Are insulin and proinsulin independent risk markers for premature coronary artery disease ?

Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin levels with the likelihood of a patient having or not having CAD disappears after adjustment for BMI, suggesting that insulin and proinsulin are not independent risk markers but are primarily dependent on obesity.

Prevalence of viremia in human immunodeficiency virus-infected patients with renal disease.

BACKGROUND: The prevalence of viremia and its relationship to the pathogenesis of nephropathy in human immunodeficiency virus (HIV)-infected patients with renal disease is unknown. To assess the prevalence of plasma viremia in HIV-infected patients with chronic renal disease, we performed a cohort study in two urban university medical centers. METHODS: Samples of blood from 11 HIV-infected patients with renal failure who were treated with hemodialysis were analyzed concurrently with control samples from three non-HIV-positive patients receiving hemodialysis treatment. Samples from four HIV-infected patients with chronic renal insufficiency were evaluated concurrently. Thirty-three HIV-infected patients with serum creatinine levels of less than 132 mumol/L (1.5 mg/dL), and trace or absent dipstick proteinuria served as controls for the population with renal disease. The patients infected with HIV were staged by CD4 cell counts and the presence of opportunistic infections. Blood samples were analyzed for plasma HIV p24 antigenemia by antigen capture enzyme-linked immunosorbent assay. Blood samples were analyzed for the presence of viremia by infection of normal stimulated peripheral blood mononuclear cell cultures with plasma samples and detection of HIV p24 antigen in culture supernatants. RESULTS: Two of the 11 patients treated with hemodialysis had evidence of HIV p24 antigenemia, while seven of the 11 had evidence of plasma viremia. The proportion of hemodialysis patients with detectable antigenemia and viremia was similar to that in patients with chronic renal insufficiency. A significantly greater proportion of HIV-infected patients with renal disease had plasma viremia and antigenemia, compared with HIV-infected patients without renal disease. In logistic regression analysis, race, CD4 cell count (either on a continuous scale or dichotomized at 0.2 x 10(9)/L), and treatment with zidovudine were not significantly associated with the presence of plasma viremia, but patient age and the presence of renal disease were factors independently associated with viremia. CONCLUSIONS: The similar proportions of HIV-infected patients with viremia in groups of patients with chronic renal insufficiency and with renal disease treated with hemodialysis suggest that dialysis treatment does not increase the prevalence of plasma viremia in HIV-infected patients with renal disease. The similar proportions of HIV-infected hemodialyzed patients and patients with chronic renal insufficiency with plasma viremia, and the greater prevalence of viremia in patients with renal disease compared with HIV-infected patients without clinical renal disease suggest that plasma viremia and renal dysfunction are related. Whether this represents a cause and effect relationship is unknown. The greater prevalence of viremia in HIV-infected patients with renal disease has implications for the pathogenesis of HIV-related renal diseases and for caregivers in clinical settings and dialysis units.

Behavioral compliance with dialysis prescription in hemodialysis patients.

The relationship between compliance and outcome is poorly understood, partially because there has been no gold standard for measuring compliance in hemodialysis patients. To investigate interrelationships between psychological, medical, and compliance factors, hemodialysis (HD) patients were studied with the Beck Depression Inventory, and a subset, the Cognitive Depression Index, the Perception of Illness Effects scale, and the Multidimensional Scale of Perceived Social Support. Behavioral compliance was measured in three ways: (1) percent time compliance (signifying "shortening behavior"); (2) percent attendance (signifying "skipping behavior) (3) percent total time compliance, assessing patients' time on dialysis normalized for prescribed time, including all shortenings and absences. Standard compliance indicators (predialysis serum potassium and phosphorus concentrations and interdialytic weight gain) were also analyzed. The patients' mean Beck Depression Inventory was in the range of mild depression. The prevalence of depression was 25.5%. Both depression indices correlated with Perception of Illness Effects scale scores. In general, social support was related to both measures of depression and perception of illness effects. Total time compliance was 95.8 +/- 5.0%. Younger patients were more likely to skip treatments compared with older patients. Time compliance comprised a wide spectrum, with most patients relatively compliant, whereas a small proportion received far less than their prescribed dialysis. Skipping and shortening behaviors did not correlate, suggesting that these constitute two separate types of noncompliant behaviors. Time compliance parameters did not correlate with potassium levels or interdialytic weight gain, but did correlate with phosphorus levels. Interrelationships between behavioral compliance measures and other parameters varied between units and patients of different gender. Finally, behavioral compliance patterns were stable over months in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group.

The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)