Diabetes: ‘Gold Standard’ HbA1c Test Not So Great For Dialysis Patients ‎

In situations where rapid changes occur in blood sugar, the glycated albumin (GA) test gives a more accurate picture of diabetes control

BLOOD sugar monitoring is a vital part of diabetes management. Patients and physicians rely on the hemoglobin A1c (HbA1c) test to measure an individual’s average blood sugar level over the prior three months. It is the most commonly used long-term blood sugar test, and the gold standard for the medical community.

While the American Diabetes Association has deemed the HbA1c test an effective tool for diagnosing diabetes, kidney doctors recently determined that the HbA1c is not as useful for managing patients with diabetes and advanced kidney failure. Another test, the glycated albumin or GA assay, appears to be far more effective in this setting, they say.

The GA test, developed by Tokyo-based Asahi Kasei Pharma Corporation, measures blood sugars over the past 17 days, as opposed to the longer time frame for HbA1c. In situations where rapid changes occur in blood sugar, the GA gives a more accurate picture of diabetes control. The GA test used in this study is available in Japan, China and South Korea, but is not yet FDA approved in the United States.

According to a new study at Wake Forest Baptist Medical Center, which appears online in the Clinical Journal of the American Society of Nephrology and is scheduled for the July print issue, many organs don’t function properly in severe kidney failure. For example, most dialysis patients have anemia with fewer red blood cells than they should, which has a dramatic impact on the accuracy of the HbA1c reading.

Hemoglobin inside red blood cells carries oxygen in the body. Blood sugar chemically interacts with the hemoglobin to identify a value for HbA1c. But HbA1c results are only accurate when red cells have a normal lifespan. Dialysis patients have shorter red cell survival, reducing the time that sugar in the bloodstream has to interact with hemoglobin, and causing lower HbA1c values.

“Doctors long thought the HbA1c predicted outcomes in diabetes. This test is not predictive of outcomes in diabetes patients with kidney disease on dialysis. Dialysis patients and physicians get a false sense of security because their lower HbA1c actually relates to shorter red cell survival, yet suggests diabetes control is better than it really is,” explained Barry I. Freedman, M.D., John H. Felts III Professor and lead investigator.

“This is the first study showing that a blood sugar test predicts risk of death in diabetic dialysis patients, as well as risk of hospitalization,” Freedman said. “This test provides the missing link that will allow dialysis patients and physicians to accurately gauge risk. The association is clear: high GA readings predict higher risk.”

Freedman and colleagues evaluated 444 patients with diabetes undergoing dialysis. Patients continued their normal treatment and HbA1c monitoring, but also agreed to have a GA test every three months for an average of more than 2.3 years.

Wake Forest Baptist researchers compared the patients’ HbA1c and GA test results, assessing their ability to predict hospitalizations and survival. They found that the HbA1c failed to predict these important medical outcomes. In contrast, the GA was a strong predictor of patient survival and hospitalizations.

Nearly 500,000 people are on dialysis in the Unites States and diabetes is the cause of kidney failure in nearly 50 percent of them. Diabetes is the most common cause of kidney failure worldwide and is associated with high mortality rates – more than 20 percent of dialysis patients die each year. As such, there is an urgent need for accurate blood sugar testing in diabetic dialysis patients.

Freedman suggests physicians not rely on the HbA1c in dialysis patients, instead suggesting that blood glucose levels be directly monitored with multiple daily readings until the GA test is available in the states.

The GA test is not limited only to dialysis patients. Some studies have shown that shorter-term markers for glucose control may lead to better management of glucose than longer-term measures with the HbA1c test. So, instead of waiting 3-6 months for an HbA1c test, which is the current recommendation, the rapid and inexpensive GA test could be performed monthly.

Several studies have confirmed that measurements of GA and HbA1c are closely correlated. Though the GA test has been available in labs for years, Epinex Diagnostics, the developer of the rapid result GA measurement called G1A™, believes the mounting scientific evidence that supports GA testing will eventually gain wide acceptance among professionals. Numerous studies show the need for a mid-range test that could be performed monthly as another means of helping people with diabetes manage their glucose levels more effectively.

Sources: Wake Forest Baptist Medical Center, Epinex Diagnostics

Diabetes Can Be Predicted 7 Years Before Pregnancy With Blood Sugar And Body Weight

A woman’s risk of developing diabetes during pregnancy can be identified up to seven years before she becomes pregnant based on routinely assessed measures of blood sugar and body weight, according to a Kaiser Permanente study published in the online issue of the American Journal of Obstetrics and Gynecology.

Researchers at the Kaiser Permanente Division of Research in Oakland, Calif., studied 580 ethnically diverse women who took part in a multiphasic health checkup at Kaiser Permanente Northern California between1984 and 1996. The researchers looked at women who had a subsequent pregnancy and compared those who developed gestational diabetes mellitus (GDM) during pregnancy to women who did not have GDM.

The study found that the risk of GDM increased directly with the number of adverse risk factors commonly associated with diabetes and heart disease (high blood sugar, hypertension and being overweight) present before pregnancy. In addition, the authors found that adverse levels of blood sugar and body weight were associated with a 4.6-fold increased risk of GDM, compared to women with normal levels.

The study is among the first to look at routinely measured cardio-metabolic risk factors before pregnancy in women who later became pregnant and developed GDM. The research provides evidence to support pre-conception care for healthy pregnancies as noted in a 2006 report by the Centers for Disease Control and Prevention. That report suggested that risk factors for adverse outcomes among women and infants can be identified prior to conception and are characterized by the need to start, and sometimes finish, interventions before conception occurs.

Women who develop GDM during pregnancy are more likely to develop Type 2 diabetes after pregnancy, previous research has shown. GDM is defined as glucose intolerance that typically occurs during the second or third trimester and causes complications in as much as 7 percent of pregnancies in the United States. It can lead to early delivery and Cesarean sections, and increases the baby’s risk of developing diabetes, obesity and metabolic disease later in life.

Dr Monique M. Hedderson

“Our study indicates that a woman’s cardio-metabolic risk profile for factors routinely assessed at medical visits such as blood sugar, high blood pressure, cholesterol and body weight can help clinicians identify high-risk women to target for primary prevention or early management of GDM,” said lead author Monique Hedderson, PhD, a research scientist at the Kaiser Permanente Division of Research.

Although the established risk factors for GDM are older maternal age, obesity, non-white race/ethnicity, giving birth previously to a very large baby and a family history of diabetes, these risk factors are absent in up to half of women who develop GDM. This study is significant because it gives a better understanding of pre-pregnancy predictors of GDM that may help identify women at risk and get them into intervention programs before pregnancy to prevent GDM and its associated risks, researchers said.

