Feature article:

THE FUTURE OF DIABETES CARE—MAYBE!

Every week it seems that a study somewhere shows that there is a hot new item or medicine or theory that will revolutionize diabetes care. Our patients usually find these things before we do and the often come to us thinking “why aren’t you using this for me?” Usually we either don’t know what they are talking about or we have to explain that it is not available yet. I have put together a synopsis of the latest new ideas. They all seem to be feasible but it will be some time before our patient can ever expect to benefit from them

This could be very promising, but no company has even submitted a proposal to the FDA, but research is continuing.

Could the next new diabetes drug be a Ghrelin inhibitor?

Ghrelin, a Natural GH Secretagogue Produced by the Stomach,

Induces Hyperglycemia and Reduces Insulin Secretion in Humans

Fabio Broglio, Emanuela Arvat, Andrea Benso, Cristina Gottero, Giampiero Muccioli, Mauro Papotti, Aart Jan van der Lely, Romano Deghenghi and Ezio Ghigo

Division of Endocrinology and Metabolism, Department of Internal Medicine (F.B., E.A., A.B., C.G., E.G.); Department of Anatomy, Pharmacology and Forensic Medicine (G.M.); Department of Biomedical Sciences and Oncology (M.P.); University of Turin, Italy; Division of Endocrinology, Department of Internal Medicine, Erasmus University of Rotterdam (A.J.V.D.L.), The Netherlands; and Europeptides (R.D.), Argenteuil, France

Abstract

Ghrelin, a 28 amino acid gastric hormone is a natural ligand of the GH Secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion though, like synthetic GHS, it shows other endocrine and non-endocrine activities. Aim of the present study was to clarify whether ghrelin administration influences insulin and glucose levels in humans. To this goal, we compared the effects of ghrelin, hexarelin, a synthetic GHS, or placebo on insulin and glucose as well as on GH levels in 11 normal young volunteers (age [mean ± SEM]: 28.5 ± 3.1 yr; BMI: 22.2 ± 0.9 Kg/m²). Ghrelin induced very marked increase in GH secretion ( AUC^0–180: 5777.1 ± 812.6 µg/l/h; p < 0.01) which was not modified by placebo. Placebo administration did not modify insulin and glucose levels. On the other hand, ghrelin administration induced a prompt increase in glucose levels ( AUC^0-180: 1343.1 ± 443.5 mg/dl/h; p < 0.01 vs. saline). Absolute glucose levels at +15' were already higher than those at baseline (93.9 ± 7.1 mg/dl; p < 0.01) and persisted elevated up to 165' (90.3 ± 5.8 mg/dl; p < 0.01 vs. 0'). Ghrelin administration was also followed by a decrease in serum insulin levels ( AUC^0-180: -207.1 ± 70.5 mU/l/h; p < 0.05 vs. saline). Absolute insulin levels were significantly reduced from 30' (11.4 ± 0.9 mU/l, p < 0.1 vs. 0'), showed the nadir at +45' (10.0 ± 0.6 mU/l, p < 0.01 vs. 0') and then persisted lower (p < 0.01) than baseline up to +105'. Hexarelin administration did not modify glucose and insulin levels despite its marked GH-releasing effect ( AUC^0-180: 4156.8 ± 1180.3 µg/l/h; p < 0.01 vs. saline) that was slightly lower (p < 0.05) than that of ghrelin. In conclusion, these findings show that, besides stimulating GH secretion, ghrelin is a gastric hormone possessing metabolic actions such as hyperglycemic effect and lowering effect on insulin secretion in humans, at least after acute administration

This one would make all your insulin dependent patients happy, but is many years in the future. I really like the title.

Swell gel spells knell for needles

Daily injections of insulin will soon be a thing of the past for people who suffer from diabetes.   What if a device could monitor blood sugar level constantly and introduce exactly as much insulin into the bloodstream as is needed for good health, without relying on the user to apply the right dose at the right time.

 In a report in the 9 December 1998 edition of the Journal of the American Chemical Society, Kazunori Kataoka of the University of Tokyo and colleagues describe a new material that acts both as a sugar sensor and an insulin-releasing agent. When the material "smells" sugar, it automatically delivers a dose of insulin.

The dream-machine of diabetes treatment is a miniature device that can be implanted under the skin to administer insulin whenever the need arises, without the user even noticing: Kataoka and colleagues have synthesized a "smart" polymer gel that does exactly that.

