[show abstract][hide abstract] ABSTRACT: Although etomidate is a preferred anesthetic agent for rapid sequence intubation (RSI) in critical illness, as an inhibitor of cortisol synthesis (11β-hydroxylase), it may be associated with adrenal dysfunction. The objectives are to review the effects of etomidate versus comparator anesthetics in critical illness for: primary outcome of mortality and secondary outcome of adrenal insufficiency (AI).
Studies were extracted using MEDLINE and SCOPUS, regardless of language, between 1983 and 2010 using the keywords etomidate, intensive care units (ICU), critical illness, intensive care, glucocorticoids, and adrenal insufficiency. Studies of single dose etomidate versus comparator anesthetics with outcomes of adrenal function and/or mortality were included. All reviewers performed electronic data searches. One reviewer extracted data, which were checked by the other reviewers. Authors of trials were contacted for supplemental data. Primary outcome was 28-day mortality. AI was defined per article.
Two hundred sixty-three articles were screened, and 21 articles (19 independent data sets) were evaluated. Meta-analysis comparing etomidate versus non-etomidate anesthesia demonstrated an increased risk ratio (RR) for AI of 1.64 (range 1.52-1.77; 14 studies, 2,854 patients, P<0.0001, I(2)=88%) and an increased RR for mortality of 1.19 (1.10-1.30; 14 studies, 3,516 patients, P<0.0001, I(2)=64%). Significance of re-analysis for mortality within the subset of sepsis was maintained [RR 1.22 (1.11-1.35), 7 studies, n=1,767, I(2)=74%, P<0.0001], but not for trials without sepsis [RR=1.15 (0.97-1.35), 7 studies, n=1,749, I(2)=53%, P=0.10].
There is an increased rate of AI and mortality in critically ill patients who received etomidate.
European Journal of Intensive Care Medicine 03/2011; 37(6):901-10. · 5.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the effect of prior duration of diabetes, glycated hemoglobin level at study entry, and microalbuminuria or macroalbuminuria on the extent and severity of coronary artery disease (CAD) and peripheral arterial disease.
We studied baseline characteristics of the 2368 participants of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study, a randomized clinical trial that evaluates treatment efficacy for patients with type 2 diabetes and angiographically documented stable CAD. Patients were enrolled from January 1, 2001, through March 31, 2005. Peripheral arterial disease was ascertained by an ankle-brachial index (ABI) of 0.9 or less, and extent of CAD was measured by presence of multivessel disease, a left ventricular ejection fraction (LVEF) of less than 50%, and myocardial jeopardy index.
Duration of diabetes of 20 or more years was associated with increased risk of ABI of 0.9 or less (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.26), intermittent claudication (OR, 1.61; 95% CI, 1.10-2.35), and LVEF of less than 50% (OR, 2.03; 95% CI, 1.37-3.02). Microalbuminuria was associated with intermittent claudication (OR, 1.53; 95% CI, 1.16-2.02) and ABI of 0.9 or less (OR, 1.31; 95% CI, 0.98-1.75), whereas macroalbuminuria was associated with abnormal ABI, claudication, and LVEF of less than 50%. There was a significant association between diabetes duration and extent of CAD as manifested by number of coronary lesions, but no other significant associations were observed between duration of disease, glycated hemoglobin levels, or albumin-to-creatinine ratio and other manifestations of CAD.
Duration of diabetes and microalbuminuria or macroalbuminuria are important predictors of severity of peripheral arterial disease and left ventricular dysfunction in a cohort of patients selected for the presence of CAD.
Mayo Clinic Proceedings 01/2010; 85(1):41-6. · 5.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although atypical antipsychotics (AA) are associated with weight gain and diabetes mellitus (DM) in younger patients, it is not known whether these drugs would have a detrimental effect on weight gain or diabetes in a long-term care elderly population.
Retrospective chart review.
Two community nursing homes (NH).
