Weight loss and diabetes are new risk factors for the development of invasive aspergillosis infection in non-immunocompromized humans.

Well-established risk factors for aspergillosis include HIV, cancer, recent corticosteroid (prednisone) therapy, chemotherapy, or thoracic surgery. Non-established risk factors may include weight loss and a history of diabetes. Twenty-three patients without the classical risk factors for IA were identified retrospectively at Harbor UCLA Medical Center by discharge diagnosis over a 20 year period (1992-2012). None of the well-known risk factors are for Invasive Apergillious (IA). A history of weight loss was seen in 66% of the patients with IA (15 of 23). The weight loss ranged from 3.3 lbs to 43 lbs. In patients with weight loss the average loss was 22±3 lbs (mean±SEM). In this small group of patients with IA, diabetes was seen in 8 of the 23 (34%), which is significantly higher than the 19% incidence of diabetes seen in 100 patients with severe sepsis (p<0.05). Likewise, the 34% incidence of diabetes was higher than the 21% incidence reported in immunocompromised patients with invasive aspergillus (IA) infection (p<0.05). A reduced serum albumin concentration was seen in 33% of the study patients, which was less common than the 87% incidence seen in patients with severe sepsis or candidaemia (54%). Seventeen of the 23 patients had pulmonary involvement. While no one had a well-established risk factor for aspergillious, four patients had alcoholism as a potential risk factor. Eleven of the 23 (48%) died during the hospital stay despite antifungal therapy. Immunocompromised patients are known to have a mortality rate of approximately 45% for pulmonary or disseminated disease. CONCLUSION: The incidence of diabetes was greater than seen in immunocompromised patients and may be considered an additional risk factor for the development of aspergillois infection. In addition, a history of weight loss should increase the suspicion for the diagnosis of IA in otherwise a non-immunocompromised patient. Early recognition and treatment of aspergillosis in the non-immunocompromised patient may improve outcome. Weight loss and diabetes should be added to the list of well-known risk factors for invasive aspergillosis and its high mortality rate.

Growth hormone administration increases glucose production by preventing the expected decrease in glycogenolysis seen with fasting in healthy volunteers.

Twelve volunteers were fasted overnight and infused with [ 13 C]glucose (ul) to measure glucose production (GP), gluconeogenesis, and by subtraction, glycogenolysis. Glucose production, gluconeogenesis, and glycogenolysis were measured after a 3-hour baseline infusion and two 4-hour infusions. The first 4 hours of the pituitary-pancreatic clamp study (PPCS) with replacement insulin, cortisol, and glucagon was without growth hormone (GH) administration. The second 4 hours of the PPCS was with high-dose GH administration. Six fasting volunteers acted as controls over the 11-hour study period. Overnight 12-hour fasting measurements of hormones, glucose, GP, gluconeogenesis, and glycogenolysis were similar in both groups. The PPCS had no significant effect on GP (2.43 +/- 0.19 vs 2.07 +/- 0.11 mg/kg per minute, PPCS vs controls, mean +/- SEM). Glycogenolysis, as a percent of GP (43%-49%), was similar between PPCS and controls (43% +/- 3% vs 49% +/- 4%). High-dose GH for 4 hours increased GH (20.8 +/- 3.8 vs 2.0 +/- 0.9 ng/mL), blood glucose (127 +/- 28 vs 86 +/- 4 mg/dL, P < .05), GP (2.21 +/- 0.21 vs 1.81 +/- 0.12 mg/kg per minute, P < .05). The increase in GP was due to sustained glycogenolysis as compared to the observed fall in glycogenolysis seen with fasting alone (0.94 +/- 0.21 vs 0.53 +/- 0.07 mg/kg per minute, P < .05). Glycogenolysis, as a percent of GP, was significantly increased with high-dose GH (43 +/- 5% vs 29 +/- 3%, P < .05). High-dose GH had no effect on gluconeogenesis (1.26 +/- 0.15 vs 1.29 +/- 0.12 mg/kg per minute). High-dose GH prevents the fall in glycogenolysis observed with fasting alone.

Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control.

OBJECTIVE: To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size. METHODS: We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically. RESULTS: Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3). CONCLUSION: This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.