function in Patients With Diabetes Mellitus

To evaluate islet beta cell response to intravenous glucagon (a non-glucose secretagogue) stimulation in diabetes mellitus. Nineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intravenous injection of 1 mg of glucagon. Both fasting and 6-minute post-glucagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0.76 +/- 0.36 ng/mL vs. 1.81 +/- 0.78 ng/mL, P < 0.05; 0.88 +/- 0.42 ng/mL vs. 3.68 +/- 0.98 ng/mL, P < 0.05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45 +/- 0.93 ng/mL vs. 1.61 +/- 0.68 ng/mL, P < 0.05; 5.26 +/- 1.24 ng/mL vs. 2.15 +/- 0.76 ng/mL, P < 0.05). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups (r = 0.76, P < 0.05). The 6-minute glucagon test is valuable in assessing the function of islet beta cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

Effect of the 2004 Mid Niigata Prefecture earthquake on glycemic control in type 1 diabetic patients

At 5:56 p.m. on October 23, 2004, a major earthquake of magnitude 6.8 on the Richter scale struck the Chuetsu district of Niigata Prefecture, Japan, a rural area with mountain villages. Strong aftershocks of grade 5–6 on the Japanese Intensity Scale continued for 2 months. We investigated changes in the HbA1c levels of 65 type 1 diabetic patients with insulin therapy before and throughout the 12 months of aftershocks that followed the earthquake. All patients received insulin therapy via pens with replaceable cartridges or continuous subcutaneous insulin infusion (CSII). Most patients needed four daily insulin injections with rapid- and long-acting insulins. Nineteen percent of patients had the CSII therapy using rapid-acting insulin. The mean HbA1c level in all patients increased significantly ( P < 0.01) from 6.7 ± 0.9% to 7.0 ± 1.0% in the third month, peaked at the fifth month, and decreased at 12 months. Sixty percent of the patients stayed in their own houses after the initial shock, while 40% of patients moved into other houses. Seventeen percent of the patients had severely destroyed houses. The median PTSD score was low in all patients. Within 1 month after the earthquake, the pens with replaceable cartridges were discontinued and disposable pens with prefilled insulin cartridges were used. The incidence of nephropathy increased by 7% by the third month and returned to the pre-earthquake level by the sixth month. Over the 12-month observation period, no other micro- or macro-vascular diseases were newly diagnosed. One patient had transient severe acute hyperglycemia and one needed hemodialysis. However, none of the patients had ketoacidosis, and no other clinical manifestations of disease were noted. In conclusion, it is essential that neighboring organizations respond quickly with sufficient medical support for diabetic patients with insulin therapy following an earthquake. In particular, treatment with rapid- and long-acting insulin injections via disposable pens with prefilled insulin cartridges or CSII therapy is useful during a disaster. To take the medical support, patients should always have a note or copy of their medical records, including medical history and medications used.

The Effects of Combined Insulin and Metformin Therapy in Obese Patients with Diabetes Mellits Type 2 in the Early Stage of the Disease

Combination of insulin and metformin has been shown to improve glycaemic control in clinical trials, particularly in obese patients with diabetes type 2. Insulin therapy can improve function of pancreatic beta cells and periphery insulin activity in target cells in order to enhance glycaemic homeostasis (1, 2, 3). In our study we included obese patients with diabetes type 2 in the early stage of the disease. The study is partially retrospective and partially prospective. The study encompassed 40 patients split in two groups. The first group of 20 patients received insulin therapy combined with metformin, while the patients of the second group were treated with oral antidiabetic drugs, sulfonylureas and metformin. Three months later, the group treated with insulin and metformin showed improvement in the monitored parameters, namely significant reduction in HbA1c (p = 0.003), MFBG (p = 0.0009), PPG (p = 0.028). Insulin therapy administered together with metformin, in obese patients with diabetes type 2, in the early stage of the disease, resulted in well regulated fasting blood glycaemia, as well as post challenge glycaemia and HbA1c.

