Trends in delivery hospitalizations with pregestational and gestational diabetes mellitus and associated outcomes: 2000-2019.

BACKGROUND: Pregestational diabetes mellitus and its associated risks may be increasing in the obstetrical population. OBJECTIVE: This study aimed to characterize the trends in delivery hospitalizations with pregestational diabetes mellitus, the prevalence of chronic diabetes complications, and the risk for adverse outcomes. STUDY DESIGN: This repeated, cross-sectional study used the United States National Inpatient Sample to identify delivery hospitalizations with pregestational diabetes mellitus between 2000 and 2019. Trends in delivery hospitalizations with pregestational diabetes mellitus were assessed using joinpoint regression to determine the average annual percent change. Trends in chronic diabetes complications, including chronic kidney disease, neuropathy, peripheral vascular disease, and diabetic retinopathy, were also analyzed. The risk for adverse obstetrical outcomes was compared between patients with and those without pregestational diabetes mellitus using adjusted logistic regression models that were adjusted for demographic, clinical, and hospital characteristics with adjusted odds ratios with 95% confidence intervals as measures of association. RESULTS: Of 76.7 million delivery hospitalizations, 179,885 (0.23%) had type 1 diabetes mellitus, 430,544 (0.56%) had type 2 diabetes mellitus, and 99,327 (0.13%) had unspecified diabetes mellitus. From 2000 to 2019, the prevalence of diabetes mellitus increased from 1.8 to 7.3 per 1000 deliveries for type 2 diabetes mellitus (average annual percent change, 8.0%; 95% confidence interval, 6.9%-9.2%), from 1.5 to 3.2 per 1000 deliveries for unspecified diabetes mellitus (average annual percent change, 3.9%; 95% confidence interval, 1.4%-6.3%), and from 2.7 in 2000 to 2.8 per 1000 deliveries (average annual percent change, 0.2%; 95% confidence interval, -0.8% to 1.3%) for type 1 diabetes mellitus. The prevalence of chronic diabetes mellitus complications increased from 2.7% to 5.6% over the study period (average annual percent change, 5.9%; 95% confidence interval, 3.7%-8.0%). Pregestational diabetes mellitus was associated with severe maternal morbidity, cesarean delivery, hypertensive disorders of pregnancy, preterm birth, and shoulder dystocia. CONCLUSION: Pregestational diabetes mellitus increased over the study period, driven by a quadrupling in the prevalence of type 2 diabetes mellitus. Notably, the prevalence of chronic diabetes mellitus complications doubled concomitantly. Pregestational diabetes mellitus was associated with a range of adverse outcomes. These findings are further evidence that pregestational diabetes mellitus is an important contributor to maternal risk and that optimizing diabetes care in women of childbearing age will continue to be of major public health importance.

A Multicenter Randomized Trial Evaluating the Insulin-Only Configuration of the Bionic Pancreas in Adults with Type 1 Diabetes.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using insulin aspart or insulin lispro in adults with type 1 diabetes (T1D). Methods: In this multicenter, randomized, controlled trial, 161 adults with T1D (18-79 years old, baseline HbA1c 5.5%-13.1%, 32% using multiple daily injections, 27% using a pump without automation, 5% using a pump with predictive low glucose suspend, and 36% using a hybrid closed loop system before the study) were randomly assigned 2:1 to use the BP (N = 107) with insulin aspart or insulin lispro (BP group) or a standard-of-care (SC) control group (N = 54) using their usual insulin delivery plus continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 7.6% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% confidence interval -0.6% to -0.3%, P < 0.001). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 11% (2.6 h/d) and mean CGM glucose was reduced by 16 mg/dL with BP compared with SC (P < 0.001). Improvement in these metrics was seen during the first day of BP use and by the end of the first week reached levels that remained relatively stable through 13 weeks. Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose all favored the BP group (P < 0.001). The CGM-measured hypoglycemia was low at baseline (median time <54 mg/dL of 0.21% [3 min/d] for the BP group and 0.11% [1.6 min/d] for the SC group) and not significantly different between groups over the 13 weeks (P = 0.51 for time <70 mg/dL and 0.33 for time <54 mg/dL). There were 7 (6.5% of 107 participants) severe hypoglycemic events in the BP group and 2 events in the SC group (1.9% of 54 participants, P = 0.40). Conclusions: In adults with T1D, use of the BP with insulin aspart or insulin lispro improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Postpartum Readmissions Among Women With Diabetes.

