NIH – Understanding Skeletal Effects of Type 1 Diabetes (R01 Clinical Trial Optional)

May 21, 2018 by School of Medicine Webmaster

There is growing evidence that the skeleton is negatively affected in type 1 diabetes (T1D). Early age of onset, long duration, frequency and severity of episodes of hypoglycemia and hyperglycemia, and diabetic ketoacidosis at the time of diagnosis may increase risk for impaired bone integrity.  However, the dearth of large-scale studies involving longitudinal assessment of glycemic control and skeletal involvement in T1D has limited our knowledge of how specific parameters associated with T1D (e.g., age of onset, disease duration, glycemic control, frequency, and severity of hypoglycemic and hyperglycemic episodes) may lead to changes in bone accrual, bone structure and function, that in turn increase the susceptibility for fractures across the lifespan.   Recent advances in assessment of bone quality, turnover and other parameters could lead to improvements in characterizing bone structure/function, and promote the understanding of the link between T1D and bone fragility.  If specific bone defects and risk factors for adverse bone outcomes could be defined, treatment protocols could be developed to limit these complications associated with T1D. Definition of when during the course of T1D bone abnormalities develop, and how they relate to glycemic excursions and glycemic control, may yield strategies to improve skeletal health in T1D.

Research Objectives

Types of studies and study questions include but are not limited to:

  • New, studies specifically focused on bone health in individuals with T1D involving comprehensive skeletal assessment (e.g., radiological testing, mechanical assessments) and deep metabolic and clinical phenotyping, including associated factors of relevance to skeletal complications of T1D (e.g., glycemia, adiposity, renal function, vascular status, inflammatory markers).
  • Addition of comprehensive skeletal measures (e.g., imaging, biomarkers) and associated factors of relevance to skeletal integrity (e.g., diet, metabolic control, adiposity, vascular, inflammatory markers), to existing studies of T1D cohorts with well-characterized clinical correlates and course of disease.
  • Ascertainment of the role of co-morbid conditions, such as celiac disease or chronic kidney disease, that may interact with T1D to alter bone health.
  • Ascertainment of endocrine or paracrine factors mediating the interaction of muscle and/or adipose tissues with bone and how T1D might alter these interactions.
  • Addition of cohorts with T1D to studies that are already obtaining detailed measurement of bone status (e.g., including individuals with T1D in studies of bone health in individuals with type 2 diabetes to compare the effects of the two conditions and associated risk factors on skeletal integrity).

Longitudinal study designs are strongly encouraged. Particularly if new cohorts are being established, the project should describe what can be accomplished during the project period and how further follow-up might subsequently build on the findings during the project period supported by this award.

Research across the lifespan and health span is responsive to this FOA.  Studies that ascertain initiation of skeletal manifestation of T1D and how these progress over the course of T1D are encouraged.  Such studies could involve early stage T1D (autoimmunity or dysglycemia) prior to clinical recognition of disease.  Because established skeletal disease may be less modifiable as individuals advance in age and disease burden increases, research earlier in the clinical course of T1D is encouraged.  However, projects may also address skeletal health with established diabetes complications (chronic kidney disease, cardiovascular disease, neuropathy, etc.) and differences between skeletal health in those with T1D compared to type 2 diabetes.

Strong expertise in T1D and nutrition and skeletal physiology and skeletal ascertainment will be required of the research teams that will carry out the research supported by this FOA. It is anticipated that many of the funded research studies will involve the analysis and interpretation of complex, high-dimensional datasets. Therefore, it is strongly encouraged to include data scientists with relevant expertise on the research team. Collaborations between basic and clinical scientists are also encouraged but not required.

Applications with the following foci will be considered nonresponsive to this FOA:

  • New clinical trials to test the efficacy of interventions for skeletal complications of T1D.
  • Studies involving joints and arthropathies
  • Studies involving fracture repair
  • Animal studies

Applicants can propose ancillary studies to ongoing R01 or equivalent studies as well as to major ongoing clinical trials or longitudinal observational epidemiological studies.  While new clinical trials to test efficacy of interventions for skeletal complications of T1D are not responsive, ancillary studies to ongoing clinical trials may be responsive if they have the potential to elucidate the etiology of bone abnormalities function in T1D.

In addition, for ancillary study applications, this FOA will not fund the following:

  • Projects that need a new or separate clinical research infrastructure for sample collection and subject recruitment.
  • Projects that use samples or subjects from restricted clinical studies; such as those for which access to resources is only permitted to consortium members, or those that place restrictions on publications or data access that is inconsistent with NIH policy.
  • Core activities of ongoing clinical studies.

Deadline:  December 6, 2018 (letters of intent due 30 days prior to deadline)


Filed Under: Funding Opportunities