Charts of 1678 subjects admitted between 2000 and 2006 were screened; data from subjects on AA were analyzed.
DM was defined by diagnosis in the Minimum Data Set (MDS), the prescription of diabetes medications, fasting blood glucose (BG) 126 mg/dL or higher, or random BG 200 mg/dL or higher. Worsening of DM was defined as beginning a medication in those treated with diet alone, or adding an additional medication to those already on antiglycemic therapy.
There were 154 subjects on AA, mean age 82.8 +/- 8.0 (SD) years. Although there was no difference in age between the 101 women and the 53 men, there was a greater proportion of women 85 years or older compared with men (57% versus 40%, P = .04). Alzheimer's disease (AD) was diagnosed in 17% and non-AD dementia in 34%. Weight was normal (BMI less than 25 kg/m(2)) in 63%, overweight (BMI higher than 25 but less than 30 kg/m(2)) in 29%, and obese (BMI higher than 30 kg/m(2)) in 8%. Subjects were followed on AA for a median of 13.1 weeks (interquartile range 1.9-41.9). Despite these medications, 32% lost more than 5% of body weight. DM was an admitting diagnosis in 21%. There were 4 new and 5 worsening cases of DM during their stay in the nursing home; however, of these 9 cases, 4 occurred before the institution of AA. There was no increased frequency of weight gain or DM among the various atypical agents.
In an elderly NH population, there was no evidence that short-term use (median 13.1 weeks) of atypical antipsychotic agents was associated with the onset or worsening of DM.
Journal of the American Medical Directors Association 03/2009; 10(2):115-9. · 5.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Guidelines for diabetes foot care are available and should be part of the routine care and evaluation of all elderly patients who have diabetes. Those individuals who have good sensation, good vascularity, without foot deformities, and are capable of reaching and seeing their feet may do well with education and reasonable approaches to footwear and foot care. Those who have advanced diabetic complications of neuropathy or vascular insufficiency should be seen by professionals and given intensive education. An experienced team familiar with the progression of illness should follow those who have ulcers. Guidelines are presented for the management of outpatient and inpatient therapy of foot ulcers.
Clinics in Geriatric Medicine 09/2008; 24(3):551-67, viii. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dietary and nutritional supplements are modulators of HDL cholesterol levels and production of apolipoprotein (apo) AI. Previously, in vitro treatment of hepatocyte cell lines with glucosamine increased apoAI production by stabilization of apoAI mRNA. The hypothesis is that the neutraceutical glucosamine, when given in conventional doses (1,500 mg/day) may increase apoAI and HDL cholesterol levels in subjects with diabetes and low HDL cholesterol.
Twelve subjects (three men and nine women) with type 1 (n = 2) and type 2 (n = 10) diabetes, aged 55 +/- 12 years (mean +/- SD), who had low HDL cholesterol (1.03 +/- 0.20 mmol/l), were randomly assigned to a double-blind, placebo-controlled, cross-over trial of 500 mg glucosamine or placebo orally three times daily for 2 weeks, followed by a 4-week washout phase and a 2-week cross-over to the alternate therapy.
Fasting serum glucose, fructosamine, and total cholesterol remained stable during the drug and placebo phases. Glucosamine had no significant effect after therapy on serum levels of HDL cholesterol (from baseline of 1.02 +/- 0.15 to 1.05 +/- 0.16 mmol/l compared with placebo from 1.04 +/- 0.21 to 1.06 +/- 0.16 mmol/l) nor in changes in apoAI levels (from baseline of 147 +/- 15 to 140 +/- 126 mg/dl with glucosamine and from 146 +/- 25 to 142 +/- 17 mg/dl with placebo).
These observations suggest that glucosamine at commonly consumed doses does not have significant effects on glycemic control, lipid profile, or levels of apoAI in diabetic subjects after 2 weeks of supplementation.
