Diabetes in urban African-Americans. XIX. Prediction of the need for pharmacological therapy.

OBJECTIVE: To develop a prediction rule that will identify patients who will require pharmacological therapy within 6 months of first presentation to a diabetes clinic. RESEARCH DESIGN AND METHODS: Among the patients who came to the Grady Diabetes Clinic between 1991 and 1997, we randomized 557 frequent attenders to a development group and 520 frequent attenders to a validation group. Using multiple logistical regression, we derived a prediction rule in the development group to project whether patients would require pharmacological intervention to achieve HbA1c levels <7% after 6 months. The utility of the prediction rule was then confirmed in the validation group and tested prospectively on an additional group of 93 patients who presented from 1997 to 1998. Performance of the prediction rule was assessed using receiver operating characteristic (ROC) curves. RESULTS: The rule (-4.469 + 1.932 x sulfonylurea Rx + 1.334 x insulin Rx + 0.196 x duration + 0.468 x fasting glucose, where "Rx" indicates a prescription) predicted the need for pharmacological intervention in the development group (P < 0.0001). Use of insulin or sulfonylurea therapy at presentation, duration of diabetes, and fasting glucose levels were significant predictors of the future need for pharmacological management. The prediction rule also performed well in the validation group (positive predictive value 90%, correlation between predicted and observed need for medical management 0.99). ROC curves confirmed the value of the prediction rule (area under the curves was 0.91 for the development group, 0.85 for the validation group, and 0.81 for the prospective group). CONCLUSIONS: Early identification of individuals who will require pharmacological intervention to achieve national standards for glycemic control can be achieved with high probability, thus allowing for more efficient management of diabetes.

Diabetes in urban African-Americans. XVII. Availability of rapid HbA1c measurements enhances clinical decision-making.

OBJECTIVE: To assess the impact of rapid-turnaround HbA1c results on providers' clinical decision-making and on follow-up HbA1c levels. RESEARCH DESIGN AND METHODS: The research design was a randomized clinical trial in which rapid HbA1c results were made available to providers on even days of the month (rapid, n = 575), but delayed by 24 h on odd days (conventional, n = 563). Adjustment of therapy for patients with type 2 diabetes was considered appropriate if therapy was intensified for HbA1c values >7% or not intensified for HbA1c values < or =7%. A post-hoc analysis was also performed using patients (n = 574) who returned for follow-up 2-7 months later to ascertain the effect of rapid HbA1c availability on subsequent glycemic control. RESULTS: Rapid HbA1c availability resulted in more appropriate management compared with conventional HbA1c availability (79 vs. 71%, P = 0.003). This difference was due mainly to less frequent intensification when HbA1c levels were < or =7% (10 vs. 22%, P < 0.0001) and slightly to more frequent intensification for patients with HbA1c values >7% (67 vs. 63%, P = 0.33). For both groups, intensification was greatest for patients on insulin (51%) compared with patients on oral agents (35%) and diet alone (14%) (P < 0.0001). Regression analysis confirmed that providers receiving conventional HbA1c results were more likely to intensify therapy in patients who already had HbA1c levels < or =7%. Over 2-7 months of follow-up, HbA1c rose more in patients with conventional HbA1c results compared with rapid results (0.8 vs. 0.4%, P = 0.02). In patients with initial HbA1c >7%, rapid HbA1c results had a favorable impact on follow-up HbA1c independent of the decision to intensify therapy (P = 0.03). CONCLUSIONS: Availability of rapid HbA1c determinations appears to facilitate diabetes management. The more favorable follow-up HbA1c profile in the rapid HbA1c group occurs independently of the decision to intensify therapy, suggesting the involvement of other factors such as enhanced provider and/or patient motivation.

The low dose (1-microg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency.

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 microg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 microg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-microg test performs significantly better than the 250-microg test compared to the gold standard, insulin tolerance test. We suggest that the 1-microg ACTH stimulation test replace the conventional 250-microg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-microg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-microg vials.

In vivo hemoperfusion studies of bilirubin removal from jaundiced dogs.

Removal of bilirubin by hemoperfusion (HP) on a macroreticular ion-exchange resin is suggested as a novel clinical procedure for the treatment of jaundiced newborn babies. The efficiency and biocompatibility of the proposed macroreticular (MR) ion exchange column was tested in vivo with jaundiced dogs. An animal model with a choledocho-suprarenal vein shunting allowed to test the column capacity for the adsorption of conjugated and unconjugated bilirubin. A second animal model, based on infusing unconjugated bilirubin directly into the blood stream, enabled to test the column operation at desired unconjugated bilirubin concentrations. The results of the in vivo hemoperfusion tests are very encouraging and compare favorably with bilirubin removal from babies by exchange transfusion (ET). Operating a column containing 10 ml resin per kg body weight for 3 hours removed over 1.7 times the initial unconjugated bilirubin content. Furthermore, the animals seemed to be unaffected by the HP procedure; the changes due to hemoperfusion on blood chemistry, hematology and some hormone levels were practically insignificant.