The gel is a network of polymer strands cross-linked to one another by chemical bonds in a kind of disorderly three-dimensional, molecular-scale spider's web. The strands are made of a non-toxic polymer, poly(N-isopropylacrylamide). To some of these strands, the researchers attached molecular pendants of phenylboronic acid - the 'spiders' that catch the glucose "flies". When a glucose molecule passes through the gel, a phenylboronic acid group will latch on to it and bind it to the network.

 The researchers were able to capitalize on this swelling behavior to cause the gel to release insulin in response to glucose. In its shrunken form, the gel network can be loaded up with insulin molecules, which it traps within the tangle of strands. Then, when the gel expands, the insulin escapes through the gaps in the net. Hence, Kataoka and colleagues demonstrated the switching, on and off, of insulin release from their gel in response to repeated pulses of glucose. In other words, the insulin is released only when it is needed.

 The beauty of smart gels is that they are without moving parts. Bringing a product like this into clinical use is a huge challenge, involving stringent tests of effectiveness and safety that typically take many years to complete. But already this work hints that chemistry has the potential to produce the soft machines of medicine's future.

In addition researchers at the University of Washington in Seattle have previously developed a gel containing insulin and the enzyme glucose oxidase. As the name suggests, the enzyme "burns up" glucose, making an acid that reacts with the polymer gel to place positive charges on the strands, again causing the gel to swell and release its bounty  

This next device uses a totally different technology than any other product available. Although the information states “CAUTION - Investigational device. Limited by federal law to investigational use.

It is interesting to note that, Abbott, the makers of Medisense products, has exclusive worldwide marketing rights to SpectRx's interstitial fluid continuous glucose monitoring technology. Abbott just recently upped their share of SpectRx to 5.9%. No expected date of release has been stated.

CONTINUOUS GLUCOSE MONITORING RESEARCH CONTINUOUS U

SpectRx is researching and developing a continuous glucose monitoring system based on its patented laser microporation technology to access skin interstitial fluid (ISF). ISF is the clear fluid found between all the cells in the body. A stream of ISF is drawn continuously into a patch through an array of micropores made in the stratum corneum - the outer dead layer of skin cells. The micropores formed by the laser poration process are approximately the width of a human hair in diameter. Clinical studies by SpectRx and

others indicate a high correlation between the concentration of glucose in ISF and in blood. Because the SpectRx system samples ISF directly from the skin, it is able to utilize conventional

glucose assay technology to measure the glucose concentration. The meter is designed with a detachable display to provide access to current glucose readings. The continuous glucose monitoring concept involves a patch that may be placed almost anywhere on the body. The patch is connected to a meter with a detachable display.

It appears that our patients now could have something else to blame for their obesity and diabetes.

HUMAN VIRUS COULD CAUSE OBESITY AND DIABETES AND MAY BE CONTAGIOUS

(Don’t let this information get into the wrong hands!) 

Sitting next to an obese person may have greater repercussions than loss of personal space. A human virus that turns skinny roosters into chubby chickens is contagious, US researchers have shown. The overweight birds are causing a re-examination of the controversial idea that obesity could be catching¹.

Chickens and mice injected with a human virus put on fat, Nikhil Dhurandhar and his team at Wayne State University in Detroit, Michigan found last year.

Birds injected with blood from their infected friends also start to gain flab, the researchers have now shown, proving that the virus is responsible. "They don't visibly become fat," says Dhurandhur, but their fat stores grow. Within 5 weeks the birds carried at least 35% extra fat, qualifying many of them as obese. Yet the big birds ate the same as their buddies in the brood.

Catching the virus isn't limited to direct exchange of bodily fluids. Chickens that shared a cage with an infected bird also showed signs of the virus in their blood within 12 hours, suggesting that the virus can also be spread by nose or mouth secretions.

The data are compelling," says David Allison, an obesity researcher at the University of Alabama at Birmingham, on the link between the Ad-36 and fat gain.

Several different viruses have been linked to obesity in animal models, explains Allison. "But no-one thought they could be a common contributor to obesity in humans," he says. Yet preliminary studies have found higher levels of antibodies against Ad-36 in obese patients, showing that they may have experienced an infection.

 Paradoxically, the chubby chickens have lower blood levels of triglycerides, the form in which fat is transported and stored. The human virus "affects how energy is put into fat cells," thinks Allison: by increasing numbers of fat cells and the amount of triglycerides they store, levels circulating in the blood could be lowered.

But the idea that viral infection could be partly to blame for human obesity leaves many "skeptical and cautious," says Arthur Frank, director of the George Washington University Obesity Management Program in Washington, DC. Yet even he wonders whether changes in lifestyle are enough to explain the rapidly escalating rates of obesity. "It's reasonable to think that some of them could be of an infectious origin," he says. "You have to have an open mind."

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