Glucagon-like peptide 1

Potentiates insulin secretion when stimulated by other agents; Delays gastric emptying; May decrease food intake.

A stable analogue or non-peptide GLP-1 receptor agonist may be developed, allowing this to be used in conjunction with other agents.

Imidazolines

Some imidazoline derivatives stimulate glucose-independent insulin secretion and may be developed as orally active agents.

BTS 67 582

This agent is a morpholinoguanidine and stimulates insulin secretion by way of potassium channel closure but does not act at sulphonylurea receptors. It has activity in situations where sulphonylureas no longer work and so may also have other mechanisms of action. Its effect is short lived and would suit a pre-meal administration regimen.

Agents to enhance insulin biosynthesis

A suitable agent has yet to be developed despite some promising work with succinate esters. This approach may yet bear fruit.

Genetic engineering

The bioengineering of surrogate β-cells or the use of genetic techniques to recruit replacement β-cells from undifferentiated ductal cells are possibilities.

The loss of bone mineral density and the subsequent risk for osteoporosis are higher for those with Type I diabetes than those with Type II, according to researchers from the University of Turku in Finland. The increased risk seems to be due to rapid bone loss that occurs at or soon after the onset of Type I diabetes, though why this bone loss occurs in unknown.

Most studies agree that Type I diabetes contributes to the loss of bone mineral density (BMD). But when it comes to people with Type II, the studies disagreed: Some found no change in bone mineral density, some found an increase, and others a decrease.

This study was the first to include both groups in the same study. There were 56 Type I participants, 62 with Type II diabetes, and 498 people serving as the control group. The participants ranged in age from 52 to 72, and all had developed diabetes after age 30, which means they’d had a chance to reach their highest level of bone mass.

Lower bone density was found in both men and women with Type I diabetes. However, when the researchers adjusted for age and body mass, the difference between males and females decreased somewhat.

The rate of bone fractures was higher in women with Type I diabetes than in women with Type II, which also indicates that bone mineral loss is more pronounced for women with Type I.

Researchers stated that the difference in bone density couldn’t be due to insulin therapy, since all participants were taking insulin. Previous studies suggest that insulin therapy may increase bone loss in Type I diabetics.

While the exact reason for the increased loss of bone density is not yet known, researchers urge people with Type I diabetes to make sure their health-care providers test them for low bone density and osteoporosis. Diabetes practitioners should test these patients for low-bone density and treat it immediately to prevent onset of osteoporosis and fractures.

Diabetes By David M. Nathan, MD With John F. Lauerman Times Books, New York 283 pp., $14.00

The Johns Hopkins Guide to Diabetes: For Today and Tomorrow By Christopher D. Saudek, MD, Richard R. Rubin, PhD, CDE, and Cynthia S. Shump, RN, CDE Johns Hopkins University Press, Baltimore 422 pp., $16.95

Keeping up-to-date on diabetes is not easy, and that is a good thing. More Americans have the disease than ever before, according to a statement last week by the federal Centers for Disease Control and Prevention, but new studies and changing treatment recommendations are indications that the disease is receiving the attention from researchers it deserves.

It is also inspiring its share of books, and “Diabetes” and “The Johns Hopkins Guide to Diabetes” are two of the best. The Hopkins book is more comprehensive and easier to look things up in, but both are accurate, thoughtful and useful.

New terminology was adopted this past June for the two “flavors” of diabetes, as David M. Nathan cleverly calls the types. Insulin-dependent diabetes mellitus (the rarer of the two) is now “type 1,” and non-insulin-dependent diabetes mellitus (formerly called adult-onset) is now “type 2.” Nathan emphasizes the importance of the Diabetes Control and Complications Trial (DCCT), a study in which he took part as an investigator.

The DCCT, which ended in 1993, was a nine-year study of 1,441 people with type 1 diabetes designed to answer the long-debated question of whether blood sugar control prevented or slowed the progression of the disease’s long-term complications. Thanks to the DCCT, we now know that control is very important for people with type 1 diabetes.

The next question is: Should “tight control” be recommended for type 2 diabetes?

This was not studied in the DCCT. A small study conducted in Japan with type 2 patients had findings similar to the DCCT; the researchers recommended intensive management of type 2 diabetes. But Nathan maintains that there are important differences between the two and warns that type 2 diabetes (with complications including obesity, heart disease, insulin resistance, high blood pressure and abnormal levels of such lipids as cholesterol) may necessitate different treatment choices. Blood sugar control may be secondary to control of weight or lipids.

Furthermore, the 1,441 people in the DCCT were highly motivated individuals: “Less than 1 percent dropped out of the study over a nine-year period of time. They followed their complicated therapies more than 97 percent of the time.” Not the “typical” profile of the 10 million Americans who already know they have diabetes! (The CDC estimates that at least another 5 million have it without knowing.) But this success in diabetes management and the improved long-term outcomes might become typical if people with diabetes and their health care teams had the resources in manpower, support and dollars that were available to those in this study.

Nathan states that it can cost up to $4,000 a year to intensively manage people with type 1 diabetes. Increased costs go against the grain of the current health care revolution. But another revolution in the legislative arena has occurred; about 25 states (17 in 1997) have passed comprehensive bills that pay for diabetes education, equipment and supplies. The federal government has followed the states’ lead with changes in Medicare reimbursement for diabetes education, equipment and supplies starting in July 1998.

