Advancement: reproducing human beta cells that make insulin

transplant cell insulin cluster

Research aimed at treating diabetes through beta cells that can be transplanted just took a step forward:

Researchers at Washington University School of Medicine in St. Louis have identified a way to trigger reproduction in the laboratory of clusters of human cells that make insulin, potentially removing a significant obstacle to transplanting the cells as a treatment for patients with type 1 diabetes.

Efforts to make this treatment possible have been limited by a dearth of insulin-producing beta cells that can be removed from donors after death, and by the stubborn refusal of human beta cells to proliferate in the laboratory after harvesting.

They … used a novel conditioned medium expressing Wnt3a, R-spondin-3 and Noggin to engage Wnt signaling at the receptor level in combination with RhoA/ROCK inhibitors, SB-431542 and Y-27632, to significantly enhance adult human β-cell proliferation and maintain β-cell specific gene expression, insulin secretion and content in intact islets.

The new technique uses a cell conditioning solution originally developed to trigger reproduction of cells from the lining of the intestine.

“Until now, there didn’t seem to be a way to reliably make the limited supply of human beta cells proliferate in the laboratory and remain functional,” said Michael McDaniel, PhD, professor of pathology and immunology. “We have not only found a technique to make the cells willing to multiply, we’ve done it in a way that preserves their ability to make insulin.”

The findings are now available online in PLOS ONE. (A Novel Strategy to Increase the Proliferative Potential of Adult Human β-Cells While Maintaining Their Differentiated Phenotype)

The current method for harvesting human islets, which are comprised primarily of the insulin-producing beta cells, makes it necessary to find two or three donors to extract enough cells to produce an adequate supply of insulin to treat a single patient with diabetes.
The idea for the new technique came from an on-campus gathering to share research results. Lead author Haytham Aly, PhD, a postdoctoral research scholar, reported on his work with beta cells and was approached by Thaddeus Stappenbeck, MD, PhD, associate professor of pathology and immunology, who studies autoimmune problems in the gut. Stappenbeck had developed a medium that causes cells from the intestine’s lining to proliferate in test tubes.

“He said, why don’t you try it, and he gave us some samples,” Aly said. “We put the solution in our freezer for a month or so, and when we finally gave it a try, we were amazed at the results: human beta cells in Dr. Stappenbeck’s solution reproduced at a rate that was 20 times higher than beta cells in a solution that contained the sugar glucose.”

The ability to produce large quantities of human beta cells in the laboratory gives the researchers hope that they could one day be transplanted into patients with type 1 diabetes.

The advantage of Stappenbeck’s solution may be that it is designed to activate multiple growth signaling pathways in cells, according to the researchers. Earlier attempts to make beta cells proliferate focused on one or two growth pathways. The solution also activates genes that help prevent beta cells from dying.

Because pancreatic cancers are among the most deadly tumors, the scientists checked to make sure the proliferating beta cells weren’t becoming more like cancer cells. They found that none of the factors known to contribute to pancreatic cancer were active in the laboratory-grown beta cells.

“This is an important concern to keep in mind if we are to expand human beta cells in culture with this medium and subsequently transplant them into patients,” said Aly.
If the new availability of laboratory-grown beta cells makes it possible to treat patients with transplants from one donor instead of multiple donors, McDaniel noted, that might reduce the risk of immune system rejection of the transplants.

“Another benefit in using this novel growth medium to expand isolated human beta cells is that the cells remain healthier and have reduced levels of cell damage or death,” Aly said. “That may also reduce the chances of immune system rejection.”


Prediabetes Treatment – improves health and is cost effective!

Islet Transplantation for Type 1 Diabetes

At one time I believed that islet translation would lead to a therapeutic treatment and cure for Type 1 diabetes. Presentations by noted surgeons and their endocrinologist partners were hopeful and suggested that short-term trials were highly successful.
However, long term observations seem to have revealed two key factors: (1) the effectiveness of the transplanted cells diminishes through time and (2) their are risk factors associated with the immunosuppression drugs.

