Examining primary care physician rationale for not following geriatric choosing wisely recommendations

Background The objective is to understand why physicians order tests or treatments in older adults contrary to published recommendations. Methods Participants: Physicians above the median for ≥ 1 measures of overuse representing 3 Choosing Wisely topics. Measurements: Participants evaluated decisions in a semi-structured interview regarding: 1) Screening men aged ≥ 76 with prostate specific antigen 2) Ordering urine studies in women ≥ 65 without symptoms 3) Overtreating adults aged ≥ 75 with insulin or oral hypoglycemic medications. Two investigators independently coded transcripts using qualitative analysis. Results Nineteen interviews were conducted across the three topics resulting in four themes. First, physicians were aware and knowledgeable of guidelines. Second, perceived patient preference towards overuse influenced physician action even when physicians felt strongly that testing was not indicated. Third, physicians overestimated benefits of a test and underemphasized potential harms. Fourth, physicians were resistant to change when patients appeared to be doing well. Conclusions Though physicians expressed awareness to avoid overuse, deference to patient preferences and the tendency to distort the chance of benefit over harm influenced decisions to order testing. Approaches for decreasing unnecessary testing must account for perceived patient preferences, make the potential harms of overtesting salient, and address clinical inertia among patients who appear to be doing well.

Ketosis Prone Diabetes in an Obese Male Adolescent: A Case Report

Introduction: Ketone-prone diabetes (KPD) is an atypical type of diabetes with features from both Type 1 and 2 diabetes, which may lead to its misdiagnosis. Patients usually present with an attack of DKA, but after its resolution, Insulin can be discontinued gradually in most patients with the maintenance of sufficient glycemic control with oral hypoglycemic medications. Clinical Case: A 14 -year-old Saudi male student, presented to the emergency department of our tertiary hospital in November 2017 complaining of nausea and vomiting of two days duration proceeded by a one-week history of generalized fatigue, polydipsia, and polyuria. The patient suffered from long-standing obesity since childhood; otherwise, past medical history was unremarkable. Family history was positive for Type II diabetes in his mother at the age of 48. On examination, the patient was dehydrated, tachypneic, and obese with a BMI of 34 kg/m2 and has patches of acanthosis nigricans over the neck and both axillae. Laboratory investigations showed blood glucose of 455 mg/dL, metabolic acidosis with a pH of 7.22, HCO3 of 11, and a high anion gap of 17, with urine being strongly positive for ketones (++++), HbA1c was 11.6%, and lipid profile showed dyslipidemia. The patient was diagnosed with diabetes ketoacidosis (DKA) and managed with Fluid, Insulin, and potassium infusions according to the Hospital’s DKA protocol. DKA resolved, and the patient was discharged with the impression of ketone prone diabetes based on the presentation of DKA along with features of insulin resistance. Discharge medications were Insulin Glargine 30 units SC once daily, Metformin 500 mg twice daily, and Gliclazide 60 mg Once daily. He was educated on usage and titration of insulin dosage according to glucose readings and monitoring. In subsequent follow-ups as an outpatient, it was noticed that the insulin requirements were gradually declining until it was possible to stop it completely after around six months of follow-up. The patient was transitioned from insulin to GLP-1 agonist (Liraglutide), which helped to achieve significant weight loss. After about one year, Liraglutide (Victoza) was not available in the hospital. However, the patient was controlled on Metformin and Gliclazide. Consequently, the patient has been in remission with adequate glycemic control and had not developed another attack of DKA. Latest review in the clinic in April 2020 showed his BMI of 27.4 kg/m2 and HbA1C of 7.5%. Conclusion: Although it is a rare and atypical type of diabetes, Ketosis Prone diabetes should be kept in mind when a patient presents with DKA but has features of insulin resistance to avoid misdiagnosis and inappropriate management, with proper education to patients and their families on the importance to titrate insulin requirements.

Risk Factors for Dementia Incidence Based on Previous Results of the Specific Health Checkups in Japan

Dementia is a common disease in elderly people, with its prevalence expanding rapidly worldwide. Longitudinal and cohort studies on lifestyle and health conditions are needed to identify the risk of dementia. This study aimed to identify the risk factors for dementia incidence in Japan and to clarify the strategy for its primary care. In this study, an analysis was performed to investigate the association between the cognitive faculty level of the long-term care certification survey and the previous results of the specific health checkups in Japan. To investigate the risk factor for dementia incidence, a multivariable logistic regression analysis was performed, which showed a significant odds ratio for the incidence of dementia for two items, including abdominal circumference and insulin injections or oral hypoglycemic medications. The findings of our study suggested that a lower abdominal circumference had a higher risk for dementia incidence, and individuals who received insulin injections or oral hypoglycemic medications had a higher risk for dementia incidence based on the results of the health checkups conducted 10 years previously. Further, longer duration study with a larger sample is needed to identify the items from the specific health checkups that are associated with the risk of dementia.

Reducing the Burden of Diabetes Treatment: A Review of Low-cost Oral Hypoglycemic Medications

Background: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. Objective: We conducted a narrative review of low-cost OHMs. Results: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. Results: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500–2,000/1,500–2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5–5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12–20 (sulfonylureas), 25–39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment. Conclusion: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.

