The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI34. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.

Purpose of ReviewThis paper seeks to summarize the impact of the one-step International Association of Diabetes and Pregnancy Study Groups (IADPSG) versus the two-step gestational diabetes mellitus (GDM) criteria with regard to prevalence, outcomes, healthcare delivery, and long-term maternal metabolic risk.Recent FindingsStudies demonstrate a 1.03–3.78-fold rise in the prevalence of GDM with IADPSG criteria versus baseline criteria. Women with GDM by IADPSG criteria have more adverse pregnancy outcomes than women with normal glucose tolerance (NGT). Treatment of GDM by IADPSG criteria may be cost effective. Use of the fasting glucose as a screen before the 75-g oral glucose tolerance test to rule out GDM with fasting plasma glucose (FPG) < 4.4 (80 mg/dl) and rule in GDM with FPG ≥ 5.1 mmol/l (92 mg/dl) reduces the need for OGTT by 50% and its cost and inconvenience. The prevalence of postpartum abnormal glucose metabolism is higher for women with GDM diagnosed by IADPSG criteria versus that for women with NGT.SummaryData support the use of IADPSG criteria, if the cost of diagnosis and treatment can be controlled and if lifestyle can be optimized to reduce the risk of future diabetes.

BackgroundIt is estimated that 9.3% of the population in the United States have diabetes mellitus (DM), 28% of which are undiagnosed. The high prevalence of DM makes it a common comorbid condition in hospitalized patients. In recent years, government agencies and healthcare systems have increasingly focused on 30-day readmission rates to determine the complexity of their patient populations and to improve quality. Thirty-day readmission rates for hospitalized patients with DM are reported to be between 14.4 and 22.7%, much higher than the rate for all hospitalized patients (8.5–13.5%). The objectives of this study were to (1) determine the incidence and causes of 30-day readmission rates for patients with diabetes listed as either the primary reason for the index admission or with diabetes listed as a secondary diagnosis compared to those without DM and (2) evaluate the impact on readmission of two specialized inpatient DM services: the Hyperglycemic Intensive Insulin Program (HIIP) and Endocrine Consults (ENDO).MethodsFor this study, DM was defined as any ICD-9 discharge diagnosis (principal or secondary) of 250.xx. Readmissions were defined as any unscheduled inpatient admission, emergency department (ED) visit, or observation unit stay. We analyzed two separate sets of patient data. The first pilot study was a retrospective chart review of all patients with a principle or secondary admission diagnosis of diabetes admitted to any adult service within the University of Michigan Health System (UMHS) between October 1, 2013 and December 31, 2013. We then did further uncontrolled analysis of the patients with a principal admitting diagnosis of diabetes. The second larger retrospective study included all adults discharged from UMHS between October 1, 2013 and September 30, 2014 with principal or secondary discharge diagnosis of DM (ICD-9-CM: 250.xx).ResultsIn the pilot study of 7763 admissions, the readmission rate was 26% for patients with DM and 22% for patients without DM. In patients with a primary diagnosis of DM on index admission, the most common cause for readmission was DM-related. In the larger study were 37,702 adult inpatient discharges between October 1, 2013 and September 30, 2014. Of these, 20.9% had DM listed as an encounter diagnosis. Rates for all encounters (inpatient, ED and Observation care) were 24.3% in patients with DM compared to 17.7% in those without DM (p < 0.001). The most common cause for readmission in patients with DM as a secondary diagnosis to the index admission was infection-related.During the index hospital stay, only a small proportion of patients with DM (approximately 12%) received any DM service consult. Those who received a DM consult had a higher case mix index compared to those who did not. Despite the higher acuity, there was a lower rate of ED /observation readmission in patients followed by the DM services (6.6% HIIP or ENDO vs. 9.6% no HIIP or ENDO, p = 0.0012), though no difference in the inpatient readmission rates (17.6% HIIP or ENDO vs. 17.4% no HIIP or ENDO, p = 0...