Related articles on gestational diabetes:

• A study in the American Journal of Epidemiology found that cardio-metabolic risk factors such as high blood sugar and insulin, and low high density lipoprotein cholesterol that are present before pregnancy, predict whether a woman will develop diabetes during a future pregnancy.
•  A study in the American Journal of Obstetrics and Gynecology found there is an increased risk of recurring gestational diabetes in pregnant women who developed gestational diabetes during their first and second pregnancies.
•  A study in Diabetes Care of 10,000 mother-child pairs showed that treating gestational diabetes during pregnancy can break the link between gestational diabetes and childhood obesity. That study showed, for the first time, that by treating women with gestational diabetes, the child’s risk of becoming obese years later is significantly reduced.
•  A study in Obstetrics & Gynecology of 1,145 pregnant women found that women who gain excessive weight during pregnancy, especially in the first trimester, may increase their risk of developing diabetes later in their pregnancy.

Via EurekAlert

Related Video:

After Cracking Metformin Code, Scientist Makes Breakthrough Discovery That Points The Way To New Class Of Diabetes Drugs

HDAC inhibitors may provide a novel way to cut excessive blood glucose levels at the source

RESEARCHERS have uncovered a novel mechanism that turns up glucose production in the liver when blood sugar levels drop, pointing towards a new class of drugs for the treatment of metabolic disease, the Salk Institute for Biological Studies announced in a press statement on Tuesday.

Dr Reuben J. Shaw

In a uniquely collaborative study, the scientists have found evidence ‒ published in the May 13, 2011 issue of the journal Cell ‒ that a group of enzymes, or proteins, currently under investigation for the treatment of cancer could potentially also work as a treatment for type 2 diabetes. This is significant because it not only portends a new treatment for diabetes, but it also could mean that a new treatment has already gotten through the costly and lengthy early stages of drug development.

The Salk discovery revolves around enzymes called histone deacetylases, or HDACs, which help the liver produce sugars when blood glucose runs low after prolonged periods of fasting, particularly at night. After a meal, insulin “instructs” muscle cells to store this glucose and turns off sugar production in the liver. In patients with type 2 diabetes, however, the body effectively doesn’t “listen” to insulin, and the liver keeps producing sugar.

In liver cells, so called class II HDACs (shown in green) are usually sequestered in the cytoplasm.

“These exciting results show that drugs that inhibit the activity of class II HDACs may be worthwhile to be pursued as potential diabetes drugs,” said lead author Reuben Shaw, an assistant professor in Salk’s Molecular and Cell Biology Laboratory.

Up to this point, all experiments had been performed in cultured cells but the researchers were really interested in whether class II HDACs controlled blood glucose in mouse models of diabetes. Strikingly, suppression of all three HDACs simultaneously restored blood glucose levels to almost normal in four different models of type 2 diabetes.

In response to glucagon, HDACs quickly move into the nucleus, where they help turn on genes needed for the production of glucose in the liver

“The key will be to specifically block HDACs involved in glucose control,” said Shaw, “but the fact gluconeogenesis takes place in the liver makes this task easier as most drugs sooner or later travel to the liver once they hit the bloodstream.”

“Our results predict then that some of those drugs, probably not the same ones that work on cancer but some of the ones that are sitting on the shelf that maybe weren’t effective for cancer but in fact hit these enzymes, that they could be potential therapeutics for diabetes,” said Shaw. “That means that the time from this initial discovery until the time that this can be tested in the clinic is much shorter.”

Dr. Ronald Evans, a professor in Salk’s Gene Expression Laboratory, said that while this discovery is novel, scientists have long noticed a link between cancer and diabetes, particularly because the risks of both diseases are increased in obese patients. This discovery — that suppressing HDACs can treat diabetes as well as cancer — is a way of turning this theory into a potential treatment.

“We know that along with increased weight and obesity there is an increased risk of cancer. We also know that cancer cells undergo a profound metabolic change and so the cancer metabolism has become a very big area (of study),” Evans said.

“So for those of us who study metabolism and study cancer, the link between these two seemingly separate areas, actually at the level of the genome, happen to work with several common pathways,” he continued, “because they’re both dealing with either consuming energy, which is what happens with cancer, or storing energy, which is what happens with obesity.”

Does Periodic Fasting Lower Diabetes Risk?

Currently, metformin (Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet), an oral biguanide anti-diabetic drug, is the most widely prescribed agent for treatment of type 2 diabetes. The drug mainly works by lowering glucose production by the liver, and thus lowering fasting blood glucose. Although metformin – approved in the United States in 1994, and in Europe prior to that – has been used for many years, its mechanism of action is not well understood.

Galega officinalis (Goat's Rue)

“Metformin is originally derived from a plant found in Western Europe called ‘French lilac’ or ‘Goat’s Rue’ because goats didn’t like to eat it. They steered clear of the plant because it contains a compound that acts to naturally lower blood glucose in animals that eat it ‒ to prevent them from eating it again,” Shaw explained.

A few years ago, Shaw discovered how metformin helps insulin to control glucose levels:  It binds to a “metabolic master switch” known as AMPK that blocks glucose production in the liver. Trying to identify novel targets of AMPK that might be relevant to diabetes, Maria Mihaylova, a graduate student in the Shaw laboratory, focused her efforts on a family of HDACs known as class II HDACs. They function as negative regulators of gene activity by stabilizing the tightly coiled structure of DNA in chromosomes, making it inaccessible to proteins that transcribe DNA.

Working closely with Ronald M. Evans and his team, Mihaylova found that inhibiting class II HDACs shut down genes encoding enzymes needed to synthesize glucose in liver. “We identified class II HDACs as direct targets of AMPK in a bioinformatics-based screen, but we didn’t know which genes they might regulate in liver since they weren’t even known to be found there,” said Mihaylova.

In collaboration with her colleagues in Marc Montminy’s lab, a professor in the Clayton Foundation Laboratories for Peptide Biology, and like Shaw and Evans a member of the Center for Nutritional Genomics at the Salk Institute, Mihaylova discovered that HDACs themselves associated with the DNA regulatory elements controlling the expression of the glucose synthesizing enzymes, but they only flocked there after she had treated cells with the fasting hormone glucagon.

“In response to the glucagon, chemical modifications on class II HDACs are removed and they can translocate into the nucleus,” she explains. There, they bind to FOXO, a key metabolic regulator, which had been shown previously to be shut down by insulin.

“It came as a big surprise that FOXO is activated by glucagon,” explains Shaw. Further experiments confirmed that the genetic suppression of class II HDACs in liver cells led to an increase in acetylated FOXO, which now can neither bind DNA nor activate the genes encoding glucose-synthesizing enzymes.

A parallel study, led by Montminy and published in the same issue of Cell as Shaw’s paper, shows that in fruit flies, FOXO not only controls the expression of a fat-digesting enzyme but is activated by a glucagon-like hormone in a manner similar to human FOXO.

“The central circuitry of how animals regulate metabolism in response to fasting and feeding is conserved from fly all the way to man emphasizing the importance of class II HDACs in coordinating how different hormones direct the creation and use of glucose,” says Shaw, who is a co-author on Montminy’s paper.

Shaw next plans to test whether these glucose loving HDACs may also play roles in certain forms of cancer as well.

