Systemic markers of microvascular disease and bone mineral density in older adults

Summary

Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders.

Introduction

Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together.

Methods

BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors.

Results

AWMD was associated with lower hip, spine, and total body BMD in women (β ?3.08 to ?4.53; p < 0.01 for all) and lower hip and total body BMD in men (β ?2.90 to ?4.24; p = 0.01–0.03). Albuminuria was associated with lower hip (β ?3.37; p = .05) and total body (β ?3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women.

Conclusion

AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies.

     

Management of Graft Duodenal Leak in Simultaneous Pancreas Kidney Transplant—a Case Report from India and Review of Literature

Pancreatic transplantation is currently the only effective cure for Type 1 diabetes mellitus. It allows long-term glycemic control without exogenous insulin and amelioration of secondary diabetic complications. In India, pancreas transplant has not yet established with only a single successful transplant reported so far in the literature. We report a 24-year-old Type 1 diabetic patient with renal failure who underwent a simultaneous pancreas kidney transplant. On postoperative day 15, he had leak from the graft duodenal stump for which a tube duodenostomy and proximal diversion enterostomy was done. He had a high output pancreatic fistula following the procedure which was managed conservatively. The tube duodenostomy was removed at three and half months and enterostomy closure with restoration of bowel continuity was done at 6 months. After a follow up of 7 months, patient is doing well with a serum creatinine of 0.8 mg/dl and normal blood sugars, not requiring any exogenous insulin or oral hypoglycemic drugs. Managing patients with graft duodenal complications after pancreas transplant is challenging. Tube duodenostomy is a safe option in management of duodenal leak, although can lead to a persistent pancreatic fistula. A proximal diversion enterostomy allows early oral feeding and avoids the cost as well as the long term complications associated with parenteral nutrition.     

Gut microbiota differs a decade after bariatric surgery relative to a nonsurgical comparison group

BackgroundFew studies have assessed differences in the gut microbiota composition after bariatric surgery in the long term or whether differences are correlated with remission of type 2 diabetes.ObjectivesThis observational study assessed differences in the gut microbiota between individuals at up to 13 years after surgery and a comparison group of individuals with severe obesity. The relationship between type 2 diabetes remission and the gut microbiota was also assessed.SettingUniversity.MethodsStool samples were collected from individuals completing bariatric surgery (surgery group; n = 16) and individuals with severe obesity that did not receive surgery (nonsurgery group; n = 19) as part of the 12-year follow-up in the Utah Obesity Study. Metabolic health data were collected at baseline and the follow-up examination. The gut microbiota was quantified by sequencing the V4 region of the 16 S rRNA gene. Significant differences in microbiota composition with surgery and other covariates were determined by Unifrac distance analysis and permutational multivariate analysis of variance. Significant differences in the relative abundance of individual bacterial taxa were assessed using analysis of composition of microbiomes software.ResultsThe surgery group had higher relative abundances of Verrucomicrobiaceae (5.7 ± 1.3% versus 1.1 ± .3%) and Streptococcaceae (6.3 ± 1.0% versus 3.2 ± .8%), but lower relative abundances of Bacteroidaceae (8.8 ± 1.8% versus 18.6 ± 2.3%) 10.6 years after surgery. In a small subset of 8 individuals, a higher relative abundance of Akkermansia muciniphila was correlated with type 2 diabetes remission.ConclusionsDifferences in the gut microbiota are evident a decade after bariatric surgery compared with individuals with severe obesity that did not undergo surgery. The observed long-term differences are consistent with previous findings.     

Mid-Adulthood Risk Factor Profiles for CKD

Early identification of CKD risk factors may allow risk factor modification and prevention of CKD progression. We investigated the hypothesis that risk factors are present ≥30 years before the diagnosis of CKD in a case-control study using data from the Framingham Offspring Study. Patients with incident CKD (eGFR≤60 ml/min per 1.73 m²) at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to patients without CKD at baseline (examination 5). CKD risk factors were measured at each examination cycle. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls. During follow-up, 441 new cases of CKD were identified and matched to 882 controls (mean age 69.2 years, 52.4% women). Those who ultimately developed CKD were more likely to have hypertension (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.23 to 2.51), obesity (OR, 1.71; 95% CI, 1.14 to 2.59), and higher triglyceride levels (OR, 1.43; 95% CI, 1.12 to 1.83) 30 years before CKD diagnosis, and were more likely to have hypertension (OR, 1.38; 95% CI, 1.07 to 1.79), higher triglyceride levels (OR, 1.35; 95% CI, 1.11 to 1.64), lower HDL_c (OR, 0.89; 95% CI, 0.81 to 0.97), and diabetes (OR, 2.90; 95% CI, 1.59 to 5.29) 20 years before CKD diagnosis. These findings demonstrate that risk factors for CKD are identifiable ≥30 years before diagnosis and suggest the importance of early risk factor identification in patients at risk for CKD.     

Diuretic Use and Risk of Vertebral Fracture in Women

Background

Vertebral fracture is the most common type of osteoporotic fracture. While thiazide diuretics, which are commonly prescribed for the treatment of hypertension, decrease calciuria, they may also induce hyponatremia, which has been associated with increased vertebral fracture risk. Loop diuretics increase calciuria, which would reduce bone mineral density and increase vertebral fracture risk, but they rarely cause hyponatremia. Recent studies on diuretics and fractures did not include or specifically examine vertebral fracture. The few studies of diuretics and vertebral fracture have been limited by cases defined by self-report or administrative data, relatively small number of cases, study design that was not prospective, and lack of long-term follow-up with updated information on diuretic use.

