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Metabolism. Author manuscript; available in PMC 2013 Aug 19.
Published in final edited form as:
PMCID: PMC3746516
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PMID: 21134520

Ebenezer A. Nyenwe

aDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA

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Terri W. Jerkins

bLipscomb University, Nashville, TN 37204, USA

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Guillermo E. Umpierrez

why do type 2 diabetes take insulin meal plan (πŸ”΄ treatment home remedies) | why do type 2 diabetes take insulin in young childrenhow to why do type 2 diabetes take insulin for cEmory University School of Medicine, Atlanta, GA 30303, USA

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Abbas E. Kitabchi

why do type 2 diabetes take insulin dinner recipes (πŸ‘ diet plan pdf) | why do type 2 diabetes take insulin exercise planhow to why do type 2 diabetes take insulin for aDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA

Find articles by Abbas E. Kitabchi
aDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
bLipscomb University, Nashville, TN 37204, USA
cEmory University School of Medicine, Atlanta, GA 30303, USA
*Corresponding reviewer. Tel.: +1 901 448 2610; fax: +1 901 448 4340. address: [email protected] (A.E. Kitabchi)
The publisher''s prior diabetes status [70]. In this study, a total of 620 patients with admission glucose values greater than 198 mg/dL were randomized to receive either conventional diabetes care or IV glucose-insulin-potassium immediately after acute myocardial infarction to maintain levels of blood glucose less than 210 mg/dL followed by intensive subcutaneous insulin therapy for 3 or more months. In this study, mean blood glucose at 24-hour admission to the hospital was 173 mg/dL in the experimental group vs 211 mg/dL in the control group. At discharge, the glucose values were 173 vs 148 mg/dL, respectively. Although the mortality rate in the hospital (control 11% vs insulin glucose infusion 9%) or in 3 months (1% vs 12%) were not significantly different, the values at 1 year were reduced from 26% (control) to 19% (insulin glucose infusion), with a 28% reduction in mortality (P = .01).

The Portland Diabetic Project, a prospective, nonrandomized study of 3554 consecutive diabetic patients who underwent coronary artery bypass graft [67], reported that aggressive insulin therapy with IV insulin with blood glucose range of 177 ± 30 mg/dL compared with subcutaneous insulin with blood glucose levels of 213 ± 4 mg/dL resulted in significantly lower mortality rate (2.5% vs 5.3%). Similarly, the rate of deep sternal wound infection, hospital length of stay, and hospitalization costs were significantly reduced in patients treated with IV insulin [71]. Also, Krinsley [72] reported that the implementation of an insulin infusion protocol designed to keep the blood glucose level lower than 140 mg/dL reduced hospital mortality from 20.9% to 14.8% in a prospective study in a medical/surgical intensive care unit (ICU). In the landmark Leuven trial [63], a prospective, randomized study of intensive insulin therapy for patients admitted to a surgical ICU, treated to a target glucose between 4.4 and 6.1 mmol/L (80 and 110 mg/dL), reduced hospital mortality by 34%, sepsis by 46%, acute renal failure requiring hemodialysis by 41%, and need for blood transfusions by 50%. Compared with conventional therapy, there was also less critical illness neuropathy, and shorter durations of mechanical ventilation and ICU stays in these patients [63].

In contrast to these early positive studies, the results of recent randomized controlled studies have raised questions on the safety and efficacy of tight glucose target (80–110 mg/dL) in improving clinical outcomes (reduced hospital complications and mortality) without increasing the risk for severe hypoglycemia[7376]. The Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction 2 trial [77] included 1253 patients with acute myocardial infarction and a history of diabetes mellitus or admission blood glucose greater than 198 mg/dL reported no difference in mortality among patients randomized to an intensive insulin-glucose infusion protocol or to routine metabolic management according to local practice. In addition, there were no significant differences in morbidity expressed as cases with nonfatal reinfarction, congestive heart failure, and stroke among treatment groups.

The Leuven medical ICU trial failed to replicate the results of the surgical ICU study [78]. In this study, 1200 adult patients considered to need at least 3 days or more of medical ICU care were randomly assigned to receive intensified insulin treatment to achieve a target BG of 80 to 110 mg/dL or to conventional insulin therapy started when blood glucose is greater than 215 to achieve a target blood glucose between 180 and 200 mg/dL. In the intention-to-treat analysis, despite reduction in blood glucose levels, there were no differences inhospital mortality (40% in the conventional-treatment group vs 37.3% in the intensive-treatment group, P = .33). Among 433 patients who stayed in the ICU for less than 3 days, mortality was greater among patients treated with intensive insulin therapy. However, among patients who stayed in the ICU for 3 or more days, intensive insulin treatment reduced in-hospital mortality (from 52.5% to 43.0%, P = .009). A 6-fold increase in severe hypoglycemic events (blood glucose < 40 mg/dL [2.2 mmol/L]) was observed in the intensively treated group (18.7% vs 3.1%), and hypoglycemia was identified as an independent risk factor for mortality [78].