Source: Salk Institute for Biological Studies

UK Trials to Determine if Metformin Given to Overweight Expectant Mothers Can Stop Them From Having Fat Babies Begin

HUNDREDS of overweight mothers-to-be are being given metformin up to three times a day during their pregnancy to stop them from having obese babies as part of a controversial trial in the UK. The trial involves 400 obese but non-diabetic volunteers at hospitals in Liverpool, Edinburgh and Coventry.

Half will take metformin from around 12 weeks into their pregnancy and half will take a placebo. Their health and their babies’ health will be monitored and the results are expected in four years. It is hoped the treatment will prevent the birth of overweight babies and bring down the need to carry out caesarean sections as well as preeclampsia.

The latest figures show that almost half of women of childbearing age in Britain are overweight or obese and more than 15 percent of pregnant women are obese. This raises their odds of dying in pregnancy, of their baby being stillborn and of a host of pregnancy complications, some of which can be fatal.

Indeed, one of the most alarming facts to emerge after the trails were announced is that each year the Liverpool Women’s Hospital, for example, cares for more than 500 pregnant women who have a body mass index of more than 40 – which translates as severely obese.

Doctors believe many overweight adults can trace their problems back to the womb, when the fetus absorbs too many sugars and fats because of the high levels of insulin in their mother’s blood. But rather than trying to help the expectant mother lose weight, the drug would help keep the weight of the unborn baby down by reducing the levels of blood sugar passed to babies in the womb

Metformin, long cleared for the treatment of diabetes in pregnancy, has been safely used by diabetics for decades and the UK researchers think early intervention administering it to obese expectant mothers could save youngsters from a lifetime of weight problems and ill-health.

The doctors behind the trial say obesity among pregnant women is reaching epidemic proportions and they need to protect the health of tomorrow’s children. However, many healthy women are likely to be uneasy about mass medication in pregnancy for a problem that can be treated through changes to diet and exercise.

Ian Campbell, medical director of charity Weight Concern, said: “In an ideal world we would be in a position to assist women to be of a near-normal bodyweight prior to conception. But that is not realistic in the current environment. The reality is that many women go through pregnancy carrying too much body fat and it is important we do something about it because it causes serious problems.”

Defending the exercise which has raised the hackles of several groups, Andrew Weeks, who is leading the trial, said: “It is about trying to improve outcomes in pregnancy for women who are overweight. The problem is babies tend to be larger and many of the downsides of being overweight during pregnancy relate to the birth.”

Documents for the trial state: “Rates of obesity in adults and children are rising exponentially in the UK, as in other developed nations, and there are major causes for concern. The problem of maternal obesity, leading to programming of future life obesity risk in offspring, and manifest by excess birth weight, is reaching epidemic proportions. We believe that metformin will likely be an effective therapy in interrupting this cycle.”

Professor Norman, of Edinburgh University, said metformin was judged as a safe drug but the trial is needed to ensure the benefits outweighed any risks.  She added that if the trial does show metformin to be of benefit, it is unlikely to work in all women and is most likely to be prescribed alongside advice on diet and exercise.

Nonetheless, women rightfully feel “uneasy” about the trial, said Alison Wetton, CEO of Britain’s fastest growing weight loss organization, All About Weight. “No mother-to-be likes to take medication, and the fact that the widely-used diabetes pill, metformin, is being trialed to prevent obese babies being born to overweight mothers is disturbing to me, and I am sure most other women as well,” she said.

Will Williams, scientific advisor for All About Weight, said that although there were “reasonable grounds” for the trial, it was “a shame that it is needed at all.” He said women wanting to conceive could instead lose weight by following a healthy weight loss plan, including diet and exercise, and “thus achieve all the things that the metformin trial is hoping to do, without the risks or costs of adding a drug with uncertain long term effects.”

“This would be far preferable to popping a pill that may help pregnancy outcomes but is unlikely to break the cycle of an unhealthy lifestyle leading to overweight children and the continuing rise of obesity and diabetes in the general population,” he stressed.

Related posts:

Bad Diet for Expectant Mother Can Mean a Fat Baby

Fat Fathers Pass on Diabetes

Looking Beyond HbA1c: Research To Find New Diabetes Biomarkers Gains Traction

The discovery of several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes

BETA cells within the pancreas produce and release insulin. Loss of the function of these cells compromises the body’s ability to control blood sugar and underlies the development of diabetes. So, one of the next frontiers of diabetes therapeutics is to change the progression rate of beta cell failure.

Recognizing this as a research priority, the Foundation of the National Institutes of Health (FNIH) Biomarkers Consortium announced Tuesday the launch of a multi-year clinical study to improve tools for measuring the function of insulin-producing beta cells in people with type 2 diabetes mellitus. Researchers hope the initiative will lead to improved techniques for tracking progression of the disease and pave the way for more effective treatments.

The project ‒ “Diabetes Drug Development: Identification and Validation of Markers that Predict Long-Term Beta Cell Function and Mass” ‒ is being managed by the Metabolic Disorders Steering Committee (MDSC) of the FNIH Biomarkers Consortium.

It is a three-year, $5.1 million clinical study to standardize tests for measuring beta cell function in the clinical setting that aims to improve methods for the early prediction of the long-term response to an intervention and for identification of patients at risk for rapid beta cell function deterioration, thereby enabling future clinical studies that examine diabetes progression.

A biomarker is a biochemical feature or facet that can be used to measure the progress of disease or the effects of treatment. So the validation of biomarkers to measure the progression of diabetes will greatly facilitate the development of better medicines to treat and potentially prevent this disease and its often disabling complications.

Experts believe biomarkers will become one of the major driving forces of pharmaceutical research and drug development in the coming years.

Currently, diabetes researchers are working without the benefit of agreed-upon standards for gauging beta cell function and this initiative will give researchers practical tools that can be used to measure beta cell function over time and stimulate research to maintain and improve that function.

The project was developed through a rigorous consensus-building process by a team of experts from across the entire scientific community. The pharmaceutical industry, academic, and government representatives contributed their clinical trials expertise and scientific support to the design and execution of the studies.

Utilizing a collaborative approach, the FNIH Biomarkers Consortium has brought together diabetes experts from the National Institutes of Health (NIH), Food and Drug Administration (FDA), leading academic institutions, the pharmaceutical industry, and non-profit sector to develop the project.

Biomarkers play an integral part in conducting clinical trials and treating patients. In most instances, they help medical practitioners, researchers, and regulatory officials make well-informed, scientifically sound decisions.

However, in clinical studies, there is often uncertainty in how much weight to place on biomarker results versus clinical outcomes. This uncertainty emanates from opposing goals of the drug approval process. On one hand, the process must ensure that all therapeutics tested are safe and that the benefits outweigh the risks. On the other hand, the process should allow therapies to be accessible to patients as quickly as reasonably possible.

