Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial.

CONTEXT: Hashimoto's thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid found in Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto's thyroiditis. OBJECTIVE: The effects of anatabine in patients with Hashimoto's thyroiditis were studied. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a double-blind, randomized, placebo-controlled multisite study. A total of 146 patients (70 treated with anatabine and 76 with placebo) completed the study. Approximately 50% of patients in each group were taking levothyroxine. Anatabine lozenges (9-24 mg/d) or placebo, each containing vitamins A and D3, were administered orally 3 times a day for 3 months. MAIN OUTCOME MEASURES: Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were assessed. Safety was assessed through adverse events, clinical laboratory evaluations, and vital sign measurements. RESULTS: Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those receiving placebo (P=.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels. Mean±SD TgAb values decreased by 46.2±101.1 and 3.9±83.9 World Health Organization units for the anatabine and placebo groups, respectively. Significantly more patients had a >20% drop in TgAb levels in the anatabine than placebo group (P=.023). Overall, the anatabine supplement was safe and well tolerated, although significantly (P<.05) more patients in the anatabine group reported adverse events. CONCLUSIONS: These results demonstrate an immunological effect of anatabine on TgAb levels. Further studies are warranted to determine the longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis.

Glycemic management in the inpatient setting.

Hyperglycemia occurs frequently in hospitalized patients and affects patient outcomes, including mortality, inpatient complications, hospital length of stay, and overall hospital costs. Various degrees of glycemic control have been studied and consensus statements from the American Diabetes Association/American Association of Clinical Endocrinologists and The Endocrine Society recommend a target blood glucose range of 140 to 180 mg/dL in most hospitalized patients. Insulin is the preferred modality for treating all hospitalized patients with hyperglycemia, as it is adaptable to changing patient physiology over the course of hospitalization. Critically ill patients should receive intravenous insulin infusion, and all noncritically ill patients with hyperglycemia (individuals with and without diabetes) should be managed using a subcutaneous insulin algorithm with basal, nutritional, and correctional dose components. Hypoglycemia remains a limiting factor to achieving optimal glycemic targets. Similar to hyperglycemia, hypoglycemia is an independent risk factor for poor outcomes in hospitalized patients. Improvement in glycemic control throughout the hospital includes efforts from all health care providers. Institutions can encourage safe insulin use by using insulin algorithms, preprinted order sets, and hypoglycemia protocols, as well as by supporting patient and health care provider education.

Safe insulin use in the hospital setting.

Inpatients have a high rate of diabetes (12%-26%) and hyperglycemia (~38%). All patients should have their glycosylated hemoglobin (A1C) checked on admission to help differentiate between long-term and new-onset hyperglycemia. Good glycemic control throughout the hospital stay is associated with decreases in short- and long-term risk of mortality, inpatient complications, length of hospital stay, and health care costs. Insulin is first-line therapy for hyperglycemia; patients with hyperglycemia should be managed using either intravenous (IV) or subcutaneous (SC) insulin algorithms. A hypoglycemia management protocol should be in place at the hospital for safety purposes. For successful glycemic control, insulin algorithms should have dynamic scales, require frequent glucose monitoring, and be simple and easy to use. The algorithm should address transitioning patients from IV to SC insulin and a discharge plan. Insulin analogues are preferred for basal, mealtime, and correction doses instead of human insulins (regular and NPH) because analogues have a more predictable absorption and action profile and less pharmacokinetic fluctuation. Institutions can increase safe insulin use by utilizing insulin algorithms, preprinted order sets, and hypoglycemia protocols; by supporting patient and health care provider education; and by implementing needle-stick prevention techniques.

Insulin resistance following cardiothoracic surgery in patients with and without a preoperative diagnosis of type 2 diabetes during treatment with intravenous insulin therapy for postoperative hyperglycemia.

OBJECTIVE: To assess insulin resistance postoperatively in patients with (DM) and without (nonDM) a prior diagnosis of diabetes. RESEARCH DESIGN AND METHODS: Following cardiac surgery, 122 nonDM and 33 DM were treated with insulin infusions to obtain glucose levels <110 mg dl(-1). Glucose levels, insulin infusion rates, and insulin infusion rate/glucose ratios were calculated to assess insulin resistance. RESULTS: The average blood glucose at insulin drip initiation (209 vs. 173 mg dl(-1); P<.001) and during the first 12 h (146 vs. 135 mg dl(-1); P<.05) was higher in DM, but during Hours 12-24 glucose levels were not different. The peak (5.7 vs. 4.1 U h(-1); P<.001) and average insulin drip rates (3.7 vs. 2.9 U h(-1); P<.01) were higher in DM. Insulin resistance (insulin drip rate/glucose ratio) was higher in DM during Hours 1-12 (0.029 vs. 0.022 U h(-1) mg(-1) dl(-1); P<.001), but not during Hours 12-24 (P=.57). To eliminate glucotoxicity as a cause of the insulin resistance, 23 DM patients were pair matched with 23 nonDM patients based first on glucose levels at drip initiation then by body mass index (BMI) and then catecholamine use to maintain blood pressure. The average blood glucose levels, insulin drip rates, and insulin resistance ratios were not significantly different between the pair-matched groups at all time points. CONCLUSIONS: When matched for initial glucose levels, insulin resistance is not different between DM and nonDM following cardiac surgery, likely due to the overwhelming stress response. Insulin drip protocols used postoperatively do not have to be modified for those with a prior diagnosis of diabetes.

