BRUCE ROSEMAN, M.D.
330 WEST 58th Street .# 408    NY NY 10019
M-F 9:00-5:15     Wed  12-8
New Telephone: (212) 957-8256  Cell/VM  1-917-414-3201
New Fax: (212) 265-2616
Hospital:  Mt. Sinai  (click for info)
BRUCE ROSEMAN, M.D.
NICOLE LIVESCU, R.N.

Metformin May Up Alzheimer's
March 16, 2009 — Diabetes mellitus is associated with increased risk for Alzheimer's disease (AD), but a new study of metformin suggests that diabetes treatments might bear some of the blame.
Yaomin Chen, PhD, from the Burnham Institute for Medical Research, in La Jolla, California, and colleagues report in the March 10 issue of the Proceedings of the National Academy of Sciences that metformin increased insulin's reduction of intracellular and extracellular beta-amyloid accumulation, but metformin by itself actually increased levels of the Alzheimer's-linked peptides.
This finding, which was observed in vitro and in animal models of AD, raises the specter of a wave of new Alzheimer's cases in diabetic patients who have been taking metformin for years. It is the most popular antidiabetic drug in the United States and 1 of only 2 oral antidiabetics on the World Health Organization List of Essential Medicines (along with glibenclamide). In 2006, there were 35 million prescriptions for generic metformin filled in the United States.
Senior author Francesca-Fang Liao, PhD, told Medscape Psychiatry that although this was an animal study, the findings are worrisome enough that physicians should promptly follow up any complaints of cognitive decline in patients taking metformin.
"Our data suggest that metformin used alone might potentially facilitate development of AD pathology," Dr. Liao said. "This raised the question of whether the increased AD risk in diabetes mellitus patients might be due to the medication itself.
"Extensive animal studies as well as epidemiological data from clinical patients should be collected and carefully analyzed to address this question." Dr. Liao was at the Burnham Institute for Medical Research when this study was done but is now at the University of Tennessee Health Science Center, in Memphis.
Safer to Use Metformin in Combination Therapy?
The upregulation of beta-amyloid generation by metformin in animal models of AD occurred at steady-state plasma levels at and even below those reported in diabetic patients.
Metformin is an insulin-sensitizing drug, and the researchers found that giving it together with insulin added to insulin's known ability to reduce beta-amyloid generation.
"Our data suggest that the potentially deleterious effects of metformin to AD patients may be avoided by using it in combination with insulin; the combination may result in a beneficial effect in treating both type 2 [diabetes mellitus] and in mitigating AD progression," the researchers write.
AD expert Michal S. Beeri, MD, from the Mount Sinai School of Medicine, in New York, told Medscape Psychiatry, "The report by Chen is very interesting and consistent with a study from our group showing that brains of diabetics who, when alive, received combination therapy (ie, insulin plus an insulin sensitizer) had 80% less neuritic plaques (1 of the hallmark lesions of AD).
"This paper is also consistent with another study published in the Proceedings of the National Academy of Sciences [De Felice FG et al. Proc Natl Acad Sci. 2009;106:1971-1976] showing that soluble beta-amyloid oligomers (precursors of neuritic plaques) promote loss of surface of insulin receptor, that this loss can be prevented by insulin, and, most interesting, that adding the insulin sensitizer rosiglitazone [Avandia, GlaxoSmithKline] to insulin potentiates this protection.
"These studies suggest that there might be some protective mechanism that is triggered when the brain is exposed to insulin and insulin sensitizers at the same time, and this in turn has therapeutic potential," she said.
Randomized Control Trials Needed
With regard to the apparent deleterious effects of metformin, Dr. Beeri is more cautious, noting that large, placebo-controlled, double-blind trials will be required to establish that this happens in human patients as well as in animal models and in vitro.
"I think Chen's study is very important and strengthens the concept of diabetes medication effects on Alzheimer's neuropathology, but at this point I do not think that there is clinical evidence for clinicians to be concerned when treating their diabetic patients with metformin," she said.
The study was supported by National Institutes of Health grants, the Alzheimer's Association, and a Zenith Award. The authors report no conflicts of interest.
Proc Nat Acad Sci 2009;106:3907-3912. Abstract

Once-Weekly Exenatide Safe and Effective
New findings suggest an extended-release formulation of exenatide (Byetta, Amylin/Lilly) appears to be a safe and effective once-weekly therapy to control blood glucose and body weight in people with type 2 diabetes.
Investigators studied a long-acting release (LAR) formulation of exenatide in 45 people with type 2 diabetes who were poorly controlled with metformin and lifestyle modification. Participants were randomized to receive 0.8 or 2 mg injection of LAR exenatide or a placebo injection once weekly for 15 weeks.
At the end of the study period, glycated hemoglobin (A1C) was lower among study subjects: the mean A1C value was 7.2% for the .8 mg exenatide group and 6.6% for the 2 mg group, down from a mean 8.5% A1C value before the study. By comparison, there was a slight rise to 9% among those receiving placebo. Subjects also showed improvements in fasting glucose levels. Those receiving the 2 mg dose lost an average of 3.8 kg (8.6 lb). There was no weight loss among those who received the 0.8 mg dose of LAR exenatide or placebo.
The most common side-effect from LAR exenatide was nausea. However, none of the participants receiving LAR exenatide withdrew from the study.
If clinical research continues to show promise, this long-acting formulation of exenatide may one day be introduced as a once-weekly therapy option for type 2 diabetes, the authors suggest.
Kim A, MacConell L, Zhuang D, et al.: Effects of once-weekly dosing of a longacting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 30:1487-1493, 2007.




Cholesterol-Lowering Effect of Concentrated Pomegranate Juice Consumption in Type II Diabetic Patients with Hyperlipidemia.
This study was undertaken to assess the effect of concentrated pomegranate juice consumption on lipid profiles of type II diabetic patients with hyperlipidemia (total cholesterol or triglycerides >/= 200 mg/dL). In this pilot study 22 diabetic patients were recruited from the Iranian Diabetes Society. They were free of any other chronic diseases. The patients were followed for eight weeks to obtain more detailed data about their diet before concentrated pomegranate juice (CPJ) consumption period began. In this pre-study period a 24-hour food recall and a food record (containing flavonoid-rich foodstuffs) were completed every ten days. At the end of the eighth week, anthropometric and biochemical assessments were done. Thereafter the patients consumed 40 g CPJ for eight weeks. During this period, dietary assessment was continued. After completion of the study anthropometric and blood indices were evaluated again. The Wilcoxon signed-rank test was used for statistical analysis. P-value was considered significant at p < 0.05. There were 14 women (63.6%) and 8 men (36.4%) in this survey. Mean (+/- SD) of age, weight, and duration of diabetes were 52.5 (+/- 5.2) years, 71.5 (+/- 10.3) kg, and 7.9 (+/- 6.6) years, respectively. After consumption of concentrated pomegranate juice significant reductions were seen in total cholesterol (p < 0.006), low-density lipoprotein-cholesterol (LDL-c) (p < 0.006), LDL-c/high-density lipoprotein-cholesterol (HDL-c) (p < 0.001), and total cholesterol/HDL-c (p < 0.001). However there were no significant changes in serum triacylglycerol and HDL-c concentrations. Anthropometric indices, physical activity level, types and doses of oral hypoglycemic agents, and the intake of nutrients and flavonoid-rich foodstuffs did not change during the CPJ consumption period. It is concluded that CPJ consumption could modify heart disease risk factors in these hyperlipidemic patients. Therefore, its inclusion in their diets may be beneficial.

Men With Diabetes, Hypertension, or Hyperlipidemia More Likely to Be Hypogonadal
By Maggie Schwarz WASHINGTON, DC -- May 25, 2005 -- According to results of the Hypogonadism in Males (HIM) study, men with diabetes, hypertension, or hyperlipidemia are also more likely to be hypogonadal than is the general population. Scott Segal, MD, director of men's health at Solvay Pharmaceuticals in Atlanta, Georgia, United States, presented the findings here May 19[th at the American Association of Clinical Endocrinologists (AACE) 14th Annual Meeting and Clinical Congress.

"The percentages of men with diabetes, hypertension, or hyperlipidemia who also had low testosterone are higher than we would have expected," said Dr. Segal.

The HIM study was a 2004 investigation undertaken by Solvay Pharmaceuticals looking at 2,162 men aged 45 years and older in 95 primary care practices nationwide. Dr. Segal noted that only 75% of men in this age group see a physician with any regularity.

Blood samples were assayed for total testosterone, free testosterone, and bioavailable testosterone. Patient characteristics that were studied included comorbid conditions, demographics, and reason for presenting to a physician. Patients were queried about the presence of common symptoms associated with hypogonadism, including sexual dysfunction, fatigue or weakness, and mood changes.

Hypogonadism was defined as a total testosterone <300 ng/dL. Of the 2,162 men enrolled, 836 (38.7%) had hypogonadism, and 80 were receiving testosterone replacement therapy.

In men with a history of diabetes, 50% were hypogonadal. In men with a history of hypertension, 42% were hypogonadal, and in those with a history of hyperlipidaemia, 40% were hypogonadal.

