Prevalence of obesity and disturbances in glucose homeostasis in HIV-infected subjects and general population - missed diagnoses of diabetes?

OBJECTIVES: Comparative data on glucose disorders using fasting blood samples between people living with HIV (PLWH) and the general population are lacking. The objective of this study was to compare the prevalence and risk factors of obesity and disturbances in glucose homeostasis between PLWH treated with modern antiretroviral therapy and the general population. METHODS: Adjusted prevalence of obesity, features of insulin resistance (triglyceride:high-density lipoprotein cholesterol ratio and alanine aminotransferase), impaired fasting glucose (IFG), diabetes mellitus (DM) and combined dysglycaemia (presence of IFG or DM) were determined using fasting blood samples among 1041 PLWH and 7047 subjects representing the general population. RESULTS: People living with HIV had a lower prevalence of obesity [18.2%, 95% confidence interval (CI): 15.1-21.2 vs. 23.9%, 95% CI: 22.4-25.4], but a higher prevalence of insulin resistance and IFG (20.0%, 95% CI: 16.6-23.4 vs. 9.8%, 95% CI: 8.7-10.8) than the general population. Fasting glucose concentration was higher, but glycated haemoglobin (HbA1c) was lower, among PLWH. Prevalence of dysglycaemia for a given body mass index (BMI) was higher in PLWH than in the general population. The prevalence of DM did not differ between PLWH (13.2%, 95% CI: 10.2-15.9) and the general population (14.5%, 95% CI: 13.6-15.4). CONCLUSIONS: The prevalence of obesity was lower, but the risk of dysglycaemia for a given BMI was significantly higher, among PLWH, highlighting the importance of prevention and treatment of obesity among HIV-infected subjects. Regardless of the increased prevalence of insulin resistance and IFG, DM was surprisingly not more common among PLWH, raising concern about the under-diagnosis of DM, possibly due to low sensitivity of HbA1c in this patient population.

Comprehensive nationwide analysis of mother-to-child HIV transmission in Finland from 1983 to 2013.

HIV-positive children are still born in Europe despite low mother-to-child transmission (MTCT) rates. We aimed to clarify the remaining barriers to the prevention of MTCT. By combining the national registers, we identified all women living with HIV delivering at least one child during 1983-2013. Of the 212 women delivering after HIV diagnosis, 46% were diagnosed during the pregnancy. In multivariate analysis, age >30 years (P = 0.001), sexual transmission (P = 0.012), living outside of the metropolitan area (P = 0.001) and Eastern European origin (P = 0.043) were risk factors for missed diagnosis before pregnancy. The proportion of immigrants increased from 18% before 1999 to 75% during 2011-2013 (P < 0.001). They were diagnosed during the pregnancy equally to natives and achieved similar, good treatment results. No MTCT occurred when the mother was diagnosed before the delivery. In addition, 12 women had delivered in 2 years prior their HIV diagnosis, most before implementation of the national screening of pregnant women. Three of these children were infected, the last one in 2000. Our data demonstrate that complete elimination of MTCT is feasible in a high-income, low-prevalence country. This requires ongoing universal screening in early pregnancy and easy access to antiretroviral therapy to all HIV-positive people.

Hyperglycemic Episodes Are Associated With Postoperative Infections After Cardiac Surgery.

BACKGROUND AND AIMS: To describe the incidence of and risk factors for postoperative infections and the correlation between postoperative hyperglycemia despite tight blood glucose control with infectious and other complications after contemporary cardiac surgery. MATERIAL AND METHODS: The study comprised 1356 consecutive adult patients who underwent cardiac surgery between January 2013 and December 2014 and were followed up for 6 months. Patients surviving the first 2 days were included in the analysis. Preoperative demographic information, medical history, procedural details, and the postoperative course were recorded. The target range for blood glucose levels was 4-7 mmol/L and repeated arterial blood samples were obtained during the intensive care unit stay. The associations of blood glucose levels during the first postoperative day and the occurrence of postoperative infections and other significant complications were analyzed. RESULTS: Of the study cohort, 9.8% developed infectious complications which were classified as major surgical site infections in 2.2%, minor surgical site infections in 1.1%, lung infections in 2.0%, unclear fever or bacteremia in 0.3%, cannula or catheter related in 2.6%, multiple in 1.5%, and other in 0.2%. The incidence of deep sternal wound infection was 2.0%. Repeated hyperglycemia occurred in 39.7% of patients and was associated with increased rates of postoperative infections, 12.1% versus 8.2%, p = 0.019; stroke, 4.9% versus 1.5%, p < 0.001; and mortality, 6.1% versus 2.1%, p < 0.001, when compared to patients with single or no hyperglycemia. CONCLUSION: Every 10th patient develops infectious complications after cardiac surgery. Repeated hyperglycemia is associated with increased rates of infectious complications, stroke, and mortality.

Gene expression and immunohistochemistry in adipose tissue of HIV type 1-infected patients with nucleoside analogue reverse-transcriptase inhibitor-associated lipoatrophy.

BACKGROUND: Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms. METHODS: Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed. RESULTS: mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group. CONCLUSIONS: Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.

European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV.

