To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The ...Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice.
Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report.
The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions.
Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012.
The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.
The abundance of mRNA is mainly determined by the rates of RNA transcription and decay. Here, we present a method for unbiased estimation of differential mRNA decay rate from RNA-sequencing data by ...modeling the kinetics of mRNA metabolism. We show that in all primary human tissues tested, and particularly in the central nervous system, many pathways are regulated at the mRNA stability level. We present a parsimonious regulatory model consisting of two RNA-binding proteins and four microRNAs that modulate the mRNA stability landscape of the brain, which suggests a new link between RBFOX proteins and Alzheimer's disease. We show that downregulation of RBFOX1 leads to destabilization of mRNAs encoding for synaptic transmission proteins, which may contribute to the loss of synaptic function in Alzheimer's disease. RBFOX1 downregulation is more likely to occur in older and female individuals, consistent with the association of Alzheimer's disease with age and gender."mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer's disease."
Objective:
To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and ...The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice.
Participants:
Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The sponsors had no input into the development of or content of the report.
Evidence:
The writing group considered data from recent clinical trials and other studies to update the prior workgroup report. Unpublished data were not used. Expert opinion was used to develop some conclusions.
Consensus Process:
Consensus was achieved by group discussion during conference calls and face-to-face meetings, as well as by iterative revisions of the written document. The document was reviewed and approved by the American Diabetes Association's Professional Practice Committee in October 2012 and approved by the Executive Committee of the Board of Directors in November 2012 and was reviewed and approved by The Endocrine Society's Clinical Affairs Core Committee in October 2012 and by Council in November 2012.
Conclusions:
The workgroup reconfirmed the previous definitions of hypoglycemia in diabetes, reviewed the implications of hypoglycemia on both short- and long-term outcomes, considered the implications of hypoglycemia on treatment outcomes, presented strategies to prevent hypoglycemia, and identified knowledge gaps that should be addressed by future research. In addition, tools for patients to report hypoglycemia at each visit and for clinicians to document counseling are provided.
Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one ...of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies.
The original version of this Article contained an error in Figure 3, where panel d was inadvertently replaced with a duplicate of panel c during typesetting. Also, the legend of Figure 5f incorrectly ...read '310 AD patients (blue dots, r = -0.4) and 157 non-demented individuals (green dots, r = -0.1)', and should have read '310 AD patients (blue dots, r = -0.1) and 157 non-demented individuals (green dots, r = -0.4)'. Both of these errors have now been corrected in both the PDF and HTML versions of the Article.
To compare the effectiveness of 2 insulin protocols to treat glucocorticoid-induced hyperglycemia in the nonintensive care hospital setting.
A randomized, open-label, parallel-arm study was conducted ...comparing standard recommended care of complete insulin orders (CIO) (i.e., 3-part insulin regimen of long-acting basal background, rapid-acting bolus mealtime, and rapid-acting correction factor) to an experimental group following a regimen of Neutral Protamine Hagedorn (NPH) plus CIO (NPH-CIO). The primary outcome was mean blood glucose (BG), and the secondary outcome was percent of BG in target range of 70 to 180 mg/dL. Hypoglycemia was also evaluated.
Sixty-one patients completed 2 to 5 consecutive inpatient days (31 CIO; 30 NPH-CIO). Baseline mean BG results were 237.2 ± 50.2 and 221.9 ± 35.8 mg/dL (P = .30) in the CIO and NPH-CIO groups, respectively. No significant difference in overall mean BG between the 2 groups was detected; however, a significant difference arose on day 3: mean BG 181.8 ± 32.6 mg/dL (CIO) versus 157.2 ± 6.1 mg/dL (NPH-CIO) (P = .03). Moreover, the total daily doses (TDDs) of insulin did not differ: 34.8 ± 43.0 units (CIO) versus 35.8 ± 25.0 units (NPH-CIO) (P = .13). Percent of BG in target was 54.6% (CIO) and 62% (NPH-CIO) (P = .24). Incidence of severe hypoglycemia (<50 mg/dL) was the same in both groups (0.1%).
NPH added to 3-part insulin regimen (CIO) may be an effective way to a combat glucocorticoid-induced hyperglycemia, though further research is needed in a larger population.
