Prevalence of metabolic syndrome assessed by IDF and NCEP ATP 111 criteria and determinants of insulin resistance among HIV patients in the Eastern Cape Province of South Africa

AimsTo determine the prevalence of metabolic syndrome (MS) and insulin resistance (IR) and their determinants in HIV on ART, ART naive HIV and HIV negative patients.MethodsCross sectional study. ART experienced HIV, ART naive HIV and HIV negative patients were compared for differences in prevalence of MS and IR. Determinants of MS and IR were assessed.ResultsPrevalence of MS by NCEP criteria was 26.6%, 15.7% and 21.9% (P = 0.3) respectively for HIV on ART, ART naive HIV and HIV negative groups. The MS rates with the IDF definition were 22.7%, 23.2% and 19.3% (P = 0.8) for HIV on ART, ART naive HIV and HIV negative patients respectively. Increased waist circumference by IDF criteria (P = 0.03), visceral to subcutaneous fat ratio (P = 0.049), hypertriglyceredemia (P < 0.001) and high LDL-Cholesterol (P < 0.001) were more common in HIV patients on ART than other groups. IR was found in 12.8%, 3.6% and 2.4% (P = 0.003) of HIV on ART, ART naive HIV and HIV negative groups respectively. Male gender (odds ratio (OR) 11 95% CI 3–48; P < 0.001) was independently associated with MS. HIV patients on ART (OR 6.6 95% CI 1.3–32.3; P = 0.020), IDF definition of MS (OR 3.4 95% CI 1.1–10.7; P = 0.040), NCEP definition of MS (OR 3.2 95% CI 1.01–10.3; P = 0.049) and low HDL-Cholesterol (OR 5.7 95% CI 1.2–27; P = 0.029) were independently associated with IR.ConclusionPrevalence of MS with IDF and NCEP definitions was similar across groups. HIV patients on ART and MS were independently associated with IR while male gender was independently associated with MS.     

Association between alcohol consumption patterns and metabolic syndrome

AimsExamine associations between self-reported alcohol consumption patterns and metabolic syndrome.Materials and methodsSample (N = 7432) included adult (≥20 years) participants in the 1999–2006 National Health and Nutrition Examination Survey.ResultsAbove moderate alcohol consumption (AMAC) was negatively associated with waist circumference among those in the 20–29, 40–49, and 70–79 age groups (β = −6.21, β = −8.34, and β = −6.60, respectively) and moderate alcohol consumption (MAC) was negatively associated with waist circumference among those in the 30–39, 40–49, and 70–79 age groups (β = −4.60, β = −5.69, and β = −2.88, respectively). AMAC was negatively associated with triglycerides among those in the 70–79 and 80+ age groups (β = −23.62 and β = −34.18, respectively) and positively associated with HDL-C levels in all groups (β range 8.96–18.25). MAC was positively associated with HDL-C in the age groups spanning 20–69 years (β range 3.05–5.34) and those over 80 (β = 5.26). AMAC and MAC were negatively associated with fasting glucose levels in the 20–29 and 70–79 age groups (β = −3.38 and −15.61, respectively). MAC was negatively associated with fasting glucose levels among those 70–79 and those over 80 years of age (β = −7.06 and β = −5.00, respectively).ConclusionMAC and AMAC may favorably impact metabolic health.     

Trichomonas vaginalis and associated factors among women living with HIV/AIDS in Amazonas,Brazil

ObjectivesOur goal was to determine the prevalence of Trichomonas vaginalis and its associated factors among women living with HIV attending an AIDS clinic in Manaus, Amazonas, Brazil.MethodsCross-sectional study among women attending an AIDS clinic in Manaus between March and December 2010 for gynecological examination were invited to participate. Enrolled patients answered a face-to-face interview including demographic, behavioral and clinical data. They also underwent a gynecological evaluation and cervical scrape samples were collected for wet mount, Gram stain, culture and cytological analysis. A blood sample was obtained to determine TCD4+ lymphocytes and viral load.ResultsA total of 341 (91.2%) women participated in the study. The prevalence of T. vaginalis was 4.1% (95% CI: 2.0–6.2%). Median age was 32 (interquartile range 27–38) years and median years of schooling was 9.0 (interquartile range 4–11). A total of 165 (53.2%) HIV women were classified as patients with AIDS. In multivariate analyses, squamous intraepithelial lesions in cytology [OR = 2.46 (95% CI: 1.31–4.63, p = 0.005)] and anal sex practice [OR = 3.62 (95% CI: 1.08–12.19, p = 0.037)] were associated with T. vaginalis.ConclusionsThese results highlight that HIV-infected women should be screened for T. vaginalis. The control of this infection may have an impact on preventing reproductive complications among these women.     