Consider the summary from a recent British Medical Journal Commentary:

Summary points
Islet of Langerhans transplantation is used in a select group of patients with type 1 diabetes with severe glycaemic lability, recurrent hypoglycaemia, and hypoglycaemia unawareness
The procedure is minimally invasive, with few procedure related complications
Two to three islet infusions are usually needed to achieve insulin independence

Most patients need insulin by five years post-transplantation owing to declining graft function; beneficial effects on the frequency of hypoglycaemic episodes and hypoglycaemia awareness remain

Most long term complications are related to systemic immunosuppression

The risk-benefit ratio of islet transplantation should be carefully weighed by the treating physician and the potential recipient, who should be given adequate information

As I understand it, the target population as those individuals with Type 1 Diabetes who are unable to achieve satisfactory (safe) results with conventional therapy. So, islet transplantation is not (yet) the holy grail many of us had hope but it is never-the-less beneficial for some individuals.

Gastric Bypass Surgery Reverses Heart Ailments!

gastric-bypass-surgery.jpgThis is fairly significant news…. gastric bypass does help lose weight and treat diabetes (more here):

Well- who is a candidate for these procedures? Usually patients with a BMI of over 40 or over 35 with health consequences that are obesity related. Does gastric bypass have any effect on diabetes? In a series of 1000 patients, 150 of whom had diabetes, 83% experienced resolution of their diabetes (defined by a normalization of A1c and coming of medications for diabetes) after the surgery

However, there now appears to be additional benefits:

A new report from the Journal of the American College of Cardiology reports that patients who had received gastric bypass surgery not only lost weight but had maintained healthier cardiac health, while also reducing previous cardiac complications spurred by obesity.

Often times when a patient is obese, an increase in the largest portion of the heart, the left ventricle can become larger in mass causing the heart to work harder to pump blood into the body. According to the study, echocardiograms, or ultrasounds of the heart showed a remodeling of the heart structure which included a reduction of left ventricular mass and right ventricular cavity area in patients that had received Gastric Bypass Surgery, a procedure Texas Bariatric Specialists performs.

“Patients now have another reason to add to their check-off list of the benefits of a gastric bypass. Why would anyone severely obese wait any longer when the health risks are too high,” says Texas Bariatric Specialists founder Dr. Nilesh A Patel.
A gastric bypass is a bariatric procedure that is the single largest contributor to these findings and is offered at Texas Bariatric Specialists. In the Laparoscopic gastric bypass surgery procedure, the surgeon makes a small stomach pouch at the top of the stomach, the pouch is later connected to the small intestine bypassing the larger stomach. The gastric bypass can result in complete resolution in type 2 diabetes, hypertension, high blood pressure, sleep apnea, and the loss of 65 percent of excess body fat.

Source: press release

Promising New Anti-cancer Treatment Approved For HER2-Positive Breast Cancer

The FDA has approved Tykerb (lapatinib), a new targeted anti-cancer treatment that is significantly more effective than current medicines in fighting advanced stage of breast cancer, for use in combination with capectabine (Xeloda), another cancer drug, for patients with advanced, metastatic breast cancer that is HER2 positive (tumors that exhibit HER2 protein): The combination treatment is indicated for women who have received prior therapy with other cancer drugs, including an anthracycline, a taxane, and trastuzumab (Herceptin). According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year. Approximately 8,000 to 10,000 women die from metastatic HER2 positive breast cancer each year.
more at Hyscience

Chromium picolinate

A double blinded study, published in Diabetes Technology and Therapeutics, reports that glycaemic control can be improved through Chromium picolinate /biotin supplementation:

The study looked at the effect of the commercially available Diachrome supplement (Nutrition 21) on the glycaemic control and blood lipids of 36 overweight or obese people with type 2 diabetes.
Writing in the journal Diabetes Technology and Therapeutics, lead author Gregory Singer said: “This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements.”
“Chromium picolinate /biotin supplementation may represent an effectuive adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism
Source: Diabetes Technology and Therapeutics
Volume 8, Number 6, Pages 636-643
“The effect of chromium picolinate and biotin supplementation on glycaemic control in poorly controlled patients with type-2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial”
Authors: G.M. Singer, J. Geohas

The results also showed a significantly greater reduction in the total area under the curve for glucose (AUCg) during the oral glucose tolerance test (OGTT) for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%).