A decrease in ability or frequency of sexual performance was reported by 65.5%, 55.8%, and 52.0% of men with a history of either diabetes, hypertension, or hyperlipidemia, respectively. Within each group, rates of reporting were significantly higher in hypogonadal versus eugonadal (P less than or equal to .014). Differences in sexual desire or libido (P less than or equal to .014) and physical exhaustion or a lack of vitality (P less than or equal to .023) were statistically significant for hypogonadal versus eugonadal men who were also diagnosed with either diabetes or hyperlipidemia. A decline in general feelings of well-being was significantly different in hypogonadal men with hyperlipidemia versus eugonadal men (P = .011).

According to Dr. Segal, the numbers of hypogonadal men with diabetes, hypertension, or hyperlipidemia are 10 to 20 points higher than would have been expected.

"These numbers mean that physicians should check testosterone levels in these men with risk factors for the metabolic syndrome," he concluded. "Testosterone insufficiency is not only associated with sexual dysfunction, but exhaustion and lack of vitality. Their quality of life could be improved with replacement therapy."


[Presentation title: Association of Testosterone Deficiency and Symptoms With Diabetes, Hypertension, and Hyperlipidemia: Data From the Hypogonadism in Males (HIM) Study. Abstract 790.]

Chromium supplements good for the diabetic heart
Chromium supplementation may be good for the heart in people with type 2 diabetes, according to study findings. It appears to lead to a shortening of a harmful heart rhythm, which may lower cardiovascular risk in type 2 diabetics.

The heart rhythm disturbance known as a prolonged QT interval has been linked to fatal heart arrhythmias. Therefore, the changes in QT interval observed with chromium supplementation in patients with type 2 diabetes may also translate into a survival benefit, study investigator Dr. Bojan Vrtovec from Ljubljana University Medical Center in Slovenia told Reuters Health.

In the study, researchers had 30 diabetic patients take 1000 micrograms of chromium daily for 3 months followed by an inactive placebo for 3 months. Another 30 diabetic patients started with 3 months of placebo and then crossed over to chromium for 3 months.

At the start of the trial, the QT interval viewed on a standard electrocardiogram or ECG was similar in both groups -- 422 milliseconds in the first group and 425 in the second group.

However, at 3 months, the QT interval was significantly shorter in the supplementation group (406 milliseconds) than in the placebo group.

In the next 3 months, QT shortening was observed in the second group but not in the first group. At the end of the study, the OT interval duration was similar in both groups and was markedly lower overall than at the start of the trial before chromium supplementation.

This study shows that increased intake of chromium may lower cardiovascular risk in type 2 diabetic patients, the researchers say.

They also note in the American Heart Journal that blood insulin levels decreased significantly after 3 months of chromium supplementation and this may be partly responsible for the QT interval shortening.

A prolonged QT interval has been associated with high blood sugar levels, high insulin levels and reduced sensitivity to insulin in type 2 diabetics, they explain. Chromium supplementation improves sensitivity to insulin, lowers blood insulin levels and improves glucose homeostasis.

SOURCE: American Heart Journal April 2005.

Caffeine Ingestion Is Associated With Reductions in Glucose Uptake Independent of Obesity and Type 2 Diabetes Before and After Exercise Training
SoJung Lee, PHD1, Robert Hudson, MD, PHD2, Katherine Kilpatrick, MD3, Terry E. Graham, PHD4 and Robert Ross, PHD1,2

1 School of Physical and Health Education, Queen’s University, Kingston, Ontario, Canada
2 Department of Medicine, Division of Endocrinology and Metabolism, Queen’s University, Kingston, Ontario, Canada
3 Department of Medicine, Division of Geriatrics, Queen’s University, Kingston, Ontario, Canada
4 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada

Address correspondence and reprint requests to Robert Ross, PhD, School of Physical and Health Education, Queen’s University, Kingston, Ontario, Canada, K7L 3N6. E-mail: rossr@post.queensu.ca

OBJECTIVE—We investigated the effect of caffeine ingestion on insulin sensitivity in sedentary lean men (n = 8) and obese men with (n = 7) and without (n = 8) type 2 diabetes. We also examined whether chronic exercise influences the relationship between caffeine and insulin sensitivity in these individuals.

RESEARCH DESIGN AND METHODS—Subjects underwent two hyperinsulinemic-euglycemic clamp procedures, caffeine (5 mg/kg body wt) and placebo, in a double-blind, randomized manner before and after a 3-month aerobic exercise program. Body composition was measured by magnetic resonance imaging.

RESULTS—At baseline, caffeine ingestion was associated with a significant reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (33%), obese (33%), and type 2 diabetic (37%) groups in comparison with placebo. After exercise training, caffeine ingestion was still associated with a reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (23%), obese (26%), and type 2 diabetic (36%) groups in comparison with placebo. Exercise was not associated with a significant increase in insulin sensitivity in either the caffeine or placebo trials, independent of group (P > 0.10).


Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes
Results of a 6-month, randomized, comparative trial

CONCLUSONS—Inhaled insulin is effective, well tolerated, and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen.

Tomato Juice May Cut Clotting in Diabetics  Wed Aug 18, 7:03 PM ET
By Amanda Gardner
WEDNESDAY, Aug. 18 (HealthDayNews) -- For people with type 2 diabetes, tomato juice may help stave off the heart troubles that often complicate the disease.

Researchers have found that drinking tomato juice for three weeks had a blood-thinning effect in people with the disease. The juice reduced "platelet aggregation" -- the blood's ability to clot.

The finding appears in a research letter in the Aug. 18 issue of the Journal of the American Medical Association (news - web sites).

If corroborated by larger studies, the finding may one day also help "individuals with increased clotting tendency such as smokers, long-distance air travelers (deep vein thrombosis), etcetera," said Manohar L. Garg, one of the authors of the letter detailing the results. Garg is an associate professor of nutrition and dietetics at the University of Newcastle in Australia.

"When platelets aggregate, they form the plug that clots the vessels," explained Dr. Stuart Weiss, a clinical assistant professor of medicine at New York University School of Medicine. "In diabetes patients, platelets are more sticky." Platelets are responsible for the blood's ability to clot which, in the case of an injury, is a good thing. Clotting can go too far, however, and cause strokes, heart attacks and other life-threatening problems.

As a result of this excessive "stickiness," for instance, people with type 2 diabetes have an increased risk of atherosclerosis and cardiovascular problems, such as heart attack and stroke. Anti-clotting medications have been shown to reduce this risk.

"In diabetes, there are a lot of pro-inflammatory markers that contribute to increasing platelet aggregation, so if there's something we can do that can reverse or limit that, that would be a very positive thing," Weiss added.

Consumption of tomato products has been shown to reduce the incidence of various heart ailments, so the researchers behind the research letter decided to test the hypothesis in people with type 2 diabetes.

For the study, they recruited 14 men and six women aged 43 to 82 years old with type 2 diabetes but no prior history of clotting problems. None was taking aspirin, nonsteroidal anti-inflammatory drugs or other medications that might influence clotting.

The participants were randomly assigned to drink 250 milliliters of tomato juice or a placebo -- a tomato-flavored beverage -- every day for three weeks. All were instructed to maintain their normal diet.

Blood samples were collected at the beginning and at the end of the study, then analyzed. Platelet aggregation turned out to be significantly lower at the end of the trial for the group drinking tomato juice. There was no significant difference in platelet aggregation in the placebo group.

It's not clear why the juice had this effect, Garg said. Knowing why could be instrumental in helping to decide if tomato juice needs to be part of a dietary plan for those with type 2 diabetes.

"Mechanisms of how tomato juice inhibits platelet aggregation need to be delineated prior to issuing practical recommendations," said Garg. "A substance named P3 has been isolated from the yellow, jelly-like fluid around the seeds of the tomato... P3 has been shown to possess anti-aggregatory effects."

For now, a little tomato juice may be a fine thing for diabetics, but don't overdo it.

"There's some sugar in tomato juice but it's not particularly large," Weiss said. "Depending on your blood glucose control, you don't necessarily want to have a lot. It's also acidic so your stomach can get a little unhappy with large amounts."

In time, Weiss predicted, "we'll find that more and more vegetables and more and more foods have things in them that keep us healthy."