Glycemic Relapse in Type 2 Diabetes

To characterize the occurrence of glycemic relapse after initial improvement in blood glucose levels and to describe predictors of relapse in patients with type 2 diabetes. Occurrence of glycemic relapse was analyzed in 393 consecutive patients with type 2 diabetes after participation in a 3-month intensive outpatient intervention. All patients had hemoglobin A1c (A1C) values (3)7% before the intervention and had achieved adequate glycemic control (nadir A1C<7%) afterward. The median follow-up time was 26.5 months. Relapse was defined as a subsequent increase in A1C to (3)7%. The probability of glycemic relapse was 45% at 1 year after the intervention and was 76% at 3 years. The median time to relapse was 15.2 months. Cox multivariate regression analysis indicated that treatment with insulin was associated with a greater risk of relapse-- hazard ratio=1.5 (95% confidence interval, 1.1 to 2.2), after controlling for the patient's age, sex, race, body mass index, duration of diabetes, weight change during the intervention, and nadir A1C value. Among those patients not treated with insulin at the end of the intervention, a shorter duration of diabetes and weight loss during the intervention period were significantly associated with decreased risk of relapse. The majority of study patients with type 2 diabetes who attained satisfactory glycemic control after intensive outpatient intervention had a relapse after the end of the intervention period. Patients receiving insulin therapy were at particular risk of glycemic relapse. Therefore, such patients should receive high priority for continuation of intensive care or for other relapse prevention measures.

Efficacy of glimepiride on insulin resistance, adipocytokines, and atherosclerosis

Plasma adiponectin levels increase after the administration of glimepiride. This unique effects would also be expected to improve other adipocytokines and have anti-atherosclerotic action in patients with metabolic syndrome. Thirty-four patients with type 2 diabetes mellitus who were administrated glibenclamide were randomly divided into two groups. In 20 patients glibenclamide was changed to glimepiride (GP group), and the administration of glibenclamide (GB group) was continued in 14 patients. Twelve patients receiving insulin therapy (INS group) were enrolled for comparison. The levels of plasma adiponectin, high sensitive-CRP, TNF-alpha, interleukin-6, homeostasis model assessment-insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity (baPWV) and augmentation index (AI) were measured before and 28 weeks after the therapy. HOMA-IR in the GP group was significantly decreased compared to the GB group. Plasma adiponectin levels were significantly increased in the GP group but not in the other groups. TNF-alpha, interleukin-6 and high sensitive-CRP levels were significantly decreased in the GP group, but not in the other groups. The baPWV and AI levels did not change in either the GB or the INS group, but were significantly decreased in the GP group. Glimepiride appears to improve insulin resistance and atherosclerotic disorders.

Hyperglycemia in the Intensive Care Unit: No Longer Just a Marker of Illness Severity

Hyperglycemia is a common occurrence in critically ill patients. Recent evidence has demonstrated improved survival in patients in surgical intensive care units (SICUs) receiving "tight glycemic control." The mechanisms of this survival advantage are not well understood. A review of the English language literature pertaining to potential mechanisms affecting outcome in critically ill patients receiving insulin therapy, including recently published human trials evaluating mortality outcomes. This review discusses the results of clinical trials of "tight glycemic control," considers mechanisms of hyperglycemia in critical illness, and reviews potential mechanisms of improved outcome related in the critically ill patient. A number of human studies have demonstrated improved outcomes in critically ill patient populations receiving insulin therapy with a target of euglycemia, suggesting at least part of the benefit of this therapy is normal blood sugar and not the effects of insulin. An important population not studied to date is patients in the medical ICU. However, aggressive control of hyperglycemia now remains an important component of care for all surgical patients in the ICU.

Preconditioning: evolution of basic mechanisms to potential therapeutic strategies.

Preconditioning describes the phenomenon by which a traumatic or stressful stimulus confers protection against subsequent injury. Originally recognized in dog heart subjected to ischemic challenges, preconditioning has been demonstrated in multiple species, can be induced by various stimuli, and is applicable in different organ systems. Tremendous progress has been made elucidating the signal transduction cascade of preconditioning. Preconditioning represents a potent tissue-protective condition, and mechanistic understanding may allow safe clinical application. This review recalls the history of preconditioning and how it relates to the history of the investigation of endogenous adaptation; summarizes the current mechanistic understanding of acute preconditioning; outlines the signal transduction cascade leading to the development of delayed preconditioning; discusses preconditioning in noncardiac tissue; and explores the potential of using preconditioning clinically.