The Holy Grail

No, I’m not talking about a medieval legend and I’m not going to use the “c-word”. However, three groups of scientists report that they independently replicated a controversial finding: severely diabetic mice can recover on their own if researchers squelch an immune system attack that is causing the disease. This is an important finding published here by the New York Times.

It is a discovery that was first published in 2001 and raised the hopes of people with Type 1 diabetes, which usually occurs in puberty and afflicts an estimated half-million to a million Americans. If the findings applied to humans, they might mean reversing a disease that had seemed incurable.

Even better, the potential treatment is not based on embryonic stem cell research, a controversial (and unproven) medical technology that involves the destruction of human life:The findings also gave rise to questions about using embryonic stem cells as replacement cells for diabetics, a method that is the focus of intense interest. If it is possible, in mice, for the pancreas to cure itself, and if the same finding holds true in humans — which, so far, is entirely unknown — adding embryonic stem cells as the source of new pancreas cells might provide little added benefit, if any.

The investigators of the reported study treated diabetic mice by injecting them with Freund’s Complete Adjuvant, a mixture of water, oil and parts of dead bacteria. It overstimulates the immune system cells that are attacking the pancreas, making those white blood cells self-destruct, effectively stopping the attack and allowing the pancreas to cure itself.

Dr. John Buse, director of the Diabetes Care Center at the University of North Carolina, urged caution.
“There are two possibilities,” Dr. Buse said. “This treatment works for mice but no derivation of it will ever work for humans. Or this is the paradigm leap that is necessary to find the cure for Type 1 diabetes.”

Of course, all the convential disclaimers apply – years away, etc.. However, if billions are being spent on embryonic stem cell research on the basis of speculation, what kind of resources should be put behind this technology with provides hope based on substance?

Individuals with Diabetes Should Lower Cholesterol with Statin Therapy

Individuals with diabetes should aggressively reduce their cholesterol levels and seek intensive statin therapy even if their levels of low-density lipoprotein (LDL) cholesterol is within the normal range, according to the American Diabetes Association.
The ADA recommendations state that diabetics who are older than 40 years of age whose total cholesterol exceeds 3.5 mmol/L (135 mg/dL) should be placed on statin therapy to achieve a 30% to 40% reduction in LDL level, regardless of their baseline LDL level and even if they do not have overt cardiovascular disease.
In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE-IT) study, treatment with atorvastatin 80 mg/day lowered LDL cholesterol levels to a median of 1.6 mmol/L (62 mg/dL) in diabetics and nondiabetics alike, compared to 2.5 mmol/L (97 mg/dL) with the standard pravastatin40-mg regimen.
Among patients taking atorvastatin, the hazard ratio for a cardiovascular event was 16% less than it was for patients on pravastatin after the mean follow-up period of 24 months, a significant difference (Cannon C. et al. N Engl J Med 2004;350:1495-1504).
more from Diabetes in Control

Treatment of Sleep Apnea Lowers Glucose Levels in Diabetics

Patients with Type 2 diabetes who also suffer from obstructive sleep apnea can lower their glucose levels by receiving the most common sleep apnea therapy.
Dr. James Herdegen, associate professor of medicine at the University of Illinois at Chicago and medical director of the UIC Center for Sleep and Ventilatory Disorders, and his co-authors measured glucose levels of participants before and after continuous positive airway pressure therapy, or CPAP.

[Read more...]