Dr. Rita Kalyani is a junior faculty member in the Division of Endocrinology and Metabolism at the Johns Hopkins School of Medicine where her clinical practice is dedicated to the prevention and treatment of diabetes. She previously completed a Masters of Health Science in Clinical Investigation at the Johns Hopkins School of Public Health where she applied her training in epidemiology and study design to characterize the association of diabetes with disability in routine physical tasks. With the support of this Mentored Career Development Award (CDA), Dr. Kalyani seeks to establish the role of dysglycemia and/or insulin resistance (IR) in accelerated muscle loss and the role of current diabetes treatment modalities such as exercise or insulin-sensitizing medications in mitigating these effects. She also aims to better characterize skeletal muscle mitochondrial dysfunction in type 2 diabetes as a pathway connecting IR with subsequent loss of muscle mass and strength. Dr. Kalyani will (1) enhance her research knowledge and skills with training in clinical translatio research including: trial management, biostatistics, gerontology, body composition assessment, skeletal muscle physiology, and hyperinsulinemic-euglycemic clamp, (2) be mentored by an interdisciplinary team of experienced researchers, and (3) be immersed in the research and clinical environments of the Johns Hopkins Diabetes Center, the Welch Center for Epidemiology, Prevention and Clinical Research, the Johns Hopkins Exercise Physiology and Body Composition Core, the Johns Hopkins Center on Aging and Health, and intramural National Institute on Aging--Clinical Research Branch. This CDA will provide her with the skills she needs to become an independent investigator in accelerated muscle loss as a complication of type 2 diabetes. Building upon her prior experience in applying functional outcomes to diabetes research, she has developed a novel approach to understand and clinically assess the association of dysglycemia and/or IR with muscle loss that draws upon the fields of endocrinology, epidemiology, gerontology, and exercise physiology.
In Aim 1, she will use two established datasets, one cross-sectional and one longitudinal, to identify clinical biomarkers of dysglycemia and indices of IR that predict decreased lower extremity muscle mass and strength.
In Aim 2, she will determine the extent to which the ability of exercise to attenuate muscle loss in persons with diabetes depends upon the existing severity of dysglycemia or IR, in a trial comparing a 6 month exercise training intervention to a control condition.
In Aim 3, she will recruit drug-naive adults with diabetes into a novel clinical study to investigate how an oral agent (pioglitazone) that improves peripheral insulin sensitivity, directly assessed with clamp, can effect changes in distinct but related aspects of skeletal muscle mitochondrial function--in vitro using percutaneous muscle biopsy and in vivo using 31P magnetic resonance spectroscopy-- versus placebo and whether effects differ by age. These findings should establish a framework to evaluate the ability of existing diabetes therapies to preserve muscle and potentially identify new therapeutic targets.

Public Health Relevance

The factors related to accelerated muscle loss in diabetes are poorly understood, despite the growing prevalence of diabetes and increasing recognition of higher disability in this population. Studying the direct relationship of abnormal glucose metabolism with the subsequent loss of muscle mass and strength will give insights into how current diabetes treatments and novel future therapies targeted to underlying pathways can be used to preserve muscle and ultimately improve the health of persons aging with diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DK093583-01A1
Application #
8442963
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2012-09-01
Project End
2016-07-31
Budget Start
2012-09-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$158,705
Indirect Cost
$11,756
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Godino, Job G; Appel, Lawrence J; Gross, Alden L et al. (2017) Diabetes, hyperglycemia, and the burden of functional disability among older adults in a community-based study. J Diabetes 9:76-84
Kalyani, Rita R; Golden, Sherita H; Cefalu, William T (2017) Diabetes and Aging: Unique Considerations and Goals of Care. Diabetes Care 40:440-443
Kalyani, Rita Rastogi; Ji, Nan; Carnethon, Mercedes et al. (2017) Diabetes, depressive symptoms, and functional disability in African Americans: the Jackson Heart Study. J Diabetes Complications 31:1259-1265
Fabbri, Elisa; Chia, Chee W; Spencer, Richard G et al. (2017) Insulin Resistance Is Associated With Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants Without Diabetes From the Baltimore Longitudinal Study of Aging. Diabetes 66:170-176
Quartuccio, Michael; Buta, Brian; Kalyani, Rita R (2017) Comparative Effectiveness for Glycemic Control in Older Adults with Diabetes. Curr Geriatr Rep 6:175-186
Quartuccio, Michael; Simonsick, Eleanor M; Langan, Susan et al. (2017) The relationship of health literacy to diabetes status differs by sex in older adults. J Diabetes Complications :
Buta, Brian; Choudhury, Parichoy Pal; Xue, Qian-Li et al. (2017) The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases. J Am Geriatr Soc 65:619-624
Quartuccio, Michael; Hall, Erica; Singh, Vikesh et al. (2017) Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet Autotransplantation. J Clin Endocrinol Metab 102:801-809
Williams, Marlene S; Cushman, Mary; Ouyang, Pamela et al. (2016) Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis. J Womens Health (Larchmt) 25:166-72
Buta, Brian J; Walston, Jeremy D; Godino, Job G et al. (2016) Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev 26:53-61

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