Association between dysglycemia and the Charlson Comorbidity Index among hospitalized patients with diabetes

AimInpatient dysglycemia has been linked to short-term mortality, but longer-term mortality data are lacking. Our aim was to evaluate the association between inpatient dysglycemia and one-year mortality risk.MethodsRetrospective chart review of adults with diabetes hospitalized between 2015 and 2019. The Charlson Comorbidity Index (CCI) was used to estimate 1-year mortality risk, stratified into low (CCI ≤ 5) and high risk (CCI ≥6). Simple and multivariable logistic regression was used to evaluate the association between dysglycemic measures and high mortality risk.ResultsAmong 22,639 unique admissions, BG ≥ 180, ≥300, ≤70, <54 and <40 mg/dL were associated with adjusted odds of 1.43 (95 % CI, 1.33, 1.54), 1.58 (95 % CI, 1.48, 1.68), 2.16 (95 % CI, 2.01, 2.32), 2.58 (95 % CI, 2.32, 2.86), and 2.56 (95 % CI, 2.19, 2.99) for high mortality risk, respectively. Older age and Black race were positively associated with hyperglycemia and hypoglycemia. Myocardial infarction, congestive heart failure (CHF), and moderate to severe liver disease were most strongly associated with hyperglycemia, while renal disease, CHF, peripheral vascular disease, and peptic ulcer disease were most strongly associated with hypoglycemia.ConclusionsInpatient hypoglycemia and hyperglycemia were both positively associated with higher one-year mortality risk, with stronger magnitude of association observed for hypoglycemia. The association appears to be mediated mainly by presence of diabetes-related complications.     

Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM).MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively.ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: ?0.494 to ?0.054; P = 0.015) and gait speed (95 % CI: ?0.039 to ?0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001).ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.     

Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes – A systematic review and meta-analysis

AimsThe effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders.MethodsWe conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis.ResultsGLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05–1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00–1.43), using placebo as a comparator (1.22, 1.05–1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99–1.42) or with subjects enrolled from multiple countries (1.2, 0.99–1.46), the association appeared to be evident but did not reach statistical significance.ConclusionsGLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Cerebrotendinous xanthomatosis,sitosterolemia, Smith-Lemli-Opitz syndrome and the seminal contributions of Gerald Salen,MD (1935–2020)

Cerebrotendinous xanthomatosis (CTX), sitosterolemia, and Smith-Lemli Opitz syndrome (SLOS) are rare inborn errors of metabolism. The diagnoses of CTX and sitosterolemia are often delayed for many years because of lack of physician awareness, often resulting in significant and unnecessary progression of disease. CTX may present with chronic diarrhea, juvenile onset cataracts, strikingly large xanthomas, and neurologic disease in the setting of a normal serum cholesterol, but markedly elevated serum or plasma cholestanol levels. These patients have a defect in producing the bile acid chenodoxycholate, and oral chenodeoxycholate therapy is essential for these patients in order to prevent neurologic complications. Sitosterolemia can present with xanthomas, anemia, thrombocytopenia, splenomegaly, very premature heart disease, and serum cholesterol levels that may be normal or elevated, along with marked elevations of plasma β-sitosterol. These patients have a defect causing overabsorption of β-sitosterol, and the treatment of choice is oral ezetimibe. SLOS presents with growth delay, intellectual disability, multiple structural anomalies, and low serum cholesterol levels, and the defect is reduced cholesterol production. Treatment consists of dietary cholesterol supplementation and oral bile acid therapy which raises serum cholesterol levels and may improve symptoms. The metabolic and genetic defects in these disorders have been defined. There is no one in our field that has contributed more to the diagnosis and treatment of these disorders than Gerald Salen, MD, who died in late 2020 at 85 years of age. He will be greatly missed by his family, friends, and colleagues from around the world.