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular,but not macrovascular,disease in individuals with and without (pre)diabetes: The Maastricht Study

AimsReactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown.MethodsSubjects with normal glucose metabolism (n = 1796; age: 57.9 ± 8.2 years; 43.3% men), prediabetes (n = 478; age: 61.6 ± 7.6 years; 54.0% men) and T2DM (n = 669; age: 63.0 ± 7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2 h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA_1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO.ResultsFasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥ 30 mg/24 h [fasting: 1.12 (95% CI: 0.97–1.29); post-OGTT: 1.19 (1.01–1.41)], eGFR < 60 mL/min/1.73 m² [fasting: 1.58 (95% CI: 1.38–1.82), post-OGTT: 1.57 (1.34–1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01–2.53), post-OGTT: 1.38 (0.77–2.48)]. No associations with prior CVD were found.ConclusionFasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.     

Residual cardiovascular risk in patients with stable coronary heart disease over the last 16 years (Czech part of the EUROASPIRE I–IV surveys)

IntroductionMany patients with coronary heart disease (CHD) who achieve target low density lipoprotein cholesterol (LDL-C) values still experience vascular events because of a residual vascular risk due to other risk factors, particularly non-LDL-C dyslipidemia, because of non-adherence to non-pharmacological and pharmacological management.Method and aimsWe used simple markers and inexpensive screening tools for metabolic disorders associated with insulin resistance and metabolic syndrome identifying subjects at a high cardiovascular (CV) risk – atherogenic dyslipidemia [triglycerides (TG) ≥2.0 mmol/l and high-density lipoprotein cholesterol (HDL-C) ≤1.0 mmol/l in males and ≤1.2 mmol/l in females], hypertriglyceridemic waist (TG ≥2.0 mmol/l and waist circumference ≥90 cm in males and ≥85 cm in females), atherogenic index of plasma [AIP = log (TG/HDL-C)] and non-HDL-C (non-HDL-C = total cholesterol − HDL-C)]. We focused on the development of these risk factors among patients with established stable CHD over more than the last 16 years.ResultsWe examined 1484 patients, 1152 males (78%) and 332 females (22%) from the Czech parts of EUROASPIRE I–IV (EA I–IV) surveys. In males, TG, HDL-C, and non-HDL-C decreased significantly from EA I to IV (p for trends NS; 0.0001; 0.0001, respectively). In females, there was no change in TG; HDL-C, and non-HDL-C decreased significantly (p for trends NS; 0.03; 0.0001, respectively). Atherogenic dyslipidemia prevalence decreased significantly in both sexes (p for trends 0.004 and 0.0012, respectively). Hypertriglyceridemic waist prevalence showed no change in either sex. There were no significant changes in AIP risk strata in either sex. About 30–40% of males and 24–30% of females had their AIP in the high-risk strata, which tended to increase in males. The prevalence of type 2 diabetes (T2DM) and waist circumference increased significantly from EAI to IV (from 23% to 48%, and from 98 cm to 105 cm, respectively; both p for trend <0.0001). The prevalence of all above mentioned residual vascular risk markers was higher in patients with T2DM and impaired fasting glucose than in those with normal fasting glucose in both sexes.ConclusionDespite the increase in T2DM prevalence and waist circumference from EA I to IV, hypertriglyceridemic waist prevalence showed no change and atherogenic dyslipidemia prevalence decreased significantly in both sexes, because not all obese patients are insulin-resistant and not all patients with glucose metabolism disorders present all characteristics of metabolic syndrome. Simple markers of the atherogenic phenotype, especially AIP, should be used in CV risk assessment.     