Judicious use of biomarkers in the drug development process can bring these goals into alignment. More efficient discovery and use of biomarkers in the development of anti-diabetes drugs will depend on advancing current understanding of the pathogenesis of diabetes and especially its macrovascular (pertaining to the larger blood vessels) complications.

The idea of using biomarkers to predict diabetes is not entirely new. Glycated hemoglobin (HbA1C) values are now routinely being monitored to screen for at-risk patients. A study published in PLoS One last year shows that several new biomarkers in the blood may further our understanding of exactly who’s at risk for diabetes, and increase our knowledge of the etiology of the disease.

Veikko Salomaa and colleagues from the Department of Chronic Disease Prevention at the National Institute for Health and Welfare in Helsinki, Finland, tested nearly 13,000 people and found almost 600 cases of diabetes during routine follow-up exams.

According to the study, low levels of adiponectin, and high levels of apoB, C-reactive protein (CRP), and insulin, increase the chance that a woman will develop diabetes. When these factors were measured, proper diabetes prediction increased by 14% compared to when doctors only use classic risk factors, such as BMI and blood glucose levels, to predict disease.

The biomarkers that best predicted diabetes in men were low adiponectin, and high levels of CRP, interleukin-1 receptor antagonist (IL-1RA), and ferritin. Accounting for these biomarkers led to a 25% increase in correct diabetes detection in the cohort. Adiponectin is a hormone found in the body that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.

The use of adiponectin, a hormone derived from fat cells, which is abundant in plasma and easy to measure through commercially available kits, was also confirmed as a robust biomarker predictive of glycemic efficacy in Type 2 diabetes and healthy subjects, after treatment with peroxisome proliferator-activated receptor-agonists (PPAR), but not after treatment with non-PPAR drugs such as metformin by the first project to be completed by the Biomarkers Consortium.

The project conducted a statistical analysis of pooled and blinded pre-existing data from Phase II clinical trials contributed by four pharmaceutical companies and analyzed under the direction of a diverse team of scientists from industry, the National Institutes of Health (NIH), U.S. Food & Drug Administration (FDA), and academic research institutions.

Source: FNIH Biomarker Consortium

D-Blog Week: As If Managing Diabetes Is Not Enough, We Have To Contend With Poorly Trained Doctors As Well

Dear Dr Endo,

You’ve done a great job helping me manage my diabetes and I don’t doubt your credentials one bit. But recently I read with alarm an unsettling news report which was headlined: 100,000 ‘received wrong diabetes diagnosis’. The report went on to reveal that a research study had found “substantial evidence” that people in the UK are being “miscoded, misclassified and misdiagnosed with diabetes” on GP (general practitioner or family physician) lists.

One of the experts behind the report, Professor Simon de Lusignan from the University of Surrey, conceded that around 50,000 people were diagnosed with diabetes but did not have it, and another 50,000 were classified with the wrong type.

This means some people were been told they had Type 2 diabetes when in fact they have Type 1, and vice versa! The damning report says “the most widespread misunderstanding” among health professionals was changing somebody’s diagnosis from Type 2 to Type 1 when they go on to insulin.

A misdiagnosis could have a considerable impact on my life as the guidelines for insulin use in Type 2 are very different from those in Type 1. And what happens to diabetics who aren’t familiar with these things and follow the doctor’s advise faithfully.

But before I strike off Britain from the list of countries I’d like to visit, I must say this problem is not limited to the UK. In fact, like diabetes, it may be a global epidemic. Indeed, I have read many reports of doctors being clueless when it comes to treating diabetes.

Back in February, I had written about an Australian diabetic who died because emergency room doctors were ignorant about treating hypoglycemia. And stories like these have only strengthened my belief that in the age of ‘superspeciality’, our medical schools are producing graduates who miss the wood for the trees.

This, of course, has been borne out by a study published in the American Journal of Medicine which shows that there is currently an imbalance in the training of primary care physicians.  The researchers say that despite the fact that 90 percent of doctor visits are outpatient, most medical schools focus on inpatient situations. This leaves future primary doctors unprepared to deal with chronic disease like diabetes.

Dr. Stephen Sisson, who led the study, said: “When I graduated from residency here, I knew much more about how to ventilate a patient on a machine than how to control somebody’s blood sugar… The average resident doesn’t know what the goal for normal fasting blood sugar should be.”

After administering a test commonly used to gauge the knowledge of medical students to a group of first-, second- and third-year residents, Dr Sisson discovered to his horror that ALL the first-year residents were poorly prepared to treat chronic illness. (Fortunately, knowledge improved somewhat among community hospital residents over time.)

Dr Sisson concluded that this is happening because training for all residents is particularly poor on outpatient diagnosis and management of diabetes, lipid disorders, dizziness, anemia, and alcoholism. The culture at university hospitals, where specialists often assume leadership roles in resident education, is not hospitable toward primary care, where specialized medicine is emphasized over a broad education in general internal medicine, he says. (You can read my report on this study here.)

My poser is: If family physicians don’t know what needs to be done, how are they going to guide us patients?

Alas, poorly trained family physicians are not the only problem we diabetics face. If I were to be hospitalized and be cared for by ‘specialists’, I’d fare no better.

Recently, a UK national audit found that 37% of diabetic inpatients are subject to medication errors by doctors and nurses, including being given the wrong dose of drugs or at the wrong time. More than one in four (26%) medical charts contained errors about prescriptions and a fifth contained one or more errors on how medicines were being managed in hospital. The errors related to drugs, including insulin as well as tablets, to keep blood sugar under control.

The report pointed to “significant issues” concerning the use of insulin drips in hospitals. Some 13% of diabetic patients had been on an insulin drip for the previous seven days but 8% of drips were considered “inappropriate”. Overall, 10% of insulin drips exceeded seven days and 12% were considered “inappropriately long”.

In more than a quarter of cases (26%), the transfer of the patient back on to insulin injections “was not managed appropriately”, the audit said. Those who had undergone surgery were more likely to have been given an inappropriate drip and more likely to encounter problems when going back on to injections.

The audit also discovered that over one third (37.1%) of inpatients with diabetes experienced at least one medication error, a quarter (26%) of their charts had prescription errors and a fifth (20%) had one or more medication management errors.

My understanding is that insulin overdoses can result in potentially fatal hypoglycemic episodes (‘hypos’) and insufficient insulin can lead to diabetic ketoacidosis (DKA) which, if left untreated, can also prove fatal.

For too long many of us diabetics have experienced poor care at the hands of physicians and in hospitals. And if we were to swap stories, I’m sure Karen, who’s hosting the second Diabetes Blog Week, would need to organize another event devoted to horror stories. In the meanwhile, what do I do?

Given the fact that many family doctors do not have enough knowledge to effectively advise diabetes patients (borne out by many studies), and visits to a specialist like you involves long waiting periods and longer commutes, I personally support the concept of diabetes self-management education (DSME). And guess what, doc? IT WORKS!

