100 Years, 100 JDRF Scientists: Gian Franco Bottazzo, M.D.

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Publication Islet-Cell Antibodies for Type 1 Diabetes, Gian Franco Bottazzo - 1974

During our 50+ years of advancing diabetes research, JDRF has funded the best and the brightest investigators. But which of them have contributed the most to what we know about type 1 diabetes (T1D) today? In honor of the 100th anniversary of the first administration of insulin, JDRF is launching “100 Years, 100 JDRF Scientists,” the story of the scientists who contributed to discoveries that played a part in the vast knowledge that we have about diabetes today.

The first up: Gian Franco Bottazzo, M.D. Born in Venice, he obtained his M.D. degree in 1971 at the University of Padua. Shortly after, he began a research fellowship with immunologist Deborah Doniach, M.D., at Middlesex Hospital, and, in 1998, he returned to Rome. He died in 2017.

Aha! An Autoimmune Disease!

When JDRF was founded, there were no types of diabetes. There was no type 1, no type 2. It was all diabetes.

But, early on in Bottazzo’s fellowship, in 1974, he discovered—for the first time—that diabetes is associated with the development of islet cell antibodies (ICA), leading to a landmark publication in the field.1 This was instrumental in establishing type 1 diabetes (T1D) as an autoimmune disease.

The discovery of ICA introduced a new era of diabetes research and understanding:

Gian Franco Bottazzo, M.D.
Gian Franco Bottazzo, M.D.

1. A chronic disease: Together with Andrew Cudworth, M.B., and funded with a JDRF grant, Dr. Bottazzo measured ICA in samples from relatives of individuals with T1D. In 1981, they reported that ICA was detectable years before the clinical onset of disease,2 a finding that eventually led to the notion that T1D was a chronic disease.

2. Before clinical symptoms: Moreover, ICA were shown to have value in identifying individuals who would later develop T1D, providing new staging for presymptomatic T1D. It also enabled the discovery of more antibodies that were associated with T1D. There are now five antibodies—ICA, GAD65, IAA, IA-2, and ZnT8—connected with the disease. The presence of two or more means that your lifetime risk of getting T1D is nearly 100 percent. Dr. Bottazzo’s research contributed to a number of studies about the genetic risk of developing T1D.3,4

3. Refine the tests for T1D-related antibodies: These were quantified by “Juvenile Diabetes Foundation (JDF) units,”5,6 a measure of the number of T1D-specific antibodies that were detected in a person. This led to the formation of a number of clinical studies to determine the risk of T1D—DAISY, ASK, and TrialNet in the United States, BABYDIAB in Germany, DIPP in Finland, and DiPiS in Sweden.

More recently, JDRF initiated T1Detect, an education and awareness program to expand screening to the general population. The program’s aim is to make people understand what type 1 is, how screening is advantageous to the public, how they can be involved, and what to do if you are positive for T1D-specific antibodies.

4. Conduct clinical trials: It also enabled clinical trials aimed at delaying the clinical onset of diabetes, before symptoms appear. This includes teplizumab—a drug that blocks CD3, a blood marker that helps activate immune cells. It was the first study to significantly delay the onset of T1D, for nearly 3 years, in individuals at-risk of developing the disease.

I hope you enjoyed reading about a T1D champion. Follow up each week to find out who we selected and their major discoveries, in honor of the 100th anniversary of the first administration of insulin.

Research is how insulin was discovered as a therapy for diabetes, and JDRF research is advancing us toward cures and the next generation of life-changing breakthroughs for T1D.

  1. Bottazzo GF, Florin-Christensen A, Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974 Nov 30; 2 (7892): 1279-83. PMID: 4139522.
  2. Gorsuch AN, Spencer KM, Lister J, McNally JM, Dean BM, Bottazzo GF, Cudworth AG. Evidence for a long prediabetic period in type I (insulin-dependent) diabetes mellitus. Lancet. 1981 Dec 19-26; 2: 1363-1365. doi: 10.1016/S0140-6736(81)92795-1. PMID: 6118756.
  3. Bottazzo GF, Pujol-Borrell R, Hanafusa T, Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983 Nov 12; 2 (8359): 1115-1119. doi: 10.1016/S0140-6736(83)90629-3. PMID: 6138647.
  4. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985 Aug 8; 313 (6): 353-60. doi: 10.1056/NEJM198508083130604. PMID: 3159965.
  5. Bonifacio E, Bingley PJ, Shattock M, Bean BM, Dunger D, Gale EA, Bottazzo GF. Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet. 1990 Jan 20; 335: 147-149. doi: 10.1016/0140-6736(90)90013-U. PMID: 1967440.
  6. Gleichmann H, Bottazzo GF. Progress toward standardization of cytoplasmic islet cell-antibody assay. Diabetes. 1987 May; 36 (5): 578-584. doi: 10.2337/diab.36.5.578. PMID: 2436962.