Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors.

OBJECTIVES: To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (PI). DESIGN: Prospective cross-sectional study. METHODS: Thirty-eight HIV-1-infected patients receiving at least one PI were compared with 17 PI-naive HIV patients in an oral glucose tolerance test (OGTT). Serum glucose, insulin, proinsulin, and C-peptide were determined. The fasting lipid pattern was analysed using electrophoresis and the assessment of apolipoproteins including lipoprotein (a). Fibrinogen, homocysteine, and anticardiolipin antibodies were also assessed. RESULTS: Twenty-seven (71%) of the PI-treated group had detectable hyperlipidaemia. Isolated hypertriglyceridaemia was present in 12 patients (44%), two (7%) of them had type V and 10 (37%) subjects had type IV hyperlipidaemia (Frederickson classification). Type IIb hyperlipidaemia defined as an increase of both very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) was found in 10 (36%) subjects, and five (18%) patients presented with isolated hypercholesterolaemia (type IIa). PI treatment was associated with significant higher fasting cholesterol, triglycerides, LDL and VLDL levels. Apolipoprotein B and E concentrations were significantly increased in patients receiving PI. Elevated concentrations of lipoprotein (a) (> 30 mg/dl) were detected in six (16%) of the hyperlipidaemic patients on PI. Eighteen (46%) patients on PI had impaired oral glucose tolerance and five (13%) had diabetes. Although four (24%) of the PI-naive patients were glucose intolerant, none had diabetes. Fasting concentrations and secretion response of insulin, proinsulin, and C-peptide to glucose ingestion was significantly increased in the PI-treated group suggesting a beta-cell dysfunction in addition to peripheral insulin resistance. Beta-cell abnormalities were associated with the abnormal lipid pattern and PI treatment. CONCLUSION: Combination drug regimens including PI are accompanied by impaired glucose tolerance, hyperproinsulinaemia as an indicator for beta-cell dysfunction, and lipid abnormalities proved to be significant risk factors for coronary heart disease. Moreover, PI may have an impact on the processing of proinsulin to insulin.

Lipid evaluation in HIV-1-positive patients treated with protease inhibitors.

There is accumulating evidence that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) can induce hyperlipidaemia. To evaluate the frequency and type of hyperlipidaemia in PI-treated patients, 98 outpatients were prospectively analysed for their lipoprotein characteristics at the Medizinische Hochschule in Hannover, Germany. Fifty-seven percent of the patients studied presented with hyperlipidaemia. Both hypertrigylceridaemia (type IV and V hyperlipoproteinaemia, 33%) and hypercholesterolaemia (type IIa hyperlipoproteinaemia, 6%) were detectable. The remaining 18% had a type IIb hyperlipoproteinaemia. Increased lipid levels were highly statistically significant compared to a control group of PI-naive HIV-1-infected patients [low-density lipoprotein (LDL) 146 mg/dl (range, 53-274 mg/dl) versus 105 mg/dl (range, 22-188 mg/dl; P=0.0006); very-low-density lipoprotein (VLDL) 35.5 mg/dl (5-253 mg/dl) versus 18 mg/dl (range, 3-94 mg/dl; P=0.0002)]. All PIs used (saquinavir, indinavir, nelfinavir and ritonavir) were associated with this variable form of hyperlipidaemia according to the Fredrickson classification. There was no significant correlation of any determined lipid value with the duration of treatment. A higher frequency of the apolipoprotein E2 allele and E4 allele was observed in the hyperlipidaemic subjects. Patients with excessive hypertriglyceridaemia showed a reduced lipoprotein lipase activity. Lipodystrophy was observed especially in hyperlipidaemic patients and to a lesser extent in normolipidaemic subjects. The frequency of hyperlipidaemic risk factors was surprisingly high in the group studied, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 PI-treated patients. Therefore, PI-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions.

Long-term outcomes of minor troponin elevations in the intensive care unit.

The aim of our study is to determine the short-term and long-term outcomes of intensive care unit (ICU) patients with minor troponin elevations. The retrospective study compared ICU patients with peak troponin elevation less than 0.1 ng/ml to those with only negative tests during their hospital stay. Data were gathered from ICUs at Beth Israel Deaconess Medical Center between 2001 and 2008. A total of 4224 patients (2547 controls and 1677 positives) were analysed. The primary outcome was mortality at one year. Secondary outcomes were 30-day mortality and hospital and ICU lengths of stay. After adjusting for age, sex, Simplified Acute Physiology Score, Sequential Organ Failure Assessment and combined Elixhauser score, we found that minor troponin elevations (peak troponin elevation between 0.01 and 0.09 ng/ml) were associated with a higher one-year mortality (Hazard Ratio 1.22, P <0.001 for binary troponin presence; Hazard Ratio 1.03, P <0.001 for each 0.01 ng/ml troponin increment). This relationship held for the subgroup of seven-day post-discharge survivors (Hazard Ratio 1.26, P <0.001). Minor elevations of troponin also significantly increased the net reclassification index over traditional risk markers for mortality prediction (net reclassification score 0.12, P <0.001). Minor troponin elevation was also associated with 30-day mortality (odds ratio 1.33, P=0.003). Importantly, troponin testing did not increase the adjusted mortality odds (P=0.9). Minor elevations in troponin substantially increase one-year, all-cause mortality in a stepwise fashion; it was also independently associated with 30-day mortality. We propose that minor elevations in troponin should not be regarded as clinically unimportant, but rather be included as a prognostic element if measured. We recommend prospective ICU studies to assess prognostic value of routine troponin determination.