News & Research

1916-1949 | 1950-1969 | 1970-1979 | 1980-1989 | 1990-Present

1990

A new anti-rejection drug, FK506, is used in transplant patients.

Glucose is discovered to be distributed into muscle and fat cells via a transporter known as GLUT-4. Understanding how glucose is transported from the bloodstream into cells to be used as fuel is important to locating different drug targets that can improve insulin sensitivity.

GAD is identified as the 64K autoantigen. In mice, it is initially targeted as the body’s immune system attacks and destroys beta cells.

1991

Insulin receptor substrate-1 (IRS-1) is discovered. IRS-1 plays a role in intracellular signaling when insulin is present. This discovery opens the door to understanding insulin signaling.

1992

Researchers are able to prevent the destruction of beta cells in mice by specifically neutralizing the immune cells that would have attacked GAD. This therapy prevented the autoimmune process from the beginning, thereby preventing the mice from developing diabetes.

Daniel Kauffman, PhD, Mark Atkinson, PhD, and Noel MacLaren, MD identified the protein that is initially targeted as the body’s immune system attacks and destroys the beta cells that manufacture insulin in the pancreas. This protein, GAD, or glutamate decarboxylase, is an important enzyme involved in cellular communication in the brain and pancreas. The immune system’s attack on GAD triggers a progressive autoimmune response that leads to diabetes. After the researchers pinpointed the cause of the onset of diabetes, they were able to prevent the destruction of the beta cells in the mice by specifically neutralizing the immune cells that would have attacked GAD. This therapy prevented the autoimmune process from the beginning, thereby preventing the mice from developing diabetes.

1993

The showed that keeping blood glucose levels as close to normal as possible slows the onset and progression of eye, kidney, and nerve diseases caused by diabetes. In fact, it demonstrated that any sustained lowering of blood glucose helps, even if the person has a history of poor control.

1993-1997

An initiative to develop a resource consisting of comprehensive data and genetic material of type 2 diabetes families, GENNID (Genetics of Non-Insulin Dependent Diabetes), is begun. This material is made available to the scientific community for genetic studies of type 2 diabetes. Since 1993, DNA and data for over 6,100 individuals in over 1,800 families has been collected.

1994

Captopril is FDA approved to treat end-stage renal disease.

The Diabetes Prevention Trial – Type 1 (DPT-1) is started based on evidence in mice and a small study in humans. The study will determine whether or not injecting insulin or ingesting insulin tablets can prevent or mitigate the immune system attack on the beta cells that make insulin. Atkinson; Eisenbarth.

Leptin, the fat cell hormone that modulates feeding behavior and hormone secretion, is cloned. The Scandinavian Simvistatin Survival Study (4S) showed that cholesterol lowering with statins markedly reduced the risk of myocardial infarction, stroke or death. The effect was greatest in individuals with diabetes.

Mid-1990’s

The incretin hormone GLP-1 is discovered. Incretin hormones are secreted from the gut in response to food, and encourage the body to produce insulin. Discovery of GLP-1 will later lead to a new class of diabetes drugs that can increase insulin secretion in response to glucose, and even increase the amount of beta cells in the pancreas. Habener 1987; Weir G 1988.

PPAR gamma is cloned. PPAR gamma is a key regulator of fat cell differentiation and fat metabolism.

In addition to IDDM1 and IDDM2, researchers find 18 different chromosome regions which show some positive evidence of linkage to diabetes. However, there are probably no genes with large effects aside from IDDM1.

1995

The hormone adiponectin is discovered by American and Japanese investigators.

The drug metformin becomes available in the U.S.. Metformin is a biguanide that prevents glucose production in the liver.

Researchers discover different subsets of T helper cells in type 1 diabetes. T helper 1-like cells actively promote diabetes, while T helper 2-like cells invade the islets but do not prevent or promote disease.

The carbohydrate-counting approach to meal planning, based on the idea that carbohydrate is the main nutrient affecting glucose levels, becomes a popular option.

1996

The drug acarbose, brand name Precose (Bayer Corporation) becomes available in the U.S. Acarbose is an alpha-glucosidase inhibitor that slows digestion of some carbohydrates.

Lispro (a lysine-proline analog) is introduced by Eli Lilly and Company as the world’s fastest acting insulin.

Mutation in the gene HNF4 is shown to cause maturity onset diabetes of the young (MODY). Subsequently, mutations in an additional 5 genes are discovered to be associated with -cell dysfunction leading to MODY.

The Diabetes Prevention Trial – Type 2 (DPT-2) begins. This study will determine whether or not diet, exercise, and medications can prevent type 2 diabetes from developing in those with impaired glucose tolerance.

A noninvasive blood glucose meter (the Diasensor 1000, by Biocontrol Technology, Inc.) is submitted to the FDA for the first time. The application for approval is rejected and research continues.

1997

Troglitazone, brand name Rezulin (Parke-Davis), is approved by the FDA. It is the first in a class of drugs known as thiazolidinediones, and it improves insulin sensitivity in muscle cells. It is eventually removed from the market due to liver toxicity. Rosiglitazone and pioglitazone, also in this drug class, are later developed.

Type 1 and type 2 diabetes are now defined by cause rather than treatment. In addition, the fasting glucose level for diabetes is lowered from 140 mg/dl to 126 mg/dl.

1998

Repaglinide, brand name Prandin (Novo Nordisk) is developed. Repaglinide belongs to a class of drugs known as meglitinides. It stimulates insulin secretion in the presence of glucose.

The United Kingdom Prospective Diabetes Study (UKPDS) proves that people with type 2 diabetes who practice tight control of blood sugar levels and blood pressure levels reduce their risk of complications. The study also suggested that metformin could reduce the risk of cardiovascular deaths. Two small studies indicate that is as effective as injected insulin.