Modification of liver fibrosis,glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents

IntroductionThere is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels.Methods445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48).ResultsThe SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3–14.3) kPa at baseline to 6.4 (IQR 4.9–8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1–3.3) to 1.3 (IQR 0.9–2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5–1.7) to 0.3 (IQR 0.2–0.4) and from 6.2 (5.0–7.5) to 4.9 (IQR 3.8–5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172 mg/dL and 101.5 mg/dL to 191 mg/dL and 117.5 mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7 mg/dL at baseline to 127.2 mg/dL at SVR48 (p < 0.001).DiscussionSVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.     

Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes

AimsInterindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FR_GLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR).MethodsFR_GLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FR_GLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90–60 (G2); 59–30 (G3); and < 30–16 (G4) mL/min/1.73 m². Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6 mmol/L); intermediate (6–11 mmol/L); and high (>11 mmol/L).ResultsMedian (interquartile range, IQR) FR_GLU levels were blood glucose-dependent: 99.90% (0.05) for low (n = 106); 99.90% (0.41) for intermediate (n = 288); and 96.36% (12.57) for high (n = 243) blood glucose categories (P < 0.0001). Also, FR_GLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n = 135); microalbuminuria, 96.56% (5.94) (n = 77); macroalbuminuria, 99.12% (5.44) (n = 31; P < 0.001); eGFR G1, 94.13% (16.24) (n = 111); G2, 96.35% (11.94) (n = 72); G3 98.88% (7.59) (n = 46); and G4, 99.11% (2.20) (n = 14; P < 0.01). On multiple regression analyses, FR_GLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group.ConclusionHigh glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels > 11 mmol/L.     

Dysglycemia,brain volume and vascular lesions on MRI in a memory clinic population

ObjectiveIt is unclear, if the association between abnormalities in glucose metabolism (dysglycemia) and impaired cognitive functioning is primarily driven by degenerative or vascular brain damage. We therefore examined the relation between dysglycemia and brain volume and vascular lesions on MRI in a memory clinic population.MethodsThe relations between markers of glycemia (HbA1c and fasting glucose levels) and normalized brain volume, medial temporal lobe atrophy and vascular lesions (white matter hyperintensities, lacunes) were assessed in 274 consecutive patients attending a memory clinic, using linear regression analyses.ResultsClinical diagnoses were subjective complaints (n = 117), mild cognitive impairment (n = 62), Alzheimer's disease (n = 61) and other type of dementia (n = 34). Twenty patients had a history of diabetes. Across the whole study population there was no relation between HbA1c or fasting glucose and the brain MRI measurements, after adjustments for age, sex and diagnostic group. Secondary analyses after stratification by diabetes status, diagnosis and median age (67 years) did not change the results.ConclusionIn this memory clinic population, dysglycemia was not associated with either brain volume or vascular lesions. Apparently, dysglycemia is not associated with a specific class of brain pathology in patients with cognitive complaints.     

Neurocognitive and quality of life study in perinatally HIV-infected young people and their peers. NeuroCoRISpeS study

BackgroundAssessing the role of HIV and non-HIV related factors is essential for a better understanding of the neurocognitive outcomes in perinatally HIV-infected (PHIV+) young people. The aim of our study was to assess cognition and quality of life (QoL) of a PHIV+ cohort of young people and to compare it with a control group.MethodsThirty PHIV+ and 30 HIV(−) healthy young adults matched by age, sex and socioeconomic status completed a protocol that included neurocognitive tests, a psychosocial semi-structured interview and a QoL questionnaire (PedsQL). Neurocognitive domain-specific and domain-general (NPZ-5) Z-scores were calculated. CDC AIDS-defining category C or not C (PHIV+/C, PHIV+/noC) was considered to evaluate differences within the PHIV+ group. Univariate and multivariate analysis were performed.ResultsSixty patients were included; 67% were female; median age (IQR) 19 years (18–21). Regarding PHIV+ young people, 27% showed CDC C category (none encephalopathy), 93% were on ART and 77% had undetectable viral load. No differences regarding occupation were found, although the HIV(−) group repeated less grades (p = 0.028) and had a higher education level (p = 0.021).No differences were found between PHIV+/noC and HIV(−) participants. However, the PHIV+/C group showed poorer performance than PHIV+/noC (NPZ-5, p = 0.037) and HIV(−) subjects (crystallised intelligence, p = 0.025; intelligence quotient, p = 0.016). Higher nadir CD4+ T-cell count was related to better Z-score in memory (p = 0.007) and NPZ-5 (p = 0.025). Earlier and longer exposure to ART resulted in better performance in memory (p = 0.004) and executive functions (p = 0.015), respectively.ConclusionsNo significant differences were found in the neurocognitive profile nor QoL between PHIV+/noC and HIV(−) adolescents; however, PHIV+/C participants obtained lower scores. The use of longer and earlier ART seems to have a beneficial effect.     

