An insulin resistance syndrome (IRS) score was developed based on clinical risk factors in adults with childhood-onset type 1 diabetes in the Epidemiology of Diabetes Complications (EDC) Study and was validated using euglycemic-hyperinsulinemic clamp studies. Hypertension, waist-to-hip ratio (WHR), triglyceride and HDL cholesterol levels, family history of type 2 diabetes, and glycemic control were risk factors used to define the score. A score of 1 (lowest likelihood IRS) to 3 (highest likelihood IRS) was assigned for each risk f a c t o r. Eligible subjects (n = 24) were recruited from the EDC cohort based on tertile of IRS score. Subjects received an overnight insulin infusion to normalize glucose levels, then underwent a 3-h euglycemic-hyperinsulinemic (60 mU · m -2 · min -1 ) clamp. Glucose disposal rate (GDR) was determined during the last 30 min of the clamp. The GDR differed significantly by IRS group (9.65 ± 2.99, 8.02 ± 1.39, and 5.68 ± 2.16 m g · k g -1 · m i n -1 , P < 0.01). The GDR was inversely correlated with the IRS score (r = -0.64, P < 0.01). Using linear regression, the combination of risk factors that yielded the highest adjusted r 2 value (0.57, P < 0.001) were WHR, hypertension, and HbA 1 . This study found that clinical risk factors can be used to identify subjects with type 1 diabetes who are insulin resistant, and it provides validation of a score based on clinical factors to determine the extent of insulin resistance in type 1 diabetes. This score will be applied to the entire EDC population in future studies to determine the effect of insulin resistance on complications. D i a b e t e s 4 9 :6 2 6-632, 2000

OBJECTIVE -To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. RESEARCH DESIGN AND METHODS-This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8 -47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis Ն50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death.RESULTS -A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or Ն50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P Ͻ 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P Ͻ 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P ϭ 0.016), whereas HbA 1 showed no association with subsequent CAD.CONCLUSIONS -These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points. Diabetes Care 26:1374 -1379, 2003B oth type 1 and type 2 diabetes increase the risk of coronary artery disease (CAD) (1). However, the reasons underlying this are largely unknown, although renal disease (2) and the standard CAD risk factors seem important (3). The role of glycemic control is controversial; two studies (3,4) suggest little relationship to CAD, although others report such an association (5).Although it has been an accepted practice to consider all CAD manifestations together, because they are believed to be linked by the same underlying atherosclerosis, important differences have been noted in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of type 1 diabetes. This study suggested somewhat distinct pathophysiologic mechanisms; for example, depressive symptomatology was more related to morbidity than mortality (3).To further address these issues, risk factors, including glycemic control, for angina, ischemic electrocardiogram (ECG), and hard CAD (myocardial infarction [MI], CAD death, or angiographically proven stenosis) were investigated in this prospective study of type 1 diabetes using, for the first time, the ...

Periodic VLCDs improved weight loss in diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed particularly promising, because more subjects in this group attained a normal HbA1c. Moreover, the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks, and it was a better predictor of the 20-week response than initial or overall weight loss.

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotoninreleasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend ‫؍‬ 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10 -3.

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BACKGROUND Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. STUDY DESIGN AND METHODS A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. RESULTS Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9–9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1–13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. CONCLUSION This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting.

The prevalence of being overweight in type 1 diabetes remains lower than that in the general population. Moderate weight gain did not adversely affect the cardiovascular risk profile in the setting of improved glycemic control.

A controversial area in understanding the contribution of obesity to skeletal muscle insulin resistance is the distribution of control of glucose metabolism across proximal steps of glucose delivery, trans-membrane transport, and intracellular trapping via phosphorylation. Dynamic positron emission tomography (PET) imaging of skeletal muscle [(18)F]2-deoxy-2-D-glucose ((18)F-FDG) uptake provides an in vivo method for assessment of these steps in humans. In the current study we have examined the application of a four-compartment skeletal muscle-specific model for assessment of (18)F-FDG metabolism that takes interstitial (18)F-FDG kinetics into account and compared this to the classic three-compartment model in lean and obese volunteers. We assessed the effects of insulin infusions at three rates (0, 40, and 120 mU/m(2).min). In comparison with the classic model, the skeletal muscle-specific model reveals more clearly definable effects of insulin on transmembrane glucose transport and an impairment of this response in obesity. Compared with the classic model for assessment of (18)F-FDG metabolism, both the skeletal muscle-specific and the classic model indicate that, with respect to distribution of control, glucose phosphorylation has an important effect at low to moderate levels of insulin stimulation in both lean and obese subjects.