Indeed, in case of emergencies, like hypos, I’d rather have my family members  tell the doctors what to do or I’d carry a note detailing the measures to be taken ‒ in case I have passed out ‒ in my wallet along with my card that identifies me as a diabetic.  If it offends the health professionals in the emergency room, so be it.

No offence to your profession, doc, but it’s my life!

Regards

“Normal” Blood Sugar Levels May Still Mean You Have Prediabetes

FPG between 91 and 99 mg/dl is a strong independent predictor of type 2 diabetes, claims new study

Type 2 diabetes is a lifestyle disease in which the body no longer responds appropriately to the hormone insulin, which helps ferry sugar from the blood into our cells after a meal. When fasting blood sugar levels reach 126 mg/dl or more, doctors will diagnose diabetes

Prediabetes means that your blood sugar level is higher than normal, but it’s not yet increased enough to be classified as type 2 diabetes. Still, without intervention, prediabetes is likely to become type 2 diabetes in 10 years or less. (Scroll to end for Prediabetes FAQs)

Traditionally, blood sugar levels below 100 mg/dl have been considered “safe”, whereas levels between 100 and 126 signal a “higher risk” of diabetes (prediabetes). But according to the new study by Dr. Paolo Brambilla and colleagues at the University Milano Bicocca in Italy, the currently accepted “normal” blood sugar range might be too wide.

“FPG (Fasting Plasma Glucose) between 91 and 99 mg/dl is a strong independent predictor of type 2 diabetes and should be used to identify people to be further investigated and aided with preventive measures,” the researchers say. The conclusion significantly expands the “prediabetes” label.

To back their claim, the researchers report that in the course of their study they discovered people at the high end of what’s considered the “normal” blood sugar range are twice as likely to get the disease as are those in the low end. The findings are in line with an earlier study from Oregon, and the Italian researchers say they can help identify the people who need extra medical attention.

The researchers looked at data for nearly 14,000 men and women who’d had blood drawn several times at their clinic. The patients were between 40 and 69 years old and all of them had normal blood sugar levels at first. Over the next seven to eight years, on average, about two percent of the women and nearly three percent of the men developed diabetes.

Less than one percent of those who started out with fasting blood sugar levels between 51 and 82 mg/dl wound up with the disease, while more than three percent did so if they had values between 91 and 99. After controlling for other factors that might influence the likelihood of getting diabetes, that corresponded to a two-fold difference in risk of developing the disease.

Research has shown that if you have prediabetes, the long-term damage of diabetes — especially to your heart and circulatory system — may already be starting. If your blood sugar tests over 100 mg/dl fasting more than once, your fasting blood sugar is likely to go over the 125 mg/dl level used to diagnose full diabetes within 3 years.

More importantly, if your blood sugar is at 100 mg/dl fasting, it is very likely that your post-meal blood sugar is heading towards the diabetic range, which is over 200 mg/dl which is why your fasting blood sugar is deteriorating. High post-meal blood sugars kill beta cells. If you can bring down those post-meal highs, you may be able to prevent the beta cell death that is destroying your fasting control!

While opinion is divided on the question whether doctors should treat these people any different, as the researchers suggest, everyone agrees that people should strive to manage their weight and be physically active irrespective of what their blood sugar level is.

The bald reality is that, according to the American Diabetes Association, in the US alone there are three times as many prediabetics as people with diabetes (79:27 million). And It is estimated that there will be 418 million people worldwide with prediabetes by 2025.

How to Tell if You Have Prediabetes

The American Diabetes Association says while diabetes and prediabetes occur in people of all ages and races, some groups have a higher risk for developing the disease than others and warns that Diabetes is more common in African Americans, Latinos, Native Americans, and Asian Americans/Pacific Islanders, as well as the aged population. This means they are also at increased risk for developing prediabetes.

There are three different tests your doctor can use to determine whether you have prediabetes:

• The A1C test

• The fasting plasma glucose test (FPG)

• The oral glucose tolerance test (OGTT).

The blood glucose levels measured after these tests determine whether you have a normal metabolism, or whether you have prediabetes or diabetes.

If your blood glucose level is abnormal following the FPG, you have impaired fasting glucose (IFG); if your blood glucose level is abnormal following the OGTT, you have impaired glucose tolerance (IGT). Both are also known as prediabetes.

The American Diabetes Association Risk Test for Diabetes can help you determine if you are at increased risk for diabetes or prediabetes. A high score may indicate that you have prediabetes or at risk for prediabetes. Take the test and find out for sure.

ADA Prediabetes FAQs

What is prediabetes and how is it different from diabetes?

Prediabetes is the state that occurs when a person’s blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes. About 11 percent of people with prediabetes in the Diabetes Prevention Program standard or control group developed type 2 diabetes each year during the average 3 years of follow-up. Other studies show that many people with prediabetes develop type 2 diabetes in 10 years.

What are the symptoms of prediabetes?

The reason why so many people suffer from prediabetes and are completely unaware of it is because it is quite possible for no symptoms to manifest themselves. Both diabetes and prediabetes develop at a gradual rate.

How do I know if I have prediabetes?

Doctors can use either the fasting plasma glucose test (FPG) or the oral glucose tolerance test (OGTT) to detect prediabetes. Both require a person to fast overnight. In the FPG test, a person’s blood glucose is measured first thing in the morning before eating. In the OGTT, a person’s blood glucose is checked after fasting and again 2 hours after drinking a glucose-rich drink.

How do I stop prediabetes developing into Type 2 diabetes?

The good news may be that, if you have become aware of the disease early, your condition can still be cured. The two principle factors for consideration are the changing of diet and the addition of appropriate physical exercise to your lifestyle. By making these changes, it may be possible to return blood sugar levels to normal. Prediabetes is a serious medical condition that can be treated.

The good news is that the recently completed Diabetes Prevention Program study conclusively showed that people with prediabetes can prevent the development of type 2 diabetes by making changes in their diet and increasing their level of physical activity. They may even be able to return their blood glucose levels to the normal range. But for a comprehensive and individual plan you should see your doctor.

Is prediabetes the same as Impaired Glucose Tolerance or Impaired Fasting Glucose?

Yes. Doctors sometimes refer to this state of elevated blood glucose levels as Impaired Glucose Tolerance or Impaired Fasting Glucose (IGT/IFG), depending on which test was used to detect it.

Why do we need to give it a new name? Has the condition changed?

The condition has not changed, but what we know about it has. We are giving IGT/IFG a new name for several reasons. prediabetes is a clearer way of explaining what it means to have higher than normal blood glucose levels. It means you are likely to develop diabetes and may already be experiencing the adverse health effects of this serious condition. People with prediabetes are at higher risk of cardiovascular disease. People with prediabetes have a 1.5-fold risk of cardiovascular disease compared to people with normal blood glucose. People with diabetes have a 2- to 4-fold increased risk of cardiovascular disease. We now know that people with prediabetes can delay or prevent the onset of type 2 diabetes through lifestyle changes.

How does the FPG test define diabetes and prediabetes?