Combined therapy of mixed dyslipidemia in patients with high cardiovascular risk and changes in the lipid target values and atherogenic index of plasma

PurposeTo evaluate the safety and efficacy of combined lipid-modifying agents (statin + fenofibrate) on plasma lipid profile including the atherogenic index of plasma (AIP = log[TG/HDL-C]) in patients at high and very high cardiovascular (CV) risk and mixed dyslipidemia.MethodA total of 81 patients (53 males, 28 females; 60 ± 9.8 years) were included. Mixed dyslipidemia was defined as having 2 of the following 3 lipid abnormalities: LDL-cholesterol (C) >2.5 mmol/l, HDL-C <1.0 mmol/l in males and <1.3 mmol/l in females, triglycerides (TG) >1.7 mmol/l. Global CV risk was estimated according to the current European guidelines. Management with fenofibrate (160–267 mg) + atorvastatin (10–20 mg) or simvastatin (20–40 mg) was indicated for 6 months. Males and females were stratified according to the AIP risk categories: AIP <0.11 (low risk), AIP >0.21 (high risk).ResultsAbout 3/4 of high or very high CV risk patients with mixed dyslipidemia (n = 81) suffer from impaired glucose metabolism (44% had type 2 diabetes, 30% had impaired fasting glucose). Six-months combined therapy reduced LDL-C (by 29%) and TG (by 40%) significantly, but the increase of HDL-C (by 3%) was not significant. There were 47% of males and 57% of females who achieved the target LDL-C levels (<25 or <1.8 mmol/l) and 14% of males and 37% of females who received non-HDL-C <2.6 mmol/l at the end of the study. Also AIP was decreased significantly in majority of the patients (high risk AIP decreased from 87% to 47% of males and from 71% to 25% of females).ConclusionThe combined lipid-modifying therapy led to a significant improvement of the plasma lipid profile, particularly of LDL-C, TG, non-HDL-C and AIP. Atherogenic index of plasma seems to be a very useful marker of CV risk in high and very high CV risk patients with mixed dyslipidemia and glucose abnormalities. More intensive management is needed in those patients.     

Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women

ObjectivesThe endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors.MethodsBaseline serum MMP-9 was measured in incident MI (n = 368) and stroke (n = 299) cases and two controls per case, ‘nested’ in prospective studies of 4252 men and 4286 women aged 60–79 years, sampled from General Practices in Britain in 1998–2000, with 7-year follow-up for fatal and non-fatal MI and stroke.ResultsGeometric mean MMP-9 was 528 ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in controls, p = 0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p = 0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522 ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p = 0.045; however adjustments similarly attenuated the associations.ConclusionsWhile serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.     

Burns in older people. Epidemiology,surgical management and outcome in a university hospital referral burn unit, 1994–2004

BackgroundBurn injuries in older people are becoming more frequent as the population ages. Burn management in older people remains controversial.ObjectivesThe aim of this retrospective study was to describe the epidemiologic profile of older people in our university hospital burn unit, to report their surgical management, and to identify factors associated with the risk of death.MethodsWe included all patients aged 70 years and over who were admitted between January 1994 and December 2004.ResultsThere were 84 men (43%) and 111 women (57%), with a median age of 79.0 (IQR 75.0–85.0) and a median total body surface area (TBSA)% of 12.3% (IQR 5.0–23.5). Most injuries occurred at home (85.1%). Most patients had pre-existing co-morbidities (78.5%). Conservative treatment was performed in 74 (37.9%) patients, while 121 (62.1%) patients underwent surgery. Early excision was performed in 17 (14.0%) patients, who were both significantly younger (P = 0.02) and more severely burned (P = 0.004). Forty-seven (24.1%) patients died in hospital. Factors associated with death were TBSA% (P < 10^?4), full-thickness TBSA% (P = 0.0016), inhalation injury (P = 0.02) and conservative treatment (P < 10^?4). The overall median length of hospital stay was 29.0 days (IQR 11.0–54.0, range 0.0–375.0). One-third of the 148 discharged patients were able to return home alone.ConclusionBurn prevention in older people, by adapting their daily living environment, is a major public health issue. Treatment modalities, i.e. conservative versus surgical, must be evaluated and planned specifically for each patient, depending on overall health status, which should ideally be assessed in collaboration with a geriatrician.     

Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3 years in the RISC study: Interaction with weight gain

AimsThe importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little studied.MethodsIn an analysis of data from the European RISC study, sedentary time and time spent in activity of moderate or vigorous intensity were assessed by accelerometry at baseline in 313 men and 414 women, aged 30–60 years, with insulin sensitivity as measured by euglycaemic–hyperinsulinaemic clamp. Three years later, cardiometabolic risk factors (anthropometry, glucose, insulin, lipids) were available for 549 participants.ResultsIn cross-sectional analyses using baseline data, after adjusting for age, gender, recruitment centre and time spent in activity of moderate or vigorous intensity, significant unfavourable associations were observed between higher sedentary time with body weight, HDL cholesterol, triglycerides, clamp-measured insulin sensitivity and insulin secretion (all P_trend < 0.002). Sedentary time remained significantly associated with insulin secretion after adjusting for insulin sensitivity (P_trend = 0.02). In longitudinal analyses, higher baseline sedentary time was associated with 3-year increases in fasting glucose, fasting insulin and the HOMA insulin-resistance index score for the 50% of the study population who increased their BMI by at least 0.3 kg/m² (all P_trend < 0.01); these relationships remained significant after adjusting for time spent in activity of moderate or vigorous intensity. The 3-year increase in insulin secretion was lower in those spending more time doing activity of moderate or vigorous intensity (P_trend = 0.03).ConclusionThese prospective data suggest that less sedentary behaviour may partly counteract some of the negative effects of increasing body weight on glucose–insulin homoeostasis.     

Efficacy of lifestyle interventions in the reversion to normoglycemia in Korean prediabetics: One-year results from a randomised controlled trial

AimThis study aimed to determine the efficacy of personalized lifestyle interventions on the reversion of a prediabetic state to normoglycemia compared with regular blood glucose testing alone in prediabetes.MethodsA randomized, multicenter trial was conducted in prediabetes aged 30–70 with fasting blood glucose level of 5.6–6.9 mmol/L (100–125 mg/dL) and/or HbA1c level of 39–46 mmol/mol (5.7–6.4%) recruited from health checkups at 16 health-promotion centers in Korea. The 799 recruited individuals were randomized to either the personalized lifestyle intervention group (LIG) or the control group (CG) by a computer generated random number list prepared by an independent statistician. The CG was provided with fasting blood glucose and HbA1c tests alone every 3 months during the first year. The LIG was provided not only blood glucose test but five sessions of personalized lifestyle counseling by nutritionists every 3 months during the first year aimed at improving the diet, alcohol and exercise behaviors. Data from lifestyle assesments and laboratory measurements were analyzed at 1-year after baseline. The primary outcome was the reversion rate from prediabetes to normoglycemia. Additional outcome include the effect of the lifestyle intervention program on lifestyle changes in the LIG to support primary outcome.ResultsThe 799 participants randomly allocated to the LIG (n = 398) or the CG (n = 401). For the analyses of outcomes, 629 participants (313 men and 316 women; mean age, 53.7 ± 9.4 years; mean body mass index (BMI), 24.7 kg/m²) were included: 325 in the LIG; 304 in the CG. Diet (7.03, 95% CI = 4.56–10.86, P < 0.001), alcohol (2.24, 95% CI = 1.48–3.41, P < 0.001), and exercise behaviors (1.85, 95% CI = 1.31–2.63, P < 0.001) were improved relative to baseline by the personalized lifestyle intervention in the LIG after adjusting age, sex, and family history of diabetes. In terms of main outcome, the cumulative incidence of reversion from prediabetes to normoglycemia at the first year was 37.9% (123/325) [95% CI = 32.6–43.1%] in the LIG and 29.6% (90/304) (95% CI = 24.5–34.7%) in the CG. After adjustment for age, sex, family history of diabetes, BMI, blood pressure, and lipids, the hazard ratio for reverting to normoglycemia remained significantly higher in the LIG (1.40, 95% CI = 1.06–1.83, P = 0.017) than in the CG.ConclusionPersonalized lifestyle intervention could be more effective compared with regular blood glucose testing alone in the reversion of a prediabetic state to normoglycemia in Korean prediabetics. This finding suggests that diabetes prevention care would be benefited by incorporating personalized lifestyle counseling.This study was registered at cris.nih.go.kr (KCT0001580).     

Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort

ObjectiveTo study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort.MethodsOGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3 years apart.ResultsThe OGTT-glucose curve had the same baseline shape after 3 years in 540 people (59%; κ = 0.115; p < 0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3 years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084–2.116; p = 0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310–0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228–1.066; P = 0.043) after 3 years. Increased risks of IFG (OR 1.509; 95% CI 1.008–2.260; p = 0.05) and IGT (OR 1.947; 95% CI 1.085–3.494; p = 0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT = 3.085; 95% CI 1.377–6.912; p = 0.001).ConclusionAfter 3 years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism.     

Hyperhomocysteinaemia and poor vitamin B status in chronic obstructive pulmonary disease

Background and aimsPatients with chronic obstructive pulmonary disease (COPD) are at increased atherothrombotic risk. Preliminary findings have suggested that COPD patients may have increased plasma total homocysteine (tHcy), a cardiovascular risk factor often caused by a poor B vitamin status, but plasma levels of such vitamins were not measured. The aim of this study was to investigate hyperhomocysteinaemia in COPD and to determine whether it may be secondary to poor plasma concentrations of B vitamins.Methods and resultsWe performed a case–control, cross-sectional study of 42 patients with COPD and 29 control subjects. Folate, vitamin B12, vitamin B6, tHcy, renal function, C-reactive protein, blood gases and lipids were measured in patients and controls. COPD patients had higher plasma tHcy (median: 13.9 μmol/l, interquantile range [IQR]: 12.1–18.5 versus 11.5, IQR: 10.1–14, p = 0.002) and lower circulating folate (median: 2.5 ng/ml, IQR: 1.2–3.3 versus 2.8, IQR: 2.1–4 of controls, p = 0.03) than controls had. Compared to the control group, COPD was associated with higher tHcy concentrations also after adjusting for smoking, heart failure, renal function and C-reactive protein with logistic regression analysis (OR 1.36, 95% CI 1.06–1.72, p = 0.01). In the COPD group, low levels of folate (β = −0.27, p = 0.02) and vitamin B12 (β = −0.24, p = 0.04), and hypertriglyceridaemia (β = 0.580, p < 0.0001) were independent predictors of the presence of high tHcy concentrations in a multiple linear regression model (adjusted R² = 0.522).ConclusionCOPD patients have a poor B vitamin status and, as a consequence, increased tHcy. These abnormalities may contribute to the COPD-related atherothrombotic risk.     

Peri-aortic fat,cardiovascular disease risk factors,and aortic calcification: The Framingham Heart Study

ObjectivePerivascular fat through the secretion of paracrine and pro-inflammatory mediators may play a role in obesity-mediated vascular disease. We sought to examine associations between adipose tissue depots immediately surrounding the thoracic aorta, metabolic risk factors, and vascular calcification.MethodsIn participants free of cardiovascular disease (CVD) from the Framingham Heart Study Offspring cohort who underwent computed tomography (n = 1067, mean age 59 years, 56.1% women), thoracic peri-aortic fat depots were quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and abdominal aorta were also measured.ResultsPeri-aortic fat depots were correlated with body mass index, waist circumference (WC), VAT (all p < 0.0001), hypertension (p = 0.007), low HDL (p < 0.0001), serum triglycerides (p < 0.0001), impaired fasting glucose (p = 0.005), and diabetes (p = 0.02). These associations generally remained significant after adjustment for BMI and WC (all p-values < 0.05), but not after VAT adjustment. Thoracic aortic fat was associated with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01–1.71, p = 0.04), but was not significant after adjustment for CVD risk factors (OR 1.16, 95% CI 0.88–1.51, p = 0.30). Thoracic aortic fat, however, was associated with abdominal aortic calcification (OR 1.48, 95% CI 1.11–1.98, p = 0.008) and coronary artery calcification (OR 1.47, 95% CI 1.09–1.98, p = 0.001) even in models including CVD risk factors and VAT.ConclusionsThoracic peri-aortic fat is associated with measures of adiposity, metabolic risk factors, and coronary and abdominal aortic calcification.     