Metabolic syndrome management.

Overweight, obesity and the metabolic syndrome occur in genetically susceptible individuals with environmental influences, and may be further compounded by other disorders of metabolism or pharmacological therapy that increase insulin resistance or promotes weight gain. Treatment of the metabolic syndrome should focus on treatment on [corrected] each individual component, but first, lifestyle modification, including diet and exercise with weight reduction, should be [corrected] the foundation of any successful treatment regimen for the metabolic syndrome. Pharmacological therapy should be individualized and targeted to normalize blood pressure, HDL cholesterol, triglycerides and glucose values. If successful, comprehensive management of the metabolic syndrome promises to delay or prevent the development of coronary heart disease and Type 2 diabetes mellitus.

Reduction of surgical mortality and morbidity in diabetic patients undergoing cardiac surgery with a combined intravenous and subcutaneous insulin glucose management strategy.

OBJECTIVE: To determine if glucose management in postcardiothoracic surgery patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen reduces mortality and morbidity in patients with diabetes and stress-induced hyperglycemia. RESEARCH DESIGN AND METHODS: Retrospective review of 614 consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was performed to evaluate the incidence and treatment of postoperative hyperglycemia and operative morbidity and mortality. Hyperglycemic patients (glucose >6.05 mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery bypass grafting (CABG)-only patients. RESULTS: Among all CT surgeries, patients with a preoperative diagnosis of diabetes had higher rates of postoperative mortality (7.3 vs. 3.3%; P = 0.03) and pulmonary complications (19.5 vs. 11.6%; P = 0.02) but had similar rates of infections and cardiac, renal, and neurological complications on univariate analysis. However, on multivariate analysis, a preoperative diagnosis of diabetes was not a significant factor in postoperative mortality or pulmonary complications. In CABG-only patients, no significant differences were seen in outcomes between diabetic and nondiabetic patients. Independent of diabetic status, glucose > or =11 mmol/l on ICU admission was predictive of higher rates of mortality and renal, pulmonary, and cardiac postoperative complications. CONCLUSIONS: A combination of IV insulin (in the ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive therapy than 3 days of IV insulin postoperatively, results in a reduction of the increased surgical morbidity and mortality in diabetic patients after CT surgery.

Inpatient management of hyperglycemia: the Northwestern experience.

OBJECTIVE: To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). METHODS: An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. RESULTS: The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. CONCLUSION: Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.

Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia.

OBJECTIVE: To determine the optimal dose of insulin glargine needed to maintain glycemic control in patients undergoing conversion from intravenous regular insulin infusions to a subcutaneous insulin regimen. METHODS: Seventy-five hospitalized patients receiving continuous insulin infusions were randomized to receive 40%, 60%, or 80% of their total daily insulin requirement, calculated from the rate during the final 6 hours of the infusion, as insulin glargine at the time of conversion to a subcutaneous regimen. Prandial insulin aspart was added to the subcutaneous regimen when patients began oral intake, and the dosage was left to clinical judgment. Capillary blood glucose monitoring (CBGM) was performed before every meal and at bedtime. All CBGM values for the 24-hour period after conversion were collected. RESULTS: Three hundred ninety-two CBGM values were recorded and analyzed. The mean for all CBGM values during the 24-hour period after conversion to the subcutaneous insulin regimen was 151.9 +/- 42.5 mg/dL in the 40% group, 164.0 +/- 41.6 mg/dL in the 60% group, and 153.2 +/- 66.2 mg/dL in the 80% group (P = 0.66). The percentage of CBGM values in the predefined study target range (80 to 140 mg/dL) was 43.2%, 34.8%, and 48% in the 40%, 60%, and 80% groups, respectively (P = 0.09). Secondary analysis with use of a glycemic target of 80 to 150 mg/dL and removal of outliers resulted in CBGM values within that range in 58.7%, 44.4%, and 67.6% for the 40%, 60%, and 80% groups, respectively (overall, P = 0.001; 40% group versus the 60% group, P = 0.03; 60% group versus the 80% group, P = 0.0004; and 40% group versus the 80% group, P = 0.18). CONCLUSION: Conversion from continuous insulin infusion to subcutaneously administered insulin glargine at a dose equal to 80% of the total daily insulin requirements resulted in the highest percentage of CBGM values in the glycemic target range of 80 to 150 mg/dL within the first 24 hours after regimen conversion in comparison with conversion at 40% and 60%, albeit the difference between the 40% and 80% groups was not statistically significant.