Normal fasting blood glucose is below 100 mg/dl. A person with prediabetes has a fasting blood glucose level between 100 and 125 mg/dl. If the blood glucose level rises to 126 mg/dl or above, a person has diabetes.

How does the OGTT define diabetes and prediabetes?

In the OGTT, a person’s blood glucose is measured after a fast and 2 hours after drinking a glucose-rich beverage. Normal blood glucose is below 140 mg/dl 2 hours after the drink. In prediabetes, the 2-hour blood glucose is 140 to 199 mg/dl. If the 2-hour blood glucose rises to 200 mg/dl or above, a person has diabetes.

Which test is better?

According to the expert panel, either test is appropriate to identify prediabetes.

Why do I need to know if I have prediabetes?

If you have prediabetes, you can and should do something about it. Studies have shown that people with prediabetes can prevent or delay the development of type 2 diabetes by up to 58 percent through changes to their lifestyle that include modest weight loss and regular exercise. The expert panel recommends that people with prediabetes reduce their weight by 5-10 percent and participate in some type of modest physical activity for 30 minutes daily. For some people with prediabetes, intervening early can actually turn back the clock and return elevated blood glucose levels to the normal range.

What is the treatment for prediabetes?

Treatment consists of losing a modest amount of weight (5-10 percent of total body weight) through diet and moderate exercise, such as walking, 30 minutes a day, 5 days a week. Don’t worry if you can’t get to your ideal body weight. A loss of just 10 to 15 pounds can make a huge difference. If you have prediabetes, you are at a 50 percent increased risk for heart disease or stroke, so your doctor may wish to treat or counsel you about cardiovascular risk factors, such as tobacco use, high blood pressure, and high cholesterol.

Who should get tested for prediabetes?

If you are overweight and age 45 or older, you should be checked for prediabetes during your next routine medical office visit. If your weight is normal and you’re over age 45, you should ask your doctor during a routine office visit if testing is appropriate. For adults younger than 45 and overweight, your doctor may recommend testing if you have any other risk factors for diabetes or prediabetes. These include high blood pressure, low HDL cholesterol and high triglycerides, a family history of diabetes, a history of gestational diabetes or giving birth to a baby weighing more than 9 pounds, or belonging to an ethnic or minority group at high risk for diabetes.

How often should I be tested?

If your blood glucose levels are in the normal range, it is reasonable to be checked every 3 years. If you have prediabetes, you should be checked for type 2 diabetes every 1-2 years after your diagnosis.

Could I have prediabetes and not know it?

Absolutely. People with prediabetes don’t often have symptoms. In fact, millions of people have diabetes and don’t know it because symptoms develop so gradually, people often don’t recognize them. Some people have no symptoms at all. Symptoms of diabetes include unusual thirst, a frequent desire to urinate, blurred vision, or a feeling of being tired most of the time for no apparent reason.

Sources: American Diabetes Association, Diabetes Care, Diabetes UK

Diabetes Management: Analysis Shows Value of Structured Exercise Programs

Insurance Benefits for Exercise Programs Can Cut Health Costs

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FOR the person with type 2 diabetes, or the high-risk individual who is trying to prevent the development of diabetes, there is an enormous body of research literature documenting the benefits of exercise. Indeed, research shows that just six weeks of exercise is enough to change both brain chemistry and body chemistry for the better; diets alone don’t have the same effect. But some questions still remain ‒ how much exercise is needed, and what kind?

A host of studies have linked exercise programs with improved health measures related to blood pressure, lipid levels — including cholesterol and triglycerides — cardiovascular events, cognition, physical performance, premature death and quality of life. Analyses of interventions to promote physical exercise in adults have found that compared with no intervention, exercise programs are cost-effective and have the potential to improve survival rates and health-related quality of life.

A recent systematic review and meta-analysis ‒ undertaken by scientists led by Daniel Umpierre of the Hospital de Clinica de Porto Alegre in Brazil ‒ compares the association between physical activity advice and structured exercise programs, respectively, and markers of diabetes.  It reveals that implementing structured exercise training — including aerobic, resistance or both — is associated with a greater reduction in HbA1c levels for patients with diabetes compared to patients in control groups. Results of the study are published in the May 4 issue of the Journal of the American Medical Association (JAMA).

A structured exercise is a task, activity, or question posed by a leader that pushes everyone to reflect, focus, offer ideas and insights, and become engaged in learning. Structured exercises offer group leaders a variety of options for encouraging group participation and discussion, practicing skills, and involving adults who have a range of learning styles and capabilities.

After analyzing the results of 47 randomized clinical trials, the researchers also found that exercising for longer periods of time was better at bringing blood sugar levels down than exercising more intensively. Longer weekly exercise duration was also associated with a greater decrease in these levels, according to results of the analysis of previous studies.

The meta-analysis shows that greatest reductions in HbA1c occurred in patients exercising for more than 150 minutes in total per week. Exercise intensity did not appear to matter. Exercising a minimum of 150 minutes a week (usually broken down to 30 minutes of exercise five days a week) is recommended by such institutions as the American College of Sports Medicine.

“People with type 2 diabetes should engage in regular exercise training, preferentially supervised exercise training,” says Beatriz Schaan, the study’s senior author. “If these patients can perform training for more than 150 minutes per week, this would be more beneficial concerning their glucose control. However, if they cannot reach this amount of weekly exercise, lower exercise amounts are also beneficial.”

The Importance of Exercise in Diabetes Management

A recent joint statement from the American Diabetes Association (ADA) and the American College of Sports Medicine (ACSM) has already underscored the importance of physical exercise to prevent and manage insulin resistance, type 2 diabetes mellitus, gestational diabetes mellitus, and the complications of diabetes.

“Current guidelines recommend that patients with type 2 diabetes should perform at least 150 minutes per week of moderate-intensity aerobic exercise and should perform resistance exercise three times per week,” the authors of the Brazil study wrote. “Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear.”

Indeed, although some clinical trial evidence suggests that aerobic exercise and resistance training can each improve glucose control in patients with type 2 diabetes mellitus, not all clinical trials are consistent with regard to this finding.

However, differences in results of clinical trials about the ability of aerobic exercise and resistance training to improve glucose control are primarily due to differences in trial design, including modality, intensity, exercise program duration, adherence to the programs, sample size, and patient populations.

In the Brazilian study, the authors analyzed 47 randomized controlled trials (RCTs) into the effect of exercise on HbA1c, with a total of 8538 patients. In 23 of these RCTs, patients took part in structured exercise training, and in the other 24 they were simply given advice on physical activity.

Across all studies analyzed, engaging in structured exercise was associated with decreased HbA1c levels compared with controls, whether this was structured resistance training (fall in HbA1c of 0.57%), structured aerobic exercise (fall of 0.75%), or a combination of both (0.51% fall).

A longer total time spent in structured exercise was associated with better glycemic control. If total weekly time in structured exercise exceeded 150 minutes, the average drop in HbA1c was 0.89%, against 0.36% for a time of 150 minutes or less.