Research shows people with diabetes often have serious heart problems early in life. Aggressive treatment for all risk factors is encouraged.

2000

Researchers at the University of Alberta in Edmonton, Canada report on the success of an islet cell transplant technique known as the Edmonton protocol. This technique can restore long-term insulin production and glucose control in those with type 1 diabetes and unstable control, but insulin independence is usually not sustainable.

The Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) begins. HAPO is a study to determine whether hyperglycemia in pregnancy is associated with a high risk of poor maternal, fetal and neonatal outcomes. Metzger 2000.

2001

For the first time, investigators evaluate use of an insulin pump in older patients with type 2 diabetes. The study ultimately shows that both the insulin pump and multiple daily injections achieve excellent glycemic control with good safety and patient satisfaction. Raskin 2001; Herman 2001.

2001- 2002

The Finnish Diabetes Prevention Study showed in 2001 that moderate diet and exercise could reduce the onset of type 2 diabetes in individuals with impaired glucose tolerance by 58%. This is followed in 2002 by the U.S. Diabetes Prevention Program (DPP) which showed identical results and also showed that metformin could reduce the incidence of type 2 diabetes by 31%.

2002

Treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala), slows the deterioration of insulin production and improves metabolic control during the first year of type 1 diabetes in the majority of patients.

The American Diabetes Association defines pre-diabetes as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). IFG is defined as a fasting blood glucose of 100-125 mg/dl, and IGT is defined as a glucose level from 140 mg/dl – 199 mg/dl two hours after consuming a glucose-rich drink.

The DPT-1 study showed that neither low-dose insulin injections in people at high risk for developing type 1 diabetes, nor insulin capsules taken orally by people at moderate risk for type 1 diabetes were successful at preventing or delaying diabetes.

2003

Investigators begin to collaborate to develop basic science, clinical and translational research aimed at better understanding or preventing the onset of type 2 diabetes. Hirschhorn 2003; Hollenberg 2005

The Troglitazone in Prevention of Diabetes (TRIPOD) study treats women at risk of developing type 2 diabetes with TZDs. The results were dramatic: The drugs were apparently effective in preventing the onset of the disease.

2004

Researchers step-up efforts to find alternative sources of insulin producing cells for transplantation. The work of these researchers could lead to procedures that would ultimately restore the body’s ability to produce insulin. Burant 2004; Dong 2004; German 2004; Garfinkel 2004; Inverardi 2004; Robbins 2004; Yoon 2004.

Educational and behavioral clinical outcomes studies begin to support patients with type 2 diabetes in making the decision to choose, initiate and continue insulin therapy. Montori 2004; Rothman 2004.

Research into gaining a better understanding of diabetes during pregnancy and its effects on both mother and baby continues. Sharma 2004; Lernmark 2004; Catalano 2004.

2005

Exenatide, brand name Byetta, is approved in the U.S. as a first-in-class incretin mimetic (GLP-1) drug to treat type 2 diabetes. An injectable drug, exenatide works by increasing insulin production in response to blood glucose levels. Beinborn 2000.

Spurred by the obesity epidemic and increasing rates of type 2 diabetes in children, researchers focus on educational, behavioral, and nutritional outcome studies supporting a better understanding of healthy food choices in children and adolescents. Duffy 2005; Naar-King 2005; Raynor 2005.

Pramlintide, brand name Symlin, is approved in the U.S. as an injectable adjunct treatment for people (with type 1 or type 2 diabetes) who use insulin at mealtimes but still fail to achieve desirable blood glucose levels.

2006

The drug liraglutide enters phase 3 clinical trials. Liraglutide is a form of the natural hormone, GLP-1, that stimulates insulin production in the presence of glucose.

The first inhaled form of insulin to be FDA approved for adults with type 1 or type 2 diabetes, Exubera is found to be just as effective as short-acting insulin injections in controlling blood glucose levels.

Data from the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) study were reported at a meeting of the European Association for the Study of Diabetes (EASD). The results suggest that TZD treatment may prevent type 2 diabetes in patients at high risk.

FDA approves JANUVIA (sitagliptin phosphate), the first in a new class of drugs known as DPP-4 inhibitors that enhances the body's own ability to lower elevated blood sugar. DPP-4 is an enzyme that naturally blocks GLP-1 from working, so by inhibiting this enzyme, we are able to keep GLP-1 working in the gut to promote insulin secretion.
For the first time in our history an algorithm is developed for drug treatment of diabetes. This is having enormous implications for treatment, since doctors have a wide-array of treatment options.

A consensus paper is published on treatment of pre-diabetes (lifestyle modification versus drugs, and if the latter, what drug (s)).

Using a mathematical model, a "virtual" animal with type 1 diabetes is developed. This virtual animal model allows scientists to study the various ways in which type 1 diabetes develops, the impact of interventions to prevent diabetes, and to study the immunologic similarities/differences between humans and other animals.

Ongoing

Glycemic Control and Complications in Diabetes Mellitus Type 2, a Veterans Affairs Adminstration study, researches the effect of intensive glucose control on in patients with type 2 diabetes.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study sponsored by NHLBI and NIDDK, seeks to heart attack, stroke, or cardiovascular death in adults with type 2 diabetes using intensive glycemic, blood pressure, and lipid management.

The HEALTHY Trial [Formerly STOPP-T2D (Studies to Treat or Prevent Pediatric Type 2 Diabetes)], an NIDDK study to test a program to lower risk factors for type 2 diabetes in middle school students by improving cafeteria lunches, vending machine offerings, and physical education and promoting behavioral change.

The TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) Trial, an NIDDK study to identify the best treatment of type 2 diabetes in children and teens.

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