Long-term functional outcome after ileal pouch anal anastomosis in 191 patients with ulcerative colitis

BackgroundA long-lasting good functional outcome of the pelvic pouch and a subsequent satisfying quality of life (QoL) are mandatory. Long-term functional outcome and QoL in a single-center cohort were assessed.Patients and methodsA questionnaire was sent to all patients with an IPAA for UC, operated between 1990 and 2010 in our department. Pouch function was assessed using the Öresland Score (OS) and the ‘Pouch Functional Score’ (PFS). QoL was assessed using a Visual Analogue Score (VAS).Results250 patients (42% females) with a median age at surgery of 38 years (interquartile range (IQR): 29–48 years) underwent restorative proctocolectomy. Median follow‐up was 11 years (IQR: 6–17 years). Response rate was 81% (n = 191). Overall pouch function was satisfactory with a median OS of 6/15 (IQR: 4–8) and a median PFS of 6/30 (IQR: 3–11). 24-hour bowel movement is limited to 8 times in 68% of patients (n = 129), while 55 patients (29%) had less than 6 bowel movements. 12 patients (6.5%) were regularly incontinent for stools, while 154 patients (82%) reported a good fecal continence. Fecal incontinence during nighttime was more common (n = 72, 39%). Pouch function had little impact on social activity (4/10; IQR: 2–6) and on professional activity (3/10; IQR: 1–6). 172 patients (90%) reported to experience an overall better health condition since their operation. The OS and the PFS correlated well (Pearson's correlation coefficient = 0.83). Overall pouch function was stable over time.ConclusionMajority of patients report a good pouch function on the long-term with limited impact on QoL.     

The effect of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes: Results from a prospective pharmacological study

IntroductionThiopurine therapy is often discontinued in inflammatory bowel disease (IBD) patients. The xanthine oxidase (XO) inhibitor allopurinol has previously shown to enhance thiopurine efficacy and to prevent adverse reactions, the mechanism of this beneficial interaction is not completely clarified. The aim of this study is to observe possible effects of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes.MethodsA prospective study of IBD patients failing thiopurine therapy due to a skewed thiopurine metabolism was performed. Patients were treated with allopurinol and azathioprine or mercaptopurine. Xanthine oxidase, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and thiopurine S-methyl transferase (TPMT) activities, and thiopurine metabolites concentrations were measured during thiopurine monotherapy, and after 4 and 12 weeks of combination therapy.ResultsOf fifteen IBD patients, XO activity decreased from 0.18 (IQR 0.08–0.3) during thiopurine monotherapy to 0.14 (IQR 0.06–0.2) and 0.11 (IQR 0.06–0.2; p = 0.008) mU/hour/ml at 4 and 12 weeks, respectively. HGPRT activity increased from 150 (IQR 114–176) to 180 (IQR 135–213) and 204 nmol/(h × mg protein) (IQR 173–213; p = 0.013). TPMT activity seemed not to be affected. 6-Thioguanine nucleotide concentrations increased from 138 (IQR 119–188) to 235 (223–304) and to 265 pmol/8 × 10^8 (IQR 188–344), whereas 6-methyl mercaptopurine ribonucleotides concentrations decreased from 13230 (IQR 7130–17420) to 690 (IQR 378–1325) and 540 (IQR 240–790) pmol/8 × 10^8 at 4 and 12 weeks of combination therapy (both p < 0.001).ConclusionAllopurinol and thiopurine combination-therapy seems to increase HGPRT and decrease XO activity in IBD patients, which at least in part may explain the observed changes in thiopurine metabolite concentrations.     

Disease severity in familial cases of IBD

BackgroundPhenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence.AimTo know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases.Methods5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case.ResultsIn UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25–44] vs 37 years [IQR 27–49]; p < 0.0001); (CD: 27 years [IQR 21–35] vs 29 years [IQR 22–40]; p < 0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p = 0.04); (CD: 30.1% vs 23.6%; p < 0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p = 0.0001), penetrating behavior (21% vs 17.6%; p = 0.01) and perianal disease (32% vs 27.1%; p = 0.003). Differences are not influenced by degree of consanguinity.ConclusionWhen a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.