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Cited by 25Pancreatic function and diabetesDiabetes Management and ResearchDiabetes and associated disorders

Islet transplantation for hypoglycemia unawareness/severe hypoglycemia: caveat emptor

Harlan, David M.·2016·Diabetes Care
DOI 10.2337/dci16-0008
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Abstract

Current estimates are that 1.25 million Americans have type 1 diabetes (T1D) (1) caused by the gradual loss of nearly all pancreatic insulin-producing β-cells via a presumed T cell–mediated autoimmune process (2). Eventually, all with T1D display severely impaired endogenous insulin production (3) and are dependent upon injected insulin for survival. Because subcutaneously administered insulin displays sluggish “on” and delayed “off” kinetics compared with that from pancreatic β-cells, the glycemic control patients achieve using subcutaneous insulin is suboptimal. For too many individuals, chronic episodic hypoglycemia dulls the typical compensatory responses, leading to impaired hypoglycemia awareness. Absent the usual warning symptoms of a blood glucose too low to sustain higher cognitive functions, such individuals are susceptible to severe hypoglycemic events defined as those requiring assistance from others to recover. Some die as a result of severe and prolonged hypoglycemia (4). Severe hypoglycemia occurs with alarming frequency among patients with T1D (5). Scientists have long dreamed of restoring endogenous insulin production for those with T1D. One approach has been allogeneic pancreas transplantation. However, most pancreatic tissue makes digestive enzymes, and any damage to the organ can lead to leakage and potentially serious complications. In the 1970s, investigators reasoned that isolated pancreatic islets (only about 2% of the pancreatic mass) might be transplanted via a percutaneous cannula avoiding surgical and other complications associated with pancreas transplantation (6). Early clinical islet transplantation results, however, were disappointing (7). Then in 2000, Shapiro et al. (8) reported seven consecutive T1D patients achieving 1-year insulin independence following islet transplantation, but serious issues remained. For instance, the only currently viable islet source is cadaveric donors. In 2015, the U.S. had only ∼9,000 such donors, of which ∼1,300 were deemed suitable for pancreas transplantation (9). Also, islets suitable for transplant are successfully isolated from approximately …

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  • For people with type 1 diabetes with level 3 hypoglycemia and hypoglycemia unawareness that persists despite medical treatment, human islet transplantation may be an option, but the approach remains experimental.

    “For people with type 1 diabetes with level 3 hypoglycemia and hypoglycemia unawareness that persists despite medical treatment, human islet transplantation may be an option, but the approach remains experimental (96,97).”

    From 6. Glycemic Targets: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [97]

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Authors
Harlan, D. M.
Affiliations
University of Massachusetts Chan Medical School (US)
Corresponding author
Harlan, David M.
ORCID
Harlan, David M.
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2016-06-09
Volume
39
Issue
7
Pages
1072-1074
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dci16-0008
OpenAlex
W2464749673
Cited by
25
References
24
Citations by year
2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 1
FWCI
3.32
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
islet transplantation, type 1 diabetes, hypoglycemia unawareness, severe hypoglycemia, endogenous insulin production, beta cell destruction, islet isolation, insulin independence, glycemic control
MeSH terms
Blood Glucose, Diabetes Mellitus, Type 1, Humans, Hypoglycemia, Islets of Langerhans Transplantation

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