Diabetes care 12/2007; 30(11):2800-3. · 8.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 59-year-old man with type 1 diabetes mellitus presented with severe resistance to subcutaneously injected insulin. Histological analysis of the injection sites, demonstrated foreign body type granulomas surrounding areas of amyloidosis. It is suggested that the granulomas were the source of an insulin-degrading enzyme (IDE) which simultaneously degraded amyloidogenic precursors into localized amyloid deposits. These findings may add insight into the role of insulin-degrading enzymes in the etiology of subcutaneous insulin resistance syndromes.
Diabetes Research and Clinical Practice 04/2007; 75(3):374-6. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obese subjects have functional growth hormone deficiency (GHD). Recombinant human GH (rhGH) treatment of pituitary GHD improves serum levels of leptin, adiponectin and C-reactive protein (CRP). This study was undertaken to determine whether these rhGH-induced changes occur in obese subjects during rhGH supplementation.
Randomized double-blind placebo-controlled trial of low-dose rhGH (200 microg/day for the first month, then 400 microg/day for men and 600 microg/day for women thereafter) or placebo supplementation as an adjuvant to a standard weight loss program.
Forty healthy obese subjects, 28 premenopausal menstruating women (35+/-7 SD years) and 12 men (37+/-6 years).
Body weight, BMI, body composition (assessed by dual energy X-ray absorptiometry [DEXA]), and serum levels of glucose, insulin, IGF-I, IGFBP-3, insulin resistance index (homeostasis modal assessment [HOMA]), leptin, CRP and adiponectin were performed at baseline and at 6 months.
For similar entry BMI values, women when compared with men had higher percent body fat (BF) (43.5+/-4.6% vs. 29.8+/-4.0%, p<0.001), higher leptin levels (16.9+/-8.4 microg/L vs. 4.2+/-3.0 microg/L, p<0.001), and higher CRP levels (13.8+/-16.8 mg/L vs. 2.4+/-3.2mg/L, p=0.04). Serum levels of leptin and CRP, but not adiponectin, correlated significantly with BF in both sexes. Recombinant human GH treatment increased levels of IGF-I Z-Score between baseline and 6 months (from -0.7+/-0.9 SD to 0.1+/-1.1 SD, p=0.01) and modestly decreased BF (from 38.4+/-7.8% to 35.6+/-7.5%, p=0.046). Despite increased IGF-I, there were no differences between rhGH and placebo with regard to changes in leptin, CRP, or adiponectin.
It is concluded that in obesity, although rhGH treatment significantly increases IGF-I and modestly reduces body fat, the lack of significant changes in serum leptin, adiponectin or CRP levels suggests that rhGH treatment does not have a significant effect on these serum markers of adiposity.
[show abstract][hide abstract] ABSTRACT: The emergence of multiple insulin products has provided new opportunities to achieve diabetes control. However, the number of options has raised concerns about the optimal choices of products.
To briefly review the pharmacologic characteristics of currently available insulin products and to suggest an initial insulin regimen based on common blood glucose profiles among patients with diabetes.
Relevant manuscripts were identified through a MEDLINE search (1996 to 25 February 2006) of the English-language literature. The key phrase used was therapeutic use of insulin. The literature search was limited to core clinical journals that have accessible full texts.
Clinical trials and authoritative reviews published between 1996 and February 2006 were selected. A total of 420 manuscripts was reviewed.
The authors independently reviewed the relevant available literature. This literature, along with the authors' clinical experience, was used to construct practical suggestions.
Several new insulin and insulin analogue preparations are now available for clinical use. Used as prandial insulin (for example, insulin lispro, insulin aspart, or insulin glulisine) and basal insulin (for example, insulin glargine or insulin detemir), the analogues simulate physiologic insulin profiles more closely than the older conventional insulins. There is currently no strong rationale favoring glargine, neutral protamine Hagedorn insulin, insulin detemir, or fixed-ratio insulin preparations as the preferred agent for initiating insulin therapy.
This was a retrospective review of previously published manuscripts chosen at the authors' discretion.
