Ozlem Soyluk

Interleukin-6-producing pheochromocytoma presenting with fever of unknown origin

Pheochromocytoma usually presents with typical signsand symptoms, such as headache, sweating, and palpita-tions due to excessive catecholamine release. Few publica-tions have reported that these tumors are capable ofsecreting a variety of bioactive neuropeptides and hormonesother than catecholamines, resulting in unusual clinicalmanifestations.

True Vitamin D Deficiency with Secondary Hyperparathyroidism

To the Editor: We read with interest the article by Koeckhoven, et al 1 suggesting that upper leg strength is associated with 25-hydroxy Vitamin D [25(OH)D] levels in patients with knee osteoarthritis (OA). The association seems to exist when adjustment is made for several confounding factors. However, adjusting for body mass index attenuated this association. One important limitation of their … Address correspondence to Dr. F. Tufan, Istanbul University, Istanbul Faculty of Medicine, Department of Geriatrics, Fatih, P.B. 34093, Istanbul, Turkey. E-mail: drfatiht{at}istanbul.edu.tr

Importance of hypoglycemia on the risk of Alzheimer's disease in elderly subjects with diabetes mellitus.

Dear editor We read the article on the study of “Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment” by Li et al.1 The review is very detailed and rational, considering the link between diabetes and Alzheimer’s disease and giving a new outlook as type 3 diabetes. It provides important information about the effects of the hyperglycemic complications of diabetes and treatment of dementia. We would like to emphasize a very important aspect of the diabetes–dementia association. The negative effects of acute hypoglycemia on executive function in adults with diabetes are well known.2 Recent data indicate that hypoglycemic events may also precipitate dementia in the chronic period.3–5 In a 27-year long longitudinal study involving 16,667 diabetic subjects with a mean age of 65 years, 11% developed dementia.3 Among subjects who developed dementia, 16.95% had at least one episode of hypoglycemia. Another prospective population-based study that involved 783 elderly adults suggested that subjects who experienced hypoglycemic events had a twofold increased risk of developing dementia compared with those who did not.4 Another study involving 169,114 cases with new-onset dementia indicated that subjects with diabetes had a higher risk of dementia if they had prior cerebrovascular disease, peripheral vascular disease, chronic kidney disease, or a history of one or more hospital admissions for hypoglycemia.5 Contribution of hypoglycemia to the development of dementia was also observed in a cohort study that consisted of 1,342 diabetic patients in Italy.6 In this study, multivariate analysis showed that advanced age, female sex, and hypoglycemic events were independently associated with increased risk of dementia. Moreover, the risk was higher in subjects under oral hypoglycemic drugs. There are also experimental studies regarding the effects of hypoglycemia on the risk of dementia. Hypoglycemia leads to hyperphosphorylation of tau in a study performed on rat brain cells.7 Patients with elderly-onset type 2 diabetes have better glycemic control and lower rates of microvascular complications than elderly subjects with adult-onset diabetes.8 Furthermore, hypoglycemic complications have the potential to be more dangerous because adrenergic symptoms of hypoglycemia are more silent in elderly diabetics.9 Thus, consideration of the adverse effects of hypoglycemia is crucial, especially in frail elderly subjects. Although it is important to control hyperglycemia in elderly subjects, avoidance from hypoglycemia is of paramount importance to lower the risk of dementia. In this context, individualized glycemic targets should be utilized.

Confounders Regarding the Association of Insulin Resistance and Alzheimer Disease.