OBJECTIVE: To estimate whether women with diabetes are at risk for 60-day postpartum readmissions and associated complications. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was analyzed to determine risk for 60-day postpartum readmissions among women with type 1 diabetes mellitus (DM), type 2 DM, gestational diabetes mellitus (GDM), and unspecified DM compared with women with no diabetes. Secondary outcomes included evaluating risk for overall severe maternal morbidity during readmissions, as well as wound complications, acute diabetic complications such as diabetic ketoacidosis, venous thromboembolism, and hypertensive diseases of pregnancy. Billing data were used to ascertain both exposures and outcomes. Adjusted log-linear regression models including demographic, hospital, medical and obstetric, and hospital factors were performed with adjusted risk ratios (aRRs) and with 95% Cis as measures of association. RESULTS: Of an estimated 15.7 million delivery hospitalizations, 1.1 million occurred among women with diabetes, of whom 3.2% had type 1 DM, 9.1% type 2 DM, 86.6% GDM, and 1.1% unspecified diabetes. Compared with women without diabetes (1.5% risk for readmission), risk for readmission was significantly higher for women with type 1 DM (4.4%), unspecified diabetes (4.0%), type 2 DM (3.9%), and GDM (2.0%) (P<.01). After adjusting for hospital, demographic, medical, and obstetric risk factors, type 1 DM (aRR 1.77, 95% CI 1.69-1.87), type 2 DM (aRR 1.46, 95% CI 1.42-1.51), unspecified (aRR 1.73, 95% CI 1.59-1.89) and gestational diabetes (aRR 1.16, 95% CI 1.14-1.17) retained increased risk. Among women with diabetes public insurance, lower ZIP code income quartiles, and hospitals with high safety net burdens were associated with higher risk for readmission. In both unadjusted and adjusted analyses, all diabetes diagnoses were associated with readmissions for wound complications, hypertensive diseases of pregnancy, and severe maternal morbidity. CONCLUSION: Although overall risk for readmission is low, pregnancies complicated by pregestational diabetes in particular are at increased risk. Women in this high-risk group should receive coordinated care and be monitored closely in the postpartum period.

RAGE binds preamyloid IAPP intermediates and mediates pancreatic ß cell proteotoxicity.

Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in ß cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) ß cell and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion protected pancreatic islets, ß cells, and smooth muscle cells from h-IAPP-induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were protected from amyloid deposition, loss of ß cell area, ß cell inflammation, stress, apoptosis, and glucose intolerance. These findings establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting the IAPP/RAGE axis is a potential strategy to mitigate this source of ß cell dysfunction in metabolic disease.

Diabetes as a model for the disparate public response to acute versus chronic diseases.

The public health outcry toward infectious entities appears to dwarf chronic diseases such as diabetes. This disparity is particularly astonishing given the considerable prevalence of diabetes and prediabetes. Diseases associated with short-term morbidity and mortality therefore seem to garner attention and demand an immediate public health response, whereas chronic illnesses, which can be considerably more devastating in the longer term, receive relatively less notoriety. It should not, however, be misconstrued that one disease entity is more important than the other--it is critical that both acute and chronic entities are given balanced attention in the public health, governmental, and scientific realms. The current perspective reflects on the disparate public health purviews toward acute and chronic illnesses, describes why prevention is so difficult and challenging, and addresses what can be done to reverse this trend. If there is any hope of conquering the spiraling prediabetes and diabetes epidemics, the medical community must grapple with the complex issues herein raised.

Endovascular repair of contained abdominal aortic aneurysm rupture with aortocaval fistula presenting with high-output heart failure.

Aortocava fistula is a rare condition ranging from 0.22% to 6% of all ruptured aortic aneurysms. Recognition and diagnosis of this entity can often be difficult and requires heightened clinical suspicion to ensure that prompt surgical management leads to a favorable outcome. We herein describe the diagnosis and the technical points of successful endovascular management of aortocaval fistula in the setting of a ruptured abdominal aortic aneurysm.