Serum Ferritin and Risk of Metabolic Syndrome in US Adults: The Third National Health and Nutrition Examination Survey Abstract Information Presented during: Novel Predictors of Type 2 Diabetes - 06/07/2004 (02:15 - 04:15 PM) Abstract Number: 281-OR Authors: MEGAN L. JEHN, ELISEO GUALLAR Institution: Baltimore, MD Results: Several studies have suggested that elevated iron stores may be a risk factor for cardiovascular disease and diabetes, but limited data are available on the association between iron stores and the metabolic syndrome. The aim of this study was to examine the relationship between serum ferritin, metabolic syndrome and insulin resistance among 6,151 adults >20 years of age who participated in the Third National Health and Nutrition Examination Survey (NHANES III). The Homeostasis Model Assessment (HOMA) was used to estimate insulin resistance. Mean (95% CI) serum ferritin values were 140.3 (134.2-146.8) µg/L in men, 94.5 (88.9-100.4) µg/L in post-menopausal women and 33.8 (31.7- 35.9) µg/L in pre-menopausal women. After adjustment for age, ethnicity, body mass index, and C-reactive protein, the odds ratios (95% CI) of the prevalence of the metabolic syndrome for the highest compared to the lowest quartile of serum ferritin were 2.3 (1.5-3.5) in men, 1.9 (0.9-3.8) in pre-menopausal women, and 2.1 (1.3-3.2) in post-menopausal women. In all three groups, serum ferritin levels increased as the number of metabolic syndrome components increased (Figure). Ferritin levels also correlated with insulin resistance in men (r = 0.14, p < 0.001) and post-menopausal women (r = 0.19, p<0.001), but not in pre-menopausal women (r=0.04, p=0.13). Additional sensitivity analyses excluding individuals with suspected infection, inflammation and liver disease produced similar results. These findings indicate that elevated iron stores are positively associated with prevalence of the metabolic syndrome and insulin resistance in a representative sample of the US population. [figure1]

Lipitor Halves Stroke Risk in Diabetics
By Ben Hirschler, European Pharmaceuticals Correspondent
LONDON (Reuters) - Pfizer Inc.'s cholesterol fighter Lipitor (news - web sites) halved the risk of stroke in patients with diabetes in a study and cut cardiovascular events, including heart attacks, by more than a third, researchers said on Sunday.
The clear benefits mean doctors should now consider giving so-called statin drugs routinely to patients with diabetes, according to investigators involved with the British clinical trial.
That could open up a huge new market for the cholesterol-lowering drugs -- already the world's top-selling medicines -- and Lipitor in particular, which has annual sales of $10 billion.
"We need to shift thinking toward a presumption that most people with type II diabetes are likely to receive very substantial benefit," Helen Colhoun, professor of genetic epidemiology at University College Dublin, told Reuters.
Type II diabetes, which typically occurs in adulthood and is closely linked with obesity, is one of the world's fastest growing health problems
It is closely related to cardiovascular disease, with two out of three sufferers dying from heart disease and stroke. Yet most of the world's diabetics, estimated by the International Diabetes Federation to number 194 million, are not currently given statins.
That may be about to change.
GROWING EVIDENCE
he findings from the Lipitor study, which were presented at the annual meeting of the American Diabetes Association in Orlando, add to the growing body of evidence favoring statins in the treatment of diabetes.
A similar study last year on Merck & Co Inc's rival statin Zocor showed it cut the risk of heart attack and stroke by a third.
And it was already clear last June that Lipitor was having a significant impact when the British trial was halted two years early to allow patients on placebo to take the drug.
Now the full results of the study -- sponsored by British charity Diabetes UK, Britain's Department of Health and Pfizer UK -- are being made available.
They show that a 10 mg dose of Lipitor, known generically as atorvastatin, reduced cardiovascular events by 37 percent in diabetics with no previous history of cardiovascular disease, while the incidence of stroke fell by 48 percent.
Current best practice is to use statins in diabetics only when they have elevated cholesterol levels or established heart disease.
But researchers say the British trial demonstrates that a much wider group of patients would actually benefit and statins could become a third leg of a strategy that already includes treatment for blood sugar levels and high blood pressure.
"We are hoping this will provide the necessary evidence base for policy to shift," said Colhoun.
"The challenge is really whether there is anybody with type II diabetes at sufficiently low risk of heart disease not to warrant this treatment," she added.


Gila May Be Healer for Type 2 Diabetes
By Kathleen Doheny HealthDay Reporter

SATURDAY, June 5 (HealthDayNews) -- A new type 2 diabetes drug derived from the saliva of a huge, venomous lizard may control blood sugar without the weight gain associated with other diabetes medications.The trial drug, which has not yet won approval from the U.S. Food and Drug Administration (news - web sites), "will mean a new method, a novel treatment for type 2 diabetes patients, the likes of which we have not seen before," said Dr. Dennis Kim, director of clinical affairs for Amylin Pharmaceuticals in San Diego, which funded the study and makes the medication.The findings were presented June 5 at the annual meeting of the American Diabetes Association in Orlando, Fla.The origin of the novel drug, called exenatide, is itself novel. It is a synthetic version of the hormone exendin-4, found in the saliva of the Gila monster, a lizard native to several Southwestern U.S. states. The Gila monster eats just four times a year and turns its pancreas off between those meals. When it's time to turn its pancreas on again, it secretes exendin-4.The exendin-4 is similar in action to human GLP-1, a hormone produced in the gut that can stimulate insulin production without causing threateningly low blood sugar, which can occur after taking insulin and some oral anti-diabetes pills.Unlike other oral agents taken for type 2 diabetes, the drug has not been linked with weight gain and actually resulted in weight loss, according to the researchers."This class of drugs has been shown to suppress appetite in humans," Kim said.More than 18 million Americans have diabetes, and most suffer from type 2, in which the body fails to use insulin properly.In the study, exenatide was given to 336 people whose type 2 diabetes was not controlled well with the maximum doses of metformin (Glucophage), a commonly used oral drug for type 2 diabetes. The study, which lasted 30 weeks, involved three groups, receiving five micrograms or 10 micrograms of exenatide or placebo, injected twice daily.Those on exenatide lost weight and reduced blood sugar, said Dr. Ralph DeFronzo, a physician at the University of Texas Health Science Center at San Antonio, who was to present the research at the meeting. Those on the higher dose lost 6.3 pounds on average and reduced their blood sugar levels. Those on the lower dose lost an average of 3.5 pounds and also lowered their blood sugar.The most common side effects were mild to moderate nausea.In animal studies, when exenatide was given, the formation of new beta cells resulted. Beta cells are the insulin-producing cells in the pancreas, and as type 2 diabetes progresses, they begin to fail. In the human study, markers of beta-cell function improved in those on the exenatide."If everything goes as planned, we foresee being able to market the drug the middle of next year, hopefully," Kim said.Other experts agree the drug may be good news for type 2 diabetics. "The drug is acting like the hormone GLP, which is a gut hormone, and GLP is having a direct effect on the beta cells and causing the beta cells to secrete more insulin," said Dr. Martin Abrahamson, acting chief medical officer for the Joslin Diabetes Center in Boston, who serves on the scientific advisory board of Amylin.In type 2 diabetes, Abrahamson said, there is a gradual loss of beta cell function over time. "Will the drug reverse that decline? We don't know the answer to that.""This is a drug that will help control blood sugar, but [also] help with weight reduction," added Dr. Nathaniel Clark, a spokesman for the American Diabetes Association, who is familiar with the research on exenatide.

Statins for Every Diabetic?
Thu Jun 3, By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - Almost everyone with diabetes should consider taking a statin drug to lower cholesterol, even if they already have low cholesterol levels, the American Diabetes Association advised on Thursday.

Diabetes patients are at such high risk of heart disease that the statins almost certainly will do them some good, the group said in its latest treatment guidelines.

People with diabetes should all consider taking a daily aspirin, too, the new guidelines say.

"It may well be that everybody with diabetes should be on a statin," said Dr. Nathaniel Clark, vice-president for clinical affairs for the group.

"We know that statins lower low-density cholesterol but they may also have some other qualities that have not been tested," Clark said in a telephone interview.

An estimated 18 million Americans have diabetes, 90 to 95 percent of them type-2 diabetes. This once was called adult-onset diabetes but it is showing up in children more often now.

Type-1 diabetes is an autoimmune disease caused when the body mistakenly destroys insulin-producing pancreas cells.

Type-2 diabetes is strongly associated with being overweight and sedentary. It greatly raises the risk for heart disease, stroke and heart attack and can also lead to blindness and limb loss.

Clark said the Association decided to add statins to the guidelines after seeing the results of a British study, published earlier this year in the Lancet medical journal, that showed people who took statins had a one-third lower risk of stroke.

Their study included adults over the age of 40 whose total cholesterol levels were as low as 135 -- considered extremely low by most standards. Among normal healthy people, doctors do not usually consider giving drugs to lower cholesterol until total levels hit 200.

But Clark said diabetics are a special case.

"It is now a consensus that having diabetes is the equivalent in terms of cardiovascular risk of already having had a heart attack," Clark said.

"We are talking about what we would consider a high-risk group."

Statins are becoming more and more popular with doctors as study after study finds they can lower the risk of a range of heart conditions and may also help patients with multiple sclerosis and Alzheimer's disease (news - web sites).

Worldwide, 25 million people take statins, but up to 200 million could be eligible.

The drugs are not cheap, however. The United States already spending $12.5 billion on statin drugs, more than any other type of medicine, and the drugs can cause a rare type of side-effect called rhabdomyolysis, which damages muscles.

Study Finds Iron Storage Raises Diabetes Risk  

CHICAGO (Reuters) - A study has found that storing abnormal amounts of iron in the body can lead to adult onset diabetes in women, raising the possibility that a blood test earlier in life could help identify those at risk from the disease, researchers said on Tuesday.

The finding came from a look at 698 women among thousands of nurses who gave blood samples between 1989 and 1990 as part of a multiyear study. The 698 women developed diabetes over the course of the study even though they were free of it and free of heart disease as well at the start.

When their initial blood samples were compared with others who did not develop diabetes over a 10-year period, it was found that the diabetic group had significantly elevated levels of ferritin when the initial blood samples were taken.