The advent of recombinant DNA technology made it possible to overcome limitations in the time-action profiles of conventional insulins. Insulin therapy must be individualized. Nevertheless, certain subgroups of patients with diabetes can be differentiated from each other according to the pattern of blood glucose changes during the day. On the basis of the blood glucose profile, the authors suggest an initial insulin regimen that can be used to evaluate individual responsiveness and plan a long-term regimen.
Annals of internal medicine 08/2006; 145(2):125-34. · 13.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although aspirin is cardioprotective in high-risk populations, many with diabetes mellitus (DM) are unresponsive to these benefits. We questioned whether cardiovascular unresponsiveness might be demonstrated by lack of aspirin sensitivity to in vitro platelet functions especially in subjects with poorly controlled diabetes. Six women and 4 men (48+/-8 years [mean+/-S.D.]), selected for poor control (glycohemoglobin 11.9+/-2.2%) and 10 sex-age (+/-5 years) matched controls received 81 mg aspirin daily. There was a 2-week washout from aspirin and related drugs. After the aspirin dose on day-7, blood for platelet aggregation assays, and 24-h urine for 2,3 dinor thromboxane B2 (TxB2) and 2,3 dinor 6-keto (PGF1alpha) were obtained. Aspirin sensitivity was defined as inhibition (i.e., lower than expected) platelet aggregation after exposure to an agonist. Those with diabetes and controls were sensitive to aspirin inhibition of platelet aggregation induced by 1.6 mM arachidonic acid (9.5+/-3.9% versus 9.1+/-3.1%, normal range 40-100%) and by 0.83 microg/mL collagen (17.4+/-13.9% versus 13.2+/-9.3%, normal range 60-93%), respectively. Aspirin sensitivity to 2 microM ADP was present in five with diabetes and five controls. Urinary prostaglandin metabolites were suppressed below reference ranges, without differences between those with DM or controls for TxB2 (350+/-149 pg/mg versus 348+/-93 pg/mg creatinine) and PGF1alpha (255+/-104 pg/mg versus 222+/-88 pg/mg creatinine). In conclusion, in poorly controlled diabetes, there was no differential lack of aspirin sensitivity to platelet aggregation, or lack of aspirin suppression of urinary TxB2 or PGF1alpha, compared with controls on aspirin. Despite suppression of urinary prostaglandin metabolites, aspirin resistance was most apparent to ADP-mediated platelet aggregation. It is not known what level of inhibition of in vitro tests is necessary for the cardioprotective benefits of aspirin in diabetes mellitus. Thus, the lack of aspirin protection in diabetes may be due to undefined aspects of platelet function.
Diabetes Research and Clinical Practice 12/2005; 70(2):195-9. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mechanism of the pubertal delay seen in some adolescents with type 1 diabetes mellitus is not entirely clear. Since leptin has been implicated as a neuroendocrine modulator of puberty, we measured serum leptin levels longitudinally in 24 post-'honeymoon' patients with diabetes mellitus (M/F = 15/9) with a mean (+/- SD) age of 10.5 +/- 0.9 years and 26 controls (M/F = 15/11) with a mean age of 10.0 +/- 1.1 years. Physical examinations; serum leptin, IGF-I, IGFBP-3 and IGFBP-1 levels; and bone age X-rays were performed annually for up to 48 months. Glycosylated hemoglobin (HbA1c) was measured 2-4 times a year in patients with diabetes mellitus. Serum leptin levels strongly correlated with the body mass index z-scores (BMI-Z) in both controls (r = 0.666, p <0.00001) and diabetic patients (r = 0.577, p <0.00001). Girls had increased serum leptin levels for a given BMI compared to boys (p <0.005). There were no significant differences in serum leptin levels of patients with diabetes mellitus compared to controls, nor were differences seen when the groups were stratified by age, Tanner stage, or gender. There were also no significant correlations between serum leptin levels and degree of metabolic control (i.e. HbA1c) or insulin dose standardized for body weight. Although there was no significant diabetes-related or metabolic control-related delay in bone age z-score or pubertal development, there was a significant negative correlation between HbA1c and growth velocity z-score, indicating that children with poor diabetes control had modest but significant slowing of growth. It is concluded that neither pubertal development nor serum leptin levels are significantly altered in adolescents with diabetes mellitus managed with standard therapy. The potential role of leptin in initiation of pubertal development is not easily demonstrable in observational studies.