Physical activity advice was only associated with a decline in HbA1c if it was combined with dietary advice.

The authors said: “This systematic review and meta-analysis of RCTs demonstrates important findings regarding the prescription of structured exercise training. First, aerobic, resistance, and combined training are each associated with HbA1c decreases, and the magnitude of this reduction is similar across the three exercise modalities.

“Second … structured exercise of more than 150 minutes per week is associated with greater declines in HbA1c than structured exercise of 150 minutes or less per week in patients with type 2 diabetes. This finding is important because the current guideline-recommended exercise duration is at least 150 minutes per week.

They added: “Although high-intensity exercise has been previously shown to have an association with HbA1c reduction, our findings did not demonstrate that more intensive exercise was associated with greater declines in HbA1c.”

In an accompanying editorial, Marco Pahor, director of the University of Florida Institute on Aging, argues that “the meta-analysis … and cumulative evidence from a large number of randomized controlled trials conducted over the past few decades in the area of physical activity and exercise provide solid evidence for public policy makers to consider structured exercise and physical activity programs as worthy of insurance reimbursement to promote health, especially in high-risk populations.”

Insurance Benefits for Exercise Programs Can Cut Health Costs

With respect to type 2 diabetes, Medicare reimburses for approved self-management education and medical nutrition therapy programs. But no specific reimbursement is given for any physical activity or exercise program, despite evidence that such programs can help improve health and cut costs.

Questions remain as to what format reimbursable exercise and physical activity programs should take, what population group should be targeted, and at what stage of life or health status would a lifestyle intervention be most cost-effective to implement.

Some insurance providers already include a fitness benefit for members, such as monthly membership at certain fitness centers or access to personal trainers or exercise classes at reduced cost. Indeed, use of such health plan-sponsored club benefits by older adults has been linked to slower increases in total health care costs.

In one study, older adults who visited a health club two or more times a week over two years incurred $1,252 less in health-care costs in the second year than those who visited a health club less than once a week. Programs among people with lower incomes can also pay off, because people in that group are otherwise more likely to forego health-promoting physical activity because of economic constraints or safety concerns.

“People are willing to invest in improved health, but if you have a fixed amount of resources then you want to choose where you get the most health for the dollar,” said Erik Groessl, an assistant professor of family and preventive medicine at the University of California, San Diego, and director of the UCSD Health Services Research Center. Groessl was not involved in the current analysis.

Group training or walking programs, for example, can be cost-effective, sustainable forms of physical activity that don’t require expensive health care professionals or equipment. But more costly interventions that yield dramatic results might also be worth the expense.

“There is a lot of evidence that physical activity works, and I think it’s time to start putting it into practice more widely,” Groessl said.

Sources: JAMA, University of Florida News, Medpage Today

Type 2 Diabetics Also At Increased Risk Of Hypothyroidism

THYROID is an important endocrine gland of human body and plays vital role in the normal functioning of the body. It has important effects on glucose metabolism along with lipids and proteins and conversely can be affected by abnormal glucose metabolism.

Recently new research has found a strong link between type 2 diabetes and an increased risk of hypothyroidism, the most common type of thyroid disorder. It is the situation where the thyroid fails to make enough thyroid hormone to regulate the body’s metabolism. The findings were presented at the American Association of Clinical Endocrinologists (AACE) 20th Annual Meeting and Clinical Congress in San Diego last month.

Symptoms of underactive thyroid gland functioning, no matter what the cause, include fatigue, dry, coarse skin and hair, inability to tolerate cold weather, weight gain, hoarse voice, and heavy or irregular menstrual periods. The symptoms develop so slowly that sometimes people just think they are growing old prematurely.

Thyroid disorders (hypothyroidism or hyperthyroidism) and diabetes mellitus are quite common endocrinopathies (diseases of endocrine glands) seen in general population. Thyroid disorder in the general population is estimated to be 6.6%, while the prevalence in diabetic population has been estimated at 10.8%. The prevalence of sub-clinical (early stage) hypothyroidism is 5.4% and clinical hypothyroidism is 4.1%, while the prevalence of sub clinical hyperthyroidism is 5.8% and the clinical hyperthyroidism is 5.1%, the researchers noted.

The cross-sectional study comparing 1,848 adult patients with type 2 diabetes with 3,313 individuals without diabetes, showed the prevalence of hypothyroidism on the study group to be 5.7% compared with 1.8% in the control group (P ≤.0001).

Citing the Whickham survey, the researchers said thyroid function affected 6.6% of adults. A higher prevalence of abnormal TSH concentration in Type 2 diabetic patients (31%) was reported by Celani et al, they pointed out. In their study, sub-clinical hypothyroidism was detected in 11.66% of evaluated diabetic patients and hypothyroidism was evident in 35% of diabetic patients, which is a quite high ratio as compared to other reported data. “This may be because of only concentrating diabetes mellitus and its complications rather than thinking other diagnosis partly or misreporting by patients,” they noted.

“Although there is a recognized association between thyroid disease and diabetes, this association has been perceived mostly for type 1 diabetes. However, in type 2 diabetes, there is no consensus as to whether screening for hypothyroidism is necessary. We were surprised that the results showed an association that was this high,” said lead author Hector Eloy Tamez-Perez, MD, Autonomous University of Nuevo Leon, Monterrey, Mexico.

The study included patients who were enrolled in a private outpatient clinic in 2009, had a diagnosis of type 2 diabetes, and were treated with levothyroxine (Levothroid, Levoxyl, Synthroid, Tirosint, Unithroid), although patients with thyroid neoplasia (the process of abnormal and uncontrolled growth of cells. The product of neoplasia is a neoplasm, i.e. a tumor), panhypopituitarism (a deficiency involving all the hormonal functions of the pituitary gland), or have surgical complications of a multinodular goiter or a thyroid nodule were excluded.

It was found that around 10 per cent to 31 per cent of patients with type 2 diabetes had thyroid dysfunction, and that those with subclinical (early stage) hypothyroidism were the most common thyroid condition.

“So it is important to evaluate diabetic population regarding hypothyroidism whether clinical or sub-clinical, as one condition can worsen the other if left untreated by causing worsening control of diabetes mellitus, worsening dyslipidemias and causing diverse complications. Therefore, it is imperative to screen diabetic population regarding hypothyroidism. Moreover further studies on large scale should be planned to evaluate the magnitude of the disorder,” they concluded.

Popular Health Central columnist Dr Bill Quick, a physician living with diabetes, writes:

Treatment for hypothyroidism is straight-forward: give the patient thyroid hormone replacement. How much thyroid hormone to give is about the only question: give too little, and the symptoms continue; give too much and the patient can become hyperthyroid. Physicians adjust the dose of thyroid hormone replacement by rechecking the TSH (thyroid stimulating hormone) level rather than judging by symptom levels: when the TSH is in the normal range, it can be assumed that the amount of thyroid hormone replacement therapy is appropriate.

