Objective Anti-HMGCR antibodies are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed subjects with autoimmune myopathy. The main objective of this study is to define the association of anti-HMGCR antibody levels with disease activity. Methods Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR positive subjects. Associations of antibody level with CK and strength at visit 1 were analyzed in 55 subjects, 40 of whom were statin-exposed. In 12 statin-exposed and 5 statin-unexposed subjects with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated. Results Antibody levels were associated with CK levels (p < 0.001), arm strength (p < 0.05), and leg strength (p < 0.05) at visit 1 but these associations were only significant amongst statin-exposed patients in stratified analyses. With treatment over 26.2 +/− 12.6 months, antibody levels declined (p < 0.05) and arm abduction strength improved (p < 0.05) in 17 subjects followed longitudinally. When analyzed separately, statin-exposed subjects developed decreased antibody levels (p < 0.01), decreased CK levels (p < 0.001), improved arm strength (p < 0.05), and improved hip flexion strength (p < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any subject. Conclusion In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with treatment, antibody levels declined and arm strength improved. Statin-exposed but not statin-unexposed subjects had significant improvements in CK and strength, suggesting a phenotypic difference between statin-exposed and -unexposed anti-HMGCR patients.

Background There is a lack of consensus across international organizations regarding definitions of prediabetes. Associations with complications can inform the comparative value of different prediabetes definitions. Methods We conducted a prospective cohort study of 10,844 Atherosclerosis Risk in Communities (ARIC) study participants without diagnosed diabetes who attended visit 2 (1990–92) and 7,194 who attended visit 4 (1996–98). Fasting glucose and HbA1c were measured at visit 2 and fasting glucose and 2-hour glucose were measured at visit 4. We compared prediabetes definitions based on fasting glucose (American Diabetes Association [ADA] 5.6–6.9 mmol/L and World Health Organization [WHO] 6.1–6.9 mmol/L), HbA1c (ADA 39–46 mmol/mol and International Expert Committee [IEC] 42–46 mmol/mol), and 2-hour glucose (ADA/WHO 7.8–11.0 mmol/L). Findings ADA fasting glucose-defined prediabetes (prevalence 37.9%) was the most sensitive for major clinical outcomes, while ADA and IEC HbA1c and WHO fasting glucose-based definitions (prevalence 18.7%, 9.0%, 11.2%, respectively) were more specific. After demographic adjustment, HbA1c-based definitions of prediabetes had higher hazard ratios and demonstrated better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality compared to fasting glucose (modestly larger C-statistics, all p<0.05). For example, the C-statistic for incident chronic kidney disease was 0.636 for ADA fasting glucose categories and 0.640 for ADA HbA1c clinical categories (difference −0.005, 95%CI −0.008, −0.001). Additionally, ADA HbA1c-defined prediabetes also demonstrated significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared to glucose-based definitions. Comparing ADA and WHO fasting glucose and ADA/WHO 2-hour did not reveal statistically significant differences in risk discrimination for chronic kidney disease, cardiovascular, or mortality outcomes. Interpretation Our results suggest that HbA1c-defined prediabetes definitions were more specific and provided modest improvements in risk discrimination for clinical complications. ADA fasting glucose was a more sensitive definition overall.

OBJECTIVETo characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG).RESEARCH DESIGN AND METHODSWe compared fasting serum from an oral glucose tolerance test at ∼28 weeks’ gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (>90th percentile) FPG with 50 mothers with low (<10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation.RESULTSHigh-FPG mothers had a metabolic profile consistent with insulin resistance including higher triglycerides, 3-hydroxybutyrate, and amino acids including alanine, proline, and branched-chain amino acids (false discovery rate [FDR]-adjusted P < 0.05). Lower 1,5-anhydroglucitol in high-FPG mothers suggested recent hyperglycemic excursions (FDR-adjusted P < 0.05). Pathway analyses indicated differences in amino acid degradation pathways for the two groups (FDR-adjusted P < 0.05), consistent with population-based findings in nonpregnant populations. Exploratory analyses with newborn outcomes indicated positive associations for maternal triglycerides with neonatal sum of skinfolds and cord C-peptide and a negative association between maternal glycine and cord C-peptide (P < 0.05).CONCLUSIONSMetabolomics reveals perturbations in metabolism of major macronutrients and amino acid degradation pathways in high- versus low-FPG mothers.

(AHA) guideline, the definition of hypertension was lowered from a blood pressure (BP) of greater than or equal to 140/90 to greater than or equal to 130/80 mm Hg. The new diastolic BP threshold of 80 mm Hg was recommended based on expert opinion and changes the definition of isolated diastolic hypertension (IDH). OBJECTIVE To compare the prevalence of IDH in the United States, by 2017 ACC/AHA and 2003 Joint National Committee (JNC7) definitions, and to characterize cross-sectional and longitudinal associations of IDH with outcomes.

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