Objective:To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes.Methods:Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data.Results:PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE).Conclusions:Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary form of primary hyperaldosteronism that presents with hypokalemia and hypertension from childhood onward. GRA is characterized by the ectopic production of aldosterone in the cortisol-producing zona fasciculata under the regulation of adrenocorticotrophic hormone. Despite the early age of onset, no previous reports of pregnancy and GRA exist. Therefore, we set out to describe the maternal and fetal outcomes of pregnancy in women with GRA. Data regarding the blood pressure and pregnancy outcomes were collected in a retrospective chart review of prenatal and hospital records of 35 pregnancies in 16 women with genetically proven GRA. A total of 6% of pregnancies in women with GRA (GRA) were complicated by preeclampsia. The published rates of preeclampsia in general obstetric populations vary from 2.5% to 10%. Despite the lack of an apparent increase in the rate of preeclampsia, GRA women with chronic hypertension had a high rate (39%) of pregnancy-aggravated hypertension. Starting with a higher baseline blood pressure, maternal blood pressure plotted over the time course of pregnancy followed a quadratic curve similar to that previously described in normal pregnancy. Mean gestational age at delivery was 39.1 weeks. Mean birth weight, excluding the 3 sets of twins, was 3219 g. However, infants of GRA mothers with pregnancy-aggravated hypertension tended to have lower birth weights than those that did not (3019 g versus 3385 g, respectively; P0.08). The primary cesarean section rate was 32%, which is approximately double that seen in other general or hypertensive obstetric populations. In summary, GRA women did not seem to have an increased risk of preeclampsia. However, GRA women with chronic hypertension seem to be at an increased risk for an exacerbation of their hypertension during pregnancy. (Hypertension. 2000;35:668-672.) Key Words: hypertension, chronic pregnancy blood pressure hyperaldosteronism renin-angiotensin system glucocorticoids G lucocorticoid-remediable aldosteronism (GRA) is an increasingly recognized form of hereditary primary hyperaldosteronism. 1 Presenting from childhood onward, GRA is clinically characterized by severe hypertension, variable hypokalemia, volume expansion, and suppressed plasma renin activity. 2 GRA is caused by a chimeric gene duplication that results from an unequal crossing over between the 11-hydroxylase and aldosterone synthase genes. 1 Pregnancy outcomes in women with GRA have not been previously reported; they are of interest for several reasons. First, pregnancy-related hypertensive disorders are one of the leading causes of maternal and perinatal mortality and morbidity in the United States. 3 Chronic hypertensive disorders like GRA are considered risk factors for the development of preeclampsia and poor fetal outcomes. 4 Therefore, studying pregnancy outcomes provides essential information for the clinician caring for a patient with GRA. Second, because GRA is a state of endogenous suppression of the renin-...

Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites. We analyzed the health and epigenome data by taking two independent associative approaches: the parametric regression-based approach and a non-parametric machine learning approach followed by GO ontology analysis. Our results indicate that DNA methylation at CpG sites in the promoter region of PCDHGA3 is associated with biological age. PCDHGA3 belongs to clustered protocadherin genes, which are all located in a single locus on chromosome 5 in human. Previous studies of the clustered protocadherin genes showed that (1) DNA methylation is associated with age or age-related phenotypes; (2) DNA methylation can modulate gene expression; (3) dysregulated gene expression is associated with various pathologies; and (4) DNA methylation patterns at this locus are associated with adverse lifetime experiences. All these observations suggest that DNA methylation at the clustered protocadherin genes, including PCDHGA3, is a key mediator of healthy aging.

Postoperative breast irradiation is well tolerated by older women. Age is not a contraindication to breast preservation.

Insulin induced neuropathy has been reported previously in people with diabetes treated with insulin, and subsequently reported in patients with insulinomas. However, neuropathy caused by rapid glycaemic control in patients with poorly controlled diabetes with chronic hyperglycaemia is not a widely recognised entity among clinicians worldwide. It is expected that this phenomenon of paradoxical complication of neuropathy in the face of drastic decreases in glycosylated haemoglobin concentrations will assume greater importance with clinicians achieving glycaemic targets at a faster pace than before.