Ferritin is an iron-protein complex in blood that is a marker for iron storage.

Women with higher ferritin levels at the start of the study had a nearly threefold increased risk of developing diabetes, the study found, even after taking into account such things as obesity and other risk factors including family history of diabetes, physical activity, alcohol use and diet.

"The results provide the strongest evidence to date that increased iron stores in the body are an independent risk factor for type 2 diabetes," said Rui Jiang of the Harvard School of Public health, lead author of the study appearing in this week's Journal of the American Medical Association (news - web sites).

Frank Hu, a senior author, added: "The findings suggest that a simple blood test which measures ferritin levels can be used to predict the development of type 2 diabetes in otherwise healthy people. This may help in identifying high-risk people who would possibly benefit from further lifestyle or therapeutic interventions that can lower iron stores in the body."

It was known that excessive iron stores could cause diabetes among patients with hemochromatosis, a genetic defect in the regulation of iron absorption, the study said. But it had not been clear whether moderately higher iron stores raised the risk of developing diabetes in otherwise healthy individuals, it said.

The authors said iron excess seems to contribute to insulin resistance and later to decreased insulin secretion.



Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes
CONCLUSIONS—The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

Heart Dis. 2003 May-Jun;5(3):231-40.

Tight Glucose Control In Diabetes Lowers Risk Of Atherosclerosis
BETHESDA, MD -- June 5, 2003 -- Strict glucose control in type 1 diabetes reduces the risk of atherosclerosis, a benefit that persists for years, according to a study published in the June 5, 2003 issue of the New England Journal of Medicine. Since 1993, when the Diabetes Control and Complications Trial (DCCT) ended, researchers have known that intensive glucose control greatly reduces the eye, nerve, and kidney damage of type 1 diabetes. Now, researchers conclude, the benefits of tight control also extend to the heart. "Intensive control is difficult to achieve and maintain, but its benefits are even greater than we realized," says study chair Dr. Saul Genuth of the Case Western University. "The earlier intensive therapy begins and the longer it can be maintained, the better the chances of reducing the debilitating complications of diabetes." The DCCT was a multicenter study that compared intensive versus conventional management of blood glucose in 1,441 people with type 1 diabetes. Patients on intensive treatment kept glucose levels as close to normal as possible with at least three insulin injections a day or an insulin pump and frequent self-monitoring of blood glucose. Intensive treatment aimed to keep hemoglobin A1c (HbA1c), which reflects average blood sugar over 2 to 3 months, to as close to normal (6 percent) as possible. Conventional treatment at that time consisted of one or two insulin injections a day with daily urine or blood glucose testing. After 6½ years of the DCCT, HbA1c levels averaged 7 percent in the intensively treated group and 9 percent in the conventionally treated group. When the DCCT ended, those who had been assigned to conventional treatment were encouraged to adopt intensive control and shown how to do it, and researchers began a long-term follow-up study of the participants, called the Epidemiology of Diabetes Interventions and Complications (EDIC) study. The DCCT could not study atherosclerosis because the participants were relatively young, and heart disease takes years to develop. In 1994-95 and again in 1998-2000, EDIC researchers used ultrasound to measure the thickness of participants' carotid arteries, the two blood vessels in the neck that carry blood from the heart to the brain. Carotid wall thickness reflects the amount of atherosclerosis, or plaque build-up, in the artery: the thicker the arterial wall the greater the risk of later heart attack and stroke. At the time of their first ultrasound, the diabetic participants' carotid wall thickness was similar to that of non-diabetic controls matched for age and gender. Five years later, however, the participants had thicker arterial walls than those of the non-diabetic group. In addition, the thickness of the carotid walls had increased less in the intensively treated group during the 5 years than in the conventionally treated group. "This finding strongly suggests that atherosclerosis progressed more slowly in the intensively treated group," noted Dr. Genuth. Carotid thickening was also linked to known cardiovascular risk factors including age, higher systolic blood pressure, smoking, LDL:HDL cholesterol ratio, and urinary albumin (a measure of kidney function). After adjusting for these factors, the study found that the differences in carotid wall thickness between the two groups were due to the differences in blood glucose levels during the DCCT. "The risk of heart disease is about 10 times higher in people with type 1 diabetes than in people without diabetes, but it was unclear to what extent blood glucose contributed to the development of heart disease," said Dr. David Nathan of Massachusetts General Hospital, who co- chaired the DCCT/EDIC research group. "Now we know that intensively controlled glucose significantly reduces the atherosclerosis underlying heart disease just as it reduces damage to the eyes, nerves, and kidneys in people with type 1 diabetes. What's striking is that the benefits of intensive control persisted despite a gradual rise in the HbA1c levels of the intensively treated group during the 5 years after DCCT ended." "For many people, diabetes is difficult to manage with today's tools. Every new finding about the importance of blood glucose control in preventing complications heightens our determination to foster research that results in new therapies that take the burden off the patient," said Dr. Judith Fradkin, director of the Diabetes, Endocrinology, and Metabolic Diseases Division of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). About 17 million people in the United States have diabetes, the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke. About 1 million have type 1 diabetes. Formerly known as juvenile onset or insulin-dependent diabetes, type 1 diabetes usually begins in children and adults under age 30. It develops when the body's immune system attacks the insulin-producing cells of the pancreas. Type 2 diabetes accounts for up to 95 percent of all diabetes cases. Most common in adults over age 40, type 2 diabetes affects 6.2 percent of the U.S. population. It is strongly associated with obesity (more than 80 percent of people with type 2 diabetes are overweight), inactivity, family history of diabetes, and racial or ethnic background. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Pacific Islanders are at particularly high risk for type 2 diabetes. The prevalence of type 2 diabetes has tripled in the last 30 years, due in large part to the upsurge in obesity. SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)




"Regression of Microalbuminuria with tight controld of gjucose
New England Journal of Medicine (NEJM)

06/12/2003
By Martha Kerr

Elevated urinary albumin excretion does not imply inexorably progressive nephropathy, say investigators.

Researchers with the Joslin Study of the Natural History of Microalbuminuria in Boston, Massachusetts, United States, report that modification of factors that lead to elevated urinary excretion can reduce those levels back to normal.

Lead investigator Dr. Bruce A. Perkins of the Joslin Diabetes Center and colleagues studied 386 patients with type 1 diabetes and persistent microalbuminuria with urinary albumin excretion rates ranging from 30 micrograms/min to 299 micrograms/min over a 6-year period. Excretion rates were grouped into 2-year intervals during follow-up.

Regression of microalbuminuria occurred frequently during the study period, with a 6-year cumulative incidence of 58%. Only 19% went on to develop overt proteinuria.

Regression of microalbuminuria was associated with glycosylated haemoglobin levels below 8%, systolic blood pressure below 115 mmHg, cholesterol levels below 198 mg/dL and triglyceride levels below 145 mg/dL.

Dr. Perkins notes that "our study results indicate that microalbuminuria is more likely to subside to normal levels than to progress to overt proteinuria" with modification of risk factors.

He adds that "although our findings support a new model of early diabetic nephropathy, the contributing variables are not known with precision. Clinical trials that assess the optimal target level of albumin excretion - in terms of the regression of microalbuminuria - as well as the optimal levels of other factors are warranted."
N Engl J Med 2003;348:23:2285-2293. "Regression of Microalbuminuria in Type 1 Diabetes"



transplant trial WITH JUST AN IV
WASHINGTON (Reuters Health) - Twelve diabetic patients who have taken part in a transplant trial no longer need to take insulin shots, according to early data released here Monday.

  The patients have all had at least one transplant of pancreatic islet cells, which are meant to replace their own non-functioning cells. Islets are clusters of cells in the pancreas that contain insulin-producing beta cells.


The hope is that these patients, who have type 1 diabetes, will never have to be insulin-dependent again, and that they won't experience the disease's common complications, such as blindness, and heart and kidney disease, said James Shapiro, the trial's principal investigator and director of the islet transplant program at the University of Alberta in Edmonton, Canada.


Shapiro and colleagues at nine sites around the world began transplanting islet cells into diabetic patients in late 2001, and have reported on a few patients before. They gave an update Monday at a briefing held in conjunction with the American Transplant Congress.


Twelve patients have stopped taking insulin, and 16 others are showing good donor islet function, but are still taking some insulin.


One of the patients, Anthony Pecora of Ashland, Virginia, has been insulin-free for almost a year. "On July 7, 2002, at 7 p.m., I took my last dose of insulin," Pecora told reporters.


He had been taking insulin for 29 years, and no longer had good control of his blood sugar when he was accepted into the study at the University of Minnesota. Pecora was given two islet cell transplants.


In the procedure, patients receive an infusion of islet cells into their main liver vein. After a two-day hospital stay, they are put on a regimen of immune-suppressing drugs.


Most of the side effects have come from the drugs, not the procedure itself, said Shapiro.


Eighty-three percent of the patients had severe mouth sores, and a majority also had low white blood cell counts. Almost forty percent of the patients had to start taking cholesterol lowering drugs to counteract the increase brought on by the anti-rejection medications, said Camillo Ricordi, another lead investigator from the University of Miami.