Clinical case of factitious hypoglycemia

Hypoglycemic syndrome (HGS) is a significant decrease glucose in blood, manifested by neurological symptoms, and stopped by the introduction of glucose. Among the many causes of HGS the special place is taken by the factitious hypoglycemia, as one of the variants of Munchausen syndrome. Hypoglycemia in such cases is achieved by the intentional introduction of hypoglycemic drugs. The most commonly used medications are sulfonylurea derivatives, which are affordable, inexpensive and legal. The close collaboration of clinicians with the laboratory service plays a key role in the diagnosis of factitious hypoglycemia. Since the results of biochemical and hormonal analyzes in patients with hypoglycemia due to reception of oral hypoglycemic medications and pancreatogenous HGS are identical, the only way to differentiate these conditions is by detection of insulin secretagogue substances in the blood (or urine).The determination of oral hypoglycemic medications in cases of suspicion of artificial reception is not implemented in Russia. Factitious hypoglycemia in most cases is the diagnosis of exclusion, and its confirmation if often based on detection of medications among the personal effects of patient. This is a significant difficulty given the ethical standards. However, since 2018 we conduct in our Centre the determination of 7 oral hypoglycemic medications (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in patient’s blood using the liquid chromatography–tandem mass spectrometry (LC-MS). This article presents a clinical case of a patient without diabetes mellitus taking glibenclamide and detection of this drug using highly selective LC-MS.

SUN-687 MODY-14: A Rare Cause of Inherited Diabetes

Case: A 29-year-old physically active, lean man presented with a three-year history of poorly controlled diabetes diagnosed during a flu-like illness and no history diabetic ketoacidosis. Despite treatment with various oral hypoglycemic medications his glycated hemoglobin was consistently above target (never falling below 9.3%) and correlated with home blood glucose readings. His mother had gestational diabetes with all three of her pregnancies. His maternal grandmother was also known to have diabetes. Pancreatic islet antibodies were negative. C-peptide levels were low. Monogenic diabetes (MODY) was suspected. Discussion: Genetic testing revealed a mutation in the Adaptor Protein, Phosphotyrosine Interaction, PH domain, and leucine zipper containing 1 (APPL1) gene. APPL1 is involved in insulin secretion and insulin signaling via the Akt pathway [1,2,3]. Other mutations of APPL1 causing MODY-14 have been previously described [4]. In our case, the substitution of glutamate for aspartate at the 265 position occurs within the unique fourth alpha helix of the BAR domain of APPL1 [5]. Generally, BAR domains contribute to APPL1 dimerization and plasma membrane association [5]. Substitution of glutamate could disrupt protein folding, impairing dimerization and phosphorylation of Akt, thereby decreased insulin secretion as seen in other mutations of the BAR domain of APPL1 [4]. Although this remains a hypothesis, loss-of-function of APPL1 would explain the lack of insulin secretion without evidence of pancreatic autoimmunity. If the hypothesis is correct, it would be a novel mutation attributable to this MODY subtype. 1. Cheng KKY, Lam KSL, Wu D, et al. APPL1 potentiates insulin secretion in pancreatic β cells by enhancing protein kinase Akt-dependent expression of SNARE proteins in mice. Proc Natl Acad Sci U S A. 2012;109(23):8919–8924. doi:10.1073/pnas.1202435109 2. Ryu J, Galan AK, Xin X, et al. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor. Cell Rep. 2014;7(4):1227–1238. doi:10.1016/j.celrep.2014.04.006 3. Saito T, Jones CC, Huang S, Czech MP, Pilch PF. The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. J Biol Chem. 2007;282(44):32280–32287. doi:10.1074/jbc.M704150200 4. Prudente S, Jungtrakoon P, Marucci A, et al. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet. 2015;97(1):177–185. doi:10.1016/j.ajhg.2015.05.011 5. Li J, Mao X, Dong LQ, Liu F, Tong L. Crystal Structures of the BAR-PH and PTB Domains of Human APPL1. Structure. 2007;15(5):525–533. doi:10.1016/j.str.2007.03.011

Abstract 13252: The Effects of Pre-LVAD Diabetes on Post-LVAD Outcomes

Introduction: Diabetes Mellitus (DM) is a major risk factor for adverse cardiovascular (CV) outcomes. In this study, we investigated the effects of DM on post HeartMate II left ventricular assist device (LVAD) outcomes. Methods: In this retrospective study, 244 patients (Pts) were enrolled. Pts were stratified based on the presence or absence of pre-LVAD DM. DM was defined as a pre-existing history of DM requiring insulin or oral hypoglycemic medications or a new diagnosis of DM based on HgbA1C> 7mg/DL. Baseline information and post adverse outcomes were tabulated. Results: The cohort comprised of 108 diabetics and 136 non-diabetics. DM pts had a slightly worse baseline medical profile than non-DM. DM pts were more likely to be obese, had worse creatinine, and higher systolic and mean arterial blood pressure. DM pts also had a higher prevalence of atrial fibrillation, obstructive sleep apnea, and renal insufficiency. HgbAIC profiles revealed sub-optimal diabetic control at baseline (Table1). Post-LVAD, other than a higher incidence of hemolysis in the diabetic pts (12% vs 4%; p= 0.03), there were no differences between the two groups. Post LVAD HgbA1C was statistically significantly better (7.2 vs 6.1 P-value <0.001). Conclusions: Although DM is a poor risk factor for many adverse CV outcomes, there are no differences in adverse events in our pts post-LVAD placement compared to non-diabetic pts. This may be a result of improved access to care for diabetics, improvement in hemodynamics and biochemical derangements after normalization of cardiac output, or increased pancreatic blood flow. Our results indicate that diabetic pts who receive LVAD therapy are overall not at higher risk for adverse outcomes compared to non-diabetics. Further larger prospective studies are needed to validate our findings.