Increased Intact Proinsulin in the Oral Glucose Challenge Sample is an Early Indicator for Future Type 2 Diabetes Development - Case Reports and Evidence from the Literature.

BACKGROUND: Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic ß-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of ß-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for ß-cell dysfunction and prediabetes. METHODS: A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours. RESULTS: All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes. CONCLUSIONS: As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for ß-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.

Iatrogenic osteoporosis, bilateral HIP osteonecrosis, and secondary adrenal suppression in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted highly active antiretroviral therapy.

OBJECTIVE: To report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy. METHODS: We describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature. RESULTS: A 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy. Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma. CONCLUSIONS: Given the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavir-boosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression.

Quantifying amount of adsorption of levothyroxine by percutaneous endoscopic gastrostomy tubes.

BACKGROUND: It has been the authors' clinical experience that hypothyroid patients who achieve a euthyroid state on a steady dose of oral levothyroxine often become hypothyroid over time if the medication is given via a feeding tube. The authors hypothesize that the tubing and enteral feeds may adsorb a significant percentage of the levothyroxine and thereby reduce its bioavailability. To the authors' knowledge, no previous research has been reported on this subject. They therefore performed an in vitro assessment of the degree of levothyroxine adsorption to quantify the amount of drug adsorbed to the percutaneous endoscopic gastrostomy (PEG) tube and how enteral tube feeds mitigate or exacerbate this adsorption. METHODS: Using levothyroxine radiolabeled with an I 125 tracer, a known dose of levothyroxine was passed through 60 new PEG tubes. One-half of the tubes were pretreated with Jevity feeds, and the other half were not. The authors measured the activity of the radiolabeled levothyroxine before and after it had passed through the tubes and, using a subtraction analysis, inferred the amount of thyroxine left within the tube. RESULTS: Tubes presoaked with feeds had a greater uptake in radioactivity by 326.4 cpm (95% confidence interval, 226.7-426.1), corresponding to a 45.08% relative increase in uptake compared with virgin PEG tubes without feeds. CONCLUSIONS: Although the authors found statistically significant differences in mean drug concentrations, they conclude that the amount of uptake of levothyroxine by PEG tubes and adsorption of levothyroxine by PEG tubes is probably clinically insignificant. The differences found may be attributed to the amount of drug lost during crushing and transfer.