The transplants seemed to work best at centers that had more experience -- Miami, Edmonton and Wisconsin. "That was expected somewhat," said Shapiro, noting that it is difficult to prepare islet cells for transplant and to figure out proper dosing of anti-rejection drugs.


The researchers will report final results when all 36 patients being studied have had a chance to respond to up to three transplants. That could be a year from now, said Shapiro.


It is not easy to find donor islet cells because they have to come from donor pancreases that can't be transplanted whole. The researchers are hoping that rules will be issued by the United Network for Organ Sharing to set aside a certain percentage of pancreases for islet cell harvesting.


That policy is under consideration now.


"I think we could do much better and move forward faster if we had access to better pancreases," said Bernhard Hering, another investigator who directs the islet transplant program at the University of Minnesota.


Type 1 diabetes is sometimes called juvenile diabetes because it usually strikes at a younger age than the more common type 2 diabetes. In type 1 diabetes, the immune system launches a misguided attack against insulin-producing cells in the pancreas. This leads to low or nonexistent levels of the sugar-regulating hormone. People with this type of diabetes must take daily insulin injections to survive.



Vitamins boost immunity of diabetics - study

March 04 2003 at 06:19AM

Philadelphia - Daily multivitamin and mineral supplements could help adults with diabetes fight off some minor infections, according to a study released on Monday.

The year-long study of 130 patients in North Carolina showed that daily vitamin use reduced the rate of minor respiratory and urinary tract infections, influenza and gastrointestinal infections among all people aged 45 and older.

But the findings were most striking among subjects with adult-onset diabetes. Results showed infection occurring among only 17 percent of diabetic patients who took multivitamins, compared with the 93 percent of diabetics who received a placebo.

The supplements proved effective enough to reduce absenteeism due to infectious diseases. Diabetic patients who received multivitamins recorded no days of absenteeism. But 89 percent of those who took a placebo were absent from work for one or more day.

Subjects who received supplements were given a mix of multivitamins and minerals similar to so-called one-a-day tablets sold at most supermarkets.

"Our trial, which was performed in a sample of middle-aged persons, demonstrated a benefit in incidence of infection. However, this benefit was almost entirely observed in participants with diabetes," said the study, which was published in the Annals of Internal Medicine.

Researchers from the University of North Carolina's School of Medicine believe the supplements were useful to diabetics because people who suffer from the disease often lack nutrients in their systems.

In an accompanying editorial that appeared in the Annals, officials from the Harvard School of Public Health suggested that multivitamins could play a larger role in preventing deadly infectious diseases in developing regions of the world where many are malnourished.

Diabetes Risk Higher in Those with Shorter Thighs
NEW YORK (Reuters Health) - People who have relatively short thighs appear to have an increased risk of developing diabetes or a condition that often precedes the disease compared to those with longer gams, researchers said Friday.

But study author Dr. Keiko Asao cautioned that the study does not mean that thigh length in any way causes diabetes.

Asao explained that a third factor, such as the environment in the womb or nutrition in childhood, likely influences both leg length and future diabetes risk.

The precise identity of that third factor remains unclear, she added.

"We are struggling with how to explain that," said Asao, who is at the Johns Hopkins University in Baltimore, Maryland.

People who have relatively short thighs are not doomed to develop diabetes, Asao said. These results are preliminary, she said, and diabetes is a "multifactorial disease" that results from many different causes.

Those with relatively short thighs would not harm themselves if they chose to spend extra energy trying to ward off diabetes, Asao noted. But she recommended people who are concerned about diabetes pay more attention to well-established risk factors, such as obesity.

The study focused on type 2 diabetes, the most common form of the disease, and not type 1 diabetes, which often develops in children or young adults and requires daily insulin injections for survival. Type 2 diabetes more commonly occurs in adults and can sometimes be controlled with diet and exercise.

Asao and her colleagues presented their findings at the American Heart Association (news - web sites)'s 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention in Miami.

To obtain their findings, Asao and her team reviewed information about 8,738 adults between the ages of 40 and 74 collected during national surveys conducted by the US government.

The authors found that the shorter people's thighs, the greater their risk of having diabetes or insulin resistance, a condition marked by a loss of sensitivity to this key blood-sugar-regulating hormone that often precedes diabetes. After taking into account other risk factors, the researchers found the link remained true for white and Mexican-American women, but not blacks or men.

Previous research has suggested that shorter people may be at an overall higher risk of diabetes, Asao noted, but added that in the current study, height was not linked to diabetes risk. She suggested that differences in the people included in the two studies may explain the diverging results.

She noted that previous research has also linked height to other chronic diseases, with one study suggesting that taller people have an elevated risk of high blood pressure. The relationship between height and blood pressure could also stem from early growth factors that resemble those that may explain the link between thigh length and diabetes risk, she said.

Whether the length of other body appendages could also be linked to diabetes risk remains unknown, Asao added.

Test: Drug Stops Diabetes-Related  eye Disease
Sun Feb 16, 3:23 PM ET  Add Health - AP to My Yahoo!

By RANDOLPH E. SCHMID, Associated Press Writer

WASHINGTON - A synthetic form of vitamin B1 that is used in Europe to treat nerve problems has been found to prevent the most common form of diabetes-related eye disease in rats.

Diabetic rats treated with benfotiamine for 36 weeks did not develop any of the retina damage found in a similar group of untreated rats, according to a research team led by Dr. Michael Brownlee of the Albert Einstein College of Medicine in New York.


Brownlee said he hopes to begin a clinical trial to determine whether a similar result would occur in humans once an effective dose for the drug in people is determined. That could happen as soon as a year, he said.

"We can't say it works in humans because there has never been a double-blind clinical study" of it, Brownlee said.

The new findings are published Monday in the online edition of the journal Nature Medicine.

In the United States, diabetes is the leading cause of blindness in people age 20 to 70. Diabetic retinopathy — damage to the small blood cells in the retina — is the most common problem. The American Diabetes Association estimates that between 12,000 and 24,000 people lose their sight each year because of diabetes.

In diabetics (news - web sites), excess sugar in the blood can damage some cells, especially those lining blood vessels, that are unable to block the sugar from entering. That sugar is burned for fuel by mitochondria, the energy engines of cells.

In cells that cannot regulate their amount of sugar, byproducts accumulate that can activate three different pathways of cell damage that can lead to blindness and other complications.

Brownlee's group focused on two compounds involved in this damage. Those compounds are affected by an enzyme called transketolase, which depends on thiamine — also known as vitamin B1 — for its activity.

The researchers sought to block the cell damage by using thiamine to boost the activity of transketolase, but this increased the enzyme activity only about 20 percent.

German researchers on the team suggested trying the synthetic thiamine form, benfotiamine, and it increased the enzyme activity by 300 percent to 400 percent, Brownlee said.

"So that was a stroke of luck," Brownlee said in a telephone interview. Benfotiamine blocked all three damage pathways by converting the damaging compounds into harmless chemicals.

While benfotiamine is a synthetic derivative of thiamine, it is different from that vitamin, Brownlee said. He cautioned diabetics that "going out to a health food store and buying (news - external web site) a lot of thiamine is not going to help."

Dr. Francine Kaufman, president of the American Diabetes Association, said the findings are exciting because they show a way to block all three damage pathways in cells lining blood vessels.

There are other products in the pipeline dealing with one or another of the pathways but not all three, she said.

In addition, benfotiamine has been in use in Germany for years to treat painful types of nerve damage, including nerve damage caused by diabetes, and seems to have few side effects. Thus "it might not take forever to get into clinical trials," said Kaufman, a pediatric endocrinologist at Children's Hospital in Los Angeles.

"It's a big leap from animals to humans, but this is quite encouraging," she said.




Diabetes and Chronic Kidney Disease: Ten Facts
Diabetes is the leading cause of kidney failure in the United States. Because a cure for diabetic kidney disease has not yet been found, treatment involves controlling the disorder and slowing its progression to kidney failure. Current research suggests that control of high blood pressure is a key factor in slowing this disease. Careful control of blood sugar levels and reduction of dietary protein intake is also very important. Treatment to prevent diabetic kidney disease should begin early — before kidney damage is obvious. It is important for everyone to know more about diabetic kidney disease and to learn to recognize its early warning signs.
Nearly 16 million Americans, or about 6 percent of the U.S. population, have diabetes. Of these, 10.3 million are diagnosed and 5.4 million are undiagnosed. Diabetes is more prevalent in older people. However, the most common type of diabetes, type 2 diabetes, is becoming more common in younger people. This change may be related to poor diets and increasing prevalence of obesity among younger people.

Diabetes is the single leading cause of kidney failure in the U.S., accounting for 45 percent of the people who start treatment for kidney failure each year, and 38 percent of all Americans being treated for kidney failure. Each year, nearly 25,000 people with diabetes develop kidney failure.

In the U.S., diabetes is more common among certain minority groups: Nearly 10 percent of American Indians and Alaska Natives have diagnosed diabetes. Among 35 million African-Americans, 1.5 million have been diagnosed with diabetes, but an estimated 730,000 do not know they have the disease. Hispanic Americans are almost twice as likely to have diabetes as non-Hispanic whites of similar age. Some Asian Americans also are at increased risk for diabetes; for example, Native Hawaiians are twice as likely to have diagnosed diabetes as white residents of Hawaii.