Confounders Regarding the Association of Insulin Resistance and Alzheimer Disease To the Editor We read the article by Willette et al1 with interest. The findings of this study are important because insulin resistance is a growing health problem, and measures to decrease the incidence of Alzheimer disease (AD) are urgently needed. However, we have some comments on this welldesigned and well-performed study. First, checking fasting glucose levels only once may be insufficient to diagnose or exclude diabetes mellitus (DM). For an accurate diagnosis of DM, fasting glucose levels of 126 mg/dL or greater on 2 occasions (to convert to millimoles per liter, multiply by 0.0555), a glycated hemoglobin level of 6.5% or greater (to convert to proportion of total hemoglobin, multiply by 0.01), a random blood glucose level of 200 mg/dL or greater with accompanying symptoms, or a second-hour blood glucose level at 75-g oral glucose tolerance test of 200 mg/dL or greater are needed. Older adults with DM, especially, may have normal fasting blood glucose levels.2 To draw more accurate conclusions regarding the association of insulin resistance and AD, measuring postprandial glucose levels and/or glycated hemoglobin levels would prove beneficial. Second, reactive hypoglycemic episodes and glucose variability may also increase the risk for AD in those with insulin resistance. A prospective population-based study that involved 783 elderly adults suggested that patients who experienced hypoglycemic events had a 2-fold increased risk for developing dementia compared with those who did not.3 Kim et al4 observed that a greater degree of visit-to-visit glucose variability resulted in deterioration of certain cognitive functions in patients with DM. Notably, this association was independent from mean glucose levels. Thus, in the study by Willette et al,1 glucose variability might have affected brain glucose metabolism negatively in individuals with insulin resistance. Matthews et al5 investigated the association between adherence to a Mediterranean diet and physical activity and brain glucose metabolism and amyloid burden. They showed that physical activity and adherence to a Mediterranean diet were associated with better brain-glucose metabolism and decreased brain-amyloid burden. Interestingly, important confounders, such as apolipoprotein E genotype, hypertension, and insulin resistance, did not attenuate these associations. Thus, physical activity level and diet characteristics may also be important confounders. In conclusion, we suggest that consideration of the factors mentioned here (reactive hypoglycemia, glucose variability, physical activity level, and diet characteristics) would make interpretation of the findings of Willette et al1 more accurate. Future studies regarding the association of insulin resistance and AD would better assess these factors as well.

Under-representation of frail older people in meta-analysis of dipeptidyl peptidase-4 inhibitors and hypoglycaemia.

Salvo and colleagues’ meta-analysis is limited by the under-representation of frail older people.1 The study by Barnett and colleagues was the only …

Potential Risk of Increased Risk of Falls Associated With High Doses of Vitamin D.

Witte el al. [(1)][1] reported beneficial effects of 1-year high-dose vitamin D treatment on left ventricle structure and function, despite a tendency toward worse 6-min walk distance (6MWD), which was the primary outcome of this trial. We would like to make a comment about a potential adverse

Healthy Behaviors Potentially Due to Calorie Restriction.

1. Patel KK, Young L, Howell EH, et al. Characteristics and outcomes of patients presenting with hypertensive urgency in the office setting. JAMA Intern Med. 2016;176(7):981-988. 2. Wolf SJ, Lo B, Shih RD, Smith MD, Fesmire FM; American College of Emergency Physicians Clinical Policies Committee. Clinical policy: critical issues in the evaluation and management of adult patients in the emergency department with asymptomatic elevated blood pressure. Ann Emerg Med. 2013;62(1):59-68. 3. Levy PD, Mahn JJ, Miller J, et al. Blood pressure treatment and outcomes in hypertensive patients without acute target organ damage: a retrospective cohort. Am J Emerg Med. 2015;33(9):1219-1224. 4. McNaughton CD, Self WH, Zhu Y, Janke AT, Storrow AB, Levy P. Incidence of Hypertension-Related Emergency Department Visits in the United States, 2006 to 2012. Am J Cardiol. 2015;116(11):1717-1723. 5. Brody A, Rahman T, Reed B, et al. Safety and efficacy of antihypertensive prescription at emergency department discharge. Acad Emerg Med. 2015;22(5): 632-635.

Potential contribution of diabetes mellitus to orthostatic blood pressure fall and conversion of mild cognitive impairment to dementia.