[show abstract][hide abstract] ABSTRACT: Obese individuals are in a reduced GH/IGF-I state that may be maladaptive. Fifty-nine obese men and premenopausal menstruating women (body mass index, 36.9 +/- 5.0 kg/m(2)) were randomized to a double-blind, placebo-controlled trial of low dose recombinant human GH (rhGH). During the 6-month intervention, subjects self-administered daily rhGH or equivalent volume of placebo at 200 micro g (1.9 +/- 0.3 microg/kg for men, 2.0 +/- 0.3 microg/kg for women); after 1 month, the dose was increased to 400 microg (3.8 +/- 0.5 microg/kg) in men and 600 microg (6.0 +/- 0.8 microg/kg) in women. rhGH was then discontinued, and subjects were followed up after 3 months. Forty completed the intervention, and 39 completed the follow-up. Drop-out rates between rhGH vs. placebo groups were not different (chi(2) = 1.45; P = 0.228). One subject discontinued the drug due to an rhGH-related side effect. Body weight (BW) decreased with rhGH from 100.4 +/- 13.2 to 98.0 +/- 15.6 kg at 6 months (P = 0.04) and was sustained at 98.1 +/- 16.6 kg at 9 months (P = 0.02). BW loss was entirely due to loss of body fat (BF). Intention to treat analyses demonstrated changes from baseline between rhGH and placebo in BW (-2.16 +/- 4.48 vs. -0.04 +/- 2.67 kg; P = 0.03) and BF (-2.89 +/- 3.76 vs. -0.68 +/- 2.37 kg; P = 0.01). rhGH increased IGF-I from -0.72 to +0.10 SD (P = 0.0001). rhGH increased high-density lipoprotein cholesterol 19% from 1.11 +/- 0.34 to 1.32 +/- 0.28 mmol/liter (P < 0.001). Neither group had changes in fasting glucose, insulin sensitivity, or resting energy expenditure. In conclusion, in obesity, rhGH normalized IGF-I levels, induced loss of BW from BF, and improved lipid profile without untoward effects on insulin sensitivity.
[show abstract][hide abstract] ABSTRACT: The anti-hyperglycemic effect of alpha-glucosidase inhibitors (AGI) is partly attributed to their ability to stimulate the secretion of glucagon-like peptide-1 (GLP-1), a gut hormone with insulin stimulating capability. To determine if this mechanism of action contributes significantly to the therapeutic efficacy of AGI in the elderly, 10 type 2 diabetic subjects over the age of 65 years were given a standardized test meal with or without 25, 50, or 100 mg acarbose. The serum glucose, insulin, triglycerides and GLP-1 levels were measured at baseline and at 1 and 2 h postprandially. The anti-hyperglycemic effect of acarbose was maximal at 25-mg dose under these experimental conditions. Serum postprandial insulin and triglycerides levels were not significantly altered with acarbose treatment. The postprandial serum GLP-1 levels rose significantly only in two subjects and only during treatment with 100-mg acarbose. There were no significant correlations between serum GLP-1 and serum glucose or insulin levels. It is concluded that in most elderly type 2 diabetic subjects, maximal anti-hyperglycemic effects can be achieved with relatively small doses of acarbose and that GLP-1 is unlikely to contribute to the clinical efficacy of this agent in this subgroup of subjects.
Diabetes Research and Clinical Practice 06/2002; 56(2):101-6. · 2.74 Impact Factor