The Glucontrol Trial [79], a prospective randomized controlled trial (RCT) in a mixed population of critically ill patients, compared the effects of 2 regimens of insulin therapy aimed to achieve a blood glucose level between 80 and 110 mg/dL and between 140 and 180 mg/dL. The study was stopped prematurely because a high rate of unintended protocol violations and safety concerns. During treatment, the mean blood glucose was 118 vs 144 mg/dL. There were no differences in ICU mortality (16.97 vs 15.20), hospital mortality (24.6 vs 20.7), 28-day mortality (19.8 vs 16.1), or ICU length of stay (6 vs 6 days). The rate of hypoglycemia was greater in the intensified treatment regimen (8.6% vs 2.4%). Of interest, mortality among people with a blood glucose of less than 40 mg/dL during treatment was increased (32.6% vs 53.8%). The Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) Study [73], an RCT in 600 subjects with sepsis randomized to conventional (blood glucose 180–220 mg/dL) or to intensive insulin therapy (blood glucose 80–110 mg/dL), reported no decrease in 28-day mortality (26% vs 24.7%) and 90-day mortality (35.4% vs 39.7%), but reported higher rates of severe hypoglycemia with intensive insulin therapy (17% vs 4.1%; P < .001). Hypoglycemia (blood glucose <40 mg/dL [<2.2 mmol/L]) was identified as an independent risk factor for mortality (RR, 2.2 at 28 days; 95% confidence interval, 1.6–3.0) [73].

In a similar RCT, De La Rosa et al [74] reported that intensive glycemic control in a mixed medical-surgical ICU resulted in no decrease in morbidity or mortality, while increasing the rate of hypoglycemia 5-fold. The largest study to date, Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation trial compared outcomes among 6104 the 1 last update 15 Jul 2020 ICU patients randomized to an intensive glucose control (81–108 mg/dL) and conventional treatment (blood glucose 144–180 mg/dL) [75]. The 2 treatment groups showed good glycemic separation, with a mean absolute difference of 29 mg/dL in overall blood glucose levels (118 vs 145 mg/dL). They reported an absolute increase in the rate of the primary end point, death at 90 days, with intensive glucose control (27.5% vs 24.9% with conventional control; odds ratio, 1.14; P = .02). The rate of severe hypoglycemia (blood glucose <40 mg/dL) was significantly higher in the intensive-control group than in the conventional-control group (6.8% vs 0.5%, P < .001) [69]. Two independently conducted meta-analyses of randomized studies comparing intensive insulin therapy with conventional management in the critically ill revealed that intensive insulin therapy conferred no mortality benefit but increased the risk of hypoglycemia [80,81]; although patients in surgical ICU appeared to benefit from tight glucose control [80].In a similar RCT, De La Rosa et al [74] reported that intensive glycemic control in a mixed medical-surgical ICU resulted in no decrease in morbidity or mortality, while increasing the rate of hypoglycemia 5-fold. The largest study to date, Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation trial compared outcomes among 6104 ICU patients randomized to an intensive glucose control (81–108 mg/dL) and conventional treatment (blood glucose 144–180 mg/dL) [75]. The 2 treatment groups showed good glycemic separation, with a mean absolute difference of 29 mg/dL in overall blood glucose levels (118 vs 145 mg/dL). They reported an absolute increase in the rate of the primary end point, death at 90 days, with intensive glucose control (27.5% vs 24.9% with conventional control; odds ratio, 1.14; P = .02). The rate of severe hypoglycemia (blood glucose <40 mg/dL) was significantly higher in the intensive-control group than in the conventional-control group (6.8% vs 0.5%, P < .001) [69]. Two independently conducted meta-analyses of randomized studies comparing intensive insulin therapy with conventional management in the critically ill revealed that intensive insulin therapy conferred no mortality benefit but increased the risk of hypoglycemia [80,81]; although patients in surgical ICU appeared to benefit from tight glucose control [80].

8.3. Studies in medical and surgical patients in non-ICU settings

There are no RCTs examining the effect of intensive glycemic control on mortality and clinical outcomes in hospitalized patients in general medical/surgical settings. However, several observational studies point to a strong association between hyperglycemia and poor clinical outcomes, including prolonged hospital stay, infection, and disability after hospital discharge, and death [61,8284]. In such patients, the presence of hyperglycemia is associated with prolonged hospital stay, infection, disability after hospital discharge, and death [61,62,65]. In a retrospective study of 1886 patients admitted to a community hospital, mortality on the general floors was significantly higher in patients with newly diagnosed hyperglycemia and in those with known diabetes than in those who were normoglycemic (10% vs 1.7% vs 0.8%, P < .01)[61]. Admission hyperglycemia has also been linked to worse outcomes in patients with community-acquired pneumonia [85]. In a prospective cohort multicenter study of 2471 patients, those with admission glucose levels of greater than 11 mmol/L (198 mg/dL) had a greater risk of mortality and complications than those with glucose less than 11 mmol/L. The risk of in-hospital complications increased 3% for each 1 mmol/L increase in admission glucose. In a retrospective study of 348 patients with chronic obstructive pulmonary disease and respiratory tract infection, the relative risk of death was 2.10 in those with a blood glucose of 7 to 8.9 mmol/L, and 3.42 for those with a blood glucose of >9.0 mmol/L compared with patients with a blood glucose 6.0 mmol/L [86]. A 1 mmol/L (18 mg/dL) increase in blood glucose was associated with a 15% increase in the risk of an adverse clinical outcome, which was defined as death or length of stay of greater than 9 days.

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Insulin therapy is the preferred method of glycemic control most patients in the hospital setting [87]. In the ICU, IV infusion is the preferred route of insulin administration. Outside critical care units, subcutaneous insulin administration is used much more frequently. Oral agents have a limited role and should be avoided in the inpatient setting. In the critical care setting, continuous IV insulin infusion has been shown to be the most effective method for achieving specific glycemic targets [65,87]. Because of the very short half-life of circulating insulin, IV delivery allows rapid dosing adjustments to address alterations in patients''Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;23(299):316–23. [PubMed] why do type 2 diabetes take insulin bread (πŸ”₯ dinner recipes) | why do type 2 diabetes take insulin in youthhow to why do type 2 diabetes take insulin for [Google Scholar]

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