Nathan gives the DCCT volunteers their due and credits their courage, tenacity, dedication and spirit for the success of the study. As he affirms, the DCCT has rewritten the standards of diabetes care. He calls blood glucose meters and glycated hemoglobin monitoring revolutionary tools that have made intensive management of diabetes possible. Knowing what their blood sugar is right now and what it has averaged over the past 120 days enables people with diabetes and their treatment teams to make adjustments in medication, meal plans or exercise. Both books stress the importance of knowledge in managing diabetes, to which Nathan would add self-discipline, concentration, a positive attitude and honesty.

The authors of the Johns Hopkins guide say they believe in people’s ability to get back on track, in separating the more important things from the less important, in communication, and in taking advantage of available resources. This authentic philosophy of the human spirit lends credibility to the way they write about caring for the person with diabetes. And their varied professional perspectives — as physician, mental health counselor and nurse educator — compliment each other well.

Saudek, Rubin and Shump are strong believers in teaching people how to adjust their self-care. They say that “you can’t call your health care professional for every larger or smaller meal you eat, every cold you catch or every period of stress that you undergo.” People with diabetes can be taught how to modify their own insulin regimen, sliding scales, meal plans, exercise programs, etc.

Though this may not seem controversial to those who have or care for people with chronic illnesses, it is a relatively uncommon attitude among health care professionals. And in stating that “there is no necessary link between good self-care and overall character,” they invite people with diabetes or those who care for them to get rid of the guilt that so often sabotages the daily management of diabetes. Seemingly negative emotions are reframed as natural and normal. The important thing, they emphasize, is how we deal with them. The Hopkins authors are plainly not afraid of controversy.

They disagree with the 1994 American Diabetes Association position statement that says people with diabetes can eat concentrated sweets. They write: “At the risk of being spoilsports, we beg to differ. . . . People tend not to eat the same number of grams of concentrated sugar as they do of complex carbohydrates.” There is also disagreement as to the use of insulin in the type 2 population. Some research warns that insulin can worsen hardening of the arteries.

The Hopkins authors note the inconclusive nature of the research, and the known detrimental effects of high blood sugars; they therefore recommend the use of insulin in patients in whom diet, exercise and diabetes medications have not brought blood sugars into the desired range.

Can one be “normal” and have diabetes?

Here’s Saudek, Rubin and Shump’s counsel: “There’s no denying that some things ought to be avoided, some of life’s patterns ought to be adjusted. But none of this has to impair your quality of life. You have the choice. You define quality. You set the goals.” Margaret T. Lawlor is a research coordinator at the Joslin Diabetes Center in Boston.

Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors.

Lipodystrophy is a well-known local complication of insulin injection that has two very different outcomes, causing either the swelling or the wasting of subcutaneous fat. These two reactions appear to have two different causes and mechanisms, lipohypertrophy (swelling) being caused by a cellular reaction to the local accumulation of insulin, and lipatrophy stemming from an immune reaction to impurities in the insulin. Lipohypertrophy is common in all diabetic populations, but tends to occur with particular frequency among children and young women. A group of German physicians assembled 223 type I (insulin-dependent) and 56 type II (non-insulin-dependent) diabetes patients in order to assess what caused the complication and suggest methods whereby it might be better prevented.

Researchers found that lipohypertrophy was far more common in the type I diabetics (28.7%) than in the type II diabetics (3.6%). Lipatrophy was far rarer; only 4.5% of all patients reported having suffered the condition. In the great majority of patients only one site was affected by lipohypertrophy, but the swelling was more commonly considered distinct (over 3 cm wide and 0.5 cm high) rather than discrete (smaller). Lipohypertrophy had first appeared in some patients when they were as young as five, in others as old as 48, but in the majority of subjects it had appeared between 15 and 30 years of age, and within five years of first using an insulin syringe or pen. The type of insulin used (human, porcine or bovine) did not affect the risk of lipohypertrophy.

Use of insulin pens appeared to increase the risk of lipohypertrophy compared with those patients who used only syringes; 35.7% of those who used only pens and 35.8% of those who used both pens and syringes developed the condition, while only 23.4% of those who never used pens showed signs of it. However, neither a higher number of daily injections nor larger daily doses of insulin meant a significantly increased risk of lipohypertrophy.

A myth surrounding this disorder is that patients cause and then aggravate lipohypertrophy by continually injecting into the same site because it is less painful. Under 22% of patients said that injection into the lipohypertrophic site was actually less painful, while over 23% found it more painful. For the remainder, there was no difference in sensitivity. However, the link between the condition and patients’ failure to rotate injection sites is real: 60% of those patients who always used the same injection site were afflicted, as opposed to only 22.1% of those who rotated regularly. Women were also almost twice as likely to suffer, and patients who used the abdomen as an injection site were also at greater risk. The upper arm, followed by the thigh, were found to be the safest places. More obese people, who naturally tend to have more subcutaneous fat, were at less risk than leaner people.

Previous studies have shown that children may be at particular risk. One 1993 survey at a summer camp for diabetic kids found that 45% had the condition. Lipohypertrophy is also quite common among young women with diabetes, and is frequently a cosmetic problem. Once it occurs, it is unusual for it to regress in the short term even if the injection site is no longer used. Fortunately, liposuction can be used to remove it. While improvements in insulin purity have greatly reduced the problem of lipatrophy in recent years, lipohypertrophy rates have barely changed. Patient education might achieve what science has not. Far simpler than surgery, and far better than waiting months or years for the swelling to disappear, is to avoid lipohypertrophy in the first place. The best way to do that is by rotating injection sites, particularly in the abdomen.