Dear editor We read the article “Orthostatic blood pressure in people with mild cognitive impairment predicts conversion to dementia” by Hayakawa et al1 with interest. It is well-known that many individuals with mild cognitive impairment (MCI) progress to dementia.2 However, we do not exactly know which risk factors increase this risk and to what extent. Hypertension is a risk factor for Alzheimer’s disease and vascular dementia. However, the findings of this study make us consider hypotension as a new risk factor for dementia. Furthermore, a recently published 6-year prospective general population cohort study suggested that not only orthostatic hypotension (OH), but also symptoms of OH seemed to be risk factors for cognitive decline.3 Notably, in the study by Elmstahl et al3, hypertension and diabetes mellitus (DM) were more common in subjects with dementia. We would like to make some comments on this well-designed study. The prevalence of DM is rather high in elderly individuals, and diabetic autonomic neuropathy may cause significant autonomic dysfunction. Furthermore, reactive hypoglycemic attacks and glucose variability may also increase the risk of Alzheimer’s disease in subjects with DM.4–6 Glucose variability and hypoglycemic attacks precipitated by insulin resistance may also affect conversion of MCI to dementia.7 Accurate diagnosis of DM is especially important in older adults who may not experience typical symptoms of hyperglycemia and may even have normal fasting blood glucose levels. Thus, the diagnosis of DM may be easily overlooked in elderly subjects.8 However, in the study by Hayakawa et al1, a detailed assessment for the presence or absence of DM is not reported and the rate of DM in the study population seems to be lower than anticipated. We suggest that for an accurate diagnosis of DM, checking fasting glucose, postprandial glucose, and HbA1c levels is essential.8 In conclusion, undiagnosed DM, glucose variability, and postprandial hypoglycemia might have contributed significantly to OH and to conversion of MCI to dementia in this study.

The relationship of Beck depression inventory with vitamin D levels and visceral fat mass in cancer patients

Purpose: The aim of this study is to determine the relationship between Beck Depression Inventory (BDI) and vitamin D levels, total and visceral fat mass in cancer patients. Methods: A total of 219 patients participated in this study. Patients’ blood tests including prealbumin, vitamin D levels, BMI values and total and visceral fat masses were measured. Also, all subjects completed a self-administered BDI questionnaire. Obtained data were analyzed by using NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA). Results: A total of 219 patients consisted of 53.9% (n=118) females and 46.1% (n=101) males with median age 52.41±13.66 (range, 19-84) years. Mean BMI value was 24.70±3.75 kg/m2; mean BDI score was 13.02±8.72; and mean prealbumin level was 0.21 ± 0.07 g/L. BMI was negatively correlated with BDI in all study groups (P=0.002). Also prealbumin levels, vitamin D levels and hemoglobin levels were negatively correlated with BDI (P<0.05 for all). But no significant correlation was determined between total fat mass, visceral fat mass levels and BDI (P>0.05). Depression status had a significant relationship with BMI, vitamin D levels, prealbumin levels and malnutrition status in patients (P = 0.008, 0.001, 0.001, and 0.001, respectively). Conclusions: We have determined a significant correlation between vitamin D levels and BDI scores in cancer patients. Also prealbumin and hemoglobin levels may indicate BDI scores in cancer patients. There was no correlation between BDI score and visceral fat mass. There was a negative correlation between BDI score and BMI levels but no correlation was found between BDI score and total or visceral fat mass in cancer patients. Thus vitamin D levels could be used to determine the depression and nutritional status in cancer patients which may help to improve the clinical outcomes in those patients.

Might excess body weight be beneficial for the community-dwelling older people?

They reported thatcompared with their normal weight counterparts, the oddsratio (OR)s in underweight and obese adults were higherfor physical mobility limitation (PM) (1.30, 2.31), for largemuscle function limitation (LMF) (1.20, 1.63) for activitiesof daily living limitation (ADL) (2.02, 1.40), for gross mo-tor function limitation (GMF) (1.96, 1.77), for fine motorfunction limitation (FMF) (1.66, 1.34), respectively.Accordingly, they suggested that their findings reinforcethe importance of obesity prevention throughout people’slife span including the life transitions such as retirement,in an effort to improve health outcomes in later years.Althoughweappreciatethisdetailedstudy,wewouldliketo point out an important finding of their study which webelieve that is disregarded in the manuscript. When one ex-amines Table 2 of the study on adjusted odds ratios of func-tional limitations estimated in mixed-effect logisticregressions, it is seen that, compared with normal weight,the ORs in overweight adults were significantly lower forADL (0.926) and for FMF (0.925) (p ! 0.05) while theORwasnotsignificantlydifferentforGMFsample.