Incidence of diabetic ketoacidosis and its trends in patients with type 1 diabetes mellitus identified using a U.S. claims database, 2007–2019

Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). We found that the incidence of DKA was 55.5 per 1000 person-years in US commercially insured patients with T1DM; age-sex-standardized incidence decreased at an average annual rate of 6.1% in 2018–2019 after a steady increase since 2011.     

Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-I(Milano)-phospholipid complex

OBJECTIVES: In this study, we examined whether a reconstituted high-density lipoprotein (HDL) utilizing recombinant apolipoprotein A-I(Milano) (apo A-I(M))/phospholipid complex (PC) could restore normal endothelial function in hypercholesterolemic apolipoprotein (apo) E-null mice. BACKGROUND: We have previously shown antiatherosclerotic and vasculoprotective effects of recombinant apo A-I(M). METHODS: A perfused vessel preparation was used to examine vascular responses in control wild-type, untreated, and treated apo E-null mice. Aortic tissue cholesterol content and platelet aggregation were also measured. RESULTS: Endothelium-dependent vasodilator responses to acetycholine were significantly inhibited in untreated apo E-null mice compared with control wild-type mice (p < 0.001). Treatment of the mice for five weeks with once every-other-day intravenous bolus injections of apo A-I(M)/PC restored endothelium-dependent dilation in a dose-dependent manner (p < 0.01 at 80 mg/kg dose). The improvement in endothelial function was associated with a reduction in aortic cholesterol content and reduced platelet aggregability and occurred despite severe and persistent hypercholesterolemia. Neither treatment with free protein nor phospholipid carrier alone produced any significant effects. We performed additional experiments in vitro in isolated rabbit carotid arteries to compare the effects on lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Treatment with apo A-I(M)/PC prevented impairment of endothelium-dependent vasodilator responses to acetylcholine to a greater degree than either wild-type apo A-I or plasma-derived HDL. CONCLUSIONS: Our results indicate a rapid improvement in endothelial dysfunction with recombinant apo A-I(M)/PC that is associated with mobilization of tissue cholesterol. Taken together with previously established antiatherosclerotic and antithrombotic effects, these findings suggest significant vasculoprotective effects with apo A-I(M)/PC therapy.     

Prognostic impact of the ankle–brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study

Aims/hypothesis

The prognostic importance of the ankle–brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes.

Methods

The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index.

Results

During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p?=?0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p?=?0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p?=?0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p?=?0.033), but not with retinopathy or renal outcomes.

Conclusions/interpretation

A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.

     

Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS: Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.     

The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya,western Kenya

In spite of increasing resistance, chloroquine remains the primary drug for treatment of malaria in most sub-Saharan African countries. We evaluated the effect of drug treatment policy on the case-fatality rates of children, adjusting for differing distributions of malaria and severe anemia. In 1991, 63% of children were treated with chloroquine while the remaining 37% were treated with a regimen that would eliminate and clear parasitemia. Case-fatality rates were 13% and 4.1%, respectively; the proportion of deaths attributable to chloroquine treatment was 69%. The trend in case-fatality rates for malaria decreased as an increasing proportion of children received an effective treatment regimen; adjusted malaria case-fatality rates were 5.1%, 3.6%, and 3.3% in 1992, 1993, and 1994, respectively, when 85% of children in 1992 and 97% of children in 1993-1994 received effective therapy. These 4 years of data provide strong evidence that continued use of chloroquine in areas with resistance is contributing to excess Plasmodium falciparum-related deaths.     

High Prevalence of Depressive Symptoms in Patients With Type 1 and Type 2 Diabetes in Developing Countries: Results From the International Diabetes Management Practices Study

OBJECTIVEDepression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS).RESEARCH DESIGN AND METHODSIDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms.RESULTSOf 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10–19) were observed in 8–16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control.CONCLUSIONSDepressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction.     

Protective effects of N-(2-mercaptopropionyl)-glycine against ischemia–reperfusion injury in hypertrophied hearts

The beneficial effects of N-(2-mercaptopropionyl)-glycine (MPG) against ischemia–reperfusion injury in normotensive animals have been previously studied. Our objective was to test the action of MPG during ischemia and reperfusion in hearts from spontaneously hypertensive rats (SHR). Isolated hearts from SHR and age-matched normotensive rats Wistar Kyoto (WKY) were subjected to 50-min global ischemia (GI) and 2-hour reperfusion (R). In other hearts MPG 2 mM was administered during 10 min before GI and the first 10 min of R. Infarct size (IS) was assessed by TTC staining technique and expressed as percentage of risk area. Postischemic recovery of myocardial function was assessed. Reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and SOD cytosolic activity — as estimators of oxidative stress and MnSOD cytosolic activity — as an index of (mPTP) opening were determined. In isolated mitochondria H₂O₂-induced mPTP opening was also measured. The treatment with MPG decreased infarct size, preserved GSH levels and decreased SOD and MnSOD cytosolic activities, TBARS concentration, and H₂O₂ induced-mPTP opening in both rat strains. Our results show that in both hypertrophied and normal hearts an attenuation of mPTP opening via reduction of oxidative stress appears to be the predominant mechanism involved in the cardioprotection against reperfusion injury MPG-mediated.     

Parent–Teacher Disagreement on Ratings of Behavior Problems in Children with ASD: Associations with Parental School Involvement Over Time

ASD symptomology and behavioral problems pose challenges for children with ASD in school. Disagreement between parents and teachers in ratings of children’s behavior problems may provide clinically relevant information. We examined parent–teacher disagreement on ratings of behavior problems among children with ASD during the fall and spring of the school year. When child, teacher, and class characteristics were considered simultaneously, only ASD symptom severity predicted informant disagreement on internalizing and externalizing behavior problems. We also examined associations between informant disagreement and parent school involvement. Cross-lagged panel analyses revealed that higher informant disagreement on children’s behavior problems in the fall predicted lower parent school involvement in the spring, suggesting that greater informant agreement may foster parental school involvement over time.