Cognitive screening among older adults with diabetes across diverse clinic settings.

AIMS: Diabetes increases risk of cognitive dysfunction and dementia, which can make it harder to manage diabetes. We aimed to examine cognitive screening for older adults with diabetes in 1) endocrine (Endo), 2) geriatric (Geri) and 3) multidisciplinary endocrine-geriatric (Geri-Endo), to study differences between these settings and to elucidate risk factors of cognitive dysfunction. METHODS: We performed cognitive screening for subsets of patients ≥ age 65 with diabetes in one large healthcare system. We compared results and differences from the three clinic types and used adjusted multivariate logistic regression models to predict risk of cognitive dysfunction. RESULTS: Among 198 patients screened, those in Geri-Endo (N = 86) and Geri (N = 32) were more likely to have lower Mini-Cog scores, higher prevalence of hypertension and cardiovascular (CV) events. Endo and Geri-Endo patients had longer durations of diabetes, higher incidence of hypoglycemia, and were more likely to use insulin. Age > 75 years (p = 0.0105), previous CV events (p = 0.0006) and body mass index < 30 (p = 0.0115) were significantly associated with lower Mini-Cog scores. CONCLUSIONS: Our study shows that cognitive screening can help identify at risk older adults with diabetes. Thus, yearly screening should be part of routine diabetes care.

Program for Reducing Obesity (PRO): An institutional review of an insurance-based weight loss program utilizing shared medical appointments.

Background: Based on CDC estimates in the United States, the prevalence of obesity was 42.4% in 2017-2018, and the annual cost of obesity was $147 billion in 2008. Yet studies estimate that only 20-40% of adults with obesity received counseling from their primary care providers. Recent studies using shared medical appointments (SMA), where patients are seen by a multidisciplinary team, have shown promising results in obesity management. We developed an insurance-based weight loss program incorporating SMA, called the Program for Reducing Obesity (PRO), and report our findings here. Methods: Enrollment began in January 2019 at the UCLA Health Thousand Oaks clinic. Patients age ≥18 years with BMI ≥30 kg/m2 were eligible by referral to PRO, a program consisting of individual visits and SMAs with an obesity medicine board certified endocrinologist and registered dietitian. Primary outcomes were change in weight after 3, 6, and 12 months. Secondary outcomes included proportion that achieved ≥5% weight loss, change in percent body fat, HbA1c, HDL, triglycerides, and blood pressure. Results: 102 patients (mean age 59.7 years, 72% women, mean weight 103.6 kg, mean BMI 36.6 kg/m2) have been analyzed, with 91 patients completing at least 12 months of the program. Patients achieved significant weight loss: 3.0%, 5.0%, and 7.8% of their baseline weight after 3, 6, and 12 months respectively. 52% of patients lost ≥5% of their baseline weight after 12 months. Patients had significant reductions in body fat: 2.1%, 7.4%, and 6.7% of their baseline (all p ≤ 0.01) after 3, 6, and 12 months respectively. Improvements were also seen in HbA1c (p ≤ 0.01), triglycerides (p ≤ 0.04), and systolic blood pressure (p ≤ 0.07) after 12 months although not all results achieved statistical significance. Conclusion: Our institutional review of PRO, an insurance-based obesity program utilizing SMA, demonstrates a successful approach to promoting weight loss in a community-based setting.

Outcomes of Indeterminate Thyroid Nodules Managed Nonoperatively after Molecular Testing.

CONTEXT: Molecular testing to refine the diagnosis of cytologically indeterminate thyroid nodules has become increasingly popular, but data on long-term durability of test results and the rate of delayed operation are limited. OBJECTIVE: Determine the delayed rate of surgical resection in indeterminate nodules with benign/negative molecular testing and the risk of false-negative molecular test results. DESIGN: Prospective follow-up of the Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules randomized controlled trial comparing the diagnostic test performance of Afirma Gene Expression Classifier and ThyroSeq v2. SETTING: University of California, Los Angeles. PARTICIPANTS: Patients who underwent thyroid biopsy with indeterminate (Bethesda III/IV) cytology (April 2016 to July 2017). INTERVENTION: Ultrasound surveillance. MAIN OUTCOME MEASURE: False-negative rate of molecular testing. RESULTS: Of 95 indeterminate nodules with negative/benign molecular test results, 12 nodules underwent immediate resection (11 benign nodules, 1 noninvasive follicular thyroid neoplasm nodule with papillary-like nuclear features). Nonoperative management was pursued for 83 (87.4%) nodules. The median surveillance was 26.7 months. Ten nodules were resected during surveillance and malignancy was identified in 4 nodules (overall false-negative rate of 5.8%). In the 4 malignant nodules that underwent delayed operation, surgery was prompted by sonographic changes during surveillance. CONCLUSIONS: The majority of indeterminate nodules with negative molecular testing have a stable clinical course over 3 years of follow-up, but our finding of a 6% false-negative rate highlights the importance of continuing sonographic surveillance. Long-term studies are needed to determine the optimal length of follow-up.

