Browsing by Author "Khare, Swapnil"

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    Cystic fibrosis related diabetes (CFRD) prognosis
    (Elsevier, 2021-11-19) Sandouk, Zahrae; Khan, Farah; Khare, Swapnil; Moran, Antoinette; Medicine, School of Medicine
    Cystic fibrosis related diabetes (CFRD) occurs in at least 40-50% of adults with CF. With other forms of diabetes, microvascular and macrovascular disease are the major causes of morbidity and mortality. Macrovascular disease is rare in CF. While microvascular disease does occur in this population, there are CF-specific diabetes complications that have a more important impact on prognosis. The additional diagnosis of diabetes in CF is associated with decreased lung function, poor nutritional status, and an overall increase in mortality from lung disease. These negative findings start even before the clinical diagnosis of CFRD, during the period when patients experience abnormal glucose tolerance related to insulin insufficiency. The main mechanisms by which CFRD negatively affects prognosis are thought to be a combination of 1) protein catabolism, decreased lean body mass and undernutrition resulting from insulin insufficiency, and 2) an increased pro-inflammatory and pro-infectious state related to intermittent hyperglycemia. With the introduction of CFTR modulators, the care of CF patients has been revolutionized and many aspects of CF health such as BMI and lung function are improving. The impact of these drugs on the adverse prognosis related to the diagnosis of diabetes in CF, as well as the potential to delay or prevent onset of CFRD remain to be determined.
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    Cystic fibrosis-related diabetes: Prevalence, screening, and diagnosis
    (Elsevier, 2021-12-07) Khare, Swapnil; Desimone, Marisa; Kasim, Nader; Chan, Christine L.; Medicine, School of Medicine
    Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.
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    Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis
    (Elsevier, 2021-11-16) Kasim, Nader; Khare, Swapnil; Sandouk, Zahre; Chan, Christine; Medicine, School of Medicine
    Oral glucose tolerance testing (OGTT) is the primary method to screen for and diagnose cystic fibrosis-related diabetes (CFRD). Diagnostic thresholds as currently defined are based on microvascular complications seen in type 2 diabetes. Abnormal glucose tolerance (AGT) refers to OGTT glucose elevations outside the normal range and encompasses both impaired and indeterminate glucose tolerance. Current guidelines define impaired glucose tolerance (IGT) as a 2-hour glucose of 140-199 mg/dL (7.8-11 mmol/L) and indeterminate glucose tolerance (INDET) as any mid-OGTT glucose ≥ 200 mg/dL (11.1 mmol/L) with a normal fasting and 2 h glucose. There is growing evidence that AGT also has associations with CF-centered outcomes including pulmonary decline, hospitalizations, and weight loss. Here we aim to review the historical emergence of glucose tolerance testing, review relevance to risk stratification for CFRD, discuss alternate cutoffs for identifying AGT earlier, and highlight the need for larger, future studies to inform our understanding of the implications of IGT and INDET on CF health.
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    Maintaining Blood Glucose Levels in Range (70–150 mg/dL) is Difficult in COVID-19 Compared to Non-COVID-19 ICU Patients—A Retrospective Analysis
    (MDPI (Multidisciplinary Digital Publishing Institute), 2020-11-12) Kapoor, Rajat; Timsina, Lava R.; Gupta, Nupur; Kaur, Harleen; Vidger, Arianna J.; Pollander, Abby M.; Jacobi, Judith; Khare, Swapnil; Rahman, Omar; Medicine, School of Medicine
    Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70–150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70–150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70–150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70–150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.
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    Rapid Resolution of Megestrol Acetate Associated Adrenal Insufficiency
    (2021-06-13) Steele, Emily K.; Afshari, Sonia; Khare, Swapnil
    Introduction Megestrol acetate (MA) is a synthetic progestin commonly used for appetite stimulation. Several case reports have associated use of MA with adrenal insufficiency (AI) through suppression of the hypothalamic-pituitary-adrenal axis. To our knowledge, our case is the first to establish a timeline of onset and resolution of AI associated with MA. Case We present a 52-year-old female with a past medical history significant for hypothyroidism, systemic lupus erythematosus, Raynaud’s, chronic diarrhea, anemia, and reflex sympathetic dystrophy. She was admitted for small bowel obstruction requiring exploratory laparotomy with lysis of a single adhesion. She developed hypoglycemia blood glucose ranging from 55-60 mg/dL on hospital day 24, after starting nocturnal nasogastric tube feedings. She had poor appetite, weight loss, and intermittent nausea. She did not have a history of exogenous steroids. Physical exam was unremarkable aside from cachectic-appearing body habitus with a BMI of 17. Vital signs were stable. Her TSH, renal function, and liver studies were normal. Serum cortisol was checked on hospital day 27 and was very low, 1.1 mCg/dL (normal range, 5-25 mCg/dL). Endocrine was consulted for evaluation of hypoglycemia and adrenal insufficiency (AI). She had an adequate cortisol response to a 250 mcg cosyntropin stimulation. However, baseline ACTH was inappropriately normal, given her very low serum cortisol, suggesting secondary AI. Upon detailed chart review, we noted that she was started on megestrol acetate (MA) 20 mg PO daily on hospital day 20 for appetite stimulation. We suspected megestrol acetate to be the cause of her secondary AI and hypoglycemia. Within three days after discontinuation of MA, the patient’s hypoglycemia resolved and serum cortisol returned to normal. Discussion Megestrol acetate is a synthetic progestin frequently used as appetite stimulant. MA is known to have glucocorticoid properties with affinity for glucocorticoid receptors. There are several case reports associating MA with AI which is a potentially life-threatening condition. The mechanism is thought to be suppression of the HPA axis. AI has been noted with doses of 400-600 mg however exact dose and timeline has never been described. Our case is unique where she developed AI after a relatively very low dose of 20 mg daily for only one week. Within three days following identification of the possibility of MA as the inducing agent and subsequent discontinuation, the patient’s AI resolved. This rapid recovery is remarkable and gives important insight about possible impact of dose and duration in resolution of AI associated with MA. MA is frequently used as an appetite stimulant and it is very important to be aware of potentially life threatening side effects of AI. A timeline for development of MA induced AI and resolution has not been shown in previous case reports; ours is the first case to outline the dose and timeline for recovery, although further research is needed to confirm these findings.