Methods

We conducted a prospective cohort study of thiazide diuretic use, loop diuretic use, and risk of incident clinical vertebral fracture in 55,780 women, 55-82 years of age, participating in the Nurses' Health Study, without a prior history of any fracture. Diuretic use was assessed by questionnaire every 4 years. Self-reported vertebral fracture was confirmed by medical record review. Cox proportional-hazards models were used to simultaneously adjust for potential confounders.

Results

Our analysis included 420 incident vertebral fracture cases documented between 2002 and 2012. The multivariate-adjusted relative risk of clinical vertebral fracture for women taking thiazides compared with women not taking thiazides was 1.47 (95% confidence interval, 1.18-1.85). The multivariate adjusted relative risk of vertebral fracture for women taking loop diuretics compared with women not taking loop diuretics was 1.59 (95% confidence interval, 1.12-2.25).

Conclusion

Thiazide diuretics and loop diuretics are each independently associated with increased risk of vertebral fracture in women.     

Risk factors differ between recurrent and incident preeclampsia: a hospital-based cohort study

PurposeTo examine whether risk factors, including prepregnancy body mass index (BMI), differ between recurrent and incident preeclampsia.MethodsData included electronic medical records of nulliparas (n = 26,613) delivering 2 times or more in Utah (2002–2010). Modified Poisson regression models were used to examine (1) adjusted relative risks (RR) of preeclampsia and 95% confidence intervals (CI) associated with prepregnancy BMI; (2) maternal risk factor differences between incident and recurrent preeclampsia among primiparous women.ResultsIn the first pregnancy, compared with normal weight women (BMI: 18.5–24.9), preeclampsia risks for overweight (BMI: 25–29.9), obese class I (BMI: 30–34.9), and obese class II/III (BMI: ≥35) women were 1.82 (95% CI = 1.60–2.06), 2.10 (95% CI = 1.76–2.50), and 2.84 (95% CI = 2.32–3.47), respectively, whereas second pregnancy–incident preeclampsia risks were 1.66 (95% CI = 1.27–2.16), 2.31 (95% CI = 1.67–3.20), and 4.29 (95% CI = 3.16–5.82), respectively. Recurrent preeclampsia risks associated with BMI were highest among obese class I women (RR = 1.60; 95% CI = 1.06–2.42) without increasing in a dose-response manner. Nonwhite women had higher recurrence risk than white women (RR = 1.70; 95% CI = 1.16–2.50), whereas second pregnancy–incident preeclampsia risk did not differ by race.ConclusionPrepregnancy BMI appeared to have stronger associations with risk of incident preeclampsia either in the first or second pregnancy, than with recurrence risk. Nonwhite women had higher recurrence risk.     

Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited

Hyperinsulinemia and insulin resistance were proposed more than 30 years ago to be important contributors to elevated blood pressure (BP) associated with obesity and the metabolic syndrome, also called syndrome X. Support for this concept initially came from clinical and population studies showing correlations among hyperinsulinemia, insulin resistance, and elevated BP in individuals with metabolic syndrome. Short-term studies in experimental animals and in humans provided additional evidence that hyperinsulinemia may evoke increases in sympathetic nervous system (SNS) activity and renal sodium retention that, if sustained, could increase BP. Although insulin infusions may increase SNS activity and modestly raise BP in rodents, chronic insulin administration does not significantly increase BP in lean or obese insulin-resistant rabbits, dogs, horses, or humans. Multiple studies in humans and experimental animals have also shown that severe insulin resistance and hyperinsulinemia may occur in the absence of elevated BP. These observations question whether insulin resistance and hyperinsulinemia are major factors linking obesity/metabolic syndrome with hypertension. Other mechanisms, such as physical compression of the kidneys, activation of the renin-angiotensin-aldosterone system, hyperleptinemia, stimulation of the brain melanocortin system, and SNS activation, appear to play a more critical role in initiating hypertension in obese subjects with metabolic syndrome. However, the metabolic effects of insulin resistance, including hyperglycemia and dyslipidemia, appear to interact synergistically with increased BP to cause vascular and kidney injury that can exacerbate the hypertension and associated injury to the kidneys and cardiovascular system.     

Antiatherogenic properties of high-density lipoproteins from arterial plasma are attenuated as compared to their counterparts of venous origin

Background and aimsHigh-density lipoprotein (HDL) particles play atheroprotective roles by their ability to efflux cholesterol from foam cells and to protect low-density lipoproteins (LDLs) from oxidative damage in the arterial intima. We hypothesized that antioxidative properties of HDLs can be attenuated in the oxygen-rich prooxidative arterial environment, contributing to the development of atherosclerosis. To evaluate this hypothesis, we compared antioxidative activity of HDLs from arterial and venous plasmas.Methods and resultsArterial and venous blood samples were simultaneously obtained from 16 patients (age 68 ± 10 years; 75% males) presenting with ischemic or valvular heart disease. Major HDL subfractions and total HDLs were isolated by density gradient ultracentrifugation and their chemical composition and the capacity to protect LDLs from in vitro oxidation were evaluated. HDL-cholesterol, triglycerides and apolipoprotein (apo) B-100 levels were slightly but significantly reduced by −4 to −8% (p < 0.01) in the arterial vs. venous samples. Total mass of HDL subpopulations was similar and HDL subpopulations did not reveal marked compositional differences between the arterial and venous circulation. Potent antioxidative activity of the small, dense HDL3c subpopulation was significantly reduced in the particles of arterial origin vs. their counterparts from venous plasma (increase of +21% in the propagation rate of LDL oxidation, p < 0.05). Interestingly, antioxidative properties of venous HDLs were enhanced in statin-treated patients relative to untreated subjects.ConclusionAntioxidative properties of small, dense HDLs from arterial plasma are attenuated as compared to the particles of venous origin, consistent with the development of atherosclerosis in the arterial wall.