Insulin infusion responses in diabetic ketoacidosis alone and with a mixed hypochloremic alkalosis.

AIMS: Although diabetic ketoacidosis (DKA) commonly presents as a pure diabetic ketoacidosis (PDKA), up to 30% of cases may be associated with a mixed hypochloremic metabolic alkalosis (HMA). It is unknown whether there is a difference in treatment outcomes between these two entities. We evaluated an insulin infusion protocol (IIP), previously validated for hyperglycemia management in ICU's, for the management of PDKA and HMA. MATERIALS AND METHODS: A retrospective case series/cohort study of 41 DKA admissions was further characterized as having PDKA or HMA. HMA was defined in those having an elevated delta-delta gradient (ΔAG-ΔHCO3) ≥ 5 mmol/L and base excess chloride (BECl) > 2.7 mmol/L. The main outcome measures were times to recovery of glucose levels to ≤250 mg/dL and of anion gap to ≤12 mmol/L. RESULTS: The initial serum glucose was 553 ±â€¯265 mg/dL, serum bicarbonate of 8.8 ±â€¯5.1 mmol/L, and venous pH 7.13 ±â€¯0.2). Recovery of glucose occurred in 5 h: 25 min (±3 h:39min), and for anion gap in 11 h:25 min (±6 h:56min). HMA compared with PDKA had a delayed recovery of serum glucose (7 h: 23min ±â€¯3 h: 35min vs. 4 h: 31min ±â€¯3:h:21min, p = 0.017), which was due to the higher initial level of glucose (p = 0.02) rather than level of BECl (p = 0.17). There was no difference in time to anion gap closure between the PDKA and HMA. CONCLUSIONS: Correction of hyperglycemia and acidosis in PDKA as well as in HMA was managed through the IIP. The simultaneous fluid and electrolyte management corrected the hypochloremic alkalosis.

Pheochromocytoma as a reversible cause of cardiomyopathy: Analysis and review of the literature.

CONTEXT: Pheochromocytoma and paraganglioma are rare neuroendocrine tumors which overproduce catecholamines and arise from the adrenal gland or extra-adrenal chromaffin cells of the sympathetic and parasympathetic ganglia (1). Excessive catecholamine-induced stimulation of cardiac myocytes leads to damage which manifests in several forms ranging from Takotsubo to dilated cardiomyopathy. Diagnosis of pheochromocytoma-related cardiomyopathies is often delayed due to the atypical presentation associated with many cases. OBJECTIVE: Limited data exists on the presentation and outcomes of the various forms of pheochromocytoma-induced cardiomyopathies. We performed a literature review to assess the association of pheochromocytoma and cardiomyopathy to aide in further understanding this clinical entity. DESIGN: 163 cases from 150 articles published between 1991 and November 2016 were included from a PubMed search. RESULTS: There were 163 occurrences of pheochromocytoma and cardiomyopathy (63 dilated cardiomyopathy, 38 Takotsubo cardiomyopathy, 30 inverted Takotsubo cardiomyopathy, 10 HOCM, 8 myocarditis, and 14 unspecified cardiomyopathy). Many patients lacked classic signs or symptoms of pheochromocytoma with hypertension as a presenting symptom in 65% and the triad of headache, palpitations, and diaphoresis only in 4%. Resection of the pheochromocytoma led to improvement of the cardiomyopathy in 96% while lack of resection was associated with death or cardiac transplantation in 44%. CONCLUSION: Pheochromocytoma should be considered in the evaluation of non-ischemic, non-valvular cardiomyopathy even in the absence of symptoms of catecholamine excess. Our study highlights the importance of early suspicion and diagnosis of pheochromocytoma in cases of idiopathic heart failure as early resection may prevent progression to irreversible myocardial remodeling and death.

A unified Hyperglycemia and Diabetic ketoacidosis (DKA) insulin infusion protocol based on an Excel algorithm and implemented via Electronic Medical Record (EMR) in Intensive Care Units.