Human anti-murine antibodies interfere with CPR assays performed with commercial kits

Quantitation of C-peptide is important for the assessment of insulin secretion, in particular in patients receiving insulin therapy. Since the CPR levels become much higher than the concentration of C-peptide for several reasons, such as the high concentration of proinsulin, CPR values sometimes need to be assessed carefully. We have had two diabetic patients whose CPR values were abnormally high when determined with a Daiichi C-peptide kit III (method 1). CPR values determined by other methods were from two to ten times lower, indicating considerable interference when method 1 was used. Since method 1 uses mouse monoclonal antibodies (mmab) for detection antibodies, we suspected that human anti-murine antibodies (HAMA) were responsible for the interference. HAMA were detected in serum from both patients (45 and 460 ng/ml in case 1 and case 2 (at peak), respectively). Removal of HAMA from serum eliminated the interference. Modification of method 1 to exclude mmab from the assay system removed all interference. HAMA were, therefore, considered to be the cause of the interference. In case 2, the peak concentration of HAMA was recorded 16 months earlier than the maximum of interference. Further analysis revealed that HAMA with high affinities were responsible for the interference.

Starting Insulin Therapy in Patients With Type 2 Diabetes

Although experimental studies show that insulin therapy can be safe and efficacious in improving glycemic control in type 2 diabetes under optimal conditions (ie, using patient volunteers with close monitoring under strict study protocols), little is known about its effectiveness, complication rates, and associated resource utilization in actual clinical practice. Cohort study. Large staff-model health maintenance organization. A total of 8668 patients with type 2 diabetes cared for by generalist physicians from 1990 through 1993. Resource use (hospitalizations, outpatient visits, laboratory testing, and home glucose monitoring) and glycemic control were evaluated using combined clinical, survey, and administrative information systems data. Detailed clinical case-mix data, including a newly validated case-mix method, the Total Illness Burden Index, were collected on a subsample of 1738 patients. Among patients starting insulin therapy, hemoglobin A1c (HbA1c) decreased by 0.9 percentage point (95% confidence interval, 0.7-1.0) at 1 year compared with those receiving stable medication regimens; however, 2 years after starting insulin therapy, 60% still had HbA1c levels of 8% or greater. There was no evidence that some primary care physicians achieved better results than other primary care physicians when starting insulin therapy in their patients. Patients with the poorest baseline glycemic control achieved substantially greater HbA1c reductions; those with a baseline HbA1c level of 13% had a 3-fold greater decline in HbA1c than those whose baseline HbA1c level was 9%. For a subset of all patients for whom detailed clinical case-mix data were obtained, those taking insulin had higher resource use than those taking sulfonylureas, independent of illness severity. After adjusting for age, sex, race, socioeconomic status, disease duration, and severity of diabetes and comorbidities, insulin users had slightly more laboratory tests performed, 2.4 more outpatient visits per year, and almost 300 more fingersticks for home glucose testing per year compared with sulfonylurea users (all P<.01). Although 15% of patients receiving insulin therapy reported weekly symptoms of hypoglycemia, insulin therapy was not associated with an increase in emergency department visits (after case-mix adjustment) and resulted in only 0.5 hypoglycemia-related hospitalizations per 100 patient-years. For patients with type 2 diabetes who were cared for by generalist physicians, starting insulin therapy was generally safe and effective in achieving moderate glycemic control in patients who initially had poor glycemic control. However, insulin therapy was associated with increases in resource use and was rarely effective in achieving tight glycemic control, even for those with moderate control.

Significance of diabetes mellitus in patients with acute myocardial infraction receiving thrombolytic theraphy

Objectives. The purpose of this study was to evaluate the risks and benefits associated with thrombolytic theraphy in patients with diabetes presenting with acute myocardial infarction.Background. Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy.Methods. Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients).Results. There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p < 0.0001). Whereas diabetes of 5 years' duration was associated with a mortality rate similar to that of nondiabetic patients, a >5-year duration was associated with a relative mortality risk of 1.38 (95% cofidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic was patients lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p < 0.05).Conclusions. The relative mortality of diabetis versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients.

The Effect of Acarbose on Blood Glucose Profiles of Type 2 Diabetic Patients Receiving Insulin Therapy

Nine patients with Type 2 diabetes receiving insulin therapy were treated with acarbose 100 mg thrice daily for 1 week to investigate the effect of acarbose on blood glucose control. Daily blood glucose profiles contained fewer excursions during acarbose administration and low levels were maintained. The M-value, an indicator of blood glucose fluctuation, decreased significantly from a run-in period value of 37.6 +/- 8.7 (SEM) to 16.7 +/- 4.0 during the acarbose period (p < 0.05) and rose again to 28.9 +/- 6.7 (p > or = 0.05) in the follow-up period. The 24-h urinary glucose excretion similarly decreased during acarbose administration. As expected, no decrease in HbA1C was observed due to the short treatment period. The 24-h urinary C-peptide excretions and serum lipids were not influenced by acarbose therapy. Frequent episodes of clinical hypoglycaemia were experienced while on acarbose therapy, indicating a decrease in insulin requirements. Adverse events such as flatulence and abdominal distention were observed in six out of nine cases. Symptoms were generally mild and well tolerated, only one patient dropped out because of diarrhoea and abdominal pain. We conclude that acarbose could usefully be administered to Type 2 diabetic patients treated with insulin to improve blood glucose control and reduce insulin requirement if the appropriate selection criteria were met.