Testing for hypothyroidism is easy to do, thyroid disease is common in the age group that has T2DM,  treatment for hypothyroidism is easy and rewarding in relieving symptoms and decreasing the risk of future disease.

Lab tests for hypothyroidism are done using a standard blood sample, and include measurement of the TSH levels, thyroid hormone levels (called T3 and T4), and sometimes thyroid antibodies. In a patient with the symptoms, an elevated TSH level with simultaneous low levels of T3 and T4 are conclusive evidence that the thyroid gland is underactive. Indeed, a high level of TSH with normal levels of T3 and T4 are considered very suggestive evidence of impending hypothyroidism and worthy of treatment.

By the way, note the paradox: the TSH level is high in most underactive thyroid disorders. This is easy to understand when it is understood that TSH is made elsewhere, in the pituitary gland, and if the thyroid is failing to make its thyroid hormone, then the pituitary gland attempts to stimulate the thyroid to make more thyroid hormone, hence the TSH level goes up. For people without symptoms of hypothyroidism, measurement of the TSH level can be used as a screening test to look for early thyroid gland problems; sometime, it’s also recommended that thyroid antibodies be part of the screening process.

The American Diabetes Association suggests for patients with T1DM that “TSH concentrations should be measured after metabolic control has been established. If normal, they should be re-checked every 1-2 years, or if the patient develops symptoms of thyroid dysfunction…” But there’s no ADA recommendation for people with T2DM. The authors of the abstract advised testing “similar to what occurs in type 1 diabetes.”

If you have diabetes, whether T1DM or T2DM, it seems reasonable that you should have your TSH level checked every year or two.

Benchmark Cambridge Trial In Quest For Ambulatory Artificial Pancreas

I had reported earlier that once perfected and approved by regulators, safe and robust ambulatory artificial pancreas ‒ or to use the scientific term ‘closed loop insulin delivery system’ ‒ has the potential to greatly improve the health and lives of people with type 1 diabetes. The idea itself is not new but the old generation closed loop insulin delivery systems were cumbersome and unsuitable for long term or outpatient use.

Artificial pancreas concept

The newer systems link a continuous glucose monitor and a subcutaneous insulin infusion pump via a control algorithm, which retrieves continuous glucose monitoring data in real time (for example, every five minutes) and uses a mathematical formula to compute insulin delivery rates that are then transmitted to the insulin pump.

However, artificial pancreas that can be worn by diabetics on their person as they go about their daily lives is still in development, with the first in-clinic studies now being reported. Preliminary results have been promising ‒ the most notable improvement is in overnight control of type 1 diabetes, with improvements in safety and a reduction in nocturnal hypoglycemia being reported.

These improvements result from the fine adjustment of insulin delivery provided by closed loop control overnight being superior to a generally fixed basal rate and less likely to cause hypoglycemia. The first application of closed loop control is therefore likely to be in glucose regulation overnight, a step that has the potential to improve dramatically the safety of insulin delivery during crucial, generally unsupervised, periods.

Now a University of Cambridge research tem led by Roman Hovorka has demonstrated the safety and efficacy of overnight closed loop insulin delivery with conventional insulin pump therapy in adults with type 1 diabetes.

Artificial Pancreas Best Hope For Diabetics In Near Term

The trial group consisted of 24 adults (10 men and 14 women) aged 18-65, who had used insulin pump therapy for at least three months and the research team used two protocols ‒ a medium sized meal (60 g carbohydrate) and a large size meal (100 g carbohydrate + alcohol) ‒ to see whether artificial pancreas were effective in overcoming nocturnal hypoglycemia.

As in previous studies carried out by Boris Kovatchev and others in the U.S. and France, the Cambridge closed loop system significantly increased the time that plasma glucose was in the target range (70-144 mg/dl), reduced incidence of hypoglycemia, and better overnight control.

But what makes the Cambridge study important is that the randomized crossover trial design is virtually unique in the field of closed loop control. Because this design is the gold standard for clinical research, the results set a benchmark for future studies.

The only other randomized controlled trial of closed loop control was recently presented by the University of Virginia research team led by Kovatchev at the 4th International Conference on Advanced Technologies and Treatments for Diabetes. This study recruited 24 adults and adolescents with type 1 diabetes in the United States and in France and achieved results similar to those reported by Hovorka and colleagues ‒ more time within the target range of 70-180 mg/dl and a threefold reduction in hypoglycemia.

Dr Roman Hovorka

Moreover, the control algorithm used by Hovorka and colleagues belongs to an advanced class of closed loop control technologies known as “model predictive control”. Algorithm designs for artificial pancreas have generally used either “proportional-integral-derivative control” or “model predictive control”.

Proportional-integral-derivative control algorithms are reactive, responding to changes in glucose levels with adjustment in insulin delivery. Model predictive control algorithms are built over a model of the human metabolic system and are therefore proactive, delivering insulin in anticipation of changes in glucose concentrations.

This compensates partially for the time delays inherent in subcutaneous glucose control (the time delay in insulin action, which can amount to 60 minutes or more). For this reason, model predictive control has become the approach of choice more recently.

The algorithm developed by Hovorka and colleagues has certain distinct features, such as real time adaptation of the underlying model to changing patient parameters implemented as a selection from several predefined models. However, this potential advantage remains to be evaluated.

Most importantly, this is one of the first studies to test realistic meal scenarios and challenge the participants with a large dinner that included alcohol. As such, the study is a clear advance in the quest for an artificial pancreas that can be used by a diabetic while performing normal daily activity.

However, as the authors admit, one limitation is the exclusively manual control of the artificial pancreas used relied on study personnel to transmit data manually from the continuous glucose monitor (CGM) to the computer running the closed loop control, and to transmit insulin injection recommendations from the computer to the insulin pump because of technological and regulatory barriers

In fully automated systems ‒ which is what researchers and medical device makers are hoping to make a reality for diabetics ‒ these processes are handled by data transmission and pump control devices, respectively. However, Cambridge method limited the investigation to testing only the control algorithm, not the artificial pancreas as a whole. The testing of other key components, such as sensor-pump communication and error mitigation, would require much more effort and thorough system validation.

Studies using fully automated systems have already been reported by the Artificial Pancreas Project and offer hope for the future of ambulatory systems i.e. devices that be worn by diabetics on their person in their daily lives.

Lastly, despite the sophistication of the control algorithm and the significant reduction in nocturnal hypoglycemia, four episodes of severe hypoglycemia (<70 mg/dl) occurred, three of which the authors thought were attributable to the preceding prandial insulin dose and could not be prevented by the artificial pancreas suspending insulin delivery.

This finding reinforces the recently proposed idea that a dedicated hypoglycemia safety system ‒ a separate algorithm responsible solely for the assessment and mitigation of the risk of hypoglycemia ‒ may need to accompany closed loop control. Such safety systems already exist, and have proved useful.

Based on ‘Boris Kovatchev: Closed Loop Control For Type 1 Diabetes (BMJ 2011; 342:d1911)

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