Aims Diabetic ketoacidosis (DKA) is an emergency with high morbidity and mortality. This study examined patient factors associated with hospitalization for recurrent DKA. Methods Characteristics of ...265 subjects admitted for DKA at Hennepin County Medical Center between January 2017 and January 2019 were retrospectively analyzed. Differences between subjects with a single admission versus multiple were reviewed. Results Forty-eight out of 265 patients had recurrent DKA. Risk factors included African American race (adjusted odds ratio (aOR) versus white non-Hispanic = 4.6, 95% CI 1.8-13, p = 0.001) or other race/ethnicity (aOR = 8.6, 2.9-28, p < 0.0001), younger age (aOR 37-52y versus 18-36y = 0.48, 0.19-1.16, p = 0.10; aOR 53-99y versus 18-36y = 0.37, 0.12-0.99, p = 0.05), type 1 diabetes mellitus (aOR = 2.4, 1.1-5.5, p = 0.04), ever homeless (aOR = 2.5, 1.1-5.4, p = 0.03), and drug abuse (aOR = 3.2, 1.3-7.8, p = 0.009). DKA cost a median of $29,981 per admission. Conclusions Recurrent DKA is costly, and social determinants are strong predictors of recurrence. This study highlights the need for targeted preventative care programs. Keywords: Recurrent DKA, Insulin cost, Barriers to care
Abstract
Background
The current guidelines on Cushing's Disease management recommend surgically resecting adenomas larger than 10 mm in size.1 For smaller adenomas, inferior petrosal sinus sampling ...(IPSS) is considered the gold standard to distinguish between Cushing's disease and ectopic ACTH production. We report a case where IPSS testing and the size of the adenoma on MRI were misleading in determining the final diagnosis, prompting us to challenge the existing guidelines.
Clinical Case
A 40-year-old female with a past medical history of hyperlipidemia, obesity (BMI 42) and prediabetes presented with secondary infertility, galactorrhea, headaches, blurred vision and weight gain (30 lbs) over the past year. Physical examination was notable for acanthosis nigricans of the neck and bilateral milky nipple discharge. Prolactin level was elevated to 46.9 ng/ml (n 4.8-23.3 ng/mL). ACTH was elevated to 83.5 pg/mL (n 7.2-63.3 pg/mL) and cortisol to 17.4 ug/dL (n 2.7-10.5 ug/dL). Salivary cortisol was elevated to 0.216 ug/dL (n <0.112 ug/dL), 24-hour urinary cortisol elevated to 60.2 ug (n <45 ug) and on 1 mg dexamethasone suppression testing, morning cortisol was elevated to 7.2 ug/dL (n <1.8 ug/dL). MRI revealed a 6×7×7 mm right sided pituitary mass. Referral to Neurosurgery for resection was made. Neurosurgery recommended bilateral IPSS for pre-operative tumour lateralisation. 10 ug of DDAVP was used to increase test sensitivity. Central to peripheral ACTH ratio was 1: 1. No significant laterality was noted. In the absence of other identifiable sources on CT imaging, endoscopic endonasal surgical resection was pursued. On pathology, the adenoma was immunoreactive for ACTH, confirming Cushing's Disease. Post-operative morning cortisol was 1.3 ug/dL. The patient was started on hydrocortisone 50 mg in the morning and 20 mg in the afternoon with outpatient taper two weeks following discharge to prednisone 10 mg daily.
Conclusion
Current guidelines recommend surgery for adenomas >10 mm in size, IPSS for adenomas < 6 mm and further diagnostics (IPSS or serum CRH and DDAVP stimulation tests plus whole-body CT) for those 6-9 mm. IPSS is strongly preferred. 1 IPSS is operator dependent and has low efficacy in tumour lateralisation. With the advent of high-resolution CT imaging and emerging data corroborating non-invasive stimulation tests,2 it may be time to shift away from IPSS as a first line test for adenomas irrespective of size. IPSS can present a costly, invasive, oft misleading, and hence superfluous testing strategy; it is high time the medical community re-evaluates its reliance on it.References1. Fleseriu M et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol. 2021 Dec;9(12): 847-875.2.Caroline Frete et al. Non-invasive Diagnostic Strategy in ACTH-dependent Cushing's Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 10, October 2020, Pages 3273–3284
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.