Design of insulin analogues for meal-related therapy

The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and β-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands ( J Lab Clin Med 7:464–472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy. A primary goal of such efforts has been the development of insulin analogues with a reduced tendency to self-association, a property of native human insulin that delays absorption of the hormone when exogenously administered. An overview of these efforts and results of early studies with such analogues is presented.

Protein A-sepharose used to measure free insulin in plasma

Diabetic patients receiving insulin therapy generally develop anti-insulin antibodies that must be eliminated, usually by extraction with polyethylene glycol (PEG), before determining the concentration of free (active) insulin in plasma. We describe a new method for removing such antibodies, with the use of Protein A coupled to Sepharose microspheres. The results correlate well with those by the PEG method, although values are systematically higher or lower for given samples, according to the initial titer of the antibody measured in terms of binding capacity. Further studies are required to clarify this observation.

Variations of 1-deoxyglucose(1,5-anhydroglucitol) content in plasma from patients with insulin-dependent diabetes mellitus.

The concentration of 1-deoxyglucose(1,5-anhydroglucitol) in plasma from patients with insulin-dependent diabetes mellitus was measured by gas-liquid chromatography with an all-glass capillary column. Twenty-one plasma samples were obtained from 21 patients before insulin therapy, and 34 more from 13 patients receiving insulin therapy. 1-Deoxyglucose was generally not detectable in plasmas of diabetic patients before they received insulin; it was measurable in the patients who had received insulin, although its concentration was low compared with that of healthy subjects. We therefore suggest that the absence of 1-deoxyglucose in plasma is one of the markers of metabolic states of diabetes, perhaps reflecting a disturbed function of carbohydrate metabolism; its presence in plasma within a normal range may reflect the better control of diabetic patients.

Determination of glycohemoglobins by a rapid batch separation.

Glycohemoglobin, a minor component of hemoglobin, reaches elevated levels in uncontrolled diabetes mellitus. Because of the long-term effects of glycosylated hemoglobin, its determination in blood can prove to be an effective clinical tool in the management of the diabetic patient. This paper will describe a new batch ion exchange method for the determination of glycohemoglobins that precludes the necessity for specialized equipment. Eighty-four ambulatory subjects having no indication of diabetes mellitus and 32 diabetic patients receiving insulin therapy were assayed for blood glycohemoglobin content by the rapid batch method. The effectiveness and reliability of this method were tested by correlating parallel assays of the method with commercially available column methods. The diagnostic usefulness of the rapid batch method was determined by its predictive value. Results from this study support the validity of the rapid batch method.

THE EMERGENCY MANAGEMENT OF DIABETES MELLITUS

Some of the acute metabolic derangements of unstable diabetes have been discussed. The management of patients undergoing surgical operations has also been considered. No problems are usually encountered in diabetic patients treated with diet alone or with oral hypoglycaemic compounds, although chlorpropamide may need to be stopped sometime before operation. Patients receiving insulin therapy should be stabilised pre-operatively on a regimen which will allow more flexible management during operation and in the postoperative period; this can be readily performed by placing the patient on soluble insulin and giving spaced dosages. Other routines may be used for minor procedures. Adequate supplies of carbohydrate should be given in the form of intravenous dextrose and under no circumstances should oral glucose be given in the 6 hours before operation.

The emergency management of diabetes mellitus.

Some of the acute metabolic derangements of unstable diabetes have been discussed. The management of patients undergoing surgical operations has also been considered. No problems are usually encountered in diabetic patients treated with diet alone or with oral hypoglycaemic compounds, although chlorpropamide may need to be stopped sometime before operation. Patients receiving insulin therapy should be stabilised pre-operatively on a regimen which will allow more flexible management during operation and in the postoperative period; this can be readily performed by placing the patient on soluble insulin and giving spaced dosages. Other routines may be used for minor procedures. Adequate supplies of carbohydrate should be given in the form of intravenous dextrose and under no circumstances should oral glucose be given in the 6 hours before operation.