Diabetes is a group of diseases characterized by high levels of blood sugar resulting from insufficient production of insulin by the pancreas or defects in insulin action in the body. The most common forms of diabetes are type 1 diabetes, which develops in childhood and is sometimes called insulin-dependent diabetes, and type 2 diabetes, which generally develops in adulthood, and is sometimes called non-insulin-dependent diabetes. Type 2 diabetes is far more common, accounting for about 90 to 95 percent of all diagnosed cases of diabetes.

Risk factors for type 1 diabetes may include autoimmune, genetic and environmental factors. Risk factors for type 2 diabetes include older age, obesity, family history of diabetes, prior history of gestational diabetes (diabetes during pregnancy), impaired glucose tolerance, physical inactivity and race or ethnicity.

Diabetes damages small blood vessels throughout the body, affecting the kidneys as well as other organs and tissues, including skin, nerves, muscles, intestines and the heart. Patients with diabetes can develop high blood pressure as well as rapid hardening of the arteries, which can lead to heart disease and eye disorders.

Researchers feel that the presence of high blood pressure may be the most important predictor of which diabetics develop chronic kidney disease. Therefore, the detection and control of high blood pressure are very important for people with diabetes. Specific high blood pressure medicines, such as the angiotensin converting enzyme inhibitors, may be the most effective in preventing diabetic kidney disease. About 60 to 65 percent of people with diabetes have high blood pressure.

The risk of developing chronic kidney disease increases with the length of time a patient has diabetes. For those surviving 20 to 30 years with type 1 diabetes, about 30 percent develop chronic kidney disease — making it a frequent, but not inevitable, complication among people in this group. About 10 to 40 percent of people with type 2 diabetes develop chronic kidney disease and kidney failure.

Some of the signs that someone who has diabetes may be developing chronic kidney disease are:
Protein in the urine
High blood pressure
Leg swelling, leg cramps
Increased need to urinate, especially at night
Abnormal blood tests, such as a rise in blood urea nitrogen (BUN) and creatinine
Less need for insulin or anti-diabetic pills
Morning sickness, nausea and vomiting
Weakness, pallor and anemia
Itching
A cure for diabetic kidney disease has not yet been found; the treatment involves controlling the disorder and slowing its progression to irreversible kidney failure. Some of the treatments that may be effective are:
Controlling high blood pressure
Controlling blood sugar levels
Reducing dietary protein intake
Avoiding medications that may damage the kidneys
Treating urinary tract infections
Exercise and weight loss (under the supervision of a physician)
Last Modified: 07/09/01
Source:
American Diabetes Association
National Institute of Diabetes, Digestive and Kidney Diseases
National Kidney Foundation
United States Renal Data System


toxic compound is formed when sugar, proteins and fat are processed at cooking temperatures for long periods of time. This compound may increase blood vessel damage in diabetics

In a study appearing this week in the Proceedings of the National Academy of Sciences (news - web sites), researchers say a toxic compound is formed when sugar, proteins and fat are processed at cooking temperatures for long periods of time. This compound may increase blood vessel damage in diabetics, the study suggests.
Dr. Helen Vlassara, a diabetes researcher at Mount Sinai School of Medicine in New York and first author of the study, said the compound, called advanced glycation end products or AGEs, can prompt an angry reaction from the immune system, eventually damaging blood vessels.
"AGEs attack virtually every part of the body," said Vlassara. "It is as if we have a low-grade infection. They tend to aggravate the immune cells."
She said a lifelong diet high in AGEs leaves the immune system in a constant state of low-grade inflammation which damages the small and mid-sized arteries. This, in turn, can prompt heart disease and other problems common to diabetics, she said. Diabetics are particularly sensitive to the effects of vessels damaged by AGEs, she said.
But dietary AGEs can be controlled by cooking foods differently, she added.
Dr. Eugene Barrett, a professor of medicine at the University of Virginia and the president-elect of the American Diabetes Association, said the study by Vlassara is potentially important in the control of diabetes, but more research is needed to understand the role AGEs may play in heart disease.
He said research into AGEs is still at an early stage and it may be too soon to conclude that limiting AGEs will reduce heart disease among diabetics.
Vlassara's study used 24 diabetic patients divided into two groups. One group maintained a normal diet recommended for diabetics which included chicken, fish and meat. The other group had the same foods, but cooked differently.
At the end of six weeks, said Vlassara, the AGEs in the test group registered declines ranging from 33 percent to 40 percent. She said the study was too short to detect any fundamental changes in the patients' health.
However, she said studies using diabetic animals have shown that a reduction in AGEs can reduce the incidence of heart disease or delay its onset. Such studies need to be conducted in humans to prove the value of AGE control, she said.
The key to lowering AGEs, said Vlassara, is to cook for a short time in the presence of high humidity. This means either boiling or steaming meats for the minimum time required. Meat can be sauteed, she said, but it should be cut very thin and cooked quickly with a small amount of oil.
She said one of the worst AGE offenders is turkey cooked in the traditional American way.
"We cook for many hours," she said. "That would tend to make a tremendous number of AGEs."
Vlassara said coffee, cola and chocolate drinks also are loaded with AGEs. For diabetics, she recommends sugar-free versions of clear sodas instead of the diet versions of dark drinks. Some of the dark colas, she said, add caramelized products which are heavy in AGEs.


insulin and coronary artery disease
"Insulin promotes growth of endothelial cells,
cells that line blood vessels. Extra insulin in
the body could mean extra cell growth in the
blood vessels. This, in turn, may cause
atherosclerosis and lead to the progression
of coronary artery disease.



Men: Going for the Grains May Cut Diabetes Risk
Fri Aug 23, 5:52 PM ET
NEW YORK (Reuters Health) - In the long run, men who chow down on a diet rich in whole-grains may reduce their risk of type 2 diabetes, researchers report.
   
According to a study in the August issue of the American Journal of Clinical Nutrition ( news - web sites), whole-grain products--such as brown rice, oats, corn and barley--were protective against diabetes. Men who ate the most whole-grain products were less likely to be diagnosed with type 2 diabetes than men who consumed mostly refined grains--like those found in cookies, doughnuts, pasta or white rice, the study results show.
Because whole grain results in lower levels of blood glucose (sugar), the body does not have to produce as much insulin to process the food. Refined grains, on the other hand, result in more than double the amount of sugar in the blood and cause more insulin to be secreted than whole-grain products.
And experts point out that whole grains contain vitamins and nutrients that may be important in modifying the risk of the disease.
Type 2 diabetes occurs when the body fails to respond to insulin, the hormone that clears the blood of sugar after a meal and deposits it into cells to use for energy. High blood sugar can increase the risk of complications from diabetes such as heart disease, kidney failure and blindness.
"Efforts should be made to replace refined-grain with whole-grain foods," writes Teresa T. Fung of Simmons College in Boston, Massachusetts and colleagues.
The team of researchers looked at the eating and lifestyle habits of nearly 43,000 healthy men and followed them for roughly 12 years.
At the end of the study period, 1,197 men had developed type 2 diabetes. Men who consumed the least amount of whole grains, about 0.4 servings per day, were nearly 60% more likely to develop type 2 diabetes compared with men who consumed the most--about 3.2 servings of whole-grains per day.
In other findings, Fung's team discovered that the benefit of eating whole grains wasn't just limited to lean men. Obese men who were getting exercise and consuming whole grains were 52% less likely to develop type 2 diabetes, the authors report.
"Given the current overall low intake of whole grains, efforts should be made to decrease the cost and increase the availability and consumption of whole-grain products," Fung and colleagues conclude. "This has the potential to reduce substantially the incidence of type 2 diabetes and possibly other chronic diseases when sustained over time."
The National Institutes of Health ( news - web sites) and the American Diabetes Association funded the study.
SOURCE: American Journal of Clinical Nutrition 2002;76:535-540.