BACKGROUND: To assess the efficacy of a unified hyperglycemia and diabetic ketoacidosis (DKA) insulin infusion protocol (IIP), based on an Excel algorithm and implemented as an electronic order set, in achieving glycemic targets and minimizing hypoglycemia. METHODS: An IIP was instituted in medical and surgical intensive care units for post-cardiac surgery (PCS) and other stress hyperglycemia (SH), diabetes hyperglycemia (DH), and DKA. The IIP initiated therapeutic insulin rates at elevated blood glucose (BG), and decreased insulin when target range was achieved. A convenience sample (n=62) was studied; 20 PCS, 15 with DH, 9 with SH, 8 with diabetes on vasopressors, 7 with diabetes on glucocorticoids and 3 with DKA were assessed. RESULTS: The protocol maintained BG at 144±24.7mg/dL for PCS and 167±36mg/dL for patients with diabetes mellitus. It maintained acceptable target range (ATR) (100mg/dL-180mg/dL) 89% of the time for PCS and 67% of the time for patients with diabetes mellitus. There were no measurements of BG<70mg/dL. The protocol lowered the BG at a similar rate and time period in those with diabetes, DKA and those with or without vasopressors or glucocorticoids. To determine long-term efficacy, a retrospective review of Point of Care (POC) RALS (Remote Automated Data System) BG data 2 years post implementation demonstrated fewer episodes of hypoglycemia<70mg/dL and hyperglycemia>240mg/dL and more BG values within ATR. CONCLUSIONS: This IIP maintained ATR without hypoglycemia for patients in the ICU setting without requiring complex nursing calculations.

Hypothalamic-pituitary-adrenal (HPA) axis and aging.

Human aging is associated with increasing frailty and morbidity which can result in significant disability. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to aging-related diseases like depression, cognitive deficits, and Alzheimer's disease in some older individuals. In addition to neuro-cognitive dysfunction, it has also been associated with declining physical performance possibly due to sarcopenia. This article reviews the pathophysiology of HPA dysfunction with respect to increased basal adrenocorticotropic hormone (ACTH) and cortisol secretion, decreased glucocorticoid (GC) negative feedback at the level of the paraventricular nucleus (PVN) of the hypothalamus, hippocampus (HC), and prefrontal cortex (PFC), and flattening of diurnal pattern of cortisol release. It is possible that the increased cortisol secretion is secondary to peripheral conversion from cortisone. There is a decline in pregnolone secretion and C-19 steroids (DHEA) with aging. There is a small decrease in aldosterone with aging, but a subset of the older population have a genetic predisposition to develop hyperaldosteronism due to the increased ACTH stimulation. The understanding of the HPA axis and aging remains a complex area with conflicting studies leading to controversial interpretations.

Over-nutrition, obesity and insulin resistance in the development of ß-cell dysfunction.

The incidence of type 2 diabetes mellitus (DM2) has increased dramatically over the last several decades, largely driven by equally worrisome growing rates of obesity. Chronic diabetic complications are leading causes of morbidity and mortality worldwide. Key players in the pathophysiology of DM2 are insulin resistance and ß cell dysfunction, which in turn is a result of both ß cell functional abnormality as well as reduced ß cell mass. The mechanisms implicated are multifactorial and include genetic and environmental factors related to obesity. Glucose homeostasis is critically dependent on a finely regulated balance between insulin sensitivity and output in the pancreas, and insulin resistance demands a corresponding rise in insulin output in order to maintain normal glycemia. However, this compensation is lost in individuals predisposed to DM2, resulting in overt hyperglycemia. Furthermore, insulin resistance related to excess adiposity is linked to several abnormalities which impact ß cell function and viability. These include glucotoxicity, lipotoxicity, increased oxidative stress, and inflammation. In addition, insulin signaling in the ß cell is essential to its own functionality and viability, and obesity-related abnormalities in insulin signaling are known to induce failure of insulin secretion and hyperglycemia. Insulin resistance in the ß cell arises from defects in phosphorylation/activation of insulin receptor substrates (IRS) proteins, which result in impairment in glucose sensing, glucose stimulated insulin secretion, and also in increased loss of ß cells. This review intends to provide an update on the main characteristics and mechanisms that link obesity and insulin resistance to ß cell dysfunction in the pathogenesis of DM2.

Phosphate Metabolism in Cardiorenal Metabolic Disease.

Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.