BACKGROUND: Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). SUMMARY OF GUIDELINES: All HIV-infected persons should be screened at regular intervals for a history of metabolic disease, dyslipidaemia, diabetes mellitus, hypertension and alteration of body composition; cardiovascular risk and renal function should also be assessed. Efforts to prevent cardiovascular disease will vary in intensity depending on an individual's absolute risk of ischaemic heart disease and should be comprehensive in nature. Lifestyle interventions should focus on counselling to stop smoking, modify diet and take regular exercise. A healthy diet, exercise and maintaining normal body weight tend to reduce dyslipidaemia; if not effective, a change of ART should be considered, followed by use of lipid-lowering medication in high-risk patients. A pre-emptive switch from thymidine analogues is recommended to reduce the risk of development or progression of lipoatrophy. Intra-abdominal fat accumulation is best managed by exercise and diet. Prevention and management of type 2 diabetes mellitus and hypertension follow guidelines used in the general population. When using medical interventions to prevent and/or treat metabolic disease(s), impairment of the efficacy of ART should be avoided by considering the possibility of pharmacokinetic interactions and compromised adherence. Specialists in HIV and specialists in metabolic diseases should consult each other, in particular in difficult-to-treat cases. CONCLUSION: Multiple and relatively simple approaches exist to prevent metabolic diseases in HIV-infected persons; priority should be given to patients at high risk of contracting these diseases.

Increased expression of the macrophage markers and of 11beta-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity.

OBJECTIVE: To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-alpha), HSD11B1 (gene encoding 11beta-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects. DESIGN: Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity. SUBJECTS: Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2+/-1.0 kg/m(2)) and 10 healthy obese/overweight (33.1+/-1.7 kg/m(2)) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1+/-0.7 kg/m(2)) and seven healthy obese/overweight (36.9+/-2.2 kg/m(2)) women. MEASUREMENTS: Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR. RESULTS: In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects. CONCLUSION: Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.

In the lipodystrophy associated with highly active antiretroviral therapy, pseudo-Cushing's syndrome is associated with increased regeneration of cortisol by 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue.

AIMS/HYPOTHESIS: Highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV) is associated with a poorly understood lipodystrophic and hypertriglyceridaemic syndrome, which resembles Cushing's syndrome, but in which plasma cortisol is not elevated. We tested the hypothesis that this HAART-associated lipodystrophy is explained by increased local regeneration of cortisol from inactive cortisone within adipose tissue, catalysed by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). METHODS: In this cross-sectional study, a previously described cohort of 30 HIV-infected patients with lipodystrophy were compared with 13 HIV-infected patients without lipodystrophy. Intra-abdominal and subcutaneous adipose tissue were quantified using magnetic resonance imaging. Gene expression in subcutaneous fat was measured using real-time PCR. Urine cortisol and its metabolites were analysed by gas chromatography/mass spectrometry. RESULTS: Patients with lipodystrophy had significantly higher 11beta-HSD1 mRNA concentrations (relative to beta2-microglobulin mRNA) in subcutaneous adipose tissue than non-lipodystrophic patients (0.29+/-0.20 vs 0.09+/-0.07, p=0.0004) and higher ratios of urinary cortisol : cortisone metabolites. Adipose tissue 11beta-HSD1 mRNA correlated with multiple features of insulin resistance and with mRNA concentrations for glucocorticoid receptor and angiotensinogen. CONCLUSIONS/INTERPRETATION: In adipose tissue of patients with HAART-associated lipodystrophy, 11beta-HSD1 mRNA is increased and its concentration is correlated with features of insulin resistance. We suggest that increased adipose tissue 11beta-HSD1 may explain the pseudo-Cushing's features in patients with HAART-associated lipodystrophy, and is a potential therapeutic target.

Etiology of central nervous system infections in the Philippines and the role of serum C-reactive protein in excluding acute bacterial meningitis.

OBJECTIVES: The value of measurements of serum C-reactive protein (CRP) in differentiating central nervous system (CNS) infections of varying etiologies in the Philippines was investigated. METHODS: A wide array of bacteriologic and virologic methods as well as computed tomography, typical clinical presentation, and autopsy were used for etiologic diagnosis. RESULTS: Among 103 patients with CNS infection, etiology was identified in 60 (58%) cases. Bacteria were found in 19 (including 7 Streptococcus pneumoniae, 5 Haemophilus influenzae, 3 Neisseria meningitidis), tuberculosis in 4, viruses in 38 (including 20 coxsackievirus, 8 measles, 4 adenovirus, and 4 poliovirus infections), and brain abscess in 3 patients. C-reactive protein was elevated on admission in all 18 cases of bacterial meningitis tested, exceeding 50 mg/L in 17 (94%), and was not affected by prior antibacterial treatment. The mean CRP was significantly higher in the bacterial group than in the viral group (207 +/- 111 mg/L vs. 39 +/- 34 mg/L; P < 0.001). In the viral group one third had CRP above 50 mg/L. In patients with tuberculous meningitis, brain abscess, or cryptococcal meningitis, CRP was moderately to highly elevated. CONCLUSIONS: In the presence of a normal CRP concentration (below 10 mg/mL) acute bacterial meningitis is excluded even in a developing country setting and antimicrobial therapy is not warranted.

Hepatitis A outbreak amongst intravenous amphetamine abusers in Finland.

This article describes a widespread outbreak of hepatitis A virus (HAV) infection amongst drug abusers in Finland. Although attempts to demonstrate the virus in amphetamines failed, the infection was assumed to be linked to intravenous use of the drug. The unusual mode of transmission prompted us to analyse possible atypical clinical features as well as the spread of the virus to the general population, nowadays practically without protective immunity. Serologically verified cases that occurred in Helsinki were interviewed, their hospital records were analysed and their contacts were serology tested. Amphetamine lots, as well as faecal samples from patients, were examined with RT-PCR. Detailed information was obtained from 238 subjects, among whom 131 admitted drug abuse and 67 cases were classified as secondary cases. Phylogenetic analysis of virus strains from HAV-infected cases suggested a common origin, and epidemiological observations linked it with particular lots of amphetamine. Three cases died, and 3 presented with severe clinical disease. Icterus was more common among i.v. drug abusers than others. Infection with hepatitis A virus was probably related to the faecal contamination of amphetamine associated with the transportation of the drugs in the gastrointestinal tract.