Niacin Drug Cuts Blood Fat in Diabetics

Extended-Release Niacin Safe, Effective in Type 2 Diabetes
Laurie Barclay, MD
Medscape Medical News 2002. © 2002 Medscape
July 26, 2002 — Although niacin has long been relatively contraindicated in type 2 diabetes due to its adverse effects on glucose control, a report in the July 22 issue of the Archives of Internal Medicine suggests that once-daily extended release niacin was well tolerated and effective for improving lipid levels in type 2 diabetics. However, the higher dose did significantly worsen glycemic control compared with placebo.
"Extended-release niacin may be considered as therapy in combination with statins, or in some cases, without statins, in the management of dyslipidemia associated with type 2 diabetes," write Scott M. Grundy, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues from the Diabetes Multicenter Research Group.
In this double-blind, placebo-controlled trial, 148 patients with type 2 diabetes were randomized to treatment with 1,000 mg per day extended-release (ER) niacin, 1,500 mg per day ER niacin, or placebo. Subjects were allowed to continue medications used to treat underlying conditions; 47% were receiving statins, and 81% took drugs for diabetes control.
Mean high-density lipoprotein cholesterol (HDL-C) levels were essentially unchanged in the placebo group, increased by 13% to 19% in the group taking 1,000 mg ER niacin, and increased by 22% to 24% in the group taking 1,500 mg ER niacin (P<.05). Triglyceride (TG) levels decreased by 5% to 8% in the placebo group, by 15% to 20% in the 1,000 mg ER niacin group, and by 28% to 36% in the 1,500 mg group.
At 16 weeks, low-density lipoprotein cholesterol (LDL-C) levels were 9% higher in the placebo group, 5% higher in the 1,000 mg ER niacin group, and 7% lower in the 1,500 mg group. Mean total cholesterol levels increased by 4% in the placebo and 1,000 mg ER niacin groups and decreased by 6% in the 1,500 mg ER niacin group.
Subjects in the 1,000 mg ER niacin group had higher body mass indexes, which the authors suggest may have dampened the triglyceride-lowering effect of niacin.
Glycated hemoglobin levels at baseline and at week 16 were 7.13% and 7.11% in the placebo group, 7.28% and 7.35% in the 1,000 mg group (P=.16 vs. placebo), and 7.2% and 7.5% in the 1,500 mg group (P=.048 vs. placebo). Four patients withdrew from the study because of inadequate glycemic control.
In a telephone interview with Medscape Cardiology, Grundy noted that low HDL and high triglyceride levels are particularly problematic in diabetic patients. Grundy was chairman of the Third Adult Treatment Panel (ATP III), which recently published guidelines that establish recommended approaches for the hypercholesterolemic patient.
Grundy said that treatment of the dyslipidemias may become analogous to the current approach to antihypertensive treatment, in which the push to ever higher doses of monotherapy is being replaced with combination agents that incorporate multidrug regimens into a single prescription. The future of optimal lipid management may follow the same path, Grundy said, using low-dose combinations of proven anticholesterolemic agents, instead of prescribing ever-higher doses of statins. At the present time, the most likely complement would be niacin, especially in a time-release formulation, and therefore the present results, showing that low-dose niacin is safe and useful in diabetic patients, are particularly interesting.
Kos Pharmaceuticals in Miami, Florida, supported this study.
Additional reporting by David Good, editor of Medscape Cardiology.
Arch Intern Med. 2002;162:1568-1576
Reviewed by Gary D. Vogin, MD


Did you know…?
More than 17 million Americans have diabetes
Of the 17 million, an estimated 5.9 million people are not aware that they have the disease
Over 200,000 Americans die from complications associated with diabetes each year
Diabetes kills more Americans than AIDS and breast cancer combined
Over 2,700 people are diagnosed with diabetes daily
Experts estimate that almost one million people will be diagnosed with diabetes this year
Health care and other costs directly related to diabetes care totals almost $100 billion annually in the United States





Aspirin May Improve Glucose Tolerance In Type 2 Diabetes Through Serine Kinase Inhibition
Journal of Clinical Investigation (JCI)  06/04/2002 By James Adams

High-doses of aspirin appear to improve glucose metabolism in patients with type 2 diabetes through the inhibition of the serine kinase IKKß.

Previous studies have implicated IKKß, which is involved in tissue inflammation, in the pathogenesis of insulin resistance. Studies have also shown that high doses of salicylates inhibit IKKß, which could potentially improve insulin resistance and glucose tolerance in patients with type 2 diabetes.

Investigators from the Yale University School of Medicine in New Haven, Connecticut, and Harvard Medical School in Boston, Massachusetts, United States, tested this hypothesis in nine type 2 diabetic subjects who received seven grams of aspirin per day for 14 days.

Mixed meal-tolerance tests and hyperinsulinemic-euglycemic clamps were performed to assess glucose turnover before and after aspirin administration.

Results showed a 25 percent reduction in fasting plasma glucose, a 15 percent reduction in total cholesterol and C-reactive protein, a 50 percent reduction in triglycerides and a 30 percent reduction in insulin clearance after high-dose aspirin treatment. There was no change in body weight during treatment.

Also, a 20 percent reduction in basal rates of hepatic glucose production and a 20 percent improvement in insulin-stimulated peripheral glucose uptake were observed after aspirin treatment.

These results support the hypothesis that IKKß is a potential target for treatment of type 2 diabetes, the investigators conclude.

J Clin Invest 2002; 109(10): 1321-1326

Fish Oil Compound May Help Ward Off Diabetes
Mon Apr 22, 1:30 PM ET
By E. J. Mundell

NEW ORLEANS (Reuters Health) - An omega-3 fatty acid found in fish oil appears to improve insulin function in overweight individuals who are vulnerable to type 2 diabetes, researchers report.

Three months of daily supplementation with docosahexaenoic acid (DHA) produced a "clinically significant" improvement in insulin sensitivity in overweight study participants, according to Dr. Yvonne Denkins, a nutrition researcher at the Pennington Biomedical Research Institute, Louisiana State University in Baton Rouge. She presented the findings here Saturday at the annual Experimental Biology 2002 conference.

More than 9 out of 10 diabetics (news - web sites) have the type 2 form of the disease, where the body's gradual failure to respond to insulin can cause blood sugar levels to rise to dangerous levels.

Previous population studies have suggested that fish oil might help protect against diabetes. "There were epidemiological studies on the Greenland Eskimos, a population of people that eat mainly whale blubber," Denkins pointed out. "These are people that are overweight, that should be diabetic and have heart disease, but they do not. The scientists that studied them thought it was probably because of what they eat, and they found that it was the omega-3s."

In their study, Denkins and colleagues had 12 overweight men and women, aged 40 to 70, consume 1.8 grams of DHA at breakfast for 12 weeks. While none of the study participants had full-blown diabetes, they all suffered from insulin resistance--a pre-diabetic condition in which the body fails to efficiently respond to insulin.

Using blood tests taken at the start and end of the study, the researchers assessed changes in each person's insulin resistance.

"We did see a change in insulin sensitivity after 12 weeks of DHA supplementation," Denkins told Reuters Health. A full 70% of the study participants showed an improvement in insulin-related function, she said, "and in 50% it was a clinically significant change."

Denkins stressed that the small size of the study sample means that the results remain preliminary, and diabetics should never replace their medications with any dietary supplement, including fish oil. Individuals considering upping their intake of fish oil should also consult their doctor beforehand, especially if they are being treated for any cardiovascular condition, she added. This is because DHA has a slight blood thinning effect.

Nutrition experts currently recommend a daily intake of 0.6 grams of omega-3 fatty acids, preferably from fish. According to Denkins, that works out to about two servings of cold-water fish--species like halibut, herring, mackerel or salmon--per week.



Overweight Kids and Diabetes Risk

Source: American Diabetes Association
Publication date: 2002-03-14  From the March 14, 2002 issue of USA Today:
Overweight Kids May be at Risk for Diabetes
- By Anita Manning
     Up to one-fourth of seriously overweight youngsters may be on the road to diabetes, a new study finds.
Researchers at Yale University tested 55 obese children ages 4-10, and 112 ages 11-18. They found 25% of the younger group and 21% of the adolescents have a condition called impaired glucose tolerance, a higher-than-normal level of blood sugar that often precedes full-blown diabetes.
In recent years, the incidence of type 2 diabetes, the form that usually occurs in adults, has increased in young people, especially Hispanics, blacks and Native Americans. Some regional studies suggest the incidence of type 2 in children has jumped from less than 5%, before 1994, to up to 50%.
     Type 2 diabetes results from the body's inability to produce enough insulin or to use it effectively. In type 1 diabetes, which is caused by the destruction of insulin-producing cells in the pancreas, no insulin is produced at all.
     The children most likely to have impaired glucose tolerance were "far more obese and far more insulin-resistant" than the other children, says Yale endocrinologist Sonia Caprio, lead researcher.
     "They're in a stage of pre-diabetes," Caprio says, and if they develop diabetes before age 20 they are at a much higher risk of complications later in life, including stroke, blindness and amputation.
In the study, reported in today's New England Journal of Medicine, white children were as likely as minorities to have impaired glucose tolerance, the researchers found.
     Four of the teens were diagnosed with "silent" type 2 diabetes, which means they had not developed symptoms, and three of the children progressed to full-blown diabetes during the course of the four-year study.
In many cases, says Caprio, diabetes can be headed off.
     "Stop the weight gain. It really is time to take it seriously," she says. Children should be encouraged to eat less, eat better food and exercise more.
     "We should not blame the child," Caprio says. "It's really the society. Every one of us is getting worse."




Diabetes Study Looks At Blood Pressure ;  Kidney Woes, Blindness, Strokes May Be Reduced
Source: Denver Rocky Mountain News
Publication date: 2002-03-01
Diabetes patients can dramatically reduce strokes, blindness and kidney failure by lowering their blood pressure with a couple pills a day, a landmark five-year study based in Denver has found.
The implications are huge because 16 million Americans have diabetes and new cases are skyrocketing as fast as the nation's obesity rate.
"We have an epidemic of both diabetes and obesity in this country," said Dr. Robert Schrier, who headed the study and chairs the department of medicine at University of Colorado Health Sciences Center. "Sixty percent of all Americans are overweight, and 30 percent are obese."
Most previous studies focused on lowering blood sugar to control diabetes, and the results have been disappointing, Schrier said. But the Colorado Prevention Center's diabetes trial focused on blood pressure.
The breakthrough finding is reported in this month's Kidney International: Blood pressure that is low enough for non-diabetics isn't low enough for those with the disease - or those with propensity for the disease. "They already have abnormal blood vessels," Schrier said. "It's not enough to get them down to 140 over 90."
     Of the 950 diabetic volunteers, some were given medications to lower their blood pressure to the moderate level - 137 over 81.
Others had their blood pressures lowered to 125 over 75.
The difference in the two groups was dramatic. Those with the lower blood pressure were one-third as likely to suffer strokes and significantly less likely to lose sight or use of their kidneys.
Marylou Gunderson, 65, has had diabetes since she was 48, and enrolled in the trial in 1993.
"I praise this program to the skies to anyone," said Gunderson, who is grateful for her sight, her working kidneys and ability to walk and swim for exercise.
     The upsurge in diabetes in the United States can hardly be overstated. In 1990, 11 states, including Colorado, had a diabetes rate of less than 4 percent. Eight years later, just two states - Arizona and Montana - had rates that low. The diabetes rate has jumped 76 percent among 30- to 39-year-olds. "Just controlling blood sugar is not the answer," Schrier said. Diabetics probably need to be seen by doctors four or six times a year - not once or twice - to make sure medications are doing the job. "It can have a huge impact on health care in this country."

.''


Processed Meat And Diabetes
Men whose diets contain a lot of processed meats may be raising
their risk for adult-onset (type 2) diabetes. That's the finding
of a study, published in the American Diabetes Association
journal Diabetes Care, which suggests an increased diabetes risk
in men who eat processed meat more than four times per week. In
the study, researchers from the Harvard School of Public Health
looked at the eating habits of 42,504 men age 40 to 75 who were
participating in the Health Professionals Follow-Up Study. When
the study began in 1986, all the subjects were healthy. Over the
next 12 years, those who ate processed meats five times a week or
more appeared to raise their risk of developing type 2 diabetes
by 46 percent. This link persisted even after researchers took
into account other diabetes risks such as smoking, obesity, fat
intake and physical inactivity. The more the men ate foods such
as hot dogs, bacon and packaged lunch meats, the higher their
diabetes risk climbed. The researchers say their findings
suggest that people should eat processed meats in moderation, The
Associated Press reports. They note that the high-fat condiments
and side dishes often eaten with processed meats may also affect
diabetes risk, the AP says. The researchers say more research is
needed to confirm their findings.


C-reactive Protein (CRP) and Diabetes
The success of statins has spawned many studies considering the possible mechanisms by which statins alter the atherosclerotic process or its complication of plaque rupture. The 2001 Scientific Sessions provided a wealth of data regarding mechanisms of atherosclerosis. Particularly exciting is the ongoing convergence between cardiovascular epidemiology and vascular biology, given recent data suggesting that elevated markers of inflammation, such as CRP, predict the risk of future myocardial infarction. Evidence also exists to suggest that the benefits of statin therapy may derive to some extent from its anti-inflammatory effects, and a considerable number of presentations at this year's AHA meeting focused on these non-LDL, pleiotropic effects. Earlier basic science studies had suggested that perhaps CRP is not simply a marker for, but also a mediator of, inflammatory processes in the vasculature, and this theory is now supported by reports that CRP may increase uptake of oxidized LDL.
This question of the role of CRP has also been extended to diabetes, a disease that, like atherosclerosis, is a chronic process in which inflammatory mechanisms may contribute to its natural history. Congruent with this were recent reports that inflammatory markers such as CRP may predict the occurrence of new-onset diabetes.
As a result of this expanding line of investigation, therapies for diabetes have begun to consider whether they might have an effect on inflammatory markers such as CRP and interleukin-6 (IL-6). The hypothesis is that it should be possible to prevent the onset of type 2 diabetes with drugs that improve insulin sensitivity, given the role of insulin resistance in this disease. Similarly, insulin sensitizers should provide good tools for investigating whether conversion occurs because of changes in inflammatory pathways. Several ongoing studies with insulin-sensitizing agents -- eg, thiazolidinediones (TZDs; pioglitazone [Actos] and rosiglitazone [Avandia]) or metformin (Glucophage) -- are considering the issues of conversion to diabetes and changes in inflammatory markers.
Haffner and colleagues[6] presented an important abstract at the AHA Sessions suggesting that rosiglitazone did in fact lower CRP levels. This abstract included results from ~ 350 patients with type 2 diabetes who were randomized to 1 of 3 regimens: rosiglitazone 4 mg/day, rosiglitazone 8 mg/day, or placebo. Effects of rosiglitazone on CRP levels were assessed (along with levels of matrix metalloproteinase 9). After 26 weeks of treatment, the placebo group demonstrated a small, nonsignificant decrease from baseline CRP levels (-13.9% [95% CI, -26.7, 1.2]). Conversely, statistically significant decreases from baseline were seen in both of the rosiglitazone treatment groups (rosiglitazone 4 mg/day, -40.7% [95% CI,-50.2, -29.3]; rosiglitazone 8 mg/day, -35.6% [95% CI, -44.7, -25.1]). Differences compared to placebo were significant for both treatment groups. Similar results have been seen in response to pioglitazone, with several abstracts at the AHA reporting anti-inflammatory effects in vitro and in animal models with these agents.

Caffeine Linked to Pre-Diabetic Condition
Wed Feb 20, 5:29 PM ET
By Charnicia E. Huggins
NEW YORK (Reuters Health) - Preliminary findings from a small study suggest that drinking moderate amounts of coffee may put healthy individuals at risk for decreased insulin sensitivity, or an inability to process blood sugar efficiently. Decreased insulin sensitivity is a precursor to diabetes.
   
"Our finding may have serious health implications, especially when superimposed on already-disturbed glucose tolerance or established (type 2) diabetes," write lead study author Dr. Gerben B. Keijzers and colleagues from University Medical Center in Nijmegen, the Netherlands.
But because more study is needed, "it is currently premature to advise against caffeine use," the researchers add.
Keijzers and colleagues studied 12 healthy individuals who, after abstaining from caffeine for 72 hours, were intravenously given moderate doses of either caffeine or an inactive substance.
Caffeine reduced insulin sensitivity by 15% among the study group, the researchers report in the February issue of Diabetes Care. The decrease in insulin sensitivity was comparable to the increase in sensitivity produced by taking diabetes drugs.
The caffeine group also had higher blood levels of free fatty acids than their peers in the comparison group, the report indicates.
Caffeine's ability to decrease insulin sensitivity could occur because the drug boosts levels of free fatty acids, as well as the hormone epinephrine, the authors suggest. The caffeine group exhibited a five-fold increase in blood levels of the hormone, the report indicates.
In an accompanying editorial, Drs. Italo Biaggioni and Stephen N. Davis of Vanderbilt University in Nashville write that Keijzers' study "adds another item to the list of potential deleterious effects of caffeine."
But coffee drinkers should not panic, Biaggioni told Reuters Health.
"The study was performed under artificial experimental conditions in normal people," he said. "The conclusions, therefore, are not immediately applicable to the rest of us, to obese people or to patients with diabetes."
"Coffee is, in general, a safe substance," Biaggioni said. "However, every substance, even aspirin, may be dangerous to some people, or if we take too much of it."
"Talk to your doctor if you think you are drinking too much coffee or if your diabetes is not well controlled," he advised.
SOURCE: Diabetes Care 2002;25:364-369.



  NEW ENGLAND JOURNAL OF MEDICINE Volume 346:393-403  February 7, 2002  Number 6
Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin
ABSTRACT

Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups.

Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin.

Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin









INSULIN RESISTANCE
METABOLIC SYNDROME
GLYCEMIC INDEX
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ROBOT.TXT
Does use of metformin protect against cancer in Type 2 diabetes mellitus?;
Bo S, Benso A, Durazzo M, Ghigo E; Journal of Endocrinological Investigation 35 (2), 231-5 (Feb 2012)
BACKGROUND Type 2 diabetes mellitus has been associated with an increased cancer risk, which can be modified by specific hypoglycemic drugs. In particular, metformin, the most frequently prescribed biguanide, is now considered a protective agent against cancer incidence and mortality in Type 2 diabetic patients. AIMSTo review the potential associations between metformin use and cancer incidence and mortality and the possible biological links implicated in these associations. MATERIALS AND METHODSWe searched Englishlanguage original investigations published through September 2011. RESULTSMetformin could block the mitogenic effects of insulin, but this effect does not entirely explain the reduction in cancer incidence. Metformin also plays a direct inhibition of cancer cell growth via the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation. Accordingly, many epidemiological studies have shown that metformin use is associated with a lower cancer incidence and mortality through a dose-response relationship, with greater exposure being associated with stronger risk reduction. Randomized clinical trials testing the effects of metformin on both recurrence and survival in early-stage breast cancer are on-going; these trials are based on pilot studies demonstrating an adjuvant effect of this drug in breast cancer.
CONCLUSIONS Metformin is an inexpensive and safe drug, that may modify the increased cancer risk of Type 2 diabetic patients. On-going clinical trials will show whether this drug can enhance the effect of chemotherapy in the treatment of cancer.